Interferon-alpha-induced sarcoidosis in a patient being treated for hepatitis C

Abstract

Patient: Female, 43Final Diagnosis: —Symptoms: Diarrhea • generalized weakness • headache • lightheadedness • nausea • rash • short of breath • vomitingMedication: —Clinical Procedure: —Specialty: PulmonologyObjective:Rare diseaeBackground:IFN-alpha-2b in combination with ribavirin is now the standard of care for the treatment of hepatitis C. Sarcoidosis is a chronic multisystem granulomatous disorder characterized by noncaseating granulomas in the involved organs. The pathologic hallmark of sarcoidosis is the presence of noncaseating granulomas in the interstitium that typically involve the lymphatics.Case Report:A 43-year-old woman presented to our care with 2-week history of nausea, vomiting, diarrhea, shortness of breath, migraine headache, maculopapular rash, generalized weakness, and lightheadedness. She had been treated for hepatitis C with telaprevir, ribavirin, and interferon-alpha-2b for 6 months. Chest radiograph showed bilateral diffuse prominence of bronchovascular markings. CT of the chest revealed bilateral diffuse centrilobular nodules with associated intralobular septal thickening, thickening of the central peribronchovascular interstitium, nodularity of the major fissures, and mediastinal lymphadenopathy. These findings were suspicious for atypical pulmonary sarcoidosis, possibly interferon-induced. The pathology of the mediastinal lymph node biopsy revealed noncaseating granulomatous inflammation consistent with the diagnosis of pulmonary sarcoidosis. Pathology of the skin punch biopsy showed giant-cell granulomatous inflammation without necrosis. The patient was started on prednisone 40 mg daily with a steroid tapering course for 8 weeks.Conclusions:The management of IFN-induced sarcoidosis includes the discontinuation of IFN therapy with or without the administration of systemic corticosteroids. With the increasing prevalence of HCV in the United States, it is likely that more IFN-alpha-induced sarcoidosis will be encountered by clinicians.

Interferon alfa–induced sarcoidosis resolving without drug withdrawal

“…The prognosis of interferon-induced sarcoidosis is very good. 2 , 7 , 11 Some investigators recommend discontinuation of interferon therapy, 4 but cases resolving in several months regardless of interferon course have also been reported. 7 …”

“…Some cases of sarcoidosis after treatment with interferon alfa have been reported in the literature. 4 , 5 , 6 Improvement of sarcoidosis has been reported with discontinuation of treatment, but in other cases an independent course of disease has been proposed, raising the belief that interferon discontinuation is unnecessary in mild-to-moderate cases of interferon-related sarcoidosis. 7 …”

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

“…IFI27 is involved in type-I interferon-induced apoptosis characterized by a rapid release of cytochrome C, related pathways include innate immune system and interferon gamma signaling. The IFN immune related pathways that contribute to sarcoidosis etiopathogenesis are reported to be exacerbated by immunotherapy with IFN alpha [49][50][51]. Further investigation is needed to explain the pathogenic effect of the observed differences at the gene expression level.…”

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas

“…IFI27 is involved in type-I interferoninduced apoptosis characterized by a rapid release of cytochrome C, related pathways include innate immune system and interferon gamma signaling. The IFN immune related pathways that contribute to sarcoidosis etiopathogenesis are reported to be exacerbated by immunotherapy with IFN alpha (49)(50)(51). Further investigation is needed to explain the pathogenic effect of the observed differences at the gene expression level.…”