Nonspecific capillary proliferation and vasculopathy indicate skin hypoxia in erythromelalgia

To report on the histopathologic findings of affected skin in consecutively collected biopsy specimens from 49 patients with erythromelalgia (EM).

Skin biopsy specimens were obtained from the foot arch and analyzed by light microscopy, immunofluorescence microscopy, and electron microscopy.

Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway.

Thirty-one patients had primary EM, 17 patients had secondary EM, and 1 patient had erythromelalgic syndrome.

Evidence of microvascular abnormalities in skin biopsy specimens.

Light microscopy showed evidence of capillary proliferation in 10 of 31 patients with primary EM and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient with erythromelalgic syndrome showed numerous capillary nests with endothelial cell defects and a slight perivascular inflammatory reaction. Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus. Eleven patients also had signs of vasculopathy based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with primary EM showed endothelial abnormalities on electron microscopy. All 3 investigations showed unremarkable biopsy results in 16 cases.

Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain.