Vascular changes in erythropoietic protoporphyria: Histopathologic and immunohistochemical study

Background: Erythropoietic protoporphyria (EPP) is an inherited disease cau sed by deficient activity of ferrochelatase in the heme biosynthetic pathwa y. Accumulation of protoporphyrins and light exposure results in acute phot otoxic skin reactions. The histopathologic findings of the light-exposed sk in are thickening of the superficial dermal vessel walls and amorphous depo sits around the vessels, but the origin and detailed composition of the per ivascular material have been unclear. Objective: The vascular morphology and composition of the perivascular mate rial were studied in the skin samples of patients with EPP. Methods: Skin biopsy specimens of 8 patients with EPP representing 7 Finnis h 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-pos itive vessel walls caused by concentric reduplication of basal lamina and e xcess of fine granular material at the basal membrane zone in the superfici al dcl mis. The perivascular deposits in the vicinity of vessel walls had a homogeneous or fine granular appearance without filaments. Direct immunofl uorescence showed constant IgG deposits together with IgA, IgM, and C3 in t he vessel walls. In immunohistochemistry, collagen IV and laminin could be demonstrated at the vascular basal membrane together with serum amyloid P p rotein, 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 ph otoreaction. The repealed acute damage and repair processes in the basement membrane zone result in thickening of the vessel walls. Perivascular depos its are a secondary and irreversible phenomenon resulting from the leakage and accumulation of different serum components. These changes were not foun d in the nonexposed skin, indicating that an increased level of erythrocyte protoporphyrin per se is not responsible fur the cutaneous manifestations, but the interaction of solar radiation is mandatory. Amorphous deposits di stinguish EPP from variegate porphyria and porphyria cutanea tarda; a histo pathologic examination may be a helpful tool in differentiating porphyric a nd nonporphyric photosensitivity.