April 2005 PES Bulletin

Avoiding Pesticides in Porphyria

Insecticides can induce heme synthesis.

Insecticides can also cause skin irritation to sensitive individuals.

Many household bug sprays are fairly non-toxic chemicals called pyrethrins. Pyrethrins may cause life-threatening asphyxiation if the chemicals are inhaled.

Industrial insecticides contain many extremely toxic, life-threatening materials.

Many new and extremely toxic insecticides are continuously being developed.

Not only does the chemical toxins in pesticides induce heme synthesis in porphyria patients, a number of symptoms have been clinically indicated.

Clinical symptoms of exposure to pesticides include general body weakness.

Sweating, convulsions, difficulty in breathing, urinary problems, irritation of the nose, eyes and throat, and skin discoloration may present.

Gastrointestinal affects of exposure to chemical toxins in pesticides can cause abdominal discomfort, loss of appetite, nausea, vomiting and diarrhea.

With a severe exposure there is often anxiety, dizziness, blurry eyes and a operson may experience coma.

Serious chemical toxin poisoning can occur from just handling many pesticides without gloves or without washing hands soon after exposure.

Pesticides are often absorbed through the skin unless proper precautions are observed.

Life-threatening paralysis and death can occur very quickly especially in acute porphyria patients who are all ready sensitive to chemical toxins.

Skin redness or inflammation is often seen in those with cutaneous porphyrias who are exposed to pesticides.

If pesticides come in contact with the skin, wash area thoroughly for at least 15 minutes.

For those with acute porphyrias it is best to begin preventive therapy immediately including medications to prevent electrolyte loss through vomiting and diarrhea.

IV fluids are essential in keeping a person hydrated as well as furnishing adequate carbohydrates to avoid a full acute episode of porphyria. In some types of pesticide exposure an antidote may be given. Check with your primary care physician.

Admission to the hospital may be necessary for observation and proper treatment.

Many porphyria patients list their contact information with commercial companies which apply pesticides.

Porphyria patients are thus contacted prior to any spraying applications so that they may avoid any surprise exposures to the chemical toxins.

Pepper Pfeiffer MNS RN
Toxicology

Environmental Factors and the Porphyrias

Environmental factors are a trigger for some types of porphyria.
No doubt about it anymore.
More and More is being learned and studies are now showing that a large number of porphyric patients have an exacerbation of symptoms due to environmental causes.
In an abstract published in "Nature and Genetics" [1996 12:195-199] by Dr. Grandchamp of Paris, France and a world reknown porphyria expert, he states: "It is now known that attacks of acute intermittent porphyria are often precipatated by environmenta; factors.
For this reason, early detection of gene carriers is important in the prevention of acute attacks, because affected patients, even though asymptomatic, can be instructed to avoid precipating factors."
So it is necessary to detect who the gene carriers are in our families and begin preventative majors as to avoid carriers going from asymptomatic to acute active porphyrics.
It can be done, and we must move in this direction.
We also need to move to more and more preventative treatment rather than waiting for acute attacks to cause us unneccesary and costly hospitalization.
In a paper titled "Redefinition of Abnormal Susceptibility to Environmental Chemicals: given by the respected and knowledgeable Dr. William E. Morton MD, a porphyria diagnostian, before an International gatherings some years back in Atlanta, Georgia, Dr. Morton recognizes that many doctors are missing the correct diagnosis.
Dr. Morton states: "For some time we have known of persons who manifest extreme intolerance for small exposures to environmental chemicals."
He goes on to say that "During the last several years, Mayo Laboratory's introduction of several new blood-cell porphyrin enzyme tests has permitted recognition of a broader spectrum of porphyria cases than previously.
Many of these milder and more chronic porphyria cases have characteristics of MCSS, which appear after the porphyrin enzyme deficiency has converted from latency to metabolic activity by porphyrogenic substance exposure."
In talking about the symptomology of porphyria Dr. Morton stated "Porphyria symptoms can be quite variable, ranging from severe acute attacks to continuing low-grade smoldering symptoms to asymptomatic latency.
The porphyrias used to be considered very rare conditions [under 200,000 known cases], discoverable only during an acute attack when porphyrin excretion was markedly excessive.
Happily today as Dr. Morton points out, " The newly available and much more sensitive blood-cell enzyme tests have naturally resulted in greatly increased population frequency estimates (4%- 9%, up from 0.01-0.1%) in agreement with estimates made more than a century ago."
So what are the environmental factors that cause this increase of acute porphyrics?
Environmental porphyrogenic substances include paints and paint fumes, expoxies, metal dusts and fumes,alcohols [especially ethanol], freons, arsenic, biphenyls [PCBs], DDT, chlordane, glycols, glycol ethers and derivatives, vinyl chloride fumes and dust, , polychlorinated [substances], formaldehyde, other aldehydes, freons, dioxins, hexachlorobenzene chlorophenoxy acetic acids, heavy vehuicle exhaust fumes, perfumes and other fragrances, tetracloro dibenzodioxins [TCBCs] chlorine, chlorinated cleaning agents,and many others that continue to be identified by medical researchers around the world.
In respect for the environmental factors porphyrics and those who are highly suspect for porphyria because of familial histories of porphyria should seek testing and then take all precautions known for avoiding exposure to these environmental factors.
This can come through identification of index and related latent cases allowing for the control of symptoms by preventive avoidance of porphyrogenic materials.

