Erythropoietic protoporphyria: causes, symptoms, diagnosis, treatment

Characteristic clinical manifestations of erythropoietic protoporphyria can develop in newborns in the form of skin burns even after a short exposure to the sun. The development of cholelithiasis is typical for a later age, as the disease progresses, and acute liver failure develops in approximately 10% of patients. Diagnosis is based on clinical symptoms and increased levels of protoporphyrin in erythrocytes and blood plasma. Treatment consists of prescribing beta-carotene and protecting the skin from direct sunlight.

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Causes of erythropoietic protoporphyria

Erythropoietic protoporphyria results from a deficiency of the enzyme ferrochelatase in erythroid tissue. Phototoxic protoporphyrins accumulate in the bone marrow and red blood cells, enter the plasma, and are deposited in the skin or excreted by the liver in the bile and stool. Excretion of heavy biliary protoporphyrin may contribute to gallstone formation. These cytotoxic molecules sometimes damage the hepatobiliary tract, resulting in accumulation of protoporphyrin in the liver, leading to acute liver failure (ALF); clinical manifestations of acute renal failure may progress to acute symptoms within a few days.

Inheritance is autosomal dominant, but clinical manifestations are observed only in those patients who have both the defective EPP gene and an unusual, poorly functioning (but otherwise normal) allele from healthy patients. The prevalence of the pathology is 5/1,000,000.

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Symptoms of erythropoietic protoporphyria

The severity of the developing pathology varies even among patients from the same family. Usually, newborns or small children scream for hours after a short stay in the sun without stopping. However, they usually have no skin symptoms, and the child cannot describe their symptoms, so erythropoietic protoporphyria often goes unrecognized.

If the disease is not diagnosed, latent erythropoietic protoporphyria can cause psychosocial problems in the family because the child inexplicably refuses to leave the house. The pain can be so severe that it can cause patients to become nervous, tense, aggressive, or even feel alienated from others or to attempt suicide. In childhood, crusting of the skin may form around the lips and on the back of the hands after prolonged sun exposure. Burn blisters and scarring do not develop. If patients chronically neglect to protect their skin, they may develop rough, thickened, animal-like skin, especially around the joints. Perioral striations (carp mouth) may develop. Excretion of large amounts of protoporphyrin in the bile may cause cholestasis, which may result in nodular cirrhosis and acute liver failure in 10% or more of patients; symptoms include jaundice, malaise, upper abdominal pain (in the right hypochondrium), and diffuse liver enlargement.

Diagnosis of erythropoietic protoporphyria

Erythropoietic protoporphyria should be suspected in children or adults with painful cutaneous photosensitivity but no history of burn blisters or scars. There is usually no family history. The diagnosis is confirmed by finding high levels of protoporphyrin in red blood cells and plasma. Genetic markers predisposing to the development of cholestatic complications have been identified.

Screening of potential carriers of the abnormal gene among the patient's relatives illustrates increased protoporphyrin content in red blood cells and decreased ferrochelatase activity (when examining lymphocytes) or genetic testing in the case of an identified gene mutation in typical cases. The predisposition of carriers to cutaneous manifestations of the disease is recognized by the detection of a poorly functioning ferrochelatase allele.

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Treatment of erythropoietic protoporphyria

Acute symptoms are relieved by prescribing cool baths, wet towel wraps and analgesics. Of utmost importance are regular consultations of the patient with the doctor, receiving from him the necessary recommendations, information brochures, joint (with the doctor) discussion of his condition and the possibility of receiving the necessary consultations on issues of conducting genetic analysis under the supervision of a specialist.

Patients should avoid sun exposure, use dark titanium dioxide or zinc oxide sunscreens, and UV-absorbing screens (such as those containing dibenzylmethane), which may help protect the skin to some extent. Patients should avoid alcohol and fasting when there is an increase in red blood cell production and when protoporphyrin levels are elevated. Drugs that trigger acute porphyria are not contraindicated.

Beta-carotene administration of 120 to 180 mg orally once a day for children or 300 mg once a day for adults causes the appearance of a light yellow protective skin color and neutralizes the toxic radicals in it, which cause the development of skin symptoms. Another antioxidant, cysteine, can also help reduce photosensitivity. The appearance of a brown protective skin color with local deposition of dihydroxyacetone-3 is the main effect, cosmetically more preferable to the yellowish skin tone obtained with the use of beta-carotene.

If the above measures are ineffective (e.g., with increased photosensitivity, increased porphyrin concentrations, progressive jaundice), treatment involves hypertransfusion (i.e., above normal hemoglobin levels) of red blood cells, which will help reduce the production of porphyrin-containing red blood cells. Administration of bile acids facilitates biliary excretion of protoporphyrin. Oral administration of cholestyramine or activated charcoal can stop the intrahepatic circulation, which results in increased excretion of porphyrin in the stool. If severe liver failure develops, liver transplantation may be required.