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Prevalence of Axonal Sensory Neuropathy With IgM Binding to Trisulfated Heparin Disaccharide in Patients With Fibromyalgia

Malik, Asma, MD*; Lopate, Glenn, MD; Hayat, Ghazala, MD*; Jones, Jacqueline, BS*; Atluri, Rama, MD*; Malo, Bassam, MD; Pestronk, Alan, MD

Journal of Clinical Neuromuscular Disease: March 2019 - Volume 20 - Issue 3 - p 103–110
doi: 10.1097/CND.0000000000000236
Original Article

Objective: To assess the intraepidermal nerve fiber density in patients diagnosed with fibromyalgia (FM) and to evaluate the role of IgM binding to trisulfated heparin disaccharide (TS-HDS) in these patients.

Methods: FM is a poorly understood pain disorder with several proposed pathophysiologic mechanisms. It is characterized by widespread pain, fatigue, and sleep abnormalities. Small fiber neuropathy (SFN) has been proposed as an underlying mechanism, and patients with FM have been shown to have a reduction in the intraepidermal nerve fiber density. An underlying inflammatory process that could be a result of autoimmune phenomena has also been suggested. Non–length-dependent SFN (NLDSFN) has been shown to have a higher incidence of autoimmune disease. Twenty-two patients with established diagnosis of FM underwent skin biopsy at 2 sites; 10 cm above the lateral malleolus and 10 cm above the patella. Serum IgM binding to TS-HDS was assayed using an ELISA method.

Results: A total of 5/22 patients had positive TS-HDS antibodies; of these, 4 had NLDSFN (P = 0.0393). Comparison with a control group at Washington University showed no significant difference in percentage with TS-HDS antibodies (P = 0.41). When compared with Washington University database of skin biopsy, there was a trend for an increased percentage of NLDSFN in patients with FM (P = 0.06).

Conclusions: This study further supports the hypothesis that a subgroup of patients with FM has SFN. We suggest a correlation between the presence of NLDSFN and TS-HDS antibodies.

*Saint Louis University, Saint Louis, MO; and

Washington University in Saint Louis, Saint Louis, MO.

Reprints: Asma Malik, MD, Department of Neurology, Saint louis University, 1438 South Grand Boulevard, Saint Louis, MO 63104 (e-mail:

The authors report no conflicts of interest.

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