Diagnosis Of Juvenile Dermatomyositis Research Articles

O08 Severely pruritic juvenile dermatomyositis

Abstract A 7-year-old female with type IV skin and autism spectrum disorder presented with a 4 month history of progressive proximal myopathy, weight loss and 20 month history of a worsening, intensely pruritic rash. Cutaneous examination showed a widespread eczematous eruption, post-inflammatory hypopigmentation, heliotrope rash and firm subcutaneous changes, in addition to palmar-plantar papules, pustules and burrows. Extra-cutaneous findings included multiple fixed flexion deformities and muscle wasting. Investigations revealed a normocytic anaemia, elevated muscle enzymes, strongly positive anti-nuclear antibodies and negative myositis-specific antibodies. Whole body MRI reported proximal muscle oedema. Skin biopsy demonstrated lichenoid and perifollicular inflammation, dermal mucin and subcutaneous calcification. Clinical findings were consistent with a diagnosis of juvenile dermatomyositis (JDM), complicated by concurrent scabies. Prednisolone in combination with methotrexate was commenced as first-line therapy in line with current consensus JDM treatment plans, in addition to topical steroids and sun protection. Muscle power started to improve after 5 months but ongoing cutaneous inflammation prompted second-line therapy with IV immunoglobulin. Oral ivermectin was required for the management of scabies due to topical permethrin failure. JDM is a rare autoimmune small-vessel vasculopathy with significant morbidity and limited evidence-based guidelines. Unlike adult-onset disease there is no racial predilection or association with malignancy. Calcinosis is more common in children but early treatment reduces disease complications. JDM has a variable disease course with a median time to remission of 4.67 years. Residual skin changes are increasingly recognised to be an early predictor of prolonged recovery time and these patients may benefit from biologic agents.

Clinical improvement in early onset interstitial lung disease using rituximab in children with anti-MDA5 positive juvenile dermatomyositis.

Children with juvenile dermatomyositis (JDM) and antibodies to melanoma differentiation associated gene 5 (anti-MDA5) are at increased risk of severe disease complications, including interstitial lung disease (ILD). Data regarding treatment of disease complications in this patient population is limited. In this study, we examined the disease course of children with JDM and anti-MDA5 antibodies before and after treatment with rituximab (RTX). Patients (age 2-21 years) seen at the Children's Hospital at Montefiore between July 2012 and August 2021, with a diagnosis of JDM, positive anti-MDA5 positive antibodies, evidence of ILD, and who were treated with rituximab were eligible for inclusion. Retrospective clinical and laboratory data were reviewed. Five out of 8 patients with positive anti-MDA5 antibodies had evidence of ILD (62.5%). Four patients had data available for review. All patients received at least 5 courses of RTX infusions, with discontinuation of steroids by an average of 12 months after starting RTX and a decrease to fewer than two concurrent medications by fifth course of RTX. Indicators of ILD on high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) either improved or fully resolved over the course of RTX treatment for all patients. Patients also demonstrated resolution of active cutaneous manifestations and musculoskeletal disease activity. This is the first study to examine the use of RTX in children with JDM and anti-MDA5 antibodies, with notable improvements ILD, cutaneous and musculoskeletal manifestations. Further studies are needed to better understand the efficacy of RTX on JDM disease related complications.

Risk factors for developing calcinosis in juvenile dermatomyositis: subcutaneous and myofascial edema in initial magnetic resonance imaging.

