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Iatrogenic immune-mediated neuropathies: diagnostic, epidemiological and mechanistic uncertainties for causality and implications for clinical practice
  1. H Stephan Goedee1,
  2. Shahram Attarian2,
  3. Thierry Kuntzer3,
  4. Peter Van den Bergh4,
  5. Yusuf A Rajabally5,6
  1. 1 Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2 Service de Neurologie, Hopital La Timone, Marseille, France
  3. 3 Service of Neurology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
  4. 4 Centre de Référence Neuromusculaire, Cliniques Universitaires St-Luc, Brussels, Belgium
  5. 5 Inflammatory Neuropathy Clinic, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  6. 6 Aston Medical School, Aston University, Birmingham, UK
  1. Correspondence to Prof. Yusuf A Rajabally, Inflammatory Neuropathy Clinic, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, UK; y.rajabally{at}


Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases.

  • guillain-barre syndrome
  • systematic reviews
  • neurotoxicology
  • neuropathy
  • neuromuscular

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  • Contributors HSG and YAR: Review of the literature, selection of relevant reports, drafting of first version of manuscript. SA, TKa nd PVdB: Selection of relevant reports, review of first version of manuscript for intellectual content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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