EDUCATIONAL SERVICES BULLETIN
Vol. 1 No.
8 February 1999
Bulletin Focus: Porphyria Cutanea Tarda
Porphyria cutanea tarda which is better known as (PCT)
is one of present eight known and confirmed types of
porphyria. Unlike the other eight types of porphyria, PCT
can be acquired as well as
inherited. Statistics among patients with a confirmed dx
of PCT indicate that only about 20% have the inherited
type, with the remaining the acquired form.
PCT a form of porphyria caused by a deficiency in
activity of the enzyme uroporphyrinogen decarboxylase.
Uroporphyrinogen decarboxylase is the fifth enzyme along
the heme pathway
of eight enzymes which are responsible for the synthesis
of heme. As aforementioned, PCT may be acquired, often in
later life. The last of the PCT name,
"tarda" is the Latin for the word
late. Whether a person has the acuired form or the
inherited form, either way the activity of
uroporphyrinogen decarboxylase will be decreased to
approximately 50 of the normal value. Even with the
decreased values it is thought that the majority of the
reduced level of activity will be sufficient to carry out
normal heme synthesis.
When it is not sufficient, the activity is insufficient
resulting in a decreased synthesis of heme. When this
happens there is an accumulation of the products of the
part of the heme biosynthetic pathway. The earlier stages
of the this heme pathway continue to work normally. When
the PCT is active the porphyrins accumulate in the site
Most synthesis occurs in the liver. From this point the
excess porphyrins flow out into the blood. From
here the porphyrins may be either eliminated into
or deposited in various tissues around the body.
When such porphyrins deposits are found in
the skin, they can absorb light. Most porphyrins are able
to absorb light and store the energy in the form of
carbohydrates. However in PCT the porphyrins which
accumulate are unable to store the energy of the
light. This energy is released into the skin in
photochemical reactions that cause
damage to the skin. When a PCT patient has continuous
exposure to light, it will lead to skin damage,
which includes blistering, and scarring. It is
rare, for patients to display the signs of PCT
before their teenage
years, it is still possible.
Historically or typically, the symptoms of the
disease are first observed when patients are in
their 30's or 40's.
The most common symptoms or signs are the fragility and
blistering of the skin. This usually occurs on the
backs of the hands and on the face. With out a doubt this
is probably because these two areas are most
to sunlight. The blisters usually contain fluid.
Following the breaking of the blister, the
underlying exposed tissues are usually slow to heal.
Infections of the skin can and do occur.
Sometimes this will lead to scarring and changes in skin
coloration. Patients often notice that their skin is
unusually fragile. Even the slightest bumps or
knocks may lead to the upper surface of the
skin being scraped away.
Excessive growth of facial hair is another sign/symptoms
of PCT. The reason for this hair growth is not
presently understood. However,once the PCT is under
control, the hair can usually be easily and
effectively removed by conventional methods. Nair is a
painless way, if a person is not otherwise sensitive to
the materials used in the formula.
Certain factors are known to be important in
precipitating the symptoms of PCT.
The drinking of alcohol has long been known to be a major
trigger of PCT. It is particularly important to
discontinue alcohol use, not only to enable effective
treatment of the disease, but also because alcohol is
well known to damage the liver. PCT is directly related
to liver disease If PCT remains out of control, and the
concentration of porphyrins continues to elevate in the
liver, there is a progressive risk of direct damage to
liver caused by the porphyrins. So, if a patient with PCT
continues to drink alcohol, they will be at a double risk
by damaging the liver both directly, and indirectly by
overproduction of porphyrins.
Estrogens are also well known to precipitate the symptoms
of PCT. Contraceptive pills with high estrogen contents,
or post-menopausal women
who are taking estrogen for treatment of menopausal
symptoms can cause serious problems for women.
Men are sometimes treated with estrogens (for example,
for cancer of the prostate). It is not known precisely
how estrogens influence the course of the
disease, but but it known by medical researchers
that they do.
Iron is another factor. Iron will often cause the
exacerbation of PCT. Often patients with blistering and
skin disease caused by PCT are found to have extremely
high levels of iron in their tissues.
