Secukinumab for children and adolescents with enthesitis-related arthritis and psoriatic arthritis: lessons from treatment in adults and the way forward.

INTRODUCTION: Targeting IL-17A using Secukinumab, a humanized monoclonal immunoglobulin G1 (IgG1)/κ against IL-17A is a therapeutic option for immune-mediated disorders such as psoriasis and ankylosing spondylitis. The US Food and Drug Administration and the European Medicines Agency have approved it for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondylarthritis. Recently it has also been approved for use in children with severe plaque psoriasis, active psoriatic arthritis, and enthesitis-related arthritis. AREAS COVERED: This review focuses on the role of Secukinumab in the management of children and adolescents with enthesitis-related arthritis and psoriatic arthritis. We discuss the salient findings of pivotal RCTs and other studies supporting the use of Secukinumab in adults and children, in particular, focusing on its safety and efficacy. EXPERT OPINION: Secukinumab is a therapeutic target for psoriasis, psoriatic arthritis, and spondyloarthropathies in both adults and children. No major safety signals are observed with its use in short-term follow-up. Thus far, Secukinumab has not been found to significantly increase the risk of tuberculosis (TB).

Long-Term Outcomes of Survivors of COVID-19 with Moderate to Severe Infection and Children with Multisystem Inflammatory Syndrome or MIS-C.

The study aims to evaluate the long-term outcomes - functional, pulmonary and non-pulmonary (other organs) - in children hospitalized with COVID-19 infection or with Multisystem inflammatory syndrome (MIS-C) after 1-2 y of discharge. All children with moderate or severe COVID-19 or MIS-C were enrolled. Out of 45 enrolled subjects, 19.8% had COVID-19 infection and 82% had MIS-C. Four children (8.9%) had abnormal baseline echocardiography; two each with cardiac dysfunction and coronary dilatation. At baseline, 44% had moderate disability and 24% had mild disability as per Pediatric Cerebral Performance Category (PCPC). On follow-up, only 8.9% (n = 4) had mild and 2.2% (n = 1) had moderate disability as per the PCPC score. One child developed new onset tuberculosis of the bone. None had any pulmonary morbidities. Follow-up echocardiogram was also within normal limits for children with abnormal findings. Further studies in different populations (settings) are required to draw meaningful conclusions about long-term effects of COVID-19 on children.

Can Whole-Body Magnetic Resonance Imaging Predict Relapse in Juvenile Idiopathic Arthritis? A Longitudinal Pilot Study.

OBJECTIVE: To determine the utility of whole-body magnetic resonance imaging (WB MRI) to predict relapse in children with juvenile idiopathic arthritis (JIA) in clinical remission. METHODS: Consecutive patients with JIA who fulfilled the Wallace criteria for remission were recruited into this longitudinal pilot study and underwent WB MRI. A radiological score was devised, incorporating synovitis, bone marrow edema, sacroiliitis, enthesitis, and bone erosions. Two readers independently scored the MR data sets. The same score was calculated for both knee joints individually and correlated with outcome for that joint. Score-based models incorporating clinical and laboratory variables were generated. Logistic regression analysis was done to determine predictors for relapse. Receiver operating characteristic curve was drawn for significant variables. RESULTS: Twenty-two children (median age, 12 years; interquartile range, 9.5-14.25 years) were included in the final analysis. At 24 months' follow-up, 15 joints in 5 children relapsed; knee was the most common site. Seven knee joints had disease relapse. On univariate analysis, synovitis and total score on WB MRI were significant predictors of relapse at follow-up, with odds ratios of 9.46 (bias-corrected 95% confidence interval, 3.07-29.13) and 2.8 (bias-corrected 95% confidence interval, 1.23-6.39) respectively. Two models, which included a higher number of joints involved at presentation and abrupt drug withdrawal strategy as predictor variables, were also statistically significant (odds ratio, approximately 1.9). On multivariate analysis of the predictors variables in models where p < 0.6, it was found that only synovitis score and total score were near statistical significance ( p = 0.06); no clinical or laboratory variables were significant. The areas under the receiver operating characteristic curve for relapse prediction were approximately 0.82, 0.87, 0.79, and 0.81 for synovitis score, total MRI score, and both models, respectively. CONCLUSION: Synovitis on WB MRI is the strongest independent predictor for disease relapse in children with JIA in remission.

Scope of JAK Inhibitors in Children: Recent Evidence and Way Forward.

Over the last decade, there has been an increase in the use of targeted therapy using small molecules such as Janus kinase (JAK) inhibitors. Since the introduction of ruxolitinib, the first non-selective JAK inhibitor approved for use in myelofibrosis, many other JAK inhibitors have been tried in a wide spectrum of immune-mediated disorders. Although various trials have shown the promising efficacy of JAK inhibitors in immune-mediated inflammatory disorders (IMIDs), there is a growing concern over the major cardiovascular events and malignancies associated with the use of these molecules in older adults, particularly those over 65 years of age. In this review, we aim to discuss the immunology of the JAK-STAT pathway, the scope of use of JAK inhibitors, and their safety in paediatric practice. Here, we discuss high-quality evidence favouring the use of JAK inhibitors in children with juvenile idiopathic arthritis (JIA) who are refractory to one or more conventional/biological disease-modifying drugs, demonstrated in two randomised controlled trials (RCTs). In addition to JIA, there are reports favouring the role of JAK inhibitors in other IMIDs such as systemic-onset JIA and interferonopathies. Thus far, the existing literature suggests an acceptable safety profile for JAK inhibitors in children. With the expanding scope of JAK inhibitors in a wide range of IMIDs in children, there is a significant need for long-term close vigilance for any potential harm.

