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Importance: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35 000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management., Objective: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2., Evidence Review: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence., Findings: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined., Conclusions and Relevance: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2.

Objective: To develop a standardized steroid dosing regimen (SSR) for physicians treating childhood-onset systemic lupus erythematosus (SLE) complicated by lupus nephritis (LN), using consensus formation methodology., Methods: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%., Results: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6)., Conclusion: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials., (© 2021, American College of Rheumatology.)

Competing Interests: The authors declare no conflict of interest.

Background: Intraarticular injections (IAI) were first reported in adult rheumatology in the 1950s and subsequently gained acceptance as a safe and efficacious treatment in Juvenile idiopathic arthritis (JIA). IAIs are now widely performed and recommended as the initial or only treatment of oligoarticular JIA and ancillary treatment of actively inflamed joints in other varieties of JIA. However, the performance of the procedure is currently not guided by standardized recommendations, and several practice variations are observed., Methods: This worldwide survey of pediatric rheumatologists (with 48.5% response from Pediatric Rheumatology International Trials Organization [PRINTO and Pediatric Rheumatology Collaborative Study Group [PRCSG] members) captures the differences in pre-procedural, procedural and post-procedural protocols and practices observed across the globe and asks the necessity of developing consensus in this area of Pediatric Rheumatology., Results: This worldwide survey of Pediatric Rheumatologists had a response rate of just under 50% and the views of about 42% who routinely performed the procedure. It captured the differences in IAI protocols and practices observed across the globe. Significant variations in practice were noted in use of Local anesthesia, choice, and dose of therapeutic agent for the intraarticular injection and use of ultrasound to guide injections. While some practice variations may be explained by institutional protocols in different parts of the world, the clinical implications of these are largely unknown and beg the need for further studies., Conclusions: Given these practice variations, the authors recommend further studies to explore the cost and clinical implications and subsequently work towards developing consensus plans to ensure uniformity in this widely used procedure in Pediatric Rheumatology.

Neonatal-Onset Multisystem Inflammatory Disease (NOMID) or Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome is a monogenic autoinflammatory disorder characterized by urticarial skin rash, fever, chronic meningitis and joint manifestations. Here we report a case of an Indian male child who presented at the age of 9 months with fever, respiratory distress, urticarial skin rash, arthritis, and neuroregression. Suspecting NOMID/CINCA syndrome, the child's blood was sent to the Jaslok Hospital and Research Centre for mutation analysis of the CIAS1/NLRP3 gene. The DNA was screened for mutations in exon 3 of CIAS1/NLRP3 gene by automated Sanger sequencing. DNA sequencing showed a novel heterozygous c.1813A➔G, p.R605G mutation in exon 3 of CIAS1/NLRP3 gene (ref no NM_001243133.1). His parents tested negative for this mutation. We therefore identified a novel de novo mutation in this family in the CIAS1/NLRP3 gene responsible for the child's clinical features.

Objectives: To assess the course, outcome and complications in a mono-centric cohort of 53 patients with systemic onset juvenile idiopathic arthritis (s-JIA)., Methods: In an observational study, 53 consecutive patients diagnosed with s-JIA on or before October 2009 were enrolled and followed up between October 2009 and September 2012. At each 6-12 weekly visit, clinical examination, laboratory investigations and details of on-going treatment were recorded. Disease course was classified as monocyclic, intermittent and persistent. At last visit, outcome was studied with respect to remission (Wallace criteria) and Steinbrocker functional classification. Juvenile Arthritis Damage Index (JADI) was measured on a subset., Results: In 53 patients analysed, the mean follow-up period was 5.5 ± 1.85 y, with a cumulative follow-up period of 291.5 patient-years. The mean age at diagnosis was 6.3 ± 3.4 y. Thirty-three patients suffered from disease and/or drug related complications. Infections were observed in 16 (30%) and macrophage activation syndrome in 5 (9.4%). Nine (17%) had a monocyclic course, 31 (58.5%) had an intermittent course and 13 (24.5%), a persistent course. At last visit, 9/9 patients of the monocyclic group, 17/31 in the intermittent group and 3/13 in the persistent group were in remission. At the end of the study, 96.2% of the index patients were Steinbrocker functional class I and II with the monocyclic group having the best functional outcome. JADI was performed on 20/53 patients. Nine had significant articular damage. The range of Juvenile arthritis damage index-articular (JADI-A) was 0-25/72 (median-6) and of Juvenile arthritis damage index-extra articular (JADI-EA) was 0-4/17 (median-1)., Conclusions: The outcome of patients with s-JIA in a resource limited setting where early diagnosis, multidisciplinary care and availability of biologics are hurdles, is further altered by complications related to longstanding disease and over use of steroids.

