Pediatric Rheumatology Research Articles

Serum interleukin-18 levels can improve the diagnostic performance of the PRINTO and ILAR criteria for systemic juvenile idiopathic arthritis

ObjectiveRecently, the Pediatric Rheumatology International Trials Organization (PRINTO) has proposed revisions to the current International League of Associations for Rheumatology (ILAR) criteria for systemic juvenile idiopathic arthritis (s-JIA). Interleukin (IL)-18 overproduction plays a significant role in the pathogenesis of s-JIA. This study aimed to evaluate the performance of the PRINTO criteria compared with the ILAR criteria and determine whether serum IL-18 levels improve their diagnostic performances. MethodsOverall, 90 patients with s-JIA and 27 patients with other febrile disease controls presenting with a prolonged fever of > 14 days and arthritis and/or erythematous rash were enrolled. The ILAR and PRINTO classification criteria were applied to all patients and examined with expert diagnoses. Enzyme-linked immunosorbent assay was used for measuring serum IL-18 levels. ResultsThe PRINTO criteria had higher sensitivity but lower specificity than the ILAR criteria (sensitivity: PRINTO 0.856, ILAR 0.533; specificity: PRINTO 0.259, ILAR 0.851). With the addition of serum IL-18 levels ≥ 4,800 pg/mL, the sensitivity of the ILAR criteria and specificity of the PRINTO criteria were improved to 1.000 and 1.000, respectively. PRINTO plus serum IL-18 levels ≥ 4,800 pg/mL showed the highest value in Youden’s index (sensitivity – [1 − specificity]). ConclusionSerum IL-18 levels could improve the diagnostic performance of the PRINTO and ILAR criteria for s-JIA. The PRINTO criteria plus serum IL-18 levels ≥ 4,800 pg/mL could be the best diagnostic performance for s-JIA.

IgG4-связанное заболевание с вовлечением тканей глазницы у пятилетнего ребенка

Case study IgG4-related disease involving the tissues of the orbit in a five-year-old child Yu.V. Kotova, E.E. Grishina, E.I. Kondratieva, G.I. Fokanova, I.M. Tarabanko Moscow Regional Research Institute of Childhood, Mytishchi, Moscow Region, Russian Federation M.F. Vladimirsky Moscow Regional Research Institute, Moscow, Russian Federation Purpose. To demonstrate a rare clinical case of IgG4-related disease in the practice of a rheumatologist, a pediatrician and an ophthalmologist. Material and methods. A 5-year-old child had a lesion in the left orbit, manifested by left-sided exophthalmos, medial displacement of the left eye, and limited outward eye mobility. He underwent an orbitotomy with histological and immunohistochemical examination of the biopsy specimen in the ophthalmology department of M.F. Vladimirsky Moscow Regional Research Institute. A diagnosis of IgG4-related disease involving the left orbital tissue was made. Results. In the rheumatology department of the Moscow Regional Research Clinical Institute of Childhood, the boy received pulse therapy with glucocorticoids. When trying to reduce the dose of glucocorticoids, exophthalmos and swelling of the eyelids on the left increased again. Cyclophosphamide therapy was ineffective. In addition to oral Prednisolone, Rituximab, a drug from the group of synthetic chimeric monoclonal antibodies, was prescribed. A stabilization of the process in the left orbit and an improvement in the general condition of the child ocurred. The duration of remission is 2 years. Discussion. IgG4-related disease is characterized by lymphoplasmacytic infiltration of tissues with a predominance of IgG4-positive cells and subsequent formation of fibrosis. Ophthalmological manifestations of IgG4-related disease are most often characterized by damage to the tissues of the orbit and lacrimal gland. Usually develops in middle-aged people; it is rare in pediatric practice. Conclusion. Patients with IgG4-related disease can be encountered in the practice of a rheumatologist, pediatrician and ophthalmologist. If diagnosis and treatment are not urgent, the disease is prone to progression, which leads to disability of the patient. The main treatment method is long-term use of glucocorticoids. In case of steroid resistance or steroid dependence, early use of immunosuppressive drugs or monoclonal antibodies could be considered. Key words: immunoglobulin G4-related disease, autoimmune orbital myositis, pediatric rheumatology, immunosuppressive therapy

Elicitation of expert prior opinion to design the BARJDM trial in juvenile dermatomyositis.

