INTRODUCTION: Catastrophic antiphospholipid syndrome (CAPS) is an infrequent potentially devastating syndrome that can involve every organ, including the lungs. Our patient with CAPS with multiple thrombosis and diffuse ground glass pulmonary opacities was refractory to conventional therapies. To our knowledge, this is the first report documenting the efficacy of rituximab in resolving pulmonary manifestations.
CASE PRESENTATION: A 38 year old man presented with a 4 year history of intermittent episodes of dyspnea, fatigue and thrombocytopenia. Our work up yielded restricted lung volumes with a severely decreased DLCO. A CT of the chest revealed bilateral areas of ground glass opacities. Serologies were positive only for lupus anticoagulant and anticardiolipin antibodies. Weeks later he developed a deep vein thrombus (DVT) and was anticoagulated with warfarin. Factor II activity was monitored with a goal of 5-35% activity. An open lung biopsy revealed plexiform pulmonary arteriopathy, pulmonary emboli, mild emphysematous changes and interstitial lymphoid hyperplasia. Despite achieving factor II activity goal, he developed a second DVT. At this point enoxaparin was initiated along with cyclophosphamide at 500mg/m2 monthly and prednisone 60mg daily. Two months later he was diagnosed with bilateral pulmonary emboli and was hospitalized. This was complicated by acute renal failure, digital ischemia, acute non-ST elevation myocardial infarction, transient ischemic attack (TIA) and significant hypoxia requiring 4 lpm oxygen. A CT chest revealed significant worsening of bilateral areas of ground glass opacity in a similar distribution compared to the original CT of the chest. A diagnosis of CAPS was made and emergent plasmapharesis along with parenteral methylprednisolone 2mg/kg was begun. Failing both first and second line therapies, rituximab was added to his steroid regimen. Over the following 10 days he was stabilized and discharged home. Fifteen days after the first dose of rituximab, a second dose was administered. One week after that, a repeat CT chest revealed complete resolution of the ground glass opacities. This was accompanied by a clinical resolution of digital ischemia, renal failure and TIAs. The prothrombin time and partial thromboplastin times also improved.
DISCUSSIONS: Proposed criteria to diagnose CAPS are as follows: 1. 3 or greater organ system involvement 2. Simultaneous (within 1 week) multiorgan involvement 3. Histopathologic confirmation of small vessel occlusion 4. Presence of antiphospholipid and/or anticardiolipin antibodies. 1 There is considerable heterogeneity in the presentation of CAPS. The most common precipitating event is infection (22%) followed by surgical procedures (10%) and difficulty managing anticoagulation (8%)2This case illustrates the pulmonary parenchymal and vascular manifestations of primary antiphospholipid syndrome and highlights the challenges in its management. Evidence to support the use of a third line agent such as rituximab in controlling the pulmonary manifestations is limited. After exhausting more conventional means, rituximab, an anti-CD20 monoclonal antibody, induced a remission in this life-threatening disease. Following the second dose, the patient continued to demonstrate a sustained improvement in his dyspnea and complete resolution of the pulmonary abnormalities. We believe that the rituximab was effective as a rescue therapy after failure of cyclophosphomide and prednisone. He is expected to get 5 more doses of rituximab with close clinical follow up.
CONCLUSION: Rituximab, an anti CD 20 antibody, proved to be an effective rescue therapy for our patient with catastrophic primary antiphospholipid antibody syndrome with pulmonary manifestations who was resistant to conventional therapy including cyclophosphomide.
DISCLOSURE: Anthony Loschner, No Financial Disclosure Information; No Product/Research Disclosure Information