Objectives: To evaluate the benefits of the addition of leflunomide (LEF) in children with polyarticular course juvenile idiopathic arthritis (JIA), non-responsive to standard dose parenteral methotrexate (MTX)., Methods: In an observational study, 32 children with polyarticular course JIA failing standard dose MTX (up to 15 mg/m2/week sc for at least 3 and up to 6 months) received additional LEF. Permitted concomitant drugs included pulse steroids for flares and/or low bridging dose of prednisolone, intra-articular steroids and non-steroidal anti-inflammatory drugs. No other DMARDs had been used before enrolment. Patients underwent 8-12 weekly assessment. At each visit, core set of outcome variables and laboratory parameters, viz. haemogram and liver enzymes were recorded. The primary efficacy outcome was the ACR Pedi 30 criteria. At the last follow up, Wallace's criteria were used to determine children achieving remission., Results: 25 of 32 children who followed up for at least 3 months were analysed. Mean follow up duration following addition of LEF was 1.61 years (range: 0.29 to 3.0 years). At 3 months, 68% of the patients met the ACR Pedi 30 response. 17 of the 20 children (85%) showed an ACR Pedi 30 response at 6 months and 16 out of 18 (88.8%) at 1 year. Of the 18 children followed up till the end of the study, 12 (66.6%) met the ACR Pedi 30 criteria and 9 (50%) were in clinical remission on medications (off steroids). Adverse effects were observed in 2 children (gastritis in one and elevated liver enzymes in the other)., Conclusions: Our findings support further study of the role of this combination in the management of polyarticular course JIA refractory to standard dose MTX, especially in resource challenged settings where biologicals are unaffordable. The open observational nature of the study is its limitation.

Background: TRAPS, an autosomal dominant autoinflammatory disorder occurs due to mutations of the TNFRSF1A gene. Mutation negative TRAPS (TRAPS like illness) is also known. Anti TNF molecules (etanercept) is the mainstay of therapy., Case Characteristics: A 11-year-old boy with a 5 year clinical profile indicative of a TRAPS like illness and with negative mutation studies is described. He has been followed up for nearly 2 years after starting etanercept., Outcome: He had sustained response to etanercept which has subsequently been titrated (0.4 mg/kg subcutaneously every 23-24 days) to keep him symptom free., Message: Mutation negative cases of TRAPS can be diagnosed with a high index of suspicion. Treatment with etanercept is expensive but possibly intervals between doses could be titrated to reduce cost.

A retrospective assessment of clinical characteristics, complications/ associations, laboratory investigations, treatment modalities and outcome in an inceptional cohort of 22 (male-13) children with juvenile dermatomyositis (JDM) receiving treatment at Jaslok Hospital, Mumbai during 1997- 2012 was performed . Mean age at diagnosis was 7.52 ± 3.99 years. Typical skin rash and muscle weakness were present in all children. Common complications included cutaneous ulcers (27.27%), dysphagia (22.72%) and calcinosis (18.18%).All patients presented with at least one of the serum muscle enzymes elevated. Absence of mortality and cardio-pulmonary complications and a monocyclic course in 72.7% of our patients are at variance from Western series.

Systemic onset juvenile idiopathic arthritis (SOJIA) is the most common autoimmune auto inflammatory disease in childhood. A sizeable number of these patients run a recalcitrant disease course, resistant to the conventional line of management, ultimately resulting in permanent disability from joint destruction, local growth deformities or iatrogenic side effects. The new biological agents although very effective, are beyond the affordability of most in our country. Thalidomide, a cheaper option has been shown to be very effective in the disease control of patients with SOJIA. We report three Indian children with a chronic refractory course of SOJIA, all of whom had failed conventional line of treatment but improved with thalidomide.

