Primary Antiphospholipid Syndrome–Associated Diffuse Alveolar Hemorrhage

Abstract

Objective. Diffuse alveolar hemorrhage (DAH) is an uncommon complication of primary antiphospholipid syndrome (APS). We aimed to describe the clinical characteristics, treatment, and outcomes of primary APS-associated DAH in a single center. Methods. We conducted a retrospective review of all adults with primary APS-associated DAH evaluated at Mayo Clinic over a 15-year period. DAH was defined as bilateral pulmonary infiltrates and bronchoalveolar lavage (BAL) fluid documenting progressively bloody returns and/or the presence of >20% hemosiderin-laden macrophages. Patients with other causes of DAH were excluded. Results. Eighteen patients were identified (median age 43 years). Capillaritis was present in surgical lung biopsy samples of 3 patients. BAL differential cell counts revealed predominantly neutrophils. All patients were treated initially with glucocorticoids. Cyclophosphamide (CYC) was used in 8 patients; complete remission was achieved in 3 patients treated with CYC alone and in 1 patient receiving combination therapy with rituximab (RTX). RTX was used in 9 patients; 2 patients achieved remission with RTX alone, whereas 3 patients required combination therapy with CYC or mycophenolate mofetil (MMF). No patient achieved complete remission while receiving single therapy with MMF, azathioprine, or plasma exchange. Intravenous gamma globulin therapy was administered in 5 patients; no patient achieved control of the disease. Six patients died, all because of complications related to uncontrolled DAH or its therapy. Conclusion. We present the largest case series of primary APS-associated DAH reported in the literature. DAH carries a very poor prognosis and therapeutic options are limited. Immunosuppression with either CYC or RTX is associated with the highest likelihood of remission induction and should be considered early.

Difficulties in the Treatment of Recurring Diffuse Alveolar Hemorrhage Accompanying Primary Antiphospholipid Syndrome: A Case Report and Literature Review

“…In our case, owing to recurrent disease and a high risk of new DAH episodes, we decided to start with CYC treatment. Although there are currently no randomized trials to support any recommendations regarding the choice of a steroid-sparing drug, CYC has been used effectively in vasculitides such as granulomatosis with polyangiitis and is suggested, along with rituximab, to be one of the most effective steroid-sparing agents in this setting [3,4,10]. However, CYC www.journals.viamedica.pl treatment failed to maintain remission in our patient.…”

“…Yachoui et al [4] published a case series report in which only one out of six patients subjected to lung biopsy showed neutrophilic infiltration, while the remaining five presented as bland hemorrhage [4]. Others have underlined [2] that neutrophilic interstitial infiltration alone, [3,4,10,11] without perivascular or vascular infiltrates does not allow for recognizing vasculitis. However, lack of these features does not allow for a virtual ruling out of vasculitis because histological findings may vary depending on both the lung region and the activity of the disease [12].…”

“…Our patient is a male [3-6, 10, 11], in the fourth decade of life [3,4,6,10,11], with a neutrophilic (49%) BALF [4,10] and high APLA titer [3-5, 10, 11]. Due to lack of the histopathological examination and normal bone density values, we cannot dismiss that pathological fractures, which our patient experienced, were a result of osteonecrosis, reported in other patients with PAPS as well [2].…”

Primary Antiphospholipid Syndrome Associated with Diffuse Alveolar Hemorrhage and Pulmonary Thromboembolism

“…Other immunosuppressive agents, such as cyclophosphamide, azathioprine, and mycophenolate mofetil, have been used in an attempt to achieve complete remission. Additionally, some case reports noted that intravenous immunoglobulin treatment (4,12,16), plasmapheresis (13), and rituximab (15, 16) may be effective for patients who do not respond to corticosteroids. Cartin-Ceba et al reported that immunosuppression with either cyclophosphamide or rituximab may have a higher likelihood of success (16).…”

“…Additionally, some case reports noted that intravenous immunoglobulin treatment (4,12,16), plasmapheresis (13), and rituximab (15, 16) may be effective for patients who do not respond to corticosteroids. Cartin-Ceba et al reported that immunosuppression with either cyclophosphamide or rituximab may have a higher likelihood of success (16). In the present case, DAH responded well to corticosteroids and is currently being controlled without other immunosuppressive agents.…”