Quarter in review: Paediatric Rheumatology

Himanshi Chaudhary MD, DM Pediatric Clinical Immunology & Rheumatology
Consultant, Clinical Immunology & Pediatric Rheumatology. Alpha Superspeciality Clinics and Ruby Hall Clinics, Pune, Maharashtra, India

Study in focus 1: Elevation of IL-17 cytokines distinguishes Kawasaki Disease from other paediatric inflammatory disorders

Kawasaki disease (KD) is a childhood vasculitis that can result in serious cardiovascular complications. The diagnosis of KD is based on the fulfilment of a set of clinical criteria, which could be challenging, especially in cases of incomplete KD. In an attempt to develop a sensitive biomarker to differentiate KD from other childhood inflammatory conditions, the authors from Boston Children’s Hospital performed a high-fidelity proteomic profiling of cytokine, chemokine and growth factor expression across paediatric inflammatory diseases such as KD, multisystem inflammatory syndrome in children (MIS-C), macrophage activation syndrome and other paediatric rheumatological conditions using proximity extension assay (PEA). This method offers better sensitivity and a wider detection range while requiring very small amounts of blood samples.

In comparison to other conditions including MIS-C, samples of patients with KD demonstrated considerably increased expression of IL-17 cytokines [IL-17A, IL-17C, IL-17F, IL-13, and C-C chemokine ligand 13]. Enzyme-linked immunosorbent assay was used to further validate these results. In further derivation analysis using a larger validation cohort, IL-17A performed best at discriminating KD from other febrile conditions. Patients with KD who had coronary abnormalities (CAA) also had higher levels of IL-17A, IL-17C and IL-17F as compared to the ones without CAA.

These findings suggest that IL-17 cytokines may have an important pathogenic role in KD and also in the development of coronary complications. Authors suggest that IL-17 may contribute to coronary vasculitis by inducing the production of myeloid cell chemo-attractants to endothelial cells. They have also made suggestions on further studies on IL-17 antagonists and their possible benefits for KD patients.

Study in focus 2: Is it possible to predict a disease course prone to macrophage activation syndrome at systemic juvenile idiopathic arthritis diagnosis?

Systemic juvenile idiopathic arthritis (SJIA) is a subtype of JIA wherein arthritis is accompanied by systemic features like fever, lymphadenopathy, hepatosplenomegaly and serositis. Macrophage activation syndrome (MAS), a potentially life-threatening complication of SJIA has been reported in around 10% of patients with SJIA during the disease course. An uncontrolled activation and proliferation of macrophages and T lymphocytes in MAS results in a massive cytokine storm. 

Batu et al. evaluated various features that are present at the time of diagnosis and potentially indicate a MAS-prone disease progression in patients with SJIA. In this single-centre study, clinical data of 126 patients with SJIA was retrospectively analysed, out of which 31.8% experienced MAS during follow-up. The authors have shown that a younger age at symptom onset, longer duration of fever, low platelet count, high triglyceride, and high ferritin levels at SJIA diagnosis were independent predictors of MAS occurrence during the subsequent disease course. They have proposed that ferritin: platelet ratio can be considered a useful biomarker with values ≥1.1 having a sensitivity of 90% and a specificity of 82.6% to predict the occurrence of MAS during the disease course.

Although this is a small single-centre retrospective study, it underscores the practical utility of simple and readily accessible biomarkers in predicting the long-term disease severity in patients with SJIA

References:

  1. Brodeur KE, Liu M, Ibanez D, de Groot MJ, Chen L et al Elevation of IL-17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders. Arthritis Rheumatol. 2024;76(2):285-292
  2. Batu ED, Sener S, Balık Z, Bayındır Y, Cam V et al Is it possible to predict a disease course prone to macrophage activation syndrome at systemic juvenile idiopathic arthritis diagnosis? Clin Rheumatol. 2024;43(1):415-421.