Assessment of digital clubbing in medical inpatients by digital photography and computerized analysis Assessment of digital clubbing in medical inpatients by digital photography and computerised analysis Daniela Husarik, Stephan R. Vavricka, Michael Mark, Andreas Schaffner, Roland B. Walter Department of Internal Medicine, Medical Clinic B, University Hospital, Zürich, Switzerland Introduction Background: Digital clubbing has been associ- ated with a large number of disorders. To over- come the limitation of subjective clinical assess- ment, several objective measurements have been developed among which the hyponychial angle was considered most accurate for quantification of finger clubbing. Methods and results: Here we investigated hyponychial angles in 123 healthy subjects and 515 medical inpatients from a tertiary hospital. Healthy subjects had a mean angle of 178.87 ± 4.70° (range: 164.78–192.10°), a finding that is well in accordance with previous results obtained using other techniques, underlining the accuracy of the chosen method of assessment. The mean angle of patients was 181.65 ± 7.18° (range: 162.22–209.19; p <0.0001 compared to healthy controls). When the upper limit of normality, i.e. 192.10°, was used to define digital clubbing, the prevalence of digital clubbing in our patients was 8.9%; the percentage of clubbed fingers varied substantially among the various disease states (up to 80% in patients with cystic fibrosis). Conclusion: The use of digital photography with computerised analysis was found to be an easy, fast and inexpensive method for the quantification of hyponychial angles with excellent intra and inter observer reliability whilst causing no discomfort to patients. This tool may therefore be useful in fur- ther longitudinal and cross-sectional studies of finger morphology and may become an accepted standard in the diagnosis of digital clubbing. Key words: digital clubbing; digital photography; hyponychial angle; prevalence; quantification Summary Since the first description of finger clubbing in a patient with empyema by Hipprocrates in the fifth century BC, this deformity has been associ- ated with a large number of disorders [1, 2]. Fea- tures of clubbed fingers on physical examination are a shiny and smooth appearance of the cuticle with increased sponginess, a flattening of the nor- mal obtuse angle on the dorsal surface of the fin- ger at the base of the nail, an increase in volume of the distal segment of the finger and an increase in the curvature of the nail in one or both planes [2, 3]. However clinical assessment is subjective, often difficult in mild cases and therefore unreliable [4–8]. To overcome this limitation several methods have been developed over the past century for quantification of clubbing. Attempted approaches include matching brass templates with arcs of var- ious sizes to measure longitudinal curvature [9], plethysmography [10], casts with planimetry [11] or measurement of finger depth rates [12, 13] and a shadowgraph technique [14–16]. None of these, however, was accepted as a standard of diagnosis, Figure 1 Construction of hyponychial angle. The hyponychial angle was constructed by a line AB drawn from the distal digital skin crease to the cuticle, and a line BC drawn from the cuticle to the hyponychium (thickened stratum corneum of epidermis lying under the free edge of the nail [11]. Distal digital crease Cuticle Hyponychium No financial support declared. 