| |
N7GCW > VETS 26.03.05 02:56l 355 Lines 22088 Bytes #999 (0) @ WW
BID : 40273_WA7V
Read: GUEST
Subj: Porphyria - caused by Agent orange
Path: DB0FHN<DB0FOR<DB0SIF<DB0EA<DB0RES<ON0AR<VK6HGR<ZL2TZE<WA7V<WA7V
Sent: 050325/1726z @:WA7V.#SEWA.WA.USA.NOAM [Walla Walla] $:40273_WA7V
Sept 11, 2004
Chemical Injury and Disorders of Porphyrin Metabolism
Some chemically-injured patients with Multiple Chemical Sensitivity
(MCS) show disturbances in their body's system for making heme, which is
the primary component of hemoglobin in red blood cells. Their lab tests
reveal abnormal activity in one or more of the eight enzymes involved in
heme production. Since most heme is made in the bone marrow, these
"disorders of porphyrin metabolism" are usually found there or in the
liver. They can have a disruptive effect on numerous processes that rely
on heme and hemoglobin. Of clear concern to MCS patients are the
"cytochrome P450" enzyme system, which uses heme to detoxify chemicals
in the liver and other vital organs, and the oxygen transport system,
which relies on hemoglobin to carry oxygen from the lungs to other body
organs.
Porphyria, Porphyrinuria and Porphyrinopathy
The term porphyria (pour-'fury-a) refers specifically to a group of
diseases in which cells in the liver and/or bone marrow (primarily) are
unable to properly carry out all the steps involved in making heme, due
to an inherited defect (or "inborn error") in one or more of the eight
enzymes involved. The symptoms that result may involve any part of the
nervous system (central, peripheral and autonomic) or just the skin or
both. Symptoms are triggered by exposure to sunlight (in photosensitive
cases) and/or by exposure to "porphyrogenic" drugs or chemicals,
infections and other stressors. When the heme-making pathway is
disrupted in this way, the excess porphyrins which are no longer
metabolized start to accumulate in certain body organs where they can
have toxic effects.
The most common type is Porphyria Cutanea Tarda, or PCT, which is one of
four non-acute porphyrias. Patients with PCT and the other non-acute
porphyrias have a variety of skin symptoms as a result of often severe
"photosensitivity" to sunlight. PCT also may be acquired in response to
toxic drug or chemical exposure and is made worse by such exposures. (In
1993, the Department of Veterans Affairs accepted an Institute of
Medicine recommendation to pay compensation to Vietnam Veterans with
PCT, on the assumption that their PCT was most likely caused or
aggravated by exposure to the dioxin in Agent Orange.)
There also are four "acute" types of inherited porphyria which may
display an even wider variety of symptoms. They all feature neurological
problems and many also have psychological and/or skin symptoms. In three
of these types, an estimated 90% of those with the inherited enzyme
deficiency have no symptoms until their disease is triggered, often in
mid-life, by some toxic drug, chemical or metal exposure or by some
internal stress such as liver disease, hormonal changes, or dieting. In
acute types (and in PCT), once symptoms begin they usually continue in
response to many kinds of exposures and often include chronic as well as
acute aspects.
The term porphyrinuria (pour-'frin-ur-E-a) is used to categorize
disorders of porphyrin metabolism and excretion that are acquired from
diseases, drugs or chemicals with or without inherited enzyme
abnormalities. These porphyrin disorders usually are found in the liver
and are called coprophyrinuria when limited to coproporphyrins. Physical
symptoms may be chronic, evident only during periods of acute attack,
both chronic and acute, or they may be absent altogether. Drugs and
chemicals can cause porphyrinurias by triggering the cytochrome P450
system which in turn can overload the heme pathway. A secondary
porphyrinuria or coprophyrinuria is a porphyrin abnormality that occurs
secondarily to some other disease which usually test positive for some
but not all of the diagnostic markers associated with true porphyrias.
