J Neurogastroenterol Motil 2024; 30(1): 116-118  https://doi.org/10.5056/jnm23039
Can Small Fiber Neuropathy Explain the Overlap Gastrointestinal and Non-gastrointestinal Symptoms in Some Irritable Bowel Syndrome Patients?
Amanda C Y Chan1,2 and Kewin T H Siah2,3*
1Division of Neurology, University Medicine Cluster, National University Hospital, Singapore; 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and 3Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Hospital, Singapore
Published online: January 30, 2024
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

TO THE EDITOR: We are writing to address a potentially important and unexplored pathology linking irritable bowel syndrome (IBS) and other chronic pain syndromes. The readers of this journal are not foreign to IBS. Suffice to say, IBS constitutes both gastrointestinal (GI) and extra-GI symptoms including chronic pain syndromes, such as fibromyalgia and chronic fatigue syndrome.1-4 Recent studies have shown that fibromyalgia and chronic fatigue syndrome often coexist with small fiber neuropathy (SFN).5-7 SFN is underdiagnosed as health care professionals have little knowledge of the condition, yet it is also a common neurological disorder that manifests with pain, numbness, paresthesia, and/or autonomic dysfunction.5 One study published in Seminars in Arthritis and Rheumatism found that 49% of fibromyalgia patients also had SFN.6 Another study published in the American Journal of Respiratory and Critical Care Medicine found that 30% of chronic fatigue syndrome patients had definite SFN.7 Unfortunately, the diagnosis of SFN is complex and requires a combination of symptoms, signs, absence of a large fiber neuropathy, and the highest diagnostic standard for confirmation of SFN is by skin biopsy for intra-epidermal nerve fiber density.8

Can SFN patients present with IBS-like symptoms: indeed, SFN can cause symptoms that overlap with those of IBS, including abdominal pain, bloating, diarrhea, and constipation. SFN can affect the autonomic nerves that control the digestive system, leading to problems with bowel movements and other GI symptoms.9 These symptoms can be similar to those of IBS, making it difficult to differentiate between the 2 conditions. We have performed a retrospective review of the patients attending the SFN clinic in a tertiary hospital to investigate the prevalence of patients with physician-diagnosed IBS and other functional gastrointestinal disorders (FGIDs) (Table). We found that 53.9% had physician-diagnosed FGIDs before they were diagnosed with SFN. When comparing SFN patients with and without previous FGIDs diagnoses, there was no difference in gender, age, topographical presentation of neuropathic symptoms, or presence of positive autoimmune blood tests. Most of the diagnoses of SFN were confirmed as definite with skin biopsy.

Table. Comparison of Small Fiber Neuropathy Patients With and Without Gastrointestinal Symptoms

Patient characteristicsNo GI symptomsGI symptomsP-value
Total number41 (53.2)36 (46.8)



21 (51.2)12 (33.3)0.166
Age (yr)49.9 ± 12.346.64 ± 15.80.369

Length dependent

Non-length dependent

28 (68.3)

13 (31.7)

27 (81.8)

6 (18.2)

SFN diagnostic category




2 (2.44)

8 (19.5)

30 (73.2)

4 (11.1)

1 (2.78)

31 (86.1)

Positive autoimmune blood tests (high ESR, ANA ≥ 1:80, positive anti-ENA or ANCA)17 (41.5)16 (44.4)0.293





26 (63.4)

6 (14.6)

7 (17.1)

4 (9.8)

19 (52.8)

9 (25.0)

3 (8.33)

6 (16.7)





aDrug induced, paraneoplastic, hepatitis B, hepatitis C, HIV, etc.

GI, gastrointestinal; SFN, small fiber neuropathy; ESR, erythrocyte sedimentation rate; ANA, antinuclear antibody; ENA, extractable nuclear antigens; ANCA, antineutrophil cytoplasmic antibodies; DM, diabetes mellitus; NA, not applicable.

Data are presented as n (%) or mean ± SD.

Of the SFN patients with GI symptoms, 41.6% of them had a formal diagnosis of IBS, while functional constipation was the second most common presentation in 30.6%, and the third was functional dysphagia and dyspepsia at 13.9% (Figure).

Figure 1. Composition of functional gastrointestinal disorders in small fiber neuropathy patients.

Our study showed that IBS and functional constipation were the 2 most common FGIDs in SFN patients. SFN may cause IBS-like symptoms with their involvement of the autonomic nervous system and the enteric nervous system. GI dysautonomia, also known as GI autonomic dysfunction, is a condition that affects the autonomic nervous system. It can cause a range of GI symptoms, including bloating, constipation, diarrhea, nausea, and vomiting.10 Dysautonomia can be one of the presentations of SFN and can be caused by central causes, such as lesions of the hypothalamus, and peripheral causes, such as neuropathy. SFN is the peripheral cause of dysautonomia. While SFN can present with varying degrees of dysautonomia and neuropathic pain, the cause for these varying presentations is unknown. This may explain some of the FGID overlap symptoms of different anatomical regions of GI tracts.

In conclusion, the association between IBS and SFN is an interesting area of research that has the potential to improve the diagnosis and treatment of these conditions. More formal studies are needed to investigate the shared pathology of FGIDs and potential novel treatment. Clinicians should be aware of this association and consider screening patients with IBS for SFN, especially those with more severe overlap GI symptoms and peripheral neuropathic complaints.

Financial support

This study was supported by the Singapore Ministry of Health’s National Medical Research Council under its NMRC Research Training Fellowship (MOH-000437-0) (to Amanda C Y Chan).

Conflicts of interest


Author contributions

Amanda C Y Chan and Kewin T H Siah: study conception and design, data collection, analysis and interpretation of results, draft manuscript preparation, and review of the results, and approval of the final version of the manuscript.

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