To elicit and quantify expert opinion concerning the relative merits of two treatments for a rare inflammatory disease: Juvenile dermatomyositis (JDM). The formal expression of expert opinion reported in this paper will be used in a Bayesian analysis of a forthcoming randomised controlled trial known as BARJDM (baricitinib for juvenile dermatomyositis). A Bayesian prior elicitation meeting was convened, following a previously described methodological template. Opinion was sought on the probability that a patient in the BARJDM trial would achieve clinically inactive disease, off glucocorticoids (GC) within a 12-month period with either methotrexate (standard of care); or baricitinib (a Janus kinase inhibitor, JAKi), with GC schedules identical in both arms of the trial. Experts' views were discussed and refined following presentation and further discussion of summated published data regarding efficacy of methotrexate or JAKi for JDM. Ten UK paediatric rheumatology consultants (including one adolescent paediatric rheumatologist) participated in the elicitation meeting. All had expertise in JDM, leading active National Health Service clinics for this disease. Consensus expert prior opinion was that the most likely probability of clinically inactive disease off GC within 12 months was 0.55 on baricitinib and 0.23 on methotrexate, with a greater degree of uncertainty for baricitinib. Experts currently think that baricitinib is superior to MTX for the treatment of JDM, although there is uncertainty around this. BARJDM will therefore integrate randomised trial data with this expert prior opinion to derive a posterior distribution for the relative efficacy of baricitinib compared with MTX.

Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry.

Ensuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry. This is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis. Across six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion. About one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

Intra-articular corticosteroid utilization and characterizations of use in juvenile idiopathic arthritis within the PR-COIN registry.

Intra-articular corticosteroid injections (IACI) have been shown to be effective at improving arthritis across juvenile idiopathic arthritis (JIA) categories. The American College of Rheumatology (ACR) recommends IACI use as primary and adjunctive therapy for JIA patients. However, there remains minimal data describing actual IACI use in North America. The objective of this study was to describe and to evaluate IACI use in JIA, utilizing the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry. Study participants from 13 sites were enrolled in the PR-COIN registry from 2011 to 2015. Demographic and clinical variables were summarized and Chi-squared and t-tests were used to evaluate differences between participants who did or did not receive IACI. Multiple logistic regression models were used to evaluate characteristics associated with IACI treatment. Our study included 3,241 participants, the majority of whom were white (85%), female (71%) and had oligoarticular JIA (39%). IACI was administered at least once in 23% of participants, the majority of whom had oligoarticular disease (52.5%), but overall use in oligoarticular participants was low at 30.8%. IACI use varied significantly between treatment centers and use was associated with oligoarticular disease, ANA positivity, and use of other systemic medications. This study demonstrates that participants with JIA enrolled in the PR-COIN registry between 2011 and 2015 with persistent oligoarticular disease, ANA positivity, and use of other systemic medications were more likely to receive IACI. However, IACI use was lower than expected for oligoarticular participants.

Clinical characteristics and prognostic factor in juvenile dermatomyositis: data of the Spanish registry

BackgroundJuvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients.MethodsWe retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity.ResultsOne hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5–10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22–47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5–34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6–22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications.ConclusionsWe describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication.

Development of the paediatric society of the African league against rheumatism (PAFLAR) JIA registry and clinical profile of JIA in Africa from the PAFLAR JIA registry

