Distinguishing fibromyalgia syndrome from small fiber neuropathy: a clinical guide

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TL;DR

This study directly compares women with fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) to identify distinguishing clinical features. Key differences include pain location (widespread in FMS vs. acral in SFN), accompanying symptoms (fatigue, sleep disturbance, cognitive issues in FMS vs. sensory symptoms in SFN), and small fiber test patterns (proximal denervation in FMS vs. distal denervation and prolonged A-delta latencies in SFN). These findings provide a practical clinical guide for differentiating the two conditions, which is crucial for appropriate treatment.

Full summary

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**Background:** Small fiber pathology, characterized by damage to small caliber nerve fibers, is present in a subgroup of patients with fibromyalgia syndrome (FMS), raising the question of whether FMS equals small fiber neuropathy (SFN). However, the clinical distinction is crucial because prognosis and treatment differ substantially. This study aimed to identify clinically applicable characteristics that can help distinguish FMS from SFN.

**Methods:** The authors retrospectively analyzed clinical data from 158 women with FMS and 53 women with SFN, recruited monocentrically at the University of Würzburg, Germany. All patients underwent standardized interviews, neurological examinations, and a comprehensive set of investigations including pain characterization (using numeric rating scale, Neuropathic Pain Symptom Inventory [NPSI], Graded Chronic Pain Scale [GCPS], Pain Catastrophizing Scale [PCS], Mainz Pain Staging System), assessment of comorbidities and family history, laboratory tests (oral glucose tolerance test [oGTT], HbA1c, TSH, vitamin B12, blood count), and small nerve fiber assessment (intraepidermal nerve fiber density [IENFD] from skin biopsies, corneal confocal microscopy [CCM], quantitative sensory testing [QST], and pain-related evoked potentials [PREP]). Statistical analysis used IBM SPSS Statistics version 27, with significance set at P < 0.05.

**Key Results:** - **Epidemiology:** Patients with FMS had a younger median age at symptom onset (35.0 vs. 47.0 years, P < 0.001) and a longer time to diagnosis (8.0 vs. 2.8 years, P < 0.001) compared to SFN. - **Pain characteristics:** Burning pain was more common in SFN (84.9% vs. 41.8%, P < 0.001), while FMS patients more often reported widespread pain (e.g., neck 89.2% vs. 34.6%, shoulders 95.6% vs. 34.0%, trunk 77.8% vs. 13.2%, all P < 0.001). SFN patients had more acral pain (hands/fingers 64.2% vs. 14.6%, feet/toes 98.1% vs. 72.8%, both P < 0.001). Pain triggers also differed: cold (67.1% vs. 22.6%), stress (63.9% vs. 11.3%), and weather (20.3% vs. 1.9%) were more common in FMS, while heat (34.0% vs. 2.5%) and touch (37.7% vs. 2.5%) were more common in SFN (all P < 0.001). - **Additional symptoms:** FMS patients reported more additional symptoms (median 8.0 vs. 4.0, P < 0.001), including fatigue (88.0% vs. 5.7%), sleep disturbance (63.3% vs. 20.8%), concentration problems (72.2% vs. 1.9%), and depressed mood (18.4% vs. 1.9%, all P < 0.001). SFN patients more often reported tingling (67.9% vs. 16.5%), numbness (28.3% vs. 12.0%), and hypersensitivity to touch (13.2% vs. 0.6%, all P < 0.01). - **Family history:** FMS patients had more family history of chronic pain (49.4% vs. 32.1%, P < 0.05) and mental disorders (19.0% vs. 5.7%, P < 0.05), while SFN patients had more family history of neurological diseases (41.5% vs. 16.5%, P < 0.001). - **Laboratory tests:** SFN patients had higher HbA1c (median 5.5% vs. 5.4%, P < 0.05) and more pathological oGTT results (29.8% vs. 14.6% with 2h >140 mg/dL, P < 0.05). - **Small fiber tests:** Proximal IENFD reduction was more common in FMS (30.6% vs. 15.1%, P < 0.05). QST showed small fiber impairment in 15.3% of FMS vs. 35.8% of SFN (P < 0.01). CCM revealed reduced nerve branching density (NBD) more often in SFN (36.0% vs. 11.3%, P < 0.001). PREP showed prolonged N1 and P1 latencies in SFN (35.9% and 38.5% vs. 2.4% and 1.6%, both P < 0.001), while reduced peak-to-peak amplitude was more common in FMS (41.5% vs. 18.4%, P < 0.05).

**Clinical Implications:** This study provides a direct head-to-head comparison of FMS and SFN, offering practical clinical guidance. Key distinguishing features include pain location (widespread vs. acral), accompanying symptoms (fatigue, sleep, cognitive issues vs. sensory symptoms), family history (chronic pain vs. neurological diseases), glucose metabolism (more impaired in SFN), and small fiber test patterns (proximal denervation in FMS vs. distal denervation and prolonged A-delta latencies in SFN). These findings can help clinicians differentiate the two conditions, leading to more appropriate treatment strategies.