Multiple Chemical Sensitivity ... or MUSES Syndrome ?

1
Multiple Chemical Sensitivity... or MUSES
Syndrome ?

Presented to the Occupational Medicine
Residents Seminar Series Environmental
Occupational Health Sciences InstituteRutgers
University, Piscataway NJ 17 February 2004 by
Albert Donnay, MHS, adonnay_at_jhu.eduMCS Referral
Resources, www.mcsrr.org
2
What is Multiple Chemical Sensitivity ?

• 1999 Consensus Definition (Arch Env Health
  199954147-9) 1 MCS is a chronic condition
  
• 2 marked by multiple symptoms in multiple
  organs
• 3 that recur reproducibly
• 4 in response to low levels of exposure
• 5 to multiple unrelated chemicals and
• 6 improve or resolve when incitants are
  removed.
• Best of 7 MCS Definitions at identifying MCS
  cases (McKeown-Eyssen et al, Arch Env Health
  200156406-12)

3
How Many MCS Symptoms Have Been Reported ? List
compiled by JHU Multi-Center Study of MCS
Immunology

• CARDIOVASCULAR 9
• DIGESTIVE 18
• EARS // HEARING 7
• EYES // VISION 12
• GENITO-URINARY 10
• HEAD 6
• MOUTH // TASTE 14
• MUSCULOSKEL. 14
• NECK 3

• NERVOUS SYSTEM 43
• NOSE // SMELL 10
• SYSTEMIC // OTHER 17
• VASCULAR 5
• REPRODUCTIVE 17
• RESPIRATORY 6
• SKIN // TOUCH 7
• THROAT 5
• TOTAL SYMPTOMS 203

4
What Objective Findings Are Reported in MCS ?

• Abnormal Blood Plasma
• Impaired Circulation
• Impaired Heart Function
• Impaired Detox Pathways
• Ear Hearing Abnormalities
• Endocrine Deficiencies
• Eye Vision Abnormalities
• Gastrointestinal Impairment
• Immune System Activation
• Increased Mast Cells
• Mineral Deficiencies

• Musculoskeletal Abnormalities
• Neurocognitive Deficiencies
• Nose Smell Abnormalitites
• Porphyrin Enzyme Abnorm.
• Respiratory Impairment
• Sensory Nerve Impairment
• Skin Tone Abnormalities
• Vestibular Impairment
• Vitamin Deficiencies
• Xenobiotics in Fat, Blood, Urine and
  HairRefs online at www.mcsrr.org

5
Who is Funding This MCS Research ?

• Most MCS-related papers do not acknowledge any
  funding !
• But 10 US federal agencies fund over 25M per
  year ATSDR, CDC, DOD, DOE, DVA, EPA, NIDCD,
  NIEHS, NIH NIOSH
• US Dept of Defense also funds MCS studies of UK
  veterans
• State governments in California, Maryland,
  Missouri, New Jersey, New Mexico Washington
  have funded MCS studies
• Both patient support groups (eg. CIIN) and
  chemical industry front groups (eg. ESRI) have
  funded MCS conferences and pilot studies that
  reflect their respective biases.

6
Which View Predominates Physical or Psychiatric
?

• OverlapsOnly 11 of First Authors and
  30 of Publishers have ever supported more than
  one view !!!

7
On What Do All Agree? Prevalence is Very High !

• 5 US studies find 28 - 37 of adults say they
  are especially sensitive to common chemical
  exposures
• 4 US studies find 15 - 17 say theyre
  unusually sensitive
• 6.3 in CA and 1.9 in NM say they have been
  diagnosed by a medical professional with MCS or
  environmental illness
• US, Canadian and UK studies of Gulf War veterans
  all find an increased prevalence of (still
  undiagnosed) MCS with a relative risk of 2 to 4
  compared with undeployed era controls
• Whatever cause(s), must be very common and moreso
  in war.

