WR '99r THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES RESEARCH STUDIES IN PSORIASIS By JAY F.[SCHAMBERG, M.D., Director of the Research; JOHN A. KOLMER, M.D., Pathologist and Bacteriologist; A. I. RINGER, M.D., and G. W. RAIZISS, Ph.D., Physiological Chemists. Reprinted from THE JOURNAL OF CUTANEOUS DISEASES, INCLUDING SYPHILIS, \ for October and November, 1913. REBMAN, COMPANY HERALD SQUARE BUILDING 141-145 WEST 36TH STREET NEW YORK Bioir.edu: al Library WR 2.05 Reprinted from THE JOUHXAL or CUTANEOUS DISEASES, IXCLUDINO SYPHILIS, for October and November, 1913. RESEARCH STUDIES IN PSORIAISS A PRELIMINARY REPORT.* (From the Dermatological Research Laboratories of the Philadelphia Polyclinic and College for Graduates in Medicine.) By JAY F. SCHAMBERG, M.D., Director of the Research; JOHN A. KOLMER, M.D., Pathologist and Bacteriologist; A. I. RINGER, M.D., and G. W. RAIZISS, Ph.D., Physiological Chemists. FOR two thousand years physicians have been familiar with the clinical appearances of psoriasis. Much is known of its symptomatology, its course, its diagnosis, its histopathology and not a little concerning its local treatment; of its cause and nature however, we are in ignorance. Auspitz remarked some years ago "Was Psoriasis ist, weiss bis heute noch kein Mensch." Through the philanthropy of a generous donor, we have been enabled to inaugurate at the Philadelphia Polyclinic and College for Graduates in Medicine, a research investigation into the nature and treatment of psoriasis. It is obvious that a research into the nature of a disease should be prosecuted without preformed judgments and with a mind free to receive impressions from the results of experimental work. In the investigations that have been carried out, no attempt has been made to prove any theory of the causation of psoriasis. Two lines of inquiry were outlined one bacteriological and pathological, and the other physiological-chemical ; the work in each department has been carried out with the dominant thought of recording the findings, whether they proved to be of a positive or a negative character. In this manner it is hoped that some illumination may be shed upon a * Read in abstract before the 37th Annual Meeting of the American Derma- tological Association, Washington, D. C., May 6-8, 1913. 63586S 2 SCHAMBERG, KOLMER, RINGER, AND RAIZISS disease, concerning whose nature the widest divergence of opinion exists, and yet of which we know definitely no more than did Hip- pocrates. PART I. PATHOLOGY. CONCERNING COMPLEMENT FIXATION IN PSORIASIS. The original conception and explanation of the Wassermann re- action in syphilis, as being an example of complement fixation through the interaction of a specific antigen and its antibody, is now generally regarded as untenable. This reaction occupies a unique position owing to the fact that the "antigen" in the reaction need not be the Treponema pallidum but any suitable lipoid. The essen- tial factor is the presence in the body fluids of a reactionary product of cellular activity, "a reagin," due to infection with Treponema pallidum, which possesses as a chief characteristic a marked affinity for lipoids and is capable, in the presence of a suitable lipoid, of in- activating complement in the test tube, the phenomenon being better known as complement fixation. Similar lipoidophilic "antibodies" are to be found in the body fluids of persons infected with leprosy and yaws. The latter is also a spirochsetal infection while the exact nature of the microorganism of leprosy is unsettled. It is of signifi- cant importance, however, that certain parasites possess the power of stimulating the production of this peculiar lipoidophilic "reagin," best seen in luetic infection and thus the investigation of diseases of unknown aetiology by a study of complement fixation, using a lipoid as "antigen," offers the possibility of shedding some light upon the nature of the antibodies and possibly upon the question of para- sitism. Among other infections, however, examples of specific complement fixation through the interaction of antigen and its amboceptor are well known. Of serum reactions, that of complement fixation is probably the most exact for demonstrating the presence of anti- bodies due to the activities of bacterial or other protein substances and, therefore, if the antigen is known the antibody may be found, or, conversely, if the antibody is present in the tissues and body fluids the specific antigen may be found by complement fixation ex- periments with different substances supposed to contain the specific RESEARCH STUDIES IN PSORIASIS 3 antigen. In this manner we were led to study the question of local parasitism in psoriasis by preparing extracts of the scales and of various cultures of bacteria isolated from psoriatic lesions, with the idea of determining their setiological relationship by specific com- plement fixation with the sera of psoriatic persons, based upon the possibility that a specific immune* amboceptor was present in the sera of such subjects. These reactions, however, have distinct limi- tations ; even in pneumonia, tuberculosis, etc., where the specific anti- gen is known, inconstant results are obtained. It is to be remem- bered, therefore, in this connection, that while positive results are of considerable value, negative results do not necessarily mean that the specific antigen is absent from the extracts of infected tissues used in the reactions. The object of this study was mainly two- fold: 1. To apply the Wassermann reaction to the study of psoriasis, to ascertain the presence or absence of lipoidophilic antibodies (reagin). 2. To study complement fixation with the sera of psoriatic pa- tients, using extracts of scales and organisms cultured from the lesions, with the view of shedding light on the question of parasitism. THE WASSERMANN REACTION IN PSORIASIS. The available literature bearing upon this question is quite meagre. 1. Gjorjevic and Savnik 1 studied the reaction with sera of 20 patients, using an alcoholic extract of guinea pig heart as anti- gen. One of their cases gave a history of lues and must, therefore, be excluded from the series. Of the 24 remaining cases giving nega- tive histories of luetic infection, 20 yielded weakly positive reactions. In one case the reaction was found positive with active and negative with inactive serum ; 2 cases giving weak positive reactions, reacted negatively after treatment. 2. Bruck 2 questioned these results, re- porting negative results with both active and inactive sera in 42 psoriasis cases of 45 examined. The remaining 3 cases were strongly positive, but gave positive histories of luetic infection. However, it should be mentioned that he did not consider as positive, reactions showing a weak or slight degree of inhibition of haemolysis. 1 GJOKJEVIC, G., and SAVNIK, P. Wien. klin. Wchnsch., 1910, xxii, No. 17, p. 626. 2 BHUCK, C. Wien. klin. Wchnschr., 1910, xxii, No. 19, p. 704. 4 SCHAMBERG, KOLMER, RINGER, AND RAIZISS TECHNIQUE. 1. ANTIGENS. Owing to the observation that the lipoidophilic "reagin" in syphilis apparently varies in its affinity for various lipoids, it is advisable to use several extracts with each serum in con- ducting the Wassermann syphilis reaction. For this reason we have used the following extracts in studying the sera of 48 patients : (a) alcoholic extract of syphilitic liver; (b) acetone extract of syphilitic liver; (c) acetone insoluble lipoids; (d) alcoholic extract of guinea pig heart; (e) cholesterinized alcoholic extracts of beef and human heart. All of these extracts were titrated for their antigen ic unit with the serum of a case of secondary syphilis. In conducting the re- actions, double the titrated dose was used, providing that this amount was at least eight to ten times less than the anticomplemen- tary dose. 2. COMPLEMENT. Fresh guinea pig serum was diluted 1 :20 and used in a dose of one unit after titration with one unit of ambo- ceptor, carried over from week to week or used in a dose of 1 cc. and the amboceptor titrated with this dose and 1 cc. of a 2.5% suspension of washed sheep corpuscles. 3. H^MOLYTIC AMBOCEPTOR. Antisheep rabbit amboceptor was used in doses representing one hsemolytic unit. This is an important feature of the technique, for the quantitative relationship between complement and amboceptor is quite important, an excess being able to mask weakly positive reactions. The exact adjustment of comple- ment and amboceptor is especially desirable when using the sheep hiemolytic system, owing to the presence of varying quantities of natural antisheep amboceptor in human sera. 4. SERUMS. Sera were inactivated by heating to 55 C. for one half hour. Doses of from 0.1 to 0.2 cc. were employed. 5. CORPUSCLES. One cc. of washed sheep corpuscles in 2.5% suspension. Since all sera were tested with 3 to 5 different "anti- gens" at the same time, the usual quantities of the various compo- nents of the syphilis reaction were used in half the amounts of the original Wassermann reaction. Serum, antigen and complement were diluted to 3 cc. with sterile normal salt solution and incubated at 37 C. for one hour; 1 cc. of the corpuscle suspension and one hasmolytic dose of amboceptor were added and tubes reincubated for one to two hours, depending upon the ha-molysis of the controls. Tubes were then placed in the refrig- erator over night, readings being made and recorded next morning. For controls : the serum of each patient without antigen ; a luetic and a normal serum with each "antigen"; complement; corpuscle; amboceptor and haemolytic controls were set up each time. RESEARCH STUDIES IN PSORIASIS RESULTS. The results of the investigation of 48 sera are given in the follow- ing table: TABLE I. WASSEBMANN REACTION IN PSORIASIS. Case. Name. 1. U h 2. M n 3. Q y : 4. F n . 5. M s . 6. P s . 7. L f . 8. Sr . 9. C y . 10. R d . 11. C k . 12. P e . 13. N n . 14. D y . 15. B n . 16. S b . 17. B b . 18. S p . 19. C n . 20. D y . 21. C t . 22. M y . 23. K g . 24. S m 25. C e . 26. H n 27. Me n 28. Me e 29. A n . 30. F n . 31. B n . 32. L a . 33. C a . 34. D h . 35. B n . 36. D s . 37. M a . 38. L f . 39. R n . 40. B n . 41. T t ., 42. F m . 43. S s . ANTIGENS. Alcoholic Acetone Acetone Alcoholic Syph. liver. Syph. liver. InsoL Lip. Pig Heart. Cholest. heart. 9 6 SCHAMBERG, KOLMER, RIXGER, AND RAIZISS TABLE I. Continued. WASSKHMANU REACTION IN PSORIASIS. ANTIGENS. Alcoholic Acetone Acetone Alcoholic Cbolest. Name> Syph. liver. Syph. liver. Insol. Lip. Pig Heart. heart. 44. C e 45. H d + + + 46. R r + 47. Jy + + + + + 48. M s indicates that the particular antigen so marked was not employed. - indicates complete haemolysis (negative reaction). indicates ,less than 25% inhibition of haemolysis (doubtful reaction). + indicates 25% inhibition (weakly positive). -J-+ indicates 50% inhibition (positive reaction). -|--|--r- indicates 75% inhibition (strongly positive reaction). -f--| (--(- indicates 100% or absolute inhibition of haemolysis. An examination of the table shows the number* and degree of positive reactions. The histories of those reacting positively will be given later. It is to be noted that the occurrence and degree of positive reactions varied with the different "antigens" and these are worthy of further analysis: 1. With the alcoholic extracts of syphilitic liver, 9, or 18.7% of sera reacted positively as follows : (a) Two cases yielded less than 25% inhibition (). (b) Two yielded weakly positive reactions ( + ). (c) Four gave positive reactions (-}--|-). (d) One gave strong inhibition of haemolysis or (-f--|--}-). In this study several alcoholic extracts of luetic liver were used, including German products standardized by Wassermann and Meier. 2. With the acetone extract of syphilitic liver, 9 or 18.7% of sera reacted positively, all being with the same sera that reacted positively with the alcoholic extract of syphilitic liver. 8. With an extract of acetone insoluble lipoids, 45 sera were examined, positive reactions occurring in 6, or 13.3% of cases as follows : (a) One case showed 25% inhibition of haemolysis (+) (b) Five cases yielded 50% inhibition ( + + ). It is to be noted, however, that the difference in percentage of positive reactions with this extract compared with the results with alcoholic extracts of luetic liver is due to the fact that not all cases were tested with the extracts of acetone insoluble lipoids. In every instance where a positive reaction occurred with the alcoholic ex- RESEARCH STUDIES IN PSORIASIS 7 tract of luetic liver, a positive result likewise resulted with acetone insoluble lipoids. 4. Thirty serums were tested with an alcoholic extract of guinea pig heart, positive reactions occurring in 5 instances, the reaction with an alcoholic extract of syphilitic liver being likewise positive in each case. 5. With cholesterinized alcoholic extracts of human beef heart, the percentage of positive reactions was higher, for in 4 instances these extracts yielded positive reactions with sera which were nega- tive with alcoholic and acetone extracts of luetic liver and an ex- tract of acetone insoluble lipoids. Thus, of 22 sera tested with cholesterinized extracts, 8, or 36.3% reacted positively as follows: (a) One case yielded less than 25% inhibition (). (b) Two cases gave 25% inhibition (-{-). (c) Five cases gave 50% inhibition (-f (-). As pointed out by Kolmer 3 and his associates, cholesterinized ex- tracts, especially cholesterinized alcoholic extract of beef heart, may yield 25% or less inhibition of haemolysis with about 10% of normal sera. For this reason it is a difficult matter to properly interpret the results if using cholesterinized extracts alone, when conducting the Wassermann reaction. This is additional evidence in support of the necessity of using several extracts, plain and cholesterinized, with each serum tested for the presence of syphilis reagin. In 4 cases yielding positive reactions with the cholesterinized and negative reactions with plain extracts, the degree of the reactions was as follows : (a) Case 46, R., less than 25% inhibition (). (b) Case 37, M a., 25% inhibition (+) (c) Cases 40 and 43, 50% inhibition (+ + )- Omitting Cases 46 and 37 as possible inhibitions of haemolysis with cholesterinized extracts and normal sera, it leaves 2 cases (40 and 43) in which this possibility is not likely, as controlled by the use of these same extracts in a large number of cases of lues, the results being given in the paper by Kolmer, already alluded to. Of the 48 cases examined it is found, therefore, that slight reactions occurred in 18.7% of cases with an alcoholic extract of luetic liver, and of 22 cases in 28.5% with the cholesterinized extracts, as antigens. In 5 of our cases an opportunity was afforded for repeating the 3 KOLMER, J. A., LAUBAUGH, E. E., CASSELMAN, A, J., and WILLIAMS, "W. W. "Practical Studies on the So-called Syphilis 'Antigens,' with Special Reference to Cholesterinized Extracts." Arch. Int. Med. (in press). 8 SCHAMBERG, KOLMER, RINGER, AND RAIZISS reactions at a subsequent time. While in a few of these patients improvement had taken place, yet some reaction was present. In all of the cases the complement fixation reactions were practically the same as in- the first test. TABLE II. REPEATED WASSEKMANN REACTIONS IN PSORIASIS. Alcoholic Acetone Acetone Alcoholic d 'Syph. liver. Syph. liver. Insol. Lip. Pig Heart. 1 . U h 8 mos. 2 . M m .... 4 mos. 2. M n .... 8 mos. 1 5 . B in .... 1 mo. 43. S s 1 mo. 46. R r 1 mo. INTERPRETATION OF RESULTS. It is most remarkable that there should have been 9 cases of psoriasis out of 48 or 18.7% that have reacted positively with the complement fixation test employing the Wassermann antigen (alco- holic extract of luetic liver). We cannot, with Bruck, brush these results aside and accord no significance to them, because the reactions were weak, for some of our reactions were of medium degree. In 4 out of the 9 cases there was 50% of inhibition of haemolysis and in one 75%. Moreover, in the reactions made with cholesterinized anti- gens, in which we have considerable confidence within the limita- tions expressed by us, over 28% of the 22 cases examined gave posi- tive reactions. In Case 15, it is quite possible that the patient may have been a luetic subject, as there is a history of a "chancroid" and a subse- quent history which is not devoid of some suspicion. Cases 1 and 2 were men who presented no evidence whatsoever of lues and who firmly denied any history of infection. Cases 4 and 28 were re- spectable young single women, presenting no evidence of acquired or hereditary lues. Case 33 was a married woman who had two miscarriages, but has two healthy children, one born between the miscarriages. There did not appear in our patients to be any definite relation between the severity of the psoriasis eruption and the Wassermann reaction. Four cases giving positive reactions were severe cases, but several were very mild. Several other severe cases gave negative reactions. We cannot feel, from a clinical study of the patients whose reac- RESEARCH STUDIES IN PSORIASIS 9 tions are here presented, that the positive serum tests can all be attributed to syphilis, although this might be true of a few of them. On the other hand, some significance must be attached to them, which future research alone can reveal. We are content for the present to report the facts without attempting to suggest an interpretation of them. PART II. A. COMPLEMENT FIXATION EXPERIMENTS IN PSORIASIS WITH SCALES AND CULTURE ANTIGENS. As already stated, these were undertaken with the assumption that if an antibody existed in psoriasis it was in the nature of an ambo- ceptor and present in the body fluids of psoriasis patients in demon- strable amount. If this were true and if the antigen, presumably a parasite, were present in the scales or happened to be among the organisms isolated in pure culture from psoriatic lesions, suitable extracts of these should, with the antibody inactivate complement, or in other words, yield positive complement fixation reactions. TECHNIQUE. 1. ANTIGENS. The following antigens were prepared and used in this study: No. 1. NaCl extract of scales. The scales of three cases were lightly washed and dried. Five grams were ground with quartz sand and treated with 50 cc. of .85% salt solution containing 0.5% phenol. This mixture was shaken automatically for six hours ; extracted at 37 C. for 48 hours ; filtered and titrated. No. 2. Alcoholic extracts of scales. Five grains of scales were ground and treated with 50 cc. pure alcohol; shaken automatically for six hours ; extracted at 37 C. for 48 hours ; filtered and titrated. No. 3. NaCl culture antigen. Pure cultures of twelve different species of organisms isolated from psoriatic lesions were grown on glucose agar; washed off with NaCl solution; shaken automatically for two hours; heated to 60 C. for one hour; 1% phenol and gly- cerine were added ; titrated. No. 4. Cultures were made and washed off with NaCl solution as in preparing antigen No. 3. The emulsion was treated with equal volume of absolute alcohol and centrifuged; the supernatant fluid was decanted and the precipitate dried over calcium chloride, ac- curately weighed and ground with sufficient sodium chloride crystals to make up a 2% suspension of the ground organisms in .85% salt solution. The relative amounts of dried organisms used were as follows : 10 SCHAMBERG, KOLMER, RINGER, AXD RAIZISS 1 1 1 1 1 1 1 cc. cc. cc. cc. cc. cc. cc. diluted diluted diluted diluted diluted diluted diluted 1 1 1 1 1 1 1 :10 :20 :40 :80 :160 :S20 :640 = 2.0 mg. = 1.0 mg. = 0.5 nig. = 0.25 mg. = 0.125 mg. = 0.062 mg. = 0.031 mg. Before using this antigen with sera all the above doses were tested for anticomplementary dosage. It was found that all but the largest dose were free of anticomplementary effect and consequently were used with the various serums. No. 5. A salt solution extract was also prepared of two ascites kidney agar cultures of pieces* of psoriasis skin as follows : The oil and kidney were removed and ascites agar columns were weighed, ground with quartz sand and treated with 5 volumes of salt solution. This emulsion was then heated to 60 C. for an hour and 0.5% phenol added. Three different sets of antigens were prepared and used with a number of sera from psoriasis patients. All antigens were titrated for anticomplementary dose and one quarter of this amount used as an antigenic dose in conducting the reactions. The following table gives the results of such titrations with one set of antigens. TABLE III. ANTICOMPLEMENTAKY POWER OF ANTIGENS. Amount of Antigens. antigen. 1. 2. Oil. 1:20 3. Dil. 1:10 5. Dil. 1:10 01 cc H. H. H. H. 02 cc H. H. H H 4 cc H. H. H H 8 cc S.I.H. H. H M I H 1 cc M.I.H. S.I.H. M I.H. I H 1.5 cc I.H. M.I.H. I.H. I.H 20 cc l.H. I.H. I.H. I.H. 3.0 cc I.H. l.H. I.H. I.H Antigenic dose used 0.2 cc. 0.2 cc. 0.3 cc. 0.2 cc. H. = complete haemolysis. S.I.H. = slight inhibition of haemolysis. M.I.H. = marked inhibition of haemolysis. I.H. = inhibition of haemolysis. RESEARCH STUDIES IN PSORIASIS 11 2. Haemolytic System. The antisheep sheep system was em- ployed in the same manner as in the Wassermann reaction. 3. Patients' Serum. The sera of ten persons suffering with ex- tensive psoriasis were used. All sera were inactivated by heating to 55 C. for 30 minutes and used in ascending doses : .01 cc., .04 cc., .08 cc., 0.1 cc. and 0.3 cc. 4. Controls. The maximum dose of serum (0.3 cc.) without anti- gen ; haemolytic, complement, antigen and corpuscle controls as usual. The sera of 10 psoriatic persons were tested with all antigens. The following table of results with one serum shows the method used. TABLE IV. RESULTS OF COMPLEMENT FIXATION REACTIONS WITH PSORIASIS SERUM AND VARIOUS ANTIGENS. Amount of Serum. Antigens. No. 1. 0.2 cc. No. 2. 0.2 cc. No. 3. 0.3 cc. No. 5. 0.2 cc. .0] cc H. H. H. H. H. S.I.H. H. H. H. H. H. H. H. H. H. H. H. M.I.H. H. H. H. H. S.I.H. M.I.H. .04 cc .08 cc .1 CC .2 cc . 3 cc Control .3 cc.. None None None None With antigen No. 4, the serums were used in constant dose of 0.2 cc. with ascending doses of antigen as follows: .031 mg., .062 mg., 0.125 mg., 0.25 mg., 0.5 mg. and 1.0 mg. RESULTS. Nine other sera from active cases of psoriasis, three of which yielded slightly positive Wassermann reactions with lipoidal ex- tracts, were tested in the above manner with all antigens. In no instance was there a complement fixation reaction which could be regarded as a specific reaction. After repeating these experiments three times, we feel quite cer- tain that either the true antigen was not present in the extracts of scales and cultures used or that the psoriasis antibody if it exists, was not present in the sera in sufficient amount to inactivate complement with the extracts used in this study. 12 SCHAMBERG, KOLMER, RINGER, AND RAIZISS B. BACTERIOLOGY. LITERATURE Various organisms and "bodies" have been described from time to time as the possible cause of psoriasis, but none has been ade- quately confirmed by other investigators or accepted by competent critics. As early as 1856, Horing (Med. Correspondenzbl. d. Wurtt. Acrztl. Verein., 1856, p. 149) and Hafner (Ibid., p. 2541), reported cases of psoriasis conveyed from cattle to human beings ; they sought for the parasite without result. From the description given, the affection observed is generally believed to be "ringworm." Wertheim in 1853 ( Abstr. Gaz. hebd. de med., p. 449), examined the blood of psoriasis patients for microorganisms and failing to find any, studied the urine, in which he discovered a fungus of the Peni- cillium glaucum species, with which he carried out animal inocula- tions. In 1879, Lang (Vrtljschr. f. Dermal, u. Syph., 1879, p. 257), described in psoriasis scales a hyphomycete consisting of spores and mycelium which he termed "epidermidophyton." Eklund, in 1883 (Ann. de dermat. et de syph., 1883, No. 4), found a similar fungus which he designated "Lepocolla repens." Rics, of Strassburg, in 1888, in a splendid series of papers, dis- posed of these claims by proving that the so-called parasites were in reality artefacts produced by the action of the potassium hydrate solutions used in the examination of the scales. In 1887, the question of the parasitism of psoriasis was discussed at the Italian Congress of Pavia. De Matei found a micrococcus which he regarded as the cause of psoriasis; inoculations of this organism upon animals produced, he alleged, psoriasis-like efflores- cences. Majocchi looked upon De Matei's findings as accidental. INOCULATION EXPERIMENTS. In 1885, Lassar (Berl. klin. Wchmchr., 1885, No. 47, p. 771), demonstrated before the Berliner medizinische Gesellschaft, two rabbits that he had inoculated with psoriasis. One was inoculated with the scales, lymph and blood from a psoriatic patient and the second rabbit from the resulting lesion in the first. In both animals there was loss of hair at the inoculated site and in the first animal redness, thickening of the skin and a heap- ing up of scales. The removal of the coarse scales led to capillary h/rmorrhage. Lassar stated, however, that further research along these lines was necessary before he would draw any binding conclu- sions as to the transmissibility of psoriasis. Behrend, who was pres- ent at the demonstration, said that the lesions did not conform to psoriasis in the human subject; they resembled more herpes ton- surans. RESEARCH STUDIES IN PSORIASIS 18 Ducrey (Sulla voluta contagiosita della psoriasi, Gior. ital. d. mal. veil., 1887, No. 6, abstr. Arch. f. Dermat. u. Syph., 1888, p. 425), tried numerous experiments on man and upon rabbits, guinea pigs and dogs, to test the transmissibility of psoriasis. His experi- ments consisted of (1) vigorous inunction of a mixture of psoriasis scales with the lymph and blood that exuded, into normal, abraded and incised skin. (2) Application of the same to a blistered area. (3) Hypodermatic, rectal, intraperitoneal and intratracheal injec- tion of psoriatic diseased products. All of the results were negative. Ducrey concluded that (1) psoriasis is not transmissible either to man or lower animals; (2) the various forms of parasites found by different persons in psoriasis lesions are in all probability not the cause of psoriasis. De Amicis and Campana also inoculated rabbits and guinea pigs with entirely negative results. INOCULATIONS ON MAN. In addition to the negative inocula- tions upon man carried out by Ducrey, Alibert and De Amicis, Ham- mer and Block have attempted the same experiments without results. Wutzdorff's effort to inoculate himself was unsuccessful. With scales and lymph from a well-pronounced case of psoriasis in a young man, Schamberg (Jour. Cutan. Dis., Nov., 1909) inocu- lated an abraded area upon the flexor surface of his forearm. The inoculation was entirely negative. Inoculation experiments upon man and lower animals may be said to have all failed with the single exception of Destot, who was apparently successfully inoculated from a case of post-vaccinal psoriasis. In approaching the study of psoriasis from the bacteriological standpoint, several possibilities are to be considered: The disease, if parasitic (a), might be due to the implantation upon the skin of an exogenous parasite, as is observed in ringworm, fayus and tinea versicolor. Such an organism has hitherto not been found, but might be discoverable by the use of the ultramicroscope or by some new technique, (b) The disease might be caused by one of the common facultative organisms belonging to the group of cocci, so readily cultivable from the skin, in individuals in whom the soil is rendered favorable by some special condition, (c) The disease might be the result of the circulation in the fluids of the body and deposition in the skin of a microparasite, analogous to what is observed in syphilis and variola. The successful accomplishment of inoculation would go far toward establishing the parasitic nature of the disease and facilitate bacteriological research. 