PURPOSE: This study analyzes the efficacy and safety of tofacitinib in pediatric patients presenting with treatment-resistant uveitis and scleritis. METHOD: Retrospective Chart Review. RESULT: Nine children diagnosed with uveitis and one with scleritis received oral tofacitinib treatment. The median age of these patients was 9 years, with bilateral involvement observed in nine of them. Juvenile idiopathic arthritis was the most identifiable cause of uveitis, with anterior uveitis (50%) being the most frequent subtype of inflammation among these children. The median duration of immunosuppressive treatment before switching to tofacitinib was 18 (16-49) months. Remission of uveitis was achieved in all but two children, who experienced recurrence - manifesting as anterior uveitis. The median duration of follow-up in these children after tofacitinib treatment was 277.5 (183-549) days. At the end of follow-up, topical steroids could be withdrawn in six children, and two children were on topical steroids once a day. None of the children developed any systemic side-effect during the follow-up period. The mean BCVA at presentation was 0.62 ± 0.55, which improved to a mean of 0.27 ± 0.325 at the final follow-up (p = 0.0014). CONCLUSION: Treatment of pediatric uveitis with tofacitinib can be a valuable second-line treatment option and useful alternative in low- and middle-income countries.
Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.
Background and Aim: pGALS (pediatric Gait Arms Legs Spine) is a useful screening tool in identifying musculoskeletal problems in children. Although musculoskeletal problems are common in children, only a small fraction of them have an underlying serious pathology. There is limited data on this subject from north India but none from south India. Our aim was to identify the prevalence of musculoskeletal problems in school going boys in the local community. Methods: We conducted a prospective cross-sectional study among school boys 7-17 years of age from September 2017 to July 2019, in Chennai. The parents or the boys were asked pGALS screening questions and this was followed by the extended pGALS examination including Beighton's scoring for hypermobility. If abnormalities in the screening tool were found, the subjects were then referred to a pediatric rheumatologist for further evaluation. Results: A total of 1543 boys were included in this study. Of these 37% of the study group were found to be hypermobile. According to our study, the prevalence of growing pains was 4.6%. Of 2 boys with suspected pathology 1 boy had enthesitis-related arthritis and another had slipped upper femoral epiphysis (SUFE). The estimated prevalence of juvenile idiopathic arthritis (JIA) was 65/100000. According to our study 12.3% of the children were obese. Conclusion: pGALS is a useful tool to screen for musculoskeletal problems in school going boys. The estimated prevalence of JIA was 65/100000. Of them, 37% of the children had hypermobility. Obese children were more likely to complain of musculoskeletal pain (P value 0.00).
Children with malignancies can present with varied symptoms mimicking rheumatological or orthopedic conditions. Symptoms such as fever, myalgia, arthralgia, and arthritis usually suggest an underlying musculoskeletal condition. However, malignancies in children can also present with such symptoms. The objective of this study was to analyze the clinical and laboratory features of children with malignancies presenting with arthritic manifestations to the paediatric rheumatology clinic and to raise awareness of these presentations among practising physicians. A retrospective case review was carried out in 53 patients who presented to 2 paediatric rheumatology units in 2 tertiary care hospitals in South India. These children presented with musculoskeletal symptoms and had a final diagnosis of malignancy. The median age was 6.1 years with a range from 1 to 15 years and male:female ratio of 1.12:1. The most common presentation was bone pain (75%), followed by fever (53%), polyarthralgia (51%), refusal to bear weight in lower limbs (40%), night pain (40%), and joint swelling (15%). Anemia with Hb < 8 g/dl was observed in 26% of the patients, white cell count (WCC) < 4000 cells/mm3 in 17%, WCC > 12,000 cells/mm3 in 15%, platelets < 150,000/ml in 43%, and erythrocyte sedimentation rate > 20 mm/hr in 77%.The peripheral smear was positive for malignancy in only 40% of the patients. Before referral to tertiary units, 34% were already treated with steroids with a suspected diagnosis of juvenile idiopathic arthritis. Treatment with steroids could mask the symptoms of malignancy and could lead to a delay in diagnosis and a poor outcome.
