HLA Typing in an IFN- -induced Scar Sarcoidosis: Possible Pathogenetic and Clinical Implications

Abstract

SinSarcoidosis as a complication ofinterferon (IFN) administration was first described in 1987 in a patient with renal cancer (I). Since then, more than 50 cases of pulmonary and/or cxtra-puhnonary sarcoidosis. mainly occurring in middle-aged women, have been correlated with IFN-a therapy, sometimes associated with ribavirin, in patients with chronic viral hepatitis C (2.3). Several lines of evidence suggest that HLA class I and class II alíeles may be considered possible markers for susceptibility, clinical behaviour and prognosis of sarcoidosis (4, 5).We report here a case of scar sarcoidosis that occurred one month after completion of a course of pegylatedlFN-a therapy for chronic hepatitis C virus (HC V) infection. HLAtyping was perfomied to evaluate the potential role of an immunogenetic predisposition factor. CASE REPORTA 59-year-old woman was evaluated for a paitiless nodule that had developed slowly on her right foreami over the previous 2 months. Physical examination revealed a well-demarcated, hard, .subcutaneous nodule. 4 cm in diameter, underlying a linear posttraiimalic scar acquired during childhood (Fig. I ). The patient had previously undergone a 24-week treatment for active chronic HCV genotype 2a/2c, consisting of 180 |.ig of PEG-lFN-a, administered subcutaneously once weekly, and 800 mg/day of oral ribavirin. This treatment had had a successful outcome, leading to an undetectahle viral load and an improvement in the results of liver enzyme tests by the tburth week of therapy. The treatment was completed one month prior to the appearance of the nodule.The nodule was surgically removed and the specimen was stained with haematoxylin and eosin. Histopathologiea! examination revealed the presence of Langhans giant ceils and sarcoidal-type, non-necrotizing, round, epithelioid granulomas in both dermis and hypodermis. cireumseribed by peripheral fibrosis (Fig. 2).The patient showed neither pulmonary symptoms nor other signs of systemic sarcoidat involvement. Chest X-ray and angiotensinFig. I. Subcutaneous nodule underlying a linear post-traumatic scar on the right forearm.

Scar sarcoidosis

“…Eski yaraların in ltrasyonu ya da bu bölgelerde yeni gelişen küçük kırmızı-kahverengi nodüller şeklinde karşımıza çıkabilmektedir. Eski skar alanlarının neden etkilendiği henüz tam olarak aydınlatılamamakla birlikte genetik olarak yatkınlığı olan bireylerde sarkoidozda aktive olmuş T hücre aracılı immün yanıtın travma ile ilişkili olarak dokuyu persiste eden yabancı cisme karşı yönelmesi sonucu skar sarkoidozunun gelişebildiği ya da paterji reaksiyonunun özel bir formu olabileceği bildirilmiştir 8,9 . Skar sarkoidozu ile sistemik hastalık aktivitesi arasında paralellik olduğu düşünülmektedir.…”

Interferon-alpha Induced Sarcoidosis with Cutaneous Involvement along the Lines of Venous Drainage

“…African Americans have about a threefold higher annual incidence as compared with that of Caucasion Americans 15 . Racial differences are probably influenced by environmental exposure, predisposing HLA alleles and other genetic factors 1,6,11,16 . HLA classes I and II are associated with sarcoidosis and IFN-induced sarcoidosis patients were positive for the predisposing HLA profile 11 .…”

“…Little is known about the association between sarcoidosis and chronic hepatitis C. According to the literature, sarcoidosis rarely occurs in hepatitis C virus (HCV) patients and it is associated with interferon (IFN) treatment 1,3 . Only a few cases of IFN induced sarcoidosis have been reported in the English literature [3][4][5][6][7][8][9][10][11] . IFN has an antiviral property and it has become the standard treatment for chronic HCV infection.…”

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

“…Then, we identified 2 major haplotype of the IFN-α gene and found that an IFNA allele, overrepresented in patients with sarcoidosis, was subsequently associated with increased IFN-α and IL-12 production in vitro [8]. Moreover, in a recent reported case of IIS, HLA typing was performed and revealed that the patient was positive for HLA-DRB1*03 and HLA-DQB1*02 [62], which have a correlation with the disease course or prognosis in sarcoidosis [63][64][65]. The authors hypothesized that this HLA profile predisposed the patient to IIS development [62].…”