Background/Purpose:

Diffuse alveolar hemorrhage (DAH) is an uncommon but severe complication of primary antiphospholipid syndrome (APS). The available literature is limited to very few case reports. We aim to describe the clinical characteristics, treatment and outcomes of patients with DAH due to primary APS managed at our institution.

Methods:

A retrospective review of the medical records of all consecutive adults evaluated at Mayo Clinic with DAH secondary to primary APS between January 1, 1997 and December 31, 2011 was conducted. APS was diagnosed using the revised Sapporo classification criteria. DAH was defined as the presence of bilateral alveolar pulmonary infiltrates with a confirmatory bronchoalveolar lavage (BAL) documenting bloody return and/or >20% hemosiderin laden macrophages (HLM). Patients with documented connective tissue diseases, ANCA associated vasculitis or anti-GBM disease were excluded.

Results:

A total of 17 patients (men=12) were identified, all of them white. The median age (interquartile range, IQR) was 43 years (36-47). The median time from diagnosis of APS to development of DAH was 1661 days (495-3605). Three patients underwent lung biopsy showing capillaritis. The median percentage of HLM was 87% (81-98), BAL differential cell count was predominantly neutrophilic, median 30% (18-60). All patients were treated with high doses of glucocorticoids; six of whom did not respond, requiring more aggressive immunosuppression. Mycophenolate mofetil was used in seven patients; none achieved remission. Azathioprine was used in six patients; no remission was noted in five and one patient did not tolerate it. Cyclophosphamide was used in seven patients; remission was achieved only in three patients. Plasma exchange was performed in two patients with no response. Intravenous gamma-globulin was used in four patients with remission seen only in one patient. Rituximab was used in 6 patients; two patients achieved remission and one was lost to follow up. Only the two patients treated successfully with rituximab are off glucocorticoids. Five patients died, four from complications of uncontrolled DAH and one from complications of autologous stem cell transplant conditioning regimen for treatment of refractory DAH/ APS. Median time to death from diagnosis of DAH was 70 days (44-721).

Conclusion:

To the best of our knowledge, we present the largest series of DAH secondary to primary APS. There is a long gap between the diagnosis of APS and the first episode of DAH. Alveolar fluid shows predominantly neutrophilic inflammation. This disease carries a very poor prognosis with very limited successful therapeutic options.  B-cell targeted immunosuppression with either cyclophosphamide or rituximab may have the highest likelihood to induce remission and should be considered early.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/diffuse-alveolar-hemorrhage-caused-by-primary-antiphospholipid-syndrome/