Scleromyxedema-like lesions of patients in renal failure contain hyaluronan: a possible pathophysiological mechanism

Background: Patients with renal failure have been identified recently, some on dialysis, others with renal transplants, who have scleromyxedema-like skin changes. These lesions are characterized grossly by extensive thickening of skin, brawny pigmentation, papules, and subcutaneous nodules. Mucinous deposits are observed histologically that resemble those in scleromyxedema. Methods: Biopsies of these lesions were stained with a biotinylated hyaluronan (HA)-binding protein coupled to an avidin-peroxidase reaction. Results: These lesions are associated with marked deposition of HA in the papillary dermis. Conclusions: HA turnover is cleared rapidly in the circulation by both liver and kidney. Evidence suggests that high molecular size HA chains, which are anti-inflammatory, antiangiogenic, and immuno-suppressive are cleared by the liver. By contrast, intermediate-size fragments, which are highly angiogenic, inflammatory, and a stimulus for fibrous deposition, are cleared by the kidney. The accumulation of such fragments in renal failure can account for HA deposition in the dermis and may be a mechanism for the nephrogenic fibrosing dermopathy that can accompany these lesions.