BackgroundThe spectrum of Juvenile Idiopathic Arthritis (JIA) in Africa is still largely unknown. We thus set out to illustrate how we set up the PAFLAR JIA registry and describe the clinical profile of Juvenile Idiopathic Arthritis across various regions in Africa.MethodsWe carried out a retrospective observational cohort study where collaborators were trained on use of the existing PAFLAR REDCAP database to enter data for the JIA patients currently under their care capturing their epidemiological data, clinical features, laboratory investigations, diagnosis and therapy at initial diagnosis. Descriptive statistics including means, standard deviations, medians, interquartile ranges (IQR) for continuous variables and proportions for categorical variables were calculated as appropriate. Tests for difference between groups were performed between categorical variables using Pearson’s chi-square or Fisher’s exact tests. All analyses were performed using SPSS version 22 software.ResultsWe enrolled 302 patients, 58.6% (177 of 302) of whom were female. The median age of disease onset was 7 years (range 3–11 years) and the median age at diagnosis was 8.5 years (range 5–12 years). The median duration delay in diagnosis was 6 months (range 1-20.8 months). The JIA categories included Systemic JIA 18.9% (57), Oligoarticular JIA 19.2% (83), Polyarticular RF + ve 5% (15), Polyarticular RF-ve 17.9% (54), Enthesitis Related Arthritis (ERA) 18.2% (55), Psoriatic Arthritis 7% (21) and undifferentiated JIA 5.6% (17). As regards treatment the commonest therapies were NSAID therapy at 31.1%, synthetic DMARDs at 18.1%, synthetic DMARDs combined with NSAIDs at 17.5% and steroid therapy at 9.6%. Biological DMARDs accounted for 2.3% of therapies offered to our patients at diagnosis. The average JADAS score was 10.3 (range 4.8–18.2) and the average CHAQ score was 1.3 (range 0.7-2.0).ConclusionOur study highlights strategies involved in setting up a Pan-African paediatric rheumatology registry that embraces our broad diversity and the vast spectrum of JIA in Africa while comparing the various therapies available to our patients. The PAFLAR JIA registry strives to ensure a comprehensive representation of the diverse healthcare landscapes within the continent. Further longitudinal observation studies are required to ascertain the long-term outcomes of our patients and ultimately help inform policy to create a more favorable health ecosystem to support the healthcare needs of JIA patients in Africa.

A Study on Semaphorin 3A Level in Juvenile-onset Systemic Lupus Erythematosus Patients.

Juvenile-onset systemic lupus erythematosus (jSLE) is an uncommon yet severe autoimmune/inflammatory condition affecting multiple bodily systems, typically manifest-ing before the age of 18. This disease exhibits significant complexity, displaying considerable variation among patients. Its effects can range in severity from minor to fatal, characterized by a pattern of recurring flare-ups and periods of remission, making its natural progression difficult to predict. The aim of this work is to investigate the correlation between semaphorin 3A and systemic lupus erythematosus patients who follow up at Pediatric Rheumatology Unit Chil-dren's Hospital at Cairo University. This cross-sectional research was performed at the Pediatric Rheumatology Unit Cairo University Children's Hospital and included cases with jSLE under treatment and fol-low-up from the period of August 2021 to August 2022. Regarding demographic data of the studied subjects, highly significant variances were noted among the patient group & control group regarding age (years) & sex. However, there were non-significant variances among the patient group and control group concerning weight. In the current research, median (IQR) onset of disease was 2 (1 3) years, mean ± SD age at dis-ease diagnosis was 8.98 ± 2.13 years, median (IQR) disease duration 2 (1 3) years, family history was negative in 36 (90.0%) patients and consanguinity was negative in 28 (70.0%). The distribution of the manifestations within the patients group was as follow 7 (17.5%) with mu-cocutaneous, 7 (17.5%) with vasculitis, 4 (10.0%) with serositis, 11 (27.5%) with cardiac, 17 (42.5%) with renal, 11 (27.5%) with GIT, 5 (12.5%) with hematological, and 4 (10.0%) with neu-rological manifestations. In addition, there were 2 (5.0%) with arthritis, 31 (77.5%) with arthral-gia, and 2 (5.0%) with fever mean ± SD systolic BP was 115.95 ± 8.38 & mean ± SD diastolic BP was 75.60 ± 6.11. Regarding treatments in the patients' group, the median steroid dose was 15mg (5-25) with medi-an duration of 2 (1 3), 38 (95.0%) patients received hydroxychloroquine with mean ± SD hy-droxychloroquine dose of 205.26 mg ± 51.71. 23 (57.5%) patients received cyclophosphamide with mean ± SD number of cyclophosphamide doses 7.17 mg ± 2.42. Mycophenolate was re-ceived in 27 (67.5%) with mean ± SD dose of 614.07 mg ± 225.85. There were highly statistically significant differences between control group and patients' group concerning TLC, creatinine, & ESR. Highly statistically significant variance was noted among the control group and patients group concerning CRP. Regarding the patients' group, the mean ± SD serum C3 was 99.89 mg/dl ± 28.45, median (IQR) serum C4 was 14.5 mg/dl (8.8 25.5), and median (IQR) albumin creatinine ratio was 27 IU/ML (16 186). There was positive ANA with titre and pattern in 34 patients (85.0%), positive antids-DNA in 25 patients (62.5%), and positive anticardiolipin IgM and IgG in 5 patients (12.5%). Renal biopsy was found to be normal in 23 (57.5 percent), lupus nephritis class II, III in 3 (7.5 percent), lupus nephritis class III in 10 (25.0%), and lupus nephritis class IV in 4 (10.0%). Urine analysis results showed the following: normal in 28 (70.0%), albumin in 2 (5.0%), casts in 2 (5.0%), pus cell in 4 (10.0%), albumin + casts in 2 (5.0%) and albumin + pus cell in 2 (5.0%). Regarding semaphorin 3A level, a highly statistically significant variance was noted among the control & patients group concerning semaphorin 3A level found to be lower in cases than control with a p-value below 0.001. In patients' group, a negative correlation for semaphorin 3A with SBP, DBP, AST and ESR and also a positive correlation with steroid duration in the studied pa-tients. In addition, highly significant association between semaphorin 3A & positive CRP. How-ever, no significant relationship between semaphorin 3A & SLE manifestations except arthritis was found related to semaphorin 3A level. ROC curve shows that the semaphorin 3A cut-off point to predict SLE ≤ 3 with sensitivity = 47.50, specificity=92.50, PPV=86.4, and NPV=63.8. Reduced plasma Semaphorin 3A levels were found in this study; furthermore, their clinical relationship in SLE proposes their significant job in this illness. Furthermore, the ROC results demonstrated that Semaphorin 3A could be a new symptomatic biomarker in SLE with very high sensitivity for the determination of SLE, demonstrating that they might be helpful bi-omarkers for the evaluation of SLE. However, extra studies that focus on the potential role of Semaphorin 3A in SLE are needed.