Calcinosis is a sequela of Juvenile Dermatomyositis (JDM) with significant morbidity. A retrospective study observing risk factors for JDM calcinosis, including a possible association between higher intensity of subcutaneous and myofascial edema in initial magnetic resonance imaging (MRI) and development of calcinosis was performed at a tertiary pediatric medical center. Data from the past 20years on JDM patients with MRIs at the time of JDM diagnosis were obtained. MRIs were individually evaluated by two pediatric musculoskeletal radiologists who blindly graded the intensity of edema on a 0-4 Likert scale. Clinical data and edema scores were compared between patients who developed calcinosis and who did not. Forty-three patients (14 with calcinosis and 29 without calcinosis) were identified. The calcinosis group contained more racial and ethnic minorities, younger ages of JDM onset and longer time to reach JDM diagnosis. Muscle enzyme levels at JDM diagnosis were lower in the calcinosis group, especially Creatinine Kinase (CK) (p = 0.047) and Alanine Aminotransferase (ALT) (p = 0.015). The median score for edema in both groups was 3 (p = 0.39) with an inter-rater reliability of 95%. There was no association between increased subcutaneous and myofascial edema in MRIs at the time of JDM diagnosis and development of calcinosis. Earlier age of JDM onset, racial and ethnic minority, and delay in JDM diagnosis could be risks for developing calcinosis. The calcinosis group presented with lower muscle enzyme levels at the time of JDM diagnosis, especially CK and ALT with statistical significance. This could reflect delay in diagnosis and treatment.

Assessment of Thigh MRI Radiomics and Clinical Characteristics for Assisting in Discrimination of Juvenile Dermatomyositis.

Magnetic resonance imaging (MRI) is an important non-invasive examination in the early diagnosis of juvenile dermatomyositis (JDM). We aimed to evaluate the feasibility of radiomics to establish a quantitative analysis of MRI images. Radiomics and machine learning were used to retrospectively analyze MRI T2 fat suppression sequences and relevant clinical data. The model associated with radiomics features was established using a cohort of patients who underwent thigh MRI at the children's hospital from June 2014 to September 2021. In total, 75 patients with JDM and 75 control children were included in the training cohort (n = 102) and validation cohort (n = 48). The independent factors including lower muscle strength (OR, 0.75; 95% CI, 0.59-0.90), higher creatine kinase (CK) level (OR, 1.65; 95% CI, 1.20-2.38), and higher radiomics score (OR, 2.30; 95% CI, 1.63-3.62) were associated with a clinical diagnosis of JDM. The combined model achieved good discrimination performance compared the radiomics score model under linear discriminant analyses in the training cohort (AUC, 0.949; 95% CI, 0.912-0.986 vs. AUC, 0.912; 95% CI, 0.858-0.967; p = 0.02) and in the validation cohort (AUC, 0.945; 95% CI, 0.878-1 vs. AUC, 0.905; 95% CI, 0.812-0.998; p = 0.03). The combined model showed the diagnostic value was not weaker than the biopsy (AUC, 0.950; 95% CI, 0.919-0.981, n = 150 vs. AUC, 0.952; 95% CI, 0.889-1, n = 72; p = 0.95) and electromyogram (EMG) (AUC, 0.950; 95% CI, 0.919-0.981 vs. AUC, 0.900; 95% CI, 0.852-0.948; p = 0.10) among all the patients. The combination of radiomics features extracted from the MRI and non-invasive clinical characteristics obtained a pronounced discriminative performance to assist in discriminating JDM.

Chemotherapy induced juvenile dermatomyositis: a novel presentation- a case report

