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Abstract: PO1505

Atypical Hemolytic Uremic Syndrome and Systemic Lupus Erythematosus-Diabetes Mellitus Overlap: A Challenging Scenario

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Drexler, Yelena R., University of Miami School of Medicine, Miami, Florida, United States
  • Rodriguez, Juanly N., University of Miami School of Medicine, Miami, Florida, United States
Introduction

Overlap syndromes are rare disorders wherein at least two systemic autoimmune diseases meet diagnostic criteria. We present a case of atypical hemolytic uremic syndrome (aHUS) in a patient with systemic lupus erythematous (SLE) and anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5) dermatomyositis (DM) overlap.

Case Description

A 45-year-old woman with SLE diagnosed 8mo prior, treated with belimumab and prednisone, developed proximal muscle weakness, violaceous erythema of eyelids, neck, hands and feet with ulcers. Three weeks later, she presented with abdominal pain, shock and respiratory failure. Testing showed WBC 19,200/uL, lipase >600 and ionized calcium 0.47 mmol/L; acute kidney injury (BUN 64 mg/dL, SCr 2.4 mg/dL); anemia (Hb 7.1 g/dL); and thrombocytopenia (PLT 24,000). CT showed pancreatitis and omental nodularity. Given oliguria and hypocalcemia despite high-dose calcium infusion, she initiated renal replacement therapy. Further workup showed low C3 level 42, C4 level 7, elevated anti-dsDNA Ab 237 IU/ml and UPCR 2.2 g/g; haptoglobin <10, LDH 1,371 U/L, Positive direct Coombs, schistocytes on smear and ADAMTS13 activity 18%. Due to autoimmune vs microangiopathic hemolytic anemia, received pulse methylprednisolone and IVIG without improvement. She then started eculizumab. Within 7d, LDH decreased to 772, haptoglobin increased to 79 and platelets normalized. Further workup revealed elevated creatine kinase 1,271 U/L, aldolase 17 U/L, AST 566 U/L with normal ALT and positive anti-MDA5 and transcription intermediary factor 1-gamma (TIF-1γ) Abs, meeting criteria for DM. Patient continued eculizumab and prednisone. Eventually developed invasive aspergillosis and expired.

Discussion

We report a case of SLE–DM overlap with anti-MDA5 and TIF-1γ Abs complicated by aHUS and severe hypocalcemia in the setting of pancreatitis. The cutaneous manifestations are typical of MDA5-associated DM. Our patient did not develop interstitial lung disease, exemplifying range of variation from case to case. The presence of anti-TIF-1γ confers a 6-fold increased malignancy risk; finding of omental nodularity in this case would warrant further investigation. aHUS as a complication of SLE-DM overlap is rare, with mortality risk up to 52%. AKI, infection and low C3 are associated with highest mortality. Prompt diagnosis, high clinical suspicion and early initiation of eculizumab resulted in a rapid response.