A RECIPE FOR REFRACTORY, RESISTANT, AND RECALCITRANT SYSTEMIC SARCOIDOSIS

Abstract

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Sarcoidosis is an immune mediated, systemic granulomatous disease which may exhibit ocular and dermatological involvement apart from pulmonary disease. While corticosteroids demonstrate excellent efficacy, refractory sarcoidosis often necessitates the use of immunosuppressant or biological agents. Infliximab binds to and inhibits TNF-a, which mediates granuloma formation, and is validated for use as therapy in immunosuppressant-refractory cases. We report a case of refractory multisystem sarcoidosis to the currently recommended regimen of Infliximab 5 mg/kg every 8 weeks to discuss alternative options and literature review of the current practice. CASE PRESENTATION: A 55-year-old female with a history of multisystem sarcoidosis was diagnosed by transbronchial biopsies revealing noncaseating granulomas. She had upper lobe predominant subpleural reticulation and traction bronchiectasis, transaminitis, macular rash, and ocular disease with posterior uveitis. Treatment was changed from methotrexate 17.5 mg weekly to Infliximab due to the poor control of her ocular and skin manifestations. While treated with Infliximab 5 mg/kg every 8 weeks, she had worsening of obstructive lung disease, new skin rash and exacerbation of ocular manifestations requiring systemic steroids. Infliximab was then increased to 7.5 mg/kg every 8 weeks. However, with persistent posterior uveitis the decision was made to increase her dose to 10 mg/kg every 8 weeks, and Methotrexate 10 mg weekly was added. DISCUSSION: We present a case of a patient with multisystem sarcoidosis with pulmonary, dermatological and uncontrolled ocular manifestations despite Infliximab therapy. Increasing dosing to 7.5 mg/kg, used in previous non-randomized studies [1], did not achieve remission of her uveitis.Clinical improvement is usually observed in 64% of patients [2] and factors associated with clinical improvement on TNF inhibitors are low baseline FVC, CRP?>?0.8?mg/dL and high TNF expression [1] while refractory response is reported in 10.6% of patients [3]. Switching to another TNF inhibitor or addition of an immunosuppressant has shown complete or partial response in 62% (10/16 patients) and 77% (7/9 patients) [3] of such patients respectively. The use of Rituximab in treatment of refractory sarcoid with favorable response has also being reported in recent case series. CONCLUSIONS: Treatment options of multisystem sarcoidosis refractory to TNF-targeted therapy are limited. Increasing the dose, adding a second line steroid sparing agent to current therapy or use of a second TNF inhibitor are strategies described in the literature. Randomized clinical trials to validate their long-term safety and efficacy in such patients would be warranted. REFERENCE #1: Adler, Brandon L., et al. "Anti-tumor necrosis factor agents in sarcoidosis: a systematic review of efficacy and safety." Seminars in arthritis and rheumatism. Vol. 48. No. 6. WB Saunders, 2019. REFERENCE #2: Jamilloux Y., et al. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: a multicenter study of 132 patients. Seminars in Arthritis Rheumatism. 2017. 47(2): 288-294. REFERENCE #3: Clemence, T.C., et al. Outcome of patients with sarcoidosis refractory to TNF antagonists: A case series. Sarcoidosis Vasculitis & Diffuse Lung Diseases. 2018. 35(4):371-375 DISCLOSURES: No relevant relationships by ALAA ABU SAYF, source=Web Response No relevant relationships by Heather Bachert, source=Web Response No relevant relationships by Muhammad Hashmi, source=Web Response Grant for research relationship with Sanofi Please note: January 2021 Added 04/20/2021 by Daniel Ouellette, source=Web Response, value=Grant/Research No relevant relationships by Krishna Thavarajah, source=Web Response, value=speaker fees for IPF rally Removed 04/30/2021 by Krishna Thavarajah, source=Web Response No relevant relationships by Krishna Thavarajah, source=Web Response, value=stockholder Removed 04/30/2021 by Krishna Thavarajah, source=Web Response