BIOMARKERS of MCS and MUSES Syndrome

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BIOMARKERS of MCS and MUSES Syndrome

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Abnormal Medical Tests and Physical Signs Associated with Multi-Sensory

Sensitivity

Oxygen Uptake: unlike people with chemical sensitivity alone, people with

MUSES Syndrome have impaired oxygen uptake. Their arterial blood shows normal

levels of oxygen going into their body, but they cannot absorb it well and so

show higher than normal levels in their veins. This can be measured via

non-invasive VO2max or VO2 resting, or via invasive arterial and venous blood

gases. Our recommended threshold for considering oxygen therapy is when the

gap between arterial and venous dissolved oxygen (PaO2-PvO2) is less than

60mmHg.

Abnormal Medical Tests and Physical Signs Associated with Multiple Chemical

Sensitivity

Listed below are the medical tests physical signs that have been found to be

abnormal in some studies of MCS patients. They are listed alphabetically and

the cited references are listed the below. Some of these biomarkers are used

to confirm the diagnosis of other disorders that commonly overlap with MCS

(such as methacholine challenge testing for asthma, punch biopsy for mast cell

disorders, blood enzyme testing for porphyrin disorders).

No single one of these tests is considered " diagnostic " of MCS, but if

abnormalities are reported or suspected in any of these areas, they should be

fully evaluated and appropriately treated. Some of these biomarkers may be

abnormal at all times while others wax and wane with exposure. Given that MCS

by

definition is a disease provoked by chemical exposure, physicians should

evaluate MCS cases both before (at baseline) and after an offending chemical

exposure Ð either accidentally encountered or deliberately arranged under a

doctor's supervision, preferably as a " blinded' exposure to an odorless gas

like CO2

if inhaled or a tasteless liquid if ingested. Subcutaneous injections and

dermal patches may also be used to test " blinded " reactions to certain

chemicals.

Allergy: increased risk of IgE allergies to mold, pollen, dust, dander, etc

(Baldwin 1998b)

Blood: lhigh 2,3-DPG, low red blood cell mass, low plasma volume, high

plasma lactate, some cases involve a genetic pyrvate kinase deficiency in which

the carrier state is symptomatic (Wilcox 1996),

Breath: elevated carbon monoxide after standard 23 second breath hold, over

3ppm. This is a sensitive but not specific marker as elevated CO also has

been reported in breath of smokers, 2nd hand smokers, people who live with gas

appliances or attached garages, and people with chronic diseases of the

heart, lungs, blood and brain.

Cardiac: tachycardia, other arrhythmia, mitral valve prolapse (Ziem 1997),

abnormal echocardiogram (Bell 1998a, Baldwin 1998a)

Cerebral: reduced blood flow on SPECT (Callender 1993, Heuser 1994),

increased resting alpha on qEEG (Bell 1998b)

Circulatory: small vessel vasculitis (punch biopsy of fingertip),

nontraumatic thrombophlebitis (Rea 1976, Rea 1977), neurally mediated

hypotension (in

undifferentiated CFS patients)

Detoxification: impaired function of Phase I (cP450) and/or Phase II detox

pathway (Ziem 1997); caffeine clearance, salicylic acid conversion,

paracetamol conversion (Monro 1997); low sulphoxidation and low glutathione

(Scadding

1988, McFadden 1996, Ziem 1997), low superoxide dismutase and glutathione

peroxidase (Ziem, unpublished)

Ears: abnormal brain stem auditory evoked potentials (Cary 1997); tinnitus

is commonly reported but not quantifiable

Endocrine: variable hyper or hypo function in thyroid, adrenals and HPA axis

(Levin 1987)

Eyes: photophobia as measured by reaction time; dry eyes or weeping tear

glands in response to exposure

Gastrointestinal: esophagitis, 'nutcracker' esophagus, increased intestinal

permeability, lactose breath test, bacterial overgrowth breath test (Monro

1997)