Case 316: Progressive Pseudorheumatoid Dysplasia.

HISTORY: A 10-year-old North Indian boy presented with swelling of multiple joints in his hands for the past 3 years. This swelling involved the small joints of his hands and some restriction of joint movement, without any associated tenderness or morning stiffness. No other joints were symptomatically involved. Prior to visiting our hospital, he had received disease-modifying antirheumatoid drugs for suspected juvenile idiopathic arthritis, without any clinical benefit. On examination, the metacarpophalangeal and interphalangeal joints were nontender but had swelling and flexion deformities. He also had a short stature (below the third centile) for his age. Inflammatory markers, including erythrocyte sedimentation rate (7 mm per hour; normal range, 0-22 mm per hour) and C-reactive protein level (1.5 mg/L; normal level, <10 mg/L), were normal, and the rheumatoid factor test result was negative. A skeletal survey of the patient was performed.

Kawasaki disease or polyarteritis nodosa: coronary involvement, a diagnostic conundrum.

Polyarteritis nodosa (PAN) is a medium-vessel vasculitis presenting with cutaneous and multisystem involvement with considerable morbidity. The necrotizing vasculitis in PAN typically involves renal, celiac, and mesenteric vascular beds. Coronary artery involvement is a characteristic feature of Kawasaki disease, another medium-vessel vasculitis; however, it has been rarely reported with PAN. Here, we present 2 cases with PAN involving coronaries mimicking Kawasaki disease. A 3.5-year-old boy with classical features of Kawasaki disease with giant coronary aneurysm refractory to IVIg, methylprednisolone, infliximab presented with persistent rise in inflammatory markers and gastrointestinal bleeding. Digital subtraction angiography (DSA) revealed celiac artery branches stenosis and beading suggestive of PAN. Another 2-year-old girl presented with persistent fever, abdominal pain, and distension. She had hypertension, hepatomegaly, and splenomegaly on examination. Echocardiography revealed multiple coronary aneurysms and DSA revealed numerous renal artery aneurysms. Coronary aneurysm although is a rare presentation of childhood PAN, and can mimic Kawasaki disease. Although both are medium-vessel vasculitis differentiation between these two entities is pivotal, as there are differences in treatment modalities, duration of immunomodulatory therapy, and the outcome. This manuscript describes the salient differences which can help differentiate PAN masquerading as Kawasaki disease at initial presentation.

Case 316.

HISTORY: A 10-year-old North Indian boy presented with swelling of multiple joints in his hands for the past 3 years. This swelling involved the small joints of his hands and some restriction of joint movement, without any associated tenderness or morning stiffness. No other joints were symptomatically involved. Prior to visiting our hospital, he had received disease-modifying antirheumatoid drugs for suspected juvenile idiopathic arthritis, without any clinical benefit. On examination, the metacarpophalangeal and interphalangeal joints were nontender but had swelling and flexion deformities. He also had a short stature (below the third centile) for his age. Inflammatory markers, including erythrocyte sedimentation rate (7 mm per hour; normal range, 0-22 mm per hour) and C-reactive protein level (1.5 mg/L; normal level, <10 mg/L), were normal, and the rheumatoid factor test result was negative. A skeletal survey of the patient was performed and is shown in Figures 1-6.

Technical and Interpretive Pitfalls in Pediatric Musculoskeletal Ultrasound.

The use of musculoskeletal (MSK) ultrasound (US) in pediatric rheumatology has expanded rapidly with various diagnostic and therapeutic indications. Unlike magnetic resonance imaging (MRI), US allows real-time dynamic assessment, evaluation of multiple joints in a single session and comparison with contralateral limb. However, a long learning curve and lack of experience with MSK US in pediatric patients still precludes its routine use at many imaging centers. It is prudent for pediatric radiologists to be aware of normal US appearances of the growing MSK structures to avoid their misinterpretation as pathology. The normal MSK US findings in children which can be confused with pathology and create diagnostic difficulty can arise due to variable states of maturation of bones, cartilage and tendons, complex anatomical locations, accessory structures, and artifacts. Herein, we describe the various technical and interpretive challenges encountered with MSK US in pediatric patients.

Conception of National Biologics Registry for Pediatric Rheumatology: Need of the Hour and the Way Forward.

The outcome for children with rheumatic diseases has been dramatically altered by the use of biological therapies. Increasing use of these agents will need careful monitoring for long term safety, particularly in children. Current data on safety of these drugs stem exclusively from Western literature. There is clear need for a registry of all children with rheumatic diseases who are commenced on biological agents to ensure appropriate pharmacovigilance. In this perspective, we discuss the need for and the role of a biologics registry for children with rheumatic diseases in India.