Clinical spectrum and outcome of children with deficiency of adenosine deaminase 2 (DADA2): multicentric experience from India.

OBJECTIVES: Deficiency of adenosine deaminase-2 (DADA2) is a monogenic disorder closely resembling polyarteritis nodosa (PAN) and can present to physicians across various specialties. Through this case series, we aim to describe the clinical spectrum and outcome of Indian children with DADA2. We aimed to study the clinical spectrum and outcome of Indian children with DADA-2. METHODS: The deidentified data from all participating centres were entered in an excel sheet, and the coordinating centre (All India Institute of Medical Sciences, New Delhi) screened the data for accuracy and completeness. RESULTS: We enrolled 16 children (11 females) in the study; the mean (SD) age at the time of onset of symptoms for males and females was 46.2 (47) and 73.6 (50.4) months, respectively. The most common clinical feature in this cohort was fever and rash in 80% of patients. More than half of children n, (%) [8, (53%)] had a CNS stroke. The other clinical features were hypertension [5(33%)], anaemia [3 (20%)] and arthralgia/arthritis in 4 (26%). These children were managed with various immunomodulators: steroids [13, (86%)], anti-TNF agents [(12, (80%)], cyclophosphamide [2 (13%)] and mycophenolate mofetil [3 (20%)]. The median (IQR) duration of follow-up for this cohort was 17 (10, 29) months. Fourteen children achieved remission and none had recurrent strokes after the initiation of anti-TNF drugs. CONCLUSION: DADA-2 closely resembles PAN; early age of onset and CNS stroke are striking differentiating features from classic PAN. Most children respond well to anti-TNF agents without serious adverse events during short-term follow-up.

Cardiac findings in multisystem inflammatory syndrome in children: Short term follow up in a large Indian series.

Background: We present a large Indian series of Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) infection. The aim of the study is to present the incidence and pattern of cardiac involvement in children with MIS-C and their short-term follow-up. Methods and Results: Consecutive 144 children younger than 18 years of age diagnosed with MIS-C referred for cardiac evaluation between June 1 and November 30, 2021, were included and were followed up till February 2022. In addition to the demographics, details of COVID-19 infection, and biomarkers, their cardiovascular assessment (echocardiogram and electrocardiogram) was documented at baseline and on follow-up. The median age of children with MIS-C was 60 (24-104) months. Abnormal cardiac imaging was noted in 59% of children. Ventricular dysfunction was noted in 13.9% and coronary abnormalities were noted in 25.7% of children. The median duration when the first cardiac abnormality was reported was 7 (5-10) days. The distribution of age categories between children with and without cardiac abnormality was comparable. Children with cardiac abnormalities were followed up for a median duration of 47 (30-58) days. Complete resolution was documented in 92% of children after a median duration of 20 (9-38) days. There were no readmissions or deaths during follow-up. Conclusion: Cardiac involvement in children with MIS-C is frequent with coronary abnormalities and ventricular dysfunction being the most common manifestations. Most children exhibit complete clinical and myocardial recovery with appropriate anti-inflammatory therapy. Studies on long-term outcome of these children are needed.

Hyperinflammatory Syndrome in Children Associated With COVID-19: Need for Awareness.

The pandemic of COVID-19 initially appeared to cause only a mild illness in children. However, it is now apparent that a small percentage of children can develop a hyperinflammatory syndrome labeled as Pediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS). Features of this newly recognized condition may include persistent fever, evidence of inflammation, and single or multi-organ dysfunction in the absence of other known infections. Some of these children may share features of Kawasaki disease, toxic shock syndrome or cytokine storm syndrome. They can deteriorate rapidly and may need intensive care support as well. The PCR test is more often negative; although, most of the children have antibodies to SARS-CoV-2. Although the pathogenesis is not clearly known, immune-mediated injury has been implicated. We herein provide current information on this condition, in order to raise awareness amongst pediatricians.

Artificial intelligence for interpretation of segments of whole body MRI in CNO: pilot study comparing radiologists versus machine learning algorithm.

BACKGROUND: To initiate the development of a machine learning algorithm capable of comparing segments of pre and post pamidronate whole body MRI scans to assess treatment response and to compare the results of this algorithm with the analysis of a panel of paediatric radiologists. METHODS: Whole body MRI of patients under the age of 16 diagnosed with CNO and treated with pamidronate at a tertiary referral paediatric hospital in United Kingdom between 2005 and 2017 were reviewed. Pre and post pamidronate images of the commonest sites of involvement (distal femur and proximal tibia) were manually selected (n = 45). A machine learning algorithm was developed and tested to assess treatment effectiveness by comparing pre and post pamidronate scans. The results of this algorithm were compared with the results of a panel of radiologists (ground truth). RESULTS: When tested initially the machine algorithm predicted 4/7 (57.1%) examples correctly in the multi class model, and 5/7 (71.4%) correctly in the binary group. However when compared to the ground truth, the machine model was able to classify only 33.3% of the samples correctly but had a sensitivity of 100% in detecting improvement or worsening of disease. CONCLUSION: The machine learning could detect new lesions or resolution of a lesion with good sensitivity but failed to classify stable disease accurately. However, further validation on larger datasets are required to improve the specificity and accuracy of the machine model.