Aim To study the various pathological patterns of pediatric lupus nephritis (LN) by renal biopsies and to correlate the histopathological data with the clinical and biochemical outcomes. Methods This is a retrospective study in children between 1 month and 18 years of age with renal biopsy-proven lupus nephritis, conducted between January 2015 and December 2019. Various pathological and clinical parameters were compared between the groups with lupus nephritis activity and those without activity. Results Of 38 biopsy-proven lupus nephritis cases, 30 (78.9%) were in the adolescent age group, and the female gender was predominantly affected (n=30; 78.9%). Class IV proliferative lupus nephritis (n=17, 44.7%) was the most common biopsy finding, and the activity score for endocapillary hypercellularity, neutrophil infiltration, fibrinoid necrosis, hyaline deposits, and interstitial inflammation was significantly high in classes III and IV. Overall, attaining remission was less, and the risk of progression of chronic kidney disease (CKD) was higher in class IV (n=3; 7.8%). Mortality was reported in 1 out of 38 (2.6%) children. Conclusion Light microscopy and immunofluorescence studies play an important role in defining the extent of renal damage in the form of activity and chronicity indices, which are the key factors in the decision-making of lupus nephritis treatment. The prognostic relevance of the histological scoring has been evaluated, and it is evident that the activity index and chronicity index go a long way in therapeutic intervention.
OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.
Lung Diseases, Interstitial/complications , Scleroderma, Systemic/complications , Adolescent , Child , Female , Humans , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/pathology , Male , Missed Diagnosis , Prospective Studies , ROC Curve , Tomography, X-Ray Computed , Vital Capacity
OBJECTIVE: To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. METHODS: A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. RESULTS: At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION: Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.
Lung Diseases, Interstitial , Scleroderma, Diffuse , Scleroderma, Systemic , Skin Ulcer , Cross-Sectional Studies , Female , Humans , Male , Scleroderma, Diffuse/diagnosis , Scleroderma, Localized , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology
Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in children and is characterised by the presence of proximal muscle weakness, heliotrope dermatitis, Gottron's papules and occasionally auto antibodies. The disease primarily affects skin and muscles, but can also affect other organs. Renal manifestations though common in autoimmune conditions like lupus are rare in JDM. We describe a child whose presenting complaint was extensive calcinosis cutis. Subtle features of proximal muscle weakness were detected on examination. MRI of thighs and a muscle biopsy confirmed myositis. Nephrocalcinosis was found during routine ultrasound screening. We report the first case of a child presenting with rare association of dermatomyositis, calcinosis cutis and bilateral medullary nephrocalcinosis.
Dermatomyositis , Myositis , Nephrocalcinosis , Child , Dermatomyositis/complications , Dermatomyositis/diagnosis , Humans , Muscle Weakness , Nephrocalcinosis/diagnostic imaging , Nephrocalcinosis/etiology , Skin
In children with systemic lupus erythematosus on immunosuppressive therapy, infection is a known complication. We present a case of a 12-year-old girl who was previously diagnosed with lupus nephritis but had stopped taking allopathic medications and had been on herbal medicines for a year. She was referred to us with persistent fever and disease activity in spite of restarting immunosuppressive treatment. Results of blood tests and bone marrow aspiration were suggestive of macrophage activation syndrome. Imaging of her chest and abdomen showed features suggestive of miliary tuberculosis (TB) in the lungs and granulomas in the spleen. Mycobacterium tuberculosis was identified in bone marrow cultures, resulting in a diagnosis of disseminated TB. She was successfully treated with intravenous steroids, anti-tuberculous therapy and intravenous immunoglobulin. Mycophenolate mofetil was added after 6 weeks. The patient recovered from TB and her lupus was under control during follow-up.
BACKGROUND: X-linked agammaglobulinemia, a primary immunodeficiency, can present with musculoskeletal manifestations. CASE CHARACTERISTICS: A 4-year-old boy, diagnosed as systemic juvenile idiopathic arthritis at the age of 3 years and treated with biological agents, presented with fever, dyspnea and chest pain. Blood culture and pericardial fluid culture revealed Achromobacter xylosoxidans. OUTCOME: Investigation revealed normal serum ferritin but low levels of serum immunoglobulins. Further immunological work-up revealed diagnosis of X-linked agammaglobulinemia. Child improved on antibiotic therapy; treatment with steroids and biological was discontinued. MESSAGE: Underlying immunodeficiency disease must be looked for in children suspected to have juvenile arthritis, more so if they develop unusual serious infection in response to immunomodulatory therapy.
