Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet

Abstract

Background and aim

Peripheral neuropathy is a common extraintestinal manifestation of gluten sensitivity (gluten neuropathy). We aimed to establish the prevalence of neuropathic pain in patients with otherwise idiopathic PN and gluten sensitivity (positive antigliadin, endomysial, and/or transglutaminase antibodies, with or without enteropathy) and to describe any contributory factors.

Methods

All consecutive patients with gluten neuropathy (GN) attending a specialist gluten/neurology clinic were invited to participate. Pain was assessed via the DN4 questionnaire and the visual analog scale. Overall Neuropathy Limitations Scale was used to assess the severity of neuropathy. The Mental Health Index (MHI-5) was used to measure participants’ general mental health status.

Results

In total, 60 patients (76.7% males, mean age 69.9 ± 10.1 years) with GN were recruited. Neuropathic pain was present in 33 patients (55.0%). Comparison between groups of painful and not painful GN did not show significant differences regarding age, gender, neuropathy severity and neuropathy type. Patients with painless GN were more likely to be on a strict gluten-free diet (55.6 versus 21.2%, p = 0.006). Patients with painful GN presented with significantly worse MHI-5 score (75.9 ± 13.8 versus 87.4 ± 8.1, p < 0.001). Multivariate analysis showed that, after adjusting for age, gender and MHI-5, strict gluten-free diet was associated with lowering the odds of peripheral neuropathic pain by 88.7% (95% CI 47.2–97.6%, p = 0.006).

Conclusion

Neuropathic pain is very prevalent in GN and is associated with poorer mental health status. Strict gluten-free diet might be protective as it is associated with a significant reduction of the odds of peripheral neuropathic pain associated to GN.

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References

  1. 1.

    Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D (2010) Gluten sensitivity: from gut to brain. Lancet Neurol 9(3):318–330

    CAS  Article  Google Scholar 

  2. 2.

    Zis P, Sarrigiannis PG, Rao DG, Hewamadduma C, Hadjivassiliou M (2016) Chronic idiopathic axonal polyneuropathy: a systematic review. J Neurol 263(10):1903–1910

    Article  Google Scholar 

  3. 3.

    Zis P, Rao DG, Sarrigiannis PG, Aeschlimann P, Aeschlimann DP, Sanders D, Grünewald RA, Hadjivassiliou M (2017) Transglutaminase 6 antibodies in gluten neuropathy. Dig Liver Dis 49(11):1196–1200

    CAS  Article  Google Scholar 

  4. 4.

    Kelkar P, Ross MA, Murray J (1996) Mononeuropathy multiplex associated with celiac sprue. Muscle Nerve 19(2):234–236

    CAS  Article  Google Scholar 

  5. 5.

    Thawani SP, Brannagan TH 3rd, Lebwohl B, Green PH, Ludvigsson JF (2015) Risk of neuropathy among 28,232 patients with biopsy-verified celiac disease. JAMA Neurol 72(7):806–811

    Article  Google Scholar 

  6. 6.

    Hadjivassiliou M, Rao DG, Wharton SB, Sanders DS, Grünewald RA, Davies-Jones AG (2010) Sensory ganglionopathy due to gluten sensitivity. Neurology 75(11):1003–1008

    CAS  Article  Google Scholar 

  7. 7.

    Hadjivassiliou M, Grünewald RA, Kandler RH, Chattopadhyay AK, Jarratt JA, Sanders DS, Sharrack B, Wharton SB, Davies-Jones GA (2006) Neuropathy associated with gluten sensitivity. J Neurol Neurosurg Psychiatry 77(11):1262–1266

    CAS  Article  Google Scholar 

  8. 8.

    Leonard MM, Sapone A, Catassi C, Fasano A (2017) Celiac disease and nonceliac gluten sensitivity: a review. JAMA 15(7):647–656 318(

    Article  Google Scholar 

  9. 9.

    Zis P, Sarrigiannis PG, Rao DG, Hadjivassiliou M (2018) Quality of life in patients with gluten neuropathy: a case-controlled study. Nutrients 10(6):662

    Article  Google Scholar 

  10. 10.

    Hadjivassiliou M, Kandler RH, Chattopadhyay AK, Davies-Jones AG, Jarratt JA, Sanders DS, Sharrack B, Grünewald RA (2006) Dietary treatment of gluten neuropathy. Muscle Nerve 34(6):762–766

    CAS  Article  Google Scholar 

  11. 11.

    Peltier A, Goutman SA, Callaghan BC (2014) Painful diabetic neuropathy. BMJ 348:g1799

    Article  Google Scholar 

  12. 12.

    Smith HS (2011) Treatment considerations in painful HIV-related neuropathy. Pain Physician 14(6):E505–E524

    PubMed  Google Scholar 

  13. 13.

    Zis P, Varrassi G (2017) Painful peripheral neuropathy and cancer. Pain Ther 6(2):115–116

    Article  Google Scholar 

  14. 14.

    Zis P, Paladini A, Piroli A, McHugh PC, Varrassi G, Hadjivassiliou M (2017) Pain as a first manifestation of paraneoplastic neuropathies: a systematic review and meta-analysis. Pain Ther 6(2):143–151

    Article  Google Scholar 

  15. 15.

    Vadalouca A, Raptis E, Moka E, Zis P, Sykioti P, Siafaka I (2012) Pharmacological treatment of neuropathic cancer pain: a comprehensive review of the current literature. Pain Pract 12(3):219–251

    Article  Google Scholar 

  16. 16.

