key: cord-0008996-a4qyflwd authors: Duvic, Madeleine; Rapini, Ronald; Hoots, William Keith; Mansell, Peter W. title: Human immunodeficiency virus—associated vitiligo: Expression of autoimmunity with immunodeficiency? date: 2008-09-03 journal: J Am Acad Dermatol DOI: 10.1016/s0190-9622(87)70252-7 sha: 3242e90cc391f81ca83db8cbd601f0af139cbafb doc_id: 8996 cord_uid: a4qyflwd Persistent viral infections have been postulated to be trigger factors for the development of autoimmune disease. We report the development of vitiligo in four patients with human immunodeficiency virus (HIV)—related conditions and in one patient with hepatitis who later developed both psoriasis and acquired immunodeficiency syndrome (AIDS). Other common features were hepatitis and multiple other viral infections. Ribavirin was associated with repigmentation in one patient. Vitiligo may be an example of an autoimmune disease triggered by viral infection in a genetically predisposed host. Vitiligo is frequently found in association with autoimmune diseases and autoantibodies, including cytotoxic antibodies to melanocytes. ~-19 There is an increased incidence of HLA-DR4 and an autosomal dominant pattern of inheritance in some families, suggesting genetic factors. 2.~6 Finally, abnormalities of T cell subsets, especially inverted T cell ratios, have been reported. 14 656 The human immunodeficiency virus (HIV), by infecting the helper T cell and other CD4+ cells, causes immunodysfunction and finally immunodeficiency, the most severe form of which is AIDS, the acquired immunodeficiency syndrome. 2°a4 Early HIV infection is associated with immune hyperstimulation (lymphadenopathy, polyclonal B cell activation with hypergammaglobulinemia, activated T suppressor cells (T8 +, Ia+), while AIDS patients have loss of T4 and Langerhans cells, diminished antigen response, interleukin 2 and gamma interferon production, and virus-specific cytotoxicity, zs-27 Viral infections, especially herpes simplex, activate HIV-infected cells ? 8 In the course of caring for the dermatologic problems of HIV+ positive patients, we were struck by the coincidence of seeing five patients over a short period of time who developed vitiligo while evolving AIDS-related complex (ARC) or AIDS. Four are reported here; the fifth was lost to follow-up. An additional AIDS patient gave a history of developing vitiligo and hepatitis concurrently, probably long before getting HIV infection. Vitiligo has not previously been reported in association with viral infections or HIV. If more than a coincidence, it suggests that viruses may indeed serve as a trigger factor for the autoimmune disease, vitiligo. Patients attended the clinical immunology and dermatology outpatient clinics at M.D. Anderson Hospital, The University of Texas System Cancer Center. We have followed over 1000 patients with ARC and AIDS, of whom about half had had symptomatic cutaneous complications during the preceding 3 years. Patients were tested for HIV by enzyme-linked immunosorbent assay (ELISA), followed by Western blot. Those re-the child developed symptoms of AIDS-related ceiving experimental drugs signed informed consent and the protocols were approved by the institutional review board. A 35-year-old male homosexual developed ARC (AIDS-related complex) in January 1983 after multiple infections, including mumps, Coxsackie virus, hepatitis, and syphilis. He received azimexon (BM 12,531) with stable symptoms until December 1985, when he developed fever, fatigue, and night sweats. At the same time he noted white patches in the scalp and beard hair and on the extensor surfaces of the arms and back (Fig. 1) . His evaluation showed T4/T8 ratio of 0.29, anergy to skin tests, and markedly elevated cytomegalovirus and Epstein-Barr virus titers (Table I) . Hepatitis B core antibody and HIV tests showed positive results. Ribavirin (1-beta-ribofuranosyl-1,2,4,-riazole-3carboxamide) was begun at 800 mg three times daily for 7 days, and then daily for 23 weeks. He developed a photosensitivity eruption after 6 weeks, At 12 weeks repigmentation hair and skin lesions began; he continued to take ribavirin and showed improvement. The other cases are summarized in Table II . Patients 1 to 3 developed vitiligo within 2 years of HIV symptoms. Patient 2, a child with transfusion-induced ARC, developed acral vitiligo (Fig. 2) at the same time he developed parotiditis, fever, diarrhea, weight loss, and hypergammaglobulinemia. Patient 3 developed 1-to 2-cm areas of vitiligo in the month following disseminated herpes zoster. These were not in previous zoster lesions, nor was inflammation noted. Three weeks after starting ribavirin he developed alopecia areata. Repigmentation did not occur in the skin. Patient 4 had multiple persistent and