Sick Building Syndrome

is a distinct clinical
entity: we have the
proof
Senate Health, Education, Labor and Pension
Committee
1/12/06
Ritchie C. Shoemaker MD
Center for Research on Biotoxin Associated Illnesses
Pocomoke, Md
 Proof of Causation
 Koch’s Postulates
 Repetitive exposure trials
 Double blinded, placebo controlled
trials
 Prospective hyperacute acquisition
studies
 Reproducibility at multiple sites
 Peer-reviewed publications
 EVIDENCE-BASED MEDICINE!
 Treatment leads to
definition
 Priorstudies showed there were
health problems in patients exposed
to water-damaged buildings hosting
toxigenic organisms, including fungi
 Effective therapy, beginning with
cholestyramine, gives us the ability
to correct and then study the disease
 Multiple sequential steps
 Application of causation
 Case definition
 Individual cases
 Screening
 Documentation of acquisition of
illness
 Risk management
– High risk occupations
– New hires in water-damaged buildings
– Verify effective remediation occurred
 Case definition-1
 103 patients /43 buildings (Brescia, Italy)
 156 patients /150 buildings (Saratoga, NY)
 21 patients/ 5 buildings (NT and T)
 288 patients /125 buildings (ASTMH)
 26 patients/5 buildings (DB-PC trial)
 20 patients in hyperacute model (ASM
biodefense conference)
 40 patients, eight year follow-up
 152 patients, age under 19
 Case definition-2
FIRST TIER

 Potential for exposure

 Multisystem, multisymptom illness
 Absence of confounders
 Differential diagnosis
 Case definition-3
SECOND TIER

 Genetic susceptibility; HLA DR by PCR

 Hypothalamic impairment; low MSH
 Neurotoxic illness; VCS deficit
 Cytokine activation; MMP9 elevation
 Pituitary involvement
– ACTH/cortisol
– ADH/osmolality
 Why use such unusual
tests?
 Biologically produced neurotoxins activate
innate immune responses NOT acquired
immune responses
 Illness is hidden by looking only at
“standard lab tests”
 Illness is obvious to anyone when looking
at what is wrong
 Tests might look unusual, but are readily
available to any physician; insurance
approved, Medicare approved
 Is mold illness rare?
NO!

 We see 10 new patients a week

 Total in treatment data base exceeds
2900 mold illness patients
 Total biotoxin illness patients
exceeds 5000
 We have data on over 4000 controls
 The Biotoxin Pathway High cytokine levels in the capillaries attract white blood
cells , leading to restricted blood flow, and lower oxygen
Capillaries levels. Reduced VEGF leads to fatigue, muscle cramps,
In genetically susceptible people , biotoxin binds to fat-cell receptors, and shortness of breath (may be over-ridden by
causing continuing, unregulated production of cytokines. replacement with erythropoietin).

Bo
d Immune system symptoms
bio y ac
t ox t o qu Surface
org in-p xins ires Biotoxin (“Toll”)
Increased Cytokines
foo anis r odu or (HLA susceptible) Fat Cell Patients with certain HLA genotypes (immunity-
c receptor
or d, wa ms f ing related genes) may develop inappropriate
ins te rom immunity. Most common are antibodies to:
ec r, a
t b ir, -- Myelin basic protein (often from fungal
ite
s biotoxins; affects nervous-system functions)
-- Gliadin (affects digestion)

Inc
Fat cells then -- Cardiolipins (affects blood clotting)

rea
I nc
(H Bi produce more The “complement” alternative immune pathway

se
LA oto

rea
leptin, leading to may be triggered (detectable as an increase in

dL
su xin

se
sce levels of the proteins C3a C4a).

ep
obesity (which

dC
pt i

tin
ble doesn’t respond to

yto
)
exercise and diet).

k in
Cytokine-related symptoms

es
Nerve cell Excessive
cytokine levels
can damage leptin Leptin High levels of cytokines produce flu -like
receptors in the receptor Damaged leptin symptoms: Headaches, muscle aches , fatigue,
Biotoxins have direct effects, including hypothalamus. receptors lead to unstable temperature, difficulty concentrating.
impairment of nerve cell function. One reduced production by High levels of cytokines also result in increased
Hypothalamus levels of several other immune-response related
result is poor performance on contrast the hypothalamus of
Bio t HL le)

sensitivity test . MSH, a hormone with substances, including TNF, MMP-9, IL-1B, and
su
(no ept i

VIP AVP PAI-1. MMP-9 delivers inflammatory elements

t ox A

many functions.
sc

in

from blood to brain, nerve, muscle, lungs, and

joints. It combines with PAI-1 in increasing clot
b

formation and arterial blockage.

