Sarcoidosis is an immune-mediated multisystemic disorder that is pathologically characterized by noncaseating granulomas. While any portion of the nervous system may be affected, symptomatic polyneuropathy is rare and seen in only 1% to 2% of patients with systemic disease. Axon loss polyneuropathy usually manifests as either a stocking-glove polyneuropathy or subacute non-length-dependent polyradiculoneuropathy in which patients present with asymmetric limb pain and sensorimotor deficits. Other polyneuropathy types include pure sensory or motor neuropathy and, rarely, mononeuritis multiplex.
As the clinical manifestations and electrodiagnostic findings are nonspecific, nerve biopsy and evaluation for systemic sarcoidosis are often required for diagnosis when neuropathy is the presenting symptom. In those with known sarcoidosis, nerve biopsy may still be necessary to exclude other potential causes (eg, infection or malignancy) that may be related to chronic immunosuppression.
Biopsy may demonstrate granulomatous compression or direct infiltration of large nerve fibers as well as vasculitis. Prompt treatment with IV corticosteroids or IVIg can result in improvement, although a number of patients may go on to a relapsing-remitting course or chronic progressive decline. Unlike large fiber disease, small fiber neuropathy is frequently seen in sarcoidosis and has been found in over 30% of patients with systemic disease. Patients often present with migratory burning pain and paresthesia that affect various parts of the face, trunk, and proximal limbs in a non-length-dependent distribution, although a distal painful neuropathy is also common. In one series, autonomic involvement (eg, orthostatic hypotension, sweating abnormalities, and gastrointestinal disturbances) accompanied the somatic symptoms in about half of the cases. Also of note, sarcoidosis-associated small fiber neuropathy was seen more often in whites (87%) than African Americans (10%), which is unusual as the latter group has a higher prevalence of systemic disease.
Sarcoidosis small fiber neuropathy is categorized under ‘‘paraneurosarcoidosis’’ rather than true neurosarcoidosis as the underlying pathophysiology is not granulomatous in nature but likely cytokine mediated.
As with large fiber nerve involvement, the clinical presentation of sarcoidosis small fiber neuropathy is also nonspecific. Diagnosis thus requires histologically confirmed systemic disease in addition to specialized testing (eg, skin biopsy) to detect small fiber involvement
Response to standard immune-modulating therapies such as corticosteroids is poor. In some patients, IVIg and infliximab may be helpful in treating both the somatic and autonomic manifestations. More recently, cibinetide, an experimental erythropoietin agonist that reduces inflammation, was shown to improve nerve fiber density in the skin and corneas of patients with sarcoidosis small fiber neuropathy.
First Tier
Blood tests
CMP, LFTs. CBC, ACE, soluble interleukin-2 receptor level
Chest radiograph (CXR or CT)
Pulmonary function testing
Ophthalmologic evaluation with slit lamp
Skin examination and referral to dermatology as needed
Purified protein derivative or interferon gamma assay for Mycobacterium tuberculosis ECG
Second Tier
CT body with biopsy of abnormal tissue suggestive of sarcoidosis
Bronchoscopy or endobronchial ultrasound-guided transbronchial needle aspiration
Third Tier
Fluorodeoxyglucose positron emission tomography (FDG-PET)
Gallium 67 scanning
Conjunctival biopsy