Longitudinal program evaluation of an inter-institutional mentorship network for pediatric rheumatology using a quality improvement framework

BackgroundThe American College of Rheumatology (ACR)/Childhood Arthritis and Rheumatology Research Alliance (CARRA) Mentoring Interest Group (AMIGO) is an inter-institutional mentorship program launched to target mentorship gaps within pediatric rheumatology. Initial program evaluation indicated increased mentorship access. Given the small size of the pediatric rheumatology workforce, maintaining a consistent supply of mentors was a potential threat to the longevity of the network. Our aims were to: (i) describe the sustainability of AMIGO over the period 2011–2018, (ii) highlight ongoing benefits to participants, and (iii) describe challenges in the maintenance of a mentorship network.MethodsA mixed-methods approach centered on a quality improvement framework was used to report on process and outcomes measures associated with AMIGO annual cycles.ResultsUS and Canada Pediatric rheumatology workforce surveys identified 504 possible participants during the time period. As of fall 2018, 331 unique individuals had participated in AMIGO as a mentee, mentor or both for a program response rate of 66% (331/504). Survey of mentees indicated high satisfaction with impact on general career development, research/scholarship and work-life balance. Mentors indicated increased sense of connection to the community and satisfaction with helping mentees despite limited perceived benefit to their academic portfolios. Based on AMIGO’s success, a counterpart program for adult rheumatology, Creating Adult Rheumatology Mentorship in Academia (CARMA), was launched in 2018.ConclusionsDespite the challenges of a limited workforce, AMIGO continues to provide consistent access to mentorship opportunities for the pediatric rheumatology community. This experience can inform approaches to mentorship gaps in other academic subspecialties.

Ready to leave? – Adolescents’ and parents’ perceptions of transition from paediatric to adult rheumatology care

BackgroundIn Sweden, approximately 2000 children live with Juvenile Idiopathic Arthritis (JIA). About half of them continue to have an active disease and need to transfer to adult rheumatology care. This study aimed to investigate Swedish adolescents’ and parents´ perceptions of readiness for transition from pediatric to adult rheumatology care.MethodsThe study was a cross-sectional quantitative study. Patients at the pediatric rheumatology clinic at a university hospital in Sweden and members of The Swedish National Organization for Young Rheumatics aged 14–18 and their parents were invited to participate in the study. Data was collected with the Readiness for Transition Questionnaire (RTQ) focusing on adolescents' transition readiness, adolescents' healthcare behaviors and responsibility, and parental involvement. Data were analyzed with descriptive statistics. Comparative analyses were made using non-parametric tests with significance levels of 0.05 as well as factor analyses and logistic regression.ResultsThere were 106 adolescents (85 girls, 20 boys) and 96 parents answering the RTQ. The analysis revealed that many adolescents and parents experienced that the adolescents were ill-prepared to take over responsibility for several healthcare behaviors, such as booking specialty care appointments, calling to renew prescriptions and communicating with medical staff on phone and to transfer to adult care. Parents and adolescents alike stated that it was especially difficult for the adolescents to take responsibility for healthcare behaviors meaning that the adolescents had to have direct interaction with the healthcare professionals (HCPs) at the paediatric rheumatology clinic, for example to renew prescriptions. It was evident that the adolescents who perceived they were ready to take responsibility for the aspects related to direct interaction with HCPs were more overall ready to be transferred to adult care.ConclusionAdolescents need more support to feel prepared to transfer to adult care. With the results from this study, we can develop, customize, and optimize transitional care programs in Sweden for adolescents.