The broader term "porphyrinopathy" is used here to refer to any disorder
of porphyrin metabolism, inherited or acquired. The porphyrinopathies
being seen in chemically-sensitive patients do not fit the patterns of
any known type of inherited porphyria. This suggests that they may be
the result of an acquired abnormality, due either to the direct effects
of a chemically-induced porphyrinopathy or the secondary effects of some
other disease.
What kinds of symptoms are seen in Disorders of Porphyrin Metabolism?
The "acute" porphyrias always display neurological symptoms affecting
the central, peripheral and/or autonomic nervous systems. These may
include any combination of abdominal pain, nausea, vomiting,
constipation, seizures, headaches, difficulty concentrating, personality
changes, weakness and aching in muscles and joints, unsteady gait, poor
coordination, numbness/ tingling of arms and legs, retaining fluids,
rapid heart rate, increased blood pressure, increased sweating, and
intermittent fever.
Acute and chemically-acquired cases also show increased sensitivity to a
long list of exposures that may both bring on symptoms and make them
worse. These include certain medications (the focus of much porphyria
research), toxic chemicals (such as PCBs and dioxin), alcoholic
beverages (including beer and wine), other liver diseases (like
Hepatitis C and cancer) as well as more subtle factors like hormonal
changes and a low carbohydrate diet. (Skipping meals and dieting make
symptoms worse, while chemicals that mimic the female hormone estrogen
are known to trigger acute porphyrias--both of which may contribute to
the higher incidence of acute porphyrias in females.) There is also one
report documenting acute skin sensitivity to copper in dental patients
with coproporphyria. (Copper is found in significant amounts in the
silver and gold used for both dentistry and jewelry, and skin
sensitivity can be tested easily by wearing a copper bracelet; if
sensitive, symptoms should appear in a few minutes to a few hours.)
When the skin is involved, as it is in all non-acute and some acute
types, symptoms from sensitivity to sunlight may include a wide variety
of problems such as rashes, blisters, changes in skin pigment, changes
in facial hair, and fragile skin that injures more easily.
Porphyrinopathy patients also may occasionally notice discolored urine,
either dark brown or pink to red ("port-wine" colored) and not due to
blood. It is from this sometimes dark purplish color--"porphyra" in
Greek--that porphyria takes its name. (In the "Madness of King George,"
a 1995 film about the acute porphyria that afflicted King George III,
the urine is portrayed as blue.) Any change in urine color is most
likely to occur during an illness reaction, and the dark color may be
more obvious after the urine has been left standing for a few hours
exposed to light or heat. (None of the underlined symptoms above would
be expected in cases of MCS unless due to a disorder of porphyrin
metabolism.
Some persons with "acute" types of porphyria excrete porphyrin
substances in the urine and/or stool only in response to exposures that
make them ill. Their tests are more likely to show changes in the first
2 to 3 days after the onset of a reaction. Thus, urine and stool testing
is most sensitive and accurate during that time. Dr. Ziem recommends you
not induce a reaction, but have the lab form, and when a reaction
occurs, go for the testing. The form explains how to collect the
specimens.
How are Disorders of Porphyrin Metabolism diagnosed?
Each type of porphyria is defined by specific symptoms and diagnostic
signs or "markers," although these overlap considerably in some types.
If a disorder of porphyrin metabolism is suspected on the basis of
symptoms, diagnostic tests are usually ordered of urine and stool and
sometimes also of blood and plasma to look for characteristic
abnormalities of enzyme(s), porphyrin(s) and/or porphyrin "precursors"
(substances called ALA and PBG which are measured to check the activity
of the first two enzymes in the heme pathway). If acute porphyria is
suspected, this testing must be done when patients symptoms are worse
than usual. Chemically-acquired porphyrinopathies are more variable and
often mimic one or more elements of the different inherited types, but
they can be tested and treated in the same way. Since ALA and PBG are
always elevated in urine during acute attacks, these porphyrin
precursors are sometimes used alone for screening potential cases. They
may normal, however, in latent cases as well as those in remission, in
between attacks, and/or those with more chronic symptoms. They also
cannot distinguish between different types of porphyrinopathy.
