Interferon is used to treat hepatitis C virus infection and its cutaneous side effects are well known. Recently, interferon-induced sarcoidosis has been reported. We report a new case of sarcoidosis during pegylated interferon alfa and ribavirin treatment with an unusual presentation in a woman with previous episodes of erythema nodusum and nodular vasculitis related to HCV.
Sarcoidosis is a systemic granulomatous disorder characterized by the presence of noncaseating granulomas. Its precise pathogenesis remains unclear but several cytokines, like interferon, may play a key role in the formation of granulomas.
Interferon is used to treat hepatitis C virus (HCV) infection due to its antiviral and immunomodulating properties and its cutaneous side effects are well known (Table
Cutaneous side effects of interferon.
Most common | Pruritus, xerosis, eczema, and localized inflammation at injection site |
---|---|
Relatively common | Psoriasis, lichen planus, and vitiligo |
Isolated | Eosinophilic pustular folliculitis, erythematosus lupus, Meyerson’s naevi, facial erythema, hypopigmented atrophic plaques, hyperpigmentation, alopecia, Sweet’s syndrome, calcified nodules, sclerodermatous graft versus host disease, cutaneous necrosis, fixed drug eruption, rheumatoid artritis, panniculitis, pemphigus foliaceus, Raynaud’s phenomenon, vasculitis, and urticaria |
Recent reports have noticed the development of sarcoidosis in patients receiving the combination of pegylated interferon alfa and ribavirin for the treatment of hepatitis C. In some cases there were only skin lesions but extracutaneous involvement was detected in other patients. We report a case of subcutaneous sarcoidosis developed during interferon alfa and ribavirin combined therapy for HCV infection.
A 60-year-old woman was infected by HCV (genotype 1, stage II/IV) after a blood transfusion in 1979. Treatment with subcutaneous pegylated interferon alfa (180 mcg weekly) and oral ribavirin (800 mg daily) was started in April 2007. Tolerance was poor by fatigue, weight loss (7 kg), and depressive syndrome. After six months of treatment she suffered a cutaneous eruption of painful, mobile, small, and subcutaneous nodules on her arms and legs (Figure
Subcutaneous nodule on the hand.
A skin biopsy revealed multiple noncaseating granulomas in the septal and lobulillar adipose tissue consistent with sarcoidosis. Special stains for bacterial, fungal, and mycobacterial organisms were negative. Laboratory studies demonstrated a moderate lymphopenia (
Treatment was discontinued and the skin lesions cleared after 2 months. Hepatitis remained stable with undetectable viral load and normal liver enzymes.
Chronic hepatitis C affects at least 170 million people worldwide [
Treatment regimens used for chronic hepatitis include interferon alfa (IFN-
The use of IFN-
Sarcoidosis is a systemic disease characterized by the presence of noncaseating granulomas. Although its exact etiology remains unclear, it is thought to represent an exaggerated immune response to antigenic stimuli (infections, malignancies, environmental factors
In sarcoidosis there appears to be a predominance of a helper T cells Type 1 (Th1) immune response and Th2 lymphocytes are relatively inactivated in the granulomas. IFN-
Ribavirin is a nucleoside analog of guanosine that enhances the Th1 response and inhibits Th2 production [
We think that upregulation of the Th1 immune response by pegylated interferon alfa and ribavirin in the presence of an antigenic trigger may play a key role for the induction of sarcoidosis in susceptible individuals. HCV may act as an antigenic trigger. Since 1987 when the first case of pulmonar sarcoidosis following interferon therapy was published, there have been published more than 20 observations of sarcoidosis related to interferon, in most of them combined with ribavirin.
The time to the onset of interferon-induced sarcoidosis ranges from 15 days to 30 months after the starting of treatment. Men and women are equally affected [
Usually interferon-induced sarcoidosis follows a benign course. In some cases cutaneous lesions were resolved without treatment in a few months and it was possible to continue hepatitis treatment with careful follow-up and close monitoring of systemic problems. However, there are cases where discontinuation of interferon therapy is necessary and even treatment with systemic steroids [
In summary, it is known that HCV infection may be associated with many dermatologic diseases. Our patient had recurrent episodes of erythema nodosum and nodular vasculitis associated with HCV. Development of sarcoidosis may be related to an antigenic trigger such as HCV in a susceptible patient with an enhanced Th1 response from pegylated interferon and ribavirin.
We report a case of interferon-induced sarcoidosis with an unusual presentation as subcutaneous nodules, without extracutaneous involvement, and it resolved completely after interferon was withdrawn.