Clinical and laboratory profile, disease activity and outcome of childhood systemic lupus erythematosus - A retrospective study in a tertiary care hospital in Assam

Background: Systemic lupus erythematosus in children (cSLE) represents 10-20% of all cases of SLE. However, this is still underreported from Assam. In this study, we report our experience with 25 patients of cSLE over the last 3.5 years. Materials and methods: This retrospective study was carried out at the Department of Pediatrics, Gauhati Medical College and Hospital, Guwahati, Assam. Data of patients with cSLE in the records of pediatric rheumatology and immunodeficiency clinic from April 2018 to October 2021 were collected and analysed. Results: In our cohort, the median age at presentation was 10 years (range, 4.6-14 years). The female-to-male ratio was 7:1. Hematological involvement, 21 (84%) was the most common manifestation followed by cutaneous, 19 (76%), and renal involvement, 17 (68%). Five patients also had associated HbE hemoglobinopathy. We had performed renal biopsy in 12/17 patients. Class IV lupus nephritis was the most common type in our patients. Twenty-four out of 25 patients had active disease at the time of the first presentation. There were four deaths in our cohort including two deaths that occurred due to congestive cardiac failure in patients with suspected myocarditis. Seventeen patients in our cohort had completed a median of 10 months (range, 2 – 30 months) follow-up and 6/9 biopsy-proven proliferative nephritis were in remission after a median of 9.5 months (range, 2-27 months) follow-up. Conclusion: Hematological involvement was the commonest manifestation in cSLE at our center. The majority of patients with proliferative LN were in remission with standard treatment. Keywords: hemoglobin E; lupus nephritis; myocarditis; vasculitis

Comparative analysis of pediatric rheumatic patient growth patterns against norms: A cross-sectional study conducted in an Eastern Indian hospital

Background. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease. Rheumatic diseases are a major cause of chronic illness in children around the world. SLE is a further prevalent inflammatory illness. Aims and objectives. To study different growth parameters of pediatric patients attending pediatric rheumatology clinic, to compare the growth parameters with age and sex matched controls and to compare growth among different types of pediatric rheumatic patients. Method. Different growth parameters and SMI (for children above 9 years) were recorded for patients attending pediatric rheumatology OPD having disease duration more than one year. Results. Among 121 patients, JIA was most common followed by SLE. Among JIA subtypes, SOJIA is most common. Mean age of presentation was earlier in SOJIA, late in JoAS. SLE patients had larger duration of illness prior to diagnosis than JIA patients. In JIA patients, mean height was significantly less than controls. SOJIA and polyarticular variety had significantly less weight and height compared to controls. SLE patients had significantly less weight and height compared to control. Anthropometric parameters were significantly more in SLE patients compared to JIA cohort. There was significantly more delayed puberty both in JIA and SLE patients compared to controls. Conclusion. JIA was most common, followed by SLE. Among JIA patients SOJIA variety was most common, JIA patients had significantly lower height than controls. SLE patients had significantly lower weight and height than controls. Delayed puberty was significantly more in both JIA and SLE patients compared to controls.

Evaluation of pediatric rheumatologists' approach to rituximab use: a questionnaire study.

RTX has become a common treatment option in pediatric rheumatology in recent years. Treatment management may vary between clinician such as vaccination and routine tests. • During the course of rituximab therapy, clinicians should be attentive to specific considerations in pre-treatment, during administration, and in post-treatment patient monitoring. • There are differences in practice among clinicians in the management of RTX therapy. These practice disparities have the potential to impact the optimal course of treatment. • This study highlights that standardized guidelines are needed for RTX treatment in pediatric rheumatology, particularly for vaccination policies and routine tests.