chronic viral infections, including herpes simplex, for 10 years and had recent episodes of herpes zoster. In February 1987 three depigmented 1 x 2-cm macules appeared sud- denly on the chest without prior viral vesicles or inflammation. During this time the patient had cytomegalovirus pneumonitis and retinitis, for which he received dihydroxy-2-propoxymethyl-guanine. Biopsy of a depigmented macule showed an atrophic epidermis with reduced melanin (Fig. 3) . Electron microscopy revealed absent melanocytes (not shown). Patient 5 developed genital and thigh vitiligo lesions when he contracted hepatitis. Psoriasis later developed in the vitiligo and became generalized, with ARC. Unless the incubation period of HIV exceeds 10 years, he contracted vitiligo prior to HIV, in conjunction with some form of viral hepatitis. There was evidence for previous hepatitis A and hepatitis B, as well as viral inclusions, on biopsy suggestive of non-A, non-B hepatitis. All five patients shared serologic evidence of viral hepatitis and had elevated liver enzymes in association with vitiligo. The incidence of vitiligo in the general population has been estimated at 1% to 2%. ~ Although four vitiligo cases among several hundred HIV + persons is not higher than expected, we rarely see new-onset vitiligo and found the coincidence of seeing four cases within months quite remarkable. Furthermore, premature graying, suggested related to vitiligo by Lerner and Nordlund,J is quite common as ARC patients progress to AIDS.* Thus, if HIV infection and vifiligo are related, HIV, its opportunistic viruses (especially hepatitis), or dysimmunity may trigger vitiligo in the genetically predisposed host. Evidence for a relationship between the immune system and vitiligo exists. Immunodeficiency and vitiligo have been reported in the setting of mucocutarleous candidiasis. Indeed, patients with mucocandidiasis without vitiligo may have circulating antimelanocyte antibodies. ~3 "Partial albinism" and vitiligo in association with fever, pyogenic infections, hypogammaglobulinemia, and reduced Langerhans ceils were reported in two patients from the 1960s and 1970s. 29 Finally, the Vogt-Koyanagi-Harada syndrome, a viral-like illness with aseptic meningitis, hair loss, uveitis, dysacousia, and vitiligo, has a specific HLA class II antigen LDWa and antibodies cytotoxic to melanocytes. ~8.~9.30 Similar antibodies have also been found in vitiligo patients. ~7 The mechanism of autoimmunity (in this case vitiligo) is unknown. We suggest that the following possibilities exist and could be tested experimentally. ARC-associated thrombocytopenia is a welldocumented example of HIV-associa'ted autoimmune disease. Destruction of platelets is due to an antibody that reacts with a 25,000 dalton plateletassociated protein and cross-reacts with herpes simplex-infected cells. 42 If similar antimelanocyte antibodies are being produced with antiviral cross-reactivity, this could explain vitiligo in these reported patients. If more than coincidental, the developrnent of vitiligo following viral infections such as hepatitis, HIV, herpes zoster or herpes simplex, and cytomegalovirus would support the previous hypothesis that viruses trigger autoimmunity. 4~.43 Vitiligo could be the second reported autoimmune disorder occurring in the setting of the human immunodeficiency virus. Vitiligo: what is it? Is it important? 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Syphilis patients tended to be single and male (55%) [Editorial note: the authors do not mention homosexuality as a factor] and were more likely to be unemployed, unskilled workers with a low educational level. Twenty-one patients with South American pemphigus foliaeeus were divided into two groups. Eleven were treated only with corticosteroids, while 10 also were treated with auranofin (gold), 6 mg daily. After 1 year the go/d-treated group required a medium dose of only 5.5 mg daily of corticosteroids for maintenance, whereas the non-gold-treated group required 36.5 rag. Both groups were on an average of 40 mg corticosteroid daily at the start of the study.Yehudi M. Felman, M.D. Weiler KJ, gussel HA: Derm Beruf Umwelt 1986;34:i35-9 (German)No chromium in the form of chromate was found in flour and baking powders. Contradictory reports published elsewhere have not been substantiated. The occasional incidence of chromate allergy observed in the domestic services trades, bakeries, curing houses, and bottling plants were found to be due to traces of chromate in the following substances: wood ash, 0.23 ppm, lignite ash, 0.05 to 1.7 ppm, refractory brick, 0.5 to 0.9 ppm, certain alkaline scouring agents, 0.1 to 0.2 ppm, suds produced when washing chromatecontaining glasses, 0.13 to 1.61 ppm.Yehudi M. Felman, M.D.