Thrombotic Microangiopathy Secondary to Systemic Sclerosis with Severe Complement Activation Not Responsive to...

BACKGROUND Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions and most are resolved by treating the underlying disease. Eculizumab, a human monoclonal antibody, blocks the final stages of the complement system. Several studies have shown that complement C5 monoclonal antibodies are effective in treating secondary TMA. Systemic sclerosis (SSc) is one of the most common causes of secondary TMA, and early diagnosis is important because TMA secondary to SSc has a poor prognosis. We report a case of TMA secondary to SSc that did not respond to eculizumab, despite the presence of severe complement activation. CASE REPORT A 61-year-old previously healthy man was admitted for acute renal failure and thrombocytopenia. TMA was suspected because hemolytic anemia, thrombocytopenia, and organ damage were detected. Based on the physical findings, we suspected SSc as the underlying cause. All tests for specific antibodies, including Scl-70, were negative, and C5b-9 levels were markedly elevated (11 041 ng/mL). We initiated plasma exchange on day 3, followed by eculizumab therapy, but with limited improvement. SSc with secondary TMA was identified upon further testing. After completion of the plasma exchange, the platelet count was maintained above 30 000/μL. Creatinine levels gradually decreased, and the patient was weaned off dialysis. Steroid treatment for SSc was continued, and the patient was eventually discharged. CONCLUSIONS A case of SSc-TMA was ineffectively treated with eculizumab, despite abnormal activation of the complement system. Continuous monitoring and investigation are required, and discontinuation of eculizumab should be determined according to the final diagnosis.