Chronic Inflammatory Response Syndrome (CIRS) is a form of Systemic Inflammatory Response Syndrome (SIRS). CIRS is often acquired through different mechanisms, for example, an exposure to environmental sources of biotoxins or chronic illness from Lyme disease present even after treatment with antibiotics. The exposure to environmental sources of biotoxins includes a chronic exposure to the interior environment of water-damaged buildings (WDB) or ingestion of fish contaminated with the toxins of marine dinoflagellates, such as ciguatoxins.   Other environmental sources of biotoxins that can lead to CIRS include certain compounds made by cyanobacteria, fungi, actinomycetes, bacteria, mycobacteria etc.  When CIRS is acquired because of an exposure to a WDB, it is termed CIRS-WDB (Expert Treating Physicians Consensus, 2010).

According to a report released by the World Health Organization in 2009, in a WDB people are chronically exposed to different microbes and/or compounds of microbial or other origin that are present in the indoor air of a WDB.  These compounds can be called toxins or inflammagens; all initiate an innate immune inflammatory response in the human host. These microbes and compounds include but are not limited to fungi, bacteria, actinomycetes, and mycobacteria and their toxins; as well as inflammagens from fragments of fungal structures; and beta glucans, mannans, hemolysins, proteinases, spirocyclic drimanes and volatile organic compounds (VOCs).  A constant exposure to the above microbes and/or compounds can result in a recurrent activation of immune responses leading to exaggerated immune responses and prolonged production of inflammatory mediators, especially in the absence of regulation of inflammation by neuropeptides MSH or VIP.

Some of the organisms that make biotoxins that can cause CIRS include dinoflagellates (Pfiesteria, Gambierdiscus (ciguatera), Karenia (and other species that produce brevetoxins) cyanobacteria (Microcystis, Cylindrospermopsis, Lyngbya wollei); fungi (Wallemia, Stachybotrys, Chaetomium, Trichoderma, Aspergillus versicolor, Aspergillus versicolor and others.); actinomycetes (Streptomyces and others); apicomplexans (Babesia, Sarcocystis, Eimeria); and spirochetes (Borrelia spp burgdorferi and (likely) B. lonestari).  Organisms such as commensal multiple-antibiotic resistant coagulase negative staphylococci (MARCoNS), including methicillin resistant Staphylococcus epidermidis, may also contribute to CIRS.
 
Patients with CIRS are often misdiagnosed as having depression, stress, allergy, fibromyalgia, post-traumatic stress disorder, Chronic Fatigue Syndrome somatization, etc, and are treated with various therapies, some of them being potentially toxic, which have not yet been shown to be effective and are costly.  The reason CIRS is misdiagnosed is because there are no biomarkers that have been identified yet to provide confirmatory diagnosis.   Treating CIRS patients for the above conditions do not improve their symptoms of CIRS.  With proper detection, diagnosis, and documentation of the objective basis of illness pathophysiology, CIRS may be treated effectively to improve symptoms and decrease the recurrence of uncontrolled inflammatory responses.