Vascular changes in erythropoietic protoporphyria: histopathologic and immunohistochemical study.

BACKGROUND: Erythropoietic protoporphyria (EPP) is an inherited disease caused by deficient activity of ferrochelatase in the heme biosynthetic pathway. Accumulation of protoporphyrins and light exposure results in acute phototoxic skin reactions. The histopathologic findings of the light-exposed skin are thickening of the superficial dermal vessel walls and amorphous deposits around the vessels, but the origin and detailed composition of the perivascular material have been unclear. OBJECTIVE: The vascular morphology and composition of the perivascular material were studied in the skin samples of patients with EPP. METHODS: Skin biopsy specimens of 8 patients with EPP representing 7 Finnish EPP families with different genotypes were studied by means of light and electron microscopy and immunohistochemical methods. RESULTS: The characteristic finding was thickened, periodic acid-Schiff-positive vessel walls caused by concentric reduplication of basal lamina and excess of fine granular material at the basal membrane zone in the superficial dermis. The perivascular deposits in the vicinity of vessel walls had a homogeneous or fine granular appearance without filaments. Direct immunofluorescence showed constant IgG deposits together with IgA, IgM, and C3 in the vessel walls. In immunohistochemistry, collagen IV and laminin could be demonstrated at the vascular basal membrane together with serum amyloid P protein, kappa and lambda light chains, and a 90-kd glycoprotein. CONCLUSION: The vascular involvement indicates that the blood vessel walls in the papillary dermis are the primary tissues affected during an acute photoreaction. The repeated acute damage and repair processes in the basement membrane zone result in thickening of the vessel walls. Perivascular deposits are a secondary and irreversible phenomenon resulting from the leakage and accumulation of different serum components. These changes were not found in the nonexposed skin, indicating that an increased level of erythrocyte protoporphyrin per se is not responsible for the cutaneous manifestations, but the interaction of solar radiation is mandatory. Amorphous deposits distinguish EPP from variegate porphyria and porphyria cutanea tarda; a histopathologic examination may be a helpful tool in differentiating porphyric and nonporphyric photosensitivity.

Erythropoietic protoporphyria with antinuclear antibody positivity: avoiding misdiagnosis of systemic lupus erythematosus.

A young eunuchoid man was referred to our hospital with suspected erythropoietic protoporphyria. Serum antinuclear antibody (ANA) was found to be positive immediately after the porphyria attack and disappeared 30 days later. Many authors have mentioned the coexistence of systemic lupus erythematosus (SLE) and porphyria. As these two disorders have similar clinical features, the clinician must be alert and use strict diagnostic criteria in determining the presence of SLE with porphyria. In the past, elevation of ANA was reported in the cases of acute intermittent porphyria. However, there have been no reports in the cases of erythropoietic protoporphyria. In addition, the patient was found to have hypogonadotropic hypogonadism consistent with Kallmann's syndrome. To our knowledge, this report is the first case showing the coexistence of Kallmann's syndrome and erythropoietic protoporphyria. As yet, the clinical importance of this association remains unknown.