14- SCHAMHKKG, KOLMKR, RINGER, AND RAIZISS Various cocci and to a lesser extent, bacilli, are to be found among the more common bacteria of the skin. The classification of these is quite difficult, and at the present time considerable confusion exists, so that each investigator has come in time to adopt his own classification. From the fact that the skin, especially the exposed parts, is sub- ject to contamination with air, water, etc., it becomes more difficult to determine just which species belong properly to the skin as their natural habitation and which represent contamination. The original classification of Unna and Tommasoli (Flora der- matologica, Monatsh. f. prakt. Dermat., iv, No. 2, p. 49) was based largely upon morphology, growth in gelatin and shape of colonies in agar-agar and gelatine plates. With these methods they divided the various cocci in separate species. Since then other in- vestigators would group all cocci, including diplococci, in one gen- eral class without endeavoring to separate species. Several points in this connection should be borne in mind. First, an organism cannot be properly classified upon one cultivation alone. Thus a culture of diplococci, when freshly isolated may be distinctly gonococcoid in shape ; not a few of such cultures lose this character in later sub-cultures, the cocci dividing into twos and threes with the line of cleavage poorly defined. The shape and character of colonies in agar is not entirely reliable, because the age of the colony and its depth in the agar materially alter its shape and morphological char- acters. The same is true of gelatine, only here the presence or ab- sence of liquefaction has decidedly more value. Probably the behavior of the various cocci in gelatine and milk has most value in classification. It is to be remembered, however, that the age of the culture is an important factor; thus, some cul- tures liquefy gelatine or coagulate milk very slowly indeed, but never- theless are liquifiers and coagulators. This difference between cul- tures of cocci renders the differentiation between Staphylococcus pyogenes albus and Staphylococcus epidermidis albus of Welch most difficult, because the line of demarcation between the two is not a sharp one and many cultures partake of the features of both. Next to their behavior in gelatine and milk, the question of pig- ment formation is of distinct value. Cultures, however, must be al- lowed to grow for at least a week or two* before color observation becomes trustworthy. Some cultures descend from generation to generation with fixed morphological characters and when such a cul- ture is found, the morphology becomes of aid in the proper classifica- tion of the species. RESEARCH STUDIES IN PSORIASIS 15 We have studied 24 cases of psoriasis, isolating 57 cultures, rep- resenting 16 different species, according to the classification of the cocci which we have been led to adopt. Among these were 7 different cultures of bacilli. All of these, with the possible exception of Ba- cillus pseudo-diphtheria, do not in all probability belong to the skin as their natural habitat, but represent contamination from air and water. METHOD OF STUDY. Scales were removed from psoriatic lesions before and after preliminary cleansing and planted direct in the water of condensation, in tubes of slanted 1% glucose neutral agar- agar. After various trials we have finally decided that this was the best method of obtaining primary growths. All skin cocci grow more readily with glucose than in plain media. The primary cultures are then incubated for 48 to 72 hours, be- cause many cultures are practically sterile at the end of 24 hours incubating and the mixed culture in the bottom of the tube is plated in glucose agar and in gelatin. After further incubation for 48 to 72 hours, the various colonies are studied and transplanted. After transplants have proven to be in pure cultures, as far as can be deter- mined by morphological characters of the organisms, the culture is transplanted to the ordinary culture media generally used for the study of bacteria. In the process of classification we have used the nomenclature and technique as outlined by the Association of Ameri- can Bacteriologists, each culture being recorded on a special Asso- ciation Identification card. CLASSIFICATION OF SKIN Cocci. As already stated, the available literature on the bacteriology of the skin is quite meagre. We have adopted the following classifica- tion of the cocci found in psoriasis lesions and which may be applied to the skin in general, the classification being based principally upon the following characters : 1. Liquefaction or non-liquefaction of plain gelatine culture grown at room temperature for 2 weeks. 2. Coagulation or non-coagulation of milk cultures grown in incu- bator for 5 days ; also acid and alkali production ; whey forma- tion ; peptonization, etc. 3. Pigment formation after cultures have been grown on agar for at least 10 days. 4. Morphological characters such as are transmitted in at least 2 subcultures. 16 SCHAMBERG, KOLMER, RINGER, AND RAIZISS 1. Round or coccus-shaped organisms; growing in irregular masses. 1. Liquefy gelatine slowly; coagulate milk tardily; no pig- ment: (a) Staphylococcus epidermidis albus of Welch. In- cludes the staphylococcus pyogenes albus. 2. Does not liguify gelatine; produces a yellow pigment: (a) Micrococcus cereus flavus. 2. Cocci which apparently divide in one plane, with more or less distinct gonococcoid shape. 1. Does not liquefy gelatine; does not coagulate milk; pro- duces no pigment, or cultures may become very slightly yellowish after prolonged cultivation: (a) Diplococcus albicans tardus. Includes the Diplo- coccus albicans tardissimus. 2. Does not liquefy gelatine; milk promptly coagulated; pro- duces no pigment: (a) Diplococcus X. 3. Liquifies gelatine; does not coagulate milk; produces no pigment : (a) Diplococcus albus liquefaciens. Includes the Micro- coccus albus liquefaciens. 4. Liquefies gelatine; does not coagulate milk; produces a citron yellow pigment : (a) Diplococcus citreus liquefaciens. 5. Liquefies gelatine ; does not coagulate milk ; produces a deep golden yellow pigment: (a) Diplococcus flavus liquefaciens. Includes the Mi- crococcus flavus liquefaciens. 6. Liquefies gelatine; does not coagulate milk; produces a pinkish color: (a) Diplococcus roseus. Diplococcus X. This organism which has particularly interested us, was found in 5 cases. The diplococci are irregular in shape, sometimes in fresh cultures the line of cleavage is quite distinct ; in older cultures they are oval and may occur singly, in pairs or in threes ; this organism is Gram positive. It liquefies gelatine in 5 to 7 days and causes prompt coagulation of milk. It grows very slowly, very feebly, but best on media containing glucose. Pigment is not produced, although one old culture has shown a slight yellowish tint in the water of condensation. The colonies in agar and gelatine may be round or oval ; their margins are sharp and well defined. It grows very feebly on potato and bouillon. So far we have not been able to classify this organism. RESEARCH STUDIES IN PSORIASIS 17 CULTURES ISOLATED FROM PSORIASIS LESIONS. Of (the) 24 cases studied, 57 cultures were isolated, representing 10 different species of cocci and 6 of bacilli, as follows: CULTURES Staphylococcus epidermidis albus (5 of these pyogenes albus) 22 Micrococcus cereus flavus 1 Micrococcus tetragenes 1 Micrococcus cinnabareus I 1 Diplococcus albicans tardus 6 Diplococcus (unknown diplococcus X) 5 Diplococcus albus liquefaciens . . . 3 Diplococcus citreus liquefaciens 1 Diplococcus flavus liquefaciens 5 Diplococcus roseus 3 Bacillus caudatum 1 Bacillus citreus 1 Bacillus nubilum 1 Bacillus rubium 1 Bacillus pseudo-diphtheria 2 Bacillus subtilis 3 STAPHYLOCOCCUS PYOGENES AND STAPHYLOCOCCUS EPIDERMIDIS ALBUS. Of considerable interest in this study was the attempted differen- tiation between Staphylococcus pyogenes albus and Staphylococcus epidermidis albus of Welch. From the practical standpoint, this is not so difficult when working with a culture isolated from a stitch abscess or acne pustule on one hand and with a culture isolated from the skin on the other, because the culture from the abscess will liquefy gelatine and coagulate milk sufficiently prompt to differentiate it from the skin coccus. But when working with cultures from psor- iasis lesions, it is found that they vary so much and shade one into the other, that differentiation is impossible and one is forced to classify arbitrarily as Staphylococcus pyogenes albus or epidermidis albus. In an attempt to diffenentiate still further between these cocci, we have tried their fermentative powers with various sugars in litmus agar and neutral red bouillon. As will be seen in the following table, the results were inconsistent and so similar that differentiation by this means is not possible. 18 SCHAMBERG, KOLMER, RINGER, AND RAIZISS TABLE I. ACID PRODUCTION WITH VARIOUS SUOABB BT STAPHYLOCOCCUS PYOOENES ALBUS AND STAPHYLOCOCCUS EPIDEBMIDIS ALBUS (WELCH). Name. Staph. Pyogenes Albus. NEUTBAL BED BOUILLON. Dex- Sac- Lac- Mai- Dex- Man- trose. charine. tose. tose. trin. nite. Staph. Epidermidis Albus. + TABLE II. ACID PRODUCTION WITH VABIOUS SUOAHS BY STAPHYIX>COCCUS PYOOEKEB ALBTTB AND STAPHYI/>COCCUS EPIDEBMIDIS Atsus (WELCH). Name. Staph. Pyogenes Albus LITMUS AGAR. Dex- Sac- Lac- charine. tose. Mal- tose. Dex- Man- trin. nite. Staph. Epid rmidis Albus ..... + + These results along with the behavior of the brganisms in gela- tine and milk indicate their close relationship, and for these reasons we have classified both as found on the skin, under the heading of one species. A similar study was applied to a few cultures of the diplococci. With these, however, differentiation is not so difficult according to pigment formation, growth in gelatine and in milk. It will be noted in the following tables that the reduction of neutral red bouillon RESEARCH STUDIES IN PSORIASIS 19 differed appreciably with different species, although such differentia- tion was not so well marked in litmus agar. TABLE III. ACID PRODUCTION WITH VAHIOUS SUGARS BY SKIN DIPLOCOCCI. NEUTRAL. RED BOUILLON. Dex- Sac- Lac- Mai- Dex- Man- Name, trose. charine. tose. tose. trin. nite. Diplo. albus liquefac + Diplo. albus liquefac Diplo. albicans tardus + + + Diplo. albicans tardus + + Diplo. flavus liquefac + Diplo. flavus liquefac + Diplo. flavus liquefac + Mic. cerus flavus + + Mic. tetragenes + + Diplo. roseus Diplococcus X + Diplococcus X TABLE IV. ACID PRODUCTION WITH VARIOUS SUGARS BY SKIN DIPLOCOCCI. LITMUS AGAR. Dex- Sac- Lac- Mai- Dex- Man- ' trose. charine.- tose. tose. trin. nite. Diplo. albus liquefac + + + + + Diplo. albus liquefac + t + Diplo. albicans tardus + + + Diplo. albicans tardus + + + Diplo. flavus liquefac + Diplo. flavus liquefac Diplo. flavus liquefac + -f- Mic. cerus flavus + Mic. tetragenes + + Diplo. roseus -f- Diplococcus X -f- Diplococcus X It is highly probable that these various cocci and diplococci are examples of "mutation," being derived from an original parent, but acquiring certain zymogenic and pathogenic properties as a result of environment, which they are able to transmit from generation to generation. ANAEROBIC CULTURES. As aerobic cultures failed to show the presence of any unusual organism in psoriasis, with the possible exception of the Diplococcus X, anaerobic cultures were made in nine cases. 20 SCHAMHKIU;, KOLMKR, HIXGKR, AND HAIZISS The media used included plain and glucose agar-agar and bouil- lon ; ascites kidney agar and ascites kidney serum bouillon as devised by Noguchi for the cultivation of Treponema pallidum. The pyrogallic acid method of reduction of oxygen and the use of paraffine oil were the principal methods used with the tube cul- tures. Scales, serum from the lesions after removal of the scales and after blistering with cantharides, and small pieces of the lesions them- selves, removed under ethyl chloride anaesthesia, were planted in the various media and examined at various intervals by the ordinary staining methods and with the ultra microscope. The following table gives the results. The cocci and diplocci belonged to the spe- cies already mentioned. Many cultures were grown for periods of time reaching four months, but in no instance were organisms found which could be regarded as unusual or especially noteworthy. TABLE V. ANAEROBIC CULTURES OF PSORIASIS. Name. Medium. Result. Date of inocu- lation B m. Scales and serum Ascites kidney agar and horse serum bouillon; glu- cose agar Staphyl. diplococci. 1-24-13 B m. Lesion .... Ascftes kidney agar; ascites kidney bouillon Cocci. 2-6-13 j^I( m. Lesion . . . Ascites kidney agar; plain bouillon; plain agar Cocci; diplococci. 2-11-13 M n. Scales and Ascites agar; serum bouil- lon; glucose agar Cocci; diplococci. 1-24-13 L c. Scales R k. Scales and Ascites kidney agar and serum kidney bouillon Ascites kidney agar and serum kidney bouillon Cocci; diplococci. Cocci; diplococci. 2-6-13 1-21-13 B m. Lesions . . . Ascites kidney agar and plain agar; glucose agar; glucose bouillon Cocci; slender bac. 4-5-13 B in. Emulsion Ascites kidney agar; serum kidney bouillon .... . Cocci; slender bac. 4-5-13 L e. Lesion ; se- rum of blister; scales Ascites plain agar; glucose m.. r ;ip 4-8-13 B m. Lesion; se- rum of blister; scales Ascites plain agar; glucose a trar . Sterile. 1-28-13 N w. lesion ; se- rum of blister; scales Ascites plain agar; glucose asrar Sterile. RESULTS WITH EXPERIMENTAL CULTURE MEDIA. With the assumption that an organism might be present in psoriatic lesions which would grow only in the presence of a peculiar medium, i.e., with the products of metabolism incident to the infec- tion, various culture media were prepared of the scales of psoriasis and used in culturing lesions. (a) Scale infusion: 40 grams of scales; 5 grains sodium chlor- ide; 1000 cc. water. Boiled for one hour; strained, cooled; titrated and made neutral to phenolphthalein. (b) Scale infusion: same as (a) plus 10 grams of Witte's pep- tone. (c) Scale infusion: same as (a) and (b) plus \% glucose. (d) Scale agar: same as (a) and (b) plus 2% agar-agar. (e) Glucose scale agar: same as (c) plus 2% agar-agar. (f) Culture media containing the amino-acids after digestion of the proteids by means of tryspin, were likewise tried with a number of cases. (g) The blood serum of an active case of psoriasis was likewise used as in the following: 1. Serum bouillon: serum one part; bouillon two parts. 2. Serum glucose bouillon in same proportions. 3. Serum glucose agar. 4. Serum kidney agar. These media were used in culturing two excised psoriatic lesions, but in neither case were organisms found not already isolated from other cases. RESULTS. When these various media were used for isolation or primary growth of cultures, it was found that cultures grew poorly on the peptoneless media, but the ultimate result and likewise the results in general with the remaining media were entirely similar to those obtained with the other well-known culture media. MOIST CHAMBER CULTIVATIONS. Early in the research this method of study was employed and a diplococcus was found with such' constancy that we thought it might bear an astiological relationship to psoriasis. Upon isolation and study of these diplococci it was found that they belonged for the most part, to the group described by Unna and Tommasoli. But their presence was so constant as to attract for a time our attention, especially so when controlled by preparations of other and similar cutaneous lesions. 22 SCHAMBKRG, KOLMER, RINGER, AND RAIZISS METHOD. This consisted in planting a small scale upon a sterile slide in a drop of sterile salt solution or glucose bouillon, covering it with a sterilized cover slip and partially sealing with paraffine. The slide was then placed in an improvised Plaut moist chamber, which is so designed that slides are placed over a small amount of water held in a shallow depression of the dish. In this way the preparation is kept in a constantly moist atmosphere. We grew our prepara- tions both in the incubator and at room temperature. In all, eleven cases of psoriasis were so studied. All yielded a growth after three or four days' incubation, except in one case. Groups of diplococci were found clustered about the epithelial cells. In no instance were bacilli found. Seven controls were likewise cultured; two cases of seborrhoeic dermatitis ; three cases of squamous eczema ; a case of lupus erythe- matosus and one case of pityriasis rosea. All yielded cultures of staphylococci except in two cases of squamous eczema, in which staphylococci and Bacillus subtilis were found and in the case of pityriasis rosea, in which a diptheria-like bacillus was obtained. RESEARCHES WITH THE ULTEAMICROSCOPE. With the idea that the ultramicroscope might show the presence of an organism not readily stained and not growing artificially, we have studied the serum from lesions of a large number of patients suffering with psoriasis and various other skin diseases. METHOD. After cleansing an area with xylol and alcohol, the superficial layers of epidermis were removed by means of a special scarifier down to the corium, endeavoring to produce the least pos- sible amount of bleeding. A drop of sterile solution was then placed upon a cleansed slide and some of the serum secretion from the de- nuded lesion added and mixed. A cover slide was then adjusted and the preparation examined. RESULTS. The first patient so studied had an extensive eruption with well-defined margins to the lesions. Preparations showed from 3 to 6 slender, actively motile bacillary bodies, about !/4 micron in diameter and from 8 to 16 microns in length. Repeated examina- tions of this patient showed similar organisms. In all, 19 cases of psoriasis have been examined and these bacillary bodies found in all but two. Prolonged search is sometimes necessary to discover these bodies, especially in mild cases. In addition to the above form of parasite, a shorter, thicker and less actively motile form was sometimes seen. In some instances, these bacillary bodies have a beaded appearance. RESEARCH STUDIES IN PSORIASIS 23 We have examined fresh blood by this method, to determine whether the bodies found were composed of fibrin. Fibrin is de- posited later, after the preparation is at least 15 to 30 minutes or an hour old. The filaments are quite fine, usually attached to the corpuscles, are less motile and may be of considerable length. The following diseases other than psoriasis were examined in like manner for the presence of these bodies : Seborrhoeic dermatitis ; 8 cases ; similar bodies were found in 1 case. Acne rosacea ; 1 case ; negative. Squamous eczema ; 4 cases ; negative in all but one. Lichen planus ; 1 case ; negative. Dysidrosis ; 1 case ; negative. Tinea circinata ; 1 case ; negative. Scabies ; 1 case ; negative. Syphilis, tertiary; 1 case; positive. Of these 18 cases, all were negative except three. The prepara- tions were made in exactly the same manner in all; the chances for the formation of fibrin were equal ; no claim of specific pathogenicity is warranted for these bodies at the present time; their constancy in psoriasis and their rarity in the other dermatoses examined, war- rants us, we believe, in placing the observation on record. BLOOD CULTURES IN PSORIASIS. Blood cultures were made of 10 cases. Most of these were acute and extensive cases and were cultured during the developmental stage of the eruption, with the purpose of determining if an organism could be isolated from the blood stream, that was responsible for the development of new lesions. METHOD. An all glass Burroughs and Welcome syringe was thoroughly sterilized and from 3 to 5 cc. of blood was removed by puncture of the median cephalic vein at the elbow under all aseptic precautions and after thorough sterilization of the skin. Blood was then planted directly in flasks of culture media and grown for at least ten days, with frequent subinoculations and examinations for bacterial growth. Plain glucose bouillon ; plain and glucose serum and ascites bouillon and ascites kidney bouillon were employed. RESULTS. As will be seen in the accompanying table, the results were negative with two exceptions. In one case we found in pure culture the unknown Diplococcus X and in another a short, solid, Gram positive bacillus, later identified as Bacillus pseudo-diphtheria. Many cases had dense lesions about the elbow, so that it may have 24 SCHAMBKHC;, KOLMKR, RINGKR, AND RAIZISS been impossible to avoid contamination with the deeper layers of the epiderm. In general, therefore, blood cultures have not so far re- vealed to us the presence of a bactersemia in psoriasis, either causa- tive or secondary. TABLE VI. BIOOD CULTURES IN PSORIASIS. Name. Date. Result L e 1-11-13 Sterile N n 1-24-13 Diplococcus X B m 1-26-13 Sterile L f 1-28-13 Sterile 9-22-12 Pseudo-diphtheria bacillus 2-3-13 Sterile 3-24-13 Sterile 4-17-13 Sterile (in hosp. at present) 4-4-13 Sterile (in hosp. at present) 5-4-13 Sterile BLISTER SEEUM. By means of raising a blister over a psoriastic patch with can- tharidal collodion, serum was secured which, as it were, filtered di- rectly through the involved area of skin. Blisters of the size of a silver dollar were raised quite readily in active cases of psoriasis and the serum then cultured, v examined with the ultra microscope and stained preparations examined for the bodies described by Lip- schutz. JErobic and anaerobic cultures in plain and glucose agar, plain and glucose bouillon, ascites bouillon and agar and ascites kidney bouillon and agar, yielded sterile cultures. These results were some- what surprising, as no effort was made to cleanse the patch before applying the blistering collodion. Examination by means of the ultramicroscope showed the de- velopment of fibrils of fibrin but nothing else worthy of mention. BACTERIAL VACCINES (BACTERINS) ix PSORIASIS. Having isolated a number of different species of organisms from psoriatic lesions, we considered the advisability of preparing and ad- ministering a vaccine. The supposedly common skin organisms may represent the cause as operative under special metabolic condi- tions and, therefore, their vaccine may show this relationship and be of some therapeutic value. Two different vaccines were prepared of pure cultures of organ- isms recovered from psoriasis lesions. The first, prepared on No- RESEARCH STUDIES IN PSORIASIS 25 vember 4th, consisted of 6 different cultures of diplococci from 6 different cases. The organisms were as follows: Diplo-tardus albicans. Diplo-albus liquefaciens. Diplo-flavus liquefaciens. Unknown diplococci (X). Diplo-citreus liquefaciens. The second vaccine was prepared on Feb. 19, 1913, of 24 cultures including : Diplo-tardus albicans. Diplo-flavus liquefaciens. Diplo-citreus liquefaciens. Three unknown diplococci (X). Micrococcus cereus flavus. Micrococcus tetragenes. Micrococcus flavus. Bacillus pseudo-diphtheria. Bacillus ferrugineum. Bacillus subtilis. Unknown coccus. The vaccines were prepared in the usual manner, sterilization being effected by heating to 58 C. for one hour. The dose was from 3 to 5 hundred million cocci. RESULTS. A number of psoriasis patients were treated with the above vaccines, but the results were indifferent and inconclusive. While negative results are not conclusive, yet the failure of vac- cines to aid in this chronic affection, combined with the negative results of complement-fixation reactions to detect the presence of an antibody for these organisms in the nature of an amboceptor, is evi- dence against their being active participants in the cause of psoriasis. INOCULATION EXPERIMENTS. The successful inoculation of the lower animals with psoriasis would facilitate research to a marked degree and above all would afford more conclusive evidence regarding the nature of the disease. Accordingly we have made several attempts during the past year to infect the Macacus rhesus with psoriasis, using scales, serum, im- plantation with actual buttons of psoriatic skin and Jntraperitoneal injection of defibrinated blood of an active case of psoriasis. The method of skin implantation was especially hopeful of posi- tive results if a parasite were the cause of psoriasis, because under the conditions of the experiment the infectious agent was certainly 26 SCHAMBERG, KOLMER, RIXGER, AND RAIZISS transplanted, the only question being the subsequent vitality of the "button" and the question of proper soil. Having found that cases of psoriasis were likely to improve under a low protein diet or, conversely, were apt to grow worse under a high protein diet, we kept a monkey on a diet of milk, plasmon and peanuts for two weeks until 2 gin. of nitrogen were being eliminated in 24 hours. A "button" of psoriatic skin was then implanted, which healed readily, but did not show any evidence of having transmitted psoriasis three months after the inoculation. Brief protocols of these experiments are as follows: Experiment 1, Jan. 4, 1913. Monkey. Macacos rhesus. Area on back shaved and cleansed ; skin abraded and inoculated with bloody scrum removed from beneath the scales of a well-marked case of psoriasis. Result: abrasions healed; no resultant eruption. Experiment 2, Jan 6, 1918. Monkey. Macacus rhesus. Area on back shaved and cleansed. Under ethyl chloride spray, a button of skin about 6 mm. in width was removed with a Keyes' skin punch. A similarly sized button was removed from the margin of a well- marked patch of psoriasis and implanted in the monkey. A simple protective dressing was applied. Result : the skin implantation was successful and healing occurred without infection, but there was no evidence of psoriasis resulting. Experiment 3, Jan. 22, 1913. Monkey. Macacus rhesus. Area on back shaved and cleansed and then lightly scarified as in the operation of vaccination. Secretions and scales from a lesion of psoriasis were then rubbed in quite thoroughly. Result : healing ; no evidence of psoriasis. Experiment 4, April 4, 1913. Monkey. Macacus rhesus. Kept on a diet of milk, plasmon and peanuts for two weeks. Was elim- inating in urine, according to an analysis, 2 gm. of nitrogen in 24 hours. Area of back prepared and implanted with a button of skin removed from a psoriasis plaque. Animal kept on same diet. Result: too early for definite opinion, but probably negative. Experiment 5, May 27, 1913. Monkey. Macacus rhesus. Re- ceived an intraperitoneal injection of 6 cc. of defibrinated blood re- moved from a case of psoriasis. The animal showed no ill-effects and up to five weeks later, had shown no evidences of psoriasis. General health excellent. While it is .necessary to wait even a longer period of time before a negative result can be recorded for some of these experiments, yet as they are, they indicate quite conclusively the difficulty of trans- mitting this disease (further experiments in inoculation will be made in the near future). RESEARCH STUDIES IN PSORIASIS 27 SUMMARY. 1. Nine of 48 cases of psoriasis, 18.7% yielded positive Wasser- mann reactions, using an alcoholic extract of luetic liver as antigen. With antigens of cholesternized alcoholic extracts of human and beef heart, over 28% of 22 cases reacted positively. From a clinical study of the patients whose serums were studied, the positive tests cannot all be attributed to syphilis, although this might be true of a few of them ; on the other hand, some significance must be attached to them, which future research alone can reveal. 2. Using for antigens aqueous and alcoholic extracts of psoriasis scales and of a large number of cultures of organisms isolated from lesions, complement fixation was not found to occur with 10 sera from active cases of psoriasis. These results would indicate that either the true antigen was not present in the extracts of scales and cul- tures used, or that the psoriasis antibody, if it exists, was not present in the sera in sufficient amount to inactivate complement with the extracts used in this study. 3. Sixteen different organisms were isolated from 57 cultures from 24 cases of psoriasis. No organism was found which could be regarded as bearing an aetiological relationship to the disease. 4. An unidentified diplococcus "X" was found in 5 psoriatic lesions and in 1 blood culture and is deserving of further study. 5. The use of anaerobic methods and special culture media, com- posed of the scales and secretions of psoriasis, did not show the pres- ence of any special parasite. 6. Numerous growths of scales in moist chambers showed the presence of diplococci, but no unusual organism or fungus. 7. Investigation with the ultramicroscope discovered the pres- ence of a motile bacillary body in 17 out of 19 cases of psoriasis. In 18 other dermatoses these were found in 3 instances. These bodies are being further studied. 