8
But is MCS Only a Disorder of Chemical
Sensitivity ?

• NOT JUST ODORS LIGHT SOUND HYPERSENSITIVITY ar
  e very strongly associated with MCS p lt 0.00001
  (Miller, Tox Ind Health, 199915370-85)
• When asked, many MCS patients also report chronic
  hypersensitivity to
• SPICY FOODS // FLAVORS
• TOUCH // PRESSURE // PAIN
• HOT or COLD WEATHER
• ELECTROMAGNETIC FIELDS
• HEAVY METALS (NICKEL JEWELRY)
• MENTAL or PHYSICAL EFFORT // STRESS OF ANY KIND

In poll of MCS patients in London audience at
this point, approx. 75 reported having all these
sensory sensitivities since ill. Only one (an
American) reported having just chemical
sensitivity, aka pure MCS.
9
Might MCS Be Something Else as Critics Claim ?

• MCS not new or unique in English or French
  medical literature.
• At least 136 similar syndromes Discovered
  before since.
• Few acknowledge any relation to any others, past
  or current.
• Few propose any specific cause, etiology,
  biomarker or cure.
• Most names never widely adopted or eventually
  abandoned.
• But some are still in use and many MCS cases are
  still being diagnosed by one or more of them
  depending on the doctor.
• History reveals both consistency of underlying
  syndrome and great inconsistency of evolving
  medical awareness, proving doctors rarely ever
  discover any NEW disorders, just ones they
  forgot, were never taught or did not bother to
  look up !

10
First Described in 1733 by Dr. George Cheyne as
the English Malady (EM), aka The Vapours

• To enumerate all the almost infinite Symptoms,
  Degrees and Kinds of Vapours is impossible, and
  perhaps very little to the Purpose.
• In general the symptoms are many, various,
  changeable, shifting from one Place to another,
  and imitating the Symptoms of almost every other
  Distemper described.
• Those who suffer are all of weak Nerves, have
  a great degree of sensibility are quick
  Thinkers, feel Pleasure or Pain the most readily,
  and are of most lively imagination.
• Not withstanding all this, the Disease is as
  much a bodily Distemper as the Small-Pox or a
  Fever.
• Worst in winter cities. Blamed on bad air, bad
  diet bad habits.

11
Some Symptoms of E.M. Cited by Dr. Cheyne

• Sometimes there is an Inflation, and an actual
  visible Swelling, to a very considerable Bigness,
  in the Stomach to be seen, especially in the Sex
  women
• a Coldness or Chilliness upon the Extremities,
  and sometimes Flushing and Burning in the Hands
  and Feet, Cold Damp Sweats, Faintings, and
  Sickness
• Head-aches either behind or over the Eyes
  Flies and Atoms dancing before the Eyes, a Noise
  like the dying Sounds of Bells, or a Fall of
  Water, in the Ears Yawning, and Stretching, and
  sometimes a Drowsiness or Lethargy, at other
  times Watching and Restlessness,
• and several other Symptoms, which it is
  impossible to enumerate. Some have but a few of
  these Symptoms, and some all of them, and a great
  many more. emphasis in the original

12
36 Focus on Allergy, Sensitivity, Neurology or
Toxins

• 1733 The English Malady aka The Vapours
• 1769 Dysesthesia
• 1837 Neuropathy of Nervousness
• 1849 Nervosisme (France)
• 1861 Ménière's Disease
• 1869 Neurasthenia gt1K
• 1892 Hyperaesthesia
• 1894 Autointoxication
• 1921 Chronic CO Poisoning
• 1930 Heat, Cold and Effort
  Sensitiveness

1930 Allergic Toxemia 1945 Allergic Fatigue
and Weakness 1945 Hyperventilation
Asthma 1952 Allergy of Nervous System 1954 Cerebra
l Allergy 1956 Specific Adaptation Syn. 1957
Familial Dysautonomia gt9K 1965 Minimal Brain
Dysfunction 1965 Delayed Hypersensitivity Reacti
on gt4K 1973 Sensory Integrative
Dysfunction 1K 1000 references on PubMed

