Delayed cutaneous reactions to heparin in antiphospholipid syndrome during pregnancy

Clinical symptoms related to antiphospholipid antibodies often first occur during pregnancy with the diagnosis of antiphospholipid syndrome (APS). Unfractionated heparin (UFH) and low-dose aspirin are considered as first-line treatments for pregnant women with APS and recurrent fetal loss. However, in addition to an increased incidence of hemorrhagic side-effects and thrombocytopenia there are a number of drug eruptions with cutaneous components secondary to the use of UFH. One of these eruptions has been classified as a delayed type I.V. hypersensitivity reactions at the sites of UFH injections. The majority of these reactions occur in pregnant women.

We present three pregnant patients who developed delayed hypersensitivity reactions at the sites of UFH injections. Two patients had documented APS and the other patient had two previous spontaneous abortions.

The histopathologic and immunohistochemical findings in the biopsy specimens from the sites of the delayed reactions were distinctive. The inflammatory infiltrate contained CD3+ and CD4+ lymphoid cells with plasma cells, and eosinophils. There was a marked increased in mast cells with increased stromal cells within the dermis and increased vascular proliferation.

The distinctive histopathologic and immunohistochemical features seen in the delayed hypersensitivity reactions at the sites of UFH injections may be modulated by the immunomodulatory effects of UFH as well as the hormonal levels and cytokine patterns during pregnancy. Alternative therapies may not always be successful in resolving the reactions.