Erythropoietic protoporphyria: Description, Causes and Risk Factors:
Erythropoietic protoporphyria is a rare disorder of heme biosynthesis characterized by early-childhood onset of acute photosensitivity of sun-exposed skin. It is an autosomal dominant disorder with incomplete penetrance. Its prevalence in the general population is 10 to 20 per 100,000, without any ethnic or gender predominance.
Erythropoietic protoporphyria is caused by a deficiency of ferrochelatase, the final enzyme in heme synthesis, which leads to an accumulation of protoporphyrin in various tissues, including the skin and liver. The release of protoporphyrin from erythrocytes is increased if the erythrocytes are exposed to light.
The cutaneous symptoms are a consequence of protoporphyrin sensitized photodamage of endothelial cells as well as initiating inflammatory pathways. Free oxygen radicals are released from the light-excited protoporphyrins, which leads to peroxidation of lipids and cross-linking of membrane proteins, which causes hemolysis of erythrocytes. Protoporphyrin also induces the release of mast-cell mediators such as histamine, prostaglandin D, leukotrienes, and platelet-activating factor. Complement activation with the generation of anaphylatoxins also plays a role in the phototoxicity. Polymorphonuclear cell chemotaxis also increases to the affected area after light exposure.
Erythropoietic protoporphyria is a disease state that can cause tremendous physical distress to children as well as great psychological distress to parents. This distress may be further compounded by a delayed diagnosis, or, in some cases, a lack of a diagnosis. Moreover, a lack of diagnosis may even become life-threatening in cases of severe liver damage. However, much of the distress and sequelae of this disease can be relieved by dermatologists maintaining a keen awareness of EPP in patients who present with photosensitivity irrespective of clinically evident lesions. With this awareness, a more timely diagnosis of EPP can ultimately be made resulting in both appropriate and effective management of the patient.
Typically, Erythropoietic protoporphyria presents in childhood; the affected child cries and complains of burning of the skin on the face and hands within minutes of sun exposure. Delayed effects that occur several hours later include swelling or erythema of the affected area. Petechiae
and purpura may also occur; however, blisters
or vesicles are uncommon. Patients may eventually develop a waxy cobblestone-like induration of the affected area, frequently on the knuckles and fingers.
Major presenting symptoms and signs include burning (97%), edema (94%), itching (88%), erythema (69%), and scarring of the skin (19%).
The diagnosis of Erythropoietic protoporphyria is established by finding an abnormally high free erythrocyte protoporphyrin in the FEP (free erythrocyte porphyrin) test, which is done on red blood cells. Note that the zinc protoporphyrin test (ZPP) is not appropriate so it is necessary to order the FEP test. This test may also be known as the RBC protoporphyrin or red-cell protoporphyrin test. Another appropriate test is the porphyrins, fractionation, erythrocytes or RBC test, which also measures protoporphyrin, along with other porphyrins found in the red blood cells.
EPP patients should have the following tests annually: an FEP test, a complete blood count and a blood chemistry panel including liver chemistries such as bilirubin, SGOT (serum glutamic-oxaloacetic transaminase) and SGPT (serum glutamic-pyruvic transaminase). People with EPP tend to run low hemoglobins, but not usually so low as to need treatment. To try and prevent anemia, patients should be encouraged to eat iron-containing foods such as red meat, spinach, baked potato with skin, red kidney beans, raisins, etc.
A liver biopsy specimen mayreveal an accumulation of deposits with periportal fibrosis. Molecular analysis of the ferrochelatase mutation reveals missense, deletion,and nonsense mutations, leading to functionaldeficiency of ferrochelatase.
Treatment includes avoidance of sunlight and the use of topical sunscreen agents with an SPF of > 30 and ideally containing reflective components such as zinc or titanium oxide. Oral administration of beta carotene has been used as well, at a dose of 120 to 180 mg daily to achieve a serum beta carotene level of 600 to 800 g/dL. Beneficial effects are usually seen 1 to 3 months after the initiation of therapy. The mechanism of action may be from the reducing of activated free oxygen radicals. Cholestyramine (5 g, three times daily) has also been used to decrease porphyrin levels. Vitamin E and pyridoxine have also been used, with limited success. Transfusions of red blood cells and intravenous heme have been helpful in refractory cases. At this time, ferrochelatase replacement is unavailable. The prognosis in general is good for most patients with EPP in the absence of liver failure.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.