Case Presentation: A 20 year old man with history of Systemic Lupus erythematous (SLE) with Lupus nephritis presented to the hospital with cough and hemoptysis for the past few days. He was found to have severe anemia (5.4 mg/dl), thrombocytopenia (52,000/mm3), elevated LDH (829), low haptoglobin (<8), hypocomplentemia (low C3 and C4), schistocytes on peripheral smear with diffuse infiltrates on chest x-ray and acute kidney injury (AKI). He was intubated for airway protection and got urgent hemodialysis. A regimen including Cyclophosphamide and pulse doses of IV steroids was started along with intermittent RBC transfusions and hemodialysis sessions. CT chest without contrast showed diffuse bilateral patchy ground glass airspace opacities which were beginning to consolidate in the bilateral lower lobes concerning for multilobar pneumonia for which broad spectrum antibiotics were started. Anti dsDNA antibodies were positive and anticardiolipin, Anti-Ro/La, MPO, PR3, Anti smith, CCP and lupus anticoagulant and anti-phospholipid antibodies were negative. His prothrombin and plasma thromboplastin time were normal. Urine total protein was high (220mg/dl) with ADAMTS 13 activity 86%. Over the course of hospitalization he also received 10 sessions of plasmapheresis and repeat pulse dose steroids. In spite of standard therapy, patient had recurrent hemoptysis and no renal recovery. Repeat kidney biopsy showed mixed diffuse proliferative and membranous lupus nephritis (class IV and V) with endocapillary lesions, fibrocellular crescents and global sclerosis suggestive of lupus vasculopathy and thrombotic microangiopathy. Due to weak hematological, pulmonary and renal response to prior therapies, Eculizumab (human monoclonal antibody against complement C5) was started. After initiation of Eculizumab, the patient’s pulmonary and hematological status improved.
Discussion: This patient had an ADAMTS 13 activity of 86%, thus excluding thrombotic thrombocytopenic purpura as the diagnosis. Review of literature showed that Atypical HUS associated with Lupus nephritis has been seen only in very few patients with pulmonary involvement in even fewer case reports. The diffuse alveolar hemorrhage can be attributed to pulmonary microvasculature thrombotic damage with synergistic thrombocytopenia. Lupus nephritis with systemic SLE flare (hypocomplentemia) was the apparent driver of the dysregulation in alternate complement pathway causing atypical HUS and leading to pulmonary renal syndrome.
Conclusions: Atypical hemolytic uremic syndrome (HUS) is a very rare complement mediated thrombotic microangiopathy (TMA) with incidence of 1:500,000 in adults comprised of thrombocytopenia, microangiopathic hemolytic anemia and renal failure. Pulmonary involvement is exceedingly rare with a mortality of more than 30%. Administering late complement inhibitor (Eculizumab) effectively treated the condition where usual therapies like plasmapheresis failed.