To be definitively diagnosed, an active case of inherited porphyria or
acquired porphyrinopathy should show evidence of all the following:
1. Abnormal enzyme activity in one or more of the eight porphyrin
enzymes. (Even if the patient has never had symptoms, this alone is
enough to diagnosis a latent case of porphyria.)
2. Abnormal levels of porphyrins and/or porphyrin precursors in the
urine, stool, blood and/or plasma (although they may be so only during
acute attacks).
3. Acute and/or chronic symptoms typical of porphyrinopathies that are
not explainable by other diseases or other forms of chemical injury.
How can one be tested for Porphyrin Metabolism?
MCS Referral & Resources offers a detailed testing protocol developed by
Dr. Grace Ziem and Albert Donnay to assist doctors in evaluating
disorders of porphyrin metabolism in chemically-injured patients. It
contains this fact sheet as well as a laboratory request form,
instructions for patients, diagnostic information for physicians,
interpretive tables, and a long list of drugs and chemicals known to
trigger symptoms of acute porphyrin disorders. We encourage patients to
discuss this protocol with their physician(s) to see if it is
appropriate for them. Any lab can collect the required blood, urine and
stool specimens, but the protocol requires that these be sent for
analysis to the Mayo Medical Laboratory, which is a world-renowned
center for porphyria research.
Can the patient's family be affected?
The blood relatives of patients with an inherited porphyria may have the
same enzyme defect but no symptoms. About 90% of these "latent" or
silent cases never develop symptoms, but the other 10% are usually ill
by mid-life. Since it is not known which particular exposure(s) may
eventually provoke their disease, latent cases should be informed about
the potential risk posed by exposures to "porphyrogenic" substances
(like alcohol, and specific drugs and chemicals) that may trigger their
disease. This applies both at home and in the workplace. MCS patients
who test positive for abnormalities that are characteristic of one of
the inherited porphyrias may want to encourage their immediate family
members to be tested as well, starting with their biological parents, if
possible. If both parents are normal, the porphyrin disorder is not
inherited and other blood relatives (children, brothers and sisters)
need not be tested.
How do Disorders of Porphyrin Metabolism relate to MCS?
Both conditions report increased sensitivity to certain chemicals, drugs
and alcohol. Many other symptoms are similar. Two separate medical
practices in Washington State have tested over 150 of their MCS patients
with symptoms of porphyrinopathy. According to analyses done by Mayo's
Porphyria Lab, over 70% of them had excess porphyrins and/or enzyme
abnormalities in patterns that did not match those of any inherited
porphyrias. Disorders of porphyrin metabolism may account for many of
the symptoms seen in MCS cases (and possibly also cases of CFS/CFIDS,
fibromyalgia, Persian Gulf Syndrome and silicone breast implant
disease), but they do not explain all the symptoms and may not be
present in all cases, which suggests that other mechanisms of chemical
injury must be involved. Some MCS patients, for example, show evidence
of direct neurotoxicity in the brain, as well as impaired functioning of
the limbic, respiratory and immune systems, none of which are usually
associated with porphyria or porphyrinuria (although these have not been
ruled out).
What if I have MCS symptoms but some or all of my tests are normal?
In some acute porphyrias and porphyrinurias, excess porphyrins and/or
porphyrin precursors may be evident only during an acute reaction.
Testing should be repeated when you feel your symptoms are significantly
increased and should check for an excess of porphyrins in all possible
locations: urine, stool, plasma and whole blood. If repeated testing
even when your MCS symptoms are worse than usual finds no abnormal
levels of enzymes, porphyrins or their precursors, then you do not have
a disorder of porphyrin metabolism (at least not one detectable by
Mayo's current laboratory methods). These MCS cases may be called
"non-porphyric MCS" to distinguish them from those in which porphyrin
disorders are involved.
What can people with Disorders of Porphyrin Metabolism do to get better?
