{"doi":"10.1111/ene.70474","title":"Uncovering Hidden Profiles: From Pain‐Centric to Multi‐Symptom Small Fiber Neuropathy","abstract":"We sincerely thank Drs. Blitshteyn, Stingl, and Schofield for their thoughtful and encouraging comments on our recent publication, “Uncovering Hidden Profiles: From Pain-Centric to Multi-Symptom Small Fiber Neuropathy” [1]. We are pleased that our findings resonate with clinicians who see patients across the spectrum of dysautonomia, postinfectious, and autoimmune disorders. As highlighted in their letter, our study demonstrates that small fiber neuropathy (SFN) encompasses a broad constellation of sensory, autonomic, and systemic symptoms that extend beyond neuropathic pain. Blitshteyn et al. underscore the importance of considering the full phenotypic spectrum of SFN, including fatigue and myalgia, which our analysis identified as highly prevalent and clinically meaningful. We share the authors' interest in the role of the immune system in the pathophysiology of SFN. Fatigue and myalgia are defining features of disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia, and Long COVID, where immune dysfunction and small fiber abnormalities have been documented in a subset of patients [2-6]. The convergence of these findings with the “myalgic” SFN subgroup points to potential shared immune-mediated mechanisms and underscores the need for systematic investigation of clinically and biologically distinct SFN subtypes. At present, most symptom assessment scales have focused almost exclusively on the painful symptoms [7, 8]. However, as the authors point out, this narrow focus risks overlooking patients in whom fatigue, myalgia, or dysautonomia predominate, potentially delaying diagnosis and treatment. Broader awareness and systematic incorporation of autonomic and systemic symptoms into clinical assessments, coupled with objective measures such as skin biopsy and quantitative autonomic testing, could substantially improve diagnostic accuracy and patient care. Future studies integrating detailed phenotyping with serologic, immunologic, and neurophysiologic profiling will be critical to elucidate causal mechanisms and guide the development of targeted therapies. Moreover, as the authors propose, randomized controlled trials of immunomodulatory interventions in a subset of patients with SFN represent an important future direction and could move the field toward curative rather than palliative approaches in SFN [9]. We appreciate the opportunity to engage in this important dialog and fully endorse continued collaboration across specialties to better characterize and treat multisystem forms of SFN and related disorders. Peyton Murin: conceptualization, writing – original draft, writing – review and editing. Stefanie Geisler: writing – review and editing, conceptualization. Nicholas F. Schulze, Vivian D. Gao, and Manouela V. Valtcheva: writing – review and editing. There is no funding associated with this letter to the editor. The original study received funding from NIH/National Center for Advancing Translational Sciences (UL1 TR002345) and National Cancer Institute (R37CA267905). The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.","journal":"European Journal of Neurology","year":2025,"id":586770,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9673,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1427777,"name":"Nicholas F. Schulze","orcid":null,"position":1,"is_corresponding":false},{"id":1353037,"name":"Vivian D. 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