Abstract: PUB347
Thrombotic Microangiopathy in Scleroderma: Is It Always a Crisis?
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Dweik, Loai, Cleveland Clinic Akron General, Akron, Ohio, United States
- Herlitz, Leal C., Cleveland Clinic, Cleveland, Ohio, United States
- Tomaszewski, Kristen, Cleveland Clinic, Cleveland, Ohio, United States
- Cavanaugh, Corey J., Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Thrombotic microangiopathy (TMA) is a pathological lesion seen across many diseases, initiated by endothelial injury and/or dysfunction. In systemic sclerosis (SS), the presentation has classically been described as a rapid onset of hypertension with declining kidney function and RNA polymerase III (RNApolIII) positivity. Prompt initiation of Angiotensin Converting Enzyme inhibitor (ACEi) is crucial for treatment. Here we describe an atypical case of TMA in SS and the use of complement targeted therapy.
Case Description
This case describes a 66-year-old female with a medical history of hypothyroidism, SS and myositis overlap who presented with muscle weakness and acute renal failure. Physical examination revealed blood pressure (BP) of 143/75, wheezing, decreased breath sounds on auscultation, purple discoloration of fingertips with ulceration and calcinosis of second and third right fingertips. Creatinine was 1.4mg/dl from a baseline of 0.8-0.9 mg/dl and platelets 145 k/uL, electrolytes and blood counts were otherwise normal. The patient had positive ANA and Anti-SSA titers. RNApolIII, C3, C4 were normal. Despite her BP, she was started on captopril. Kidney biopsy was pursued and revealed acute thrombotic angiopathy and microangiopathy, as evidenced by widespread fibrin thromboses, and intimal edema within arteries and arterioles with accumulation of schistocytes. There was no adventitial fibrosis or onion skinning, reflective of a relatively acute onset.
Discussion
The findings of an unexpected amount of thromboses, normal BP readings on ACEi, and lack of RNAPolIII, cued pathology and nephrology to consider a complement mediated injury. Thus, as the patient exhibited deterioration in renal function, with creatinine rising to 1.95 mg/dl and worsening thrombocytopenia to 99 k/uL, the decision was made to start eculizumab. ADAMTS13, Factor B, H, and I testing were normal. Genetic testing is currently pending. After 1 month follow-up, creatinine remains stable at a level of 1.8mg/dl. It is important to consider TMA in patients with SS and acute renal failure, even in the absence of elevated BP. The report highlights the diverse nature of TMA even within a single disease entity like SS. TMA in SS should be classified as ACEi responsive or non-responsive. The use of complement targeting therapy should be considered in atypical cases, and those not responding to ACEi.