BackgroundIdiopathic connective tissue disease juvenile dermatomyositis (JDM) is characterised by inflammatory myositis and distinctive skin abnormalities. Only a few cases of Dermatomyositis (DM) owing to chemotherapy used to treat cancer have been reported, despite the fact that the link between DM and cancer in adults is widely known. We describe the case of a female, age 14, who experienced DM as a side effect of chemotherapy following enucleation for retinoblastoma. We also discussed our patient's likely pathophysiology of JDM after treatment.Case presentationA 14-year-old female came to our facility complaining of trouble walking and bluish-black discoloration on her neck, elbows, forehead, and knees that had been present for eight months. The patient had undergone enucleation of the left eye due to retinoblastoma, followed by 40 cycles of radiation therapy and 13 cycles of chemotherapy with Cyclophosphamide, Etoposide, Carboplatin, Vincristine, and Dactinomycin. Her serum LDH and CPK levels were high, and she tested positive for ANA. The muscle biopsy was consistent with the changes of DM. When electromyography was performed, it revealed tiny, fibrillating, polyphasic motor unit potentials and sharp, positive waves that were suggestive with DM. A diagnosis of JDM was made after taking into account the symptoms, biochemical data, muscle biopsy, and electromyography results. The patient's symptoms started to get better once methotrexate and oral corticosteroids were started.ConclusionThis case report emphasises the value of ongoing observation after cancer chemotherapy because specific cutaneous and muscle symptoms may lead paediatricians to consider the possibility of chemotherapy-induced JDM, which is uncommon in young patients.

Whole-body MR imaging in evaluation of children with juvenile dermatomyositis

PurposeTo evaluate the whole-body MRI (WBMRI) findings in children with juvenile dermatomyositis (JDM) and correlate them with clinical and laboratory results. MethodWe conducted the present prospective study from October 2019 to September 2021. Thirty children (8.2 ± 3.88 years) with a diagnosis of JDM based on EULAR/ACR classification criteria underwent WBMRI using short tau inversion recovery, diffusion-weighted, and T1 modified DIXON (precontrast and postcontrast) sequences. WBMRI scans were analysed independently by two radiologists for abnormal signal intensity and enhancement in the different muscle groups. Radiological findings were correlated with clinical examination, muscle enzymes, and inflammatory markers. ResultsWBMRI revealed abnormal signal intensity and diffusion restriction, predominantly in the thigh (n = 21, 70 % children), calf (n = 18, 60 % children), and hip (n = 16, 53.3 % children) muscles. A significant positive correlation was observed between the serum total creatinine kinase and lactic dehydrogenaselevels, with altered signal intensity and diffusion restriction in the paraspinal and thigh muscles. Diffusion restriction in the hip and calf muscles also showed significant positive correlations with these enzymes. Significant positive correlations were detected between lower limb muscle strength and altered signal intensity and diffusion restriction in the thigh (p = 0.023) and calf (p = 0.002) muscles. Postcontrast images did not yield any additional useful information. ConclusionsWBMRI provided useful information in evaluation of the extent and distribution of findings in children with JDM. There were significant positive correlations between MRI findings and muscle enzymes and clinical examination results. The addition of contrast to the WBMRI protocol did not provide any additional advantage.

Myositis autoantibodies in a racially diverse population of children with idiopathic inflammatory myopathies

BackgroundJuvenile idiopathic inflammatory myopathies (JIIMs) is a group of autoimmune disorders, including juvenile dermatomyositis (JDM), juvenile polymyositis (JPM) and overlap myositis, that are characterized by proximal muscle weakness, elevated levels of serum muscle enzymes, and pathognomonic skin findings. While the exact etiology of JIIMs is unclear, the presence of myositis specific autoantibodies (MSAs) have been associated with certain clinical phenotypes, organ involvement and disease prognosis. To date, there have been few studies of the associations between MSA presence and patient ethnicity. It is important to understand the extent to which ethnicity impacts disease manifestations, organ involvement and clinical outcomes. The goal of our study is to determine MSA and myositis associated autoantibody (MAA) presence, clinical phenotype, and disease course in a racially diverse population of pediatric patients with JIIMs.MethodsPatients age 2–21 years with a prior diagnosis of JDM, JPM or overlap myositis, who had been tested for MSA/MAA, were eligible for study inclusion. Clinical and laboratory data were collected retrospectively via manual chart review in this single-center study. Descriptive statistics were performed to summarize each variable. Given the small sample size, non-parametric testing was performed using Fischer’s exact test, Wilcoxon rank sum test and Kruskal-Wallis test.ResultsThirty one patients were included in the analysis. Race and ethnicity were self-reported as Hispanic (48.4%), white (25.8%), and Black (25.8%). The most prevalent MSAs were anti-MDA5 (25.8%), anti-p155/140 (22.6%) and anti-MJ (19.4%). Presence of autoantibodies (p = 0.04) and pulmonary disease (p = 0.03) were significantly higher in patients of Black or Hispanic descent compared with white descent. Anti-MDA5 antibodies, cutaneous ulceration, cardiopulmonary involvement, hospitalizations and one death were only reported in patients with Black or Hispanic descent. Patients with anti-MDA5 antibodies were more likely to be male (p = 0.04) and to have cutaneous ulceration (p = 0.02).ConclusionsThis study describes the prevalence of MSA/MAA in a racially diverse group of patients with JIIM and further delineates clinical phenotype and disease complications in these groups. We found a relatively high proportion of children with anti-MDA5 antibodies and described potentially worse clinical courses in children of Black or Hispanic descent. Further investigation is warranted to examine these findings.

