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Porphyria Educational Services
Monthly Newsletters
April 2001 Edition


All information published in the Porphyria Educational Services Monthly
Newsletter is to provide information on the various aspects of the disease porphyria
and it's associated symptoms, triggers, and treatment.

Columnists and contributors and the information that they provide are not intended
as a substitute for the medical advice of physicians. The diagnosis and treatment
of the porphyrias are based upon the entire encounter between a physician and the
individual patient. .

Specific recommendations for the confirmed diagnosis and treatment of any
individual must be accomplished by that individual and their personal
physician, acting together cooperatively.

Porphyria Educations Services in no way shall be held responsible in part or whole
for any injury, misinformation,
neglience, or loss incurred by you. In reading the monthly newsletters you
need to agree not to hold liable any contributing writers.

FOCUS: Human Genome Project

Announcement Marks Only the Beginning of Scientific Answers

In scientific circles today the topic has been the completion of the Human Genome project. Lots of progress has been made in DNA sequencing automation.

Because of the progress that has been made in June 2000 it was formally announced that the majority of the sequence of human DNA has been determined. Such sequencing is all gathered in a database called GenBank.

In the Gen Bank about 25% of the sequencing appears in a finished form. This data is highly accurate. The only gaps in this information are those which can not be closed currently by the existing methods that are now available.

The rest of the nearly 75% of the Human Genome Project information in the Gen Bank is in what is termed a :working draft" form. This form is highly useful for looking for answers for the endless questions that appear yet in biology, Much of this material will require thirty or more months to complete.

Beyond this initial task of the sequence itself, there is the catalog project. In the this project there is a catalog of common variations in the human genome. This project all ready contain around a million variants.

Another project underway is the animal models. By obtaining the DNA sequence of the laboratory mouse, and other lab forms of life, model organisms will be able to identity and inform us of about biological development.

So where is this all leading?

The combination of all of these variants aspects puts medical science right at the threshold of the capability of identifying the genetic contributions to virtually any disease.

Discovery of genetic susceptibilities will eventually lead to the capability to make individualized predictions of future risk for the individual person. This in turn will lead to the ability to make more effective approaches to preventive medicine for a large number of diseases.

More importantly, each revelation about hereditary factors in disease will lead to the ability to determine new therapies that are more precisely targeted to the actual molecular problem individualized to a particular patient.

While all of this progress continues to proceed in the research laboratories we at the same time have to take the necessary steps to insure that the ethical, legal and social consequences of the human genome breakthroughs protect the very people such scientific discovery is designed to be helping.

It is most crucial to provide legislative protections against the misuse of genetic information in health insurance as well as in places of employment.

Another area of concern is that new genetic tests undergo appropriate reviews before they are introduced into everyday standard medical practice.

And most of all where porphyria patients are concerned as well as many other lesser known diseases, there is the major challenge to achieve genetic literacy throughout the medical community. All heath care providers of all disciplines will need to update themselves.

With all of this scientific advancement in genetics, without genetic literacy amongst medical providers, all of this effort will give rise to more confusion than enlightenment.

In porphyria the vast number of medical care providers who know little or nothing of porphyria will precisely the audience that will also need to really focus on the principles and findings of the human genome project.

Dr. Ryan E. Martell M.D. PhD.
Genetics, Molecular & Cell Biology

FOCUS: Hepatic Encephalopathy [HE]

Hepatic Encephalopathy [HE] is one of the lesser known side effects or medical conditions of aggressive hepatic porphyria. Sometimes it is called just encephalopathy and some doctors will just call it hepatic coma.

It is a culmination of a whole group of symptoms that may occur when there is damage to the brain and nervous system as a complication of liver disorders, characterized by various neurologic symptoms including changes in consciousness including the more well known porph ANS. There are also behavior changes, and personality changes in patients with HE.

While Hepatic Encephalopathy can be caused by other disorders affecting the liver, it is commonly found in the hepatic porphyrias.

HE stems from the medical conditions that reduce liver function such as cirrhosis or hepatitis, as well as just the hepatic porph itself. Also if the heme gets "bottlenecked " in the body system and the blood circulation bypasses the liver.

At this point in time the doctors say they still do not know the exact cause of the disorder. What is known is that the liver cannot properly metabolize and detoxify substances in the body.

Accumulation of toxic substances causes metabolic abnormalities that lead to damage in the central nervous system which include the brain and spinal cord.

In hematology screening it has been found that the most common toxic substance is ammonia. The ammonia is produced by the body when proteins are digested, but normally it is detoxified by the liver. During porphyria attacks the liver is on overload and does not function well. Also it is well to remember that other substances also accumulate in the body and damage the nervous system.

