Development and validation of a composite disease activity score for measurement of muscle and skin involvement in juvenile dermatomyositis.

OBJECTIVE: To develop a composite DAS for JDM and provide preliminary evidence of its validity. METHODS: The Juvenile DermatoMyositis Activity Index (JDMAI) is composed of four items: physician's global assessment of overall disease activity; parent's/child's global assessment of child's wellbeing; measurement of muscle strength; and assessment of skin disease activity. The score of the JDMAI is the arithmetic sum of the scores of each individual component. Six versions of the JDMAI were tested, which differed in the tools used to assess the third and fourth items. Validation procedures were conducted using three large multinational patient samples including a total of 627 patients. RESULTS: The JDMAI was found to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha = 0.58-0.89), fair responsiveness to clinically important change (standardized response mean = 0.82-3.12 among patients improved) and strong capacity to discriminate patients judged as being in the state of inactive disease or low, moderate or high disease activity by the physician (P < 0.001) or whose parents were satisfied or not satisfied with the course of their child's illness (P < 0.001). Overall, the six versions of the JDMAI showed similar metrological performances in validation analyses. CONCLUSION: The JDMAI was found to possess good measurement properties in a large population of patients with a wide range of disease activity, and is, therefore, suitable for use in both clinical and research settings. The final version of the JDMAI will be selected after its prospective validation.

Thirteen Indians with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (MIM# 208250) is a rare monogenic disorder, characterized by early onset of camptodactyly, progressive coxa vara, bilateral arthropathy and constrictive pericarditis. The syndrome is caused by biallelic loss-of-function variants in PRG4. Deficiency of PRG4 results in progressive worsening of joint deformity with age. Thirteen individuals with CACP syndrome from eight consanguineous Indian families were evaluated. We used exome sequencing to elucidate disease-causing variants in all the probands. These variants were further validated and segregated by Sanger sequencing, confirming the diagnosis of CACP syndrome in them. Seven females and six males aged 2-23 years were studied. Camptodactyly (13/13), coxa vara (11/13), short femoral neck (11/13) and arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. Five novel disease-causing variants (c.3636G>T, c.1935del, c.1134dup, c.1699del and c.962T>A) and two previously reported variants (c.1910_1911del and c.2816_2817del) were identified in homozygous state in PRG4. We describe the phenotype and mutations in one of the large cohorts of patients with CACP syndrome, from India.

Exploring clinical features and therapeutic outcomes in Indian children with mixed connective tissue disease: A multicenter study.

INTRODUCTION: Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast Asia. OBJECTIVES: To describe clinical and laboratory features of jMCTD diagnosed at pediatric rheumatology centers across India. METHODS: A predesigned detailed case proforma in an excel format was prepared and was sent to all the Pediatric Rheumatology centers in India. Eleven centers provided the clinical and laboratory data of their jMCTD patients, which was then compiled and analyzed in detail. RESULTS: Thirty-one jMCTD patients from 11 centers were included in the study. Our cohort had 27 females and four male patients over 12 months (August 2021 to July 2022). The median age at presentation was 12 years (range 5-18 years) and the median duration of symptoms was 24 months at diagnosis (range 2-96 months). The common features included arthritis (90%), malar rash (70.9%), and Raynaud's phenomenon (70.9%). At a mean follow-up of 43 months (range 1-168 months), 45% of them were in remission. There were two deaths reported, due to macrophage activation syndrome and sepsis respectively. CONCLUSION: We present the largest multicenter experience on jMCTD from the Indian subcontinent. The study's findings serve as a crucial stepping stone toward unraveling the complexities of jMCTD and improving patient care and management strategies.

The Intricate Dance of Infections and Autoimmunity: An Interesting Paradox.

Besides genetic susceptibility, infections due to viruses, bacteria and protozoa have been implicated in the development of autoimmune diseases (AD). AD can be triggered in a genetically susceptible individual by infections that disrupt immunological tolerance towards self-antigens. Pathogens can initiate autoimmunity by way of molecular mimicry, bystander activation, epitope spreading or persistent infection with polyclonal activation. This review covers two main topics: (i) the mechanisms by which an infectious agent can trigger or worsen autoimmunity; and (ii) the correlation between specific infectious agents and AD in humans with special emphasis on multisystem inflammatory syndrome in children (MIS-C).

Analysis of the WISP3 gene in Indian families with progressive pseudorheumatoid dysplasia.

