CASE REPORT Systemic Sarcoidosis Presenting as a Granulomatous Tattoo Reaction Secondary to Interferon- Treatment for Chronic Hepatitis C and Review of the Literature ALI NAWRAS, MD, MOHAMMAD M. ALSOLAIMAN, MD, SHAHID MEHBOOB, MD, CATHERINE BARTHOLOMEW, MD, and BENEDICT MALIAKKAL, MD KEY WORDS: hepatitis C, interferon-; sarcoidosis; tattoo. Sarcoidosis is a relatively common disease with vari- able severity that can affect multiple organs, although the respiratory tract and skin are favored. While granuloma formation is the main feature of the dis- ease, the inciting cause is unknown (1). Heightened cellular immune response plays an important role in the pathogenesis of sarcoidosis. Interferon- (IFN-) has been widely used in the treatment of hepatitis C. While interferon stimulates an immune response (2) and has been associated with immune-mediated diseases when used to treat hepa- titis C (3, 4), only 11 cases of sarcoidosis have been reported in this context (5–13). Here, we describe a patient with clinical, radiolog- ical, and histopathological features of systemic and cutaneous sarcoidosis after treatment of chronic hep- atitis C with IFN-. We discuss the salient features of this case along with other reports in the literature and briefly review the possible immunological mecha- nisms involved. CASE REPORT A 42-year-old white woman was referred for abnormal liver function tests (LFTs) and positive viral hepatitis C serology. Her past medical history was unremarkable. She had no known history of sarcoidosis. The patient denied alcohol, tobacco, or intravenous drug abuse. Her risk factor for hepatitis C was a blood transfusion 13 years ago and a tattoo on the right forearm. Her physical examination was unremarkable except for the tattoo. Blood tests revealed: alanine aminotransferase 82 IU/liter (normal up to 55), aspartate aminotransferase 85 (normal up to 45), alkaline phosphatase 94 (normal up to 115) and -glutamyl- transpeptidase 90 (normal up to 45). Liver biopsy showed moderate chronic hepatitis and mild periportal fibrosis. Chest x-ray was within normal limits. Treatment with recombinant interferon- (IFN- 2b ) at 3 million units three times a week was initiated. Four weeks later, interferon therapy was discontinued due to worsening fatigue and exertional dyspnea. Pain, erythema, and swell- ing of the old flat tattoo on the right forearm, which was surrounded by subcutaneous nodules (2–3 cm in size), was noted one month later. Chest x-ray revealed mild medias- tinal widening, lymphadenopathy in the aortopulmonic win- dow and lower right paratracheal region, along with diffuse pulmonary interstitial changes (Figure 1). A CT scan of the chest showed bulky lymphadenopathy in the right paratra- cheal region extending into the precarinal and subcarinal regions. There were several tiny nodules scattered through- out the lung fields and nonspecific patchy changes at the lung bases. Serum angiotensin-converting enzyme (ACE) level was elevated at 91 IU/liter (normal up to 29). Skin test for PPD was negative. Skin biopsy of the tattoo site re- vealed noncaseating granulomatous inflammation in close proximity to the pigments of the tattoo (Figure 2). Media- stinal (right paratracheal) lymph node biopsy demonstrated a noncaseating granuloma with lymphocytic infiltration, which supported the diagnosis of cutaneous and systemic sarcoidosis. Stains and cultures for acid-fast bacilli (AFB) and fungal organisms were negative. Treatment with pred- nisone 30 mg/day was started and tapered over the next six months with a good clinical response, including disappear- ance of skin nodules, normalization of the chest x-ray, and return of the ACE level to normal limits upon one-year follow-up. Manuscript received March 19, 2001; revised manuscript re- ceived November 19, 2001; accepted November 26, 2001. From the Department of Gastroenterology, Albany Medical College, Albany, New York 12208. Address for reprint requests: Dr. Mohammad Alsolaiman, 199 S. Allen St. Apt 3-8, Albany, New York 12208. Digestive Diseases and Sciences, Vol. 47, No. 7 (July 2002), pp. 1627–1631 (© 2002) 1627 Digestive Diseases and Sciences, Vol. 47, No. 7 (July 2002) 0163-2116/02/0700-1627/0 © 2002 Plenum Publishing Corporation