Study of Sexual Maturation in Children With Juvenile Dermatomyositis

Objective: There is complete absence of sexual maturity data on patients afflicted with juvenile dermatomyositis (JDMS) from the Indian subcontinent. Hence, this study aimed to unfold the effect of this disease on the sexual development of JDMS children. Methods: In the Growth Laboratory/Clinic of the Department of Pediatrics, 60 (25 male and 35 female) sexual maturity-related observations were made on 35 JDMS patients, aged 10–17 years, enrolled from the Pediatric Rheumatology Clinic. Breast development stage and age of onset of menarche were recorded among female patients. In male patients, besides, determining the genitalia development stage, measurement of stretched penile length and testicular volume was done. Appearance of pubic and axillary hair among JDMS patients of both sexes was recorded. Results: Most girls with JDMS (34.28%) were in breast development stage-B2 (mean age 10.91 ± 1.08 years) and 22.86% had attained menarche. However, breast stage B5 was attained at 14.62 ± 1.06 years. JDMS girls reached stage B2 at the same age as their normal healthy counterparts. Onset of menarche was delayed by almost a year in JDMS girls. Age of attainment of genitalia stage G2 in JDMS boys (12 years) was delayed by 6 months as compared to well-off Chandigarh boys (11.5 years), whereas it was advanced by 1.5 years when contrasted with affluent Indian counterparts (13.3 years). Conclusion: Comparable pubertal attainments in JDMS males and somewhat delayed start of menarche in female JDMS patients as compared to their normal counterparts show that disease activity has a smaller effect on the sexual development of JDMS patients from north-western India.

Relationship of Fatigue, Pain Interference, and Physical Disability in Children Newly Diagnosed With Juvenile Idiopathic Arthritis.

Our objectives were to quantify the relationships among fatigue, pain interference, and physical disability in children with juvenile idiopathic arthritis (JIA) and to test whether fatigue mediates the relationship between pain interference and physical disability in JIA. Patients enrolled within three months of JIA diagnosis in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry between February 2017 and May 2023 were included. Their parents completed the Patient-Reported Outcomes Measurement Information System fatigue and pain interference short proxy questionnaires and the Childhood Health Assessment Questionnaire disability index at registry enrollment. Associations were assessed using Pearson correlations and multiple linear regression. Structural equation modeling (SEM) was used to test if fatigue mediates the relationship between pain interference and physical disability. Among 855 patients (61.4% female, 44.1% with oligoarthritis), most reported fatigue and pain interference scores similar to those in the reference population, but 15.6% reported severe fatigue and 7.3% reported severe pain interference, with wide variation across JIA categories. Fatigue was strongly correlated with pain interference (r = 0.72, P < 0.001) and with physical disability (r = 0.60, P < 0.001). Pain interference (β = 0.027, P < 0.001) and fatigue (β = 0.013, P < 0.001) were both associated with physical disability after controlling for each other and potential confounders. SEM supported our hypothesis that fatigue partially mediates the relationship between pain interference and physical disability. Our findings suggest both fatigue and pain interference are independently associated with physical disability in children newly diagnosed with JIA, and the effect of pain interference may be partly mediated by fatigue.

Secondary fibromyalgia in children with immune-inflammatory rheumatic diseases

Patients with immune-inflammatory rheumatic diseases (IIRDs) often present with non-inflammatory musculoskeletal pain associated with nociceptive dysfunction, central sensitization, and secondary fibromyalgia (FM). In recent years, an increasing number of publications have appeared dealing with FM in rheumatoid arthritis and systemic connective tissue diseases in adult patients, while this problem is little discussed in pediatric rheumatology, partly due to the differences between the existing diagnostic criteria in children and adults, which complicate the diagnosis of juvenile secondary FM. The consequence of this is often the unfounded prescription or switching of synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs in patients who do not require intensified antirheumatic therapy, but rather psychotherapy and psychopharmacotherapy, as well as the wider use of physical and rehabilitation medicine methods. In a brief narrative review, we tried to trace the investigation of FM in a rheumatological clinic, including children with IIRD, from a historical perspective, to summarize current literature data on this problem and to point out possible solutions.

A pilot study of childhood-onset Takayasu arteritis using whole exome sequencing suggests oligogenic inheritance involving classical complement, collagen, and autoinflammatory pathways.