8. Cultures and microscopical examinations of fluid secured by blister over psoriasis lesions, yielded negative results. 9. Vaccine treatment carried out with vaccines made from a large number of different species of organisms found in psoriasis lesions, yielded indifferent and inconclusive results. 10. Inoculation experiments on monkeys, including the implanta- tion of buttons of psoriasis skin, scales, serum and defibrinated blood, were negative in one to six months after inoculation. PROTEIN METABOLISM IN PSORIASIS. TABLE OF CONTENTS. Earlier Researches in the Metabolism of Psoriatics 31 The Principles of General Metabolism 32 Principles of Protein Metabolism 34 The Care of the Patients 36 Food 37 Methods of Analyses 38 Patient No. 3 38 Summary of Results Obtained in the Study of Patient No. 3 47 Patient No. 4 69 Summary of Results Obtained in the Study of Patient No. 4 77 Patient No. 5 79 Summary of Results Obtained in the Study of Patient No. 5 88 Patient No. 8 88 Summary of Results Obtained in the Study of Patient No. 8 98 Patient No. 9 98 Patient No. 7 109 Discussion of Results 120 The Value of the Eliminated Nitrogen in the Interpretation of Processes of Metabolism 121 The Minimal Protein Requirements and the Minimal Protein Catabolism 122 Nitrogen Retention 125 Nitrogen Retention in Normal Adult Individuals 125 Nitrogen Retention in Growing and Convalescent Individuals 127 Nitrogen Retention in Psoriasis 128 Influence of a Low Protein Diet on the Course of Psoriasis 131 The Relationship Between Retained Nitrogen and Gain in Body Weight 133 Resum of the Clinical Results 134 Summary and Conclusions 137 Bibliography 139 RESEARCH STUDIES IN PSORIASIS 31 EARLIER RESEARCHES IN THE METABOLISM OF PSORIATICS. THEORIES which hold disturbances of metabolism responsible for certain diseases of the skin can be traced back to the early history of dermatology. Many interesting contributions have been made by French authors, presenting theories which connect va- rious cutaneous affections with disturbances in uric acid metabolism. Some of these views are held by certain clinicians at the present time. And yet these theories have no experimental foundation and are not in harmony with our modern knowledge of uric acid metab- olism. Of course there cannot be excluded the possibility that there may exist derangements in the uric acid metabolism of patients afflicted with diseases of the skin and, ultimately, perhaps some truth may be found in the teachings of the early French school. Thus far we possess no facts indicating the existence of such derangements and the speculative theories about "arthritism" or "uric acid diatheses," under discussion for nearly half a century, still await experimental demonstration. In the last two decades ^there have appeared a great number of contributions on the relationship between disturbed metabolism and skin diseases. Almost all of them are based on clinical observations, with an occasional analysis of the patient's urine. Various internal diseases were then assigned as the cause of the skin affection under investigation. If an examination of the urine showed an accidental increase of one of the urinary constituents, the cause of the skin dis- ease was ascribed to that particular condition. For instance, a tem- porary increase in the daily output of urea, or a temporary de- crease, was associated with the causation of the skin eruptions, whereas the real reason for these changes in the urea output was doubtless the diet ; in one case it was richer in nitrogen, in the other case poorer. In many instances auto-intoxication of the body was regarded as giving rise to diseases of the skin and was expressed in the abnor- mal quantitative output of different organic constituents of the urine. In general, those works were largely of a clinical character and were practically worthless as far as throwing any real light on the metabolism of skin diseases was concerned. Recently there have appeared several communications dealing with the metabolism of psoriatics. One of these deals with the nitro- gen and sulphur metabolism, 1 and seems to have been carried out in a very painstaking and accurate manner. The length of the ex- 32 SCHAMBERG, KOLMER, RINGER, AXIJ RAIZISS jK-rinu nt, liowcvcr, was too short to permit of any definite conclu- sions. The entire experiment lusted 14 days and was divided into 4 periods, 3 of four days each and 1 of two days. During these periods different diets were given containing varying amounts of nitrogen. These periods, in our estimation, are too brief to permit of any definite deductions with regard to the nature of the protein metabolism in psoriatics. In inaugurating a research on the metabolism of psoriatics, it seemed to us essential to study the protein metabolism first. We did this for several reasons. Firstly, because the different theories that were evolved in the early literature of psoriasis centered mainly around the question of disturbed protein catabolism. Secondly, be- cause the study of protein metabolism lends itself to very accurate investigations, because of the ease with which the nitrogen balances can be studied. Thirdly, because protein metabolism in the normal is most thoroughly understood and gives us a fair basis for com- parison. Before presenting the results of our experiments, however, we have considered it advisable to briefly review the general principles that govern the general and protein metabolism of normal individuals. THE PRINCIPLES OF GENERAL METABOLISM. By metabolism, we understand all the processes, chemical, physical and bio- logical, that are involved in the utilization, absorption and assimilation of food stuffs; the transformations that these undergo before, during and after their assimilation, and the elaboration and excretion of all their end products (waste products). All phenomena of living cells, whether motor, reproductive or sen- sory, are very closely associated with processes of metabolism. The chemical processes of metabolism are divided into two phases: 1. Anabolism: the upbuilding of substances or tissues. 2. Catabolism : the breaking down of complex substances into simpler 'ones. All the foodstuffs of the body, with the exception of the inorganic salts, whose function it is to maintain proper osmotic conditions in the cells and fluids of the body, are such as to be able to undergo processes of oxidation (combustion), which processes are exothermic, i.e., are associated with the formation of heat, The principal foodstuffs, all of which are capable of yielding energy, are divided' into three classes: 1. Carbohydrates. 2. Fats. 3. Proteins. The carbohydrates and fats have as their constituents carbon, hydrogen and oxygen, chemically united in definite and peculiar forms. In normal individuals these two foodstuffs undergo complete oxidation. All the carbon becomes oxi- dized to carbon dioxide and all the hydrogen becomes oxidized to water. The carbon dioxide thus formed is eliminated mainly through the respiratory tract and the water formed is eliminated through the kidneys, by perspiration, or in the moisture of the expired air. The protein molecule is composed of carbon, hydrogen, oxygen, nitrogen and RESEARCH STUDIES IN PSORIASIS 33 sulphur. The proteins that form the nuclear elements of cells contain also phos- phorus. It is at once evident that while the carbon and hydrogen that are ex- creted as waste or end products in animal metabolism may find their origin in carbohydrate, fat or protein, the nitrogen, and to a certain extent also the sulphur and phosphorus, have only one source of origin the proteins. After the protein is catabolized in the body, the nitrogen is eliminated in the form of urea, ammonia, uric acid, purin and other bodies. Most of the nitrogenous waste products are excreted through the kidneys and a small amount passes out with the faeces and perspiration. In the faeces we may find some unresorbed proteins which never played a role in metabolism. We shall have occasion later to discuss this subject in greater detail. Since the average protein contains about 16% nitrogen, we are enabled, by determining the nitrogen in the excreta and multiplying its value by 6.25, to find the amount of protein that was catabolized in the animal organism. Voit, who has played the most important role in the framing of our present conceptions of protein metabolism, was the first to recognize the relationship between urinary nitrogen and protein metabolism. The proteins are very complicated condensation products of about 16 different" amino-acids which, in the process of digestion, suffer hydrolysis, which causes a disruption of the molecule into its individual component amino-acids.* Each amino-acid has its own life history in intermediary metabolism. Here we can only refer to some of the works which deal with this subject in greater detail.^ Later, we shall return to the subject of nitrogenous, sulphur and phos- phorus end products of protein metabolism. HEAT FORMATION. Just as in the combustion of carbon and hydrogen outside the animal body, the process is associated with the formation of heat, so in the animal body, the combustion of these substances is accompanied by the evolution of heat, which serves to maintain the body temperature. The amount of heat produced depends entirely upon the amount of material burnt and the total metabolism of the cells of the body is determined by its requirements for kinetic energy and by the amount of heat given off to the surrounding atmosphere. The heat produced by an individual is measured in terms of calories. One calorie is the equivalent of the amount of heat required to raise one liter of water from to 1 C. The following amounts of heat are generated in the animal body in the com- bustion of one gram of the different foodstuffs: Starch 4.10 calories Cane sugar 3.96 " Glucose 3.75 " Animal fat 9.3 " Protein 4.1 " The total amount of heat produced by a fasting normal individual, in a state of complete rest, at a temperature corresponding to that of his body (to prevent loss of heat by radiation and conduction) is called the "basal heat production." * Amino-acids are fatty acids in which one hydrogen atom of the alkyl radical is replaced by an amino radical (NH 2 ) e.g., CH 3 COOH ) j CH 2 NH 2 COOH Acetic acid l" "j Glycocoll or amino-acetic acid CH 2 COOH -\ f CHNH 2 COOH CH 2 COOH f ^ CH 2 COOH Succinic acid 1 (^ Aspartic acid or amino-succinic acid. IM SCHAMHKKG, KOLMKR, RINGER, AND RAI/ISS This represents the lowest degree of nietabolisni compatible witli life. In a huinap individual this niuounts to about 25 calories per kg. of body weight per -21 hours. The normal individual cannot however, get along on this low basis, for the normal individual constantly finds himself in an atmosphere where the temperature is much lower than that of his body. This results in heat being constantly lost by the body by radiation and conduction to the surrounding space. To maintain the body temperature, therefore, a greater amount of heat has to be produced than is necessary for the "basal maintenance of life." From the aforesaid, it be- comes evident that to a very .large extent, the total heat production must have some relationship to the total area of body surface. Rubner3 was the first to call attention to this. The details of this were worked out by E. Voit 4 in a very beautiful way. The results of his experiments are here tabulated: Calories. Species (5) Weight in kg. Per kg. Per square meter of body surface. Pig 128.0 19.1 i()78 Man 64.3 32.1 1042 Dog 15.2 51.5 1039 Mouse 0.018 212.0 1188 This table shows to what a remarkable extent the amount of heat produced per square meter of body surface is constant for different animals and different sizes. When, however, we come to consider the amount of heat produced per kg. of body weight, we learn something that is of fundamental importance, namely, that with the diminution of the weight of the individual, there is a constant increase in the heat production per kg. of body weight. This must always be borne in mind in establishing dietaries. The small man must always be allowed a larger amount of food in proportion to his weight than a large man. This is brought out very clearly in the researches of Carnerer**: Calories per Calories per sq. meter kg. per day. of surface per day. lit i i > i Child, 1 month 91 1 .'.M Dwarf (6 kg. rest) 83 1231 Child, 2 years ' 81 1231 Child, 10 years 60 1389 Child, 14 years 52 1452 Adult (average work) . . . '. 42 1390 PRINCIPLES OF PROTEIN METABOLISM. If we feed an. animal with a sufficient amount of carbohydrates, fats and protein and compare the nitrogen in the food with the amount of nitrogen in the excreta (urine, faeces and perspiration) and find that the two balance, we consider the animal in a state of nitrogenous equilibrium, i.e., the animal is receiving as much nitrogen in the protein of its food as it is metabolizing and eliminating in the excreta. If the animal is found to eliminate less nitrogen than is ingested, it is evident that the animal is storing nitrogenous material. We consider the animal to be in a state of positive nitrogen balance. This state usually occurs in the growing child, in patients convalescent from a wasting disease and in the athlete in training. On the other hand, if the nitrogen in the excreta is found to be greater than in the ingested food, it is clear that the animal is losing its own body protein. We consider that animal to be in a state of negative nitrogen balance. This state usually occurs in starvation, undernutrition, in RESEARCH STUDIES IN PSORIASIS 35 persons suffering from wasting diseases like carcinoma, tuberculosis, fever and other forms of toxaemia. If the quantity of protein intake, in an individual who maintains nitrogenous equilibrium, is steadily increased, the nitrogen elimination of that individual will increase correspondingly, until an equilibrium is struck on a higher level. This adjustment does not take place at once, but in the course of two, three or some- times four days. During this period of adjustment, a considerable amount of nitrogen is retained in the body. On the other hand, if the nitrogen intake is diminished, nitrogen equilibrium becomes established on a lower level with the opposite effect, i.e., during the first few days more nitrogen is eliminated than is ingested (see page 74). Although it is possible to keep an individual in nitrogenous equilibrium on any level up to the point of the maximum digestive and resorptive capacities of that individual for protein, it is found experimentally that there is a low limit of protein below which it is impossible to maintain nitrogenous equilibrium and below which we cannot reduce the protein metabolism. Any attempt to keep an indi- vidual on a protein diet below that level will result in a negative nitrogen balance, i.e., a loss of protein from the tissues. Ihis low protein level was recognized by Rubner" as the "wear and tear" quota, which represents the amount of protein that goes to replace the nitrogenous material that is actually broken down during the activities of the cells in their life processes. In Voit's early researchesS he showed that nitrogenous equilibrium may be maintained on a diet consisting of protein alone. In this case very large quantities of protein are catabolized, first, to cover the "wear and tear" quota and, second, to cover the dynamic requirements of the body. If non-protein foodstuffs, as car- bohydrates and fats, were added to the diet, nitrogenous equilibrium was found to be maintained on a much lower level. The carbohydrates and fats thus exert a sparing influence on the protein metabolism. The sparing influence of car- bohydrates on the protein metabolism in man was first demonstrated by Lusk while working in Voit's laboratory at Munich^. This subject was further studied by Rubner,lo Landergren, 11 Cathcarti2 and others, who have shown that carbohydrates may even reduce the starvation re- quirements of protein. All these experiments show very plainly that within very wide limits the protein metabolism may be influenced by the amounts of carbohydrates and pro- teins in the food. By various arrangements of the quantities of these foodstuffs, it was shown to be possible to maintain nitrogenous equilibrium at any arbitrary level above the wear and tear quota. The question then naturally presented itself: What shall be considered a physiological amount of protein in one's diet? This question has absorbed the minds of a great many investigators and a tre- mendous amount of material, experimental and statistical, has been collected. Although this discussion stimulated the performance of a great many experiments that revealed to us the laws that govern protein metabolism in health and disease, the original question is as open now as it was forty years ago when it was first raised. On the basis of a great many experiments, Voit suggested that for an adult doing a moderate amount of work, a diet containing 118 grams of protein (which contains 17.28 grams of nitrogen) with a total food supply of 30o5 calories was required. This served as a starting point of one of the most heated debates recorded in the annals of physiological literature. It was soon recognized that the great physiological importance of protein in the diet was due to its ability to "repair body tissues," and the discussion cen- tered around the question: What constitutes a "repair quota" or "wear and tear" quota? Voit's protein quota of 118 grams of protein = 17.28 grams of nitrogen for an individual of 75 kg. of body weight, allows approximately 1.5 grams of protein 3(> SCHAMBKHG, KOLMKK, RINGKU, AND RAI/ISS or 0.J gram of nitrogen JUT kg. of body weight. A great many physiologists con- sidered this excessive, especially since it was demonstrated that other races maintain nitrogenous equilibrium on much lower levels. For example, it was shown that the Italian laborer does not consume more than about 30 grams of protein = l.H grams of nitrogen and that the Japanese coolies get along on a diet of rice containing not more than i?5 grams of protein = 4.0 grams of nitrogen.13 These figures, however, must not be taken by themselves, but in relationship to the aver- age body weight of the individual experimented upon. Thus the average Japanese, who lives on a i gram nitrogen regime weighs about one-half as much as the average husky Ciennan who lives on the Voit protein standard. During the past few years, however, very satisfactory evidence has been obtained in this country and abroad, which shows that men who come from races which are habitually large protein consumers can maintain for long periods of time, their well-being, nitrog- enous equilibrium and body weight, on just one-half of the Voit regime.** In the discussion of this problem, a very interesting series of observations was brought to light and one that is very closely related to the main problem of our present paper. These observations deal with the influence of a high protein diet on tissue formation and growth. Mention was previously made (see page 35) of the fact that in changing the diet from one level to another, the body required several days to aecomodate itself to the new diet, before nitrogenous equilibrium was again established. In changing the diet from a low to a high protein level, it takes two or three days before the eliminated nitrogenous waste will equal the nitrogenous intake. During this period of adjustment, nitrogenous material is retained in the system. The great important question is: what becomes of it? Is it retained only temporarily or does it become part of the body cells? The scope of this question was further broadened when it was shownis that the protein metabolism can be reduced to a very low level by feeding very large quantities of carbohydrates. It was found that if the protein intake remained the same and the carbohydrate supply was suddenly raised, there was a marked diminution in the nitrogen output in the urine. The result was a considerable retention of nitrogen in the body.ifi The question of the formation of "tissue" by the stored nitrogen now became vital. Retention of nitrogen in the growing individual and the convalescent, has long been recognized. We explain it by the generative and regenerative ten- dencies of living cells. In the case of the former, it was associated with growth; in the case of the latter, with the restorative processes of the cells. But it was found very difficult to explain the significance of the retention of nitrogen in a healthy, well-nourished adult. The problem is one of great practical importance and briefly stated, is this: Do we deal with a retention of nitrogen that is deposited in the cells of the body in an unorganized form of protein, which although it is stored in the cells, does not become a vital functionating part of the cells and does not add to the cells' efficiency any more than does a similar amount of fat or glycogen, or does this retention of nitrogen mean an increase in the living pro- toplasm of the cells, associated with increased protoplasmic physiological effi- ciency? The economic importance of this question cannot fail to be appreciated. Since the results of our investigation are very intimately connected with this problem, we shall postpone the further discussion of it until after the presentation of our experimental studies. THE CARE OF THE PATIENTS. All the experiments were performed under the strictest rulings that are necessary for exact metabolism studies. The patients were kept in private rooms at the Polyclinic Hos- pital, which were located on the same floor as the Laboratory. The RESEARCH STUDIES IN PSORIASIS 37 patients were under the nursing care of Miss Julia Dorsey, whose valuable cooperation we take pleasure in acknowledging. In each room there was a set of utensils for the quantitative collection of the urine and faeces. The urine was preserved with toluol and kept in glass-stoppered bottles. Each daily period was closed at the same hour of the morning. The fasces were transferred to the labora- tory as soon as passed. The weekly periods were marked off in the fagces by the administration of charcoal. Most of the patients spent the entire day in their respective rooms ; some were permitted to go out once a day for a 30 to 45 minute walk. In each case the patient had to report to the nurse. Most of the patients were of an intelligent class, who understood in a general way the purpose of our studies and were perfectly will- ing to cooperate with us. Special attention was paid to the quantitative collection of urine, especially in the female patients. They were instructed to void the urine before defalcation, in order to avoid any possibility of loss while straining. FOOD. One portion of the laboratory was converted into a kitchen. All of the food was prepared by the nurse and was weighed and re- corded by one of the investigators before it was taken to the pa- tients' rooms. The patients were required to eat all that was given to them. If, however, any food was not eaten by the patient, it was brought back to the laboratory and weighed and subtracted from the recorded amount. (This, however, happened in a few instances only.) Samples were taken for analysis of all the foods that were pre- pared. They were analyzed for their nitrogen content and, in many cases, the sulphur and phosphorus were also determined. Of the foods prepared outside the laboratory, as bread, large enough loaves were obtained to last for several days or a week. An analysis was made of each individual loaf. Butter was analyzed at the begin- ning of the investigation and was found to contain such a small quantity of nitrogen and the individual samples varied to such a small extent, that it was not deemed advisable to continue analyzing it and we accepted the average figure obtained, namely, 0.12%, as the amount of nitrogen in butter. Foods eaten raw, as lettuce, pears, oranges, etc., were not analyzed in our laboratory. The figures in "Bulletin 28 of the U. S. US SCHAMBKKG. KOLMKH, 1UNGKR, AND KAI/ISS Di-partnu-nt of Agriculture," 17 are very accurate and we used them as the basis of our calculations. MKTHODS OF ANALYSES. The totnl nitrogen in the urine and food was determined by Kjeldahl. Urea by Benedict's latest method. Ammonia by Folin's method. Uric acid by Folin's method. Creatinin by Folin's method. In these analyses we were assisted by E. M. Frankel and H. Dubin. In the charts are recorded the daily analyses of the urine, the nitrogen content of the faeces, the nitrogen in the food, the daily nitrogen balance and the patient's weight.* Under "diet," we have given in detail the composition and character of the food of the first day of each period. The variation from day to day within a given period was very slight ; the main difference was in the vege- tables. For the sake of convenience, we shall discuss the case of pa- tient Xo. 3 first. PATIENT No. 3. B. L. FAMILY HISTORY. Father died at age of 42; cause of death unknown. Mother living, aged 39 years. No psoriasis in parents nor in two sisters and three brothers. PERSONAL HISTORY. Patient #ged 18 years, was born in Russia. Had measles and diphtheria as a child; she has always been thin and sickly. At the age of 13, the patient first developed psoriasis. In 1909, while in Russia, she was treated in a hospital for her psoriasis, remaining in the institution 4 weeks; in 1911, she was again under treatment in the same hospital for 8 weeks. PRESENT CONDITION. The patient was admitted to the Polyclinic Hospital on Nov. 25, 1912, with an exceedingly severe and widespread eruption. She could scarcely walk because of the painful tension of the skin; the use of the anus was also considerably impaired. On admission, the patient exhibited a most extensive eruption, which was well nigh universal, save for the partial involvement of the face and extremities and partial exemption of the upper part of the back and chest. The eruption upon the trunk was of a rather superficial character; the scaling was most profuse, leading, during the first few days of her hospital sojourn, to the exfoliation of a quart Mason jarfull of lameller scales per day. The skin was dry, tense and here and there fissured, necessitating the use of vaseline as a lubricant to relieve distress and pain. Upon the arms and legs there were large, intensely red plaques, which were markedly thickened and elevated above the level of the skin. On admission, * The patients were weighed every day at ! P.M. The clothing was weighed and its weight subtracted. In the charts, the average weights for the week are given. PLATE XXVIII. To Illustrate Article on Research Studies in Psoriasis, bv DBS. SCHAMBERG, Koi.MER, RINGER and RAIZISS. G< O &* OS ft C AH ft] f if THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. PLATE XXIX. To Illustrate Article on Research Studies in Psoriasis, bv DRS. SCHAMBERG, KoLMER, RIXGER and RAIZISS. rf^ bi. THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. RESEARCH STUDIES IN PSORIASIS the eruption on the chest was limited by a sharp line of demarcation whose upper border was below the nipples anteriorly and extended across the shoulder blades posteriorly. The chest, abdomen and back were the seats of a confluent area of psoriasis, somewhat suggesting in appearance a dermatitis exfoliativa. The scalp was diffusely involved and covered with scales. This patient remained in the hospital for a period of five months. CLINICAL CONDITION IN .RELATION TO THE DIETARY. Admitted Nov. 25, 1913. Nov. 27th to Dec. 10th Dec. 18th to Jan. 8th Jan. 9th to Jan. 21st Jan. 22nd to March 3rd High Kitrogen Diet 18.63 gm. per day. Low Kitrogen Diet 6.89 gm. per day. High Nitrogen Diet 20.54 gm. per day. Low Nitrogen Diet 6 to 7 gm. per day. Notes taken from record charts. Dec. 2nd: "New papules have appeared on the upper part of the legs and arms." Dec. 6th: "New papules upon the neck and upon the clear areas on the back." Dec. 8th: "The eruption is spreading rapidly on the face." Dec. 25th: "The skin is much smoother and paler." .Jan. 7th: "The skin is much paler in color and continuing to improve. The scales are finer and less bulky." Jan. 23rd: "The feet are very red and the skin is much more inflamed on the lower part of the body." Jan. 28th: "The skin of the chest and upper portions of the arms and neck is paler." Feb. 1st: "Pronounced improvement of the skin over buttocks, thighs and legs." Feb. 5th: "Entire body much paler and shows considerable improvement." Feb. 14th: "Skin quite pale over greater part of body." Feb. 18th: "Skin is smooth and white over upper part of body and neck." Feb. 24th: "There have been no scales to collect for 12 days." March 3rd: "Skin over greater part of body free of eruption." During the period of Nov. 27 to Dec. 3, 1912 (Period I), the patient was placed on a diet consisting of an average of 18.63 grams of nitrogen per day 0.45 grams of nitrogen per kg. of body weight. The total amount of nitrogen received with the food for the entire weekly period was 130.4 grams. During this period, the pa- tient eliminated in the urine and faeces 86.29 grams, which means that 44.11 grams of nitrogen were retained in the body during the weekly period, or 6.30 grams per day. During the second week (Period 2), the patient was kept on approximately the same diet, with the result that 136.03 grams of nitrogen were ingested. The amount of nitrogen eliminated in the 40 SriIAMBKlUJ, KOLMKH. KINGKH, AND HAI/ISS urine and f.