Erythropoietic protoporphyria: causes, symptoms, diagnosis, treatment

The characteristic clinical manifestations of erythropoietic protoporphyria can develop already in newborns in the form of burns on the skin even after a short stay in the sun. The development of cholelithiasis is characteristic of a later age, with the course of the disease, and acute liver failure develops in about 10% of patients. Diagnosis is based on clinical symptoms and increased levels of protoporphyrin in erythrocytes and blood plasma. Treatment consists in the administration of beta-carotene and protection against direct sunlight on the skin.

[1], [2], [3]

Causes of erythropoietic protoporphyria

Erythropoietic protoporphyria is the result of a deficiency of ferrochelatase enzyme in erythroid tissue. Phototoxic protoporphyrins accumulate in the bone marrow and erythrocytes, enter the plasma and are then deposited in the skin or excreted by the liver with bile and stool. Excretion of heavy biliary protoporphyrin from the body can promote the formation of gallstones. These cytotoxic molecules sometimes damage the hepatobiliary tract, resulting in the accumulation of protoporphyrin in the liver, leading to the development of acute liver failure (ARF); clinical manifestations of acute renal failure may develop until acute symptoms in a few days.

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

[4], [5], [6], [7], [8]

Symptoms of erythropoietic protoporphyria

The severity of developing pathology is different even in patients from the same family. Usually newborns or small children after a short stay in the sun are screaming for hours, without ceasing. Nevertheless, skin symptoms are usually absent, and the child can not describe its symptoms, therefore erythropoietic protoporphyria often proceeds unrecognized.

If the disease is not diagnosed, secretive erythropoietic protoporphyria can cause psychosocial problems in the family due to the fact that the child inexplicably refuses to leave the house on the street. The pain can be so unbearable that it can cause such symptoms in patients as nervousness, tension, aggressiveness or even a feeling of estrangement from others or suicidal attempts. In childhood, the skin can form crusts around the lips and on the back of the hands after a long stay in the sun. Burn blisters and scarring do not develop. If patients chronically neglect the protection of their skin, they can develop coarsening, thickening of the skin, it becomes like the skin of animals, especially around the joints. Can develop a furrowed perioral striation ("carp mouth"). Excretion of a large amount of protoporphyrin with bile can cause cholestasis, which can lead to nodular cirrhosis and acute liver failure in 10% or more patients; symptoms include jaundice, general malaise, pain at the top of the abdomen (in the right hypochondrium) and diffuse enlargement of the liver.

Diagnosis of erythropoietic protoporphyria

Erythropoietic protoporphyria should be suspected in children or adults with painful skin photosensitivity, but without an anamnesis of burn blisters and scars. Family history is usually not observed. The diagnosis is confirmed after the detection of high concentrations of protoporphyrin in erythrocytes and plasma. Identified genetic markers predisposing to the development of cholestatic complications.

The screening of potential carriers of the abnormal gene among the patient's relatives illustrates the increased content of protoporphyrin in erythrocytes and the decreased activity of ferrochelatase (in the study of lymphocytes) or genetic research in the case of an identified gene mutation in typical cases. Predisposition of carriers to cutaneous manifestations of the disease is recognized by the detection of a weakly functioning ferrochelatase allele.

[9], [10], [11]

Treatment of erythropoietic protoporphyria

Acute symptoms are facilitated by the appointment of cool baths, wraps with a damp towel and analgesics. It is extremely important to regularly consult a patient with a doctor, get the necessary recommendations from him, informational brochures, discuss his condition with the doctor and get the necessary consultations on conducting an anapase under the supervision of a specialist.

Patients should avoid exposure to sunlight, use dark titanium dioxide or zinc oxide with solar screens and UV-absorbing screens (for example, containing dibenzylmethane), which in part can help protect the skin. Patients should avoid alcohol and starvation and in those cases when an increase in the production of red blood cells is observed, and in the case of an increase in the content of protoporphyrin. Drugs that provoke the development of acute porphyria are not contraindicated.

The administration of beta-carotene from 120 to 180 mg orally once a day to children or 300 mg once a day to adults causes the appearance of 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, cosmetically more preferred yellowish skin tone obtained by using beta-carotene, an effect.

If the measures described above are ineffective (for example, with increased photosensitivity, increased porphyrin concentration, progressive jaundice), the treatment uses hypertransfusion (ie, above normal hemoglobin levels) of erythrocyte mass, which will help reduce the production of porphyrin-containing red blood cells. The administration of bile acids facilitates the biliary excretion of protoporphyrin. Oral intake of cholestyramine or activated charcoal can stop intrahepatic circulation, which increases the excretion of porphyrin and stool. In case of development of severe hepatic insufficiency, liver transplantation may be required.