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
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.
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.
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.
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.
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.
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.
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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.