132Original article S W I S S M E D W K L Y 2 0 0 2 ; 1 3 2 : 1 3 2 – 1 3 8 · w w w . s m w . c h Peer reviewed article S W I S S M E D W K L Y 2 0 0 2 ; 1 3 2 : 1 3 2 – 1 3 8 · w w w . s m w . c h 133 and all proved impracticable as a method for veri- fying the clinical impression of clubbing. Recently digital cameras and computerised analysis have ac- curately been used to assess fingernail morphom- etry and offer obvious advantages over previous techniques [17]. Among several objective measurements, the hyponychial angle (figure 1) correlated strikingly with the physician’s subjective score, and was con- sidered “best discriminator” by Regan et al. [11] since it distinguished normal and clubbed fingers without overlap. The accuracy of the hyponychial angle as an indicator of finger clubbing was later confirmed by other investigators [15, 16, 18]. The original findings of these early studies are sum- marised in table 1. In a recent review of the liter- ature, a pooled weighted mean value for the hy- ponychial angle of 179.0 ± 4.5° was calculated. None of the 171 healthy subjects who have been assessed to date had angles that exceeded 192° and an angle less than 190° was therefore assumed to describe normality [2]. Although several studies reported mean values of hyponychial angles in a number of disease states [2], only very limited data on finger morphology and the prevalence of digi- tal clubbing in unselected hospitalised medical pa- tients is available [19]. Thus the present study was designed to investigate the distribution of hy- ponychial angles in a large group of both healthy volunteers and medical inpatients from a tertiary hospital. For quantification the hyponychial angle was calculated by means of digital photography and computerised analysis. Materials and methods Subjects Healthy controls: after verbal consent was obtained, fingers of subjects who reported no acute or chronic ill- ness were photographed as healthy controls. Medical inpa- tients: during the three month enrolment period from Sep- tember 25, 2000 to December 22, 2000, patients admitted as inpatients to the medical clinic of the Department of Internal Medicine (University Hospital, Zürich, Switzer- land) were eligible when hospitalised for more than 2 days. This minimal length of hospitalisation was arbitrarily cho- sen to select patients more characteristic of medical inpa- tients in a tertiary hospital and as a means of excluding pa- tients hospitalised simply for short interventions. There were no other predefined exclusion criteria, and only the patient’s verbal consent was required. Patients who were admitted repeatedly during the period of enrolment were examined only during their first admission. Acquisition of digital images A simple and inexpensive system was developed using a digital camera (Coolpix 990, Nikon, Küsnacht, Switzer- land) fixed 12 cm in front of a bar to obtain standardised and reproducible images of the radial view of the right index finger. The bar (on which the extended finger was placed for assessment) and the wooden support (on which the remaining flexed fingers were placed) was secured in a controlled position in front of the camera in order to avoid rotation. The left instead of the right index finger was used in cases where traumatic or surgical deformities prevented correct measurement of the hyponychial angle on the right side. Predefined settings of the camera were used for acquisition of images in normal resolution with an automatic flash. For further analysis digital images were stored on CD-ROM. Measurements Using Quartz PCI Scientific Image Management System Software (Version 4.20, Quartz Imaging Corpo- ration, Vancouver, Canada), the images were displayed on a computer screen. The angle measurement tool was used to calculate the hyponychial angle according to Regan et al. [11] as outlined (fig. 1). Each single picture was analysed by three investigators (DH, SRV, MM) repeating the angle calculation in triplicate and at random. Reference Regan et al. [11] Bentley et al. [15] Sinniah et al. [16] Kitis et al. [18] Healthy controls Hyponychial angle (º) 187.0 180.1 ± 4.2 180.7 ± 5.2 177.9 ± 4.6 Range 176.5–192 n.d 165–189 n.d. Age (years) n.d. 11.25 6.7 ± 3.4 29 Number of subjects 18 25 20 116 Patients Hyponychial angle (º) 209.4 194.8 ± 8.31, 194.8 ± 8.32 194.5 ± 7.5 n.d. 194.8 ± 8.33, 194.8 ± 8.34 Range n.d. n.d. 178–205 n.d. Age (years) n.d. 16.21, 12.32, 173, 114 6.9 ± 2.7 n.d. Number of patients 7 501, 252, 53, 204 19 901, 22 Characteristics Asbestos workers Cystic fibrosis1 Thalassemia major IBD1 Asthma2 Cyanotic