Interferon-induced sarcoidosis

Abstract

Interferons (IFNs) are widely used for the treatment of various medical diseases. They have marked immunomodulatory effects, and many reports have been published associating IFN therapy with the induction of autoimmune phenomena and other disorders of immune regulation such as sarcoidosis. The clinical presentation of IFN-induced sarcoidosis (IIS) is insidious and can be confused with common constitutional side effects of these drugs. The age of onset of IIS is later than that of naturally occurring sarcoidosis. The most common organs involved are the lungs and skin. In the majority of cases, IIS follows a benign course. As we show in an illustrative case report, complete resolution after discontinuation of IFN therapy can be expected. This review summarises 65 cases of IIS reported in the literature and highlights the pathophysiology, clinical features, diagnostic modalities and therapeutic options for this increasingly recognised phenomenon.

Dendritic Cells in the Pathogenesis of Sarcoidosis

“…Despite the lack of evidence for increased pDC frequency or activation in sarcoidosis, IFN-a therapy is a well documented risk factor for development of IFN-induced sarcoidosis (IIS) (112,113), occurring in 5% of patients with chronic hepatitis C treated with IFN-a (114). Also, an IFN-a17 polymorphism, that shows increased IFN-a secretion when whole blood is activated with Sendal virus, has been documented in a cohort of Japanese patients with sarcoidosis (115).…”

The Role of Type I IFN and TNF-α in the Pathogenesis of Sarcoidosis

“…The second major organ is the skin. The incidence of skin involvement appears to be much higher that reported in natural sarcoidosis (60% versus 25%) [6,38,41]. The most common skin manifestation is subcutaneous nodules, whereas erythema nodosum, reported to be the most common cutaneous manifestation in typical sarcoidosis, is less frequently observed in IIS.…”

“…Although the incidence of IIS is not known, the prevalence of sarcoidosis in IFN-treated HCV patients has been reported to be rare range from 0.09% to 0.44% [38,39]. The precise prevalence of IIS, however, may be underestimated and difficult to assess because its clinical presentation mimics the constitutional IFN-related adverse effects [6]. Actually, Hoffman et al found a 5% incidence of sarcoidosis in a cohort of 60 patients who participated in a randomized trial of IFN-α therapy for chronic HCV [40] Basically the clinical presentation of IIS resembles that of its idiopathic counterpart.…”

“…However, due to its immunomedulatory effects, it has also been reported to induce several autoimmune and/or inflammatory disorders [5]. Notably, an increasing number of sarcoidosis has been reported in chronic HCV patients who received type I IFN therapy [6,7]. In some cases, the sarcoid lesions improved following dose reduction or cessation of the therapy, suggesting the importance of type I IFN in the disease development.…”

“…Similar to other species of viruses and bacteria implicated in the etiology of sarcoidosis [48], some reports have suggested a potential role for the HCV itself in the development of sarcoidosis [38,[49][50][51]. As chronic HCV infection is associated with induction/stimulation of type 1 cellular immune response causing chronic liver damage [52] as well as various immunological diseases [53][54][55][56], it is possible that the antigenicity and viral persistence can serve as a trigger factor for the development of clinical sarcoidosis in susceptible individuals [6]. IFN-α may act as an exacerbationg factor in this situation.…”