Thrombotic thrombocytopenic purpura with juvenile systemic lupus erythematosus: successful treatment with caplacizumab and rituximab

Dear Editor,

We report a challenging case of a 14-year-old female with systemic lupus erythematosus (SLE) complicated by thrombotic thrombocytopenic purpura (TTP), which was successfully managed with caplacizumab and rituximab. The patient experienced numbness in her fingers and toes, headaches, and nausea over 3 months. Blood tests revealed thrombocytopenia, anemia, hypocomplementemia, and positive tests for anti-SS-A, anti-ssDNA, and antiphospholipid antibodies, raising suspicion of SLE. After undergoing a platelet transfusion for a renal biopsy, which revealed class III (A/C) lupus nephritis, she experienced seizures, altered consciousness, and a low platelet count. Laboratory findings confirmed TTP, with < 1% a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) activity and an inhibitor level of 20.9 BU/mL. Enhanced abdominal computed tomography revealed active bleeding from the left kidney, and emergency catheter embolization therapy was performed (Fig. 1). Initially, she received plasma exchange, methylprednisolone pulse therapy, and immunosuppressive therapy (hydroxychloroquine and mycophenolate mofetil) (Fig. 2). After confirming the absence of a further renal biopsy site hemorrhage, caplacizumab was introduced on day 4. Platelet counts improved by day 7, allowing plasma exchange discontinuation. Although TTP did not recur, the ADAMTS13 inhibitor level remained elevated at 15.6 BU/mL on day 14. Consequently, rituximab was started on day 17. After four weekly doses, the inhibitor titer normalized, ADAMTS13 activity exceeded 10% by week 8, and caplacizumab was discontinued on day 94. Subsequently, B cells were depleted for 9 months, and increased to 5% of lymphocytes at 12 months. However, the inhibitor titer did not rise, and TTP-SLE did not relapse. The patient remains free from neurological sequelae and cardiac complications, leading a normal daily life.

Fig. 1

Enhanced abdominal computed tomography of the patient

The arrow shows active bleeding from the lower area of the left kidney 1 day after the needle renal biopsy

Fig. 2

Changes in the platelet count, ADAMTS13 activity, and levels of inhibitor after plasma exchange and caplacizumab and rituximab therapy

PEX and MPT (1 g/dose × 3 days) were initiated immediately on admission. On day 3, the patient also took HCQ (5 mg/kg/day) and MMF (700 mg/m²/day) orally. On day 4, caplacizumab was administered (10 mg, daily). By day 7, PEX was discontinued. Subsequently, caplacizumab was continued, and the patient received another MPT course. Thereafter, maintenance therapy with GC (prednisolone 1 mg/kg/day), HCQ, and MMF was continued. RTX was started on day 17 (375 mg/m², weekly; 4 weeks). The ADAMTS13 inhibitor became negative 7 weeks after four RTX administrations. The range indicated by the arrows represents the treatment period. Black line, platelet count (×10⁴/µL); red line, ADAMTS13 activity (%); blue line, inhibitor level (BU/mL). C4, complement C4; ESR, erythrocyte sedimentation rate; GC, glucocorticoid; HCQ, hydroxychloroquine; MMF, mycophenolate mofetil; MPT, methylprednisolone pulse therapy (down-arrow); PEX, plasma exchange; RTX, rituximab (triangle)

This case highlights several key considerations in managing pediatric TTP-SLE. Caplacizumab, an anti-von Willebrand factor nanobody, is a recent innovation in the treatment of acquired TTP [1, 2]. Caplacizumab reduces the morbidity and mortality associated with acquired TTP in adults [1, 2]. Taylor et al.. demonstrated the efficacy and safety of caplacizumab in the pediatric population (including 4 children aged < 12 years), which is synonymous with the adult trial data [3]. However, it is still unclear whether caplacizumab is as effective in TTP-SLE as in acquired TTP. In our case, caplacizumab rapidly mitigated thrombotic microangiopathy, facilitating early platelet recovery. Balancing bleeding risks was a notable challenge. The patient’s caplacizumab treatment was delayed until bleeding from the biopsy site was controlled, demonstrating the importance of individualized treatment planning. Additionally, because caplacizumab does not suppress ADAMTS13 inhibitor production, adjunctive rituximab therapy was critical for sustained remission [4]. Rituximab’s dual efficacy in depleting autoantibody-producing B cells and controlling SLE significantly contributed to the patient’s recovery [5].

In conclusion, the combination of caplacizumab and rituximab shows promise for treating pediatric TTP-SLE, with this case serving as a reference for managing similar complex presentations. Future studies should explore the optimal timing and sequencing of these therapies to enhance the outcomes in patients with TTP-SLE.