P136 Adverse reaction with intravenous immunoglobulin (IVIG) therapy and management of symptoms: a single centre experience

Abstract Background IVIG is a therapeutic preparation comprising of pooled blood donated from large numbers of healthy people. There are different preparations of IVIG available. All should have high levels of IgG (>95%) but vary in concentrations, pH, stabilizing agents and IgA content. In inflammatory conditions, IVIG is often used as an adjunct therapy in patients with poor response to first line therapy and in general well tolerated. However adverse reactions can occur and vary in severity from mild constitutional symptoms to aseptic meningitis. The aim of this study was to identify patients who required IVIG within the paediatric rheumatology department at Great Ormond Street Hospital, the underlying diagnosis of these patients and the indication for starting treatment. The study also looked at the number of adverse drug reactions of patients requiring IVIG, the symptoms they presented with and the management of these symptoms. Methods A retrospective case review, of patients under the care of the paediatric rheumatology team who received IVIG between July 2013 to August 2018. We collected demographics including, age, sex, diagnosis of patients and indication for commencing IVIG, symptoms of any adverse drug reaction and management of symptoms. Results We identified 43 patients who required IVIG over the last 5 years as part of their treatment plan, of which 23 patients had a diagnosis of Juvenile dermatomyositis (JDM). Of the remaining patients 5 had a diagnosis of SLE, 4 with SRP positive mysositis, 2 with necrotising myositis and 2 with atypical systemic onset JIA. The main indication for starting treatment was for active or worsening skin disease, muscle weakness or both. From the 43 patients that required IVIG, 21 patients had an adverse drug reaction and 15/21 patients had a diagnosis of JDM. 5/21 patients had symptoms associated with aseptic meningitis (headache, photophobia and neck stiffness), 2 of which were unable to continue treatment. The remaining 16 patients had milder constitutional symptoms. Symptoms were managed by premedicating patients prior to subsequent IVIG treatment with a combination of paracetamol, chlorphenamine, ondansetron or by reducing the rate of IVIG infusion or reducing the dose of IVIG from 2g/kg to 1g/kg. Conclusion We identified from the study, that half the patients requiring IVIG as part of their treatment plan had an adverse drug reaction of which half had a diagnosis of JDM. However, the majority of patients who had an adverse drug reaction had mild constitutional symptoms, relieved by premedication or by adjusting IVIG rate of infusion or dose. Only 2 patients were unable to continue IVIG treatment. Disclosures S.H.A. Wildman None. M. Al-Obaidi None.

