Introduction: Tumor necrosis factor is a pro-inflammatory cytokine that plays a fundamental role in infection control through inflammatory cell recruitment and granuloma formation. Persistent TNF signaling however is implicated in the pathogenesis of many autoimmune conditions, including sarcoid. Anti-TNF drugs have emerged as effective disease modifying therapies for these conditions but there is robust evidence that they can paradoxically induce new autoimmune disease, including in the central nervous system. Demyelinating lesions are best described but sarcoid-like lesions have also been more rarely reported developing de novo in patients on anti-TNF therapy. This case adds to the literature demonstrating the first presentation of Neurosarcoid in the setting of anti-TNF therapy for a pre-existing autoimmune condition. 

Clinical Case Description: A 64-year-old female with a medical history of rheumatoid arthritis treated with adalimumab presented with sudden-onset confusion, aphasia and agraphia. MRI revealed multiple enhancing brain lesions with vasogenic edema observed within the inferior left temporal lobe. She had 3 lumbar punctures with moderate lymphocytic predominant leukocytosis, negative infectious studies, and no malignant cells in her CSF. CT chest showed mediastinal and bilateral hilar adenopathy; follow up PET also showed extensive FDG avid mediastinal and bilateral hilar lymphadenopathy as well as a left supraclavicular lymph node with FDG uptake. Lymph node biopsy was consistent with non-caseating granulomas. Humira was discontinued and she was treated with steroids acutely, then started methotrexate maintenance therapy. Clinically she recovered well from her deficits. Serial MRIs exhibited improvement, although not yet full resolution of enhancement.

Conclusions: The development of Sarcoid de novo while already under treatment with anti-TNF agents presents a particular diagnostic and treatment challenge. It is unclear if the immunological properties of anti-TNF drugs prompt granulomatous disease, or if they represent breakthrough disease from undiagnosed sarcoid that was suppressed by the anti-TNF therapy. As more cases are reported, a better understanding may emerge.