What is the treatment for Chronic Inflammatory Response Syndrome (CIRS)?

Chronic Inflammatory Response Syndrome (CIRS): Understanding and Treatment

Critical Clarification: Two Distinct Conditions

You are asking about Chronic Inflammatory Response Syndrome (CIRS), which is fundamentally different from Cytokine Release Syndrome (CRS) discussed in most of the provided guidelines. The evidence base consists primarily of CRS guidelines (related to CAR T-cell therapy complications) 1, while only limited research addresses CIRS as an environmental illness 2, 3, 4.

What is CIRS?

CIRS is an acquired illness characterized by innate immune dysregulation following respiratory exposure to water-damaged buildings, affecting up to 25% of the population in genetically susceptible individuals 3.

Key Pathophysiology

• Genetic susceptibility through HLA-DR/DQ haplotypes determines who develops chronic inflammation after biotoxin exposure 4
• Biotoxin exposures (particularly mold toxins like trichothecenes from Stachybotrys chartarum) trigger persistent immune dysregulation 4
• Multiple organ systems are simultaneously affected, creating a multisymptom presentation 3

Diagnostic Biomarkers

• Elevated TGF-β1 (transforming growth factor beta-1) indicates ongoing inflammation 2, 4
• Clinically undetectable or very low vasoactive intestinal peptide (VIP) levels 4
• Elevated MMP-9 (matrix metalloproteinase-9) 2
• Abnormal visual contrast sensitivity (VCS) testing 2
• Positive urine mycotoxin panels 4
• HLA-DR/DQ genetic testing identifies susceptible haplotypes 4

Evidence-Based Treatment: The Shoemaker Protocol

The only treatment protocol with documented clinical efficacy for CIRS is the Shoemaker Protocol, which was described in 11 of 13 articles addressing CIRS treatment and demonstrates superior outcomes compared to treatments for similar conditions like ME/CFS 3.

Treatment Algorithm Components

Step 1: Eliminate Biotoxin Exposure

• Remove patient from water-damaged environment immediately 4
• Identify and remediate mold sources through air filter testing 4
• This step is non-negotiable; continued exposure prevents recovery regardless of other interventions 3, 4

Step 2: VIP Replacement Therapy

• Administer vasoactive intestinal peptide (VIP) replacement to address the clinically undetectable levels characteristic of CIRS 4
• VIP therapy directly targets the documented deficiency in CIRS pathophysiology 4

Step 3: Address Concurrent Biotoxin Sources

• Evaluate for dental sources of biotoxin exposure; dental extractions may be necessary 4
• Screen for multiple biotoxin exposures beyond initial mold identification 4

Step 4: Adjunctive Interventions

• Implement mind-body intervention programs, specifically relaxation response (MBI-RR) techniques 4
• These support immune system regulation during recovery 4

Alternative Emerging Treatment

Hyperbaric Oxygen Therapy (HBOT)

A 2025 case study demonstrated complete resolution of all 22 CIRS symptoms following 40 shallow dive HBOT sessions over 10 weeks 2.

HBOT Protocol Details

• 40 sessions administered over 10-week period 2
• Shallow dive protocol (low-pressure hyperbaric oxygen) 2

Documented Outcomes

• Complete symptom resolution (22/22 symptoms) 2
• VCS score normalization from 68% to 93% 2
• Significant reductions in TGF-β1 and MMP-9 2
• Improved neurocognitive function 2

However, this evidence is limited to a single case study and requires extensive quantitative research for validation 2.

Monitoring Treatment Response

Objective Measures

• Serial TGF-β1 levels to track inflammatory resolution 2, 4
• VIP levels to confirm replacement therapy adequacy 4
• MMP-9 levels as inflammatory markers 2
• Visual contrast sensitivity testing for neurocognitive improvement 2

Clinical Outcomes

• Resolution of multisystem symptoms (fatigue, cognitive dysfunction, pain) 2, 4
• Return to normal daily activities and work 4
• Ability to discontinue medications 4

Critical Pitfalls to Avoid

Misdiagnosis Risk

• CIRS is commonly misdiagnosed as ME/CFS, which lacks defined etiology, biomarkers, or effective treatment protocols 3
• Unlike ME/CFS, CIRS has identifiable biomarkers and a treatment protocol that reverses underlying conditions 3
• Autoimmune disease biomarkers are typically negative in CIRS despite inflammatory presentation 4

Treatment Failures

• Continuing treatment while patient remains in biotoxin-contaminated environment guarantees failure 4
• Treating symptoms without addressing underlying immune dysregulation provides only temporary relief 3
• Failing to test for genetic susceptibility (HLA-DR/DQ) may miss the diagnosis entirely 4

Evidence Quality Assessment

The evidence base for CIRS treatment is limited, consisting primarily of case reports and case series rather than randomized controlled trials 2, 3, 4. The Shoemaker Protocol represents the best available evidence with documented clinical efficacy across multiple published reports 3. HBOT shows promise but requires larger controlled studies before widespread recommendation 2.