Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia

• Published in: Pain (Amsterdam) Vol. 154; no. 11; pp. 2310 - 2316
• Main Authors: Oaklander, Anne Louise, Herzog, Zeva Daniela, Downs, Heather M., Klein, Max M.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.11.2013; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Adolescent; Adult; Aged; Autonomic function testing; Biological and medical sciences; Chronic pain; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Data Interpretation, Statistical; Diseases of the osteoarticular system; Female; Fibromyalgia - pathology; Human-subject research; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Miscellaneous. Osteoarticular involvement in other diseases; Nerve Fibers - pathology; Nervous system (semeiology, syndromes); Neurology; Pain Measurement; Peripheral nerve; Peripheral neuropathy; Polyneuropathies - diagnosis; Polyneuropathies - pathology; Polyneuropathies - psychology; Reproducibility of Results; Sample Size; Skin - pathology; Skin biopsy; Surveys and Questionnaires; Treatment Outcome; Young Adult; Human-subject research; Skin biopsy; Peripheral nerve; Peripheral neuropathy; Autonomic function testing; Chronic pain; Human; Nervous system diseases; Diseases of the osteoarticular system; Fibromyalgia; Striated muscle disease; Chronic; Pain; Skin; Peripheral nerve disease
• ISSN: 0304-3959; 1872-6623; 1872-6623
• DOI: 10.1016/j.pain.2013.06.001

Comparing symptoms, examinations, skin biopsies, and autonomic functions in fibromyalgia as opposed to control subjects suggests that approximately half of fibromyalgia patients have previously unrecognized small-fiber polyneuropathy. Fibromyalgia is a common, disabling syndrome that includes chronic widespread pain plus diverse additional symptoms. No specific objective abnormalities have been identified, which precludes definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by the dysfunction and degeneration of peripheral small-fiber neurons. SFPN has established causes, some diagnosable and definitively treatable, eg, diabetes. To evaluate the hypothesis that some patients labeled as having fibromyalgia have unrecognized SFPN that is causing their illness symptoms, we analyzed SFPN-associated symptoms, neurological examinations, and pathological and physiological markers in 27 patients with fibromyalgia and in 30 matched normal controls. Patients with fibromyalgia had to satisfy the 2010 American College of Rheumatology criteria plus present evidence of a physician’s actual diagnosis of fibromyalgia. The study’s instruments comprised the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, plus autonomic-function testing (AFT). We found that 41% of skin biopsies from subjects with fibromyalgia vs 3% of biopsies from control subjects were diagnostic for SFPN, and MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects (all P⩽0.001). Abnormal AFTs were equally prevalent, suggesting that fibromyalgia-associated SFPN is primarily somatic. Blood tests from subjects with fibromyalgia and SFPN-diagnostic skin biopsies provided insights into causes. All glucose tolerance tests were normal, but 8 subjects had dysimmune markers, 2 had hepatitis C serologies, and 1 family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as fibromyalgia have unrecognized SFPN, a distinct disease that can be tested for objectively and sometimes treated definitively.