Pseudoporphyria

Updated: Jun 21, 2016
  • Author: Vineet Mishra, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Porphyrias are metabolic disorders of heme synthesis. Partial enzymic deficiencies result in excessive accumulation and excretion of 5-aminolevulinic acid, porphobilinogen, and/or porphyrins. Porphyria cutanea tarda (PCT) is the most common of the porphyrias in North America and Europe. First described by Waldenström in 1937, this blistering disorder is caused by a deficiency of uroporphyrinogen decarboxylase, an enzyme in heme biosynthesis. [1] Porphyrins accumulate in the liver, are transported in plasma, and are excessively excreted in the urine. Exposure of patients with porphyria cutanea tarda to sunlight results in increased skin fragility, vesicles, bullae, hypertrichosis, hyperpigmentation, sclerodermoid changes, dystrophic calcification, milia, and scarring in a photodistribution. Porphyria cutanea tarda can be inherited or acquired. Treatment options include phlebotomy and antimalarial medications.

Pseudoporphyria describes a bullous photosensitivity that clinically and histologically mimics porphyria cutanea tarda. However, no demonstrable porphyrin abnormalities are present. In 1964, Zelickson was first to describe this type of phototoxic reaction in patients after the use of nalidixic acid. [2] The skin lesions were indistinguishable from those observed in patients with porphyria cutanea tarda. Since this initial report, many other drugs have been incriminated in mediating this type of bullous photosensitivity. [3] Pseudoporphyria has been reported in patients with chronic renal failure treated with and without hemodialysis and in those with excessive exposure to ultraviolet A (UV-A) by tanning beds. [4, 5, 6]

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Pathophysiology

The precise pathophysiologic mechanism of pseudoporphyria is not fully understood. In 1983, Keane et al developed an animal model for nalidixic acid photosensitivity in CF-1 female mice. [7] Animals injected with nalidixic acid and then exposed to ultraviolet radiation for 10 weeks exhibited more severe cutaneous manifestations than mice treated with sodium chloride solution. Light and electron microscopy demonstrated a subepidermal split beneath the basal lamina at the same level as seen in histologic examination of porphyria cutanea tarda and pseudoporphyria. The authors suggested that a photosensitizing drug might behave in a similar fashion to photoactivated endogenous porphyrins and target similar structures in the skin. Several other authors have corroborated these findings.

Other mechanisms have been proposed to explain the role of ultraviolet or visible light radiation in drug-induced pseudoporphyria. An alternative theory is based on the finding that exogenous photosensitizers are deposited along the endothelium of blood vessels of lesional and nonlesional skin. An immune response targeted against antigens is proposed to develop after phototoxic injury to the dermal microvascular endothelium. Dabski and Beutner proposed a multistep mechanism in which exogenous photosensitizers (drugs) damage the vascular endothelium by the release of proteases after sunlight exposure. [8] Then, immunoglobulin G (IgG) and immunoreactants bind to the damaged endothelium, causing formation of bullae at the level of the lamina lucida as a secondary or tertiary event.

The pathophysiology of pseudoporphyria associated with hemodialysis has not been fully explained. Aluminum hydroxide has been implicated in hemodialysis-associated pseudoporphyria. Aluminum hydroxide is found in dialysis solution and has been shown to produce a porphyrialike disorder after long-term administration in rats.

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Epidemiology

Frequency

Pseudoporphyria is not uncommon. Although fewer than 100 cases are documented, pseudoporphyria is most likely underreported in the literature.

Race

Although pseudoporphyria has no predilection toward any one race, it has been shown that fair-skinned children who are highly prone to sunburn are more likely to develop naproxen-induced pseudoporphyria than those children with skin types III or higher. Wallace et al demonstrated that even in the absence of a history of blistering, children with light skin and blue or green eyes are at an increased risk of developing shallow scars on the face while taking naproxen. [9]

Sex

Pseudoporphyria affects males and females equally.

Age

The ages of patients reported with pseudoporphyria range from 2-81 years. It has been reported that the mean age at diagnosis was 50 years in a retrospective study of 20 cases. [10]

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Prognosis

The prognosis is good for pseudoporphyria once the offending agent has been discontinued. However, it may take several months for all the skin lesions to resolve, and some can be complicated by infection or prolonged scarring, which has been noted to last up to 5 years. [11, 12]

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Patient Education

Educating patients about the causes of pseudoporphyria is important. Patients should avoid solar and tanning salon radiation. If the condition was drug related, patients should avoid medications in a similar class of drugs (eg, other propionic acid NSAIDs) whenever possible.

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