Achromobacter denitrificans/isolation & purification , Agammaglobulinemia/diagnosis , Arthritis, Juvenile/diagnosis , Genetic Diseases, X-Linked/diagnosis , Gram-Negative Bacterial Infections/etiology , Sepsis/etiology , Agammaglobulinemia/complications , Child, Preschool , Diagnosis, Differential , Genetic Diseases, X-Linked/complications , Gram-Negative Bacterial Infections/diagnosis , Humans , Male , Sepsis/diagnosis
Blau syndrome (BS) is a rare autoinflammatory disorder characterized by the clinical triad of arthritis, uveitis, and dermatitis due to heterozygous gain-of-function mutations in the NOD2 gene. BS can mimic juvenile idiopathic arthritis (JIA)-associated uveitis, rheumatoid arthritis, and ocular tuberculosis. We report a family comprising a mother and her two children, all presenting with uveitis and arthritis. A NOD2 mutation was confirmed in all the three patients - the first such molecularly proven case report of familial BS from India.
Arthritis/diagnosis , DNA/genetics , Molecular Diagnostic Techniques/methods , Mutation , Nod2 Signaling Adaptor Protein/genetics , Synovitis/diagnosis , Uveitis/diagnosis , Adult , Arthritis/genetics , Arthritis/metabolism , DNA Mutational Analysis , Female , Humans , India , Nod2 Signaling Adaptor Protein/metabolism , Sarcoidosis , Slit Lamp Microscopy , Synovitis/genetics , Synovitis/metabolism , Uveitis/genetics , Uveitis/metabolism
Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud's and first non-Raynaud's symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.
Abscess/pathology , Antitubercular Agents/therapeutic use , Osteomyelitis/pathology , Tuberculosis, Osteoarticular/diagnosis , Abscess/microbiology , Child, Preschool , Humans , Male , Osteomyelitis/drug therapy , Osteomyelitis/microbiology , Referral and Consultation , Tibia , Treatment Outcome , Tuberculosis, Osteoarticular/drug therapy , Tuberculosis, Osteoarticular/physiopathology
INTRODUCTION: Outcome data in pediatric plasma exchange, especially in nonrenal indications are scarce. We aimed to evaluate its role and outcome in our patients. SUBJECTS AND METHODS: A retrospective study of children admitted in the year 2016 to the Pediatric Intensive Care Unit requiring plasma exchange for nonrenal indications was undertaken. Plasma exchange was given as adjunctive therapy along with primary treatment for the disease concerned. Demographic and clinical data were studied, and descriptive statistical analysis was carried out. RESULTS: Ten children underwent plasma exchange during this 1-year period with a male: female ratio of 3:2 and a mean age of 10 years (range 3-16 years). The indications were acute disseminated encephalomyelitis (n = 2), acute neuromyelitis optica (n = 1), catastrophic antiphospholipid antibody syndrome secondary to systemic lupus erythematosus (SLE) (n = 1), severe SLE with cerebritis/hemophagocytic lymphohistiocytosis (HLH) (n = 2), severe dengue sepsis with HLH/multi-organ dysfunction syndrome (n = 2), and thrombotic microangiopathy secondary to snake bite envenomation (n = 2). All received either 1.5 or 2 times plasma volume exchange (mean sessions - 4, range = 1-6). The mean duration of stay in hospital was 17.2 days (range = 3-40 days), and follow-up was 78 days (range = 3-180 days), with the majority of children (8/10, 80%) survived from the catastrophic illness at the time of discharge. Two children (2/10, 20%) succumbed due to the disease per se in severe dengue sepsis in one and enterobacteriaceae sepsis (hospital-acquired pneumonia) in another. CONCLUSION: Plasma exchange was found to be beneficial as complementary therapy in a critical care setting, especially for nonrenal indications.
