​Chronic fatigue syndrome following a toxic exposure https://pubmed.ncbi.nlm.nih.gov/11327394 Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc. In the National Reference Center for CFS Study at the Department of Infectious Diseases of 'G. D'Annunzio' University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression. All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56 All CFS subgroups showed low levels of serum magnesium in most of the patients.  A  similar algological  profile with a characteristic  reduction of only the muscle pain thresholds and normality of cutis and subcutis  pain  thresholds  was  documented in PVCFS  patients  and  in  those  with  a toxic exposure, while MDCFS patients showed a reduction  of  pain  thresholds in all the body  districts taken into consideration  cutis, subcutis and muscle as well as a positivity  of  more than 11 tender points to support the  existence  in  such patients of a concurrent  fibromyalgia syndrome. Furthermore, abnormal evoked auditory potentials were reported more frequently by MDCFS patients than by the other two CFS subgroups. The patients with a previous exposure to toxics had disturbances of hypothalamic functions similar to those determined in the other two subgroups: most of the patients showed low levels of DHEAS, a normal profile of the circadian rhythm of the other examined neurohormones.  Finally, an abnormal increase of prolactin  levels  followed the buspirone challenge test, to suggest an upregulation of 5HT1A hypothalamic receptors in all the three subgroups of patients. The only comparative analysis that underlined a different behavior of patients with a previous toxic exposure was the lymphocyte subsets characterization Patients with a history of toxic exposure in fact showed a more severe dysfunction of the immune system in a statistically significant way compared both to PVCFS anemics patients, and specifically:  an abnormalCD4CD8 ratio; three of such five cases also showed decreased numbers of NK CD56cells. Discussion Chronic fatigue syndrome   CFS   still remains of uncertain   definition because   of the lack of specific features both clinically and objectively. However, CFS patients complain of some alterations more recurrently than others, such as serum magnesium deficiency, muscle hyperalgesia, impaired activation of HPA axis. In our opinion, the study of the immune system status in CFS patients might help in a better characterization   of the syndrome, even if more immunologic studies prerequired as suggested by literature data. 1 A better characterization of T CD8lymphocytes so to differentiate cytotoxic cells from the suppressor ones. In fact, many researchers   Barker et.al., 1994   report a predominant reduction of CD8 CD11b lymphocytes or T suppressor lymphocytes and this agrees with the theory of a persistent immune activation in CFS   Landay et al., 1991 2 The determination in plasma and, if possible, in CSF of some cytokines frequently found increased in CFS subjects   Pat arca et al.,.1995; Ollerton et al., 1998:  IL1, IL2, IL6, TNF alpha and beta.  Our preliminary findings confirm the presence of a dysfunction of the immune system in CFS patients with an history of toxic exposure previous to CFS onset:  an abnormal CD4 CD8 ratio principally due to a reduction of T CD8 lymphocytes; three of the five examined patients also showed decreased numbers of NK CD56cells. So CFS patients with apostolic exposure onset might represent a well-defined CFS subgroup characterized by specific immune dysfunctions probably precipitated by the toxic exposure itself. In conclusion, further immunologic studies are needed for a better    understanding of the pathogenetic mechanisms involved in CFS, as well as for a better categorization of CFS patients by the immune status  New Study Provides a Link between Common Chemicals and ‘Unexplained’ Chronic Illnesseshttps://tiltresearch.org/2021/06/28/new-study-provides-a-link-between-common-chemicals-and-unexplained-chronic-illnesses The Relationship Between Chronic Fatigue Syndrome and Chemical Exposurehttps://www.tandfonline.com/doi/abs/10.1300/J092v05n03_18 Environmental Exposures as a Potential Underlying Factor in Chronic Fatigue Syndrome; a Case Report https://www.esmed.org/MRA/mra/article/view/1573

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