Pulmonary Sarcoidosis Induced by Adalimumab: A Case Report and Literature Review

To the Editor: Adalimumab is an anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody that is widely used in autoimmune diseases including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and sarcoidosis. Paradoxically, sarcoidosis can develop during treatment with adalimumab. We report an unusual case of sarcoidosis after adalimumab therapy. A 25-year-old man with ankylsoing spondylitis started treatment with adalimumab. Initial chest radiography, tuberculin skin test and interferon gamma release assay were normal. Ten months later, abnormal opacities on chest radiography were found during the follow-up period. He was asymptom-atic and appeared otherwise healthy. Tuberculin skin test and interferon gamma release assay were negative. Chest X-ray and computed tomography showed clustered small nodules, focal consolidations, some large nodules and enlarged medi-astinal lymph nodes (Fig. 1A). Acid-fast bacilli stain, tuberculosis polymerase chain reaction and bacterium or fungus culture of bronchial aspirates results were all negative. Percu-taneous lung biopsy was performed, and non-caseating gr-anulomatous lesions located along lymphatic route with pa-renchymal inflammation were observed (Fig. 1B). Angiotensin converting enzyme was elevated to 95.7 U/L (9.0–47.0). The lesion showed partial resolution after 2 months of discontinu-ation of adalimumab. Hence, diagnosis of pulmonary sarcoid-osis induced by adalimumab therapy was made. At present, 5 types of TNF-α inhibitor are available: etaner-cept, infliximab, adalimumab, certlizumab pegol and golim-umab. Since its first approval for rheumatoid arthritis, it has been widely used for psoriatic arthritis, ankylosing spondyli-tis, Crohn's disease and chronic plaque psoriasis. In addition to approved indications, TNF-α inhibitors have therapeutic effect on various diseases including sarcoidosis. Although its pathogenesis is not fully understood, TNF-α may have a role in the development of sarcoidosis. TNF-α released from alveo-lar macrophage was elevated in sarcoidosis, 1 and there was a positive relationship between sarcoidosis activity and TNF-α from alveolar macrophage. 2 A randomized controlled trial proved the efficacy of infliximab in sarcoidosis. 3 Currently, in-fliximab is preserved for refractory sarcoidosis, and the efficacy of adalimumab has also been demonstrated in a recent small study. 4 However, there have been a few cases of paradoxical occurrence of sarcoidosis during TNF-α inhibitor therapy. From a literature review, we found 59 cases of TNF-α in-hibitor-induced sarcoidosis published from January 2003 to August 2014. Mean age was 47.8 years. Female to male ratio was approximately 2:1. Twenty-eight patients had rheumatoid arthritis. Mean time to onset was 21.8 months, varying from 3 weeks to 7 years. Thirty-seven cases were induced by etaner-cept, 9 were infliximab and 12 …