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July 7, 2008

Picture of the Month—Diagnosis

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Arch Pediatr Adolesc Med. 2008;162(7):690. doi:10.1001/archpedi.162.7.690

Denouement and Comment: Erythropoietic Protoporphyria

In this case, the key to diagnosis was the localization of the rash in phototherapy-exposed areas. The differential diagnosis of photosensitivity in the newborn includes a wide range of disorders including those related to DNA-repair syndromes (xeroderma pigmentosum, Rothmund-Thomson syndrome, Bloom syndrome, and Cockayne syndrome), transplacentally transferred collagen vascular disorders (neonatal lupus erythematosus and drug-induced lupus erythematosus), and the porphyrias.

In this case, the purpuric nature of the photodistributed skin findings suggested a porphyrin-related mechanism. While transient erythroporphyria of the newborn and transfusion-associated photosensitivity may present with similar findings, these tend to occur in the context of exchange transfusions, which did not occur in this case. Laboratory data obtained on day 6 of the infant's life revealed an elevated protoporphyrin level of 1089 μg/dL (normal, 16-60 μg/dL [to convert to micromoles per liter, multiply by 0.0178]). The patient also had normal serum levels of iron and hemoglobin and was negative for the antinuclear antibody. At 10 weeks of age, the infant's whole-blood porphyrin level demonstrated a persistent elevation in protoporphyrin levels, and a diagnosis of erythropoietic protoporphyria (EPP) was made. Elevations in maternal protoporphyrin levels were subsequently confirmed.

Erythropoietic protoporphyria is a disorder defined by a deficiency in ferrochelatase, the enzyme responsible for the last step in the porphyrin pathway that produces heme. Erythropoietic protoporphyria, inherited in an autosomal dominant fashion, is the most common childhood porphyria and typically presents between ages 2 and 5 years, when the amount of sun exposure increases. Parents may report childhood irritability and crying on exposure to sunlight. A history of skin pain, burning, tingling, or itching within 1 hour after being exposed to the sun is typical.1This sensation is usually followed by acute changes of erythema, edema, urticaria, and purpura of the exposed skin developing several hours after exposure. Chronic skin changes in EPP appear on sun-exposed areas such as the face, especially on the ears and nose, in the form of erosions, scars, or waxy skin thickening. Patients may display findings of hyperkeratosis and leathery skin on the dorsum of the hands and knuckles, known as velvet knuckles. Other physical examination findings can include opacification of the nail plates, onycholysis, and tenderness of the nail beds. Besides having skin changes, patients with EPP are prone to gallstones at an unusually early age. Liver disease is uncommon, but liver function testing should be monitored, as hepatic dysfunction may be severe enough to require liver transplantation.2-4

The diagnosis of EPP is made by demonstrating an elevation in free erythrocyte proporphyrin. Most other forms of cutaneous porphyria, in which water-soluble porphyrins accumulate in the skin, will have porphyrins detectable in the urine. The pathophysiology of EPP is based on the interaction between protoporphyrins in the skin and visible light. As a lipophilic porphyrin, protoporphyrin leads to phototoxicity and blood vessel damage in the dermis on interacting with visible light with wavelengths in the Soret band (400-440 nm). Free radicals produced in the dermis may ultimately lead to pain, swelling, redness, and erosions.

The most important step in the management of EPP is avoiding exposure to sunlight and using topical sunscreens. Some sources recommend dihydroxyacetone and iron oxide along with traditional UV-B/UV-A sunscreen.5Oral β-carotene may be used to increase sun tolerance and provide more systemic protection. Doses of 120 to 180 mg daily are recommended. Effects may be expected within 1 to 3 months. During operations in patients with EPP, exposure of the internal organs to the artificial lights used in the operating room can precipitate a deadly reaction.

Case reports of a photodistributed rash following phototherapy have been documented in children with congenital erythropoietic porphyria,6-8those with an entity known as transient porphyria of the newborn,9,10as well as in association with exchange transfusions.11This article therefore documents the first case of EPP presenting in the neonatal period following visible light phototherapy.

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Correspondence:Patrick McMahon, MD, Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104 (mcmahonpa@email.chop.edu).

Accepted for Publication:June 19, 2007.

Author Contributions:Study concept and design: McMahon and Yan. Acquisition of data: McMahon and Yan. Drafting of the manuscript: McMahon. Critical revision of the manuscript for important intellectual content: McMahon.

Financial Disclosure:None reported.

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