P132 Refractory culture-negative arthritis and systemic inflammation in a child with sickle cell disease: a diagnostic and therapeutic challenge

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Abstract Introduction Systemic inflammation in children with sickle cell disease (SCD) presents diagnostic challenges, as overlapping features of vaso-occlusive crises, infection, and potential autoinflammatory processes can be difficult to distinguish. We report a 3-year-old boy with SCD (HbSS) who developed prolonged systemic inflammation and culture-negative arthritis, ultimately managed as a systemic juvenile idiopathic arthritis (sJIA)-like disease. Diagnostic uncertainty required close multidisciplinary team working and evolving immunosuppressive treatments, including IL-1 and IL-6 inhibition. This case highlights the challenges of distinguishing infection from autoinflammation in SCD, the use of targeted biologics, and the role the MDT in managing autoinflammation in this vulnerable population. Case description A 3-year-old boy, born of non-consanguineous Ghanaian parents, with homozygous sickle cell disease (HbSS), previously stable on hydroxycarbamide, presented with chest pain, fever, and elevated inflammatory markers (CRP >200 mg/L, ferritin >3000 µg/L). Imaging confirmed sternal osteomyelitis, managed with broad-spectrum antibiotics and regular transfusions. Over the next six months, he developed persistent fever, elevated inflammatory markers, and bilateral knee and ankle effusions, unresponsive to antibiotics. Joint washouts initially yielded pus, but cultures were negative. Whole-body MRI revealed significantly increased bilateral knee joint effusions, suggestive of synovitis, without additional bony changes beyond those typical of SCD. Joint biopsy showed fibrovascular connective tissue with scattered macrophages and widespread haemosiderin deposition, with no acute inflammation. Extensive infectious, immunological, and autoimmune screens were negative. After failure to respond to repeated antibiotic courses, multidisciplinary evaluation (rheumatology, haematology, immunology, infectious diseases) concluded a working diagnosis of a systemic juvenile idiopathic arthritis (sJIA)-like autoinflammatory syndrome. He was commenced on oral prednisolone at 1 mg/kg, followed by anakinra at 2 mg/kg, then escalated to 4 mg/kg and 6 mg/kg due to persistent inflammation. He underwent stretch and cast due to bilateral fixed flexion deformities, which were removed due to increased pain and fever. Inflammatory markers initially reduced with anakinra but then rose again with fever spikes and CRP >200 mg/L. Intravenous methylprednisolone mini-pulses (10 mg/kg daily for 3 days) were administered, followed by 1 mg/kg steroid maintenance, which reduced inflammation. Tocilizumab (12 mg/kg IV fortnightly) was commenced as a second-line agent and its efficacy remains under evaluation. Complications have included hypertension, likely steroid-induced, managed with amlodipine, and very poor mobility. Transfusion therapy continues to maintain low HbS levels and prophylactic oral penicillin V is ongoing. Autoinflammatory gene panel and whole exome sequencing results are awaited. Discussion Distinguishing autoinflammation from infection or vaso-occlusive crises in sickle cell disease (SCD) remains a clinical challenge, as illustrated by this case. Initially treated for osteomyelitis, the child’s condition evolved into persistent systemic inflammation with joint involvement, unresponsive to antibiotics. Negative microbiological and immunological investigations shifted suspicion towards an underlying autoinflammatory process, though diagnostic uncertainty remains. Results from an autoinflammatory gene panel and whole exome sequencing are pending and may yet reveal a monogenic cause. Anakinra, an IL-1 inhibitor, was trialled with initial benefit but proved insufficient alone to control inflammation. High-dose corticosteroids were required, and tocilizumab, an IL-6 inhibitor, was introduced as a second-line agent, its efficacy is still under evaluation. Regular transfusions have been used to maintain low HbS levels in order to minimise sickle cell-related complications, alongside ongoing prophylactic penicillin V. This case highlights the diagnostic complexity of persistent inflammation in SCD, the risks of immunosuppression in an infection-prone host, and the need for adaptable, targeted treatment strategies. It raises important questions around potential autoinflammatory triggers, the evolving role of tocilizumab, and how best to reduce steroid dependence while supporting mobility and minimising infection risk. Multidisciplinary collaboration remains central to managing these overlapping challenges. Key learning points • Culture-negative arthritis in SCD requires a high index of suspicion and broad differential thinking. Failure to identify a pathogen or respond to antibiotics, followed by ongoing synovitis and effusions after sterile washouts, should prompt early consideration of an autoinflammatory process. Infection, vaso-occlusion, and sterile inflammation may overlap or mimic one another. A high index of suspicion for an autoinflammatory process is required. • Multidisciplinary team involvement is essential when navigating diagnostic uncertainty and guiding immunosuppressive therapy. Input from haematology, infectious diseases, immunology, respiratory, and radiology was central to management. • Escalation of therapy in suspected systemic autoinflammatory disease should follow a structured, response-guided approach. Corticosteroids provided partial benefit. IL-1 blockade (anakinra) initially reduced inflammation but was followed by early relapse, prompting escalation to IL-6 blockade (tocilizumab), whose effectiveness is still under evaluation. • Regular transfusion therapy is crucial in managing SCD, particularly during systemic inflammation, to maintain low HbS levels and reduce the risk of sickle-related complications, such as infarction. • Functional morbidity is significant in prolonged PUO and joint inflammation. Prolonged immobility and joint damage contribute to disability; intensive physiotherapy and rehabilitation are essential. Delays in diagnosis and treatment can result in long-term physical impairment. • Psychological and psychosocial impacts of prolonged hospitalisation. Children with chronic inflammatory conditions, particularly those requiring repeated invasive procedures and prolonged immobilisation, are at increased risk of anxiety, depression, and post-traumatic stress symptoms. Family units also experience significant psychosocial strain, including caregiver burden and financial stress, which can affect treatment adherence and outcomes. Paediatric rheumatologists should advocate for integrated psychological support and social services involvement early in the disease course. Future learning objectives • Improve risk stratification of inflammatory presentations in SCD • Enhance diagnostic pathways for PUO in children with underlying haemoglobinopathy • Identify early markers of poor response to biologics and infection in SCD

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