Chronic Inflammatory Response Syndrome Diagnosis and TreatmentBy Kellyn Milani, ND

What is Chronic Inflammatory Response Syndrome?

Chronic Inflammatory Response Syndrome (CIRS) is a multi-symptom, multi-system illness caused by exposure to biotoxins, or neurotoxins produced from a biological source. The most common sources of biotoxins are toxic metabolic products and cell wall fragments from filamentous molds (many incorrectly refer to this as mold toxin illness) that occur in water damaged buildings, tick-borne illnesses including Lyme Disease, cyanobacteria, dinoflagellates like ciguatera and red tide, Pfiesteria, and poisonous spiders like Brown Recluse and Mediterranean Recluse. Exposure to these sources can create acute illness, and in some individuals who have long-term exposure or who are genetically unable to clear the biotoxins can create a chronic illness.1, 2 (Ch. 3,4), 3(Ch. 2)

The acute illnesses caused by exposure to biotoxins typically have a sudden onset and are most often characterized by severe malaise, fatigue, anorexia, chills, fever, headache, muscle pain, joint pain, nausea, vomiting, abdominal pain, and shortness of breath. However, each biotoxin has a slightly different acute presentation:

  • Lyme Disease: Stage 1 Lyme disease is classically characterized by erythema migrans (bulls-eye rash) and an undifferentiated febrile illness. One-third of patients do not exhibit erythema migrans, but may have flu-like symptoms including fever, chills, malaise, myalgia, arthralgia, headache, and neck stiffness. Symptoms can very depending on the presence or absence of co-infections as well. Stage 2 of Lyme disease is defined as symptoms occurring 3-10 weeks after inoculation. Classic symptoms of Stage 2 include, fever, malaise, arthritis, arthralgia, neuropathy, and headache.4, 5
  • Cyanobacteria: The most frequent exposure to this biotoxin is by swimming or drinking water containing cyanobacteria. Symptoms from exposure can include skin irritation, rashes, blisters in the mouth and nose, abdominal pain, vomiting, nausea, diarrhea, fever, sore throat, headache, muscle pain, and joint pain.6
  • Ciguatera: Exposure to ciguatera toxin is caused by eating contaminated reef caught fish. Ciguatera is an odorless and tasteless toxin that cannot be removed by cooking. Typical symptoms include diarrhea, nausea, vomiting, flu-like symptoms including myalgia, arthralgia, malaise and fatigue, neurological symptoms like numbness and tingling, headache, shortness of breath, tachycardia, severe localized itching.7, 8
  • Pfiesteria: Exposure to this biotoxin can cause eye and respiratory irritation, skin rashes, headache, stomach cramps, nausea, vomiting, and neurocognitive changes.9
  • Recluse Spider Bites: Symptoms arising after a bite by a Mediterranean Recluse or Brown Recluse often include rash or itching, pain at the site of the bite, blistering of the skin at the site of the bite, muscle pain or cramping, fever, shortness of breath, headache, nausea, vomiting, and chills.10
  • Mold: Acute reactions to mycotoxins and cell wall fragments from filamentous molds can include headache, eye irritation, nose bleeds, nasal and sinus congestion,

    cough, flu-like symptoms, gastrointestinal complaints, and shortness of breath.3 (Ch.2), 11

Even when properly treated, not everyone who becomes ill from an exposure to a biotoxin

will fully recover from the acute illness, creating a chronic illness. This is in part due to

immune activation and genetic variations in immunity. Twenty -five percent of the general

population has a HLA DR DQ haplotype that leads to decreased antigen presentation, which

results in the reduced clearing of toxins from these biological sources. The resulting

increased level of biotoxins causes the simultaneous and progressive activation of

inflammatory pathways including TH1, TH2, TH17, complement immunity, and coagulation

cascades. Ultimately this creates symptoms across many (minimum of four) or all body

systems. Some symptoms that have been found to be associated with CIRS include thefollowing: 2 (Ch. 4, 7, 11), 3 (App. 1), 12

  • Headache
  • Light sensitivity
  • Memory issues
  • Word searching
  • Difficulty concentrating
  • Difficulty comprehending new


  • Unusual skin sensations
  • Numbness and/or tingling
  • Confusion
  • Red eyes
  • Blurred vision
  • Mood disturbances
  • Icepick-like pains
  • Vertigo
  • Disorientation
  • Metallic taste
  • Tearing of the eyes
  • Difficulty regulating body


    How do we diagnose CIRS?

• Night sweats• Tremor
• Weakness
• Body aches
• Joint pain

• Muscle pain
• Morning stiffness
• Muscle cramping
• Shortness of breath
• Sinus issues
• Cough
• Increased thirst
• Urinary frequency
• High or low appetite
• Abdominal pain
• Gastrointestinal issues• Static shocks
• Low-grade fever
• Fatigue