-eces during the corresponding period was 97.39 grams, which means that 38.(>4 grams of nitrogen were retained in the body 5.52 grams per day. The patient's gain in weight above the previous week was 0.52 kg. It is at once evident that this patient presents a peculiar irregu- larity in regard to her nitrogen metabolism. A person of her weight on this diet should have established nitrogenous equilibrium long be- fore the end of the two periods. It may be argued that 45 to 49 calories per kg. of body weight, which the patient received in her diet, was too high a caloric supply and is, perhaps, responsible 'for the nitrogen retention. But this objection is not valid, because the calories are calculated upon the basis of food that is ingested; we do not take into consideration the amount that passes through the intestinal tract and comes out in. the faeces, without having ever been resorbed and without having yielded any energy to the body. Rubner 18 calculates the average fa?ces of a well-fed individual to con- tain 8 to 10% of the gross caloric supply which, in establishing the actual caloric value of a diet, has to be subtracted. However, to eliminate all possibility of error, the patient was placed (in Period 3) on a diet consisting of a gross caloric value of 37.9 calories per kg. per day and an amount of nitrogen which corresponds to a little less than the amount eliminated in the urine and faeces during the first two periods. The establishment of nitrogenous equilibrium was certainly expected during this period. To our great surprise this did not occur. The nitrogen in the urine, instead of remaining at its former level, dropped down to an average of 6.32 grams per day. The total amount of nitrogen received during the course of this period was 83.51 grams. The amount of nitrogen eliminated in the urine and faeces was 49.29 grams. This means there was a retention of 34.22 grams of nitrogen for the week, or 4.89 grams per day. The average weight of the patient for this period was 41.80 kg. a gain of 0.43 kg. During the first two periods, marked nitrogen balances were observed in favor of the patient. The problem to be solved was : Is it a bona fide retention of nitrogenous material or is it only an ap- parent retention, i.e., is the nitrogen being given off in large quan- tities through a source other than the urine and faeces? The only source of nitrogen loss that this patient presented was the skin. The patient's skin had been scaling since the beginning of the in- vestigation. In this period we made a quantitative collection of the scales. During the course of the week, 49 grams of scales were collected. The scales contained 11.22% of nitrogen, making a total RESEARCH STUDIES IN PSORIASIS 41 of 5.50 grams of nitrogen for the week. As is seen, this is a small fraction of the retained nitrogen and fails completely to account for the positive nitrogen balance. In Period 4, the patient was kept on the same caloric supply as in Period 3, but the nitrogen intake was again reduced to an amount less than was eliminated in the urine and faeces during the 3rd pe- riod, namely, an average of 6.89 grams per day. As can be seen from the table (see page 52), the patient . failed to establish equi- librium even on this diet. Contrary to all expectations, the patient retained 1.87, 2.19, 2.16 and 1.69 grams during the first four days, respectively. These retentions are the more remarkable, since nor- mally every change from a high to a low protein diet is associated with a negative nitrogen balance (see page, 35). The question then presented itself: in what form is the nitrogen retained? Is it retained in the form of the entire protein molecule, or in the form of end products, as amino-acids or urea? It also became of great importance to test the kidneys' eliminative capacities, since it has been shown that in conditions of nephritis, the patient's eliminative capacities for nitrogenous end products may be very considerably interfered with, 19 resulting in nitrogenous retention. We therefore considered it advisable to make a test, even though our patient showed no clinical evidence of kidney lesion. On December 22nd, therefore, 20.0 grams of urea, containing 9.33 grams of nitrogen, were added to the diet. Of this, 8.16 grams were recovered in the urine of December 22nd and 23rd. The total nitrogen elimination in the urine on December 22nd rose to 10.97 grams. This experi- ment shows that the patient did not suffer from any kidney dis- turbance which might account for the nitrogenous retention and shows, further, that the patient does not retain the nitrogen in the form of urea, because .the extra urea that was added to the diet was promptly eliminated. The total amount of nitrogen the patient received in her food during this period was, including the urea, 57.59 grams. She eliminated in the urine and fasces 42.11 grams, which resulted in a positive nitrogen balance of 15.48 grams. There were 58.5 grams of scales during this period, 10.20% of which was nitro- gen, equalling 5.97 grams of nitrogen. After subtracting this from 15.48, we still have a net gain in the body of 9.51 grams of nitrogen. The patient's average weight for the period was 41.35 kg., a loss of 0.45 kg. from the previous week. In Period 5, the patient received the same diet as in Period 4, both quantitatively and qualitatively. No analyses were made dur- ing this period. 4^> SCIIAMBKJUJ, KOLMKK, RINGER, AND RAIZISS In IVriod 6, the same diet was maintained. On January 6th 20.0 grams of urea, containing 9.33 grams of nitrogen, were again added to the diet. Of this, 9.16 grams were recovered in the urine. Almost quantitative elimination. The total amount of nitrogen ingested during this period was 43.62 grams; 42.5 grams of scales were collected, containing 10.66%, or 4.53 grams of nitrogen. Again, we have a net nitrogen retention in this case of 17.04 grams. In spite of this retention of nitrogenous material, there was a considerable loss of body weight. The average body weight for this period was 40.1 kg., a loss of 1.25 kg. in two weeks. This indi- cates clearly that 38 to 42 calories per kg. of body weight was not sufficient to cover the patient's bodily needs. This fact makes nitro- genous retention the more remarkable. During these periods of low nitrogen diet the skin became much paler, smooth, and continued im- proving. The scales became finer and less bulky. In Period 7, the patient was placed on a diet consisting of 20.54 grams of nitrogen per day, with an energy supply in the food of 53.6 calories per kg. of body weight. The nitrogen retention in the body during the two weeks was enormous, amounting to 66.10 grams in Period 7 and to 60.94 grams in Period 8. A total retention of 127.04 grams of nitrogen in two weeks. If we subtract from this the 1.54 grams of nitrogen found in the scales of Period 7 and the 5.58 grams of nitrogen found in the scales and perspiration of Period 8, there remains a positive nitrogen balance of 119.88 grams in a period of 13 days. A point of great significance in this con- nection is the fact that in spite of the retention of 66 grams of nitrogen 412.5 grams of protein in Period 7, the patient's aver- age weight for the period remained absolutely constant. During the 8th period, however, there was a gain of 0.75 kg. We call spe- cial attention to this, because we shall later discuss the subject in detail. When we analyze the daily relationship that exists between the ingested nitrogen either in the form of urea or protein and the daily nitrogenous elimination in the urine, we get an insight into the mechanism of the nitrogenous retention. This is brought out in table No. 1. This table shows that, after the addition of urea to the diet, the nitrogen rise in the urine was very prompt rising to almost 11 grams in one day. The addition of a much larger amount of nitro- gen in the form of protein, milk and meat, resulted in a compara- tively slight rise in the urinary nitrogen, the amount increasing slowly but steadily, for only on the sixth day did it exceed 10 grams. RESEARCH STUDIES IN PSORIASIS 3. n co - CO M -H CM CO * CO CO CD 00 s 5 s o t- o s -* . ^t 0> 1 s oo -* CM 06 co t- CO 00 CO ^ CD s s CO 10 10 oo CO CM CO CO - CD ^Ji IO CM co eo CO 1 co o C- CO co co CM en CD CO O co CM oo t- t> rH co us . CO O5 CN t^ to d CM co o co TI O CM t- CO co co Dec.19 -* o 00 t- cd co 1 1. Q* Nitrogen ingested. Nitrogen excreted in urine T t. of nitrogen were added to d otein in form of milk and of urea, contai nitrogen intake 2 T H- i &. B I 5i SOIOO5 1 CO *! CD *" CD Tf CO CM 00 CO rH t-OOO . O rH rH CD CD t- t- O5 . . CM rH IO . I&SI OOOO -OOOOOOOO .OOO . frjff COrHCM . . tD 00 IO (N rHOinoc-OOOlO ' 00 rH CM ' CM CM rH rH . rH CM CM 1-H O O O rH . . CO Tf Tl< . |s.-s oooo -oooooooo -ooo . w^- *C rj- o rt CMOloOt- ' t- rH CM t- CO to 00 CM rH ' CMCOOO ' rH -q< -^i CM OJ : u5(Noo : 1 fc W ' S io<7i[-oo ;cMcocM'i>-^'co-^'co ; ;-*io^ ; n > P ^ OrHrHrHOOOOOOSOJOJOi . rH M CM - g rH^CMOO .t-O^Mt-10CDrH10COTj.WrH N S5J Tj* 00 -^ l& .*-i CO O O T} CD l> -*f CO ^t* O ^D Oi O n ++++ +++++++++.+++++ .1 OCOrHOJ *C75COCOOOlOOrHO^1*t~CMO5CT5tD ^OlOlO 'rHCMlOOrHOOt-COOOC~>Ot-OSOO S r?fa OtOCOt- 'lOCOC-COCDt-OOCOOOCOOCOO cococoio ; CD IN ^ -* -fli TC Tf 10 TI< 10 10 10 to t- 00 "* ^ 21 osososrH CM co en CD oo m 10 en o> os oo -^ oo f CMCOCMrH ;cDrHlOC-CDOCMa>COO)CDCMasCM a o| COt-O5OJ ; CO t- CO 1O rH rH rH 00 ^< IO CM TC Tf O 2 ^H * || 1O C7i CO -^1 - OO -^* O 00 IO CO t- t- CM *# IO CO IO CO s i^ 1 CMTflOCO . 00 t> CM CO 01 CD CO O CD rH rH CM 05 TP s g.S CD Bfl fOCOt- ; * O5 OJ CO CO CM 00 CM t- IO CO rH CO 00 s IS TfCM-^lO ; IO O5 ^1< O5 CM * t- 00 00 Tjl rH rH IO 1O 10 >> ^, oo ^ rH. CM 05 ; ; ; cocoo . P rHrHCM 00 Tjl rH 00 * rH 00 IO 'J U .-< S H c c c jja^2J2^J 53^SSJj 5* QQPPco55ojta'i' r .97 grams of nitrogen. 5. Not analyzed. 6.0 gnnrs of nitrogen assumed. 6. 4.53 grains of nitrogen. 7. 1.54 grams of nitrogen. 8. 3.5)7 grams of nitrogen. 9. 1.71 grams of nitrogen. 10. 0.39 grams of nitrogen. After the 10th period, there was so little scaling that its collec- tion became impossible. The total amount of nitrogen collected through the scaling was 23.6 grams. If we assume the maximum amount of nitrogen to have been lost in the scales of the periods in which no analyses were made, then the total amount of nitrogen thus lost would not exceed 51.6 grams. The perspiration was collected during the period of January 17th to 19th and found to contain 1.02 grams of nitrogen 0.34 grams per day. During January 20th and 21st, 0.59 grams were found 0.30 grain per day. During January 23rd to 25th, 0.86 gram were collected 0.29 gram per day. Between February 12th to 18th, 0.71 gram of nitrogen was collected in the perspiration 0.10 gram per day. We are inclined to attribute the high figures in the first examinations to the inclusion of small particles of exfoliated epithelium in the underwear, which were analyzed with the perspira- tion (the patient scaled quite freely during that period) and are of the opinion that 0.1 gram per day is the more correct value for nitro- gen loss through perspiration, 20 We shall, however, accept 0.3 gram per day as the basis of calculation of the approximate amount of nitrogen lost through perspiration. In 128 days the patient could not have lost more than 38 grams of nitrogen in this way. When we add this to the 51.6 grams lost in the scales, we find a total loss of 89.6 grams through the skin. This leaves a net nitrogen bal- ance of 492.3 89.6 = 402.7 grams. This amount of nitrogen must have been added to the patient's body during the course of this investigation. From the above data, it seems that this patient, who was suf- fering from a most widespread psoriasis, had a pronounced exten- sion of the eruption under a relatively high nitrogen dietary during the first two weeks of her hospital sojourn (Fig. 1). After the in- auguration of a low nitrogen diet, the inflammation in the skin and the amount of scaling gradually became less. Later, a two weeks' regime of high nitrogen appeared to cause increased inflammation, the latter subsiding after the institution of a low nitrogen diet. RESEARCH STUDIES IN PSORIASIS 49 1 o 3 en oo oo to to tOt- CMIN IN CMrH ao H m to <* to o oo m to at to at OrHinOCOrH i i & .- PH 55 tOCM M incococnoiN CO CJ CO rH IN i-c OrHinOCO^Ji Amount Eaten in Grams ooooinm in en o -^ en co Kind of Food 1 2 '. ' 'Us 5*i4 .O*p MhJgiJE-iW i cntoo -i-icn -en OI-ITII -CON -o a hi oo co t-in cOrHcntoooinco-^ CM to O 00 Til (MOCMOOi-lOO Per Cent of Nitrogen to oooo inrH iHomooMOo Amount Eaten in Grams iniooommoo mrHOCJtOOOlOtO IH iniH CM Kind of Food '-: : 'a ' ''% f^ us oo J s i-* Ci CD t> 00 CD O 00 N tH rH iQ O i-4 -< o m *l 01 IO CD CO IO U3 CD 5* i 1 t-NOCDf-HOOCO TH CO C> t- (N ^ t> ^Pn Oi 00 t> t- OS O- 00 00 I? 2 rt III! 00 O 1C lO CO OS CC ss ^ U&&H OS OO ^H r-H CO CO 0*3 C M ^;&q.2-8 _ v-a s irt oo S.S55 c= ^ g T3 (N ^D t> -^ O ^ m : : : : : oino to | o co N : : : : : i-i 1 S'3,, en Tf ^. m rH 30 co M "o ^a co m to to c- *)< m 10 He 1 1* CSI * CO rH O 00 Tf 00 Q sa o 00000000000000 2 :::::: l z ooooooo ooooooo AH li CV1 N CJ CM (N M OJ IN IN IN IN CM S .3 TfrH 'K i ^ 8 6-5 oo o H S\ 'w C S Q> s 8 11 en oo co co co oo oo oo oo in co o oc t- rH rH CM rH CM rH rH eo o> CO 1-1 <3 a e o e? &-"" S tSs OOOOOOO " II III ine an pit c-i rH IN co in en oo co to to to oo in o 1-1 rj lillll 3 s s ooooooo WO o si in CM en rH t> m co oo co eft en I-H oo rH -i en CM t" I s5| to en c- c- o en en rH S 00 3 f i-H CM t> to O f IH co oo oo en IN en N S ^1 oo I-H en en rH IN o r- 2 11 oo oo CM -* to <* en CM > e5 1-1 o: :: o: : X Q Total.... Average SCHAMBEKG. KOI.MKK, HIXGKH. AND UAI/ISS en ot- enooo - 3 -" to M : N ^S- 3 fclt-OOOfOCfOO = > i en t- -r o "5 S .-o-rooocoo .^1 o E t - O >S O O O * i-i N M wr 1- O C! l<5 -T 00 tD M eg ^" t- a> t- C; O O O O_ O_ O ^ to f eft oo ^^ 10 o 35 o en o to ~ O w - - co O x tH x w r=i < z u 1*1 CO ID *v>4H cnot-ooencoeM i-"Of OOiHOO A N IN -^ f en c- 10 O U3 O O O O M CO 2 eeM2 OCWl ~' "S^ 1 is ^ 1 S ft- 00 rt fl O W Sri aa -- lOtCTt-^D> +++++++ I J coooo t- -r^-o Mao msiia^i r) rs O /. ooocco(?ia> M - ,1 1 S 8 ills en -> M "" t- oo -! O - x en i fc u. f w*r f cc n f 2 y-a-S-a Si- -^^ =rr=z- ll* o j z 3 1S5 os ooaom M f Mf Mf^CO oo c ts -" M -H CJ -> ^- O II 1 a 'S~-~ (ooaoooocoao o 4|* ia tons 10 >o 10 ^c s - s oo a> N t- co o S l z S<0 (N 10 OO 50 f oo QO oo t~ oo oo w 00 I 2 o S oo o o o H ii gJS t- 1- 1- 1- 1- 1~ t- ooooooo e S.s ri ri ?: ?] ri :]-) ^ i-sl I'll II CJJZ 1 < i w S 8c oo > N e e NC-OCC-C-C~ r-c M -1 N i-l i-l N 2 W 3 1 S5 ooooooo' e -ai en co CM o o> t- wt-cc0 W CO -> <- 28 = II OAOOCAOO = e z 3 OJf iOl"T O-< Nf t-iOOO^O ss E2.I N O O4 N -"-> C N z 00 ^>> OS t- O U5 1/5 eg co w t- ab r: -^ > e t- ;l 1 -TlO Wt-OOOiO M t-i h""" i! S I RESEARCH STUDIES IN PSORIASIS 51 .! 3 oo to oo c- COON i-l 00 tO 00 tO T* 00 00 f^ "s S "= < 2 N t- IO to IO 00 ^l* en 10 t- en oo co oj i-i co en o i-i IH o t* s ooooooo H oo r- en to SN 10 x> CO CO rH r-l -tf OONOOiHO Amount Eaten in Grams OOU3OIOIOO o .0 ^ji co ^ii en r-< oenTjuo'* eo Kind of Food 09 ... g . o otoo -Oi-i -en COOO--I -OlO -IO CO CO -iHCXI *> a H < 55 * t- oocn iHONOOO-tfOO ** d u N t~ U5 00 ^ CO r*0000 fc- 5 00 U3 to i-l *!" CO i-l to CXI 50 00 IN 10 i-l S3 oo t- tc to to to t- OS "> b c 3 2 s bO S b .a 1* O r4 CA ^-J t- eo en a j o TjiWoo * ..a *ji oo t- TJI en to i-i e H -*!* coeooooeenoo X 88 g O g 00 N 10 i-H tO i-l S Q ^^ (S p c- 1- 1- 1- to c- to R w - : : : : I 21 ooooooo ooooooo 05 . . : : . s 5 S ?J 3 CXI N CM CXI fe : : : : : g.a ooooooo U5 o 2 ':::: 111 ^ |jj.i I l' a l wo ' ; '"2 || I- 8 -' : : if j| jJlllf S 11 l|_.S| II ||||P 5 | [Jl a2 t- * CXI i-l * O CXI en to IIIIIl ooooooo CO O o 1 a S c? o oo t- cxi Tjno co oj t- co oo oo co co o rt c 2 to^-tfco^ 8" ll en "O en o >o oo co --. ^2 t- too to .0.0 to 5 >. eneouscot-t-^. . 8 3 ooooooo coO 31 ooooooo Ol O O tO O CO to | 1 ij:;=;: s Total.... Average s ..ja 2 + S3 Ed SH o 2 Q W C3 H - O g 1 Si ^5s ^ I ^4 I5| 2 55 i- 52 SCHAMBKRG, KOLMKK, RINGER, AND RAIZISS I'er of Nitro mount ai.-n GraiiM fi S5 Amoun Eaton in Gram oo c oo t- * i- :- - - -.: \JJC r^t^ t-l O N O O OOOOOOO i-ii-c^rOOOO oooooo to to oooenf * o 1 " OCO CC-fl-iOIN OJOSfcHO n o 01 en co o C4 o 10 O^ O5 Ci O5 O Oi Oi 0000000 o o o o d o o eo oo * e to -a m ooooooo S oS, ss M O M '-<-' N S CM N S !.,.., 111 V CT! g 8| 3.5 If 1 ^' ' 2 S : I If tia iii v Ll 15- 'a M 255 fffgg RESEARCH STUDIES IN PSORIASIS 53 1 O 1O CO OJ t- to 05 O CO 00 C5 IO t* t* ^* IM I a 3 ti 1*8 S 00 t- N CO t- CO Tj" Oi-HCDOOOr-< t. e S OT-IOOOOO to 1 I IO 00 00 CO CO 00 1C ( ' OONOOOiH Amount Eaten in Grams 10 ^-110 * OS loooiococo 1 I : : : - ': fi a xts : : BO .9 i- O _ rt 01 1 1 IB o O Oi *H i I O- *H i i t* os o- I-l O * OJ CO 10 10 1O CdOOSi-lOOOCOO < z NOOOOOOO "a g loioooosooio lONOJi-l-^-^-^O s s rHOOOOOOO Amount Eaten in Grama PSH3S- 1 ::: 8 -o : : : : : |I 1|||^||1 Daily Nitrogen Balance "tf :^ . were recovered in the urine, taken into consideration, e not included. 3 40.10 kgs, 42.0 65.19 gms. . 35.54 . 8.08 43.62 +21.57 gms. >URING PERIOD Total Nitrogen 4.53 gms. o I COC-"*COOOOt-O t- 12 : + : ++++++++ .3 SSSSc?SS5 en ao i O> CD CO CO CO CD J* Ot-NOOSorH CO CD CD CO t- 00 (2 CD E8? 2 : fl 1 s5 oooooooo oooooooo M* |l Analysis of Urine and Feces ss.s oooooooo 00 o oo "^JS aS fe ^ 2 CO **- bfl 0) O^, ?D . ~ g S we^ C5 2 M S OJ M "3 '33 |j u jl} . a o-^ gigj; lijaSlil ."2 B II 1 Jan. 6, 1913, 20.0 gms. of urea given per os = 9 > In calculating the average for this period, the fl In calculating the average nitrogen intake per d Patient's Calories Nitrogen Nitrogen Nitrogen Total nit Nitrogen ANA] Weight 42.5 1 .2 M 00 JJ JH 00 ^ CO JH 5 f\ O oooooooo lj O'flO^l'COosoCD ll NNl SCHAMBERG, KOLMKR, RINTiKR, AND RAI/ISS |^ ; in .g 00 d C|9 O *P S 03^ o _2 N - oj u " - C^MtO t^O 2S -^osa> 8 = ;. ++++++ + + ! 1 s 5, - as! t-iOt-tOt-^ ss H .5 S : .S ss Q Illi sssgss 2S g c 00 i u^>u. t-OOOXRO^ 5* ! 3 | owc-^o i X. +-V EJ r 5S i 5 J 2 3- - C 1 o >f CJOlOC-Jt- K 1 7 j g 1 ^ >5 11 ssssss J IZ g :::::: : o | CO 3 OOOQ 1-1SO *-> Z.H / t g i I 3jj 6 l g !Z f ' * - H a t- CO [- ;|| til fe c S g O *- 'C S o x 5 5 U30M005CO NOlOOi-lO (M = la 01 5 M m M felssS I g '- i jl !s!i..s| J d - M II ||||| a 2 ^ 3 ^ n ~ ' T J ~ ~ ~ 2 a a Blil3 2 -S t 5 f-lOOONO r ; . g a o 10 vt-tot-oo 2 S ,{jzz'zk4 z ^** a. 2 g | oooooo W o |j cni-iiot-iao CQIOOOVOCO 5:2 111 Jg^ggooo oo> " coioiacct-oo S* 4*5 -l 3 t- ^ ac co ~ ^o gP, 3 tot- t-oooio 00 ^ v; - i- -r . s i oooooo 1 : : i&o Sfc (^ *= jjjill 21 O>M Wt-O-T cit-oooaooi 12 : i : : : | 8'fi _. J s p fe C IliiBj ft 1 o s! '--~ JO 5" ' H < RESEARCH STUDIES IN PSORIASIS 55 si o> 0> "s o _ s IMO5 OOi OB s s | 3 cs oo oo oo o^ t oo Soo ^_ X I t- Oi CM -^ t- ^3* 00 eo t '4 o >> 3 .s (M CM N CM M IM O Oi W M -g feSpH rH C-I H-'S OOOOOOi-l *f O iz; ^ CO t- CM Tf CO O CO 'I i ooooooo tECD II OOU3OOOO to co co * c >o co t- t- d OS rH 00 CO rH rH CM 1-1 CM rH CM -S a ifltDt-ooc^Oi-i 3d. . i 3 1-5 s< f O 9 Je g 08 E a a) J3 .S M bd M " bO m t. O O O-2 O j! 9 C E K H >j o ys s s s ~-< rHOSrH 55555 U500Ot-O rHrHMrHCM 5f> SCHAMBKRG, KOLMER, RINGER, AND RAIZISS Amo of Nitro Per C of Nitro * t- o t w n 10 1-1 O C- i-> O O -H ooooooo ' ' ~ - I : . : ~' OOOr-iOOO >M "S _*: ^ ". 2 ~ ^"ES |5 _ C. 5 fi 2 Amount Eaten in Gram t-i-lOJ -O -Oi-l 0.-ii-< -to -O-H lOiot-cotooocoooea rooooo.-ii-ieo-< CNOOOOOOOri t-lOOOMlOM< ...*.. o cc i lOOOO'-lOOS Daily Nitrogen Balance f ; M> i i i |= us oo 0 ^rt- vooaoo oo oo oia to to V S3 cc co co to to %o o tN us t- -^ o to t t- 10 10 *> g^ Per Cent of Total Urinary Nitrogen tl .SS5 5 1 I 2 D j z ^"f'V CO "5" + z M I*! oooo -0 S5 gn O SK? 2 :::::: 2 & O> s i :.::::. Q^ 2 1 :::::: < 2 8 if, H :::::: d 5 I : : : : o .* 3 :S 8 A 3=- fel = 5^5 B/ Patient's average weight. . Calories per kg. of body w Nitrogen in food Nitrogen in urine Nitrogen in fecea Total nitrogen excreted. . . Nitrogen balance ANALYSIS C Jan. 23 to 25, 15.0 gms.j Jan. 23 to 25, collected p .= ? ll if II v*\ ^s si s.3 if 00 00 * 10 t- O N W rl -V tO IO CO oo ia ^ co v TT eo eo eo eo t! CGO i-c O> O> O O ooooooo SI lisllli 1 ?l?3SSSclS 2g Total.... Average . 4 RESEARCH STUDIES IN PSORIASIS 57 ! OS 00 ^ r-llO OS i *f a M TftOOOOrH IO oooooo i-i C-lQ 0-*tO : oooooo ** * .3 IO OOOOO55O Kind of Food 1 jHjH 3 :::: o _ S Ijfjfl 1 t~ W *O "00 "CO O5 O5 00 - ~. -~\ CO (N Amount of Nitrogen t- wooooooo Per Cent of Nitrogen 1M t-^oo^r NN' li-H^fOOt-^-* i-lOOOOWOO Amount Eaten in Grams Kind of Food :::::::: a . 1 I i : bo c OOlO 00 COOSrH tO A u t- j j c g 1 2 : n I OONOOCOOOO W (N IN IN r-l N (M i-l =+ J IO OS IO CXI ^" Oi -H sg WWWV 1* c-a o OD OS ^ O IO rH 00 OJ CO Tf IO IO IO Tf 00 S3 S" 1 *o i JB ll e P 6 CO 10 fries' Q (N o tf w :::::: ^1- I 55 Analysis of Urine and Feces | 'l.s 00000000000000 10 ce o :::::: H : o 2 '? : : jlj B- Patient's average weight. Calories per kg. of body w Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted . . II f J 11 II d e^j o & ."S 3 rH V> N t- CO O * P co co co co co co co 11 C35 ^H 00 CO 00 r-l Oi-HOr-IOO'H ooooooo 0> 00001000 00 00 C-l <* CO O 00 t- l> rH t- * CO i-l 1-H rH C>J rH CJ IN IN Q OS O rH rH N CO fl' ;* COIMCOCO . *f Sd -o 3 $ Rk H < IS SCHAAIHKIUJ. KOLMKR, HIXGER, AND RAIZISS PATIENT NO. 3. MISS B. L. PERIOD XI Amount Per Cent Amount Eaten of of Calories in Grams Nitrogen NitroRen - t- -J p f O4 rH U2 u} OS O H3 cc to 04 co us 10 1~ - O 04 O 04 .I O ta oo o> to 1 OOOfOOO 04O4O>WOO to t to *n r^ o co T 04 O tt O> 04 ri O OOOOOOO SotC^'CJ'-'O Kind of Food fill Calories C-CRtO -000404 o en co os oo 04 H t- SU5 04 O CO 04 t- OO Oioobtot-o 040000000 H t-ooua eoo4 ooi-i-^'OO'^'cc^ ^OOOOCJOO Amount Eaten in Grama IO IAOOU3U3OU3OO rl i-lr-104 04 Kind of Food 3 f : : : : :^ 8 liMifl ..- r. i - r ---- ^ C^l O ^- PC CS Ci to t- C 00 US O4 wto 09 CO CO CO CO CO CO C * ~. Jt C -TV X OOOOOOO OOOOOOO N -- ID C O 04 U5 ti r. n-M TI -- 04 0404040404 10 to t- oo o> o =: = I RESEARCH STUDIES IX PSORIASIS LO o uo is in 10 oo S <~ c CC O) N i-i 1-1 O_ r-l c -i3 -r r: cc c-. 74 ^ M CC i I CC O i I *-< CO ooooooo o o u; TC to t- c- o u; TC to iCC-iOi-i Amount Eaten in Gram S5 . 04GOOOOOOO i-lOOOOCNOOO : : : : T : x| :g 8 *ss en J g i> i-i w -^ >o i-< 10 co en CC = 5? *l 3333353- 5+ iz 1 ^ IQ ^H OS O5 t O5 CO X '3 .9 CD CO t- CO CO t- CO oo co fljj oooocococcco 35 .= * Tf^^TJ.^^.^ s^ 1 |l = 12 1 bo c _y bO 1 SlH IO OJt- IN 5 O """* n 'I ..2 O iH c- M i-l i-l O M "o "c ||* - . r. - ^ T- i-liH en 00 t- O oio t- Tf N cn 10 CO t^cc Q IN & cc >o IN cq I-H o IN t- 1- 1- 1> t- c- 1- . ooooooo t- o w ::.... ll ^^^,, t 0S ooooooo : 111 | | I'M m-g^ S M ll 1 g| SO * 0) oo K . " S O O OS bO O'C w e 8 | rs g Illlll II i.lllP e'l s (N N CO ^ t- CC ^ CO CO CC CO CO "^ "^ CN CO us n Illlll *o ooooooo CM .2 "3 ll 00 CO ^* i-H CO CO lO CD ^H O Ci t- Oi en cc ' < H^ ."t2 tNNCCCCCNNO) en c4 g "3 to CM 00 CM -O CO t- 00 a ! f H< fe o & a II II O & w .- "o >H g. .g ^ fc g < o. i (50 SCHAMHERG, KOLMER, RINGER, AND RAIZISS o .s^ a M t- CO t- O -" f" N -" g 4 1 Oi-lOOOOO *" M CO lOtDOO CO rH O O "" CO O a. 2 Oi-lOOOOO H- 1 ( 1 1 1 K 14 IO - tf 1 i "o j^ M hj K 03 * llg'llll 1 i 3 co 6 CON ' "'- | : * EH V- 14 ssssssss * 11-1 K t i E- 2 MOOOOOOC >0 14 C T ^ ~ 1 - V_ i ~. ', II < 2 <-ioooMooa >o Amount Eaten in Grama r ~. ~. ~. '. ~ - - 11 1 a I cu :;8'3i lliljil I ,1 .a 2.s ft I II Iz i 10 1- T -r t- >o us us us us us us 00 00 i-> O t- ~* O> i Ol O! i OS i N < 00 W W CO CO * o>aoooiao . - r t. - - 1 -. -. - 2 H - ^s f "9 062 CO *^ - ? - will I S|.s.s.s| _ c c e5 RESEARCH STUDIES IN PSORIASIS 61 1 t-CM -00 -.-I USCM * -00 .HCM at to to 1 1 n i-it-i-ccoc-oc-co ricnor-ioi-ioo I- oo OOOOO rH i-liHCM r- Kind of Food Cauliflower &1 l i 1 tDt-CJOOOOO5 eg TJI -^> N os us 5S -" a 1-lr-lOOOrH . ++++++ : C i-< ++ ,1 t--Hoooc-in | 00 t- r-t U3 . f -" 00 W ^ .9 O * ) fli us w IV 00 00 <-H rH O '. U) m S.SS5 5 a t- CO S IN 03 t- ' ^H i-l rl N N rH 1 oo a .9 .9 t-OOCOCDOO'* 00 1 | co co co co co ^ m Z b "a <^ oo.-ioco oo 3 G CacONNNN oi 3 S'S_ ocococotous ; e H "o ^r t-t-tot-oso : oo r^ i fc Ci 13 00 O5 N IO i-l IO " OO CO S" II a o 1-1 10 oo t- ts "3 oooooo' 03O .HrtrHrHrHrH g Si OOOOOOhS OOO-^COOJOZ IO IM t- 1-1 IN CM IN IN fH i-( r-l rl i Q to t- oo TH 01 co f COMIMIN 2-g. . S. . e J9 5 5: ^i- : s-- - H^ oo c d tf ^ d iJill" a .lfe23 2 < ' 5 SCHA.MBKlUi, KOI.MKK, KINGKR, AND RAI7JSS 7! |l "3 O : 3 i-*2" 5 b o 3 2 1 -S52SSSS t { t,i5 H=~ < X. O O IN O O O .a O1CJINNNNC1 ^- fill .-ICO f US CO t- t- US US B tCOO 00 Tf ScS.s-w ^-3 t t co ' o o * J_ OOUSOUSOO .|Z te o 00 .: I d ||| OO t-OOOO U5 O ^s Q SS HJ -;: 1 1 3 1 SI : -2 : a; O. m m | c ^oi'Ss 3 >-IOD -rf moo 2-9 1 e o 2 : ; g :: CM o! :::.:: g ' a : o 3 jli co 111 s < 1 y* 111 00 M ^9 "8 H *-r _ a t- " b- J | ' H ll 11 055 ^1 .o c S S rt bg-r o t^ *** O ^ CJ 5 | 11 n Eijijjl ~ ll -< e . "c c c*i gllll^ ~~! U5-T^IOOOJOU3USO<-IC>!<-I 1 8 = "j "2 2w2 3 (35 t- t- CM '-*' US If H 00 " 1 O us o> *S O> M N CO ^f S2 ^ * US -J to T US 00 C- 1 IE aaO h 15 2 n Isillli 3 1-II-BP I r :i .- -r 2 Si, - at fflSauHwoo S' " - ' RESEARCH STUDIES IN PSORIASIS Calories oooooco t- IN 04 us N = M N < z OOt-t-UMOCO . * O OT O4 C- O N OO-^OTCO Per Cent of Nitrogen 00 COt- CO CO CO TJI rH O5 i-l CO O OOrfOCOO Amount Eaten in Grams m omocn t-o Kind of Food 1 H a ; : g i^- : 1 o iH i * O ' ' O t 00 < z c- t-OOOOOr-liHO4 CM O TC i 1 Tf 00 O * tO 5O > <0 -( !0 rH OS * OfNmooiMOOO 00 5O to 1C to M .3 g .3 |> ^^ J 2s M O*5 i-c e a a oo II Si: -o |l 1 i o g .1 III 3 2 o 3 1 ^i| a 'o a g| S 2^ 1 |51 2 S2 "e3 c 00 -# 00 SO 00 "* U3 co m oo i-i 10 1-1 co ce o oo LO U3 1A tO kA CO CO M 10 z _ >, co N 10 M a> oo co ' a ooooooo ccO -1 o Q Soomooo OOOOOOOi-l CO iH C35 CO CO OlOTf OOWOO rl toiof"* fHoeSS t- 11 O O t-l r-l 10 i-iOOOONOO Amount Eaten in Grama *-< T O U3 O ^ O O i-< Kind of Food jljljljj ? ^te 4 &M a fl ' O . .*J N t 8: - -* X (O O *A CR O) t" 00 W - | Z ^ a & li "8 ll 55 S.S -eo J! ta 85 is o SS o . . .1 . . 2 :;;;;; w : Pu, II *9 ! 9> . N ; Kill!!! i w : o I'M IJ .ag s* p i !- &%||8 | 1 || U siis^i i - || . C C C 2 K i ,.|| 1? Illlll 1 n -ill I g| 1 &3 z al O> N N O CJ >O i-i t- co us oo eo o> 5S li O rH C3 rH r- 1 C*l rH TH OOOOOOO H raO CO C ii rHOC-OC^!M ii .3 s"3 1 rH r-l N CO -^ US tO "- 1 Jj a: s s ; s S<; Total.... Average . ><> SCHAMHKRG, KOL.MKR, RINGER, AND RAIZISS x - 2 OS H s NOOOOOOOOOOO i-iOOOOO OOOOO : 5.5 Sue El - v *s^3 3 = "5 2 * a'o J! o 'o ^" OO-HO -t-lOOOSM-iOOl enow -iflto^ too>NO eC'-io -i-< N i-tei NOt-OONOtCO-O'OCO'H S^l < z J i s& -o< o(Do>a^oo .9 3.S 8 ill I I 55 5i a . I * ^ __ .- ~ t] __ +++++ 1 1 1 I 1 fifi Z-9 S i z I ____ -1 ?! ~\ M-] 7171 --T "^ - ncocucocococowco 0000000000 SiOOOOOOiOOO - ^ ? i - r. r. re -: BA t 4- Patient's average wei Calories per kg. of bo Nitrogen in foo Nitrogen in uri Nitrogen in fec Total nitrogen RESEARCH STUDIES IN PSORIASIS 67 * (N * CM N O i-l CO 00 O FH i-i 0 t-i-HO O iO m M O5 ^D U3 8 fc. 'o 1 2- as 3> i& ; i o 2 S '0. 5 iii|&J 1 I oooio -cncot>jcJ5 CD t- 00 i-t Ci sO X :N g l| OO OOO5C1C5 o ;tc a z l lO O 00 t- CO O i-H 77+++? CO Ui ".. TT .. . z 5*1 rH rH CO t- CM CD CO O CO t- IN Tf N CO N .s oot-t-c-t-t-c- 1Q Q 111! CO CO rH O CO CD -^1 TH t> O ce - - tJ co co t- c- 10 oq en : c .9 J co co CM CM t- en r-i ^cn I r o CO CO 1O CO CO >O 1O :"* I 1 O 10 rH CO t- CO CO :. "Oco en CMt>co en o'oooi en p 1 1 i .2 10 1- 10 en o t- o s If* ^^^.usio^.