When secondary porphyrinurias are suspected, treatment should focus on
the primary disease causing the porphyrinuria. In the case of inherited
porphyrias and toxic acquired porphyrinurias, there is no known cure,
but proper precautions may greatly reduce symptoms and long-term damage
to the body. As with MCS, the recommended "treatment" for acute
porphyrinopathies focuses on the need for patients to avoid all
exposures that may provoke their symptoms. Patients are advised strongly
to:
1. 1. Avoid exposures to "porphyrinogenic" chemicals, medications and
other substances known or suspected of making symptoms worse, including
steroids and anything that mimics estrogen. (Women with porphyria should
inform their gynecologist, since contraceptive pills may need to be
avoided and pregnancy closely monitored.) Wear a Medic-Alert bracelet
that says "Avoid Porphyrogenic Substances: Chemically Sensitive." (Call
1-800-432-5378 to order.)
2. Avoid beer, wine and other beverages containing alcohol.
3. Avoid activities that you find stressful and seek prompt treatment
for any other illness or infection, all of which may provoke attacks.
Before prescribing antibiotics, your doctor should confirm bacterial
infection with a "white count/differential" and/or culture to avoid
unnecessary medication.
4. Avoid fasting, dieting, and a low carbohydrate intake which can
aggravate symptoms by causing the body to burn more fat, which is where
petrochemicals and many other toxins are stored. Symptoms may be reduced
by eating a regular diet of adequate carbohydrates and not skipping any
meals. Complex carbohydrates are best, such as potatoes and grains
(bread, pasta, cereal, etc. made from wheat, corn, oats, rye, and other
grains). Because people with chemical injury to the immune system are
often more susceptible to "yeast" (Candida) infections, they should not
get their carbohydrates in the form of sucrose (refined sugar), although
other kinds of sweets (such as the fructose in fruit juice) are okay in
modest amounts. If you suspect a food intolerance or allergy, you should
consult with a physician or nutritionist about ways of identifying and
avoiding problem foods.
If you are having an acute reaction, you can try to see whether sugars
such as fruit juice help your symptoms.
5. Avoid iron supplements and vitamins containing iron. Also avoid
cookware made with uncoated iron or aluminum, since these metals can
contaminate your food.
Consider having your serum iron tested if you frequently have diarrhea
or loose stools. Low normal is considered better for people with
porphyrin disorders. Another way to reduce iron levels in the body (if
near or above average) is to slowly cut your meat intake. Be careful to
get adequate protein from other sources. Many people with a history of
chemical injury have poorer absorption of foods from their intestines.
If you suspect this, discuss it with your doctor. If you frequently have
diarrhea or frequent loose stools, you probably are not absorbing food
properly, and may need more protein (and nutrient supplements without
iron) to compensate for this.
6. Avoid dehydration: drink at least two quarts of fluid over the course
of the day. Do not count beverages that act as diuretics, such as
coffee, tea and sodas containing caffeine, since these remove water from
the body. If you drink these beverages at all, you should drink extra
water to avoid dehydration. Coffee aggravates symptoms in many MCS
patients, probably because caffeine is broken down by the same
cytochrome P450 system in the liver which is affected by chemical
injury. Remember that decaffeinated coffee may still have as much as a
third of the caffeine as regular coffee.
7. In case of acute attack, try drinking beverages containing glucose or
fructose as well as lots of water (1-2 cups per hour minimum for several
hours), and eating a quick meal of carbohydrates. In cases of
respiratory paralysis or seizure, which can be life-threatening, doctors
should consider immediate injections of glucose or Panhematiheme medications such as Panhematin. These often help with acute
symptoms but offer no lasting cure.
2. In cases of sustained or severe rapid heart beat or significant
hypertension, physicians should monitor the patient closely. Propanolol
and other beta-blockers have been used to control these symptoms but
since they sometimes have severe side effects they only should be used
under close medical supervision (with monitoring of blood pressure and
heart rate).
3. Severe pain is often treated with narcotic analgesics, but also only
under a doctor's supervision. Some patients have reported benefits from
drug-free approaches such as hypnosis and acupuncture.
