Sarcoidosis complicating treatment with adalimumab for Crohn's disease.

Adalimumab is a humanised monoclonal antibody against tumour necrosis factor-alpha (TNF-α), with proven efficacy in several autoimmune diseases. We report the development of sarcoidosis with cutaneous and pulmonary involvement in a 37-year old white Irish male with refractory Crohn's disease of 13-years, commenced on maintenance therapy with adalimumab for 2 years following surgery and unsuccessful remission with methotrexate (Fig. 1). To the best of our knowledge, this is the fourth reported case in the literature of sarcoidosis complicating TNF-α therapy in Crohn's disease; the second with adalimumab, others reporting paradoxical sarcoidosis with infliximab and natalizumab.1–3 Sarcoidosis and Crohn's disease are both inflammatory barrier disorders consisting of non-caseating granulomas, dysregulated T-cell activation and similar organ involvement outside the primary affected organ system.1 Genome-wide analyses in sarcoidosis and Crohn's disease have previously detected shared common susceptibility loci on 10p12.2 and 11q13.1, most likely representing a general predisposition toward an altered immune-mediated inflammatory response. Crohn's disease is characterised by granulomatous inflammation of the intestine, which can be difficult to differentiate from sarcoidosis. The loss of function mutation at the NOD2 gene results in failure of NOD2-mediated NFkB activation, and possibly failure in defensin-mediated protection. It is hypothesised that gastrointestinal immunity is directed to a granulomatous response against bacterial invasion as a consequence of thismutation. Juvenile onset granulomatous diseases are associated with gain of function mutations of the NOD2 gene and constitutive activation of NFkB. Interestingly, in Japanese patients, sarcoidosis has been associated with a loss of function mutation in the NOD1 gene, with reduced NOD1-mediated activity to the bacterium Propionobacterium acnes. Based on these findings, TNF-α inhibition would be expected to suppress NFkB-related granuloma formation and has been used with some success in refractory sarcoidosis.4