1Department of Paediatrics and 3Department of Rheumatology, Leiden University Medical Center and 2Erasmus Medical Center/Sophia Children's Hospital Rotterdam, The Netherlands
Correspondence to: R. ten Cate, Department of Paediatrics, Leiden University Medical Center, Mailbox 9600, 2300 RC Leiden, The Netherlands. E-mail: R.ten_Cate{at}lumc.nl
SIR, Childhood-onset systemic lupus erythematosus (SLE) is a disease with considerable morbidity and mortality [1]. Treatment options, depending on the clinical expression of the disease, include non-steroidal anti-inflammatory drugs, hydroxychloroquine, corticosteroids and cytotoxic agents [2]. For immune thrombocytopenia in children corticosteroids, intravenous immunoglobulins, intravenous anti-D immunoglobulin and splenectomy are used [3].
After a 2-yr period with arthritis, lymphadenopathy and mucosal lesions on the hard palate, a 6-yr-old Caucasian girl developed thrombocytopenia and granulocytopenia. Bone marrow investigation showed no malignancy. However, she was found to have autoantibodies against erythrocytes, granulocytes and thrombocytes. Circulating antinuclear antibodies were present, but no antibodies to double-stranded DNA or cardiolipins could be detected. She was therefore diagnosed with systemic lupus erythematosus (SLE) and treated with oral corticosteroids, hydroxychloroquine and naproxen (15 mg/kg/day). Initially, there was a good response but thrombocytopenia persisted. Furthermore, the chronic corticosteroid treatment subsequently led to growth retardation and osteoporosis. A drop in thrombocyte count below 10 x 109/l immediately followed tapering of corticosteroids. Next, monthly intravenous immunoglobulins (IVIG, 2 g/kg in 5 days) in combination with azathioprine (12 mg/kg/day) were provided, after which the thrombocyte count normalized.
At the age of 10 yr, magnetic resonance imaging (MRI) of the brain, made because of two generalized seizures, revealed a cerebral lesion. Despite subsequent treatment with oral corticosteroids (prednisone 2 mg/kg/day) and an increased dose of azathioprine (3 mg/kg/day), neurological symptoms recurred, indicating exacerbation of her cerebral SLE, which was confirmed by MRI. A stereotactic biopsy of a lesion showed reactive non-specific inflammation, excluding infection, malignancy and vasculitis. Subsequent treatment consisted of monthly pulses of methylprednisolone (MP) (30 mg/kg) and cyclophosphamide (750 mg/m2) for 6 months, followed by 3-monthly pulses for another year. This was discontinued after 15 months because the next MRI revealed new cerebral lesions. In order to prevent further progression of cerebral lesions, autologous stem-cell transplantation was prepared. This procedure was postponed when a baseline MRI 6 months after cessation of all immunosuppressive therapy revealed clear improvement of nearly all lesions.
However, during the intensive immunosuppressive regimen for cerebral SLE, thrombocytopenia recurred and at the age of 13 yr splenectomy was performed. Reactive thrombocytosis and leucocytosis were observed for 3 months, after which normal counts were measured for 1.5 yr. At the age of 15 yr profuse bleeding from the gums and nose indicated a new episode of thrombocytopenia. Three daily pulses of MP (30 mg/kg) and high-dose IVIG (2 g/kg) had no effect.
As anti-CD20 monoclonal antibody (rituximab) had been reported to be successful in the treatment of autoimmune haemolytic anaemia in a patient with SLE [4] and in patients with chronic refractory idiopathic thrombocytopenic purpura [5], we initiated this treatment in our patient. After informed consent, 375 mg/m2 rituximab was administered intravenously once a week for 4 weeks. Clemastine and hydrocortisone were given as premedication. No adverse reactions were observed and the treatment was well tolerated. Monthly IVIG was given at 400 mg/kg. Within 1 month after the first rituximab infusion, thrombocyte counts returned to normal values and remained so for 6 months. Platelet recovery is depicted in Fig. 1.
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The authors have declared no conflicts of interest.
There was no pharmaco-industrial support for the use of anti-CD20.
References