^ .U) 10 Tf I- co en -* CM IN t- 1- SrH rH OS rH 5 00 00 00 t- OOOO t- SOOOOOO 000000 *! ;oo .'e .0 t-N Q T)l '~ l o w :.:::: PL, i-9 00 00 00 00 00 00 CO rH CO Cn O CO CO rH S: w : o H 1 2 ooooooo no PQ * , -0 s ti '-* O oo en CM en i 1 en o O CO CM CO CM rH CM T)< CM CO CO CO CO CO ~ ON I- 8 1 0^ ooooooo NO bO . *^ C 0) 0) 1 11 TJI co en I-H co co o CMOCOC-OOOOO rHrHOOOOrH - - weft COO > t- _, _, _i bo gj QJ S- f* K Q & C fl C-* 3 1 Si ooooooo oo C -S bfi bO bC r5 ..a! oo co co w 10 ^ en CO CO CM CO C co * ^< rH n" al 00 00 CO CM 00 00 00 co en CM * oo co st 10 t- ^1 OJ CO to IO ^f >O CO t-ce CB-& t- o co in t- -* * 11 ooooooo 03 O n ooooooo oo rH c- en CM to * o en en 10 co t- rH CM rH rH rH rH rH N : : Q en o rH CM co "* >o CO rH 03 IN IN CM N C^ S|i.> . it (58 SCHAMHKlKi. KOL.MKK, HINGKK, AND RAI/ISS ^ *-<><* :o ; I t-M -oo -n 1/3 M *f t* . <2^ ssssss ;s o "* 1 | f t- f t- O n B 10 co <* f* s a zJ m oooooo l+l 11+ ee 1 1 w C = 2cio2oooo |B x. xl SS^SSS nta C 5 3 Z oooooooo <* | .9 (^ t^ tO ^ t- D f -- ^r - Illl -Hr-MMt-M r- c g t-Wt-ft-W > S *SSJS5SS ^2 - z oooooooo jr ^"2222 is | M^iO^CDO) : 1 > M X ill 10 Z iQ kO kO iO ^* U3 t I ,i 2 w-*e :t c 1 o ,:::::: o ii z T TC v eo * 10 1^ S tf 1 w "3 aS m .... ._ . . 1 Na'uJNte-* : ^, Q w 10 Oi c Ill : ^'i : t p z t-oomtoio>a O H Pg^lii 3 2 : : : H . . c c.*J.S x3 o lijsilljl H l z oooooo c c z - - ~ is . . 02 OKOOfc<2 J H 05 2: : : OD II ggggNO S : ::::.. . S 8 O lO -O4 -tDOOlfl Sfe OOOOOO US w : : : o o O 00 * 'O ' CO *H rH Z-9 O 3 1"S ?5oowS Ol USb. 2 if i s C G "t2 oooooo w ** * ffi & z c- 1 X. r> |^| t~iOMCO^fNkOU5O)00 iaooootOf-ia>O'H ir 8SSS2S 8S So a M o O < s MOOOOOOOOO oz oooooo e 11 WtD tO O < O5 r: r |fe5.oa| COO-H-HO o e a e a aS c S & 1 tiiz oooooo ee *'! <7>CJOf-OOOMOoS 1 g| t-o- ~l - 1 |_7 ; l .-i-.-..- ll S3S5SS S2 z 5U3<0)>U5 8* II ^i 05 e^ * o oo oooooo j-s 1 5 a i :::::: :J : 9 SOlOiOOO t- to to* to M i i^frrr i! RESEARCH STUDIES IN PSORIASIS 69 From then on, under a prolonged low nitrogen dietary, the patient continuously improved, until, on discharge from the hospital, but a bare vestige of the eruption remained in a few isolated areas (Fig. 2). Curiously, a band-like streak of eruption (Fig. 4) on the left buttock and thigh, persisted for several months after the eruption had practically disappeared elsewhere. Under the continuance of the diet prescribed after the discharge of the patient, this band practically faded away. While the trunk in Fig. 1 exhibits a very superficial type of the disease, there were large, thickened and intensely hyperaemic patches on the extremities. During the last few weeks of the patient's hospital sojourn, she was placed upon an increased nitrogen diet, without any material aggravation of the eruption ; at this time, however, although she still retained nitrogen, the amount of retention was less than during any previous period of high nitrogen diet. These patches all disappeared without the use of any active medicament. Vaseline was used on the eruption to alleviate the ex- cessive dryness and tension, which gave rise to the keenest distress to the patient. No other local treatment and no internal treatment was employed whatsoever. PATIENT No. 4. N. N.; male, age, 33; born in Russia. He does not recall the diseases of early life. He served four years in the Russian Army, during which time he suffered an attack of jaundice lasting five weeks. He never had rheumatism. No history of psoriasis in parents or any other member of the family. PRESENT CONDITION. The patient is short and thick set; height, 5 feet 6 inches; weight 143 pounds. The first attack of psoriasis was experienced seven years ago; he has suffered pretty constantly with more or less eruption since then. The patient was admitted to the Polyclinic Hospital on Dec. 26, 1912. On admission, he exhibited extensive figurate psoriasis covering a considerable portion of the cutaneous surface. (Figs. 5 and 7). The scalp was markedly involved and a broad band of eruption extended to a depth of one inch around the frontal border of the hair. The eyebrows and mustache were also the seat of eruption. The chest and abdomen exhibited huge, diffuse patches covering about two thirds of the surface. The back, from the nape of the neck to the sacrum, was almost completely covered by a huge, single, unbroken patch. The only free areas were the right scapular region, the left shoulder and the lateral aspects of the lumbar region. The patient complained of tenseness and impaired suppleness of the skin, which caused pain and bleeding. The patches were of a deep-red color, palpably elevated and covered with a moderately thick layer of scales. The arms and legs were beset with a number of psoriasis plaques, varying in diameter from a pea to the palm of the hand. The nails, both of the hands and feet, were severely affected, showing marked subungual thickening and pro- nounced pittings. Under a low protein diet the patches graduallv lost their infiltration and subsided to the level of the skin. 70 SCHAMHKlUi, KOLMKK, KINGKK, AND KAIZISS The patient was under the necessity of supporting his family and was able to remain only a limited period of time in the hospital (seven weeks). He was discharged on Fell. 13, 1913. I'ndcr the use of a chrysnrohin ointment, 20 grains to the ounce of vaseline, applied two weeks liefore his discharge, the eruption rapidly improved and, with- out any interruption, progressed to the point of disappearance. Examined on March 30, 1913, the entire surface of the face, scalp, trunk, arms and legs wa.s free of the eruption, save for a few ill-defined and super- ficial, scaly areas on the sacrum and legs. The nails exhibit a marvelous im- provement, having lost their thickening and showing, in their new proximal por- tion, healthy nail tissue. No treatment was applied to the scalp; no internal treatment whatsoever was employed. The patient after discharge from the hospital faithfully continued the diet prescrilwd for him. On January 1, 1913, the patient was placed on a diet consisting of a little more than 7 grams of nitrogen per day. The total amount of nitrogen ingested during Period 1 (8 days) was 67.72 grams. The amount of nitrogen eliminated in the urine and fjeces was 62.4)1 grams, resulting in a positive balance of 5.31 grams. During the period, 9.5 grams of scales were exfoliated from the skin, 11.19% of which was nitrogen, equalling 1.06 grams which has to be sub- tracted, leaving a net gain to the bod} r of 4.25 grams. The patient's average weight for the period was 64.9 kg. The caloric value of the food was about 1800 calories, or about 28 calories per kg. of body weight. On January 6th, 20 grams of urea, containing 9.33 grams of nitrogen, were added to the diet. Of this, 8.2 grams were recovered during the days of January 6th and 7th. In Period 2, the patient was placed on a diet consisting on an average of 27.06 grams of nitrogen per day, with a caloric value of 2670 per day, or 4-1.2 per kg. The total amount of nitrogen ingested in the period was 162.37 grams. The amount eliminated in the urine and fa>ces was 105.48 grams ; 3.5 grams cf scales were collected, containing 0.39 gram of nitrogen, which leaves a net retention of 56.50 grams of nitrogen. The average weight of the patient for the period was 64.8 kg. a loss of 0.1 gram. Here, we have a tremendous retention of nitrogen, corresponding to 853 grams of pure protein, while the pateint is on a rich caloric supply, without any gain in body weight. This is very remarkable, for the same observation was made in Patient 3, Period 7. In Period 3, the patient was kept on approximately the same diet, receiving 194.77 grams of nitrogen (an average of 27.82 grams per day) and about 2800 calories per day. The amount of nitrogen eliminated in the urine and faeces was 147.62 grams. In 3 grams of scales there were found 0.34 gram of nitrogen. This leaves a posi- PLATE XXX. To Illustrate Article on Research Studies in Psoriasis, bv DRS. SCHAMBERG, Koi.SIEU. RlKGER and RAIZISS. IB -c * g * . c/2 -M O 3 c CO ' w S * j +J ;- *f oj ei r-H G > Q, jj '^ " '- S, g^ -la u 8 <" C3 ^ - V *-< I, 9 & a 03 3 cri i i m SB THE JOUKHAL or CUTANEOUS DISEASES, November, 1913. PLATE XXXI. To Illustrate Article on Research Studies in Psoriasis, bv Bits. SCIIAMBERG, Koi.MER, RINGER and RAIZISS. .8, T3 4) 4-1 V *-" 43 C *-> SS j ^ >; I aa 'Z* ^ CO rt) c a - c tu THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. RESEARCH STUDIES IN PSORIASIS 71 ^3 0> B | 00 05 U3 5) C- * M i-l 00 1 :S Q ^ n S gssss^ss n ^"S (MOO^^eoo^ Si H 1 +++++++ U O* CXI CO 00 03 ^1* v i-KOOOOiH g | ^1 g^oooglc-jg t- I < g I-HOOOOO te ! .3 ^t-t-t-t-Wft- t-. ; Q IU t-00MMt-OOi fl . 1 O gj|^ 0) w . -g. g CO CSJ ** jj^r^-S"^ oot-t-towwt-to U 0-3 g US -31 o O O T)i i ONOOOi-l coojiotooico U3000JNU5 ^ | woo coco oo-* ' ' T3 x e s S 3 O eg O -*^ - B^O TOIOOC5OO 1 ' I* us^oot-co ; ; a i c * i S>. 61 Is .5 " S "x OXNOtC^O ' *-S A C4 t- -^f - TT odt> ea iz**. Sg U ^ 1-1 C CO c 5 1 oot^t-t^-t^^oot g: S 1-i i-i.i s "Sl-tlU?! 1 E rt o. a-g ' I 8 0000000 oo ooooo ^^^^^^^^ p ; | o ;:-:::: o g og 1 52 : : s Sfe 25 .a oooooooo oo '. i w : a o u, S5 : 2 "S^ OT -uli li "a O ill coooiiNooo ; : * t- O U5 t- tD . . ~. -^ -S : iis : a n p <; Z fc <; PU ' D 2 1 1 o"o 2 NOO5OOOOTOOO II COOOOOOOCOi-l CM 03 i-l -* N * Tii -^i -a< T)< Tj< TI< O fl) .Q QJ ^*H O 0) _ M X a -< 25 NOOOOOOOO x C2 oooooo * aS si o -r * _ %* s g i -< 1 c-) * o 10 -( oo 10 * TO (N 5 * 1 II oooooo 1-1 S ffl HI 0)'fl aij 5 o ji.o O trf) fs 1 ell - z ^ s o N Ti" 1-1 1- te C-] t- 00 O 00 M IN i-l : : 7 "c a E g|S us 1 ^."tn fO t US T* CO 2"5 ^J" .s T) E-gO <~.= |j 33005300 us S us ; 2 d ooco^io.oN 5010 S; 1 ::::::::: |.& i ITOOQSTOOOi i oooooooo 3 1 T3 .s : : : : : :S :S :::::! 1 : : : : : 3 ix ooioioomoo ?S52c-3o^ ' o o * : J : : Jit O ?l O O f I- !* Q 00 - - - : / - - CJOiOOCO*" So 00 U5 9) t~ 00 W O O oooooo p-f^ooot- oooONMeo ooooooooo> oooooo 5 S S= < CQ fe o*e ?J 3 a a a 151 I < 8f b JZ r"e ol CO *j ^^ S ^ P Z999V a > RESEARCH STUDIES IN PSORIASIS 73 _C3 ooc-jocMinto *S* ^f CO ^ CD CO co CM o> 90 M - a fat CO CO O 00 t- 00 t- i-< IO Tf i-l rH O O M 9> 6 ~ OCO-*i-IOOO 1 I ?I O CM t- 00 CO 00 * CM 00 C- rH O 1-1 (S S rHininr-IOOO Amount Eaten in Grams mooo IMC-i-lCOOCO 1 "o T3 C 3 3 e Calories OS O O ^ r 000000 -CO -C 4 1 1 0-3 = ooorHoocomo 1 1 8 fl < 55 **oinoocMoe 1 g & to eocMSS^oscor > & z t-lOOOOCMO-' 1 Amount Eaten in Grams in Ofoomc-oc; 5 I 8 6* 3 p 1 . ; ffifflSHOHwo 1 i Q >>S II : w 8 PQ^ CO 1 1 IM i-l O5 Tj< 00 O i-l 1O t^ t- t- 1C C5 O5 as m a Z| n ^HO^U5C-^ltO +++++++ t^ c ++ S J CM CO WMO ^ CO t~ O) CO 00 5D t- CO IN l> M t- co ^ _g O t> t- CO 00 Cr- 00 IM Ci) hfl O -r 1 S ~* ^ o g ID c fe 73 ? I|JJW| 1 II .B iTa a fl.-tt ^|aa& c n 3 S illlll & sil SozzzH s a ^ I 8 Sg < 11 z ci "c3 bo IO O rH CO CO i-H i-l Tj O rH O5 IM 00 * S3 ^1 OOOCftOOSO C-J IM IM rH C Tf co (M cn co IM N IM r-l IM rl IM JJ ^jincot-ooejJOi-i & 5 SB. ! 3S HI H < o "> I 1 *a 3^ -So w H HJ 8 MO os 74 SCHAMHKIKi, KOLMKK, HINCiKU, AND RAIZISS PATIENT NO. 4. MR. N. PERIOD IV Amount Per Cent Amount Kind of Food Katon of of Calorie* in Grams Nitrogen Nitrogen co M co r t- m in W "" -root--TNeO*r . Ooo^OO-- S H .a :, B i i 1. Mm o a t- -i* .0 IO 8 i t 1 1 - 3 1 !,; \,.;,i Undeter- Unc N Acld mined N mcoooooo t--rm-Hco oo a T *1 5 : *I i i a o'zZ-% o.Z H J* l.s M!:!J!| oooooooooooooo W o c ft : I 1 1 iill: lo, | ^y t-. CTi . o 00 O ^HO^ > -t-10 iOWi-1 W CQ .<- H :::::: 53 0,4 ooooooo 18 3 if : : i : ^ fe III B < z ifiioc-'O'teoococot- B, Patient's average weight. Calories per kg. of body v Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted. . Nitrogen balance i Weight P 2.2 ~ a II COOOOOOOO^H 11 11 C s. (-iOC4iOM0 o o 1-1 o eo 10 S5 ::::::: Amount Eaten in Grams i-l-l- 4 CJCONMOWOO s.s 3* OOOOOOO Kind of Food ijjjjjjjj si liiiiii i g^WCO^fiQtOt-OO & 1! RESEARCH STUDIES IX PSORIASIS 75 .3 I CC -^ XCCi-1 fc O i -< ;c Si 3 >_ < z 10 c: cc t- 1- co N C- OOJ Oi-l OO O -HOO t- IO O -*r ' - III oo 10 etc 1-1 eo 15 N O C: -- '-C <"".= - s c g c 3 I : : s O CX -g " " S J o Oi 00 t- Oi OJ OON - - I 1 o 2 5SSSS5 1 1 NOOOOOOO "S o t 0-3 o Z t-lOOO t-O CM N 1 1- ^r oo t- r- -HOOOOMOO 111 IOU3 rt i-HNi-l -l 1 1 -a "H : : : : o- ; ;_; 3 ~ *ti e I sa^ CO J S W C5 CC T *-" O 00 3 X *1 +++++++ o 1 zl SSSsSSS CO 9> to o 1" _c t- cc to ^. t> t- 1- - 1115 t- t- CO T)> Tf IO >O b> O ZW-S-B "" Ol " : " 010 ' S 10 Ig Is 2 " 1 n 5 1* 1 _c CO t- Ot-CC iH 1* COW* CO 1 i .S -c <|Z HCO t ~ 1- Q w o w ; . oZ E-i li Z-3 00 00 00 00 00 or 00 ooooooo to >o s w US t- - A 11 0) O^ <0 00 X oj bi o *j^ o c 1 -T3 e 1 B.S.S.o 1 II |||||i 1 E'll llllll 3 0 | J 7(> SrilAMHKlUi. KOL.MKK. HIN(iKH, AND HAIZISS >-| : r- i o tf> O O 3 fl - rt OT rr O to t J, - T- SSSiSSS :3 B ^l _ r, _ _--, r -+ !>l -r d ', W U3 t~ t - Z 2 | 5SSSSS2 ss 5?. oooooo :- 1 .a ||l 8 -r co us >n w o -" as tfi ^r -< w ^^ ^ U5 a> oo g & us to >a to to -H < T o S 1 i i n < . i 1 a o t^ o 2 1 11 l|S.s!s| 2 * 1 . c c c5 o j g 01 Ol Oi c * ^sf W w^-^^ooo5 i i .|| lillll 1 S, X ^ 3 B | i g| oci-oiaoo-tu: i | p s * J ^CON lO CJ O> W* i "S^SJ :E|| Sfe^8slS | ifl t~ O ojcjaio t-N S5^as In o t-oent- ^ 5** ooooO'O'Oi- IS* -r *? i/3 ua ia -"i 1 6 8 eooO'-ciTr t- 8 6 H W m +++ 1 ++ + z H ^1 1 - o t- 1- t~oco 3 H 2 fc. O - s _J 5 .5 i *^ &< 2 i- e * co e N (0o A^^MB S " TAB METABOLI Total N Excreted ;1P 447.10 I 1 1 g w H 1 I OOTtOtOiOtO * K B H I 2 B .0,^,0 g O I OH 1 S "-: = S ^. 'jf. 2 '-"> , .5 "D z 100 f^r coco 9 M oowt-t-t-t- 3 co s -"OJN I C C C B -0 ^ ^ - - :, r - 14ml 1 -*>> 8 / 11* $ t O3 00 t*OO O Ol f- W t- U> N r-> t- IN 0> i-lt-l t-lrH 1 E b i& t- O O N 00 IS* O 00 U5 O9OOOO> cjcoNeowN 'C M >> S5 a 5 ^ co o co AO vp -- OS O ti t-Tf to^ntoo tin cicjn i$ ;i -r ?i - a ^ c ~ x 'xx:- t- w0 O 00 03 Tf Tji rf r- n c oo<-i rie* O M | c ' e '-S-S-2-2 a s - - ~ ~ KiUkPiKfi t-MOoccn i->CM t -l 3 C C C ^ JO ^3 Ue! 1 | ss>>t: RESEARCH STUDIES IN PSORIASIS 79 44<7.10 grams. This leaves a positive balance of 129.32 grams. Severe as the case was, the amount of scaling was comparatively slight. The following amounts of nitrogen were found in the collect scales for each of the periods : Period 1 1.06 grains. 2 0.39 " 3 0.34 4 0.25 5 0.17 " 6 0.00 " The total amount of nitrogen eliminated in the scales for the entire period of investigation was 2.21 grams. When we add to this the amount of nitrogen lost in the perspiration (assuming 0.3 gram per day, which equals 12.6 grams for the entire period) the total amount of nitrogen eliminated through the skin could not have exceeded 14.8 grams. As the positive balance over the urinary and faecal nitrogen amounted to 129.32 grams, on subtracting 14.8 grams, we find a net retention of 114.5 grams of nitrogen, an amount which is present in 716 grams of protein. PATIENT No. 5. H. B.; male; age, 47; born in the United States. FAMILY HISTORY. His father died at the age of 75. For ten years he had a large ulcer in the groin. For four or five years prior to his death, he had a "generalized scaly eczema," so diagnosed by a well-known dermatologist. His mother is living and well at the age of 77. No other members of the family ever had any skin trouble. PREVIOUS HISTORY. The patient has been married 22 years. His wife is living and well. The first pregnancy resulted in miscarriage. There are three children, all well and robust; the eldest is 19 years old. The patient had measles and scarlet fever in childhood. He had gastritis at the age of 19 and jaundice on several occasions. He is subject to "bilious attacks." He has been constipated for the past ten or twelve years. At the age of 20, he had a "chancroid," which lasted about four weeks and was treated with local applications only; he never had any manifestations suspicious of lues. In 1908, a boil-like lesion began below the left knee, which grew to a plaque about 2 inches in diameter and became elevated above the skin about 14 to i inch, with a papillomatous surface; a diagnosis of sarcoma was made. In 1910, an operation was performed to re- move the growth, but it was found to extend too deep. A month later, the leg was amputated above the middle of the thigh. Enlarged glands developed seven months later (May 1911) in the left groin, and were excised; the wound failing to heal, a second operation was performed on the glands in July, 1911, with successful result. No microscopic examination of the growth appears to have been made. PRESENT DISEASE. The patient first developed psoriasis 17 years ago, and has never been free from the eruption since then. He has usually had large areas SO SCH AMI* ERG, KOLMEK, RINGER, AND RAIZISS of the body covered. The eruption is worse in winter and usually better in summer. The patient WHS admitted to the hospital on Jan. 16, 1913. On admission, he exhibited a most extensive eruption, covering the face, scalp, trunk and extremities. The face was in large part covered with superficial, reddish patches, particularly in the bearded region. The trunk, which is shown in Figs. 9 and 11, was the seat of extensive, irregular patches, which were considerably infiltrated and covered with heavy scales. The legs and arms were enveloped in extensive, thickened patches, which involved about two thirds of the area of the extremities. The patient was on a high nitrogen diet for five days from the date of admission ; during this period, the eruption on the face be- came distinctly worse: this was independently commented upon by the physician in attendance, by the nurse and by the patient's sister. Later, the patient was placed upon a low nitrogen diet and kept upon this diet for the greater period of his hospital sojourn. The patient was discharged from the hospital on February 28, 1913. At this time a vast improvement was evident in the eruption. Large areas of the body had become pale and were relatively free of erup- tion. To properly appreciate the extent of improvement, attention is directed to Figs. 9, 10, 11, and 12. The interval elapsing be- tween the taking of the photographs was about 70 days. The scalp, which was very scaly on admission, cleared up without any remedial application whatsoever. The patient received no inter- nal treatment and nothing was used locally except, occasionally, a little vaseline to relieve the excessive dryness and tension. On February 25th, owing to a positive Wassermann reaction, an intravenous administration of salvarsan was given without any appreciable influence upon the eruption. On January 17th. the patient was placed on a diet consisting of an average of 27.79 grams of nitrogen and about 2700 calories per day (38.7 calories per kg.) The am6unt of nitrogen retained on the first day of that diet was 9.8 grams. High nitrogen re- tention continued throughout the entire period. The total amount of nitrogen ingested during the period (5 days) was 138.93 grams. In the urine and fa?ces, 104.35 grams were eliminated; 21.5 grams of scales were collected, 11.12% of which was nitrogen, equalling 2.39 grams of nitrogen. This leaves a net retention of 32.19 grams of nitrogen. The average body weight was 70.2 kg. In Period 2, the patient was placed on a diet consisting of an average of 13.45 grams of nitrogen and an energy supply of about 2500 calories per day (36 calories per kg.) During this period the patient ingested 94.12 grams of nitrogen. He eliminated 82.32 grams in the urine and faeces. During the period, 64.0 grams of PLATE XXXII. To Illustrate Article on Research Studies in Psoriasis, bV DBS. SCHAMKERG, KOLMER, RlNGER aild RAIZISS. sJ* V" S OT . 1-1 O O 05 ' pjhs o C - z 9-tio o 4r O Z O 60 fl ;r ^ ^ 2 53 Is -^ A ,a THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. PLATE XXXIII. To Illustrate Article on Research Studies in Psoriasis, by DHS. ScirAMitEitG, KOLMEII, RINGER and RAIZISS. THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. RESEARCH STUDIES IX PSORIASIS 81 scales were collected, containing 7.35 grams of nitrogen. This leaves a positive nitrogen balance of 4.45 grams. The average body weight was 69.4 kg., a loss of 0.8 kg. In Period 3, the nitrogen in the diet was reduced to almost half that of the preceding period, an average of 7.26 grams per day (0.106 gram per kg.). The caloric value of the food was about 1600 per day (23.3 calories per kg.). The change from the high to the low diet was associated with a negative nitrogen balance, which lasted for four days of the period. During the last three days, there was a positive balance. When we consider the balance for the week, we are surprised to find that the patient almost reached nitrogenous equilibrium on this low diet. He ingested 50.84 grams of nitrogen and excreted 51.54 grams, a loss of only 0.7 gram. Only 1.5 grams of scales were collected during .the period. The patient's average weight was 68.6 kg., a loss of 0.8 kg. The establishment of nitrogenous equilibrium on a diet contain- ing onty 0.106 gram of nitrogen per kg., and an energy supply that is a great deal less than is required for the maintenance of caloric equilibrium and which is associated with considerable loss in body weight, again show what a remarkable tenacity these patients' bodies have for protein. In Period 4, the diet consisted of approximately the same amount of nitrogen, but of a higher caloric value 2100 per day (30.8 calories per kg.). The amount of nitrogen ingested was 54.18 grams; the amount excreted was 43.16 grams. 7.5 grams of scales were col- lected, but no analysis was made. Since none of this patient's scales were found to contain more than 12% of nitrogen, the 7.5 grams of scales could not have contained more than 0.9 gram of nitrogen. The net gain to the body in 'nitrogen for the period was, therefore, 10.12 grams. The patient's average weight was 68.2 kg., a loss of 0.4 kg. It is remarkable to note at what a low level of nitrogen catabolism this patient lived. The average elimination of nitrogen in the urine per day was 5.14 grams. Calculated per kg. of body weight, we find that only 0.0754 gram of nitrogen was catabolized per kg. of body weight. In Period 5, the patient received a diet of about 2600 calories and an average of 8.23 grams of nitrogen per day. The total amount of nitrogen ingested was 57.58 grams. In the urine and faeces were eliminated 45.13 grams, giving a positive balance of 12.45 grams of nitrogen and a gain of 0.1 kg. in weight. SCHAMBERG, KOL.MKK. RINGKH. AND RAI/ISS PATIENT NO. 5. MR. B. PERIOD I Amount Per Cent Amount Kind of Food KaU-n of of Calorics in Urama Nitrogen Nitrogen x -^ o en u? t- N n >o -* oc t- x t- ,.-.00 oo pi al Urinary Nitrogen Daily NitroKcn Balance r ,).,( , Nitrogen Creatinin UricAcid u ' r ' Kxcretcd N N Bodv N N ""S" 1 inL'rine in Food Balance Weight N 4 Feces ' ft " c i : : : : : 00 COO OQ*O 3 t- t- t^ M C-l _i TUC OOO V Ifl CM t C-4 O CO t^ to oo i- oo ~ 5 -C1MC-JM sg t-COCO O ^ s - * ii fe H t-00 M roo t g ^ ' 2 Q w : a B ; si* J - *"::: i . ^ .* . . C * ^ 2 9 " 1-1 ill 1 l j* s EjlJ=J H O4 IO O !O 00 00000 -f - IN t- <0 N II ifa 2-3 t-t-t-t-o -i o> o |1 fi ^ z o >a o N o o 04 i sg fc ^1 a ej *t s II M S 2 lOOO O>iO 271 r. r. i 10 o f> co "go ss$aag-b O CJS t i- S ooow3OIM (N 3 i bj g 2| to JS 8 T * rH CO t- IO Tf 10 # M U9 r^Cn CO CO IM i-l CO >O CO *> n := a 111! O 00 r-l rH C7> 00 IO O IM to CO IM t- rH ft to t- -is fcf3C*H f CO O rH r-l O O M - jzijy.S^J rt SIL ! | 3 "SS5 M S S m 60 bo | a -5-a>rH eo := "i' 2 ' ' tococn oo 3 o 5 IMtOOIMrHOOO * s < Q ^.^.iO^^Tl.^ :"* rHrH o 1 eg t- oo 10 eo * ^" '* id to Q * s p* t- ^ CO O CO O5 IO 00 00 OO 00 00 C~ OO 000000 :8 o s : ; : ; ; ; g :::::: g : : ;:: 1 M ooooooo to : o |-g| i i I'M .S o Sf"o B "1 1 ! | 62 * -a S S S f _M | g 1 11 > w.g.g.S o 1 II $||| I 1 5 8 a O t- O5 * IM t- t- IO IO TJ< "* -^ Tjl CO ooooooo to oo Tf m o IJIIIJ | a O t- CO to ^3* CO O N * rH CO tO 00 O5 t- in o 1 S CO tO CO CO 00 IN rH * 0) oo | eoiMcnoocncn 10 O t! IN ^J 1 IM (M 00 rH in ooooooo j ooooooo "? CO C<1 CO O u . 2S *3 C G S"* - O + s O o;-; 3 O 8 ES Mi 1 1 ; 84- SCIIAMHERG, KOLMER, RINGER, AND RAIZISS Per Cent Amount of of Oaloow NiIniKni Nitrocrn t- f "-usao n M 10 O! CO t- < i co t- o c-i es o o o o ^* o o N r5irt{ U5 6 x i ocnto -en o ?! w -en -c f N a 4 H 55 a u f OtOOtONC 1 i S 3 2 -:------ > 1 1 t* 8 ! c. N ^5r:5 tO^tOOf rntl > 4 JS 2 noooeoe Amount Eaten in Grama to to Nootatotooe tOCQMdMiOu t 1 o, 8 1 ::::; i i -si 1 *I o oo eo co r- to N in to t- eo t- to " IS o o I 55 J 77 i i +++ o e I i 2 1 < i t t- 1~ gpcp 33 .9 i- [-'[-[-(- S" * to CO - CO C*J f tO 258 CO 00 00 C- tO (O (O S !L ii 0.555 a g 1 | J! C 2 c 1 f- | ;| Of f e ,-, .t: tOfOO tO t* 'Z ' odcoo ii o 1* U s'i so to went- co CM w Bu H 5 i z to T co ff co "* toco M -J 2 to 00 t- f i-l t- O . Q 5* g 1 I 1 * t- oo c- to eo >-i TO to o :::::: Q S :::::: : g I 2 00000 1 II 3 2 niiii g*. ; w :::::: o : 2-9 o m 2 : s w 3 :& S P! 3 'l < * 5 9 IfS S fc |- Jl &%S8S 8 2 g Sfg'C 8 c g OQ 1 11 ^45 tf 41 JS >- 5|.s.sg 5 ^ |l c c c- c 5 11 S-a iu Z ^.| MMNlf M < JS . ..at COf illOlOf 00 f eoeoNCJiN^ gss '3~^ i ^ pLiUZZZH 2 ^ 8 *2 ooooooo CM i 2J en-gSSSeSS 2S J loioiof cocof 3* if t- f -. co N us ta o 10 10 taw II to o to en o en ooooooo v.- 31 2 .9 7J _ 1 2 e" ^ 5*fli3"; ToUl.... Average RESEARCH STUDIES IN PSORIASIS 85 Calories ': en 3 M ri o to oo ooo t- r-l CO CO CO CM O M t* OO i-HOOO Per Cent of Nitrogen (NCicooo to OCOO! CMr-IO oooooo Amount Eaten in Grams U3 OO 00 t-COO Kind of Food 1 : c V ij ! LH jijiji C la u & o. IK S c g g s Calories t- -^ -osoocooa 005CO -OIMCOIN 1 1 ri oo o m o_to oj r- CM (MOOOOOOO 1 1 t- 00 CO CM CM r-ioOOCMOOO Amount Eaten in Grams 10 CO CM IM CM 10 t- t- r-t rHi-C N Kind of Food '.'.'.'.'. a> Cauliflower. . . . ^ 3 ^ O 08 o i Daily Nitrogen Balance -si 2 MS, ; N :8 i 1 ^ & rfOO tO INOS--! r-l s scj m CC I- -T -HI- C co co o> oo *! TI e- fq t~ o in a + r-C O O 1-1 1-1 TO t-l +++++++ l .9 TO 5 -* C-3 t- 00 O5 t- CO !O CO CO *) CM 00 * 1^ t* c- 1- to t- 1- o oo Tf t- w C -T* (U 3 Si * a 8 WA*3 u P K M -b fe&fc, '2-2..= * O 00 O IN to i-i O5 T? OS t- U3 OT O W3 'J3 LOlrtlO to to to c^ *o 1 o 2 *i* jr O 3 1* i a IK E o tOCOlO TJI <7>tO 05 rH U3t> Q w o 2 : : : : i'I z o to c- oo o o r-i a CO iHiH M S^J IS 53 /-s . ' Q c O Z Q Bg O M II -4-> t/) C as * 8 S3 ' r 80 SCIIAMBKlUi, K01..MKK, KINGKK, AND KAIXISS r. 1 t- co x i- s> " 5 < Ol O *T O *T "T 1 10 t- ^ - t- Ol ^ t- i_l 01 o o ^* o o 01 ~j z zl l M ^. ^, ^ e<) o Ol 01 oocotcnot- ae ww E. < I/". O~OOOOO 9> o .H il-ii O> t> 00 t- W t- 00 co co to m o oo us U* ^ = r S "3 tlOXffi-V CO Ol ?? J> Cl SO Ol t-* ^r co o - o co IsSSS to to to te to to to u -^ "S ^ "? c- c- to o> 01 o 01 e> 1 j t- o - co * us o M fll ta OO O T t- WO u I! w w w wos t- w 00 j? u 1 < .3 r-OJ'-"-' -< 1 i t- en t- us t- CM us . W CO eooio odoct-^ us M M > n : : ~; 3 p Ol OJ OJ O) O) Ol CM + o NH : fv 1 ^ i| z w us to i- e eo 1-1 co CM co eo eo co * 9 r s - fli ^^ 53 PH pi "o -3 C 2 ji ij 4 1* o * t- 1- eo eo us t- e w us 01 to co 000000 o o o oo o 4 woo Q o os : H PL. ::.:::: s 1 WOW O> O t- N te c c c g 1 j - 1 jl ooooooo e e ^|aaa' 5 i i |c v~f f. -> ~. s. - "^ -r I ,.a| OCOOOOJ WOJ :i r: -I :: S2 .2 o 2 S"3 "a "3 - -^ 'o i x 2 -IOOOC4OOOO - B a z OOOOOOO | si O W W C -f O CO 23 III 1 P z r: -r r: r: 8' 530 < .a 2 5 l^Isll ll eo t ^ to O ^ us rl rH Tf CO Cft tO CO 88 ^z us us us us to us k " II sllslss I i ] 5 ^ IHii.|!y SI ooooooo - - c :t r. o to co x o w t- , .= jjii^i | 1 M CO US to t- 00 i& !5 ojauucomSS H< RESEARCH STUDIES IN PSORIASIS 87 PATIENT NO. 5. MR. B. PERIOD VI Calorics w w " < c t- to 00 1-" t- C~, O to r-ICJ IN Per Cent of Nitrogen i- Tf to OJ CO N t> O CO i-H O i-l CO O OOi-HOOOO Amount Eaten in Grams oo toc->ocoo m OC30JOC-1O Kind of Food I : J2ti J ' Q. crt 3 .ti oj g s f S -a. w O * *?h Q* ! OCTSOO OSCC-fl'IN TtC4 IN 1=1 t- 10 to to i; 3 s o a 5. a S 1 ss 1 8 IO t- O OS IN CO OJ oONtoooioas 00 CO S a ssJ IN to CO * tO <* N CO IN N IN gg .9 Oi 00 OS 00 OS 00 00 s Q l|l 1 to IN to eg IN t- n * n o * to to to to to to to J? 10 || Jl* i 1 I -5 it 1 | OSOOCO O - 1 " tOINtO * c5 _ H C'Sfr ^1 to oo c3 Ji 1- to oo Q o S !:!!:: 1 H .OU^K, ,0^00 o : 00 A< tf g ::: w :::::: ill PI it i- 2 "i.