Takayasu arteritis (TA) is a chronic granulomatous inflammatory disease affecting the aorta and its branches. Paediatric TA (pTA) may present from 6months after birth till the adolescent age group. Genetics and pathogenesis of pTA are not fully understood. Earlier studies reported monogenic mutation in NOD2, XIAP, and STAT1 genes in patients with pTA. TA, a relatively rare disease, is more common in geographical pockets, including India. We hypothesized that South Asian patients with pTA, namely, those of Indian subcontinent origin, may have clinically relevant and unique pathogenic variants involving one or more genes, especially those linked to genetically driven vasculitic illnesses, including autoinflammatory pathologies. Children with pTA fulfilling EULAR/PRINTO/PReS classification criteria and presenting with clinical symptoms to the Paediatric Rheumatology clinic of Christian Medical College, Vellore, were included. Blood samples were collected after getting informed consent from parents or guardians and assent forms from children. DNA was extracted from whole blood using the Qiagen DNA extraction kit. Initially, the common variant in Indian population, namely, ADA2 c.139G > A; p.Gly47Arg, was screened, followed by whole exome sequencing. Fourteen children were recruited for the study. Median age of patients was 11years (4months-14years) with a male-to-female ratio of 4:10. Distribution of angiographic subsets by Numano's classification of included children were as follows: type 5 (n = 7), type 4 (n = 5), and type 3 (n = 2). We identified novel variants in ten different genes. This include variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. Two of 14 patients have heterozygous pathogenic variants; this implies that combination of heterozygous variants in C3 and COL5A1 might lead to disease development, suggesting digenic inheritance. One patient has a homozygous variant in CYBA. None of the patients were identified to have ADA2 variants. Whole exome sequencing reveals combination of rare variants in genes C3, COL5A1, and CYBA associated with disease development in children with Takayasu Arteritis. Key Points • We identified novel variants in genes of classical complement pathway, namely, C2, C3, C6, C7, and C9, and other genes, namely, CYBA, SH3BP2, GUCY2C, CTC1, COL5A1, and NLPR3. • Two of 14 patients have heterozygous pathogenic variants in C3 and COL5A1; this may have implications in disease development, suggesting digenic inheritance. • One patient has homozygous variant in CYBA. • None of the patients were identified to have ADA2 variants.

Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Protocols in Pediatric Rheumatology: Treat-to-Target is Also an Important Principle in Pediatric Rheumatology

Protocols in Pediatric Rheumatology: Treat-to-Target is Also an Important Principle in Pediatric Rheumatology

Barriers and facilitators to medical care retention for pediatric systemic lupus erythematosus in South Africa: a qualitative study

BackgroundSystemic lupus erythematosus (SLE) is a life-threatening, chronic, autoimmune disease requiring long term subspecialty care due to its complex and chronic nature. Childhood-onset SLE (cSLE) is more severe than adult-onset, and the cSLE population in South Africa has been reported to have an even higher risk than patients elsewhere. Therefore, it is critical to promptly diagnose, treat, and manage cSLE. In this paper, we aim to describe and evaluate barriers and enablers of appropriate long-term care of cSLE South Africa from the perspective of caregivers (parents or family members).MethodsCaregivers (n = 22) were recruited through pediatric and adult rheumatology clinics. Individuals were eligible if they cared for youth (≤ 19 years) who were diagnosed with cSLE and satisfied at least four of the eleven ACR SLE classification criteria. Individual in-depth, semi-structured interviews were conducted between January 2014 and December 2014, and explored barriers to and facilitators of ongoing chronic care for cSLE. Data were analyzed using applied thematic analysis.ResultsFour barriers to chronic care engagement and retention were identified: knowledge gap, financial burdens, social stigma of SLE, and complexity of the South African medical system. Additionally, we found three facilitators: patient and caregiver education, robust support system for the caregiver, and financial support for the caregiver and patient.ConclusionThese findings highlight multiple, intersecting barriers to routine longitudinal care for cSLE in South Africa and suggest there might be a group of diagnosed children who don’t receive follow-up care and are subject to loss to follow-up. cSLE requires ongoing treatment and care; thus, the different barriers may interact and compound over time with each follow-up visit. South African cSLE patients are at high risk for poor outcomes. South African care teams should work to overcome these barriers and place attention on the facilitators to improve care retention for these patients and create a model for other less resourced settings.