Objective: To put forward a new concept--Blau arteritis, a form of large-vessel vasculitis phenotypically related to Takayasu disease but genetically and clinically part of an expanded phenotype of Blau syndrome., Methods: We provide a clinical description of a new case and summarize previously published cases of arteritis associated with Blau syndrome. Genetic testing was performed by direct sequencing of exon 4 of the NOD2 gene., Results: The case described and those reviewed from the literature demonstrate the emerging phenotype of Takayasu-like arteritis in patients with Blau syndrome. Although most patients described to date depict an otherwise classic Blau syndrome phenotype, the current case was atypical in that the predominant features were arteritic. A novel substitution, G464W, in a highly conserved position near the nucleotide oligomerization domain of the NOD2 protein is also described., Conclusion: Blau arteritis can be observed in the context of both typical and atypical (incomplete) Blau syndrome. The associated mutation in the NOD2 gene raises the question of the potential importance of this gene among patients with "primary" forms of Takayasu arteritis.

Vasculitis is defined as the presence of inflammation in a blood vessel that may occur as a primary process or secondary to an underlying disease. Primary vasculitides are rare in children. These are defined by both the size of vessels involved and the type of inflammatory response. Clinical features consist of multi-organ involvement on a background of constitutional features reflecting the size and location of the blood vessels involved. Whilst some vasculitides are best diagnosed clinically, many forms require sophisticated imaging and other investigations (auto antibodies) to reveal the correct diagnosis. Prompt recognition and treatment is crucial as many of the vasculitides cause significant morbidity or mortality. Treatment options range from symptomatic therapy, immunosuppresive agents, intravenous immunoglobulin (IVIG) or biologic agents and are determined by the type of vasculitis, the severity of the inflammation, and the organ systems affected. Early detection and aggressive treatment is crucial for the best outcomes in the most severe forms of childhood vasculitis.

Objectives: To study the association between growing pains (GP) and joint hypermobility (HM ), children aged 3-9 were examined for the coexistence of HM and GP., Methods: The study group consisted of 433 children (219 boys, 214 girls; age range 3-9 years) from one public school in Mumbai, India. In the assessment of HM, the Beighton criteria were used. Any child who met > or = 5/9 criteria was considered to have HM. Children were considered to have GP if they fulfilled the Petersons criteria, namely the pains were bilateral, intermittent non-articular pains involving the lower limbs; typically occurring during late afternoons or evenings with a normal physical examination and normal laboratory parameters whenever performed. The assessment of HM and GP were carried out independently. Children with bilateral knee hypermobility were also evaluated for the occurrence of GP., Results: Of the 433 children, 177 (40.8%) were found to have HM and 122 (28.1%) GP; 75 (61.4%) of the 122 with GP had HM and 75 (42.3%) of the 177 with HM had GP. Using chi square statistical analysis, joint hypermobility and GP were found to be highly associated. Knee hypermobility also showed significant statistical association with GP., Conclusion: This study suggests that there is a strong association between joint hypermobility and GP in schoolchildren. It is possible that joint hypermobility may play a part in the pathogenesis of GP. More studies are needed to establish the clinical significance of this association.

