Progressive loss of lymphatic vessels in skin of patients with systemic sclerosis

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular and fibrotic changes in the skin and internal organs. The role of blood vessel dysfunction in the pathogenesis of SSc has been extensively investigated, but few studies have addressed the involvement of the lymphatic vascular system. Our aim was to evaluate dermal lymphatic vessels in patients with SSc according to different phases of skin involvement. METHODS: Skin biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late-stage disease) and 13 healthy controls. Skin sections were immunostained for podoplanin (D2-40), which is selectively expressed in lymphatic endothelial cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were counted in the papillary and reticular dermis. Data were analyzed using Student's t test. RESULTS: The number of lymphatic vessels was significantly reduced in the papillary and reticular dermis of SSc patients compared with controls. In early SSc, lymphatic vessel counts were not different from controls in the papillary dermis, and showed a trend toward a reduction in the reticular dermis. In late SSc, a significant reduction in lymphatic vessels compared with controls was found in both the papillary and reticular dermis. The number of lymphatic vessels in the papillary dermis of late SSc was significantly lower than in early SSc. CONCLUSION: In SSc, lymphatic microangiopathy is linked to the progression of skin involvement. The progressive disappearance of lymphatic vessels may have a critical pathogenetic role in the progression of SSc from an early edematous phase to overt fibrosis.