[Porphyria cutanea tarda and human immunodeficiency virus infection]

REPORT

PORPHYRIA CUTANEA TARDA AND HUMAN IMMUNODEFICIENCY VIRUS INFECTION ANDREW BLAUVELT, M.D., H. ROSS HARRIS, M.D., DANIEL J. HOGAN, M.D., FRANCISCO JIMENEZ-ACOSTA, M.D., ISMAEL PONCE, M.D., AND RUBE J. PARDO, M.D., PH.D.

Abstract

denied drinking during the previous 3 months. He also reported past intravenous drug abuse and sex with prostitutes. There was no known family history of PCT. Physical examination revealed blisters and crusted erosions scattered on the dorsa of both hands and forearms. Skin biopsy showed a cell-poor subepidermal blister with festooning along the base. Laboratory results were as follows: urine uroporphyrins, 1378 |ig/day (normal < 50 |ig/day); urine coproporphyrins, 234 |jg/day (normal 80-250 |ig/day); hemoglobin (HGB), 15.2 g/dL (normal 13-17 g/dL); white blood cell (WBC), 10.4 X 10VL (normal 4-10 x 107L) with a normal differential; alkaline phosphatase, 103 lU/L (normal 40-120 lU/L); aspartate transaminase (AST), 69 lU/L (normal 0-40 LU/L); alanine transaminase (ALT), 59 lU/L (normal 0-40 lU/L); lactate dehydrogenase (LDH), 517 lU/L (normal 100-200 lU/L); total bilirubin, 0.6 mg/dL (normal 0.2-1.4 mg/dL); and HIV seropositivity by Western blot and ELISA. The patient had no new blisters after being told to avoid the sun.

Porphyria cutanea tarda (PCT), a relatively uncommon disease, has recently been reported in patients infected with the human immunodeficiency virus (HIV). Although PCT and HIV infection may co-exist by chance, the increasing number of reported cases suggest that HIV or an associated factor triggers the development of PCT in predisposed individuals. We report four additional cases of PCT in HIV seropositive patients and review the previously reported cases. The possible links between PCT and HIV are discussed. We believe the diagnosis of PCT should prompt investigation for HIV infection in all patients. Porphyria cutanea tarda (I'CT) is the most common form of porphyria. The well-known clinical features, including facial hypertrichosis and skin fragility, blisters, and sclerodermatous plaques on sun-exposed sites, develop because of porphyrin accumulation and photactivation within the skin secondary to decreased production or impaired function of the enzyme uroporphyrinogen decarboxylase. Alcohol consumption, exogenous estrogens, and hepatoxic drugs have been implicated as exacerbating factors in predisposed individuals. Reports since 1987 document 36 cases of I'CT associated with human immunodeficiency virus (mv) infection.'""^ We review these cases and report four additional patients with 1>CT associated with Hiv infection. The occurrence of at least 40 cases of PCT, a relatively uncommon disease, in Hiv-infected patients suggests that HIV or an associated factor may lead to the development of PCT in predisposed individuals.

Case 2: A 38-year-old Hispanic man presented with a 12month history of abnormal facial hair growth and blisters on the dorsa of the forearms and hands. There was no history of liver disease. He reported heavy alcohol intake in the past, but denied drinking during the previous 8 years. He also reported past intravenous drug abuse and sex with men and prostitutes. There was no known family history of PCT. Physical examination revealed facial hypertrichosis and scattered vesicles and circular scars on the dorsa of the hands and forearms. Skin biopsy showed a cell-poor subepidermal blister with festooning along the base. Laboratory results were as follows: urine uroporphyrins, 1466 |ig/day; urine coproporphyrins, 567 jig/day; serum iron, 37 i^mol/L (normal 12-26 nmol/L); ferritin, 999 ng/L (normal 40-315 ng/L); HGB, 14.6 g/dL; WBC, 2.6 x 10^/L with a normal differential; alkaline phosphatase, 103 lU/L; AST, 41 lU/L; ALT, 90 lU/L; LDH, 844 lU/L; total bilirubin, 0.6 mg/dL; hepatitis A, IgM negative; hepatitis B, surface antigen negative; hepatitis C, IgM negative; hepatitis C, antibody negative; and HIV seropositivity by Western blot. The patient had no new blisters after being told to avoid the sun.

Case Reports Case 1: A 41-year-old white man presented with a 7-month history of skin fragility and blisters of the dorsa of the forearms and hands. There was no history of liver disease. He reported moderate alcohol intake in the past, although he

Case 3: A 48-year-old white man presented with a 6month history of numerous blisters on the dorsa of the fingers and hands. He had tested HIV positive 2 years prior to the onset of these blisters. There was no history of liver disease. He reported a long history of heavy alcohol intake and reported recurrent outbreaks of blisters associated with drinking binges. He also reported previous intravenous drug abuse. There was no known family history of PCT. Physical examination revealed vesicles, bullae, crusted erosions.