Severe Abdominal Manifestations in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare and heterogeneous pediatric-onset idiopathic inflammatory myopathy. Gastrointestinal (GI) involvement occurs in 22% to 37% of JDM patients but has only been described in case reports. In this retrospective, single-center, observational study, we aimed to assess the causes and management of severe GI manifestations in JDM patients. We studied a cohort of 9 patients among 110 JDM patients followed during the study period (8.3%). The GI complications were related to JDM in most cases (17/19), with digestive tract involvement (n = 10), acute pancreatitis (n = 4), and hepatitis (n = 3). Three patients died from refractory JDM 2.9 years (2-3.6) after the JDM diagnosis. We highlight the need to consider pancreatitis as a main diagnostic factor in JDM patients with severe GI manifestations and the requirement of early aggressive treatment for these patients.

General Paresis in a Child with Unusual Presentation

Introduction: Acute onset quadriparesis can be a manifestation of a variety of neurological, metabolic or autoimmune conditions. Rarely, it could be one of many clinical presentations of juvenile dermatomyositis which belongs to the group of idiopathic inflammatory myopathies of childhood. We report the case of a 9-year old girl who presented with global myopathy over a two-month period. Case report: A 9-year-old girl referred with a 2 months history of generalised muscular pain and weakness. There were no significant history of preceded illness, trauma or excessive strenuous exercises. She had no other systemic complaints such as fever or skin rash. Past medical history was unremarkable except for recurrent tonsillitis. Physical examination revealed a child with normal alertness and behaviour. She has notable generalised swelling of all four limbs. Her neurological examination revealed normal tone however her power was definitely reduced in all four limbs (Graded 3/5). She demonstrated signs of proximal myopathy. Subsequent investigations revealed high Creatinine Kinase (CK) levels of 6470U/L, ESR 84mm/hr with deranged transaminases and positive serum mycoplasma and CMV IgM. Her MRI brain and spine along with lumbar puncture results were normal. She was referred to tertiary centre for further evaluation as her weakness progressed. An MRI muscle demonstrated marked inflammation in all four limbs including paravertebral muscles. Her muscle biopsy showed inflammatory myopathy leading to a diagnosis of juvenile dermatomyositis (JDM). She is now showing sustained clinical improvements following a course of immunoglobulin and corticosteroids therapy. Discussion: The diagnosis of JDM is generally considered in patients with rash-associated muscle weakness. Essentially, it involves assessment of muscle, skin, lung and cardiac involvement on top of baseline list of investigations that has been outline by Single Hub and Access point for pediatric Rheumatology in Europe (SHARE). This case reflects that JDM is possible despite non-existent of skin involvement.

Macrophage activation syndrome in juvenile dermatomyositis: a systematic review.

Macrophage activation syndrome (MAS) is a potentially fatal complication of a number of rheumatological conditions, but few studies assessed it in juvenile dermatomyositis (JDM). Indeed, MAS is not considered as a frequent complication of JDM, but its occurrence could be under-estimated. In order to address this issue, we performed a revision of the available medical literature, describing and assessing patients with both MAS and JDM. After retrieving 253 records initially, 11 papers were selected as appropriate for our research objective, which provided a total of 12 patients affected with both MAS and JDM. Our pooled case series suggested that MAS in JDM may not be very rare, even though no final conclusion about its incidence and mortality rate can be made. However, JDM-related MAS seems to be difficult to treat, since methylprednisolone pulse therapy alone was not sufficient in most cases. Moreover, MAS in JDM patients often occurred at the onset of the rheumatic disease, before the final diagnosis of JDM could be established. Finally, MAS criteria validated for systemic Juvenile Idiopathic Arthritis (sJIA) resulted to be a very useful guidance to diagnose MAS in JDM patients as well, but their reliability may not be absolute. Therefore, cohort and multicenter studies are needed to assess the incidence and improve the diagnostic criteria for MAS in JDM patients.

