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Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)

Erythropoietic Protoporphyria is a disease of porphyrin metabolism characterized by abnormally elevated levels of protoporphyrin IX in erythocytes (mature blood cells), feces and plasma (the fluid portion of circulating blood), and by sensitivity to visible light.

This sensitivity manifests itself as a burning sensation in the skin, followed by varying degrees of erythema (redness of the skin due to capillary dilation) and edema (swelling caused by excess fluids). Consequently, patients with the disorder commonly avoid exposure of the skin to strong light. They tend to choose indoor occupations and nocturnal work, or to venture outdoors while heavily clothed to protect the skin.

Diagnosis

EPP is diagnosed in patients with light sensitivity by testing blood and stool for the presence of abnormally high levels of protoporphyrin. Contrary to what is found in the other porphyrias, urine porphyrin levels remain within normal limits in EPP. When a smear of blood from a patient is examined under the fluorescence microscope, large numbers of red fluorescing erythrocytes are seen; these are not seen in persons who do not have this disorder. In addition, if the skin of the light-exposed areas of the body is examined under the light microscope, an amorphous homogeneous substance in and around the walls of small blood vessels of the upper papillary dermis will be seen. Histologic studies suggest that this substance is a neutral mucopolysaccharide, glycoprotein or mucoprotein. EPP is genetically transmitted as an autosomal recessive trait. Some relatives of patients may also have only slightly elevated levels of protoporphyrin but are asymptomatic, suggesting the existence of a carrier state.

Clinical Features

Most EPP patients experience the onset of photosensitivity before the age of six years and some as early as eighteen months. Patients report, in decreasing order of frequency, burning, swelling, itching and redness of the skin. After severe episodes of photosensitivity, some patients acquire shallow-depressed scars over the nose and cheeks and on the backs of hands. Some patients report only subjective symptoms of itching and burning and have no redness, swelling or scarring; these patients are often dismissed by their physicians as hypochondriacs, when in reality they have EPP. Thus, it is important for the physician to investigate for the presence of the disease in all patients who report itching and burning of the skin on exposure to light, even in the absence of objective findings. The amount of exposure to sun that a patient with EPP can tolerate varies from a few minutes to several hours. This photosensitivity is to light in the visible spectrum (400 to 700 nm). These wavelengths are not absorbed by window glass. Therefore, the symptoms can also develop from light passing through glass windows. About half of the patients report decreases in photosensitivity during winter. However, those engaging in skiing report that the light reflected by snow causes severe photosensitivity reactions. EPP is generally a benign disease. Many patients have somewhat decreased levels of hemoglobin and hematocrit (percentage of the volume of a blood sample occupied by cells). This finding usually requires no treatment. One reported case with severe hemolytic anemia (anemia caused by excessive destruction of red blood cells) improved after splenectomy (removal of the spleen). There also seems to be an increased frequency of cholelithiasis (presence of the formation of solid material in the gall bladder or bile duct), with several patients requiring cholecystectomy (removal of the gall bladder). Chemical analysis of the gallstones reveals high levels of protoporphyrin. To summarize, in EPP a decreased amount of the enzyme ferrochelatase leads to the accumulation of protoporphyrin in reticulocytes (young red blood cells that appear especially during regeneration of lost blood). This excess protoporphyrin leaks rapidly into the plasma from the maturing reticulocytes and young erythrocytes. The protoporphyrin is then partially cleared from the plasma by the liver and excreted into the bile (with or without some recirculation via the enterohepatic circulation). Accumulation of this protoporphyrin in the liver may lead, in rare cases, to serious liver disease.

Aides

Patients with EPP have found that topical sunscreens, which are effective in protecting against hypersensitivity to the sunburn spectrum of light, are ineffective as protective agents. Various systemic agents, such as antimalarials, inosine and vitamin E, have been tried but with little success. Patients with EPP may develop liver abnormalities due to an excess deposition of protoporphyrin in that organ. Hence, drugs that can impair bile flow, cholestasis, as well as estrogens, should be given cautiously. Cholestyramine ingestion may lower porphyrin levels in some patients. Some patients with EPP report that drinking alcoholic beverages increases their photosensitivity. It is probably wise for all EPP patients to avoid or greatly reduce alcohol consumption. Individuals with EPP may also need to wear protective clothing, such as garments with long sleeves and trousers: each one has to decide the amount of this sort of protection needed. Certain kinds of fabric, such as denim, are quite light protective. Also certain plastic materials, such as Scotchtint, filters out harmful rays and can be used on home and automobile windows.