In people with otherwise stable liver disorders, hepatic encephalopathy may be triggered by episodes of gastrointestinal bleeding, excessive dietary protein, or electrolyte abnormalities common in porphyria attacks.

During acute attacks there is especially a decrease in potassium. Usually the low potassium results from vomiting or treatments such as diuretics.

HE disorder may also be triggered by any condition that results in alkalosis.

Other factors that can cause HE include low oxygen levels in the body, use of medications that suppress the central nervous system (such as barbiturates or Benzodiazepine tranquilizers), infections including viral hepatitis, bile duct obstruction, surgery, or any coincidental illness.

Hepatic encephalopathy occurs in approximately 4 out of 100,000 people. It may occur as an acute, potentially reversible disorder or as a chronic, progressive disorder. HE should always be considered in hepatic porphyria patients.

Dr. Brian Berge M.D. Ph.D.
Hepatology & Hematology

FOCUS: Exposure to Hydrocarbons

And so you ask what do hydrocarbons have to do with porphyria? Why are we covering this topic in a porphyria forum?

For those porphyria patients who are highly sensitive to a wide array of drugs as well as household cleaning products, pesticides, paints and metal fumes, we can add to the list those of exposures to hydrocarbons.

Hydrocarbons are contaminants. Hydrocarbons are common in our environment. As environmental contaminants the hydrocarbons are found in such products as glue, rubber, paint, gasoline, some plastics, solvents. In fact hydrocarbons are found in almost any petroleum derivative.

Exposure to hydrocarbons manifests in neurolical symptoms and especially in motor skills of porphyria patients. Those patients with peripheral neuropathy often find that after such exposure motor function slowed even further and did not respond as well to physical therapy when avoiding such triggers.

It is believed that the degree of exposure to hydrocarbons dirctly relates to the severity of symptoms. It is also related to the quality of life experienced during periods of remission from acute attacks of porphyria.

Another factor believed in regard to exposure to hydrocarbons is that porphyria patients show a poorer response to standard glucose therapy than individuals who go into attack from other triggers except for pesticides.

A preliminary study of a group of porphyria patients indicates exposure to printing ink, chemical labs, constant exposure to upholstery bolts and drapery yardage; paints, lacquers, wood glues, plastic, refrigeration coolants; leather dyes and direct contact with gasoline.

In retrospect of the findings of exposure to hydrocarbons by porphyria patients, it is felt that any hydrocarbon solvents become a high risk trigger factor for porphyria patients. Hydrocarbons are indicated for an earlier onset of attacks, accompanying peripheral neuropathy, a slowing of cognitive ability, and a more severe progression of porphyria symtemology.

While such preliminary research findings have many more aspects to explore, it is warranted at this time to warn against exposure to hydrocarbons.

Charles Lincoln O.D.

FOCUS: Reviewing Pharmaceutical Packaging Slips

Reviewing the pharmaceutical packing slip on all drugs is very important for everyone and even more so for those with a diagnosis of porphyria or a family history of porphyria.

The part on hepatic impairment should send up red flags every time you look at how a certain drug affects the body.

Porphyria has both liver and renal aspects. Any drug that is processed through the liver [most are commonly noted as cyctochrome P-450 drugs] you need to carefully evaluate just how bad you want to chance taking these drugs.

And as always, be sure to check the UNSAFE DRUG lists as well as the monthly updates found in this newsletter.

Bob Dockter, R. PH
Clinical Pharmacologist

FOCUS: Pseudoporphyria

Pseudoporphyria is a cutaneous phototoxic disorder that can resemble either porphyria cutanea tarda [PCT] or erythropoietic protoporphyria [EPP].

Other names for this condition are known as drug therapy induced bullous photosensitivity.

While pseudoporphyria resembles two forms of regular recognized porphyria there are distinct differences.

The microscopic changes are similar to that seen in porphyria cutanea tarda, but there are no laboratory abnormalities.

Lesions however have strong resemblance to those found in PCT. Those similarities include spontaneous blisters and skin fragility. This condition is usually on the dorsal of the hands.

In pseudoporphyria lesions may develop from one week to several months after the start of toxic drugs.

Another finding in pseudoporphyria is that there usually is no hypertrichosis, hyperpigmentation, or sclerodermoid changes.

In PCT which is a true porphyria,porphyrins accumulate in the liver. These porphyrins are transported in the blood plasma and are excessively excreted in the urine.

