E-Mail Scleroderma, a chronic and currently incurable orphan disease where tissue injury causes potentially lethal skin and lung scarring, remains poorly understood. However, the defining characteristic of systemic sclerosis, the most serious form of scleroderma, is irreversible and progressive scarring that affects the skin and internal organs. Published in "We found that scleroderma inflammation dramatically increases CD38, an enzyme that normally breaks down a metabolic nutrient, NAD+. When NAD+ levels decrease, tissue injury becomes chronic and progresses to scar formation rather than to healthy repair," says study author John Varga, M.D., division chief of rheumatology at Michigan Medicine. According to the study, treatments that prevented NAD+ reduction in the mice, whether by boosting the levels of the nutrient genetically or pharmacologically, prevented scarring in the skin, lungs and abdominal wall.