-l o "a O^ g^g'C g c 1 11 | fe'c c c g 1 1 II flllfj s'il mill s "^! I 1 1 II ^ c It IO O t i-H O id i-l '0'0'0'0'O'OW a s * 11 4_, 1-1 v^ e Gt H J3 Cjd W 4) ti s-gs z > OD -3 L JOURNAL OF CUTANEOUS DISEASES, November, 1913. RESEARCH STUDIES IN PSORIASIS 89 plied as infrequently as possible, without subjecting the patient to unnecessary distress. A note made on May 10th, states that "vaseline has not been applied for three days." By May 10th, the skin over the breasts and shoulders had become much paler. By reference to Figs. 13, 14, 15 and 16, the improvement in the eruption between April 23rd, and May 21st, (the dates of the re- spective photographs) is clearly seen. In view of the fact that no internal treatment whatsoever was employed and no local treatment save the use of vaseline, the change, we believe, is truly remarkable. This improvement continued up to the date of her departure. After discharge from the hospital, the patient was unable, owing to poverty and other causes, to continue the diet prescribed and she returned to the hospital some weeks later with the eruption much aggravated, In Period 1, the patient was placed on a diet consisting of an average of 6.84 grams of nitrogen and 1439 calories per day. (22.80 calories per kg.) During the period, she ingested 47.90 grams of nitrogen. She eliminated 34.62 grams in the urine and 4.67 grams in the fsces. This leaves a positive balance of 8.61 grams. 41 grams of scales were collected, containing 4.95 grams of nitrogen. On subtracting this from 8.61, we find that on 'this poor diet the patient retained 3.66 grams of nitrogen. The patient's average weight was 63.1 kg. In Period 2, the patient was placed on a diet lower than the preceding one in its caloric and nitrogen content. It contained an average of 6.08 grams of nitrogen and 1150 calories per day (about one-half the normal requirements). The total amount of nitrogen ingested was 42.55 grams. The amount eliminated in the urine and faces was 37.85 grams. 65 grams of scales were collected, containing 8.23 grams of nitrogen. This leaves a negative nitrogen balance of 3.53 grams. The patient's average weight was 60.6 kg., a loss of 2.5 kg. In Period 3, the diet consisted of an average of 7.08 grams of nitrogen and 1553 calories per day (26.42 calories per kg.). Dur- ing the period, 49.59 grams of nitrogen were ingested. Only 25.26 grams were eliminated in the urine (3.61 grams per day). 6.40 grams of nitrogen were found in the faeces and 11.20 grams in the scales. This results in a net nitrogen balance of 6.73 grams in favor of the body. On May 10th, 500 cc. of milk, containing 2.51 grams of nitrogen were added to the patient's diet. As is seen from the chart, the extra protein caused no increase in the nitrogen elimination. The patient's average weight was 58.8 kg., a loss of 1.8 kg. <)0 SCIIAMHKKG, KOLMFJt, RINGKK, AND RAIZISS w Q C WCU 1 I <>! 00 co i-iOOO UjiOOp S - '~ T,QC- RESEARCH STUDIES IX PSORIASIS 91 Calorics c 1 I I 1 4 * 2 i-IOOOOlMC > -I IOIOOOO OS > 1*1 i-c i-ii-ilN 1 I 4 : - I a c M ' IM ^ fl^ ! flJ 5 2 r o 2 to j D 1 I 1 : s 8 1 o 5C 1 1 O 00 00 IO IO i-l IO COC5OOOTtO>O o t- t> to PQ = ^^ OOOONrHO +1 I++++ n 2 J OCON^N O5 CC -l U5 Oi N -^ is co IS O =1 .= U3 U3 US IS t- CD iS 118 r r tO t- IN t- IO N C US 03 -W 2w-S IO U3 US Tl> IO 1C 10 S; 10 l-s CZ |r I _a g 1 ^ ^7- 03 CO C0 Tf * CO 0] CM f -_ g^ OOO5SOOONOO 5^ >o T-I t- m o oo 1* ooooooo 0000000 f 8 OOOOOOO5 o g.s * ( -H t-H H iH -H O t^ ; i-sl 3^1 Jl J.H Z 1 T3 a II W ^ H TO * tt> U3 O CO IO O t- CD t- *O t> M e o> t- 9 g2 ooooooo o t agl O t> -I CO rH c " So 3 Ti> fli Ta> co n< * * C9 m a-^ T)< O 5 5 <-l OS O IrtOO'-HOrH ooooooo mo " 9 ooooooo OJ 5D C- Tj" -3- ^ Ol w OJ ia co IN 10 -fl 1 1 Q O i-H N CO -f "5 CO co st| o M 3 S SCHAMBERG, KOLMER. RINGER, AND RAIZISS i ao M X fltOW 14 C-4 N *ft j g o>oi in NO t- :S n U9 1 z l +1+++++ c t- T"O .. too _ v- zl no3Sfr> en ao LOO c .~ < Z 00 000 <* .2 tO tO to 9> t- to tO en t- - |||8 o 10 to oo to f oo gg = 1 Mint- 2j|5 s ^ = i .i .-N /-s *^ ^ *~* + 99 -.sz 00 00 -f to t- tO to & 1 J t- to x rr 10 eo 2 = = 2 oooooo 1 C- 00 00 00 00 00 00 = ir |Se U3 OO OO X < a e - <*. NN--"- 1 | oo to eo so o o .0 p- oo -r 10 eoenE^o odtc'oJ - J;C_8 fi z CO lO *O ^* to iO O j U3N'! 1 =O 4-flj3"" n 5 a c .7 5 C2 1 o | 2 l z t- IO O 00 >O I- t- to to t- to to to to te S Q H :::::: a a fc : : : : : o | g : : H 2 - , ^o : -S 11 r. - -- r. r. r. r. OOOOOOO 2 p : : : : . - fe g Zg gj u oeo ^rt z : : : : g g 00 3 |-s| 10 tO O 0> O t to 10 to to .0 to -a. C S'S -t ooooooo w e BQ - .?>; d 4.S.S.S -S 2 - 1 li ooooooo 2" ifl c *c 5f 5?" 5f *^ ^ bo 08 t- tOOO 1 ..si te ?1 *9 O M P If *| * ~ *j ^ *j ** *j ** ^ ~ - Z oooooo S| ooooooo U50 e o j 5S333583 n n j 'o c I OOOOOiOO = N C4 C4 M C4 C4 M t- N I ~ 3 2 .58 4=s;i ^ni/iNus^jS ?l SSSgSSS S3 d 3 fl co eo eo eo eo S" 1 II t^ O O OS 00 oooooo 1 i 1 "3 ::; ft SI E^i^5 5 | ...... |l^;|| 1 eo ,-!_!,,< en >> if ! sffliioHo^ ' 1 H < RESEARCH STUDIES IN PSORIASIS 93 Calorics cc co rH Tt in co co t- CO CO CC CC OC CO I *> c PI < K TC rH rf U5 t- rC CO U5 rH rH rH rH TJI CO OOOOOOO 00 JJ oo 'Tfcooo U5 t- O5 CO rH O5 rC COOOOrH(MIN g OOOOOOO " 1 OOOU5000 Ijo OOOOOOO U5 K5 K5 CO US 1(5 US < _g a i S : : : : 'S ^ : ' --3 a a S3 _ *> c o cs-a.2 2 a-w S S 3 o-E $ .2 .s.g-c a. o C o I s 1 o O5 -COOOCI IN -co t-e> > } 4 *> a rH^CO^lOOSOSO COOOOrHOOCl 1 . I < 2 INOOOOOrHC > g w tc C-rHOOrHrHU5T 1 1 1 J5 g rHOOOOOOC t "a a S U510OOOOOC > O -^ fc- lOCO(NK5int>OU rH rHCJrH Ol f > ) 4 id of Food i a : : : : a :.* . . . 3 . C ( . . . O to O ( i I 9 [ i 1 g I n rH O O5 CM N rH 00 t- 05 IN n * TJ. us oo ?i | J 00 00 CM CO IN CO CO 00 rH CO O CO rH US 95 r| .9 cocct-co^cct- us Q 11-11 t- 00 CO * _ rH 00 O5 O5 O rH f, 00 CO N O CO 95 *"<"0 '""* S" 5"S 00 rH 00 CO -^ t CD n la CO CO O CM rH CO O5 rH rH IN CM CM rH rH :2 g c '3 U5 t- O N t- rH CM :- 2 F o 00 05 05 0> 05 050 : w k' ,, rH CD * CO (C CM t- : ~ CODDt-U!t-CO :* E'S> OOOU5,,^05 : US "3 ||* CM ^}* ^f CM CO ^ CO :" O S ^ K5 rH CO ao O CD t- & p 55 O5 CD O 00 OS CO O5 CO CO CD 1(5 U5 CO K3 is 1* OOOOOOO OOOOOOO p ll ooooooco OOOOOOO CO SJ IN CM IN CM CM fM CM 2 eJf *! CO CD C- J -f U5 t- US l' s i OOOOOOO 03 O 1! CO O5 CO OS ^i U5 rH IM IN CM M { CM O OrHrHOO'-l'H S2 "8 "=11 OOOOOOO S 1 4 t- 00 IN CO N t- 00 O OS OO 00 if t- U5 ceo? t> 00 CO ^f rH ^H U5 OS OS O rH ^00 CD ?i oo IN C-J CO CO N N M a-f u > CO CO OS C- t~ 00 oooooo oooooo 030 "3 a > 9 OOOOOOO O5 rH CO K5 CO CD CO IN os c- o t- co in 1 *t U5 CD t^ 00 OS O COrHrHrHrHrHrHN 2 a '. ^ S" * * " H < H : : o * '% .3 : l^l 2 -fir^ 5 .^ a Sr os p Q Q W - H O o J ." J iz;oo o ^ O oco w S l^ < fe O PL, n rH O 4) M X 0> 00 .^ C 0) O ca ocO'E e C fe- 3^2 SCHA.MHKIU;, KOI.MKR, KINCiKIt, AND RAIXISS Amount of Nitrogen Per Cent of Nitrogen c-i -x r; t- O-HOOOOOO ; t^ oooooooo oooomooo o i o m I-H ic m m S .= -0 i - c -r i - 1 - 1 - r? x * ,^00<^ < z V 8 . Eate in Gra > woe -co oortoc ! >NN -i NO OOOOOOOO ism -rt- ta >->OOO-"OOOOO 5; | 1 H S' o jfi 31 ooooooooo ooooooooo ooooo looo NHMMWeijIcOM ooooooooo gO N -- S> 1- e O ;; o o t- 1 w o 'H {5 N N -H -H S ^ ^ oeooooeoo ooooooeoo ilii cncoc- 10 ^1 t- 7-1 IO oooid o lOCOt- w : : o 3 < ( : ! 3 : ' ; O K 4j . c ; 52 if K Q i i ;ii o.5 : s5s : g^Wi : ; o> g ; . - o, ||.|.s|lx S o a o a-- 3 i IO *O IO CO CM Cn ^* (M CM oo oo en i-c oo * 10 I" 8 ! OOCMCMCNr-llOi-CCM OOOOOOOOO "3 CMi-lCnCMTjicOTO-^CO rHOTOl-CTOOlOl-Ci-l OOOOOOOOO Amount Eaten in Grama oioeniorocoooo TOc-i-ioooocnooio Kind of Food . E . . : 5 - h ^ o 2 JS i ! ^ ^ ; >o g S CO t- i-l N CO O5 rH in * t- N us >o oo e ia g 5f zj m OOO-HOOO o | ' .1 * N C- t- CO tM N CO U5 U5 CO N >O O 8 t .9 CO ^"51" Tl" Tl< T}l T}< 8" a O O CO IO CO CO H (M O 00 TI- t- OT t- S il.a-a ^" ^* co co co co TO S" -S"S ooe-CMcno ! 8.|9B ^a OJcON-^iom ! N O N iH rH M . | o L oo t- I-H o o oa iffl ; N .-s i z O N CO CO -w TO * es a q 1 OOOOOU3CNC- ! '. n P - r eooo^-iooo : '. 9* 1 S' c ^ CO CO >* ^1 00 05 00 e s ^a CDU3C-OOOO . 90 & ta 10 1- o en oo co TJ" : 5 |* TO U5 CD t- 00 CO O5 1O Tt T Tf TJ1 IO TO t ; ^ 3 2 &* 1 rt ooooooo 0000000 H g g 5c2 -- *. C^ -. ~ ~ ~, t g.a i-l rHrt^l 111 ^H -o co H oo a> ; 10 10 Tf IN IN * . & S 2 oooooo : a a 11 11 N * t- t- t- 00 * * co * co Tt 13 in OJ M R II OOOOOOO - O iS -S 1 rH (M 10 -! O !O<-iOt-t-t- i-l N SM i-l r-l i-l ao 3 gs OOOOOO . o a i-fl Tf 1-1 10 en c en -S 8 ^| ooooooo o 1 sl en us t- i-i co 10 en r-l C 00 t- 00 00 CO N O n en < *% i-lOOOOOO -' o 3 TO 00 O 00 CO CD 1O CM O 00 '? t- C35 t- e oo ".<*>. ^1 (N CM iH i-H i-l iH iH n * si. f Is CO rf rH CO CO 1O t- i-li-lOOOO oooooo ; too * y ooooooo CO C7S 00 t- "f O CO co o> co co en oo o rH r-lCMrHCMCM i Q O i-l i-l CM TO 't'O COTOTO 9&. |, , , j S 5 Total.... yverage <)<> SCHAMBERG, KOLMER, RINGER, AND RAI/ISS In Period 4, the same amount of nitrogen was administered as in Period 3, but the diet contained a higher caloric value (36.5 calories per kg.). During the period, 52.45 grams of nitrogen were ingested. Only 20.89 grams of nitrogen were eliminated in the urine, i.e., 2.89 grams per day. 14.03 grams of nitrogen were found in the freces, and 8.83 grams in 66.0 grams of scales that were collected during the period. This leaves a positive nitrogen balance of 9.3 grams. The patient's average weight was 58.5 kg., a loss of 0.3 kg. On May 18th, 1000 cc. of milk, containing 5.05 grams of nitro- gen, were added to the diet. In normal conditions, this would have caused a considerable, if not a corresponding rise, in the output of urinary nitrogen. In this case there was no increase whatsoever. The significance of this will be discussed later. In Period 5, approximately the same diet was maintained as in the preceding period. The period consisted of nine days, in which 70.21 grains of nitrogen were ingested. During this period the patient eliminated 40.57 grams of nitrogen in the urine and faeces. 114 grams of scales were exfoliated, 14.4% of which was nitrogen, equalling 16.42 grams. This leaves a net nitrogen balance of 13.22 grams in favor of the body. The patient's average weight was 58.15 kg., a loss of 0.35 kg. On May 22nd, 100 grams of sweetbread were added to the diet. This meant an additional ingestion of 3.54 grams of nitrogen, or a total of 10.65 grams. The amount eliminated in the urine was only 3.40 grams of nitrogen, an increase of less than 0.7 gram above that of the preceding and following days. On May 27th, the patient was given 20 grams of glycocoll (Kahlbaum) containing 3.74 grams of nitrogen. 2.75 grams of extra nitrogen appeared in the urine of May 27th and 28th. All of the extra nitrogen was eliminated in the form of urea. There was no increase in the undetermined nitrogen. Almost 1 gram of the glycocoll nitrogen was retained in the system. From the foregoing, two very significant facts stand out promi- nently. First, the very large amounts of nitrogen that may be lost I through the skin in exfoliated epithelium (scales) ; second, the small amounts of nitrogen eliminated in the urine. In Period 4, the daily average of urinary nitrogen amounted to 2.89 grams; in Period 5, it was 2.78 grams (excluding May 22nd, 27th and 28th, when spe- cial substances were fed). These are the very lowest amounts of nitrogen that have ever been found in the urine of an individual of that weight. 21 In Period 6, we wished to find out the lowest level RESEARCH STUDIES IN PSORIASIS 97 > W *T3 ^ o bo . CD'S OOCMCMCO C- a>< fe OOOOOO OS t. O.M OOOOOO >-'Z' oooooo 8 "3 S 3 00 tO IO rH rH O5 CO O CO U5 T)* O C-tOOOrHCMO 1 ooo^'iOTi'o O CMOS tOtOOJN CMrH(NCOCOCO fir* O ^ SO 00 00 00 00 CD O lO 1C O t- g be g O JH mcOOCOCMU5 00 H p g 1 * 00 rH 00 to 00 oo ii rHOCOCO-*tO tOl>CrH tO t- t- II oo ^ c- oo en co oo S a P c o O lf5 Cft W rH O o S3 * fa ^ Tf -^ 10 l> CO i b W g 1 O1U5 to CM !>* CMOOtOCO>OO5 n * H H S o H E o d tOO^fOrH t- S PH i * * t- tO * IM CO oo Eel CMOOOrHtO to 00 )<>J 1 1 1 1 1 1 COO C-T)>z 73 W O,M o>i-ooo ; rHrHOOO 1 SSi'gli ooooo Ifft toiooococo ooooo P^O^ ooooo * I'll SOOOCM rH C ^f Oi CO 00 G> S 'g&bb Tl.USUJtO ISM o' c-i oo o' . . c - >> iU o cot-mto tocoujto THCMrHrH III OS U3 to W3 Tj< 6 rlH sssss I B I cot>t>o IMCM-^CO N r ( g w toinwo ^ ll S552S : o II Zffl l + l + l 2 18 HI bo 13 g * to o' o to r-! . lot-coco -II Ti W 00 l 8 ^ WrHO t-U5 . 8 oo oi t t co co i" OOJIOCMU5 CMCM rHrt COrH^ci rHCMCO rH T3 1 -*>>? 98 SCHAMBERG, KOLMER, RINGER, AND RAIZISS that the urinary nitrogen can be reduced to. We therefore reduced the nitrogen intake to an average of 4.39 grams per day. The total nitrogen intake for the week was 30.70 grams. 13.78 grams of nitrogen were found in the fasces. The amount of nitrogen elim- inated in the urine sank to below two grams per day. Only 13.16 grams of nitrogen were eliminated in the urine for the period an average of 1.88 grams per day. 74 grams of scales were collected, in which were 8.75 grams of nitrogen. The nitrogen balance for the period was as follows : Ingested Excreted Scales Balance Body Urine 'Faeces Weight 30.70 13.16 13.78 8.75 4.99 0.25 kg. We believe that this experiment throws a great deal of light on the mechanism of protein metabolism in patients with psoriasis, and we shall return to this later. At this point we wished to place the patient on a nitrogen-free diet, but, to our great disappointment, family affairs required her immediate return to the home. On June 6th she left the hospital. SUMMARY OF RESULTS OBTAINED IN THE STUDY or PATIENT No. 8 In this patient, as in the preceding ones, a marked tendency to nitrogen retention was noted. The lowest figures for urinary nitro- gen (1.88 grams per day) were observed in this case, when the intake was reduced to a little less than 4 grams (table No. 5, p. 97). During the course of the investigation, which lasted 44 days, 293.4 grams of nitrogen were ingested. The amount excreted was 210.63 grams, resulting in a positive balance of 82.77 grams. 446 grams of scales were collected, in which were 58.38 grams of nitrogen. The detailed study of this case shows very clearly to what a marked extent the condition of the skin may influence the urinary nitrogen (see Period 6 and page 130). PATIENT No. 9. J. H.; female; single; 18 years of age. FAMILY HISTORY. Her father was killed by an accident six years ago, at the age of 41 ; previous to the accident he had always been in good health. He had had psoriasis on the leg, when a young man, before he was married. Her mother living, aged 45 years, in poor health; she complains of stomach trouble; she has had rheumatism for the last three years ; she is free from skin diseases. An uncle, the mother's brother, had psoriasis seven years ago and was treated in the Jefferson Hospital of Philadelphia. An aunt by marriage, had psoriasis PLATE XXXVI. To Illustrate Article on Research Studies in Psoriasis, by DKS. SCIIAMBERG, KOI.MER, RINGER and RAIZISS. o =-' 5? THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. 99 in 1912; the attack lasted five weeks; she was treated by a specialist and has not seen any sign of the psoriasis since September, 1912. The patient has three brothers living, aged, 14, 17, 21, respectively, free from skin disease; one sister is dead. $ PERSONAL HISTORY. The patient was born in Roumania; she has resided for the last ten years in the United States; she worked hard at sewing; her appetite is poor and the meals are irregular. The meals usually consist of two eggs daily, meat once a day; one glass of milk and one or two slices of bread daily, cocoa occasionally. No wines, tea, coffee or alcoholic drinks. The bowels were usually constipated until she was operated on for appendicitis in the German Hospital, in 1912. The patient has had measles; the date of the attack is not recalled. Her menses began at the age of 14. She had erysipelas in February, 1913. She has suffered from headaches since she was nine years of age. PRESEXT ILLXESS. The patient states that the cutaneous trouble started four years ago, at the age of 15. She first noticed a red scratch on the left shoulder; then papules started on the right shoulder and elsewhere. She was treated in the Jefferson Hospital Dispensary in 1912. The patient was admitted to the Polyclinic Hospital on May 12, 1913. She presented plaques of psoriasis of varying size upon the trunk and extremities. The plaques were not numerous, but were large in diameter and considerably infiltrated. An extensive psoriatic belt, having almost the shape of an abdominal binder, extended around the lower part of the abdomen; this area of psoriasis was very scaly, thickened and elevated above the surrounding healthy skin. Scattered plaques were present upon the arms and legs (Figs. 17 and IS). Vaseline was applied to the eruption to relieve the distressing tension and fissuring. The eruption improved, but did not disappear by the date of the con- clusion of the metabolic studies on this patient. Chrysarobin, in ointment form, was thereupon applied with a resulting disappearance of the patches. In Period I, the patient was kept on a diet consisting of an average of 6. -I grams of nitrogen and 1643 calories per day (30.5 calories per kg.). The total amount of nitrogen ingested during the period (8 days) was 56.18 grams. The amount excreted was 56.84 grams. During the period, 46.0 grams of scales were col- lected, containing 6.23 grams of nitrogen. The net nitrogen balance was, therefore, 6.89 grams. The patient's average weight was 53.96 kg. On May 18th, 1000 cc. of milk, containing 5.05 grams of nitro- gen, were added to the diet. As is seen from the chart (page 101) less than one gram of extra nitrogen was eliminated in the urine. The rest was retained. In Period 2, an average of 7.04 grams of nitrogen and 2317 calories vere given per day. On May 22nd, 100 grams of sweet- bread, containing 3.54 grams of nitrogen, were added to the diet. On that day there was an increase of one gram in the urinary output of nitrogen. The rest was retained in the system. On May 27th, 20 grams of glycocoll, containing 3.74 grams of nitrogen, were added to the diet. The nitrogen elimination in the urine was 3.80 and 3.98 grams on the 25th and 26th of May, 100 SCHAMHKHG, KOLMKK, RINGKK, AND RAIZISS respectively. It rose to 6.00 and 5.95 grams on the 27th and 28th of May, and came down again on the 29th to 4.12 grams. There were eliminated 3.67 grams of extra nitrogen, which is almost quan- titative elimination. A glance at the column of undetermined nitro- gen, however, reveals the fact that not all the glycocoll was catabol- i/ed. The undetermined nitrogen, which was fairly constant 0.57 and 0.53 grams per day rose to 0.93 and 1.31 on May 27th and May 28th respectively, to fall again to 0.48 gram on the 29th of May. While all the glycocoll found its way to the urine, only 2.53 grams were eliminated in the form of urea and 1.14 grams were eliminated, in all probability, unchanged. The total amount of nitrogen ingested during the period (9 days) was 70.67 grams. In the urine and faeces there were elim- inated 53.10 grams, and in the scales there were found 5.27 grams of nitrogen. The total output amounted to 58.37 grams, resulting in a net positive balance of 12.30 grams. The patient's average weight was 54.53 kg., a gain of 0.57 kg. In Period 3, the nitrogen intake was reduced to an average of 4.28 grams per day (for object of this experiment see pages 96, 98). The total amount of nitrogen ingested during the period was 30.04 grams. The faeces of this period was found to contain 13.54 grams of nitrogen. The amount of nitrogen eliminated in the urine was 20.94 grams, or 2.99 grams per day. The nitrogen excreted in the urine and faeces, therefore, exceeded the ingested nitrogen by 4.44 grams. In the 21 grams of scales collected, there were 2.47 grams of nitrogen. This results in a net loss to the body of 6.91 grams of nitrogen. The average weight of the patient was 54.6 kg., a gain of 0.07 kg. (Patient No. 8 was kept on the same diet in Period 6. Note the difference in results. See page 95.) In Period 4, the patient was kept on approximately the same diet as in Period 3, but with a higher amount of nitrogen, namely, 5.16 grams per day. The scaling diminished considerably during this period, so that only 2.5 grams of scales were collected. The total amount of nitrogen ingested during Period 4 was 36.15 grams. The amount excreted was 30.47 grams, leaving a positive balance of 5.68 grams. The average weight of the patient was 54.54 kg., a loss of 0.06 kg. The average amount of nitrogen eliminated in the urine per day was 2.47 grams. When we consider this amount in relation to the patient's weight, we find that 0.0453 grams of nitrogen were elim- inated in the urine per kg. of body weight. The question then pre- sented itself, what is the lowest amount of nitrogen that this patient RESEARCH STUDIES IN PSORIASIS 101 8 ' a u e.S'Ti w o rt 3 -w S 3 g'C cJSia O-" O-.S rt 3 H 1 "3 o 0505N -IN -0! O5IMO -to -C. CONrH > 1 0*0 g to ^ t* to TJ" t- O ^ tOOC-OOrHIMr- fl g OJOOOOOOC 3k 1 rHOOlOOOlOO, IO Ol rH Tf rH IM CO CT t- rH 10 O O rH rH I- s g PH & rHOOOOOOC Amount Eaten in Grams IW 1 ::: "d : : : : :8 .... .3 '. ' I ' M "S -2 jJ * c 3 S Z mpqiioHO^a: , 1 d i f wcooo :COTJO^ CO rl I toiooo n< IOCOIO "5 TfO oico Q T(.rH Nitrogen balance 0.66 gms. ANALYSIS OF SCALES COLLECTED DURING PERIOD Weight Per Cent of Nitrogen Total Nitrogen 46.0 13.53 6.23 gms. O U3 ifl i lO U5 U5 lO z l &ON?S8 e . O ; T < T+T++++ J a SS oo g c?g I: to .o t- to to S to to a-a (B m O>CO^CONOOt-00 V. ooo to to to to 10 10 1 "S O.SS5 ooc-ojto !t>t- CJt-OOrHCO !O1M i* t- OrHt-CTSOujrHlO '. to coiot-t-ooteoooo l NOVC-OICM IrHOS is rH rH CJ CO CO .CON 41- rH10tO(MtOJt-5 "5 ; to 00<33t-tf3^U5lOCO 1- rH^COOlO^^rH IS 2 :::::: 1: oooooooo oooooooo g :::::: 1 8 l.s :::::::: |i 1 1000 c.c. of milk added to diet, containing 5.05 gms. of nitrogen. BALANCE ] Patient's average weight Calories per kg. of body weight Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted i-si J1J SS3SS :SS ooooo -oo If 12 11 tOCOtDtOtOCOCM^ 1- 0) 0> * t- CO oi o oooooooo II SSS5:5 :S us ooooo -oo . o a $%ZZ$2 S CO 00000*00 CM o If tO 10 t- N rH U5 CO O t- o - a> 10 co o t-lOCOCOCO c 'c o ; v 102 SCHAMBKKG, KOLMKK, RINGKR, AND RAIZISS S > 5 1 2 2 ~ H 2 1 2 rHOOOOOOO 4 COU5CO -HN -000) CJfJOO -W* -MOO CONN 1-1 *+ cxoooooooo inio oot-NO>mwS"5 - ^ O ' i M M "- 1 + 1 + i- c -i t- [ - 1- s ~ : e t- o 10 o oo n t- o "" ! o> oo n t- .m-^'tDioio 5 ^1" U5 CO U9 tO *O o o o" d d o o o o .Ooooooo U9OOOOOO f M ^- M N N t- I I i i i i I, 2,o5 e!5|S "a ^T ^ O 00 t* H^ & |3 :| 's ca : 8 S SM ."5 a s o) - gj . S^-cg g Ifca-fti3 M ca S.S.S.S g - < .5 wccc-^cZ if 2 ^" RESEARCH STUDIES IN PSORIASIS 103 I 3 ^ ^i * N CO t-l 00 O n< TH ic co TJI co co U) u> U) -^ a m co Tf cq ic - s ?'S o t: g s g g e-c "is o 3 o a OPQMEHHlU a 5 to 1*32 coco -iccncMo OCM THIMrHU 5 5 k ooo -oooc ! d a) V bfi ""1 10 -oo i1'*!OO rHOCO -rHCOOU 9 ft !5 OOrH -OOOC 9 Amount Eaten in Grams 1C 1C OS 05 IN 1C 05 C CM t- rH CO rH 00 00 C CO rH rHr 9 > I i Kind of Fc ' 2 :|-o|g^' S c a tJ a s S 2 ea aj MEHOOOCK* 1 00 CO TJI 1C o 1C 1C ! e 8 1 -^ -*f Tf TJI 1C Tj* TJI 1C 1C 1C 1C 1C 1C 1C * ; >o -I s O N | .a CO * > Tf -fll Tjl Tjl o eo a OOCO1OO1C t-O O5 CO 1C 1C 1C O5 CO ao ^i 8 g^.s-e S^ 1 1-2, co cq a> I-H o Tf t- : w l-r -* O 1C . U) I A/-L t--^f*OJ>IN ' t s 5|* CO * to t- t- 5 t- > . f* OS1O < 8^ OOOOOrHNN : w oco Q NrH X 1* Oi 1C 00 f rH to -^ U> S 1C 1C CO 1.0 1C :S 2 ' 5 : : : w 1* EH ooooooo ooooooo fm ; : : : C -r> CO CO CO CO CO CO . g :::::: w : : : 2.9 w : o : : * N IM 1C 1C 1C -^ CC CO 1C 00 M o u> 3 : s : < :'| : 1^ ooooooo eo o m -i -s 1| 1C Tj" t- 00 CO IN t- CO CO C S2 5|.s.s.s| 1 'II ooooooo "llllll |-3I 10 10 en a o as iH fH rH iH rH N rH 1-1 1 N -H llllil oSogZZH 3 ^2 ooooooo o I a B o _- 4 CO rH O] O> O i-H CO OO IM 10 CO CO C- T)l 9> ce oo i 3 *c3 tt> 1C O N t- IN * T|" O Tf CO 1C CO O CO s H;H Z TJI CO N N IN CO O} o c-i N it t- oo oo co en t- oo 000000 oooooo : ; coO .SI OOOICIOOIO O r-> 1C 00 O5 CO ")! a> t- en c-i ic co t- rH rH rH CM rH CM iH i 1 p o 1-1 1-1 oj co T|I 10 CO CO CO S&. S- :5 , S' 5 Jl 5 S ^ t) Q Q P O jjr 00 C * 101 SCHAMIiERG, KOLMER, RINGER, AND RAIZISS O e LI oo co oo **f ~f i to to to W t- 2 m wooeto t- M M CO CO 1 i 3 < ; ooooooo * g *8? 00 C t~ O wi -i 1 1 00000-0 g i ! 5 o. 1 --g $ Sj *3 -o 4> * 1 : i : ; E I \ IO -OO -l-TO o to oo co o I- ! 4 E NtOC-OOOlOJO OOi-ii-iNf-ct-t 1 5 2 M ii o * o 1-1 11 co o 1 i [ 1 2 > Amount Eaton in Gram* j-U5Ot-OOO i->t-CO>OiOOOC ^ _ :; f 1 I 1 "8 1 '. : a : : : ::8:^ S i^sSal- Ullliit i I i ' X i sf CO us to co oo oo ^ f 3 so to o i i St-a t- iO i^ Tf S'oco o CO CO CO Q - 2 . -.-.-. -.-.-.- t- m 30 m to so o> +++++++ J .9 S255S5S 12 2 to 10 " u " ' ous ' fi " lfl fill za.S 5Sg^S?25 8* Per Cent of Total Urinary Nitrogen Ot- OSOIOCO e ! oo SS S22 1 Z o>o ootocoto ;3 MU5 COCOM | Z CO- -COUStC :- "" -*"'* ' :"* ii* t~ t~ CD O 5O (O i 3 0><0 000>t-OJ i- enio OON-V ii ggggggg as : a PL, 1 -c 9 s H 5-9 oo oo oo oo oo oo oo N ; 9 giiiiii H : BALANC Patient's average weight Calories per kg. of body weight . . Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted !i} * USTfXfS ;5 OO OOOO jj sS !i ; oo 6 oo oooo ii II r-e> oooto is 00 OOOO *1l into NO) t-oi Nil MC4 M is OO OOOO i! B - s -.:; woo cocoi-iio is l| SSSS5SS ss NNNNNNN I U3 toouJOOt- OOOOOOO ^ ; SI CM to to oo to to i- cc w r5 to ffi co 1 CO .-HHi-4 2S il RESEARCH STUDIES IN PSORIASIS 105 PATIENT NO. 9. MISS J. H. PERIOD V Calories CO O OrH 'S' Tft- a o S : w ..::.. | CD oj t Hi oo oo N 77 - g [hi < z i-IOJtO rH O O OOO (Q O CQOO ft cao o oo M eo e .a OONCO o'oo 10 oo r* O fin ^coeo n t-. 1 1 rHOO OOO t-to oo oo | "3 3 fr S^ Amount Eaten in Grams rH^nOS t- COCQ r o>o r-l 00 3 & lO-rX i-l (M 1 -3 ^" '. ' IO I M : .S .S ,.2 0010 | 2 So' S.sg 1 * .sg 1 ^ I 2 III :::::: : 6 00 O 00 O O IO to 1 B ll 00 00 00 ^ ; > 1 a : BALAKC Patient's average weight Calories per kg. ol body weight . . Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted Nitrogen balance 11 5000 OON do H m oo 05 to 10 oo e 5 ^ S ~s t-oo 01 Oi WIN ooooo OO 12 t-O si do' ta *1| c-o> do* ooooo Amount Eaten in Grams 1-HOOl-HCON HNrH cat- 4 rlO 3! yR IO rH Kind of Food 3 H s| II Diet, Jun Orange Apple Banana Peaches Sago pudding . . y OOO oot-o 00 O> t- Q CO i-l i-t rH tt* 2 25 rt : : o > ? H < 106 SCHAMBERG, KOLMER, RINGER, AXD RAIZISS i I zjj - /. : : Nticoco iS 1 *1 siss ss 1 J 1-1 H 1-1 52 lll 55'! |3 ll CD CO W 00 |a 0,001010 | 00 CM ~t > I 1 ooceto i - K H U5U5O NOlO 8 M 1 "8 4| 2 C000>0<7> 8 p - COU3 "TJ 'a S (2 5 ic -its P* i -I ai i >o us ot~oooo _ _ _ _ Q o S ::::i S [JHI: S HH S O5 111 ggg Nitrogen inFecee t> U9 g i; ; ::i H ::;::: d X *' .s " 111 Nt-t-i-l Miaiaio o' d d o - ii It;; S & z &-S -i E* fc K i i 1 l^ H || o^tcnt- 9MOC r. CO CONN OOOO O> M GC M -o :3 l: s . ; g \ 8 t || sill il I^.S| t| . I &2 oooo e e ?.iin |.fi _c S . 1 n} *rt-oeo o o' o o O M So .2 o S ? 04J434* | ij 5555 s'g ! ~ s -iio'cct- 5"* ^l r r. . O M O O "5. NWOCO a- tt .... O 3! IS i i 1 ^ oji-iroi-i OOOO Amount Eaten in Grams ooot- oooo M i-l i-H Kind of Food Potato cake Peaches Cornstarch pudding .... Strawberries Total 1 * 10 to i-H N anN** C-lON CONtOIN " v 1 1 TC * 10 00 r)" O O iH 00 iH r-< MOUJCOOO Si "o 1 g CO t tOIN-^OSNO l> i-H IO rH i-H rH iHOONOO |3| OOOt-OJO mcoiot-oio i-H d tHrH I 8 T3 1 >,' * 2 ^acS ^=gSSS PQP52WOO II cororacoraco 50 .H i-H 05 rH 00 OOOOrHO oooooo e-i N N c-i ca N tO 00000 Ot-r-l SCP Q O r4 M * 00 09 O O O >H O O ~ ' ~" ~''~ I-IOOOOC4OO llll -. T i - ? i e. i - -. - - 11 II 31 to X O ~ 0>* 00 0 O M i-l C- CO IO -^< t- t- to ooooooo 0000000 os to to ia ^] co co 1-1 oo 10 oa co t- 1- oo'o'oooo' |o>r-ito-*eoc5eo .000)000000000 CO Ol 00 IO C- O5 CJ tO tO 10 N CO IN O 00 t- t- IO tO to O) ^ * oooooooooo OOIOOOOOOOO os >> - - s S 8 = S al.. rag bits II <35^ 5 112 SCHAMBERG, KOLMKK, UINGKH, AND RAIZISS PATIENT NO. 7. MR. AB. PERIOD III 1 nftn t- t-o ft * JL zj to in S -)- R PERIOD 65.3 kgs. 52.7 214.10rgms. . 163.98 13.79 177.77 +36.33 gms. r oo >o N f oo N - - i- ; -- : n 2 * O O, i z |K N IH Tf C- O5 t- >O i| 3 TfOOO -ONN eo-ioo -i-i Analysis of Urine and Feces Undeter- Nitrogen mined inFeces Nitrogen 50 CO 00 to 10 -( O> * : ; BALANCE FC Patient's average weight Calories per kg. of body weight Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted Nitrogen balance 000000 >ae H < 2 ggassgg 11 sssssss N O o e NO<00 ^2 2 tOUJ to " N O r-> O> N C- t- r- lO O r-l >-l O ooooooo 41} o> to 10 to -f d oo o o o ei i-< 35 fHOOOCMOO o------ Amount Eaten in Grams IOUS Tf rH lO \Q Ob v9 l} DM^f MOJt- W 00 00 : 9 SS532S3 H.f i-< us o> o ec o o ~ X t- i~ 55 MNMCJMNO) Kind of Food ^ WCSNO5O5 t- SI OOOOOOO *r o o o o> i SN- |||? Hi 1 ^>oa * O rf CO 00 U3 N < -5 NOiOMr-lOO ij 00 i g r-l O O N N rH O Amount Eaten in Grams lA \Q CO CO O O tfi ^Ji Ci >O r-l IO O 00 CO 00 r-l Olr-l r-l 1 fa a I 5s:Soi:a5 cocooooooooooocw U3U31OOIOU3U3U51O COCONO)t-Or-f^llO W_ O 00 O 00 W r-l r-l O t-OilQWWWOOOOOO cocoiaocooooror?-.o NOOCOOt-WiOinoO 3r-lSNNr-( 3 a I ^C a ... m S v ffl Q> O *" S "3 2 ~ 1 - g 1 114- SCHAMBKRG, KOLMKll, RINGER, AND RAIZISS O t 00 00 CO ^3 *+ O i O O i M ^ OOOOtOCO CM T oa><-< t- i-l O CO W rl 00 O5^OO^>tOt-O = '--] -^ =. -< MM i-l : 8 1; il ill lO O ^* O O t- * IO tO CO C- t- OJ C M' .