heart disease Proctitis2 Cyanotic c.h.d.3 Malabsorption syndrome Acyanotic c.h.d.4 Bronchiectasis Abbreviations: c.h.d. congenital heart disease; n.d., no data available; IBD, inflammatory bowel disease. Note: the study by Kitis et al. [18] found digital clubbing present in 75 out of 200 patients with Crohn’s disease, and 15 out of 103 with ulcerative colitis, however, no precise data on mean hyponychial angles in these groups were provided. Table 1 Summary of histori- cal studies investigat- ing hyponychial an- gles for assessment of digital clubbing. Digital clubbing in medical inpatients 134 Statistical analysis Results are presented as means ± SD. Nonparametric statistical tests were used throughout. Continuous vari- ables between groups were compared using a two-tailed Mann-Whitney U test or a Kruskal-Wallis one-way analy- sis of variance test as appropriate, whereas discontinuous variables were compared using the two-tailed Fisher’s exact test. Inter-rater and intra-rater reliability were as- sessed using intraclass correlation. In addition, Spearman rank correlations were performed. Statistical calculations were done using InStat version 3.05 (GraphPad, San Diego, CA, USA); p <0.05 was considered significant. Results 123 healthy subjects participated in the study; their characteristics and the results of the mea- surement of the hyponychial angles of their right index fingers are shown in table 2. Women were significantly older than men (p = 0.0197). They also had a slightly larger mean hyponychial angle, but this difference did not reach statistical signifi- cance (p = 0.0719). The distribution of the hy- ponychial angles is shown in figure 2. Table 3 lists mean hyponychial angles of different age groups. Mean hyponychial angles among different age groups were similar for subjects of both sexes together (p = 0.9733) as well as for women (p = 0.9585) and men (p = 0.8815) separately. There was no correlation between the age of the subjects and the hyponychial angle (for both sexes: r = 0.0070, p = 0.9387; for women: r = –0.0158, p = 0.9082; for men: r = –0.0317, p = 0.7988). In a subgroup of 26 healthy volunteers, digital images of both index fingers as well as the right middle finger were taken. Measured hyponychial angles were 176.15 ± 4.34° (right middle finger), 178.60 ± 4.38° (right index finger), and 180.40 ± 5.46° (left index finger) respectively. Compared to the right middle finger, the index fingers of both sides had significantly larger hyponychial angles (right side: p = 0.0002; left side: p = 0.0043), whereas the difference between the hyponychial angle of the right compared to the left index finger did not reach statistical significance (p = 0.1427; all data not shown). During the three-month enrolment period, a total of 576 patients were eligible for study partic- ipation. Of these, 53 patients were not included for the following reasons: personal (12), impossibility of communication due to language problems (9), severe or terminal illness or death (13), patient was not accessible (19). Of the remaining 523 patients, the digital images of 8 subjects were excluded for technical reasons. Therefore, a total of 515 pa- tients were included in the final analysis; their characteristics are outlined in table 2. Although women were slightly older than men and had larger hyponychial angles, these differences did not reach statistical significance (p = 0.0802 for age and p = 0.0710 for hyponychial angles, respec- tively). However men reported a history of regu- lar alcohol consumption (p <0.0001) and a positive cigarette smoking status (p <0.0001) significantly more frequently than women. The angle distribu- tion of the patients are shown in figure 3 and mean hyponychial angles for different age groups are listed in table 3. Hyponychial angles of patients aged 30–44 years were significantly larger than those from patients between 60–98 years of age (p <0.05), otherwise no differences between hypo- nychial angles of different age groups were found. Furthermore