Diagnostic criteria for idiopathic small fiber neuropathy: A systematic review

Abstract

Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was performed to assess the published screening and diagnostic criteria for iSFN, excluding studies where SFN was of well‐established etiology. Eighty‐four clinical studies and seven guideline/review publications were included in this systematic review. Substantial heterogeneity existed in iSFN diagnostic criteria. The most common set of criteria to diagnose iSFN [presence of any symptoms of iSFN, absence of large fiber involvement, and reduced intraepidermal nerve fiber density (IENFD)] was used in only 14% of studies. Mandatory individual criteria to confirm iSFN included any sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced IENFD (38% of studies), and autonomic symptoms (1% of studies). This review highlights a clear need for standardized, evidence‐based guidelines for diagnosing iSFN.

A patient with distal lower extremity neuropathic pain and anti‐contactin‐associated protein‐2 antibodies

“…The patient did not fulfill the current criteria of SFN based on the IENFD and/or quantitative sensory testing (QST), 2 but those criteria are controversial. 4 Considering the clinical signs and symptoms, the normal EDX, and the absent LEPs, we believe the clinical painful picture was consistent with small nerve fiber involvement. In this context, the presence of anti-CASPR2 immunostaining on Aδ-fibers juxtaparanodes and C-fibers was meaningful.…”

Sensitive Skins May Be Neuropathic Disorders: Lessons from Studies on Skin and Other Organs

“…Small fiber neuropathies (SFNs) are disorders of unmyelinated C-fibers and poorly myelinated A-delta fibers, which induce pruritus and other cutaneous paresthesia [15][16][17]. A recent systematic literature review showed an unmet need of broadly accepted diagnostic criteria, although the most common set of mandatory criteria to diagnose were sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced intra-epidermal nerve fiber density (IENFD) (38% of studies), and autonomic symptoms (1% of studies) [18]. Nonetheless, the joint task force of the European Federation of Neurological Societies (EFNS) and the Peripheral Nerve Society (PNS) agreed to consider that skin biopsy with the quantification of the IENFD, using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN [19].…”

The challenge of differentiating fibromyalgia from small-fiber neuropathy in clinical practice

“…Immunohistochemistry or immunofluorescence with polyclonal anti-PGP 9.5 must be performed in a laboratory with experience in the interpretation of this diagnosis. Normative reference values of intraepidermal nerve fibre depend on age and gender [21] but are not used in all the studies [22]. Moreover, a recent small-scale study showed that the IENFD at the distal leg appeared influenced by the ethnicity : IENFD is lower in Chinese Americans than in non-Chinese Americans [23], but normative data depending on ethnicity are not available.…”