Exposure of patients with PCT to sunlight results in increased skin fragility. PCT patients can display vesicles, bullae, hypertrichosis, sclerodermoid changes, dystrophic calcification, milia and scarring in a photo-distribution. PCT patients often experience hyperpigmentation. PCT can be inherited or acquired while other forms of porphyria are inherited only.

In pseudoporphyria there is a bullous photosensitivity that mimics PCT clinically and histologically.

Pseudoporphyria was isolated in 1964 by a researcher named Zelickson.

Zelickson was first to describe this type of phototoxic reaction. This researcher happened upon this malady when reviewing patients that been prescribed nalidixic acid.

Patients on the nalidixic acid were found with skin lesions that were indistinguishable from those observed in patients with PCT.

In the following years many other drugs have been incriminated in mediating this type of bullous photosensitivity.

Among the drugs known to trigger pseudoporphyria photosensitivity are the NSAIDS naproxen, diflunisal, mefenamic acid, ketoprofen, nabumetone, oxaprozin. Some diuretics also have been indicated such as furosemide, chlorthalidone, and butanamide.

Cancer patients are at risk when 5-fluorouracil is used as a chemotherapy and cyclosporin as an immunosuppressant.

Antibiotic agents such as nalidixic acid, tetracycline, oxytetracycline, and the fluoroquinolones* must also be avoided.

Carisoprodol which is often prescribed as a muscle relaxant must be avoided. Another agent is that of the sulfone pharmaceutical known as dapsone.

In cardiology patients the antiarrhythmic amiodarone has found to trigger photosensitivity and pseudoporphyria episodes.

The non-steroidal anti-androgen flutamide is another pharmaceutical to avoid.

Pyridoxine and brewer's yeast as well as vitamin A derivatives etretinate and isotretinoin also should be avoided.

Even today the precise pathophysiological mechanism of pseudoporphyria is not fully understood.

Pseudoporphyria patients with chronic renal failure treated with hemodialysis and those with excessive exposure to ultraviolet A (UVA) by tanning beds have also been cited.

Aluminum hydroxide has been implicated in hemodialysis associated pseudoporphyria.

It is theorized that photosensitizing drugs might behave in a similar fashion to photoactivated endogenous porphyrins. In this action they target similar structures in the skin.

Pseudoporphyria is not uncommon although pseudoporphyria is most likely under reported. Also pseudoporphyria has no focus towards any one race, it has been shown that fair-skinned children who are highly prone to sunburn are more likely to develop naproxen-induced pseudoporphyria.

Pseudoporphyria affects males and females equally. And at this poiint in research a genetic factor has not been considered in pseudoporphyria.

Connective tissue disorder, which may be the underlying pathology of the photosensitivity, needs to be assessed by clinical examination before the continued prescribing of NSAIDS in patients who develop pseudoporphyria.

If the diagnosis of pseudoporphyria is suspected, biopsies for histologic evaluation with hematoxylin and eosin stains and direct immunofluorescence should be performed

The best treatment of pseudoporphyria is to stop the use of the offending agent whenever possible. Correction of the clinical findings of pseudoporphyria may take many months, particularly in drug-induced pseudoporphyria.

Dr. Travis Collins Ph.D.
Pharmacology & Metabolism

April 2001 PES Drug Update

PES drug information does not endorse drugs, diagnose patients or recommend therapy. PES drug information is a reference resource designed as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient.

OXYCODAN is the brand name for the generic drug OXYCODONE.This drug can produce drug dependence of the morphine type The administration of Percodan or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions such as a porphyric attack or other medical conditions. OXYCODAN should be given with caution to patients such as the elderly or debilitated, with impairment of hepatic or renal function, or/and hypothyroidism. The drug is metabolized through the liver.
AUDAZOL is a brand name for the generic drug OMEPRAZOLE. In clinical trials this drug was found to elevate liver functions. The drug is metabolized through the liver. There is a warning for persons with hepatic impairment.

DYAZIDE is a brand name for the generic drug HYDROCHLOROTHIAZIDE TRIAMTERENE. It is classified as a diuretic. It can cause liver enzyme abnormalities. It can also cause renal failure. This drug can also reduce levels of blood serum potassium essential to electrolyte balance. This drug also contains the ingredient of sulfate.

TRIHEXANE is a brand name for the generic drug TRIHEXYPHENIDYL. This drug is not to be taken by persons with a seizure disorder, kidney or liver disease. It is metabolized through the liver.

DEMADEX is the brand name for the generic drug TORSEMIDE. It is a diuretic loop drug. It contains sulfa ingredients. There is increased sensitivity to sunlight when using this drug. There is a warning for persons with lupus, kidney and/or liver disease. The drug is metabolized through the liver.