Immune-mediated dermatologic disease, particularly lichen planus, may accompany chronic viral hepatitis [1]. Interferon- therapy may also account for immune-mediated phenomena [2]. Psoriasis and lichen planus have been seen during interferon- treatment of cancer [2]. Despite case reports of lichen planus during interferon- therapy, a large Japanese study [3] found no immune-mediated dermatologic disease, and a retrospective Italian study [4] found a prevalence of 0.12%.

We prospectively evaluated the development of dermatologic disease in 120 consecutive patients with chronic viral hepatitis (67 with hepatitis B, 45 with hepatitis C, 6 with hepatitis B and C, and 2 with delta hepatitis) during interferon- therapy (range of therapy, 6 to 18 months). For at least 1 year, we also evaluated 120 consecutive age- and sex-matched patients with nonviral chronic liver diseases who had never received interferon-. Three to 6 months after interferon- therapy began, 3 patients with chronic viral hepatitis (2 with hepatitis C and 1 with hepatitis B) developed lichen planus; 1 patient with hepatitis C developed relapsing aphthous stomatitis. The development of these disorders was not significantly associated with the type of viral hepatitis, age, sex, smoking habit, or the type of interferon- (interferon-2a or -2b). However, these disorders were associated with the presence of antinuclear antibodies (titer, 1:160 by indirect immunofluorescence) before the initiation of interferon- therapy (8.8% of antinuclear antibody-positive patients compared with 1.2% of antinuclear antibody-negative patients; P < 0.001). Lichen planus resolved soon after therapy ended in all cases. Aphthous stomatitis required discontinuation of interferon- therapy because of the painful lesions. Similar disorders were not seen in the controls.

Our study showed that interferon- may rarely induce immune-mediated dermatologic disorders (3.3% of patients overall), particularly lichen planus (2.5%), in patients with chronic viral hepatitis. This incidence is much higher than that reported by Fattovich and colleagues [4]. As in that study, lichen planus in our patients presented with mild skin and oral manifestations that did not require discontinuation of therapy and resolved after therapy ended. The patients who developed dermatologic disorders did not differ clinically from patients who did not develop these disorders, except that patients positive for antinuclear antibodies before interferon- therapy seemed to be at increased risk for immune-mediated dermatologic diseases. These disorders may emerge with interferon- when subclinical autoimmunity exists. The presence of low titers of non-organ-specific autoantibodies in patients with chronic viral hepatitis has been reported [5]. The resolution of the dermatologic lesions after discontinuation of interferon- therapy suggests that this cytokine may be a causal factor. Thorough examination for skin rash or mucosal lesions is therefore necessary in patients who receive interferon-, particularly those positive for antinuclear antibodies.