Treatment of Acquired Factor VIII Inhibitor Associated with Childhood-Onset Systemic Lupus Erythematosus

Abstract

Acquired inhibitors to factor VIII in non-hemophiliacs are rare, occurring in one of every five million individuals, and can lead to spontaneous hemorrhages.1 They may develop in association with collagen vascular diseases such as systemic lupus erythematosus (SLE), which accounts for only 6% of cases, in malignancy, with certain drugs, and during pregnancy.2 In nearly half of the patients, no underlying cause is apparent. 2 Significant bleeding, soft tissue hematoma and hemarthrosis are common complications, especially with strong inhibitors of more than 10 Bethesda units (BU)/mL.2,3 Treatment consists of active control of bleeding, using high-dose human factor VIII, activated prothrombin complex or porcine factor VIII concentrates, together with aggressive immunosuppression to eliminate the inhibitor. 3More recently, recombinant activated factor VII (rF-VIIa) has been used for the control of bleeding due to inhibitors in hemophiliacs, and was shown to be equally effective in bypassing the inhibitory action in the management of non-hemophiliacs. 4 Immunosuppression using cyclophosphamide (CYC) with or without corticosteroids is a well-established mode of treatment in the management of factor VIII inhibitors with severe bleeding complications. 5,6 Intravenous immunoglobulins (IVIG) were also reported to be successful in the management of acquired factor VIII inhibitor in SLE refractory to other modes of treatment. [7][8][9] We report the successful use of a combination of high-dose human factor VIII, CYC and prednisolone to eliminate factor VIII inhibitor in a patient suffering from documented childhood-onset SLE. Case ReportOur patient was a 16-year-old girl suffering from childhood-onset SLE. Her symptoms started at the age of eight years, and she fulfilled the revised criteria of the American College of Rheumatology for the classification of SLE.10 She had a long history of non-erosive polyarthritis, pleuritis, mouth ulcers and positive antinuclear antibodies (ANA). Titer at diagnosis was 1:1280 coarse speckled pattern. Our patient was initially treated with oral prednisolone. During a follow-up visit nearly eight years after the onset of symptoms, she reported easy bruising. Her only medication at the time was maintenance prednisolone 10 mg daily.Physical examination revealed multiple ecchymoses on the arms, legs and trunk, and slight gum bleeding. Her father had died many years previously from undetermined causes, but her mother, brothers and sisters were all well. The presence of SLE familial element was suspected because two other members of her family, her first-degree maternal cousins, were also suffering from childhood-onset SLE. Unfortunately, HLA phenotyping studies were not done. Her family reported that her two cousins who received follow-up in another hospital, also suffered from easy bruising. One of the cousins was an 11-year-old boy with cutaneous lupus (on topical Synalar 0.025% cream and Coppertone 15 sunscreen, and later, prednisolone 10 mg/day), and the other was his five-year-old sister, w...