-i 00 us o od to 10 o to 10 oo o ii .1 oo N oo oo co M e 1-1 o en oo oo co co w co wee i-i -OO r-IO5COOOt- >OINt t- 00 rH i-l 1O COMCD Amount of Nitrogen CNOr-lOcNCOOOCO T-I m o to 03 to >a ss m I scjj IO tD CO ID 1O Tf to 00 Ui n ++ | S g-rg <-H t- N tO 00 IO t- 00 !O O Oi O ^1 -* CO . co .s to to * to co in to 000 00 t 91 US ifeSfe g(3.a-8 -IOOO.-IOO> N IN IN IN N IN r-l n o 3 N ll- 5 1 1 1 ^2: 2 1 Si S p* - I co oo cotaco -. 101000 -f i-l iH 1 a's z i*S ^a oo o ^.10 A J (Mr-l Q COrH g ...... 2 :::::: H I- Tj< Tf Tl" Tjl T)< Tjl CO CO CO CO CO CO CO CO S ::::: g :::::: Pq 52.9 u : i^g -is g) I -a 3 g ll M s| , :i| 'p 1 2| oZ a^ssi cfi M o *r* u -, p* II fc-^*2 3.2 g 5&.S.S.S? 1 II M^fiClC." > 6 8 9 a C-gMMUl^ I a i-SI ifllil s J i 1 si 1 55 K -g 5 M OOOOOOOOCM OCOTC t->OO> W 00 09 fll 2 ooooooomoooo N 00 ft 8.8 O-*CONU5COO> CM IN ^H r-( r-l .H rl ooooooo raO n ooooooo IN lO U5 <* TC * IN O O O5 O5 tO CO Tf I CO t- 00 05 T-H IN 38. - i 15 1-5 H< llf> SCHAMHKRG, KOLMKH, HINGKR, AND RAIZISS i oo 1 --" ON = 1 _i_ S : : : : : : W ft U5 CO 00 O> eoeowoo t- s x zj . 00 * ** N r-1 M ^ *1 382$SS? gs II OOOOOOUJin 3 >. .9 MMNC^ICMCIM AM - 111! O> n <"" .S p . Creatinin * N : : 2 S ~ + OIMM.I I o : J5 a :. J S 8 1 *'" ::::::: e^ ^to 06 oo Q 2^ c fill -t 1 r^ 3 w 1 & S ::::: : H CL, K S 1 "3 - 3 '3 "3 3 3 "^ e : w : 1 NU5O -^i^^TfT) S-. 11 X 1-1 i-c U5 US t- .- 1-3 NNNNMM*, so ; c 3 |ll 3 I J25 1 I :- v 1L| t-TTO^OCOt-0- w :|| i C. *K ** K TfOUSOOi- L - OD *I OOOOO>OO<-i n 71 ?: 06^: n o> R s oo C3 Illlgg t- 1 8 si 2 00000 ;- ~ ;- ;- .-. 1 1 a s : : : :| -' C 2 fi ------- r .- ' 3 Hii^ggJilSS I SI 1? ;^ H < RESEARCH STUDIES IN PSORIASIS 117 Calories 00 CO CO IO 00 c a a h! < 55 t-rHrHCO OOOO eo CO "i " U-g g J3 g CON * HOrHlXKO CO i-l i-l CO oooo Amount Eaten in Grams oooo oooo NrHrHrH Kind of Food 1 Potato cake Peaches Strawberries Cornstarch pudding l CON5ON i i M < z w^io oooo NOU3COOO Fl SO N *3< Oi N C5 t- i-C IO i-l rH rH rHOONOO Amount Eaten in Grams 1-HOOt-rHO rH CJ rH rH Kind of Food |1||| a 1 i O rH -CNI tO '. IN TJ! oo oo NCO Q "" o Pi H .::::: 33 a ? 8 | -a ! z 8 m rH CM 00 -* TJ< CO CO 00 -H Per Cent of Total Urinary Nitrogen ii z l z 1* (NCOO ^l z t-wt- : : : 10*0^ . . . i- Analysis of Urine and Feces 1 1 | ooo . M M N M CM'" NNIMNINN 10 eo 05 :::::: o : if 1-2 1 Patient's average weigh Calories per kg. pf body Nitrogen in food Nitrogen in urine Nitrogen in feces Total nitrogen excreted 11 II 5O1OCO OOO - 8 HI oot-o . . . ooo : ' : !.! rococo - rHrH rH . . - If t-iooowooo N5OCOOOOO goo S22Sr12 !: - GOO OJU50OOO rH(NNi-HrH(N OOOOOO rHrH rHrH rHrH ii SOOOOO 00 10 IN-* 00 OJ 5 00 t- Tjl 00 Q CONNININNIN ss. . Total.... Average . 118 SCHAMBERG, KOLMER, RINGER, AND RAIZISS to what extent the sojourn in the hospital alone influenced the course of the psoriasis. In Period 1, the patient was placed on a diet consisting of an average of 24.89 grams of nitrogen per day. The heat value of the food was about 2600 calories per day, or 47.8 calories per kg. The total amount of nitrogen ingested during the period (12 days) was 298.64 grams. The amount excreted was 244.48 grams, result- ing in a positive balance of 54.16 grams of nitrogen. The average body weight was 54.9 kg. In Period 2, approximately the same diet was continued. During the period (10 days) 237.11 grams of nitrogen were ingested and 208.38 grams were excreted, leaving a positive nitrogen balance of 28.73 grams. The average body weight was 55.4 kg., a gain of 0.5 kg. In Period 3 (7 days), the nitrogen intake was raised to an average of 30.59 grams per day. The total amount ingested dur- ing the period was 214.10 grams. The amount excreted was 177.77 grams, leaving a positive balance of 36.33 grams. The caloric value of the food was about 2900 calories per day, or 52.7 calories per kg. The patient's average weight was 55.3 kg., a loss of 0.10 kg. In Period 4, the average nitrogen intake was 27.36 grams. Dur- ing the course of the period (9 days) 246.27 grams of nitrogen were ingested. The amount eliminated in the urine and faeces was 210.77 grams, leaving a positive balance of 35.50 grams. The average weight of the patient was 55.7 kg., a gain of 0.4 kg. In Period 5, the nitrogen intake was raised to an average of 38.65 grams per day. The total amount ingested during the period (7 days) was 270.58 grams. In the urine and faeces were eliminated 218.43 grams, which leaves a positive balance of 52.15 grams. The patient's average weight was 56.5 kg., a gain of 0.8 kg. In Period 6, an average of 26.09 grams was ingested per day. The total amount for the period was 182.66 grams. The amount excreted was 143.98 grams, leaving a positive balance of 38.68 grams. The patient's average weight was 56.3 kg., a loss of 0.20 kg. In Period 7, 197.90 grams of nitrogen were ingested, *. e., an average of 28.27 grams per day. The amount eliminated in the urine and faeces was 157.10 grams, leaving a positive balance of 40.80 grams (see table No. 7, p. 119). This case has a special interest, inasmuch as the patient was used partly as a clinical control for the other patients. In order to determine whether psoriasis would improve as a result of the PLATE XXXVII. To Illustrate Article on Research Studies in Psoriasis, bv DBS. SCIIAMBERG, Koi.MER. RINGER and RAIZISS. a - a .22 > M.O .2 ~ CO Atf-a < pi H ^ ^J "K ~ 1 r3 t~ 80 V i 09 H d ~t Ct N 4-> rH CS ."5 'w be _3 X' 3 S E '3 o3 ^H cS s ^o &i U ^^3 o i. y. K "U 9} u V M i 1 t. -- -H C CO ^ U a 5" 05 A r! -5 4-T C tc * C G ' ?i C C o fci S _ 3 cS ^H ^ V ^ meas I ^ < j pi ^ ' tc c j SB?, g 8 Z -a c8 8 en . <" J2 -K * P-I PH O THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. PLATE XXXVIII. To Illustrate Article on Research Studies in Psoriasis, bv DKS. SCIIAMBEHG, KOI.MER, RINGER and RAIZISS. s sal ^ .y ^ PM -- . -1-* &c c 3 &' O T| , u "w . rJQ -* VJ g^|S O 2 e - rft 3 PH o t/2 <| J3 pi M t-' 2 05 THE JOURNAL OF CUTAKEOUS DISEASES, November, 1918. RESEARCH STUDIES IN PSORIASIS 119 - Ls a* a 1O rH OJ Tf CO i-l t-NCO t-OtO n"* tototo t- O w 1 *C b i& CO 04 C- 01 r)i 10 5 Q.b^ g CCfi O C-lONCOrHtO t T* 1O IO1O U5 Il 3-Q iH O TJI M * CJ C- 4j 8?! o> TJI w t- us co ii! * ^f 10 10 in o to S s Q; o be a tocoeoousooo i-l t- CO >O rH D 00 in n .B*3 g SOOtOlONCOO N CO CO "5 CO ** % w d S -g SrHOt-00)0 rH rH N "3 O O * 2.S .a fa S CO t- -* O IM t- o> co 1-1 Tf t- oo o N CSI (M J co oo t- 1- co oo o rr co t- 1- -* o> t-i en I 55 ! w -^ oo c- o oo co t- TC O t- rH <-> Tl< U3 N N iH M OJ i-l iH C4 d m o os o 01 o I-H co to t- N 10 10 to .S ""fa iH 1O CO C75 Cft rH CO O O 2 S3 as NOOt-rHCOO> t- CJJ U3 O5 "* ^ s r s (N (N CO -> 00 OJ 00 CO C5 CD Ci O CC CO M .-H rH i-l (M it H e S i*i o] o t- cn t- 1- 1- * Hl ~ l s 8 I Q OCOO05U5NOJ (Nr-lNM ^Cr-( .>.>.>. a> a> t - --! = : = ft^? CT)"*^OtOCO i-ICMCO rH ^ >>,X>.ffl 2 fe o! CS (S >p fe~ *> ! -2^f > X tm o a, t- N CO CO to U5 0> 10 loocoooTjic-t-oj OrtOOOOOO ! '''oWPQfe fa oooooooo z l*&s 3SS-| NNCOOCOtOOO coot-tototocnoo OrHOOOOOO g'SR^ oooooooo .sj^ti "y bM* lOcnco^coNioio tot->O'*Tio os en o * co o OOOtOCOr-liaiOCO *3 m rHOOrHrHOOO 1 +++ 1 + 1 + rt QJ oZ SrH O OS O U3 N tO r)< IO CO O CO O5 CO H S tot-TiicOTj Tj< ^5 * us co M oa r-i ea N 51 10 to oo co to o> en to i-i * CM csi o> co e>j f-i ^fa TfC-lOlONTf-flO hi! 13 M n N 00 O TJI to U5 I l COCOCOTj'TfiCO'*!"'!' t-c-tototoiatata s iu rj> g|g(3 J WB W cooocooot-t-t-t : : : : : : : : Author Hirschfeld I (1888) . . II (1888) . . Klemperer I (1889) . . '* II (1889).. Siven, 1901 Patient No. 8 per VI Patient No. 9 per III Patient No. 9 per IV 120 SCIIAMBKRG, KOLMKR, RINGKR, AND RAIZISS physical and mental rest incident to sojourn in a hospital, irre- spective of the character of the diet, the patient was not placed on a low nitrogen dietary, but, on the contrary, was given a high nitrogen intake. After a few weeks' residence in the hospital, there was a pronounced improvement in the patient's nervous condition ; the choreiform movements were distinctly less marked. No improve- ment, however, took place in the psoriatic eruption. Indeed, under this high nitrogen diet, the psoriasis plaques gradually increased in size and some new patches appeared. After a number of weeks, many of the patches began to clear in the centre and became cir- cinate. The patient remained in the hospital from April 8th to July 1st, a period of 84 days, and at the end of this time the psoriasis was worse than upon admission. The relative appearance of the eruption on April 10th and on May 21st is seen in Figs. 19, 20, 21 and 22. The increase in the size of the patches was verified by actual measurement. Before discharge from the hospital, a chrysarobin ointment was applied and the eruption gradually disappeared. DISCUSSION OF RESULTS. From the study of the cases presented above, the following con- clusions may be drawn: 1. That these patients possess a strong tendency to store nitrogen. 2. That the nitrogen is stored with great ease. 3. That on a low protein diet the patients may eliminate extraor- dinarily small quantities of nitrogen in their urine. 4. That a low protein diet has a distinct and a remarkably beneficial influence on the course of the psoriasis. 5. That very large quantities of nitrogen may be lost through the skin in the form of scales. 6. That on a high protein diet tremendous quantities of nitro- gen may be retained in the system. 7. That a high protein diet, although it did not bring about a relapse in a case where the active process had been checked (Pa- tient No. 3, Period 15), did stimulate very considerably the course of the existing psoriasis in active form. (Patient 3, Periods 7 and 8; Patient 5, Period 1, and Patient 7.) 8. That the retention of nitrogen is not always associated with a coi responding gain in body weight. RESEARCH STUDIES IN PSORIASIS 121 For the sake of convenience, we shall divide the discussion of our results into several chapters : THE VALUE OP THE ELIMINATED NITROGEN IN THE INTERPRETATION OF PROCESSES OF METABOLISM. In the ordinary studies of protein metabolism, two kinds of nitrogenous end products are taken into consideration. 1. URINARY NITROGEN. This represents the amount of nitrogen eliminated as urea, ammonia, creatinine, uric acid, purin bodies and other individually undeterminable nitrogenous compounds, which may consist of amino-acids and peptides, which managed to filter through the kidney before they were completely catabolized. All these are cleavage and end products of protein metabolism. 2. F.ECAL NITROGEN. The fascal nitrogen consists of two frac- tions: (1) nitrogen secreted and excreted in the form of ferments and otherwise by the epithelial cells of the mucous membrane of the intestinal tract, which may be considered a true product of cell metabolism of the intestinal wall and (2) nitrogen of the unresorbed food, which has never played any part in the body metabolism. In some experiments the nitrogen of the perspiration and nor- mal skin exfoliation is also taken into consideration. Their values, however, are so small that for all practical purposes they may be neglected. In the introductory chapter it was stated that for the estima- tion of the protein that is catabolized by an individual, it is necessary to determine the amount of nitrogen eliminated in the urine and faeces and to multiply that figure by 6.25, which is the ratio between nitrogen and protein. It is evident that while this method permits of a very accurate study of the nitrogen and protein balances, our inability to distinguish and separate the two fractions of faecal nitrogen, may cause the introduction of considerable error in the study of the Quantity of protein that is actually catabolized by .the cells of the body. The reader will, therefore, always bear in mind that the actual nitrogen metabolism of the cells of the body is less than is expressed by the sum of urinary and faecal nitrogen, or in other werds, the nitrogen of the food that is resorbed and takes part in the cell metabolism is less- than the amount ingested. In the study of the cases presented above, a third and very important factor of nitrogen has to be taken into consideration, namely, the nitrogen found in the scales of the skin. Analysis of the scales has shown that they contain from 9.92 to 14.4% of nitro- 122 SCHAMBERG, KOLMER, RINGER, AND RAIZISS gen. They also contain sulphur and phosphorus and we have every reason to believe that they consist primarily of protein. This being the case, we must include the nitrogen thus eliminated in the calcu- lation of our balances, but we must not include that nitrogen in the calculation of the body protein catabolism. This nitrogen has its own history in the body economy and, as will be shown later, exerts a tremendous influence on the metabolism of the psoriatic patient. THE MINIMAL PKOTEIN REQUIREMENTS AND THE MINIMAL PKOTEIN CATABOLISM. By "minimal protein requirements" we mean the smallest amount of protein that is necessary to maintain an individual in a state of nitrogenous equilibrium and in a normal degree of efficiency. In this discussion we are not so much interested in the lowest quantity of protein that is necessary to keep the body in nitrogenous equilib- rium, as in the question: what is the lowest quantity of protein (nitrogen) per kg. of body weight which has been found to be catabolized by human individuals under different conditions of nutrition. We shall present a brief resume of those experiments and com- pare them with our own observations on the patients with psoriasis, and we thereby hope to be able to throw some light on the patholog- ical physiology of the protein metabolism of those patients. For obvious reasons we shall limit our review to those experiments that were performed on man (see table No. 8, p. 119). Hirschfeld 23 was the first to attempt a systematic study on the influence of low protein diets on the urinary and fascal nitrogen eliminations. His object was to discover the lowest protein require- ments for nitrogenous equilibrium. The most important features of his experiments are tabulated in Table 8. The experiments were performed on a man weighing 73 kg., and they consisted of two series of 8 days each. In the first series, the diet contained an average of 4.15 grams of nitrogen per day and an energy supply of 2852 calories (39 calories per kg.). The amount of nitrogen eliminated in the urine was 4.74 grams per day and in the fseces 1.28 grams per day, giving- a total of 6.02 grams, resulting in a negative nitrogen balance of 1.87 grams per day, i. e.,,the amount, 4.15 grams, that was given in the food was not sufficient to cover all the body's needs. In the second series, therefore, the nitrogen intake was raised to an average of 7.46 grams per day. Unfor- RESEARCH STUDIES IN PSORIASIS 123 tunately, a second factor was introduced into this series which no doubt influenced the result the caloric value of the food was raised to 3462 calories per day (47 calories per kg.). Hirschfeld's point would have been brought out much more clearly had the rise in the nitrogen intake been the only variable. The nitrogen output in the urine for this period was 5.76 grams and in the faeces 1.65 grams, making a total of 7.41 grams, which, for all practical purposes, may be considered the establishment of nitrogenous equilibrium. Simultaneously with Hirschfeld, Klemperer 24 studied the ques- tion of the extent to which the protein metabolism can be depressed in normal, healthy, human individuals. For a period of 8 days, he kept two normal men on a diet containing 5.28 grams of nitrogen and a heat value of 5020 calories (79.4 calories per kg. in the first experiment and 77.4 calories per kg. in the second experiment). The nitrogen eliminated in the urine of the first subject, during the last three days of the experiment, was 3.33 grams and in the faeces, 1.26 grams. The total amount of nitrogen eliminated was 4.59 grams, resulting in a positive nitrogen balance of 0.69 gram per day. In the second subject, the urine contained, during the last three days, an average of 2.87 grams of nitrogen per day; the fseces contained 1.02 grams, giving a total excretion of 3.89 grsms and a positive balance of 1.39 grams per day. A very interesting series of experiments was carried out by Siven on himself, 25 which illustrates very clearly the relationship that ordinarily obtains between the nitrogen of the food and that of the urine. The heat value of his food was over 40 calories per kg. of body weight. Series 1. 2. 3. 4. 5. Nitrogen intake 12.69 10.35 8.71 6.26 4.52 Output in urine 9.44 7.53 6.13 4.62 3.40 From the summary of his results, as presented above, we see how closely the curve of the latter follows that of the former. These experiments of Hirschfeld, Klemperer and Siven are typ- ical ones and are selected from among a great many. They are brought in at this point to illustrate the following facts: 1. That a normal individual, on a diet containing a caloric sup- ply sufficient for the maintenance of body functions (39 calories per kg.), and containing an amount of nitrogen equivalent to 0.057 gram per kg. of body weight, is not sufficient for the maintenance of nitrogenous equilibrium. The urinary nitrogen calculated per kg. of body weight was 0.065 gram per day (Hirschfeld 1). .124 SCIIAMBKllG, KOLMKK, KINGKK, AND KAIXISS 2. That the same individual, on a diet having a heat value of 47 kg. per body weight and 0.102 gram of nitrogen per kg. of body weight, did maintain nitrogenous equilibrium. The urinary nitrogen calculated per kg. of body weight was 0.079 gram per day (Hirschfeld 2). 3. That by doubling the caloric value of the food, protein catabolism can be so greatly reduced that the administration of 0.083 gram of nitrogen per kg. of body weight will not only be sufficient to cover the cells' needs, but will also be associated with a positive nitrogen balance. The urinary nitrogen in those cases was reduced to 0.052 and 0.044 gram per kg. of body weight (Klemperer 1 and 2). 4. That on a constant and sufficient caloric supply the gradual lowering of the nitrogen in the food is accompanied by a gradual decline in the nitrogen output ; the difference between the two grad- ually diminishes as we go down the scale (Siven). When we come to examine the results of our experiments in the light of the conclusions drawn from Hirschfeld's, Klemperer's and Siven's experiments, we note a very remarkable deviation. Through- out all our studies we notice a marked and continuous disproportion existing between the food nitrogen and the urinary nitrogen. The urinary nitrogen is always much lower than is the nitrogen of a normal individual on the same diet. In Period 6, Patient 8 received 0.075 gram of nitrogen per kg. of body weight. The heat value of the food was only 32 calories per kg. The average amount of nitrogen eliminated during the period of seven days was 0.032 gram per kg. of body weight. It took over 77 calories per kg. in Klem- perer's experiments to reduce the urinary nitrogen of a normal in- dividual to 0.044 gram, per kg., while a psoriatic patient eliminated less nitrogen on a diet less than one-half tlie caloric value of Klem- perer' s patient. The same experiment was carried out in Patient 9, Period 3, in which she received 0.079 gram of nitrogen and 28.5 calories per kg. of body weight. The urinary nitrogen was 0.055 gram per kg. When compared with Siven's figures (page 123) the results ob- tained with Patient 3 are very striking. Periods. 7. 3. 4. 6. Calories per kg 53.6 38.00 38.00 42.00 Nitrogen intake 20.54 11.93 6.89 6.89 Nitrogen in urine 8.23 6.32 3.90 3.30 RESEARCH STUDIES IN PSORIASIS 125 All this shows very plainly that on a given diet, a psoriatic patient eliminates less nitrogen in the urine and that it takes a much less energy supply in the -form of food to keep the urinary nitrogen at a low level than it does in a normal individual. This problem is so intimately related to the question of nitrogen retention that we shall now proceed to a discussion of the latter subject. NITROGEN RETENTION. Closely associated with the condition of lowered nitrogen elim- ination in the urine we find a high degree of nitrogen retention. This retention is evident in Patient No. 3 throughout her entire stay of 128 days in the hospital. The nitrogen in the food was 492 grams in excess of that eliminated in the urine and faeces. Aftei 1 subtracting 89.6 grams of nitrogen eliminated by the skin (see page 48), the remains a net positive balance of 402 grams. A care- ful perusal of the columns of nitrogen balances and nitrogen in the food, reveals a great many interesting facts, the most important of which we consider the remarkable sinking of the urinary nitrogen with any reduction in the food nitrogen. . Patient No. 4 lived in the hospital for 42 days and she retained 129 grams of nitrogen during this period; Patient No. 5 retained 86 grams in 40 days. Patient No. 7 was kept on a high protein diet throughout his stay in the hospital (59 days) and in this period he retained 286 grams erf nitrogen. The quantities of nitro- gen retained do not present as remarkable a feature as do the con- ditions under which positive nitrogen balances have been maintained. From a careful study of the conditions in which nitrogen is retained normally, we are forced to some definite conclusions which seem to explain the very marked nitrogenous retentions in psoriasis. NITROGEN RETENTION IN NORMAL ADULT INDIVIDUALS. Reference has already been made (page 35) to the statement that if the quantity of protein intake, in an individual who main- tains nitrogenous equilibrium, is steadily increased, the nitrogen elimination (catabolism) of that individual will increase correspond- ingly, until an equilibrium is struck on a higher level. Under these conditions the animal body shows a, remarkable stubbornness in re- fusing to store or retain any of the ingested nitrogen. To quote Pfliiger, who has done an enormous amount of work on this subject: "Ganz wunderbar und ratselhaft ist die ungeheure Anstrengung, 12<> SCHAMliKUG, KOLMER, RINGER, AND RAIZISS welche der Korper niacht, um das wertvolle iiberschiissige Eiweiss, moglichst vollstiindig zu zerstoren." Bischoff and Voit 20 were the first to discover that the non- nitrogenous food stuffs have a marked sparing influence on protein catabolism. The question then naturally arose: if the body tends so very strongly to the establishment of nitrogenous equilibrium by raising the catabolism to equal the intake and if the giving of a high caloric diet in the form of carbohydrates and fats tends to depress the catabolism of the protein, the intake remaining the same, then there must, judged from a priori reasoning, follow a storing of nitrogen in the body. If so, to what extent, and in what form? These questions were raised by von Noorden, 27 and Krug, 28 working under his direction, attempted to find an answer to them. Krug was a young man weighing 59 kg. He placed himself on a diet consisting of 2590 calories (44 calories per kg.) and for 6 days maintained nitrogenous equilibrium on a level of 14.8 grams. Then for a period of 15 days he increased his food by 1700 calories, making a total of 4290 calories per day (71 calories per kg.) and remained on approximately the same amount of nitrogen as before (15.4 grams). This tremendous excess of food carbohydrate and fat cannot be burnt unless there is a demand for it by greatly increasing the activity of the body, for, as von Noorden expresses it, "Luxus-consumption giebt es nicht." There takes place, there- fore, a storing of all the extra material in the form of glycogen and of fat, principally fat. Associated with this storing of mate- rial, there is also a "tying-up" of nitrogenous material, a "laying- on" of protein, which manifests itself in a positive nitrogen balance, i. e. t a deficit of nitrogen in the urine and faeces. In Krug's experi- ment there was a diminution in the nitrogen output to the extent of 3.3 grams per day, totaling for the 15 days 49.5 grams of nitro- gen = 309 grams of pure protein. There are two facts in this experiment which we wish to empha- size and to bring clearly to the reader's mind: 1. The tremendous energy supply (71 calories per kg., or double the normal requirements) that was necessary to bring about a sparing of 3.3 grams of nitrogen per day. 2. The relatively small amount of protein that was retained, compared with the total retention of non-nitrogenous materials. Von Noorden calculates that Krug stored 2606 grams of fat during this period and only 309 grams of protein. This experiment is so convincing that we need not present any additional data for the demonstration of the point that, while in RESEARCH STUDIES IN PSORIASIS 127 a full-grown, healthy adult, a retention of protein is possible, it can be accomplished only by a tremendous amount of "pressure" in the form of a high supply of potential energy in the food, much in excess of the requirements an amount clearly bordering on the physiological limits of one's ingestive capacities. It is impossible to conceive of any prolonged storing of protein in healthy indi- viduals, because it is impossible to conceive of a prolonged con- tinuance of such high ingestion of food, without ultimately result- ing in the rebellion of the digestive and resorptive apparatus. 