there were no statistical differences women men both Control subjects (n) 67 56 123 Mean age (years) ± SD 39.5 ± 12.5 34.9 ± 12.4 37.4 ± 12.6 Range 22–77 19–72 19–77 Mean hyponychial angle (º) ± SD 179.60 ± 4.76 178.01 ± 4.52 178.87 ± 4.70 Range 164.78–191.98 168.01–192.10 164.78–192.10 Patients (n) 216 299 515 Mean age/years) ± SD 62.2 ± 19.5# 59.7 ± 17.3# 60.7 ± 18.3# Range 15–98 16–91 15–98 Mean hyponychial angle (º) ± SD 182.17 ± 7.00* 181.27 ± 7.29** 181.65 ± 7.18*** Range 166.28–201.82 162.22–209.19 162.22–209.19 Regular alcohol consumption (y/n) 11/205 51/248 62/453 Cigarette smoking (y/n) 187/66 70/95 257/161 Note regular alcohol consumption was assumed when patients reported drinking of >1 glass of wine daily. Smoking status was only assessed in 416 patients. # p <0.0001 compared to corresponding healthy subjects; * p = 0.0054 compared to healthy women; ** p = 0.0011 compared to healthy men. *** p <0.0001 compared to healty subjects of both sexes. Table 2 Characteristics of control subjects and patients. S W I S S M E D W K L Y 2 0 0 2 ; 1 3 2 : 1 3 2 – 1 3 8 · w w w . s m w . c h 135 between hyponychial angles of women and men within the same age groups. Angles of patients with regular alcohol consumption did not differ from those who reported no regular alcohol consumption (180.9 ± 7.7° vs. 181.8 ± 7.1°; p = 0.3321). This was also true when women and men where analysed separately (for women: 182.1 ± 7.5° vs. 182.2 ± 7.0°, p = 0.8760; for men: 180.7 ± 7.7° vs. 181.4 ± 7.2°, p = 0.5052).Where the smoking history was known, smokers had slightly larger hyponychial angles than non-smokers (181.9 ± 7.4° vs. 180.7 ± 6.9°), but this difference did not reach statistical significance (p = 0.1329). Smoking women, however, had larger angles than non-smoking women (183.5 ± 7.5° vs. N u m b e r o f su b je ct s Hyponychial angle (˚) Hyponychial angle (˚) Figure 2 Distribution of hyponychial angles in healthy subjects. The distribution of hyponychial angles assessed by digital pho- tography and computerised analysis is shown for healthy women (upper panel), healthy men (middle panel) and for both sexes (lower panel) respectively. Figure 3 Distribution of hyponychial angles in medical inpatients. The distribution of hyponychial angles assessed by digital photography and computerised analysis is shown for female patients (upper panel), male patients (middle panel) and patients of both sexes (lower panel) respectively. Age women + men control subjects women + men patients women men women men 15–29 179.0 ± 4.2 (45)* 180.3 ± 4.4 (19) 178.0 ± 3.9 (26) 183.6 ± 7.4 (40) 183.6 ± 5.6 (17) 184.0 ± 8.7 (23) 30–44 178.5 ± 4.9 (46)** 179.0 ± 4.9 (25) 177.9 ± 4.9 (21) 183.4 ± 7.5 (75)# 184.2 ± 7.8 (35) 182.7 ± 7.2 (40) 45–59 179.6 ± 5.4 (26) 179.9 ± 5.0 (20) 178.6 ± 7.1 (6) 181.6 ± 7.3 (121) 182.7 ± 6.9 (40) 181.1 ± 7.5 (81) 60–98 177.8 ± 4.1 (6) 178.4 ± 6.0 (3) 177.2 ± 2.4 (3) 180.9 ± 6.9 (279) 181.2 ± 6.9 (124) 180.6 ± 6.9 (155) Note: results are shown as mean ± SD; the number of patients is given in parenthesis. * p = 0.0027, ** p = 0.0004 compared to patients of the same age group; # p <0.05 compared to patients aged 60–98. Table 3 Age distribution of hyponychial angles among control subjects and patients. Women Women Women and Men Men Men Women and Men Digital clubbing in medical inpatients 136 181.0 ± 6.8°; p = 0.0310), whereas the angles of smoking men and non-smoking men were equal (181.4 ± 7.3° vs. 180.5 ± 7.4°; p = 0.3771). Patients were significantly older than healthy controls (p <0.0001 for both sexes as well as for women and men separately; see table 2), and mean hyponychial angles of patients were significantly larger than those of healthy subjects; for both sexes, p <0.0001; for women, p = 0.0054; for men, p = 0.0011. When mean hyponychial angles of healthy subjects and patients of different age groups were compared, patients aged 15–29 and 30–44 years had significantly larger hyponychial angles (p = 0.0027 and p = 0.0004, respectively). 