Defining Sick Building Syndrome in a case-control series as a biotoxin-associated illness in adults and children: diagnosis, treatment and disorders of innate immune response involving MSH, split products of complement, IL-1B, MMP9, VEGF, autoimmunity and HLA DR
Ritchie C Shoemaker¹, Dennis House¹
Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md
Background: Recent treatment studies on illness acquired following exposure to indoor environments with toxigenic organisms in water-damaged buildings (WDB) demonstrate the presence of physiologic and genetic factors that taken together create a case definition for illness in adults. We present a case-control series of 288 adults and 100 children with illness associated with exposure to WDB. Multiple biomarkers for illness, including visual contrast sensitivity (VCS), complement C3a and C4a, HLA-DR, MSH, dysregulation of pituitary hormones, MMP9, VEGF and antibodies to gliadin and cardiolipin are increased in cases. Repetitive re-exposure protocols following pharmacologic treatment provide proof of causation and prospective documentation of inflammatory events. A case definition of illness in children is presented.
Methods: Symptoms, VCS and laboratory parameters in 288 adults and 100 pediatric patients treated for illness possibly caused by exposure to WDB were matched to controls after informed consent. Testing included HLA DR, MSH, leptin, ADH, osmolality, ACTH, cortisol, MMP9, TNF, PAI-1, CRP, ESR, lipids, VEGF, erythropoietin, C3a, C4a, IL-1B, IL-10, alpha interferon, IgE, antigliadin and anticardiolipin. Adults were kept away from exposure after intervention; returned to exposure with prophylactic medications; treated with the diagnostic repetitive re-exposure protocol; monitored daily following re-exposure. Children were treated pharmacologically and with removal from WDB.
Results: Statistically significant differences between adult cases and control were seen in symptoms, VCS scores, HLA DR, MSH, MMP9, VEGF, simultaneous ADH/osmolality, ACTH/cortisol, autoantibodies, C3a, C4a, IL-1B, IL-10 and alpha interferon. Treatment by a published protocol reduced symptoms, VCS and lab parameters to control levels, except for MSH and IL-10. Pediatric cases demonstrated differences compared to controls in symptoms, VCS, MSH, MMP9, antigliadin and anticardiolipin adequate to create a case definition. Hyperacute illness was marked by sequential rises in C3a/C4a (4 hours); IL-1B (12 hours); leptin (24-48 hours); MMP9 (48-72 hours) and VEGF (72 hours).
Conclusions: Symptoms following exposure to WDB are identified by a diagnostic and treatment protocol. The hyperacute changes in innate immune response, persisting in chronic illness, suggest that an amplifying biological cascade underlies acute and chronic symptoms seen in “Sick Building Syndrome.” The observed autoimmune events, particularly in children, will require further investigation.