Erythema dyschromicum perstans and hepatitis C virus infection

A 48-year-old woman with a 10-month history of widespread, hyperpigmented, slightly pruritic macules, with a red border, involving the trunk and the p roximal limbs (Fig. 1) was referred to our outpatient department. The oral mucosa, palms, soles, scalp, and nails were normal. Laboratory tests showed elevated liver enzymes [alanine aminotransferase (A LT), 681U/L (normal value, <40IU/L); aspartate aminotransferase (AST), 41IU /L (normal value, <40IU/L)], the presence of antibodies to hepatitis C viru s (anti-HCV) and HCV RNA (Amplicor Roche). In addition, cryoglobulinemia ty pe III (IgM(kappa,lambda), IgG(kappa,lambda)) was,, detected with a high cr yocrit value, and there was detectable C-reactive protein, rheumatoid facto r, and a low titer of antinuclear antibodies (1:80). A percutaneous liver b iopsy showed changes compatible with mild chronic hepatitis (grade, 6; stag e, 0). The possible source of infection was unknown, as the patient had no history of parenteral transmission (e.g. blood transfusions, intravenous il licit drug use). A skin biopsy specimen from the active border of a lesion showed hyperkeratosis, parakeratosis, and hydropic degeneration of the basa l cell layer, with the formation of colloid bodies in the epidermis. A mode rate perivascular lymphohistiocytic infiltrate with melanophages and free m elanin granules was observed in the upper dermis (Fig. 2). Immunostaining o f paraffin-embedded tissue sections with the TORDJT-22 IgG, mouse monoclona l antibody to HCV (Biogenex, Son Ramon, USA), which is specific for the non structural region of HCV (NS3-NSH, C100 antigen) using the avidin-biotin-pe roxidase complex (ABC) as well as the alkaline phosphatase antialkaline pho sphatase (APAAP) methods, failed to detect HCV in the lesion of erythema dy schromicum perstans (EDP) (Nakopoulou L, Manolaki N, Lazaris A, et al. Tiss ue immunodetection of C100 hepatitis C virus antigen in major thalassemic p atients. Hepato-Gastroenterol 1999; 46: 2515-2520). Direct immunofluorescen ce showed IgG, IgM, JgA, and fibrinogen deposits on colloid bodies. EDP was diagnosed on the basis of these clinical and laboratory findings. The patient was treated with interferon-alpha (2b) (Intron-A, Schering Plou gh Athens, Greece), 3MU thrice weekly subcutaneously for 12 months, with ad ditional topical steroid application. There was no response to this treatme nt with new lesions appearing in previously unaffected areas of the trunk a nd extremities. HCV RNA remained persistently positive. Thus, a modified re gimen with interferon-alpha (2b), 6MU thrice weekly for 6 months, was tried . At the end of the treatment course, the eruption of EDP had greatly impro ved. Liver enzymes were normal.(ALT, 22IU/L; AST, 24IU/L) and HCV RNA had b ecome negative. Four months later, however, cutaneous lesions reappeared an d hepatitis C relapsed. At this time point, combination therapy of iriterfe ron-alpha (2b), 3MU thrice weekly, with ribavirin, 1000 mg daily, was given . Six months later, liver enzymes were normal (ALT, 42IU/L; AST, 39IU/L), H CV RNA was negative, and the lesions of EDP had resolved.