Erythropoietic
Protoporphyria
Erythropoietic
protoporphyria (EPP) is a blood disorder due to a hereditary enzyme defect in
the heme synthesis of the red blood cell. It presents in infancy when even after
a short exposure to sunlight there is a burning pain in the skin. These individuals
develop often gall stones later in life. The condition is inherited in an autosomal
dominant fashion. A complicated genetic constellation is necessary to lead to
a severe form of this condition. The enzyme ferrochelatase is deficient in red
blood cells and precursors of red blood cells (erythropoietic cells) in the bone
marrow. This leads to an accumulation of protoporphyrins as the heme synthesis
gets blocked. To a certain degree the body can tolerate these, but when they are
activated by sunlight that hits the skin, phototoxic protoporphyrins are formed
that get metabolized in the liver and excreted in the bile into the gut. These
phototoxic protoporphyrins act like free radicals that attack the liver, the bile
ducts and the gall bladder. After years of exposure from birth onwards the liver
can become cirrhotic, the gallbladder can form gall stones and the biliary ducts
can get scarred and become stenotic. Further studies have shown that in addition
to the ferrochelatase enzyme defect there is another gene that codes for a low
output of the protoporphyrins (low output ferrochelatase allele) that is passed
on from the overtly healthy parent. Only when this two gene constellations comes
together in the same person, is there a high risk of complications, such as jaundice,
liver enlargement and possible nodular cirrhosis with liver failure in 10% of
the cases. Only 5 in a million people in the US develop EPP. Signs
and symptoms Depending on the genetic mix the symptoms can vary
greatly. Mild forms may be overlooked until the child is older. An infant with
EPP may have unexplained screaming fits for hours after only a brief exposure
to sunlight. There may be psychosocial ramifications when a child absolutely refuses
to go outside because it has learnt that sun exposure causes excruciating pain
in the exposed skin areas. Aggressions, tensions, behavior problems can result
from feeling like an “outcast”; in the worst scenario suicidal thoughts and
actions can follow. After having been in the sun for prolonged periods skin changes
occur with crusts around the lips and the back of the hands. There is no blistering.
Without proper skin protection the skin becomes thickened, leathery, particularly
around the knuckles. Around the mouth deep skin folds develop (carp mouth). The
excretion of large amounts of phototoxic protoporphyrins can cause blockage in
the inflamed bile ducts with jaundice, cirrhosis of the liver, right upper abdominal
pain and general malaise. Diagnosis When children
or adults complain about painful skin photosensitivity without blistering, EPP
should be suspected and blood tests should be performed. Levels of protoporphyrins
in blood samples are elevated in red blood cells and plasma. The physician can
order a test of a genetic marker that has become available, which will predict
how susceptible this person is to develop jaundice and liver complications. Family
members can also be screened for the low output ferrochelatase gene mutation.
It likely would be best for the physician to refer the patient to a genetic expert
for genetic counseling. Treatment The patient’s
painful skin needs to be cooled down with cool baths; wet towels can be applied
and pain relievers are given. The treating physician should see the patient regularly
to monitor the clinical situation and order appropriate tests. Sunlight exposure
needs to be cut down as much as possible and sun screen lotions with a high sun
protection factor should be applied to the skin to absorb UVA rays. Zinc oxide
sunscreens and others that contain dibenzylmethanes or titanium dioxide may also
be useful to protect the skin. Certain drugs that have been identified as being
unsafe should be stopped and avoided. Some from this list are very common medications
such as barbiturates, lidocaine, and antibiotics like chloramphenicol, erythromycin,
sulfonamides or ketoconazole. Ergots used as anti migraine medication also belongs
to the drugs to be avoided, as does hydrazine, methyldopa, danazol and synthetic
progestins. Fasting as well as alcohol consumption need to be avoided as well
as both of these will increase red blood cell production. This in turn will increase
the protoporphyrin levels. On the other hand anti-oxidants such as beta-carotenes
and cysteine can be useful in stabilizing this condition. Another way how protoporphyrin
levels can be decreased is by hyper transfusion of red blood cells. This will
shut down the own production of red blood cells with phototoxic protoporphyrins
and thus improve symptoms. Elimination of protoporphyrins can be stimulated by
giving bile salts. In addition the elimination of bile salts through the bowels
can be achieved by charcoal and by cholestyramine, which blocks the reuptake of
bile salts through the portal vein system (enterohepatic pathway). If liver failure
develops, a swift liver transplant may save the persons life.
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