Coronary artery dilation associated with anti-synthetase syndrome in an adolescent

BackgroundIdiopathic inflammatory myopathies (IIM) are a group of systemic autoimmune disorders primarily affecting skeletal muscle. Pediatric coronary artery dilation is frequently discussed in Kawasaki disease. However, it has yet to be reported in the IIMs or antisynthetase syndrome. We report a unique case of a patient with IIM, antisynthetase syndrome and coronary artery dilation.Case presentationWe report an adolescent presenting with joint symptoms, fever, and eye swelling with a clinical diagnosis of Juvenile Dermatomyositis. He subsequently developed diastolic hypotension with evidence of coronary artery dilation. He received steroids and immunoglobulin and followed by immunosuppressants with mild improvement in his symptoms. The adolescent later developed dyspnea and cough with CT lungs evident for cystic changes; lung biopsy showed interstitial fibrosis and inflammation, and muscle biopsy was abnormal as well. The anti-pl-12 antibody was positive. Following several weeks of treatment, an echocardiogram showed improvement in coronary artery dilation. His joint symptoms, muscle strength and respiratory symptoms have also improved.ConclusionsCoronary artery dilation is not well understood in IIMs or antisynthetase syndrome. Pathobiology of coronary artery involvement, its treatment and prognosis, and association with IIM and antisynthetase syndrome needs further exploration.

Koebner Phenomenon in Juvenile Dermatomyositis

Koebner phenomenon is an isomorphic response seen in a variety of dermatoses such as psoriasis. Its key feature is the appearance of a new dermatosis in previously unaffected areas following trauma. An 8-year-old girl presented with several months history of a worsening rash on her hands and face, pruritus, and proximal muscle weakness. At age 4, a diagnosis of juvenile dermatomyositis was first established by the presence of heliotrope rash, …

Fashionably Late: A Case of Delayed Cutaneous Manifestations in Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is a rare, but well recognized multi-systemic inflammatory myopathy in children defined by proximal muscle weakness and distinctive skin lesions, that if recognized and treated early result in decreased morbidity and mortality. The 1975 criteria established by Bohan and Peter center around the propensity for early development of heliotrope and Gottron’s lesions in combination with specific laboratory abnormalities, and are still the leading diagnostic tool. The following case demonstrates a toddler with an atypical presentation of JDM in which delayed dermatologic manifestations hindered initial diagnosis. A previously healthy 2 years and 11 months old female presented to the emergency department with a 7-month history of bilateral knee pain and progressive muscular weakness. Initial evaluation yielded a diagnosis of idiopathic rhabdomyolysis but progressive deterioration prompted additional workup. During her course of care, the patient required admission at numerous facilities for specialty procedures including swallow studies, electromyography, Nissen fundoplication with G-tube insertion, and eventual muscle biopsy, resulting in pathology clinching the diagnosis. Post-diagnosis the development of a heliotrope and malar rash ensued, 11 months after commencement of original presentation. As the Bohan and Peter criteria of 1975 can help to aid in diagnosis of JDM for textbook presentations, atypical cases such as ours suggest that revision to current diagnostic criteria needs to be established. Also, with many pediatric rheumatologists opting for less invasive methods than muscle biopsy to aid in diagnosis, in combination with the heterogeneous nature of currently tracked serous markers, the risk for delayed or missed diagnosis is amplified. As prior research has demonstrated, early diagnosis leads to better outcomes for children battling JDM. Therefore, it is vital that criteria be revised and additional research be conducted for more sensitive and specific markers to help aid in early diagnosis of JDM.

Role of magnetic resonance imaging in the diagnosis of juvenile dermato-myositis and polymyositis in Chinese children

