Abstract Tumor necrosis factor alpha (TNF-a) is a key mediator of granuloma formation and may contribute to non-specific systemic symptoms in sarcoidosis. TNF-a inhibitors, including infliximab, can be effective in treating advanced pulmonary sarcoidosis (APS) but are third line agents due to risk of infection, congestive heart failure and lupus-like syndrome. Rare case reports have described Guillan-Barre Syndrome (GBS) following the use of TNF-a inhibitors, though causality remains uncertain. We report a case of GBS following infliximab initiation. An 80-year-old male with pulmonary sarcoidosis was asymptomatic for decades before developing parenchymal and tracheobronchial disease resulting in hypoxic respiratory failure, pulmonary fibrosis, and pulmonary hypertension. He improved with prednisone but was unable to be weaned due to recurrence of disease activity. He did not tolerate azathioprine due to a diffuse rash. He was started on methotrexate but without adequate control; adalimumab was added after 6 months. He had improved control for two years until he developed recurrent hypoxic respiratory failure, new heart failure with preserved ejection fraction, pre-capillary pulmonary hypertension, and methotrexate-induced pneumonitis evidenced by peripheral eosinophilia, diffuse FDG avid ground glass opacities, and transbronchial biopsies showing organizing pneumonia. He was treated with a course of prednisone; methotrexate and adalimumab were stopped. Infliximab was initiated but after receiving 3 doses he was admitted 10 weeks later with progressive ascending upper extremity weakness and numbness. MRI brain and cervical spine were unremarkable. Cerebrospinal fluid (CSF) showed albuminocytologic dissociation with a negative infectious and autoimmune work-up. Nerve conduction study (NCS) demonstrated demyelinating polyneuropathy. He was diagnosed with acute inflammatory demyelinating polyneuropathy most consistent with a Guillen-Barre pharyngeal-cervical-brachial variant and was treated with 2 g/kg of intravenous immunoglobulin over 5 days with partial improvement. His hospital course was complicated by a spontaneous retroperitoneal hemorrhage resulting in death. Treatment of APS is challenging, often requiring second-line agents such as methotrexate and, in refractory cases, TNF-a inhibitors. Infliximab’s FDA package insert lists peripheral demyelinating disorders including GBS, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy in addition to transverse myelitis without a frequency. One proposed mechanism is through TNF-a antagonists reducing apoptosis of auto-reactive T-cells, increasing the risk of immune-mediate neuropathies. In this patient, the temporal relationship, supportive CSF and NCS findings, and lack of other etiologies suggest infliximab-induced GBS variant, though causality cannot be demonstrated. This case adds to the literature and highlights the need for counseling and monitoring for new neurologic deficits after TNF-a inhibitor initiation. This abstract is funded by: None
Holman et al. (Fri,) studied this question.