46 patients (18 female/ 28 male; mean age: 54.3 ± 21.0 years) had hyponychial angles that did not overlap with the range of hyponychial angles of healthy subjects (164.78–192.10°). When the upper limit of normality is used to define the “beginning” of digital clubbing, a prevalence of 8.9% could be cal- culated; the mean hyponychial angle of these 46 patients was 195.76 ± 4.29°. The percentage of fe- male patients (8.3%) featuring digital clubbing was not statistically different compared to the percent- age of male patients (9.4%; p = 0.7554). Table 4 lists mean hyponychial angles of different patient groups and the percentage of patients with digital clubbing among patients suffering from the same specific disease. The percentage of clubbed fingers varied substantially among the various disease- states and was as high as 80% in patients with cys- tic fibrosis. As shown, patients suffering from acquired valvular heart disease, bronchiectasis, chronic hepatitis, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary emphysema, en- docarditis, heart failure, HIV infection, ischaemic heart disease, leukaemia, liver cirrhosis, pneumo- nia, pulmonary hypertension and certain solid ma- lignant tumours, as well as subjects who had had lung transplantation in the past were identified as having clubbed fingers. In addition, digital club- bing was found in patients with atrial myxoma (1), complex cyanotic congenital heart anomaly (con- sisting of a single ventricle, ventricular septum defect and pulmonary hypertension: 1 patient), cystic renal disease (1), pulmonary fibrosis (1) and lymphoma (1). As stated in the methods the hyponychial an- gles of both healthy subjects and patients were de- termined by three investigators who repeated each measurement three times in a randomised fashion. Intra-rater reliability was excellent with coeffi- cients of 0.969, 0.994, and 0.958 for assessment of hyponychial angles in healthy volunteers by rater 1, rater 2, and rater 3, and 0.981, 0.997, and 0.981 for measurement of hyponychial angles in patients Disease n1 hyponychial angle p-value2 p-value3 x4 Heart diseases Acquired valvular heart disease 81 180.57 ± 7.39 0.1342 0.1493 7 (8.6%) Endocarditis 7 186.34 ± 9.94 0.0466 0.2229 2 (28.6%) Heart failure 95 182.02 ± 6.72 0.0003 0.4834 9 (9.5%) Ischaemic heart disease 170 181.95 ± 7.32 0.0002 0.6096 16 (9.4%) Lung diseases Bronchiectasis 5 186.42 ± 7.66 0.0453 0.1653 2 (40%) COPD 62 184.83 ± 7.70 <0.0001 0.0003 9 (14.5%) Cystic fibrosis 5 193.17 ± 8.44 <0.0001 0.0050 4 (80%) Emphysema 9 181.72 ± 9.04 0.1618 0.8247 2 (22.2%) Hypertension, pulmonary 31 182.36 ± 8.62 0.0079 0.4585 3 (9.7%) Lung transplantation 12 184.99 ± 8.55 0.0219 0.2102 3 (25%) Pneumonia 47 184.32 ± 9.24 0.0002 0.0504 11 (23.4%) Infectious diseases HIV infection 19 186.55 ± 7.84 <0.0001 0.0018 3 (15.8%) Liver diseases Hepatitis (chronic) 21 185.20 ± 8.44 <0.0001 0.0115 3 (14.3%) Liver cirrhosis 19 184.08 ± 7.75 0.0049 0.1686 3 (15.8%) Malignant diseases Leukaemia* 13 183.34 ± 6.70 0.00112 0.2774 2 (15.4%) Solid tumors, malignant (all) 84 182.02 ± 6.16 <0.0001 0.3007 5 (6.0%) Anal 6 185.45 ± 6.41 0.0106 0.1463 2 (33.3%) Lung 17 182.51 ± 7.29 0.0141 0.4220 2 (11.8%) COPD = chronic obstructive pulmonary disease; 1 total number of patients suffering from the specified disease; 2 compared to healthy controls; 3 compared to remaining patients; 4 number of patients with hyponychial angles that exceed the range of normal subjects (i.d. >192.10*); * included 12 patients with acute and one patient with chronic leukaemia Note: the sum of patients with digital clubbing does not yield 46 since only diseases that affected more than 4 patients are shown and, in addition, several patients had more than one disease and were therefore listed more than once. Table 4 Hyponychial angles of various patient groups. S W I S S M E D W K L Y 2 0 0 2 ; 1 3 2 : 1 3 2 – 1 3 8 · w w w . s m w . c h 137 by rater 1, rater 2, and rater 3 respectively. Like- wise inter-rater reliability was high; corresponding coefficients were 0.839, 0.810, and 0.825 