Body mass in adolescents with chronic pain: observational study.

OBJECTIVE: In a paediatric chronic pain population, to determine whether higher body mass was associated with poorer functioning, mood or treatment outcome. DESIGN: Cross-sectional study with examination of treatment outcomes. SETTING: Tertiary specialist adolescent pain rehabilitation unit. PATIENTS: 355 adolescents with relatively severe non-malignant chronic pain. INTERVENTIONS: Intensive 3-week pain rehabilitation programme. MAIN OUTCOME MEASURES: Objective physical measures (walk, sit-to-stand); self-reported functioning and mood RESULTS: Average body mass index (BMI) in the sample was relatively high (24.2 (SD 5.6)) with 20.5% being classified as obese. However, there were no relationships between body mass and objective physical measures, physical or social functioning, depression or anxiety (all p>0.05). There was a small relationship between higher body mass and greater pain-related fear (r=0.17, p<0.01). Treatment improved all variables (p<0.001) apart from pain intensity. There were no relationships between higher body mass and poorer treatment outcome; in fact, patients with higher BMI showed slightly greater decreases in depression (r=0.12, p<0.05) and pain-specific anxiety (r=0.18, p<0.01) during treatment. CONCLUSIONS: Higher body mass does not worsen functioning, mood or treatment response in adolescents with disabling chronic pain. Childhood obesity and chronic pain are both stigmatised conditions; clinicians should avoid implying that high body mass alone is a causal factor in the struggles of a young person with chronic pain.

Multi-centre national audit of juvenile localised scleroderma: describing current UK practice in disease assessment and management.

OBJECTIVE: To describe current United Kingdom practice in assessment and management of patients with juvenile localised scleroderma (JLS) compared to Paediatric Rheumatology European Society (PRES) scleroderma working party recommendations. METHODS: Patients were included if they were diagnosed with JLS and were under the care of paediatric rheumatology between 04/2015-04/2016. Retrospective data was collected in eleven UK centres using a standardised proforma and collated centrally. RESULTS: 149 patients were included with a median age of 12.5 years. The outcome measures recommended by the PRES scleroderma working party were not utilised widely. The localised scleroderma cutaneous assessment tool was only used in 37.6% of patients. Screening for extracutaneous manifestations did not meet recommendations that patients with head involvement have regular screening for uveitis and baseline magnetic resonance imaging (MRI) brain: only 38.5% of these patients were ever screened for uveitis; 71.2% had a MRI brain. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) or biologics was widely used (96.0%). In keeping with the recommendations, 95.5% of patients were treated with methotrexate as first-line therapy. 82.6% received systemic corticosteroids and 34.2% of patients required two or more DMARDs/biologics, highlighting the significant treatment burden. Second-line treatment was mycophenolate mofetil in 89.5%. CONCLUSION: There is wide variation in assessment and screening of patients with JLS but a consistent approach to systemic treatment within UK paediatric rheumatology. Improved awareness of PRES recommendations is required to ensure standardised care. As recommendations are based on low level evidence and consensus opinion, further studies are needed to better define outcome measures and treatment regimens for JLS.

Chronic non bacterial osteitis- a multicentre study.

OBJECTIVE: To understand the demographics, clinical features and treatment outcomes of Chronic Non-bacterial Osteitis (CNO) from three tertiary paediatric rheumatology services in the United Kingdom. METHODS: Children less than 18 years of age diagnosed with CNO between 2001 to 2016 from one tertiary service and between 2001 to 2017 from two tertiary services were included. Clinical notes were reviewed and all pertinent data were collected on a pre-defined proforma. One hundred and thirty one patients were included in the study. The Bristol diagnostic criteria were applied retrospectively. RESULTS: Retrospective analysis of the data showed that the disease was more common in girls than boys (2.5:1), median age at onset of symptoms was 9.5 years (IQR 8 to 11 years). Bone pain was the predominant symptom in 118/129 (91.4%) followed by swelling in 50/102 (49.01%). Raised inflammatory markers were present in 39.68% of the patients. Whole body Magnetic Resonance Imaging (MRI) was a useful diagnostic tool. Metaphyses of long bones were most often involved and the distal tibial metaphyses 65/131 (49.6%) was the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal. The disease was in remission in 82.4% of the patients during the last follow up. CONCLUSION: Our multicentre study describes features and outcomes of CNO in a large number of patients in the United Kingdom. SIGNIFICANCE AND INNOVATION: Raised inflammatory markers were present in 39.68% of our patients. Whole body MRI is useful for diagnosis and also determining response to treatment. A greater number of lesions were detected on radiological imaging compared to clinical assessment. Metaphyses of long bones were most often involved and the distal tibial metaphyses (49.6%) were the most common site. Non-steroidal anti-inflammatory drugs were used as first line (81.67%) followed by bisphosphonates (61.79%). There was no difference in number of medications used for management in unifocal versus multifocal disease. TNF blockers were used with good effect in our cohort.