Case Presentation: A 29 year-old man presented with 3 weeks of paresthesias, fatigue, and weight loss. The patient also reported nausea, constipation, urinary urgency, and erectile dysfunction. Physical examination demonstrated decreased temperature perception and sharp-dull discrimination in the bilateral distal lower extremities. Laboratory studies revealed elevated ESR (57 mm/hour), elevated CRP (2.0 mg/dL), and decreased 25-hydroxy vitamin D (15 ng/dL). Cerebrospinal fluid had increased protein (50 mg/dL) and lymphocytic pleocytosis. Spine MRI demonstrated an expansile abnormality in the intramedullary space at C3-C4 and C6-T1 levels (Figure 1). Brain MRI revealed multiple non-specific abnormalities involving the orbital cavities, cranial nerves, and cerebellum. Chest CT was notable for bilateral hilar lymphadenopathy and peri-lymphatic pulmonary nodules (Figure 2). The patient was clinically diagnosed with neurologic and pulmonary sarcoidosis, based upon symptoms and imaging findings. The patient was initiated on high-dose corticosteroids and experienced brief improvement in neurologic symptoms. However, his paresthesias progressed when the steroids were tapered. The patient was subsequently restarted on high dose steroids, and hilar lymph node biopsy was obtained. Pathology demonstrated non-caseating granulomatous inflammation, consistent with sarcoidosis. The patient was subsequently treated with methotrexate and infliximab, in conjunction with a prolonged steroid taper, and he experienced gradual improvement in symptoms.
Discussion: Sarcoidosis is a systemic disease, which presents with neurologic manifestations in only 5% to 10% of patients. The majority of adults with neurologic sarcoidosis lack systemic symptoms and signs characteristic of sarcoidosis, which may complicate diagnostic efforts. Neurologic sarcoidosis is associated with a wide range of symptoms, and one-third of patients have more than one neurologic manifestation. Cranial neuropathy occurs in up to 75% of patients, whereas peripheral neuropathy is seen in only 25%. Small-fiber neuropathy is likely an underdiagnosed manifestation of neurologic sarcoidosis due to lack of specific symptoms and sensitive diagnostic tests. Small-fiber neuropathy affects somatic nerves, leading to paresthesia and anesthesia, and autonomic nerves, resulting in dysfunction of sweat glands, baroreceptors and cardiac muscle, and gastrointestinal and genitourinary smooth muscle. The gold standard for diagnosis of small-fiber neuropathy is skin biopsy, which demonstrates decreased intra-epidermal nerve fiber density. Peripheral neuropathy due to sarcoidosis is associated with significant morbidity, and many patients have relapsing-remitting or progressive disease course despite treatment. There is paucity of high-quality evidence related to treatment of neurologic sarcoidosis, and guidelines are based upon expert opinion. Corticosteroids are considered first-line therapy, whereas immunomodulatory agents are reserved for relapsing or progressive disease.
Conclusions: Small-fiber peripheral neuropathy is an uncommon, and likely underdiagnosed, manifestation of neurologic sarcoidosis. It is associated with sensory and autonomic disturbances and may be a significant source of long-term morbidity for patients. Despite appropriate treatment, many patients have relapsing or progressive disease and require prolonged therapy with corticosteroids and immunomodulatory agents.