13
Allergy, Sensitivity, Neurology or Toxins
continued

• 1978 Chemical Hypersusceptibility
• 1979 Perinatal Hypoxic- Ischemic Cerebral Syn.
• 1982 Total Allergy Syndrome
• 1983 Sick Building Syndrome
• 1985 20th Century Syndrome
• 1985 Allergic Irritability Syn.
• 1985 Environmental Hypersensitivities
• 1986 Hypersensitivity Syndrome
• 1987 Darkroom Disease
• 1987 Multiple Chemical Sensitivity lt1K

1990 Chronic Habitual Hyperventilation
Syn. 1994 Gulf War Syndrome 1996 Multi-Organ
Dysesthesia 1998 Toxicant Induced Loss of
Tolerance 1999 Eco-Syndrome 1999 Multi-Sensory
Sensitivity, aka MUSES Syndrome
14
30 Focus on Variations of 1869 Neurasthenia

• 1875 Spinal Neurasthenia
• 1881 American Nervousness
• 1886 Sexual Neurasthenia
• 1887 Gastric Neurasthenia
• 1889 Neurasthenia Praecox (aka Male N.)
• 1890 Psychosomatic Neurasthenia
• 1891 Female Neurasthenia
• 1893 Syphilitic Neurasthenia
• 1895 Senile Neurasthenia
• 1897 Traumatic Neurasthenia
• 1898 Encephalasthenia

• 1903 Disease of the Century
• 1906 Tropical Neurasthenia
• 1907 Endocrine Neurasthenia
• 1907 Ocular Neurasthenia
• 1908 Digestive Neurasthenia
• 1909 Battleship Neurasthenia
• 1968 Pseudoneurasthenic Syndrome
• 1976 Organic Neurasthenia
• 1976 Neurasthenic Musculoskeletal
  Pain Syndrome

15
Variations of Neurasthenia continued

• 1980 Neurasthenic Neurosis
• 1988 Neurasthenic Fatigue
• Types of Unknown Origin and Date Cited by
  Secondary Sources
• and/or Listed in Stedmans Medical Dictionary
• Angiopathic Neurasthenia
• Cardiac Neurasthenia
• Cardiovascular Neurasthenia
• Insania Neurasthenia
• Neurasthenia Chemicorum
• Neurasthenia Gravis
• Post-viral Neurasthenia
• Pulsating Neurasthenia

16
42 Focus on Psychiatry or Behavior

• 1765 Nervous, Hypochondriac or Hysteric
• 1766 Hypochondriasis, aka Hyp or Hypo
• 1859 Briquets Syndrome
• 1871 Hebephrenia
• 1895 Anxiety Neurosis gt28K
• 1904 Phrenasthenia
• 1906 Psychasthenia
• 1912 Autism gt6K
• 1914 Shell Shock Syndrome
• 1916 Battle Fatigue Syndrome
• 1918 War Neurosis
• 1930 Generalized Anxietygt1.5K

1938 Suburban Neurosis 1944 Aspergers
Syndrome 1947 Old Sergeant Syndrome 1951
Munchausens Syn gt1K 1957 Psychogenic Dyspnea
and Hyperventilation 1957 Traumatic
Neurosis 1965 Asthenic Neurosis 1965
Psychogenic Pain Syn 1966 Psychovegetative
Syn 1966 Accident Neurosis 1966 Hyperactive
Child Syn 1967 Post Accident Anxiety Syn 1968
Chronic Factitious Illness
17
Psychiatry or Behavior continued

• 1968 Pseudo Combat Fatigue
• 1968 Hyperkinetic Behavior Syn
• 1973 Ecologic Mental Illness
• 1973 Psychalgia
• 1974 Epidemic or Mass Hysteria
• 1977 Pinocchio Syndrome
• 1978 Mass Psychogenic Illness
• 1978 Psychic Possession
• 1980 Post Traumatic Stress Disorder gt6.5K
  (count incl. Traumatic Neurosis)
• Attention Deficit Disorder
• 1981 Pervasive Developmental Disorder gt7K