Objective: To evaluate the utility of magnetic resonance imaging (MRI) in diagnosis of juvenile dermatomyositis and polymyositis (JDM-PM) in children. Method: Fifty-four patients with JDM-PM in the active stage were enrolled in the study group. Twelve patients with benign acute childhood myositis and forty patients with juvenile idiopathic arthritis (JIA) complicated with myositis were enrolled as controls. MRI imaging of thighs was performed in all patients, fast spin echo T1WI, T2WI, and STIR were obtained in all patients.Muscle biopsy was performed in 41/54 patients with JDM-PM. We compared the value of MRI in diagnosis of JDM-PM with muscle biopsy, electromyography and serum aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase (CK), isoenzyme of creatine kinase (CKMB), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH) levels. Continuous normally distributed variables were reported as means and continuous non-normally distributed variables as median. Chi-square test and Fisher exact test were used to test differences between MRI and other categorical variables. Result: A total of 54 patients were included. Twenty-seven patients were male and the others were female. Average age of the patients was (7.1±3.5) years (2-13 years); 45(83%) paitests were JDM cases and 9(17%) patients had JPM. All patients had MRI examination. Of the 54 patients, 53 had multiple myositis; 10 out of 50 (19%) patients received second MRI after treatment, 6 out of 10 patients had normal findings, 4 patients showed obviously improved images; 41 out of 54 patients underwent muscle biopsy; 22 out of 41 patients had inflammatory cells infiltration and muscle fiber degeneration. The results of the muscle enzyme tests are as follows: 27 (50%) patients had elevated AST, 24 (44%) patients had elevated ALT, 22 (41%) patients had elevated CK, 18(33%) patients had elevated CKMB, and LDH rose in 30 (56%) patients, HBDH rose in 28(52%) patients. These results suggested that muscle MRI was more sensitive than muscle biopsy and muscle enzyme tests in diagnosis of JDM-PM. Conclusion: Patients with JDM-PM showed diffuse patchy hyperintense signals on T2WI of their thighs. MRI may be a sensitive, reliable, and noninvasive tool for clinical diagnosis and theraputic evaluation of JDM-PM.

A case of neonatal-onset autoinflammatory syndrome with a de novo PSMB9 mutation resembling Nakajo-Nishimura syndrome

We report a case of neonatal-onset autoinflammatory syndrome that resembles Nakajo-Nishimura syndrome (NNS), a rare autoinflammatory syndrome caused by a homozygous PSMB8 mutation. The patient is a 7-year-old boy who demonstrated clinical findings that differ from those of typical NNS. Exudative erythemas on his face, trunk, and extremities developed 2 weeks after birth. At 1 month of age, the patient developed fever, elevated serum C-reactive protein levels, and elevated hepatic amino transferase levels. A febrile convulsion caused basal ganglia calcification at 4 months of age. Severe pulmonary arterial hypertension of unknown origin (NT-proBNP 33,445 pg/mL) was diagnosed at 7 months of age. These symptoms improved after administration of bozentan and ambrisentan, which are endothelin receptor antagonists. At 9 months of age, he developed heliotrope rash, edematous erythema on his extremities, and myositis with elevated serum creatine kinase levels (16,000 IU/L). Antinuclear antibodies, as well as anti-Jo-1 and anti-DNA antibodies, were negative. Skin and muscle biopsies revealed massive cellular inflammation, consisting primarily of lymphocytes and monocytic cells, located in the epidermis and between muscle fibers with fat tissue necrosis in the subcutis. Concomitant degeneration and regeneration of muscle fibers occurred and resulted in moderate variations in the fiber size. These results initially led to a diagnosis of juvenile dermatomyositis. His symptoms temporarily improved with corticosteroid treatment but recurred periodically. Administration of systemic agents such as azathioprine, methotrexate, cyclosporine, cyclophosphamide, mycophenolate mofetil, and intravenous immunoglobulins did not lead to remission. Hepatosplenomegaly and liver cirrhosis due to pulmonary arterial hypertension induced portal hypertension beginning at age 6. The serum levels of interleukin (IL)-1β (28 pg/mL), IL-6 (84.3 pg/mL), TNFα (21.6 pg/mL), IL-18 (595 pg/mL), and IFN-γ (7.0 IU/mL) were all increased during the periodic recurrences. These periodic symptoms were refractory to several immunosuppressive agents, which suggested an autoinflammatory syndrome. Although presence of fever, erythemas, basal ganglia calcification and hepatosplenomegaly suggested NNS, some of the characteristic symptoms of NNS, such as lipomuscular atrophy in the upper body and long clubbed fingers with joint contractures, did not occur in this patient. Since no significant mutations had been detected in the NLRP3, NOD2, MEFV, MVK, TNFRSF1A, and PSMB8 genes, whole exome sequencing of the patient and his parents was performed and a novel de novo heterozygous mutation has been identified in PSMB9, encoding the immunoproteasome subunit beta1i, in the patient. Our case might represent a novel proteasome-associated autoinflammatory syndrome similar to but distinct from NNS, in which a heterozygous mutation of the PSMB9 gene is responsible. Written informated consent for publication of their clinical details was obtained from the patient/parent/guardian/relative of the patient.

