Erythropoietic protoporphyria

Erythropoietic protoporphyria is manifested as acute photoreactivity of the skin in childhood. Typical symptoms are stinging pain or itching with subsequent swelling and erythema of the exposed skin within minutes to hours after sun exposure. Hepatobiliary complications may be associated with protoporphyria: early-onset cholelithiasis is found in 10% and signs of parenchymal liver disease are seen in 5 to 20% of patients.
The main biochemical finding is massively increased concentrations of free erythrocyte protoporphyrin: the values in symptomatic patients are usually more than 10 mumol per liter (the normal value is less than 1.0 mumol). Other biochemical findings are increased fecal protoporphyrin content in most patients and a characteristic plasma fluorescence spectrum.
There is no specific treatment for erythropoietic protoporphyria. In most patients, beta carotene * increases tolerance to sunlight, but it has no influence on the erythrocyte or plasma porphyrin concentrations. The dosage of beta carotene must be adjusted to the level that clearly reduces photosensitivity. The daily effective dose varies, being 30 to 120 mg for children and 120 to 300 mg for adults. For therapeutic effects, the serum beta carotene concentration should be at least 600 to 800 mug per dL. The clinical effect is achieved concomitantly with carotenodermia, which develops over 3 to 6 weeks. In addition to beta carotene, topical sunscreens with high protection factor against long-wave ultraviolet radiation may be useful.
At present there is no effective treatment for prevention of liver complications. Many drugs such as cholestyramine, chenodeoxycholic acid, and heme have been used but without significant clinical effect. A liver transplantation is at present the only therapy for terminal liver failure associated with erythropoietic protoporphyria, although it poses specific problems. During surgery, phototoxic damage of abdominal wall and intestine, caused by standard lamps used in the operating room, has been reported. Thus, careful protection of the skin and modification of operating room lighting are needed. A long-term problem may be that protoporphyrin-induced damage may develop in the transplanted liver as well.

Congenital erythropoietic protoporphyria

Congenital erythropoietic protoporphyria (Gunther’s disease) is a rare autosomal recessive disease that is manifested as severe photosensitivity. This leads to bullae, scarring, and, ultimately, mutilation of the hands, nose, ears, and so on. Hemolysis is often present, but its mechanism is poorly understood. Congenital erythropoietic porphyria is an incapacitating disease with considerable mortality. The patients excrete massive amounts of porphyrins (mainly uroporphyrin I). Many organs, including the teeth, accumulate porphyrins, which can be detected by red fluorescence under ultraviolet light.
There is no effective therapy. Protection of the skin from sunlight is important to prevent skin reactions, skin infections, and mutilation. Topical sunscreens that give protection against radiation in the 400-nm region may be used, but their value has not been proved. Transfusion of packed red cells effectively suppresses the overproduction of porphyrins, but weekly transfusions are impracticable and lead to iron accumulation. Charcoal (60 grams three times daily) has been reported to lead to clinical improvement and to long-term reduction in the levels of porphyrins. It is not known whether charcoal is effective in every patient.
The site of overproduction of porphyrins in congenital erytropoietic porphyria is erythropoietic tissue. Bone marrow or stem cell transplantation replaces abnormally functioning cells with normal erythropoietic tissue. Some recent case reports suggest that these therapies can effect dramatic reversals of the clinical and biochemical abnormalities. At present, bone marrow or stem cell transplantation is the only curative treatment for patients with congenital erythropietic porphyrias. Although long-term results are lacking, this approach is the treatment of choice in severely disabled patients.

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