Sick Building Sick Building Syndrome is a Syndrome is a distinct clinical distinct clinical entity: we have the entity: we have the proof proof Senate Health, Education, Labor and Pension Senate Health, Education, Labor and Pension Committee Committee 1/12/06 1/12/06 Ritchie C. Shoemaker MD Ritchie C. Shoemaker MD Center for Research on Biotoxin Associated Center for Research on Biotoxin Associated Illnesses Illnesses Pocomoke, Md Pocomoke, Md
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Sick Building Syndrome Sick Building Syndrome is a distinct clinical is a distinct clinical entity: we have the entity: we have the
proofproofSenate Health, Education, Labor and Pension Senate Health, Education, Labor and Pension
CommitteeCommittee1/12/061/12/06
Ritchie C. Shoemaker MDRitchie C. Shoemaker MDCenter for Research on Biotoxin Associated IllnessesCenter for Research on Biotoxin Associated Illnesses
studiesstudies Reproducibility at multiple sitesReproducibility at multiple sites Peer-reviewed publicationsPeer-reviewed publications EVIDENCE-BASED MEDICINE!EVIDENCE-BASED MEDICINE!
Treatment leads to Treatment leads to definitiondefinition
Prior studies showed there were Prior studies showed there were health problems in patients exposed health problems in patients exposed to water-damaged buildings hosting to water-damaged buildings hosting toxigenic organisms, including fungitoxigenic organisms, including fungi
Effective therapy, beginning with Effective therapy, beginning with cholestyramine, gives us the ability cholestyramine, gives us the ability to correct and then study the diseaseto correct and then study the disease
Case definitionCase definition Individual casesIndividual cases ScreeningScreening Documentation of acquisition of illnessDocumentation of acquisition of illness Risk managementRisk management
– High risk occupationsHigh risk occupations– New hires in water-damaged buildingsNew hires in water-damaged buildings– Verify effective remediation occurredVerify effective remediation occurred
Case definition-1Case definition-1
103 patients /43 buildings (Brescia, Italy)103 patients /43 buildings (Brescia, Italy) 156 patients /150 buildings (Saratoga, NY)156 patients /150 buildings (Saratoga, NY) 21 patients/ 5 buildings (NT and T)21 patients/ 5 buildings (NT and T) 288 patients /125 buildings (ASTMH)288 patients /125 buildings (ASTMH) 26 patients/5 buildings (DB-PC trial)26 patients/5 buildings (DB-PC trial) 20 patients in hyperacute model (ASM 20 patients in hyperacute model (ASM
biodefense conference)biodefense conference) 40 patients, eight year follow-up40 patients, eight year follow-up 152 patients, age under 19152 patients, age under 19
Case definition-2Case definition-2
FIRST TIERFIRST TIER
Potential for exposurePotential for exposure Multisystem, multisymptom illnessMultisystem, multisymptom illness Absence of confoundersAbsence of confounders Differential diagnosisDifferential diagnosis
Case definition-3Case definition-3
SECOND TIERSECOND TIER
Genetic susceptibility; HLA DR by PCRGenetic susceptibility; HLA DR by PCR Hypothalamic impairment; low MSHHypothalamic impairment; low MSH Neurotoxic illness; VCS deficitNeurotoxic illness; VCS deficit Cytokine activation; MMP9 elevationCytokine activation; MMP9 elevation Pituitary involvementPituitary involvement
Why use such unusual Why use such unusual tests?tests?
Biologically produced neurotoxins activate Biologically produced neurotoxins activate innateinnate immune responses NOT immune responses NOT acquiredacquired immune responsesimmune responses
Illness is hidden by looking only at Illness is hidden by looking only at “standard lab tests”“standard lab tests”
Illness is obvious to anyone when looking Illness is obvious to anyone when looking at what is wrongat what is wrong
Tests might look unusual, but are readily Tests might look unusual, but are readily available to any physician; insurance available to any physician; insurance approved, Medicare approvedapproved, Medicare approved
Is mold illness rare?Is mold illness rare?
NO!NO!
We see 10 new patients a weekWe see 10 new patients a week Total in treatment data base exceeds Total in treatment data base exceeds
29002900 mold illness patients mold illness patients Total biotoxin illness patients Total biotoxin illness patients
exceeds exceeds 50005000 We have data on over We have data on over 40004000 controls controls
Fat Cell
Surface (“Toll”)
receptor
Biotoxin(HLA susceptible)
Increased Cytokines
Increased Leptin
Leptin receptor
Nerve cell
Body acquires
biotoxins or
toxin-producing
organisms from
food, water, air,
or insect bites
CapillariesIn genetically susceptible people, biotoxin binds to fat-cell receptors,
causing continuing, unregulated production of cytokines.
Removal from the body
Biotoxins have direct effects, including impairment of nerve cell function. One result is poor performance on contrast sensitivity test.
Excessive cytokine levels can damage leptin receptors in the hypothalamus.
High cytokine levels in the capillaries attract white blood cells, leading to restricted blood flow, and lower oxygen levels. Reduced VEGF leads to fatigue, muscle cramps, and shortness of breath (may be over-ridden by replacement with erythropoietin).
In most people, biotoxins are either removed from the blood by the liver or attacked by the immune system, broken down, and excreted harmlessly. In people who don’t have the right immune-system genes, however, biotoxins can remain in the body indefinitely.
Damaged leptin receptors lead to reduced production by the hypothalamus of MSH, a hormone with many functions.
Reduced ADH
Cytokine-related symptoms
High levels of cytokines produce flu-like symptoms: Headaches, muscle aches, fatigue, unstable temperature, difficulty concentrating.High levels of cytokines also result in increased levels of several other immune-response related substances, including TNF, MMP-9, IL-1B, and PAI-1. MMP-9 delivers inflammatory elements from blood to brain, nerve, muscle, lungs, and joints. It combines with PAI-1 in increasing clot formation and arterial blockage.
Fat cells then produce more leptin, leading to obesity (which doesn’t respond to exercise and diet).
Biotoxin
(HLA susceptible)
Biotoxin
(not HLA
susceptible)
Immune system symptoms
Patients with certain HLA genotypes (immunity-related genes) may develop inappropriate immunity. Most common are antibodies to:-- Myelin basic protein (often from fungal biotoxins; affects nervous-system functions)-- Gliadin (affects digestion)-- Cardiolipins (affects blood clotting)The “complement” alternative immune pathway may be triggered (detectable as an increase in levels of the proteins C3a C4a).
Reduced sex hormones
Reduced MSH can cause the pituitary to produce lower levels of anti-diuretic hormone (ADH), leading to thirst, frequent urination, and susceptibility to shocks from static electricity.
Reduced MSH can cause the pituitary to lower its production of sex hormones.
Changes in cortisol and ACTH levels
The pituitary may produce elevated levels of cortisol and ACTH in early stages of illness, then drop to excessively low levels later. (Patients should avoid steroids such as prednisone, which can lower levels of ACTH.)
Resistant Staph bacteria
Colonies of Staph bacteria with resistance to multiple antibiotics may develop in mucous membranes. The bacteria produce substances that aggravate both the high cytokine levels and low MSH levels.
Gastrointestinal problems
Lack of MSH can cause malabsorption in the gut, resulting in diarrhea. This is sometimes called “leaky gut” and resembles (but is not) celiac disease. Patients must avoid gluten, whey, and amylose.
Prolonged illness
White blood cells lose regulation of cytokine response, so that recovery from other illnesses, including infectious diseases, may be slowed.
Sleepdisturbance
Production of melatonin is reduced, leading to light, non-restorative sleep.
Chronic pain
Endorphin production is suppressed. This can lead to chronic, sometimes unusual, pain.
– Just about the best marker beyond 4 Just about the best marker beyond 4 days of biotoxin-associated/cytokine days of biotoxin-associated/cytokine illnessillness
Mean IgE, by illness, all patients Mean IgE, by illness, all patients
Cases N=Cases N= IgEIgE
ControlsControls No illnessNo illness 234234 2424
Mold casesMold cases Confirmed caseConfirmed case 367367 3131
Asthma Asthma casescases
Inhaled steroids + 1 Inhaled steroids + 1 other med, > 6 other med, > 6
months/yearmonths/year 4545 567567
Nasal Nasal allergyallergy
Nasal steroid + 1 Nasal steroid + 1 other med, > 6 other med, > 6
months/yearmonths/year 3838 432432
CONCLUSIONSCONCLUSIONS Mold illness is a distinctive, readily recognizable Mold illness is a distinctive, readily recognizable
clinical entity in adults and childrenclinical entity in adults and children
Significant objective differences exist between cases Significant objective differences exist between cases and controlsand controls
Findings support inflammatory cascades initiated by Findings support inflammatory cascades initiated by toxin exposure in genetically susceptible patientstoxin exposure in genetically susceptible patients
Abnormalities in innate immune responses point the Abnormalities in innate immune responses point the way to additional interventionsway to additional interventions
Use of a predictive model could make diagnosis Use of a predictive model could make diagnosis easiereasier