1981 Somatization Dis. gt7K 1988 Attention
Deficit Hyperactivity Disorder, aka ADHD,
gt6K (count includes ADD HCS) 1995
Environmental Somatization Syndrome 1996 Iatrog
enic Hypochondriasis 1996 Idiopathic
Environmental Intolerances (not
WHO) 1999 Functional Somatic Syndromes
18
28 Focus on Infection, Trauma, Fatigue or Pain

• 1941 Chronic Fatigue
• 1950 Epidemic Neuromyastheniaaka Icelandic
  Disease, aka Akureyri Fever
• 1956 Encephalomyelitis simulating
  Poliomyelitis, aka Royal Free Hospital
• 1956 Benign ME, aka Myalgic
  Encephalomyelitis lt100
• 1957 Epidemic Postinfectious Neuromyasthenia
• 1958 Irritable Colon Syn
• 1959 Irritable Bowel Syn gt3.5K

• 1857 Remittent Fever, aka Crimea Fever
• 1866 Railway Spine
• 1871 Irritable Heart, aka DaCostas Syndrome
• 1887 Undulating Fever, aka Malta Fever aka
  Mediterranean Fever
• 1904 Fibrositis
• 1934 Chronic Brucellosis
• 1936 Morbid Industrial Fatigue
• 1938 Neurocirculatory Asthenia, aka
  Effort Syndrome

19
Infection, Trauma, Fatigue or Pain continued

• 1960 Temporomandibular Joint Pain gt3K
• 1970 Myofascial Pain Syndrome gt4.5K
• 1975 Fibromyalgia gt2.5K
• 1982 (Familial) Chronic Mononucleosis
• 1984 Chronic Active Epstein Barr Virus
• 1986 Sporadic Postinfectious Neuromyesthenia
• 1987 Chronic Fatigue Syndrome gt2K
• 1988 Chronic Fatigue and Immune Dysfunction
  Syndrome
• 1990 3 types of Asthenia Episodic, Recurrent
  and Chronic
• 1997 Chronic Pain and Fatigue Syndrome
• 1998 Chronic Multi-Symptom Illness
• 2001 Chronic Neuroendocrineimmune Dysfunction
  Syndrome

20
In USA, Not Even Discovered By Physicians
First Described in the Tales of Edgar Allan Poe

• 1832 1st Report of Symptoms in Loss of Breath
• 1839 Over 50 Specific Symptoms in Fall of House
  of Usher
• 1839 1st Report of Facial Sign in The Man Who
  Was Used Up
• 1840 1st Report of Cause in Philosophy of
  Furniture
• 1843 1st Report of Psych Misdiagnosis in The
  Tell Tale HeartNow have I not told you that
  what you mistake for madnessis but overacuteness
  of the senses?
• 1844 1st Report of Successful Therapy in
  Premature Burial
• 1849 Poe dies as he predicted of Congestion of
  the Brain

21
But Only Charles Baudelaire in Paris Recognized
Gas Lighting as the Cause of Poes Symptoms

• "All the documents I have read led me to the
  conviction that for Poe the United States was
  nothing more than a vast prison which he
  traversed with the feverish agitation of a being
  made to breathe a sweeter air
• nothing more than a great gas lighted
  nightmare
• and that his inner, spiritual life, as a poet or
  even as a drunkard, was nothing but a perpetual
  effort to escape the influence of this unfriendly
  atmosphere."
• Gas light made from coal contained 5 to 50
  Carbon Monoxide
• CO exposure limits today 0.0009 outdoors,
  0.005 occupational

