A Case of Atypical Hemolytic Uremic Syndrome and Scleroderma Renal Crisis Successfully Treated with Ravulizumab

Introduction: Scleroderma renal crisis is a fatal complication of scleroderma, characterized by severe hypertension, acute renal failure, rapidly progressive congestive heart failure, and possible microangiopathic hemolytic anemia. Given its relation to activation of the complement system, scleroderma renal crisis can rarely trigger atypical hemolytic uremic syndrome (aHUS), which has been documented in the literature. We present a case of concurrent aHUS and scleroderma successfully treated with ravulizumab (C5 complement inhibitor). Case Description: A 24-year-old female with no previous known medical conditions was diagnosed with diffuse scleroderma after presenting clinically with several months of skin dryness, skin tightness, Raynaud’s phenomenon sensation, and bilateral foot swelling. Two months after her initial diagnosis, she was hospitalized for fatigue and generalized weakness and found to be in acute renal failure. Renal biopsy at the time reportedly showed thrombotic microangiopathy (TMA), and skin biopsy was consistent with scleroderma. Initially, TMA on the renal biopsy was attributed to scleroderma renal crisis but then later diagnosed as aHUS which was then treated with complement inhibition with significant improvement noted. She was initially treated with eculizumab then ravulizumab leading to remission. She has now been doing well on C5 blockade for the past 10.5 years. For her scleroderma maintenance therapy, she remains on Rituximab and myfortic with close monitoring by her rheumatologist. Discussion: This case demonstrates the successful treatment of aHUS due to scleroderma and scleroderma renal crisis with C5 complement inhibitor after failure to control TMA with standard scleroderma renal crisis treatment. Scleroderma renal crisis is typically treated with ACE inhibitors, and more experimental therapies include plasma exchange therapy, bosentan, and prostacyclin. Given that scleroderma renal crisis and aHUS are both likely triggered by an overactive complement system, it is reasonable that these conditions can be associated with one another and treated with complement inhibitors. This case illustrates yet another example of safe long-term maintenance therapy on a long-acting C5 complement inhibitor in a case of scleroderma renal crisis and aHUS.