for rat- ing 1, 2, and 3 in healthy volunteers, and 0.915, 0.906, and 0.910 for rating 1, 2, and 3 in patients respectively. Discussion In the present study, we found a mean hy- ponychial angle of right index fingers among healthy subjects that was very similar to those re- ported in previous studies (see table 1 and refer- ence [2]). Since angles were determined with plas- ter cast or shadowgraph techniques in earlier re- ports, this result confirms the accuracy of digital photography and computerised analysis as a mod- ern method for quantification of finger morphol- ogy. Also in agreement with previous findings, [2] none of the healthy volunteers had angles above approximately 192°, accordingly this value was confirmed as describing the upper limit of nor- mality. Preliminary data obtained in 26 healthy volunteers indicated that hyponychial angles of index and middle fingers may be slightly but sig- nificantly different. Therefore in the future it may be important to restrict this range of normality to hyponychial angles of (right) index fingers. To date only very limited information about the prevalence of digital clubbing in unselected medical patients is available. In one study, clubbed fingers were found in 29 out of 117 adult patients (24.8%) admitted in medical wards [19]. In our group of medical inpatients from a tertiary hospi- tal, mean hyponychial angles of index fingers were significantly larger than those of healthy subjects, although the mean difference was only 2.78° and there was considerable overlap. Nevertheless 46 patients had hyponychial angles that exceeded 192.1° resulting in an overall prevalence of digital clubbing of 8.9° when the upper limit of normal- ity is used to define the “beginning” of clubbed fin- gers. Difference in characteristics of patients, as- sessment method and definition of digital clubbing may explain the difference between the results from our study and previous results. As outlined in detail in table 4, the percentage of patients with clubbed fingers varied substantially among the dif- ferent disease states: from 0% up to 80% in pa- tients with cystic fibrosis. Mean hyponychial an- gles in our patients with cystic fibrosis were very similar to those assessed by Bentley et al. [15] and Pitts-Tucker et al. [20] (193.2 ± 8.4° in our study compared to 194.8 ± 8.3° and 192° respectively), once again confirming the accuracy of the method used in the present study. An obvious limitation of our study is that the detailed analysis of the patient’s records necessary to associate digital clubbing with an underlying disease was complicated by the fact that most med- ical patients had more than one significant disease. Nevertheless patients with diseases known to be associated with digital clubbing, such as bron- chiectasis, cystic fibrosis, pulmonary fibrosis, endo- carditis, chronic hepatitis or cirrhosis, HIV in- fection, infectious lung disease and lung cancer could be identified. One patient with clubbed fin- gers was found to have an atrial myxoma, another had a complex cyanotic congenital heart anomaly. Two other patients with pulmonary hypertension were also found to have digital clubbing. In one, pulmonary hypertension was due to heart failure; in the other pulmonary hypertension was associ- ated with HIV infection. In addition, there were some diseases that so far have only rarely, if at all, been associated with digital clubbing, e.g. leu- kaemia (both patients had acute lymphoblastic leukaemia, with one having no other disease, whilst the other suffered from heart failure and fungal pneumonia) or heart failure (among these some merely had underlying ischaemic heart disease and no other concurrent disease). Two patients with anal cancer were also identified as having digital clubbing and of these only one had further disease (lung cancer). One patient with bronchiectasis and digital clubbing also had chronic hepatitis, a sec- ond one concomitantly suffered from ischaemic heart disease. In the group of patients with cystic