29 NITROGEN RETENTION JN GROWING AND CONVALESCENT INDIVIDUALS. When we turn our attention to nitrogen retentions in the grow- ing child, or in convalescents, an entirely different picture presents itself. From the works of Rubner and his collaborators, 30 it is apparent that the growing child retains nitrogen with remarkable ease, even though the caloric and protein supply of the food is but slightly above the lowest requirements wear and tear quota. Nay, nitrogen retention takes place in the growing child even on a diet insufficient to cover the heat loss. They, therefore, draw the conclusion that in the growing child (contrary to the adult) the power of nitrogen retention is not determined by the amount of nitrogenous and non-nitrogenous food, but by the "growth impulse" ( "Wachstumstrieb") . The observations made on the convalescent patient with regard to his ability to store nitrogen, are very similar to those made on a growing child. A great many experiments have been performed by different investigators which prove this point. We shall here report a few of the most interesting. Friedrich Miiller 81 had the opportunity of studying the metab- olism of a 19-year-old girl, who suffered from cesophageal stenosis, as a result of swallowing caustic soda with suicidal intent. For a period of 8 days (about a month after the accident) she could par- take of no food. During the last four days of this period, the urine and faeces were collected and analyzed. During the next 5 days it became possible to overcome the stenosis by means of a narrow stomach tube and the administration of liquid food, milk and eggs, became possible. During these five days the patient re- ceived an average of 7.6 grams of nitrogen per day, with a caloric supply of 765 calories per day (24 calories per kg.). On this low diet the patient retained an average of 1.7 grams of nitrogen per day. 128 SCHAMBKRG, KOLMER, RIXGER, AND RAIZISS During the following 7 days the nitrogenous intake was 8.99 grams per day and the fuel value of the food was 881 calories per day (27 calories per kg.). The nitrogen retention continued to the extent of 1.9 grams per day. In their experiments on typhoid convalescents, Luthje and Ber- gcr 32 obtained nitrogen retentions during the first five days of the experiment in a patient who was on a diet containing not more than 38 calories per kg. of body weight. The nitrogen retention was to the extent of 3.5 grams per day. We do not include their other experiments in which retentions of 10 grams of nitrogen per day were obtained, because the caloric supply was higher than the requirements. Benedict and Suranyi 33 carried out some beautiful experiments on typhoid convalescents and obtained a retention of 237 grams of nitrogen in the course of 33 days, with the patient on -a diet of approximately 3200 calories per day. (Unfortunately, the pa- tient's exact weight is not given.) These experiments show conclusively the differences that exist in the nitrogen-storing capacities of the normal individual and the convalescent, who has just passed through a prolonged illness asso- ciated with undernutrition and, principally, loss in body protein. They show with what velocity and comparative ease the conva- lescent's body can store nitrogen and, also, for what prolonged periods. NITROGEN RETENTION IN PSORIASIS. When we come to examine the character and extent of the nitro- gen retention in the psoriatic patient, in the light of the aforesaid, we cannot fail to observe the similarity that obtains between the behavior of the psoriatic and that of the convalescent, with refer- ence to the ease with which each can store nitrogen in large quan- tities and for long periods of time. The continuous storing of nitrogen in Patient No. 3 resembles Benedict and Suranyi's cases in almost every particular. The retention of 2.5 grams of nitrogen per day in Patient No. 8, Period 3, when receiving an average of 7.08 grams of nitrogen and only 26.4 calories per kg., is almost an exact duplication of Fried- rich Muller's case, which was certainly in a very bad state of undernutrition. When we add to this our experience with the superimposed milk feeding of 500 and 1000 cc., fed in addition to a standard diet and our failure to find any evidence of catabolism of this extra nitrogen RESEARCH STUDIES IN PSORIASIS 129 in the urine, we feel inclined to believe that patients with severe psoriasis present a state of remarkable protein undernutrition, which we choose to call "specific nitrogen hunger" (see page 130). Because of this nitrogen hunger, they possess the power of retaining nitrogen to a most marked extent, even under conditions in which a normal individual would find difficulty in maintaining equilibrium. The following questions now present themselves: Wherein is the cause of this "nitrogen hunger" to be sought; what is the relation- ship between the psoriatic lesion and the nitrogen hunger; what causal relationship may they bear to each other? Then, what be- comes of the retained nitrogen, where does it go, and in what form is it retained? Answers to these questions may be found in an analysis of the results obtained in Patient No. 8 (Table 5), in Patient No. 9, and in the pathological histology of the psoriatic lesion. Patient No. 8 lived in the hospital under our observation for a period of 44 days. During this period she ingested 293.4 grams of nitrogen. For the same period she eliminated in the urine and faeces, 210.6 grams, leaving an apparent positive nitrogen balance of 82.8 grams. There is no doubt that this nitrogen is retained in the form of protein. The question is, where is it retained? To properly understand this point, we must recognize a very important series of facts which deal with the pathology of psoria- sis. Disregarding the differences of opinion that exist with regard to the seat of the primary lesion of psoriasis, all are agreed that there are evidences of inflammation in the papillary layer of the corium and that the rete mucosum is hyperplastic. The epithelial cells proliferate with great velocity, push toward th surface, become cornified and are finally exfoliated. The chief constituents of these epithelial cells are proteins, which must be obtained by the cells from the blood. To realize the extent to which this proliferation may occur and to appreciate the amount of protein that may thus be removed from the blood and ultimately from the cells of the body, we shall state that during her stay in the hospital we col- lected 446 grams of scales, exfoliated by this patient's skin, and this amount does not represent the full amount of scaling, for a quanti- tative collection is almost impossible in a case like this, because of the fineness of the scales and the difficulty of collection. The nitro- gen content of the collected scales varied from 11.8 to 14.4%. Almost pure protein! The total amount of nitrogen in the scales was 58.38 grams. We have no idea how much nitrogen this patient lost through the scales before she came to the hospital. Judging 130 SCHAMBERG, KOLAIER, RINGER, AND RAIZISS from the amounts we obtained, the total loss must have been enormous. In what way does the loss of nitrogen in the scales influence the total nitrogen metabolism of the body? This question is an- swered very clearly in the following experiment : Patient No. 8, who scaled very profusely, and Patient No. 9, who scaled only moderately, were placed on the same diet during the period of May 80th to June 5th. The figures for the week follow : Patient Weight Nitrogen Nitrogen Nitrogen Nitrogen Net nitrogen ingested in faeces in urine in scales balance No. 8 58.4 30.70 13.78 13.16 8.75 4.99 No. 9 54.6 30.04 13.54 20.9-', 2.47 651 The amount of nitrogen ingested and the amount of nitrogen in the faeces were similar in these patients, but there was a great difference in the amounts of nitrogen in the scales. Patient No. 8 lost 6.28 grams more in the scales than Patient No. 9 did, and she eliminated 7.78 grams less in the urine. // we assume the nitrogen in the urine to represent the end products of protein metabolism of the cells of the body, we see very clearly to what an extent the condition of the skin influences the total protein metabolism. The proliferation and rapid growth of the epithelial cells of the skin deprive the cells of the body of their nutrient material and force them to subsist at a starva- tion level. During the course of the week only 13.16 grams of nitro- gen were eliminated in the urine, an average of 1.88 grams per day, or 0.0323 gram per kg. of body weight. This is the very lowest figure that has ever been reported for an individual under similar conditions of nutrition. The proliferation and growth of epithelial cells takes place throughout the entire period of the disease, commencing, in all probability, long before exfoliation begins. For this growth of cells, protein is required, which is abstracted by the multiplying epithelial cells from the blood stream, in quantities proportional to the severity of the disease. This constant drain of protein from the body into the skin, where it becomes "fixed," gradually causes the impoverishment of the body in protein producing a condition of "specific nitrogen hunger." If at any time during this process a study of the protein meta- bolism is instituted, nitrogen retention will be evident. This retained nitrogen can go in one or in two places, depending upon the stage of the disease and upon the protein status of the patient. It may RESEARCH STUDIES IN PSORIASIS 131 be carried to the epithelium of the skin to become incorporated in the proliferating cells and finally be given off as exfoliated scales, or it may be carried to the cells of the body, especially to the muscle cells, which have become impoverished of their protein. The nitro- gen may be deposited in the muscle cells of a psoriatic patient, as it is in a convalescent patient after a prolonged illness. In both classes of patients a positive nitrogen balance takes place. This theory seems to be in harmony with many of the facts and seems to explain the cause of the remarkable and prolonged nitrogen retentions. INFLUENCE OF A Low PROTEIN DIET ox THE COURSE OF PSORIASIS. On carefully reviewing the clinical histories of our patients, one cannot fail to notice that the low protein diet exercised a distinctly beneficial influence on the course of the disease. Conversely, a high protein diet had a strong tendency to exacerbate the condition. How can we explain these relationships? In what way can we conceive of the low protein diet influencing the patient's skin? Bulkley, 84 who long ago recognized the favorable influence of a low protein or vegetarian diet on the course of psoriasis, endeavored to construct a theory of disturbed protein catabolism. He deserves credit for his recognition of the influence of various dietary regimes on the course of the disease. The analytical data, however, upon which his theory is based would not stand scrutiny in the light of modern scientific and experimental research. We believe that the following consideration offers a satisfactory explanation : One of the most prominent features of the histology of psoriasis is the rapid growth and proliferation of the epithelial cells of the skin. For the present, we may leave out of consideration the primary aetiologic factor. But one thing must be clearly understood : for their growth and life, these cells require building material, which can be obtained from only one source the blood and lymph streams. The principal building material required by these cells is protein. It is at once evident that since these cells are endowed with a power- ful "growth impulse," "Wachstumstrieb," the velocity of their growth will be directly proportional to the amount of "building material" in the form of protein, that is placed at their disposal. A high protein diet therefore stimulates their growth, because it pro- vides all the necessary components of the epithelial cells. By keeping the patient on a low protein diet, on an amount 132 SCHAMHKKG, KOLMKR, RINGKR, AND RAI/ISS just enough to cover the body's "wear and tear" quota, we bring about a condition in which no extra protein can be supplied to the rapidly multiplying cells of the skin. If the "growth impulse" of these cells were not so great, this point would, in all probability, mark the end of the disease. May it not be possible therefore, that the rapidly growing cells in psoriasis, like those of malignant growths, have the power of preying on the rest of the body, withdrawing protein from the blood, and then the blood in turn attacks the pro- tein storehouses the muscles? This may go on for a long time until the body's protein reserve is exhausted, when the growth of the epithelial cells, patches and scalings becomes checked. A similar process has been described in the classic researches of Miescher. 35 He found that during the salmons' migration up the Rhine, they suf- fer from complete starvation. During this period their genital or- gans become remarkably proliferated, whereas the muscles lose up to 50% of their protein content. This is an illustration of the rapid growth of one tissue at the expense of another in a starving animal. The high "growth impulse" of the testicular tissue is the determining factor. In the psoriatic patient the same thing may take place, but to a lesser degree. The epithelial cells of the skin keep on growing as long as there is "available" or "mobilizable" protein in the system. When this is exhausted, their growth is checked. And this, in our estimation, may account for the frequent spontaneous improve- ments in cages of psoriasis. By keeping the patient on a low protein diet, we hasten this point of "exhaustion." We hasten the slow starvation of the epithelial cells. By keeping the patient on a high protein diet, we stimulate the growth of the epithelial cells and thus delay improvement. (See Patient No. 7.) We find additional support for this theory in the following clinical observations of S. Jessner: 36 "Von altersher herrscht die Anschauung, dass die Psoriasis vornehmlich Kraftige, muskulose, sonst gesunde Individuen befallt. Dies ist im allgemeinen richtig, wenn auch Ausnahmen nicht allzu selten sind.. Zuweilen kann man feststellen, dass bei kraftigen Personen eine vorhandene Psoriasis schwindet, sobald sie von einer schwereren Krankheit heimgesucht werden und Korperlich herunterkommen. Erholen sie sich spater, dann erscheint die Psoriasis wieder auf die Bildflache." Similar observations have been recorded by various writers who have reported the disappearance of psoriasis in patients suffering from acute infections, only to return after the infectious disease has subsided. RESEARCH STUDIES IN PSORIASIS 133 These facts lend support to our theory, because they show that every condition that is associated with increased protein catabolism or diminished protein ingestion results in improvement of the psoriasis. An analogy was previously drawn between malignant growths and the growth of the epithelial cells in psoriasis. Biologically, the two seem to have a great deal in common. The difference ap- pears to be one of degree only. Both are endowed with great growth impulse and power of proliferation, both have the power of living on and multiplying at the expense of the cells of the host. The difference between the two is that by exhausting the reserve depots of protein, the psoriasis will always be checked because its "growth impulse" is not as great as is that of the malignant tumors, which will go on growing until they bring about a toxic disruption of the cells of the host. Powerful as is the action of malignant tumors in this respect, it was recently shown by J. E. Sweet, Corson- White and Saxon, in a beautiful research, 37 that even the growth of adeno- carcinoma of the rat and carcinoma of mice may be checked by an improper and insufficient protein supply. THE RELATIONSHIP BETWEEN RETAINED NITROGEN AND GAIN IN BODY WEIGHT. On examining the influence of nitrogen retention on the body weight of our patients, we found that in most cases there was no relationship at all; that the retention of even large quantities of nitrogen may not be accompanied by any gain in weight. On admission to the hospital, Patient No. 3 weighed 40.85 kg. When she left, after a stay of 128 days, she weighed 42.2 kg. Dur- ing this period, she retained a net amount of 402 grams of nitro- gen, which is contained in 2512 grams of pure protein. Her body weight should have increased by at least that amount, leaving aside the amount of water that would be necessary to dissolve the protein to the consistency of the cell. A similar lack of proportion was found in Patients No. 4 and No. 5. But Patient No. 7, who was kept on a high protein diet throughout the course of the experiment, retained 286 grams of nitrogen 1.79 kg. of protein. During this same period, the patient gained 1.4 kg. in weight. Observations of this kind are not new in physiological literature. Bischoff and Voit 38 recorded them as early as 1860, but thai the lack of proportion could be as great as was observed in Patient No. 3 was most surprising. 134 SCHAMBERG, KOLiMER, RINGER, AND RAIZISS Bischoff and Voit 30 fed a dog on bread for 41 days and during this period the animal lost an amount of protein corresponding to 3717 grams of flesh. The total loss of body weight, however, was only 531 grams. The difference was made up by retention of water. As the animal's state of nutrition began to improve by the ingestion of 1800 grams of meat per day, the water was rapidly eliminated. The results obtained on the first day of the meat feeding are very interesting. In spite of this tremendous food intake the animal lost 310 grams in weight and the urine itself contained 120 cc. more water than was ingested. Very striking, also, is Liithje and Berger's 40 experiment No. 3, in which their subject received food with a fuel value of 72 calories per kg., and 49.6 grams of nitrogen per day. The amount of nitrogen retained per day was 11.4 grams and the amount of fat that was stored must have amounted to at least 200 grams per day. In the first four days there was a retention of at least 800 grams of fat and 285 grams of protein, 1085 grams of material in all, and in spite of this retention, the subject's weight was 0.6 kg. less than when the experiment started. This lack of relationship between an actual gain in body material and a failure to show it in a gain of body weight, can be accounted for by assuming a variation in the amount of water in the tissu'es. That the relative amount of solid material decreases in muscle tissue in starvation, was shown definitely in Rubner's laboratory. 41 The following changes were found in the. muscle of fasting animals : Normal Fasting Solid Water Solid Water 22.87 77.13 18.73 81.27 23.65 76.35 17.99 82.01 Average 23.26 76.74 18.36 81.6! t This table shows very plainly that in starvation the relative amounts of water may increase very considerably. Of course, we must bear in mind that our patients did not suffer from any de- privation of food, but from specific nitrogen hunger. What the influence of this condition may be on the water content of the cells will be the subject of our inquiry in the immediate future. RESUME OF THE CLINICAL RESULTS. The primary purpose of our physiological studies was to ascer- tain whether any deviation from normal occurred in the metabolism of psoriasis patients. We have seen that a disturbance of the nitro- RESEARCH STUDIES IN PSORIASIS 135 gen metabolism does exist in psoriasis, more particularly in severe cases. We have demonstrated that such patients quite constantly retain nitrogen and that this element is needed for the proliferation of the epithelial cells of the skin. Indeed, without a bountiful supply of protein from the blood and tissue juices, such rapid cellular growth as occurs in psoriasis would be impossible. We felt, therefore, that an eminently important as well as practi- cal aspect of our studies was to note the effect on the psoriasis eruption of diets containing different amounts of nitrogen. Such observations require adequate time for each experiment, as a dietary regime continued for only a short period might readily lead to con- fusion of interpretation. From our observations, we are strongly inclined to believe that a high or even relatively high nitrogen diet has a baneful influence on psoriasis. In four of our patients (Cases 3, 4, 5 and 7), in whom this experiment was tried, an aggravation of the eruption occurred. With the exception of one patient (Case 7), it was impossible to continue the high nitrogen diet for a pro- longed period, owing to the fact that we could not interne our pa- tients in the hospital for a sufficient period of time- and, moreover, because of the prejudices of the patients who feared the influence of such a diet. In Case 3, a rapid extension of the psoriasis occurred in the early days of her hospital sojourn, while she was taking a relatively high amount of nitrogen. Many weeks later, after marked improvement had taken place, so that but insignificant vestiges of the disease remained, a high nitrogen diet was resumed for several weeks without apparent harm; at this time, however, the patient was eliminating nitrogen better than at any period of our observa- tion. Whether one can stimulate the outbreak of psoriasis in a psoriatic patient free of the eruption, we have not had the oppor- tunity of determining. We shall continue our observations on the influence of a high nitrogen diet upon psoriasis patients in order to settle this question. We were in a better position to determine the influence of a low nitrogen diet upon the activity of the psoriatic process, because of the fuller cooperation of our patients. Although this diet meant a greater deprivation of articles of food to which they were accus- tomed, still they preferred this regime, as in their own opinion it was conducive to their improvement. We feel that there can exist little doubt as to the favorable influence of a low nitrogen diet on the eruption of psoriasis. This is more strikingly seen in severe cases, for in such patients improvement is more rapidly and readily evident. In support of our conclusion, we place in evidence the photographic 136 SCHAMBERG, KOLMER, RINGER, AND RAIZISS records of Cases 3, 5, 6 and 8, in whom the improvement was strik- ing if, indeed, not remarkable. It would appear that the milder the case, i.e., the more limited the eruption, the less pronounced and the less immediate is the influence of a low nitrogen diet. Some of our mild cases exhibited only a moderate degree of improvement. It is well known that psoriasis is a disease subject to variations, both improvement and exacerbation, without known cause. The question might pertinently be asked whether the improvement could not have been mere coincidence, or, whether other factors could not have been responsible for the improvement observed. We have many times asked ourselves this question. It would be difficult to account for our results on the basis of pure coincidence. The sequence of events was too direct and the number of striking improvements reached too high a proportion to admit of such an explanation. Furthermore, all must concede that the changes for better or worse in psoriasis are not in reality spontaneous merely because they occur without apparent cause. After carefully studying our patients and thoroughly scrutinizing all of the environmental conditions, we have been forced to eliminate the latter as influencing factors. It will be recalled that Case 7 was studied as a control in order to determine whether freedom from phys- ical labor and from mental harassment, in a quiet private room in a hospital, could have accounted for the improvement in some of the other patients. But this patient (who was placed on a high nitrogen diet) was, after 84 days residence in the hospital, worse than upon admission. It is interesting here to note that this patient made decided improvement with respect to the nervous disorder (chorea) from which he was suffering, at the same time that his psoriasis was growing gradually worse. This observation does not lend any support to the theory of the neuropathic origin of the disease, which is held by a number of writers. On the other hand, Patient No. 3, was frequently in* a highly nervous and apprehensive state, with numerous crying spells and periods of depression, and yet her erup- tion improved to the point of virtual disappearance. In Figs. 23 and 24 are contrasted the eruptions in the case of a young man who was treated in the dispensary. He received no in- ternal or external treatment of any kind whatsoever, but was placed upon a low nitrogen diet, which he faithfully carried out. The eruption entirely disappeared in two months, leaving pigmented spots which subsequently faded away. The second photograph was taken in the month of May. The enormous proliferation of the epithelial cells of the rete PLATE XXXIX. To Illustrate Article on Research Studies in Psoriasis, bv DHS. SCIIAMBERG, Koi.MER, RINGER and RAIZISS. O * If! H 1) II -S cS 1 s Sg o is J* a * .3 S G V t*> C -M .* S -2 S 5j !2 "C ^ C *-H tl w 3 o t* ^"3 Q'SS JJ g.S 1^ S3 II . >> 6C b THE JOURNAL OF CUTANEOUS DISEASES, November, 1913. RESEARCH STUDIES IX PSORIASIS 137 mucosum in psoriasis and their exfoliation from the skin after they have been cornified, creates a great demand for protein. This pro- tein can only be supplied through the blood and lymph streams. The diverting of the food protein to this purpose naturally lessens the amount catabolized in the system and eliminated in the excreta. Nitrogen retention may in considerable part be explained by the loss of protein through scaling. But this does not explain the entire retention because (1) the deficit of nitrogen in the excreta is greater than can be accounted for by the amount lost through the skin ; and (2) we have, in a most thoroughly studied case, observed a consider- able retention of nitrogen after the scaling had ceased and the erup- tion had virtually disappeared. This retention is difficult to account for. It is possible that the skin, during its great proliferative activity, may call upon the mobi- lizable protein in the muscles and other tissues and that, later, this reserve protein may be restored from the food protein ingested. A nitrogen retention having been established to exist in psoriasis, the question presents itself is the nitrogen retention primary and to be regarded as the astiological factor, or one of the astiological factors in the causation of the disease, or is it secondary to the pathological changes in the skin? This question cannot be definitely settled at this stage of our investigations, although the latter proposition appears to be more in harmony with the demonstrated facts. In the present stage of our research studies we are unable to set up an hypothesis as to the cause of the disease without departing from the domain of fact and entering the realm of conjecture. We are content to present our laboratory findings and set forth the re- sults of our clinical observations. We are still in the midst of our pathological and metabolic studies and many problems must be solved before any definite pronouncement as to the nature and cause of psoriasis can be safely made. SUMMARY AND CONCLUSIONS. A careful study was made of the protein metabolism of eight psoriasis patients and the following observations were made: 1. That on a given protein diet a psoriatic subject eliminates less nitrogen in the urine than does a normal individual on a cor- responding diet. The urinary nitrogen in some of our patients reached a level lower than has ever been recorded. 2. Patients suffering from psoriasis exhibit a remarkable re- 138 SCHAMBERG, KOLMER, RINGER, AND RAIZISS tention of nitrogen. This retention appears to be proportional, in a general way, to the extent and severity of the eruption present. 8. The nitrogen is retained to a greater degree than has been observed in connection with any other condition and is, furthermore, retained with great ease even on a diet low in nitrogen and insuffi- cient in caloric value, and one on which a normal individual would fail to maintain equilibrium. 4. Experiments with urea feedings show conclusively that the nitrogen retention cannot be attributed to any disturbance in the eliminative capacity of the kidneys. 5. Patients with extensive psoriasis may lose very large amounts of nitrogen in the exfoliated scales, which consist of almost pure protein. 6. The retention of nitrogen in most of our cases was greater than could be accounted for by the protein lost in the scales, and it may persist even after scaling has ceased and the eruption has virtualjy disappeared. 7. A low nitrogen diet has a most favorable influence upon the eruption of psoriasis, particularly when the latter is extensive. Mak- ing all reservation suggested by scientific caution, we feel that there can be no doubt that severe cases of psoriasis improve under such a diet, almost to the point of disappearance of the eruption. 8. Conversely, a high nitrogen diet exhibits an unfavorable in- fluence on psoriasis, commonly causing an extension of the eruption. 9. Whether a high nitrogen diet can stimulate an outbreak of psoriasis in a psoriatic subject, who is at the time free of the erup- tion, has not yet been determined. 10. The great proliferation and exfoliation of cells by the skin in psoriasis demand a large supply of protein, which can only be procured from the lymph and blood streams. This protein supply may be derived from the ingested food, and a possibility exists that the great demand of the diseased skin for protein may also be satis- fied by the protein reserve in muscle tissue, which thus may become depleted and later require restoration. This would explain the ready and persistent retention of nitrogen in our cases. 11. A protracted, low protein diet may diminish the prolifera- tive activity of the skin by diminishing the supply of the principal building material, namely, protein. On the other hand, a high protein diet may stimulate the proliferative activity of the cells by furnishing an abundant supply of the necessary protein. 12. We deem it premature at the present stage of our studies to commit ourselves to an hypothesis as to the primary cause of RESEARCH STUDIES IN PSORIASIS 139 psoriasis. Our studies are being continued and extended in various directions. BIBLIOGRAPHY. 1. GEBER. Dermat. Ztschr., 1913, xx, 377. 2. DAKIK. Oxidations and Reductions in the Animal Body. Longmans, Green & Co., London, 1912. TAYLOR. Digestion and Metabolism. Lea & Febiger, Philadelphia, 1912. DAKIN. Jour. Biolog. Chem., 1913, xiii, p. 513, and xiv, p. 321. RINGER, FRANKEL and JONAS. Ibid., xiv, pp. 525 and 539. RINGER. Ibid., 1913, xv, p. 145. 3. RUBNER. Die Gesetze des Energieverbrauchs, p. 282. Ztschr. f. Biolog., xix, p. 535. V. Leyden's Handbuch, p. 68. 4. VOIT, E. Ztschr. f. Biolog., 1901, xli, p. 120. 5. LUSK. Elements of the Science of Nutrition. W. B. Saunders Co., 2nd ed. Philadelphia, 1909, p. 41. 6. CAMERER. Der Stoffwechsel des Kindes, pp. 105 and 108. 7. RUBNER.. Arch f. Hyg., 1908, Ixvi, p. 45. 8. VOIT, C. 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E., CoHsox-WniTE AND SAXON. Jour. Biolog. Chem., 1913, xv, p. 181. 38. BISCHOFF UND VOIT. Die Gesetze der Ernahrung des Fleischfressers, 1860, pp. 211 and 214. 39. IDEND. Handbuch der Physiologic des Gesammt Stoffwechsels und der Fort- pflanzung, 1881, p. 347. 40. LUTHJE t-ND BEKGEB.. Loc. cit., p. 293. 41. RUBNEE. Handbuch der Ernahrungstherapie und Diatetic. V. Leyden, i, p. 53. UNIVERSITY OF CALIFORNIA LIBRARY Los Angeles This book is DUE on the last date stamped below. JL Form L9-50m-ll,'50 (2554)444 3 1158 00446 9275