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Practical Approach to Diagnosis and Management of IL-1-Mediated Autoinflammatory Diseases (CAPS, TRAPS, MKD, and DIRA)

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Abstract

Systemic autoinflammatory diseases (SAIDs) are a group of rare genetic and nongenetic immune dysregulatory disorders associated with high morbidity and mortality if left untreated. Therefore, early diagnosis and initiation of targeted treatment is vital in SAID patients to control the disease activity and prevent long-term immune-mediated damage. A specific group of genetically defined SAIDs is associated with increased inflammasome-mediated production of active interleukin (IL)-1. Even though progress in immunobiology and genetics has brought forth diagnostic tools and novel treatments that have been described in the literature extensively, many challenges remain in the clinical setting. Some challenges that health care providers may face on a day-to-day basis include the requirement of a multidisciplinary approach due to the complexity of these diseases, limited evidence-based treatment options, and barriers to access available therapies. Primarily, IL-1 inhibitors anakinra, canakinumab, and rilonacept are used to control the inflammation in these patients, with the goal of achieving sustainable remission. Recently published provisional points to consider from the European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR) provide diagnosis, management, and monitoring recommendations for four IL-1-mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and deficiency of the IL-1 receptor antagonist (DIRA). The goal of this paper is to aid health care professionals by providing a practical approach to diagnosis and management of these four IL-1 mediated SAIDs on the basis of the recent EULAR/ACR recommendations.

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Author notes

  1. Kader Cetin Gedik, Zehra Serap Arici have equally contributed.

Authors and Affiliations

  1. Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Kader Cetin Gedik

  2. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Kader Cetin Gedik

  3. Division of Rheumatology, Malatya Training and Research Hospital, Malatya, Turkey

    Zehra Serap Arici

  4. Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK

    Ovgu Kul Cinar

  5. Department of Pediatrics, Division of Pediatric Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, N6A 5W9, Canada

    Facundo Garcia-Bournissen, Micol Romano & Erkan Demirkaya

  6. Canadian Behcet and Autoinflammatory Disease Center (CAN-BE-AID), University of Western Ontario, London, ON, N6A 4V2, Canada

    Micol Romano & Erkan Demirkaya

  7. Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, N6A 5W9, Canada

    Erkan Demirkaya

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Cetin Gedik, K., Arici, Z.S., Kul Cinar, O. et al. Practical Approach to Diagnosis and Management of IL-1-Mediated Autoinflammatory Diseases (CAPS, TRAPS, MKD, and DIRA). Pediatr Drugs 26, 113–126 (2024). https://doi.org/10.1007/s40272-023-00615-5

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