bowel wall, wide-mouthed diverticula in the colon and esophagus, and liver fibrosis. Patients with severe gastrointestinal involvement can become profoundly malnourished. Scleroderma may also be associated with gastric antral vascular ectasia, also known as "watermelon stomach". This is a condition in which atypical blood vessels proliferate, usually in a radially symmetric pattern around the pylorus of the stomach. It can be a cause of upper gastrointestinal bleeding or iron-deficiency anemia in patients with scleroderma. Kidneys Kidney involvement, in scleroderma, is considered a poor prognostic factor and frequently a cause of death. The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis (SRC), the symptoms of which are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood), and microangiopathic hemolytic anemia (destruction of red blood cells). Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative of SRC. In the past, SRC was almost uniformly fatal. While outcomes have improved significantly with the use of ACE inhibitors, the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop kidney failure. About 7–9% of all diffuse cutaneous scleroderma patients develop renal crisis at some point in the course of their disease. Patients who have rapid skin involvement have the highest risk of renal complications. It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against RNA polymerase (in 59% of cases). Many proceed to dialysis, although this can be stopped within three years in about a third of cases. Higher age and (paradoxically) a lower blood pressure at presentation make dialysis more likely to be needed. Treatments for SRC include ACE inhibitors. Prophylactic use of ACE inhibitors is currently not recommended, as recent data suggest a poorer prognosis in patient treated with these drugs prior to the development of renal crisis. Transplanted kidneys are known to be affected by scleroderma, and patients with early-onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence. Causes No clear cause for scleroderma and systemic sclerosis has been identified. Genetic predisposition appears to be limited, as genetic concordance is small; still, a familial predisposition for autoimmune disease is often seen. Polymorphisms in COL1A2 and TGF-β1