4. Beta carotene (a vitamin found in carrots) is an antioxidant believed
to help reduce tissue damage from exposure to reactive chemicals. It has
been used to reduce skin symptoms in porphyria patients with some types
of photosensitivity, but neither it nor Vitamin E (another antioxidant)
has been found to help with other porphyria symptoms.
What drugs should be avoided by chemically-sensitive people with
Porphryinopathies?
Hundreds of drugs and chemicals that are known or suspected of
triggering symptoms in cases of acute and acquired porphyria have been
identified, and these should be avoided unless medically essential. (A
partial list is available from MCS Referral & Resources.) Unfortunately,
many thousands more have never been tested. People with porphyria are
likely to react badly to some medications, have chemical injury in other
body organ systems and beware could react to medications that are not
believed to aggravate porphyria. Medications (and chemicals) to avoid
include those broken down by means of "oxidation" or "hydroxylation,"
steroids, those which mimic the female hormone estrogen, and those which
induce the cytochrome P450 system in which heme plays such an important
role.
Although some lists of "safer" medications have been published by
porphyria researchers, new medications should be tried only one at a
time and under close medical supervision. They may not be safe in
combination and reactions among porphyria patients are known to vary
significantly.
Chemically-sensitive patients with porphyrinopathies should wear a Medic
Alert bracelet, as noted above, and be sure to provide both Medic Alert
and their local doctor with a list of the "porphyrogenic" medications to
be avoided. If your doctor prescribes any new medication, ask if it is
broken down in the body by oxidation or hydroxylation processes. If so,
an alternative medication should be considered.
Will medical insurance pay for testing and treatment of Porphryrin
Disorders?
It should. Disorders of porphyrin metabolism, although rare, are widely
accepted by the medical community, and "porphyrinurias" have been listed
by the International Classification of Diseases since 1920 (currently
ICD 277.1). The diagnostic need for detailed biochemical testing is well
established in the medical literature (urine and/or stool testing alone
are insufficient). There also is broad agreement that the primary focus
of treatment in acute cases must be on the avoidance of exposures that
may trigger an attack, just as recommended for MCS. Since so many types
of porphyria have such potentially serious consequences, there is no
excuse for denying complete and prompt evaluation in any suspected case.
Please let your physician and MCS Referral & Resources know if your
insurance company refuses to pay for porphyria diagnosis and/or
treatment. You may want to appeal, and we may be able to help.
References and Recommended Reading:
A packet of medical papers on porphyria and a brief bibliography are
available from the National Digestive Diseases Information
Clearinghouse, 301-654-3810.
You also may wish to contact the American Porphyria Foundation
(713-266-9617), which publishes a newsletter and brochures about
different aspects of the inherited porphyrias and their treatment (via
diet and hematin, for example). Except for Porphyria Cutanea Tarda,
however, they offer no information on chemically-acquired disorders of
porphyrin metabolism or "porphyrinuria."
Berkow R (ed.) 1992. The Merck Manual of Diagnosis and Therapy, 16th
edition, Rahway, NJ: Merck Research Laboratories, pp. 1026-1038.
Bloomer JR and HL Bonkovsky. 1989. "The Porphyrias," Disease-a-Month,
vol.35, no.1, pp.1-54.
Kappas A, S Sassa, RA Galbraith, and Y Norman. 1989. "The Porphyrias" in
The Metabolic Basis of Inherited Disease, Scriver CR, AL Beaudet, WS
Sly, and D Valle (editors), 6th edition, New York: McGraw-Hill
Information Services Company, pp.1305-1365.
Moore MR, KEL McColl, C Rimington, and A Goldberg. 1987. Disorders of
Porphyrin Metabolism, New York: Plenum Medical Book Company.
Scriver CR, AL Beaudet, WS Sly, and D Valle (editors). 1995. The
Metabolic Basis of Inherited Disease, 7th edition. New York: McGraw-Hill
Information Services Company, 2103-2159.
Silbergeld EK and BA Fowler (editors). 1987. Mechanisms of Chemical
Induced Porphyrinopathies, Annals of the New York Academy of Sciences,
volume 514.
< E O F >
Read previous mail | Read next mail
| |