Mary Beth Reasoner MNS
Inherited Metabolic Diseases

HCC Associated with Porphyria

Hepatocellular carcinoma better known as HCC, is often found in association with porphyhria.
HCC in common terms is known as liver cancer.
Hepatocellular carcinoma involves a malignant tumor of the liver.
Hepatocellular carcinoma (HCC) accounts for 80% to 90% of all liver cancers.
Acute porphyria patients average a 70% greater risk factor for developing HCC in the later stages of their porphyria.
Hepatocellular carcinoma (HCC) occurs more often in men than women and occurs mostly in people 50 to 60 years old.
Persons with chronic liver disease have always been known to be at a greater risk for Hepatocellular carcinoma (HCC).
Viral hepatitus, and predominantly hepatitus B and C are thought to be the main cause of Hepatocellular carcinoma (HCC) in PCT patients.
Hemochromatosis is another known cause of Hepatocellular carcinoma (HCC).
Hemochromatosis is often associated with some forms of porphyria.
In Hepatocellular carcinoma (HCC) there is usually abdominal pain and tenderness. Like the acute porphyrias, the abdominal pain most usually presents in the right-upper quadrant.
Abdominal distentoion is quite common with Hepatocellular carcinoma (HCC).
Sometimes a person with Hepatocellular carcinoma (HCC) develops jaundice and may bruise easily.
Persons with Hepatocellular carcinoma (HCC) will generally have an enlarged liver upon physical examination.
Hepatocellular carcinoma (HCC) can be determined through a liver biopsy.
Laboratory findings for Hepatocellular carcinoma (HCC) will show an elevated serum alpha fetoprotein, as well as elevated liver enzymes in a LFT (liver function panel).
Radiological testing may show an abnormal CT scan, with liver scans indicating abnormalities. Often faty liver will be found as well.
Hepatocellular carcinoma(HCC) may also alter the following test results in numerous laboratory tests associated with the porphyrias such as urine porphyrins, PBG, and Delta-ALA.
Chemotherapy and radiation treatments are not usually effective in Hepatocellular carcinoma(HCC).
Chemotherapy and radiation treatments may be used in Hepatocellular carcinoma(HCC). to shrink large tumors so that surgery has a greater chance of success.
Aggressive surgery or liver transplantation may be successful in treating small or slow-growing tumors in Hepatocellular carcinoma (HCC) if they are diagnosed early.
The prognosis for Hepatocellular carcinoma (HCC) is usually very poor. If the cancer cannot be completely removed, the disease is usually fatal within 3 to 6 months.
As a complication of Hepatocellular carcinoma (HCC) liver failure can occur and often has in porphyria patients.
Some porphyria studies in Scandinavia have found that porphyria patients who have developed co-existing diabetes usually do not develop the Hepatocellular carcinoma (HCC).
Chal Lindquist PA
Oncology & Hemotology

HEPATOERYTHROPOIETIC PORPHYRIA [HEP]

Hepatoerythropoietic Porphyria mostly usually referred to as HEP, is a very rare form of porphyria.
HEP is most usually very severe.
HEP is autosomal recessive disorder resulting from a deficiency of uroporphyrinogen decarboxylase.
Uroporphyrinogen decarboxylase deficiency occurs in all tissues and is most conveniently manifests in erythrocytes. Although the degree of deficiency is pronounced,some residual enzyme activity persists.
HEP is less severe in cases with more residual enzyme activity.
Hepatoerythropoietic porphyria (HEP) is still considered a rare disease worldwide
. Symptomology of HEP include skin blistering, red urine, and anemia are common.
Although HEP is clinically very similar to congenital erythropoietic porphyria, these conditions differ in their patterns of porphyrin accumulation.
The biochemical pattern of porphyrin accumulation of HEP resembles that of porphyria cutanea tarda, except that erythrocyte zinc protoporphyrin is also increased.
Diagnostic features of HEP include elevated fecal or urinary isocoproporphyrin and erythrocyte zinc protoporphyrin.
Phlebotomy may benefit milder cases of HEP. Treatment of more severe cases is similar to that of congenital erythropoietic porphyria.
As an interesting footnote, several of the world's HEP porphyrics are geographically located in Kentucky.

