What is Chronic Inflammatory Response Syndrome (CIRS)?

Chronic Inflammatory Response Syndrome (CIRS): Definition, Diagnosis, and Management

Chronic Inflammatory Response Syndrome (CIRS) is a multisystem, multi-symptom condition characterized by innate immune dysregulation following exposure to biotoxins, most commonly from water-damaged buildings, that affects genetically susceptible individuals. 1

Pathophysiology and Causes

• CIRS develops when environmental biotoxin exposure triggers chronic inflammation in genetically predisposed individuals, particularly those with specific HLA-DR/DQ haplotypes 2
• The most common trigger is exposure to mycotoxins from water-damaged buildings containing toxic molds like Stachybotrys chartarum 2, 3
• The condition represents a failure of the normal inflammatory response to resolve, leading to persistent immune dysregulation 1
• Unlike acute inflammatory responses that resolve with pathogen elimination, CIRS involves ongoing inflammation despite removal from the exposure source 3

Clinical Presentation

• CIRS manifests as a complex multisystem disorder with symptoms affecting multiple organ systems simultaneously 1
• Common symptoms include:
  • Severe fatigue and post-exertional malaise 2, 4
  • Cognitive impairments (brain fog, memory problems, difficulty concentrating) 4
  • Respiratory issues (similar to chronic rhinosinusitis) 5
  • Gastrointestinal disturbances (can mimic inflammatory bowel conditions) 2
  • Neurological symptoms (headaches, numbness, tingling) 4
  • Musculoskeletal pain 3
  • Temperature regulation problems 6

Diagnostic Approach

• Diagnosis requires a comprehensive assessment including:
  • Detailed exposure history focusing on water-damaged buildings 3
  • HLA-DR/DQ genetic testing to identify susceptible haplotypes 2
  • Biomarker testing including TGF-beta, MMP-9, and vasoactive intestinal peptide (VIP) levels 2, 4
  • Visual contrast sensitivity (VCS) testing, which is often abnormal in CIRS patients 4
  • Urine mycotoxin panel to identify specific biotoxin exposures 2
  • Ruling out other conditions with overlapping symptoms 3

Treatment Protocol

• The most documented effective treatment approach is the Shoemaker Protocol, which includes: 1
  • Removal from biotoxin exposure source as the first critical step 2, 3
  • Binding agents to help eliminate circulating biotoxins 1
  • Addressing VIP deficiency with replacement therapy when indicated 2
  • Treating co-infections and addressing dental sources of inflammation when present 2
  • Implementing mind-body interventions to help modulate the stress response 2

Emerging Treatments

• Low-pressure hyperbaric oxygen therapy (HBOT) shows promise as a potential treatment:
  • A case study demonstrated resolution of symptoms, normalization of visual contrast sensitivity, and reduction in inflammatory biomarkers after 40 HBOT sessions 4
  • HBOT appears to modulate systemic inflammation and improve neurocognitive outcomes in CIRS patients 4

Differential Diagnosis

• CIRS is frequently misdiagnosed as:
  • Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) 1
  • Mast Cell Activation Syndrome 3
  • Chronic rhinosinusitis, particularly with type 2 inflammation 5
  • Chronic Lyme disease or other tick-borne illnesses 3
  • Fibromyalgia 3

Clinical Pitfalls and Considerations

• CIRS remains underrecognized and underdiagnosed despite potentially affecting up to 25% of the population 1
• Failure to identify and remove the source of biotoxin exposure will result in continued symptoms despite treatment 2, 3
• Standard laboratory testing may not reveal abnormalities; specialized biomarker testing is often required 2
• Genetic susceptibility plays a crucial role - not everyone exposed to water-damaged buildings will develop CIRS 2
• Treatment outcomes are superior when the condition is correctly identified as CIRS rather than being misdiagnosed as ME/CFS 1

Prognosis

• With proper identification of biotoxin sources, removal from exposure, and appropriate treatment, many patients can experience significant symptom improvement 2, 1
• Case reports document complete resolution of symptoms, normalization of biomarkers, and return to normal functioning following comprehensive treatment 2, 4
• Without proper diagnosis and treatment, CIRS can lead to persistent debilitating symptoms affecting quality of life 1