    Zis P, Grünewald RA, Chaudhuri RK, Hadjivassiliou M (2017) Peripheral neuropathy in idiopathic Parkinson’s disease: a systematic review. J Neurol Sci 378:204–209

    Article  Google Scholar 

  17. 17.

    Camdessanché JP, Jousserand G, Ferraud K, Vial C, Petiot P, Honnorat J, Antoine JC (2009) The pattern and diagnostic criteria of sensory neuronopathy: a case-control study. Brain 132(Pt 7):1723–1733

    Article  Google Scholar 

  18. 18.

    Zis P, Hadjivassiliou M, Sarrigiannis PG, Barker AStJE, Rao DG (2017) Rapid neurophysiological screening for sensory ganglionopathy: a novel approach. Brain Behav 7(12):e00880. https://doi.org/10.1002/brb3.880

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Graham RC, Hughes RA (2006) A modified peripheral neuropathy scale: the overall neuropathy limitations scale. J Neurol Neurosurg Psychiatry 77(8):973–976

    CAS  Article  Google Scholar 

  20. 20.

    Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lantéri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114(1–2):29–36

    Article  Google Scholar 

  21. 21.

    Sykioti P, Zis P, Vadalouca A, Siafaka I, Argyra E, Bouhassira D, Stavropoulou E, Karandreas N (2015) Validation of the Greek version of the DN4 diagnostic questionnaire for neuropathic pain. Pain Pract 15(7):627–632

    Article  Google Scholar 

  22. 22.

    Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30(6):473–483

    Article  Google Scholar 

  23. 23.

    Anagnostopoulos F, Demerouti E, Sykioti P, Niakas D, Zis P (2015) Factors associated with mental health status of medical residents: a model-guided study. J Clin Psychol Med Settings 22(1):90–109

    Article  Google Scholar 

  24. 24.

    Means-Christensen AJ, Arnau RC, Tonidandel AM, Bramson R, Meagher MW (2005) An efficient method of identifying major depression and panic disorder in primary care. J Behav Med 28(6):565–572

    Article  Google Scholar 

  25. 25.

    Biagi F, Andrealli A, Bianchi PI, Marchese A, Klersy C, Corazza GR (2009) A gluten-free diet score to evaluate dietary compliance in patients with coeliac disease. Br J Nutr 102(6):882–887

    CAS  Article  Google Scholar 

  26. 26.

    Newnham ED (2011) Does gluten cause gastrointestinal symptoms in subjects without coeliac disease? J Gastroenterol Hepatol 26(Suppl 3):132–134

    CAS  Article  Google Scholar 

  27. 27.

    Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C (2013) The Oslo definitions for coeliac disease and related terms. Gut 62(1):43–52

    Article  Google Scholar 

  28. 28.

    Didangelos T, Doupis J, Veves A (2014) Painful diabetic neuropathy: clinical aspects. Handb Clin Neurol 126:53–61. https://doi.org/10.1016/B978-0-444-53480-4.00005-9

    Article  PubMed  Google Scholar 

  29. 29.

    Brozou V, Vadalouca A, Zis P (2018) Pain in platin-induced neuropathies: a systematic review and meta-analysis. Pain Ther 7(1):105–119

    Article  Google Scholar 

  30. 30.

    Laurikka P, Salmi T, Collin P, Huhtala H, Mäki M, Kaukinen K, Kurppa K (2016) Gastrointestinal symptoms in celiac disease patients on a long-term gluten-free diet. Nutrients 8(7):E429

    Article  Google Scholar 

  31. 31.

    Sansotta N, Guandalini S, Amirikian K, Jericho H (2017) Celiac disease symptom resolution: effectiveness of the gluten free diet. J Pediatr Gastroenterol Nutr. https://doi.org/10.1097/MPG.0000000000001634

    Article  PubMed  Google Scholar 

  32. 32.

    Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR (2011) Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 106(3):508–514

    CAS  Article  Google Scholar 

  33. 33.

    McGrath PA (1994) Psychological aspects of pain perception. Arch Oral Biol 39(Suppl):55S–62S

    Article  Google Scholar 

  34. 34.

    Zis P, Daskalaki A, Bountouni I, Sykioti P, Varrassi G, Paladini A (2017) Depression and chronic pain in the elderly: links and management challenges. Clin Interv Aging 12:709–720

    CAS  Article  Google Scholar 

  35. 35.

    Farhad K, Traub R, Ruzhansky KM, Brannagan TH 3rd (2016) Causes of neuropathy in patients referred as “idiopathic neuropathy”. Muscle Nerve 53(6):856–861

    Article  Google Scholar 

Download references

Acknowledgements

This is a summary of independent research supported by BRC and carried out at the National Institute for Health Research (NIHR) Sheffield Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the BRC, NHS, the NIHR, or the Department of Health. We would like to thank all participants in the study.

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Contributions

PZ and MH: drafting/revising the manuscript, data collection statistical analysis, accept responsibility for conduct of research, and final approval. DGR and PGS: drafting/revising the manuscript, data collection, accept responsibility for conduct of research, and final approval.

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Correspondence to Panagiotis Zis.

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Conflicts of interest

Panagiotis Zis, Dasappaiah Ganesh Rao, Ptolemaios Georgios Sarrigiannis, and Marios Hadjivassiliou have nothing to disclose.

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Zis, P., Sarrigiannis, P.G., Rao, D.G. et al. Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet. J Neurol 265, 2231–2236 (2018). https://doi.org/10.1007/s00415-018-8978-5

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Keywords

  • Gluten neuropathy
  • Neuropathic pain
  • Gluten-free diet