22
Do you know why I so patiently translated Poe?
It was because he was like me.

• REVERSE IMAGE
  TRUE IMAGE
• EDGAR ALLAN POE CHARLES
  BAUDELAIRE

23
And there was perceptible about them his eyes,
ever and anon, just that amount of interesting
obliquity EA Poe, 1839
24
Many Other 19th Century Creative GeniusesAlso
Apparently Poisoned by CO from Gas Lighting
Oscar Wilde
George Bernard Shaw
25
Evidence of Van Goghs gas light poisoning, like
Poes Tell Tale Face and his Purloined Letter,
is hidden in plain view
Gaughins Chairpainted by Van Gogh in their
gas-lit Yellow House in Arles in Nov. 1888, one
month before Van Gogh cut off his ear.
26
Of Course, Not Just Men and Not Just Then
Jane Austen
J.K. Rowling
27
Tell Tale Face Noted in Certain Nervous
Disorders Even Before Introduction of Gas
Lighting
Her left eyelid remained permanently half
closed and the right angle of her mouth was
considerably drawn aside. Edward Percival, 1813
28
Englands Most Famous Unrecognized Case ?
King George III 1738 1820
Presumed now to have inherited porphyria, but CO
poisoning was never considered since his illness
began decades before gas lighting.
29
Most Likely CO Source Prior to Gas Lighting
Coal bed warmer on display in bedroom of KGIIIs
grandmother, Queen Caroline, Hampton Court
30
CO Role in MCS etc Not Yet Widely Recognized
Excluding Literature on Chronic CO Poisoning,
CO is mentioned in only 11 of 90,000 other
articles

• Fibromyalgia Syndrome 2 both claim not CO
• Chronic Fatigue Syndrome 2 1 claims not CO
  the other says from CO so not
  true CFS !
• Generalized Anxiety 1 claims not CO
• MCS / MUSES Syndrome 1 claims from CO
• Post Traumatic Stress Disorder 2 both claim not
  CO
• Somatization Disorder 3 all 3 claim not
  CO Even most MCS patients fail to recognize any
  CO connection, perhaps because CO is odorless,
  tasteless and invisible.

31
First Peer-Reviewed Publication Proposing
Connection Between MCS, CO and Poe

• Donnay, A. International Journal of Toxicology
  199918(6)383-392
• On the recognition of multiple chemical
  sensitivity in medical literature and government
  policy.

32
Subsequent Citations
33
CO is Well Known as The Great Imitator and
Already Well Documented to Cause or Worsen

• Anemia
• Angina
• Anosmia (loss of smell)
• Asthma
• Birth Defects
• Blindness
• Deafness

• Depression
• Diabetes
• Hallucinations of all kinds
• Heart Disease
• Mental Retardation
• Parkinsons
• Psychoses

34
Why So Many Syndromes? CO is Both Ubiquitous
Neurotoxin Ubiquitous Neurotransmitter

• CO is 1 Cause of Unintentional Toxic Deaths in
  USA
• CO is 1 Cause of Unintentional Toxic Poisonings
  in USA
• CO is 1 Air Pollutant in USA more tons/year
  than all others primarily from industry,
  vehicles, fires, combustion appliances
• CO is also produced systemically by all mammals
  from heme breakdown by Heme Oxygenase, the
  Universal Stress Enzyme.
• HO-1 is greatly induced by exposure to any type
  of stress heat, bright light, noise, odors,
  drugs, alcohol and other chemicals, trauma,
  infection, electro magnetic fields, etc.
• Endogenous CO is not just bound to hemoglobin but
  bioactive in over 90 pathways in range of 1 to
  10ppm

35
Increased endogenous production of CO from heme
breakdown is documented in

• Heart Attack
• Heat Stress / Stroke
• Infections
• Methylene Chloride Poisoning
• Parkinsons
• Pre-Menstrual Syndrome
• Upper Respiratory Tract Infections

• Allergy
• Altitude Sickness
• Alzheimers
• Anemia
• Asthma
• Bronchiectasis
• Cystic Fibrosis
• Diabetes

36
All CO-Related Disorders Share Biomarker
Elevated Level of CO in End-Tidal Breath

• Normal bCO (maximum after holding breath 20 to 25
  seconds) Healthy Relaxed Non-Smokers
  0-2 ppm
• Mildly Elevated bCO Borderline Abnormal for
  Non-Smokers 3-4 ppm
• Moderately Elevated bCO Smokers and People
  with CO Disorders 5-24 ppm
• Highly Elevated bCO Recently Smoked or CO
  Poisoned 25-999ppm
• All healthy adults have approx. noon peak and
  midnight trough.
• Higher after supplemental oxygen if standing
  vs. sitting vs. supine.

