Small Fiber Neuropathy in Veterans With Gulf War Illness
Background: Gulf War veterans deployed to operations Desert Shield and Desert Storm returned with chronic multisystemic symptoms. This Gulf War Illness (GWI) has defied attempts to identify an underlying etiology. Pain and other symptoms attributable to autonomic nervous system (ANS) dysfunction are common, which may suggest a pathophysiologic underpinning.
Methods: A retrospective chart review of clinical data at the New Jersey War Related Illness and Injury Study Center addressed the following questions: (1) how common was biopsy-confirmed SFN in veterans with GWI; (2) do veterans with GWI and SFN report more symptoms attributable to ANS dysfunction as compared to veterans with GWI and no SFN; and (3) can SFN in veterans with GWI and SFN be explained by conditions commonly associated with SFN? Chart review abstracted GWI status, skin biopsy results, and ANS symptom burden. For veterans with GWI and SFN, additional chart abstraction was explored for commonly reported contributing conditions.
Results: From March 1, 2015, to January 31, 2019, 51 Gulf War veterans evaluated at the War Related Illness and Injury Study Center had a skin biopsy. Of these, 42 (83%) were diagnosed with GWI and 24 of 42 (57%) also had SFN. No differences were observed in ANS symptoms when compared with veterans with GWI and no SFN. A potential etiology for SFN was identified in 16 of 24 (67%) veterans with GWI and SFN, increasing to 19 (79%) when hyperlipidemia was included. Our analysis did not identify an explanation in 5 of 24 (21%) veterans with GWI and SFN.
Conclusions: SFN was common in this clinical sample of veterans diagnosed with GWI. A well-established potential etiology was identified in most cases of SFN. About 20% of veterans with GWI in our clinical sample had idiopathic SFN, and it is plausible that deployment-related exposures could have contributed to this condition. Symptoms of ANS are prevalent in GWI, though SFN cannot solely account for this. Our study does not generally support SFN as etiologic for GWI, though this may still be relevant for some. Additional research is required to explore relationships between Gulf War exposures and SFN.
Assessment of autonomic dysfunction was based on COMPASS 31 symptom reporting by an small subset of the clinical cohort. Symptom reporting may not be reflective of true abnormality in ANS function. Physiologic tests of the ANS were not performed; such studies could more objectively establish whether ANS dysfunction is more prevalent in GWI veterans with SFN.
Evaluation for all potential etiologic/contributory conditions to SFN was not exhaustive. For example, sodium channel gene mutations have been documented to account for up to one-third of all cases of idiopathic SFN.42 For those cases in which no compelling etiology was identified, it is plausible that medical explanations for SFN may be found on further investigation.
Clinical assessments at the WRIISC were performed on GWVs ≥ 26 years after their deployment-related exposures. Other conditions/exposures may have occurred in the interim. What is not clear is whether the SFN predated the onset of any of these medical conditions or other putative contributors. This observational study is not able to tease out a temporal association to make a cause-and-effect assessment.
Conclusions
Retrospective analysis of clinical data of veterans evaluated at a specialized center for postdeployment health demonstrated that skin biopsy–confirmed SFN was prevalent, but not ubiquitous, in veterans with GWI. Symptom that may be attributed to ANS dysfunction in this clinical sample was consistent with literature on SFN and with GWI, but we could not definitively attribute ANS symptoms to SFN. Our study does not support the hypothesis that GWI symptoms are solely due to SFN, though it may still be relevant in a subset of veterans with GWI with strongly suggestive clinical features. We were able to identify a potential etiology for SFN in most veterans with GWI. Further investigations are recommended to explore any potential relationship between Gulf War exposures and SFN.