Be careful of the use of Iron supplements. High iron
levels are known to inhibit the activity of the enzyme
uroporphyrinogen decarboxylase. Because of this, unusual
diets which are very rich in iron, or iron
supplementation of the diet with tablets, are
contra-indicated in PCT.
Industrial chemicals such as polychlorinated hydrocarbons
are also bad in PCT.
The diagnosis of PCT is made by the demonstration of
characteristically elevated porphyrin levels in the
plasma and urine. Depending on circumstances, at times
the activity of the defective enzyme
uroporphyrinogen decarboxylase is measured in red blood
cells. If the activity is decreased in red blood cells,
then generally the PCT has been inherited.
If it is normal in red blood cells, it is generally
acquired. However, according the American Porphyria
Foundation literature and research, this study is only
indicated in certain specific circumstances (for
example, if two or more members of the same family have
PCT, or for research purposes).
TREATMENT OF PCT
There are two steps in the treatment of PCT.
The first is to search for and remove any of the factors
which can exacerbate PCT [alcohol, chemical toxins,
estrogen] and to avoid direct sunlight.
The second is a course of frequent phlebotomies, where
approximately one pint of blood is removed at each
The reason for this treatment is to decrease the amount
of iron in the patient's body to the lower limit of
Accordinging to the medical textbook, "The Metabolic
Basis of Inherited Disease",
this happens because each time red blood cells are
removed from the body, new red blood cells have to be
synthesized, and this requires the use of
iron to synthesize the heme which is found in hemoglobin.
As a PCT patient your primary care physician should
monitor your hemoglobin count and your iron count during
therapy. According to the APF brochures on PCT,
this will also explain why the time
of treatment varies from patient to patient, because the
amount of iron in the body varies at the start of the
treatment. When the iron has been reduced to the lower
limit of normal, the activity of the enzyme responsibile
will generally improve to the level necessary
where there is no further abnormal accumulation of
porphyrins. Because of this happening the level of
porphyrins in the blood and in the urine gradually
reduces towards normal. As the porphyrins that were
stored in the skin are released, the incidence
of photosensitivity decreases and new blisters are no
longer formed. With a passage of time blisters will heal
and scarring subside.
In PCT much of the scarring and changes in pigmentation
may slowly become normal once again. In time the general
texture of the skin improves. PCT patients
eventually will no longer notice skin fragility.
As long as the porphyrin counts remain normal, there is
no reason why patients should not expose themselves to
the sun. Rarely, phlebotomy treatment by itself is
insufficient to control the
disease. With some PCT patients phlebotomy may be an
unwise choice of treatment due to other diseases, such as
anemia or heart disease For these PCT patients low dose
of chloroquine has often proved effective.
Chloroquine is the drug frequently used for the treatment
of malaria. Chloroquine it is thought, tends to
bind porphyrins and increase their rate of excretion.
According to the APF, this treatment regime is generally
safe, but there is a low incidence of damage to the
retina of the eye with prolonged exposure to chloroquine.
Therefore it is advisable for PCT patients on chlorquine
to receive periodic examinations from an ophthalmologist
to guard against this possibility.
Once remission has been induced by either phlebotomy or
chloroquine, the patient may remain in remission for two
to eight or more years. This is especially if
precipitating factors are avoided.
It must be remembered however that it is not uncommon for
PCT patients to experience a relapse with renewed
photosensitivity and blistering. It is therefore
generally advisable to monitor the plasma and urine
porphyrin levels at approximately six monthly intervals,
even during remission. With this preventative approach,
any increase in porphyrin levels can
usually be detected before the re-emergence of symptoms.
Because of this, a PCT patient can have early
reinstitution of treatment followed by a more rapid
PCT patients will have different degrees of
photosensitivity, PCT patients will also have different
severities of skin damage. In keeping with this PCT
patients will also have different responses to
therapy and different durations of symptom free
The good news is that with proper treatment, PCT is not a
progressive disease. It should be remembered that no two
PCT patients will react or response in the same way.