37
How CO Causes MUSES Syndrome

• HO-CO controls sensitization and habituation to
  stressors of all kinds.
• Chronic repeated exposures to any stressor
  induces habituation, so that higher doses are
  tolerated with less or no sensory awareness.
• Isolated acute exposures (and de-habituation, as
  in ex-smokers) induce sensitization, so that
  lower doses are less tolerated with more sensory
  awareness.
• While exogenous stressors (heat, drugs, alcohol)
  may be avoided, endogenous CO produced by HO in
  response to ANY stressor cannot.
• So if/once sensitized to CO via exogenous
  poisoning or dehabituation, increased sensory
  awareness may be provoked by ANY stressor.
• Result is multi-sensory sensitivity to odors,
  lights, sounds, foods, etc aka MUSES Syndrome
  (aka MCS in adults or Autism in children).

38
Where to Look for Evidence of CO Poisoning Today

• Test CO in end tidal breath after holding
  breath for 20 seconds (healthy non-smokers are
  0-2 ppm chronic diseased are 5-10ppm).
• Test ABG VBG at same elbow to see if
  PaO2-PvO2lt55mmHg
• Monitor indoor CO levels with a digital detector
  near combustion appliances, especially unvented
  ones like gas ovens and gas logs.
• Monitor CO levels inside homes with attached
  garages after vehicles are started with the door
  open, driven out the door closed.
• Monitor CO levels in motor vehicles while
  driving and parked idling.
• Look for asymmetrically drooping eye and mouth
  that mark The Tell Tale Face of CO Poisoning and
  ask about multi-sensory sensitivity to lights,
  odors, noises, tastes, touch and heat or cold.

39
Curing MUSES Syndrome Treatments Proposed by
Cheyne, Poe and Donnay

• Dr. George Cheyne in The English Malady, 1733
• Seldom any lasting or solid cure is performd
  till they have sucked in and incorporated the
  sweet balmy clear Air of the Country. Diet
  will do infinitely more than Exercise and have
  more lasting Effects, but both should be joined.
  Certainly the best of all is where Amusement or
  Entertainment of the Mind is joined with Bodily
  Labour and Constant Change of Air.
• Edgar Allan Poe in The Premature Burial, 1844
• I took vigorous exercise. I breathed the free
  air of Heaven. I thought upon other subjects
  than Death. I discarded my medical books.
• Donnay in CO Dx-Tx Protocol, 2000 O2 _at_ 6 L/m, 2
  hr/day for 3 mo.

40
Conclusion Distinguish MUSES from MCS !

• MCS associated only with sensitivity to
  chemicals is rare.
• Most MCS cases also report multi-sensory
  sensitivity, aka MUSES Syndrome, consistent with
  descriptions of over 130 other similar syndromes
  published since 1733.
• Sentinel case in USA of Edgar Allan Poe was most
  likely caused by chronic CO poisoning from
  exposure to gas lighting.
• MUSES syndrome caused by chronic CO poisoning is
  associated with a Tell Tale Face and
  PaO2-PvO2lt55mmHg.
• Oxygen uptake deficiency and MUSES symptoms may
  be treated successfully with daily supplemental
  oxygen at home.

41
Published Critiques, Rebuttals Objections To
Donnays Poe, CO and MUSES Theories

Unpublished Critiques, Rebuttals Objections To
Donnays Poe, CO and MUSES Theories