Erythropoietic protoporphyria

Erythropoietic protoporphyria

Maureen B. Poh-Fitzpatrick

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


In this metabolic disorder, a genetically determined deficiency of ferrochelatase enzyme activity in bone marrow erythroid cells causes abnormally high protoporphyrin levels in erythrocytes, plasma, liver, bile, and feces. Protoporphyrin is a photoactive intermediary of heme synthesis. In the skin, its exposure to long wave ultraviolet (UV) or visible light radiation can elicit oxygen-dependent acute cutaneous phototoxicity. Protoporphyrin undergoes hepatobiliary excretion, facilitating cholelithiasis. Protoporphyrin hepatotoxicity may develop and progress to irreversible liver failure. Hypochromic microcytic anemia, when present, is typically mild and rarely requires treatment.

Management strategy

Protoporphyric photosensitivity is rarely managed adequately by sun avoidance alone (i.e., lifestyle changes, protective clothing, physical barriers). Topical sunscreens containing titanium dioxide, zinc oxide, iron oxide, or dihydroxyacetone block or filter long wave UV and visible light spectra, and may offer limited relief. Epidermal melanization and hyperplasia achieved with UVB or psoralen plus UVA (PUVA) phototherapy, or an α-melanocyte stimulating hormone analogue (afamelanotide), increase sunlight tolerance. Oral agents believed to photoprotect by quenching excited oxygen species include βcarotene, cysteine, vitamin E, vitamin C, flavonoids, and possibly pyridoxine. Antihistamines may attenuate phototoxic flaring. Gallstones are managed surgically. Exacerbators of protoporphyrin-induced hepatotoxicity (alcohol, cholestatic drugs, dietary carbohydrate restriction) are best avoided. Vaccination against hepatitis A and B is recommended. Deteriorating liver function is only sporadically reversible by enteric sorbents (cholestyramine, activated charcoal) that interrupt enterohepatic porphyrin circulation, bile acids (to stimulate biliary protoporphyrin secretion), blood transfusion or exchange, hematin infusion, or glucose loading (to retard endogenous porphyrinogenesis), iron (to increase protoporphyrin conversion to heme), or various combinations thereof. Cimetidine is postulated to inhibit porphyrinogenesis. End-stage liver disease warrants liver transplantation, aided by measures to reduce pre-, intra- and postoperative porphyrin levels (exchange transfusion, hematin infusion, plasmapheresis, vitamin E). Operating room lamps should be filtered to exclude wavelengths that can severely damage porphyrin-photosensitized skin and internal organs. Bone marrow transplantation has been curative in highly selected cases, and would be optimal prophylaxis against protoporphyric hepatopathy in original or transplanted livers.

Specific investigations

Liver failure occurs in <5% of all cases. Because urine is typically free of excess porphyrins in uncomplicated protoporphyria, surveillance for coproporphyrinuria may identify patients with asymptomatic hepatic dysfunction.

First-line therapies

Beta-carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases.

Mathews-Roth MM, Pathak MA, Fitzpatrick TB, Harber LH, Kass EH. Arch Dermatol 1977; 113: 1229–32.

Of 133 patients with protoporphyria, 84% had a threefold increase in sunlight tolerance after ingesting pharmaceutical-grade β-carotene.

The same efficiently absorbed β-carotene is available without prescription (Lumitene, Tischcon). Doses producing serum levels of approximately 800 µg/dL (30–120 mg/day in children, 120–300 mg/day in adults, in two to three doses with meals), should be started four to 6 weeks before seasonal symptoms are anticipated. Efficacy varies, and is often nil. Increased incidence of lung cancer among heavy smokers treated with β-carotene in cancer prevention clinical trials raises concern about its use in smokers.

Aug 7, 2016 | Posted by in Dermatology | Comments Off on Erythropoietic protoporphyria

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