107 Anti-TNF induces sarcoidosis: a peculiar paradox

Abstract

Background: Sarcoidosis is a multisystem disease of unknown etiology that is characterised by the presence of non caseating granulomas in the affected organs. It most commonly affects the lungs and intrathoracic lymph nodes but extrapulmonary manifestations are not uncommon. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have demonstrated the efficacy of TNF-alpha inhibitors in refractory sarcoidosis. Paradoxically however, the TNF antagonists can induce inflammation, which can manifest as sarcoid-like granulomatosis. We present two cases of pulmonary sarcoidosis that developed whilst on anti-TNF treatment. Methods: Case 1: A 60 year old female with a long-standing history of sero-negative rheumatoid arthritis (RA), on etanercept monotherapy for a year, presented with shortness of cough, breathlessness, significant weight loss and hypercalcemia. Etanercept was discontinued whilst she was under investigation for a possible underlying lung malignancy as suggested by the chest x-ray. Subsequent CT thorax showed inflammatory lung nodules in both lung fields and the EBUS guided mediastinal biopsy showed non- caseating granulomas suggestive of sarcoidosis. Malignancy and tuberculosis (TB) were excluded. The patient was started on oral prednisolone (40mgOD) and etanercept was recommenced. The patient struggled to reduce the prednisolone below 30mg OD and the shortness of breath persisted. Cardiac sarcoidosis was excluded. At the advice of the specialist respiratory service, the etanercept was discontinued and within a couple of months the patient felt a lot better, the oral steroids could be weaned off and repeat CT chest showed a complete resolution of the inflammatory nodules. A diagnosis of etanercept induced sarcoidosis was made. Case 2: A 61 year old female, with a long standing history of sero-positive RA and secondary Sjogren's syndrome presented with cough, shortness of breath, weight loss and bilateral hilar lymphadenopathy on chest x-ray in May 2016. She had been on methotrexate for years and adalimumab was commenced nine months before this presentation. CT thorax confirmed mediastinal lymphadenopathy and demonstrated multiple inflammatory nodules in both lung lobes. EBUS guided biopsy showed non-caseating granulomas suggestive of sarcoidosis. Malignancy and TB were excluded. The patient had normal lung function tests and she declined prednisolone treatment. Adalimumab therapy was continued. By May 2017 her breathlessness was much improved and the cough had almost settled. The repeat CT thorax showed stable, benign looking nodules and a significant reduction in size of her mediastinal lymphadenopathy. Results: Please refer to the methods section. Conclusion: Anti-TNF induced sarcoidosis should be kept as a differential in patients developing granulomatous lesions whilst on anti-TNF treatment. Consideration should be given to withdraw the anti-TNF treatment to hasten recovery.