SNEDDONS SYNDROME - AN INFLAMMATORY DISORDER OF SMALL ARTERIES FOLLOWED BY SMOOTH-MUSCLE PROLIFERATION - IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL EVIDENCE

Sneddon's syndrome is a rare, but potentially severe, arterioocclusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized art eries of unknown cause. We have recently shown that, in skin, small to medium-sized arteries of the dermis-subcutis boundary are affected in a stage-specific sequence. An initial phase (stage I), characterized by the attachment of lymphohistiocytic cells and detachment of endothe lial cells (endothelitis), is followed by an early phase (stage II), w hich displays partial or complete occlusion of the lumen by a plug of lymphohistiocytic cells and fibrin. In an intermediate phase (stage II I), the occluding plug is replaced by proliferating subendothelial cel ls accompanied by the occurrence of dilated capillaries in the adventi tia of the occluded vessel. The late phase (stage IV) shows fibrosis a nd shrinkage of the affected vessels. We investigated sections of para ffin-embedded specimens of 18 patients by immunohistochemistry using a panel of antibodies to detect endothelial cells, macrophages, T cells , smooth muscle-specific actin, and intermediate filaments(vimentin, d esmin). We found that the cells involved in subendothelial proliferati on were vimentin and actin positive (smooth-muscle-specific), but desm in negative and thus displayed the phenotype characteristic of smooth muscle cells, which was confirmed by ultrastructural studies. CD3(+), UCHL-1(+), and HLA-DR(+) cells constituted a significant proportion of the inflammatory infiltrate in the early stages. The endothelial cell s in the dilated capillaries of the adventitia were strongly HLA-DR po sitive. In later stages, endothelial cells and leukocytes were scarce. The data confirm the hypothesis that Sneddon's syndrome starts as an inflammatory and possibly immunologically mediated disorder, leading t o a migration and proliferation of smooth cells of small arteries, res ulting in a partial or complete narrowing of the vessel lumen.