Removal from
the body
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.
© G. Alexander 2004
Sleep
disturbance
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.
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.
Reduced
MSH
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 .
Reduced ADH
Stage 1:
Reduced MSH can cause the Biotoxin effects
pituitary to produce lower levels
of anti-diuretic hormone (ADH),
Stage 2:
leading to thirst, frequent Cytokine effects
urination, and susceptibility to
shocks from static electricity .
Stage 3:
Reduced VEGF
Reduced sex hormones
Reduced MSH can cause the Stage 4:
pituitary to lower its Immune effects
production of sex hormones.
Stage 5:
Changes in cortisol and Low MSH
ACTH levels
Stage 6:
The pituitary may produce elevated
Resistant Staph bacteria
levels of cortisol and ACTH in early
stages of illness , then drop to
excessively low levels later . Stage 7:
(Patients should avoid steroids such Pituitary hormone effects
as prednisone, which can lower
levels of ACTH.)
Rev. 10, 12-12-05
 Sx CLUSTER ANALYSIS
 Fatigue  Appetite, body
 Weak, assimilation, temperature regulation,
aching, headache, light urinary freq.
sensitivity  Red tearing eyes,
 Memory, words blurred vision, sweats,
 Concentration mood, ice-pick pains
 Abdominal pain,
 Joint, AM stiff, cramps
diarrhea, numbness
 Unusual skin sensations, 
Tearing, disorientation,
tingling
metallic taste
 Shortness of breath,  Static shocks, vertigo
sinus
 Cough, thirst, confusion
 Total Symptoms

Average
  N= Symptoms

Controls 239 2.7

Cases
Pediatric 288 19.8
controls 40 1.2
Pediatric cases 112 12.2
Testing from Neurotoxicology
 Visual Contrast Sensitivity (VCS)
– used over 40 years by DOD (Air Force)
and in studies of non-biological toxicants
– Reproducible, reliable, portable, non-
invasive, cheap!
– Just about the best marker beyond 4
days of biotoxin-associated/cytokine
illness
Visual Contrast Sensitivity
 Non-invasive measure of contrast
 Neurologic function of optic nerve
 Eliminates near, far, color, static, motion,
peripheral vision
 Visual acuity better than 20/50
 Controlled light > 70 foot lamberts
 Used in prior studies for
screening/monitoring
 Measuring Visual-Pattern Detection Function:
Visual Contrast Sensitivity
VCS
High to Low Contrast

Acuity

Low to High Spatial Frequency (Cycles per Degree of Visual Arc)

 VCS results

  N= A B C D E

Controls 239 77.5 124.3 136.8 68.5 27.0

Cases 288 37.1 77.4 89.6 56.5 18.3 

Pediatric
cases  65 60.8 100.2 63.5 33.5 15.7
Previous
cases 156 23.9 80.9  97.7  62.3  16.1
 HLA Disequilibrium,
Relative Risk > 2.0
Control Cases
HLA-DR ADULT CHILD
4-3-53 - 3.6 4.4
7-2/3-53 - 2.3 2.1
11-3-52B - 2.9 5.3
12-3-52B - - 2.6
13-6-52ABC - 2.1 -
17-2-52A - 2.6 -
19 OTHER
LINKAGES - - -
N= 457 260 110
 RESULTS: Parameters of
Diagnostic Significance:
p<0.001
Adult Child

  ill well ill well

MSH, mean 15.3 23.2 9.4 45.6

MMP9, mean 506 225 419 187
VEGF % < 31 38 0 27 0
VEGF % >200 15 0 17 0
ADH/osmo dys 65% 14% ND ND
ACTH/cortisold
ys 44% 6% ND ND
MARCoNS + 80% 3% ND ND
 RESULTS: Parameters of
Diagnostic Significance:
p<0.001
Adult Child
  ill well ill well

C3a > 1100 285 757 102

C4a 7287 631 4239 553

IL-10 10.2 0.5 8.6 0.3
IL-1B 5.9 0.8 4.3 0.5
Interferon alpha 398 14 ND ND
Erythropoietin % <
7.3 25 3 ND ND
Erythropoietin % >
27.7 9 3 ND ND
 Cases by Wingspan

50
40
30
20
10
CASES WS>HT CASES, n=120 (63%)
0IgA
IgG CONTROLS WS>HT, n=19 (19%)
AC IgM
LA IgA CASES WS<HT, n=72
IgG
AG CONTROLS WS<HT, N=81
A
MB
P
 Pediatric Autoantibodies

ACLA AGA
  IgA IgG IgM IgA IgG
Controls
N=40  0  0  3% 3%   3%
Cases
N=50  6% 12%  16%   12% 58% 
 Mold toxin illness isn’t allergy
Mean IgE, by illness, all patients

  Cases N= IgE
Controls No illness 234 24
Mold cases Confirmed case 367 31
Inhaled steroids + 1
Asthma other med, > 6
cases months/year 45 567
Nasal steroid + 1
Nasal other med, > 6
allergy months/year 38 432
 CONCLUSIONS
 Mold illness is a distinctive, readily recognizable
clinical entity in adults and children

 Significant objective differences exist between

cases and controls

 Findings support inflammatory cascades initiated

by toxin exposure in genetically susceptible
patients

 Abnormalities in innate immune responses point

the way to additional interventions

 Use of a predictive model could make diagnosis

easier