renal disease, digital clubbing was found in one subject, who also had pulmonary emphysema. Over the last decades several objective meth- ods have been developed to defeat the limitations of subjective clinical assessment of finger mor- phology. However, previous techniques had sev- eral draw-backs, e.g. finger casts took several hours to make, were perhaps faulty and had to be re- peated or were too time-consuming for routine use [11–13]. Shadowgraphs allowed serial measure- ments with minimal time requirement but results could not be stored, precluding repeated analysis and long-term studies, [14, 15] shadowgrams were cheap and simple to obtain but necessitated out- lining of finger silhouettes on paper [16]. Recently digital cameras and computerised analysis have been introduced as a means of evaluating digital clubbing [17]. Moreover, the use of digital pho- tography with computerised analysis has proved to be an easy, simple and relatively cheap method of quantification of hyponychial angles. Data thus obtained showed only minimal variation in inter- and intra-rater reliability as determined by repet- itive analysis by three different investigators in the present study. Digital acquisition and storage of images offer long-term storage of original “data” and repeated analysis without loss of quality by dif- ferent investigators at different time points. It can be assumed that determination of both nail-fold Digital clubbing in medical inpatients 138 angles and phalangeal depth ratios are both accu- rate [2] and direct comparison of these methods awaits further analysis. Since the measurements can be recorded within a few minutes without caus- ing discomfort this method allows serial measure- ments or investigation of very large populations, rendering it a tool useful for further longitudinal and cross-sectional studies of finger morphology and digital clubbing. The clinical value for mod- ern medicine of a standardised assessment of dig- ital clubbing remains to be determined. We thank Silvia Märki for excellent technical support and Valentin Rousson, PhD, Department of Biostatistics, Institute for Social and Preventive Medicine, University of Zürich, Switzerland, for help with the statistical analy- sis. Correspondence: Dr. R. Walter Clinical Research Division Fred Hutchinson Cancer Research Center 1100 Fairview Ave. N., D2–373 Seattle, WA 98109–1024 USA E-Mail: rwalter@fhcrc.org References 1 Shneerson JM. Digital clubbing and hypertrophic osteo- arthropathy: the underlying mechanisms. Br J Dis Chest 1981; 75:113–31. 2 Myers KA, Farquhar DRE. Does this patient have clubbing? JAMA 2001;286:341–7. 3 Lovell RRH. Observations on the structure of clubbed fingers. Clin Sci 1950;9:299–321. 4 Lovibond JL. Diagnosis of clubbed fingers. Lancet 1938/I: 363–4. 5 Pyke DA. Finger clubbing. Validity as a physical sign. Lancet 1954/II:352–4. 6 Rice RE, Rowlands PW. A quantitative method for the estima- tion of clubbing [thesis]. Tulane University Medical School. 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Estimation of clubbing by analysis of shadowgraph. Br Med J 1970;3:43. 15 Bentley D, Moore A, Shwachman H. Finger clubbing: a quan- titative survey by analysis of the shadowgraph. Lancet 1976/II: 164–7. 16 Sinniah D, Omar A. Quantification of digital clubbing by shad- owgram technique. Arch Dis Child 1979;54:145–6. 17 Goyal S, Griffiths AD, Omarouayache S, Mohammedi R. An improved method of studying fingernail morphometry: appli- cation to the early detection of fingernail clubbing. J Am Acad Dermatol 1998;39:640–2. 18 Kitis G, Thompson H, Allan RN. Finger clubbing in inflam- matory bowel disease: its prevalence and pathogenesis. Br Med J 1979;2:825–8. 19 Dutta TK, Das AK. Clubbing – a re-evaluation of its incidence and causes. J Assoc Physicians India 1996;44:175–7 [Erratum: J Assoc Physicians India 1996;44:586]. 20 Pitts-Tucker TJ, Miller MG, Littlewood JM. Finger clubbing in cystic fibrosis. Arch Dis Child 1986;61:576–9. 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