Specific symptoms may discriminate between fibromyalgia patients with vs without objective test evidence of small-fiber polyneuropathy

INTRODUCTION: Multiple studies now confirm that ∼40% of patients with fibromyalgia syndrome meet diagnostic criteria for small-fiber polyneuropathy (SFPN) and have objective pathologic or physiologic evidence of SFPN, whereas 60% do not. Given possibilities that tens or hundreds of millions globally could have SFPN, developing screening tools becomes important. OBJECTIVES: This analysis explored whether specific symptoms might help distinguish these fibromyalgia endophenotypes. METHODS: With institutional review board approval, all adults tested for SFPN by distal-leg skin biopsy or autonomic function testing at Massachusetts General Hospital in 2014 to 2015 were queried about symptoms. Inclusion required a physician's fibromyalgia syndrome diagnosis plus meeting the American College of Rheumatology 2010 Fibromyalgia Criteria. The primary outcome was the validated Small-fiber Symptom Survey, which captures severity of all known SFPN-associated symptoms. The Composite Autonomic Symptom Score-31, Short-Form Health Survey-36, and Short-Form McGill Pain Questionnaires provided secondary outcomes. RESULTS: Among the 39 participants, 14 had test-confirmed SFPN (SFPN+) and 25 did not (SFPN−). Their pain severity did not differ. Paresthesias (“tingling”) were different (worse) in the SFPN+ group (3.14 ± 0.9 vs 2.28 ± 1.1; P = 0.16). Their component subscore for dysautonomia symptoms was also worse (10.42 ± 4.0 vs 7.16 ± 4.0; P = 0.019). Receiver operating characteristic analyses revealed that each item had fair diagnostic utility in predicting SFPN, with areas under the curve of 0.729. No secondary questionnaires discriminated significantly. CONCLUSION: Among patients with fibromyalgia, most symptoms overlap between those with or without confirmed SFPN. Symptoms of dysautonomia and paresthesias may help predict underlying SFPN. The reason to screen for SFPN is because—unlike fibromyalgia—its medical causes can sometimes be identified and definitively treated or cured.