To report autonomic findings in three patients found to have autoantibodies associated with small fiber neuropathy (SFN), including trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) antibodies.

SFN has been described in association with several autoantibodies, including TS-HDS and FGFR-3. There is a growing recognition of the association of these antibodies with autonomic dysfunction, which can occur with or without concurrent neuropathy.

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Case 1: 33-year-old woman presented with painful paresthesias and refractory orthostatic hypotension with syncope. Diagnosis of SFN was confirmed by skin biopsy with non-length-dependent decreased epidermal nerve fiber density. Antibody testing revealed elevated TS-HDS (28,000, reference < 10,000). Symptoms partially improved with plasmapheresis and rituximab.

Case 2: 74-year-old man with a history of bladder and prostate cancer presented with several years of gastroparesis, lightheadedness, Raynaud’s phenomenon, and hyperhidrosis. Cardiac evaluation showed nocturnal pauses requiring pacemaker placement. GI workup included a NM gastric emptying study with severe delay. Autonomic testing showed impaired postganglionic sudomotor function and abnormal pupillary responses. Antibody testing revealed elevated TS-HDS (11,000) and FGFR3 (3,300, reference <3,000). He was treated with plasmapheresis and rituximab;follow-up is pending.

Case 3: 50-year-old man with a history of migraine, chronic fatigue, episodic paresthesias, and gastroparesis presented with orthostatic intolerance and syncope. Tilt table testing demonstrated symptomatic postural tachycardia. Workup was notable for a positive ANA (1:640, speckled), mildly positive neuronal ganglionic alpha-3-acetylcholine receptor (0.04, reference <0.03), and elevated TS-HDS (15,000) and FGFR3 (7,000). He was started on IVIG and follow up is pending.

In this series, we describe three patients with autonomic symptoms with and without neuropathy who were found to have elevated IgM vs TS-HDS and/or IgG vs FGFR-3. These cases support the growing evidence of an association between TS-HDS and FGFR-3 antibodies and autonomic dysfunction.