Immune: chronic T-cell activation, impaired NK cell function, variable

auto-immunity especially elevated ANA (McGovern 1983, Heuser 1992, Ziem 1997),

reduced secretory IgA and other Ig (Ziem 1999)

Mast Cells: increased number on punch biopsy (Heuser 1996), increased

sensitivity to stimuli seen with scratch test, variably abnormal serum tryptase

during reactions (Schwartz 1987) Mast cell punch biopsy has 80% SENSITIVITY

(second highest of any MCS report), SPECIFICITY > 99%

Minerals: numerous deficiencies, especially magnesium, molybdenum,

manganese, zinc, selenium and copper. (Galland 1987, Ziem unpublished).

Musculoskeletal: fibromyalgia tender points (Donnay 1999)

Neurocognitive: impaired learning and/or retention in short-term memory

(visual and verbal), attention span and reaction times (Ziem 1997).

Abnormalities

seen in PASAT, WAIS-R (Ziem 1997), computerized Divided Attention Test (Bell

1995), STROOP tests (Little 1999), Knox Cubes, and in non-dominant hand on

Tactual Performance Test

Nose: degraded nasal epithelium, chronic inflammation, rhinitis and

sinusitus (Meggs 1993b)

Oxygen Uptake: unlike people with multi-sensory sensitivity, aka MUSES

Syndrome, people with MCS alone do not have abnormally low oxygen uptake (and

they cannot be cured by oxygen therapy)

Porphyrin Metabolism: multiple blood enzyme deficiencies, especially ALA-D,

PBG-D, UPG-D (Ziem 1997),

Porphyrin enzyme abnormalities have 86% SENSITIVITY (highest of any MCS

report), SPECIFICITY > 99%

Respiratory: inflammation in larynx & trachea; abnormal methacholine

challenge (Bell 1998a)

Sensory Nerves: altered somatosensory potentials (Hummel 1996), peripheral

neuropathy (Ziem 1997)

Skin: rash in response to chemicals and irritants, hypersensitive to touch,

vibration, and cold; " loose " skin if pinched

Sleep: frequently disrupted with abnormal EEG (Bell 1996)

Vestibular: impaired Romberg and other balance testing (Ziem 1997)

Vitamins: numerous deficiencies, especially in the B series (Galland 1987,

Ziem 1997)

Xenobiotics: various markers of poisoning by heavy metals (lead, mercury,

depleted uranium) and pesticides (chlorinated or organophosphate) may be

detected in urine, stool, blood, hair and/or fat (Heuser 1992)

 

REFERENCES

(abstracts for most of these articles are available free via _PubMed_

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed) )

Compiled by Albert Donnay, 2/1999, rev'd 8/2000

Baldwin, CM and Bell, IR. 1998a. Increased cardiopulmonary disease risk in a

community-based sample with chemical odor intolerance: implications for

women's health and health- care utilization. Arch Environ Health 53: 347-353.

Baldwin CM, Bell IR, O'Rourke M, Nadella S, and Lebowitz MD. 1998b. Allergen

risk ratios for a community sample with and without self-reports of multiple

chemical sensitivity. Chem Senses 20: 661-662.

Bell I.R. Baldwin, C.M. and Schwartz, G.E. 1998a. Illness from low levels of

environmental chemicals: relevance to chronic fatigue syndrome and

fibromyalgia. Am J Med 105: 74S-82S.

Bell, I.R., Schwartz, G.E., Baldwin, C.M., Hardin, E.E. and Kline, J.P.

1998b. Differential resting quantitative electroencephalographic alpha patterns

in women with environmental chemical intolerance, depressives, and normals.

Biol Psychiatry 43: 376-388.

Bell, I.R., Bootzin, R.R., Ritenbaugh, C., Wyatt, J.K., DeGiovanni, G.,

Kulinovich, T., Anthony, J.L., Kuo, T.F., Rider, S.P., Peterson, J.M.,

Schwartz,

G.E. and Johnson, K.A. 1996. A polysomnographic study of sleep disturbance in

community elderly with self-reported environmental chemical odor

intolerance. Biol Psychiatry 40: 123-133.

Bell, I.R., Wyatt, J.K., Bootzin, R.R. and Schwartz, G.E. 1995. Slowed

reaction time performance on a divided attention task in elderly with

environmental chemical odor intolerance. Int.J Neurosci. 84: 127-134.

Callender, T.J., Morrow, L.A. and Subramanian, K. 1993. Evaluation of

chronic neurological sequelae after acute pesticide exposure using SPECT brain

scans. J.Toxicol.Ind.Health 41: 275-284.

Cary, R., Clarke, S. and Delic, J. 1997. Effects of combined exposure to

noise and toxic substances--critical review of the literature. Ann Occup Hyg

41:

455-465.

Donnay A. and Ziem G. 1995. Protocol for diagnosing disorders of porphyrin

metabolism in chemically sensitive patients. Baltimore, MD: MCS Referral &

Resources

Donnay A. and Ziem, G.1999. Prevalence and overlap of chronic fatigue

syndrome and fibromyalgia syndrome among 100 new patients with multiple

chemical

sensitivity syndrome. J.Chronic Fatigue Syndrome. 5:2 [in press]

Galland, L. 1987. Biochemical abnormalities in patients with multiple

chemical sensitivities. Occup.Med. 2:713-720.

Heuser, G. and Kent, P. 1996. Mast cell disorder after chemical exposure.

124th nnual Meeting of the American Public Health Association, New York NY, 20

November 1996 [abstract and presentation]

Heuser, G., Mena, I. and Alamos, F. 1994. NeuroSPECT findings in patients

exposed to neurotoxic chemicals. Toxicol.Ind.Health 10: 561-571.

Heuser G., Wodjani A. and Heuser S. 1992. Diagnostic markers in chemical

sensitivity. In Multiple Chemical Sensitivities: Addendum to Biologic Markers

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Immunotoxicology, 117-138. Washington DC: National Academy Press

Hummel, T., Roscher, S., Jaumann, M.P. and Kobal, G. (1996) Intranasal

chemoreception in patients with multiple chemical sensitivities: a double-blind

investigation. Regul Toxicol Pharmacol 24: Pt 2):S79-86

Levin, A.S. and Byers, V.S. 1987. Environmental illness: a disorder of

immune regulation. Occup.Med. 2: 669-681.

McFadden, S.A. (1996) Phenotypic variation in xenobiotic metabolism and

adverse environmental response: focus on sulfur-dependent detoxification

pathways. Toxicology 111: 43-65.

McGovern, J.J., Jr., Lazaroni, J.A., Hicks, M.F., Adler, J.C. and Cleary, P.

1983. Food and chemical sensitivity. Clinical and immunologic correlates.

Arch Otolaryngol. 109: 292-297.

Meggs W.J., Cleveland C.H., Jr. 1993b. Rhinolaryngoscopic examination of

patients with the multiple chemical sensitivity syndrome. Arch.Environ.Health

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Meggs, W.J. 1993a. Neurogenic inflammation and sensitivity to environmental

chemicals. Environ Health Perspect 101:234-238.

Monro J.M. 1997. Laboratory tests found to be effective in the evaluation of

chemical sensitivity: derived from 12,000 patient evaluations. 32nd Annual

Meeting of the American Academy of Environmental Medicine, La Jolla CA, 24-27

October 1997 [abstract and presentation]

Rea, W.J. 1976. Environmentally triggered thrombophlebitis. Ann.Allergy 37:

101-109.

Rea, W.J. 1977. Environmentally triggered small vessel vasculitis.

Ann.Allergy 38: 245-251.

Schwartz, L.B., Metcalfe, D.D., Miller, J.S., Earl, H., and Sullivan, T.

1987. Tryptase levels as an indicator of mast-cell activation in systemic

anaphylaxis and mastocytosis. N.Engl.J.Med. 316:1622-26

Ziem, G. and McTamney, J. 1997. Profile of patients with chemical injury and

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