Objectives: To study the prevalence of joint hypermobility in children from Mumbai, India and to study its association with malnutrition., Methods: In a cross-sectional field study from September '02 to February '03 in Mumbai, 829 children of the lower urban socio-economic strata, between 3 and 19 years of age were evaluated independently by two observers for hypermobility using the Beighton 9-point scoring system. A score of >or= 4/9 was considered positive. Their nutritional status was stratified using standard Indian growth charts and hypermobility was quantified in various nutritional groups. Musculoskeletal symptoms were assessed by a questionnaire given to parents. Standard tests of significance (Chi square test, p<0.05-significant) were applied., Results: 58.7% of the population studied, had a Beighton score >or= 4/9. There was a declining prevalence of joint hypermobility noted with increasing age. Near equal sex incidence was noted. A higher incidence of finger signs was noted in comparison to elbow hyperextension, knee hyperextension and hands-to-floor. 26% of the hypermobile population had musculoskeletal symptoms as compared with 17.2% of the non-hypermobile population (p<0.05). A positive Beighton score was found in 452/734 (61.5%) children with Grade 3 and 4 malnutrition in comparison to 35/95 (36.8%) children with normal nutrition or mild grades (Grade 1 and 2) of malnutrition (p<0.05). In the group with Grade 3 and 4 malnutrition, 26.1% of those hypermobile had musculoskeletal symptoms in comparison to 17.7% of their non-hypermobile counterparts (p<0.05)., Conclusions: In our study population: 1. A high prevalence of hypermobility using Beighton's score was noted; 2. Finger signs of the Beighton score were more common than the other signs; 3. Moderate and severe malnutrition were associated with hypermobility; 4. Musculoskeletal symptoms were linked to joint hypermobility; 5. Moderate and severely malnourished hypermobile children were more likely to have musculoskeletal symptoms as compared to their non-hypermobile counterparts.

A girl with neuropsychiatric lupus demonstrated Parkinsonian features soon after commencing risperidone. The single photon emission computed tomography scan showed hyperperfusion of the basal ganglia. Symptoms abated with the addition of dopaminergic agents to immunosuppressive therapy. The literature on juvenile Parkinsonism in lupus has been reviewed.

Hemorrhagic pleural effusion associated with Kawasaki disease KD is very rare and has not been reported in the medical literature. We describe a 5-year-old male with incomplete (atypical) KD who presented with fever and severe respiratory distress due to bilateral pleural effusions. Other features included unilateral cervical lymphadenopathy, swelling of the hands and feet followed by periungual desquamation, elevated erythrocyte sedimentation rate, thrombocytosis and sterile pyuria. Pleural fluid analysis revealed a hemorrhagic exudative effusion. Therapy with high-dose i.v. immunoglobulin resulted in dramatic clinical improvement and resolution of pleural effusion. An echocardiogram obtained at presentation and at 6 weeks of illness was normal. Pediatricians should be aware that hemorrhagic pleural effusion can be a presenting manifestation of KD.

A case is reported of a four-year old child with mycoplasma pueumonia with a left atrial thrombus secondary to aPL antibodies. He was anticoagulated and the thrombus resolved in six months.

The combination of Congenital Central Hypoventilation with Hirschsprung's disease belongs to the family of diseases now designated as Neurocristopathies. The authors report a polysomnographically documented case and review literature on this disorder.

Arthritis is one of the less common, yet challenging problems that may confront a pediatrician. The potential pathology is diverse ranging from the benign with a good prognosis to the serious and ultimately fatal. From a spot diagnosis to conditions that evolve over time, few other conditions challenge and stimulate the clinical acumen. Several diagnoses can be made clinically with the laboratory investigations providing additional support. An approach through which the clinician seeks answers through a logical sequence of questions is presented to help shortlist the possible diagnosis.

A 1-year-old child with proximal femoral focal deficiency (PFFD) is presented. The clinical spectrum and associated abnormalities is described and the diagnosis and management of this entity is discussed.

The objective of this study was to evaluate the relative efficacy of 3 commonly used antipyretics viz. mefenamic acid, ibuprofen and paracetamol. The subjects were randomized to 3 groups to receive either paracetamol 10 mg/kg or ibuprofen 7 mg/kg or mefenamic acid 6.5 mg/kg. Axilla temperature was recorded just prior to drug administration and at hourly intervals for 4 hrs. The mefenamic acid group (n = 29) showed a drop of 3.5 degrees F at the end of 4 hours as compared to the paracetamol group (n = 29) (drop 2.44 degrees F) and ibuprofen group (n = 20) (drop 2.79 degrees F). Analysis of the area under the mean temperature vs. time curve showed that mefenamic acid demonstrated significantly better antipyretic activity compared to paracetamol (P < 0.05) over the entire period of observation and ibuprofen (P < 0.05) in the 2 to 4 hour range. Mefenamic acid continued to show antipyretic activity at the end of 4 hours in contrast to ibuprofen and paracetamol. Since the period of observation was restricted to 4 hours, we were unable to quantify the precise duration of its extended antipyretic efficacy.