From the Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida and the Dermatology Service, Hospital Insular, Las Palmas de Gran Canaria, Spain. Address for correspondence: Daniel Hogan, M.D., Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, P.O. Box 016250, Miami, FL 3310L 474

Porphyria Cutanea Tarda Blauvelt et al.

and milia covering the dorsa of the hands and fingers. Skin biopsy showed a cell-poor subepidermal blister with festooning along the base. Laboratory results were as follows: urine uroporphyrins, 2000 (ig/day; HGB, 14.2 g/dL; WBC, 5.5 x 10^/L with a normal differential; alkaline phosphatase, 206 lU/L; AST, 37 lU/L; and ALT, 25 lU/L. The patient was lost to follow-up. Case 4: A 40-year-old Hispanic man presented with a 6nnonth history of numerous blisters on the dorsa of the fingers and hands. He had tested HIV positive approximately 2 years prior to the onset of the blisters. There was a past history of hepatitis B infection, a 10-year history of intravenous drug abuse, and a long history of moderate alcohol abuse. He had no known family history of PCT. Physical examination revealed tense blisters containing serosanguinous fluid, atrophic scars, hyperpigmented macules, and numerous milia covering the dorsa of both hands (Fig. 1). The patient also had facial hypertrichosis. Laboratory results were as follows: urine uroporphyrin, 6013 )ag/day; HGB, 12.6 g/dL; WBC, 5400 x 10='/L; T4 lymphocytes, 321/mm^ (normal 480-1800 cells/mm^); T8 lymphocytes, 734/mm3 (normal 400-1200 cells/mm^); T4/T8 ratio, 0.043 (normal 1.13.4); AST, 115 lU/L; ALT, 83 lU/L; LDH, 403 lU/L; and ferritin, 205 ng/L. A skin biopsy showed a cell poor subepidermal blister with festooning along the base. There were amorphous hyalin deposits around the dermal vessels. Treatment consisted of abstinence from alcohol and sun avoidance. The patient improved with this regimen.

Figure 1. Case 4. Numerous blisters and erosions on dorsum of hand. treated with antimalarials, with six of these patients showing improvement. Traditional treatment of PCT with phlebotomy was used in six patients and was reported to cause initial improvement in all these patients; however, this form of therapy was probably avoided in most patients because of the anemia associated with HIV infection. At least twelve of the 40 patients have died, most from opportunistic infections. It is interesting that PCT is not associated with other immunodeficient states. All reported patients in this series were probably infected with HIV prior to the onset of PCT, which suggests that HIV or some associated factor triggered the development of PCT in predisposed individuals. Wissel et al. suggested that such a factor(s) may suppress the cytochrome p450 mixed oxidase system and thereby alter the liver's ability to detoxify porphyrins.' Lafeuillade et al. hypothesized that a deficit in glutathione, which was recently described in HIV seropositive patients," may contribute to an increase in iron binding to hepatic uroporphyrinogen decarboxylase.^° Another theory was proposed by Reynaud et al.;'-' they suggested that PCT may be a manifestation of altered endogenous hormone metabolism, which has been described in HIV seropositive individuals.-" More specifically, these authors suggest that the development of Hiv-related central hypogonadism and abnormal baseline and stimulated levels of cortisol may lead to a relative endogenous estrogen excess, which could then lead to alteration of porphyrin metabolism. Because HlVinfected patients invariably have risk factors for other viral infections, including hepatitis A, B, and C, concomitant infection could also unmask manifestations of PCT.^' A wide variety of other infectious organisms and neoplasms may affect the liver in patients with HIV infection as recently outlined by Cappell." Another possible link between PCT and HIV infection may be alcohol abuse. Patients who abuse alcohol may be more likely to engaged in high risk behaviors associated with HIV infection.'^ In addition, potentially hepatoxic drugs.

DISCUSSION

We report an additional four patients with PCT and associated HIV infection. Table 1 summarizes the 40 patients reported with these diseases. All affected patients have been men with an average age of 36.3 years. Both familial and acquired forms of PCT have been reported; five cases''^'''''-' have been clearly attributed to familia'l disease, and the remainder specifically mentioned no family history of PCT or did not comment on the occurrence of PCT among family members. Alcohol abuse was reported in many of the patients, but a few denied alcohol intake or had not been drinking for prolonged periods of time. Reported data regarding viral hepatitis infection was limited; however, 18 (65%) of 26 patients had historical or serologic evidence of hepatitis B or C infection. Transaminase levels were elevated in most patients (82%). Risk factors for HIV infection were as follows, with several patients reporting more than one high risk category: intravenous drug abuse (17 patients), homosexuality (16 patients), numerous heterosexual partners/sex with prostitutes (7 patients), blood transfusions (3 patients), hemophilia A (3 patients), and two patients reporting no risk factors. Conservative treatment of PCT, including strict sun avoidance/sun protection and decreased alcohol intake, was effective in controlling signs of PCT in many of the reported patients. In addition, eight patients were 475

International Journal of Dermatology Vol. 31, No. 7, July 1992

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