Savannah Gutierrez NP
Dermatology

Porphyric Polyneuropathy

There are many neuropathies, but a porphyric based neuropathy is a severe, rapidly advancing neuropathy.

Quite often it begins with the onset of an acute attack of porphyria.
It is often associated with the abdominal pain, psychosis may be part of this in the form of delirium or confusion, and may result in convulsions.
Such neuropathy may be more or less symmetrical polyneuropathy.
It is not a disease, but is rather a symptom or sign of a disease, and in this case, being one of the acute types of hepatic porphyria.
PN, as it is known, is always a likely manifestation of AIP [acute intermittent porphyria] pyrroloporphyria or Swedish porphyria. It is also found in the the Chester type or the sub type dubbed as Dobson's Complaint.
The types are porphyria giving way to PN ware inherited as an autosomal dominant trait.
It is not associated with cutaneous sensitivity to sunlight.
The metabolic defect is in the liver. It is marked by an increased production and urinary excretion of porphobilingen and of the porphyrin precusor, ALA. ALA is delta aminolevulinic acid.
In the VP and the HCP types, the peripheral and central nervous systems may also be affected with the PN. In the CEP the nervous system is not affacted by PN.
Studies in relation to the ALAD have not been completed in relation to PN.
The neurologic manifestations in the acute porphyrias are usually those of a polyneuropathy involving the motor nerves, more than the sensory ones.
Less often both sensory and motor nerves are affected.
The symptoms may begin in the feet and legs and ascend, or they may begin in the hands and arms and spread in a few days to the trunk and legs.
This may happen asymmetrically.
Occasionally the weakness predominates in the proximal muscles of the limbs and limb girdles.
Sensory loss, often extending to the trunk, is present in more than 50% of the cases.
Facial paralysis, dysphagia, and ocular palsies are features of the most severe cases, and often simulate Guillian Barre Syndrome.
The CSF protein content is normal or slightly elevated.
The course of the polyneuropathy is variable.
In mild cases the symptoms may regress in a few weeks.
If polyneuropathy is severe, it may progress to a fatal respiratory or cardiac paralysis in a few days.
Polyneuropathy can also advance in a salatory fashion over a period of several weeks, resulting in a severe sensorimotor pararlysis that improves only after many months and the avoidance of further acute porphyria attacks.
A disturbance of cerebral function (ie., confusion, delirium, visual field defects [fuzzy vision and brain fog]) is likely to precede the severe rather than the mild forms of PN.
Cortical blindness is often seen in the acute porphyrias.
Sometimes such signs and symptoms will not appear at all.
Death may result from respiratory paralysis or cardiac arrest and sometimes from uremia and cachexia.
In the acute porphyrias respiratory paralysis was for a number of years the leading cause of death in porphyria.
Rarely the PN developes without the other symptoms of an acute attack.

Philomene Gillespie NP
Neurology

SUICIDE AND PORPHYRIC PAIN

Throughout much of the known history of porphyria, there have been those porphyrics who have ended their lives.
Most notable of these porphyrics was of course the famed Vincent Van Gogh.
His problem of course was that when he went into a porphyic attack, he would drink a thimble of absythe to dull the severity of the pain.
And it may for a short time, but at the same time was the "trigger" for another acute attack of porphyria.
It happened so often that Van Gogh was chronic and no longer just a smoldering chronic porphyric but in severe chronic pain.
Finally, unable to handle his condition he commited suicide.
Suicide is NOT a treatment for anything.
This same thought was stated a few years back in an article in a California mainline newspaper publication where the "right to die" is being discussed.
Debate started in the California legislature regarding physician-assisted suicide with the introduction of Assembly Bill 1592.
Rather than debate such issues to end life, it should rather be the issue of requiring physicians to include courses that familiarize them with the disease porphyria and addressing pain and symptom management of the various types of porphyria.
Another issue that needs to be stressed is to be sure that pain medications are readily available to porphyria patients in pain.
Legislation also has to be made clear that allows for physician caring for porphyric patients to prescribe appropriate dosages of medications without fear of the wrath of the law enforcement officials intent on the waging of war on drugs.
Laws have been enacted to allow access to pain medications and reduced the inefficiancy of the triplicate prescription process for administering drugs to terminally ill patients.
Those suffering from a terminal illness are no longer subject to long delays in approval of non-formulary medications.
However, porphyrics are not terminal, but many days it seems as if we wish the porphyria were terminal.
It is not.
And suicide is not an answer.
We must be sure that legislation is made that will enable our physicians to prescribe the medications that we need in order to live a better quality of daily life.
All concerned parties should work together for the behalf of porphyrics and continue down the humanitarian path of treating pain in suffering individuals both porphyrics and others in severe pain.

SOURCE:
Dr. Kenneth Carlson
Neuropsychiatric Medicine