Progressive pseudorheumatoid dysplasia (PPD) is a progressive skeletal syndrome characterized by stiffness, swelling and pain in multiple joints with associated osteoporosis in affected patients. Radiographically, the predominant features resemble a spondyloepiphyseal dysplasia. Mutations in the WISP3 gene are known to cause this autosomal recessive condition. To date, only a limited number of studies have looked into the spectrum of mutations causing PPD. We report on clinical features and WISP3 mutations in a large series of Indian patients with this rare skeletal dysplasia. Families with at least one member showing clinical and radiologic features of PPD were recruited for the study. Symptoms, signs and radiographic findings were documented in 35 patients from 25 unrelated families. Swelling of small joints of hands and contractures are the most common presenting features. Mutation analysis was carried out by bidirectional sequencing of the WISP3 gene in all 35 patients. We summarize the clinical features of 35 patients with PPD and report on 11 different homozygous mutations and one instance of compound heterozygosity. Eight (c.233G>A, c.340T>C, c.348C>A, c.433T>C, c.682T>C, c.802T>G, c.947_951delAATTT, and c.1010G>A) are novel mutations and three (c.156C>A, c.248G>A, and c.739_740delTG) have been reported previously. One missense mutation (c.1010G>A; p.Cys337Tyr) appears to be the most common in our population being seen in 10 unrelated families. This is the largest cohort of patients with PPD in the literature and the first report from India on mutation analysis of WISP3. We also review all the mutations reported in WISP3 till date.

Clinical Characteristics and Course of Patients with Juvenile Dermatomyositis - Case Series.

Background: Juvenile dermatomyositis (JDM) is one of the commonest forms of inflammatory myositis in childhood. Objective: The objective study was to study the clinical characteristics and course of JDM patients. Material and Methods: Retrospective analysis of the charts of 25 JDM patients admitted to two hospitals in Bangalore from March 2011 to July 2017. Results: The mean age at onset of disease was 7.74 ± 3.74 years. The male to female ratio was 1.5:1. All patients had skin rashes typical of JDM and 24/25 had demonstrable muscle weakness. Six patients were either lost to follow-up or died. Of the remaining 19 patients, 11 (57.9%) had a monocyclic course, 5 (26.3%) patients had a chronic continuous course, and 3 (15.8%) patients had a polycyclic course. Conclusions: JDM though rare should always be considered in the differential diagnosis in any child with skin rash and muscle pains and weakness. When diagnosed early and treated appropriately, sustained remission without medications is possible in a good proportion of patients.

Chronic Recurrent Multifocal Osteomyelitis - A Case Series from India.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory disease of the bone. It tends to be multifocal and usually the symptoms tend to run for months and years before diagnosis is usually made. The objective of our study was to understand the clinical presentation and short-term response to treatment of CRMO patients. MATERIALS AND METHODS: A retrospective analysis of patients diagnosed with CRMO between 2011 and 2016 was done. Case records of these were retrospectively reviewed for clinical features, investigations and treatment received. RESULTS: Six patients were diagnosed with CRMO. The median age of onset and time to diagnosis from onset of symptoms was 8 and 3.5 years respectively. Lower limb bones were the most commonly involved. CONCLUSIONS: There is significant delay in diagnosis of CRMO and this could be because of a lack of awareness of this condition amongst clinicians. Our case series with only male affection is rather unique as compared to other case series reported in medical literature which tend to have more female predilection. Pain with or without swelling was the most common symptom. Most of patients responded to combination therapy.

Development and Testing of a Hybrid Measure of Muscle Strength in Juvenile Dermatomyositis for Use in Routine Care.

OBJECTIVE: To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing in 8 muscles (MMT-8) and the Childhood Myositis Assessment Scale (CMAS) but is more comprehensive than the former and more feasible than the latter. METHODS: The hybrid MMT-8/CMAS (hMC) is composed of all 8 items of the MMT-8 and 3 items of the CMAS: time of head lift, assessment of abdominal muscles, and floor rise. The score ranges 0-100, with 100 indicating normal muscle strength. Validation procedures were conducted using 3 large multinational patient samples, including a total of 810 JDM patients. RESULTS: The hMC revealed face and content validity, good construct validity, excellent test-retest reliability (intraclass correlation coefficient = 0.99), and internal consistency (Cronbach's α = 0.94), strong responsiveness to clinical change over time (standardized response mean = 0.8 among patients judged as improved by the caring physician), and satisfactory capacity to discriminate patients judged as being in the states of inactive disease or low, moderate, or high disease activity by the physician (P < 0.001) or patients whose parents were satisfied or not satisfied with the illness course (P < 0.001). CONCLUSION: The hMC was found to possess good measurement properties in a large population of patients with a wide range of disease activity and severity. The new tool, which is primarily intended for use in routine clinical care, should be further tested in other populations of patients evaluated prospectively.

Synovial Arteriovenous Malformation Masquerading as Arthritis.

BACKGROUND: Synovial arteriovenous malformation is rare. CASE CHARACTERISTICS: We present three children with recurrent monoarthritis secondary to synovial arteriovenous malformation. OUTCOME: Two children underwent excision of arteriovenous malformation. Another child had diffuse arteriovenous malformation, which was inoperable. MESSAGE: Synovial arteriovenous malformations should be considered in the differential diagnosis of monoarthritis, especially of the knee.