Risk factors for juvenile dermatomyositis: exposure to tobacco and air pollutants during pregnancy.

To evaluate the influence of exposure to inhaled environmental factors during pregnancy on the diagnosis of juvenile dermatomyositis (DM). We performed a case–control study comprising 20 juvenile DM patients and 56 healthy controls matched by age and sex who were residents in the metropolitan region of a large city. A questionnaire assessed demographic data and environmental inhalation exposure during pregnancy (occupational exposure to demolition, chalk, construction and/or quarry dust, paints, varnish, gasoline vapor, and/or battery fluids; stationary sources of inhaled pollution near the mother's home; and maternal tobacco exposure). Daily concentrations of inhaled particulate matter, SO2, NO2, O3, and carbon monoxide (CO) were evaluated throughout the gestational period. Maternal occupational exposure to school chalk dust/gasoline vapor in the juvenile DM group was significantly higher compared with controls (50% versus 4.6%; P = 0.001). Smoking mothers and secondhand smoke exposure at home during pregnancy were significantly higher in the juvenile DM group versus controls (smoking mothers: 20% versus 1.7%; P = 0.01, and secondhand smoke: 35% versus 19%; P = 0.07). In univariate logistic regression models, maternal smoking, occupational exposure to inhaled agents, and the highest tertile of tropospheric CO (3.2–5.4 parts per million) in the third trimester were significantly associated with juvenile DM (P ≤ 0.05). In the multivariate analysis, smoking mother (odds ratio [OR] 13.26 [95% confidence interval (95% CI) 1.21–144.29], P = 0.03), occupational exposure (OR 35.39 [95% CI 1.97–632.80], P = 0.01), and CO (third tertile) exposure in the third trimester of gestation (OR 12.21 [95% CI 1.28–115.96], P = 0.03) remained risk factors for juvenile DM. Inhaled pollutants and tobacco smoking during fetal development may contribute to juvenile DM.

Correlation between muscular edema on magnetic resonance imaging versus major histocompatibility complex type Ii overexpression on muscle biopsy at diagnosis on juvenile dermatomyositis patients

Juvenile Dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in childhood. Magnetic resonance imaging (MRI) is a non invasive tool to assess muscular edema. Its ability to distinguish between active JDM patients and inactive and healthy children is well described in the literature. However muscle biopsy still remains the gold standard in JDM diagnosis. Major Histocompatibility Complex (MHC) type I is overexpressed on sarcolemma of inflammatory myopathies and it could be detectable before inflammatory infiltrate appears on conventional tecniques and remains there in spite of treatment.

Evaluation of dystrophic calcinosis in juvenile dermatomyositis and systemic sclerosis

Background: Dystrophic calcification is associated with juvenile dermatomyositis and progressive systemic sclerosis. The clinical diagnosis is established with detection of subcutaneous and petrous nodules. Conventional x-ray methods may evidence calcium deposits; however, in the case of incipient deposits x-ray may be insufficient. There are studies that use Tc99-MPD labeled bone scintigraphy to identify dystrophic calcification. Objectives: Estimate the frequency of dystrophic calcification in patients with juvenile dermatomyositis and progressive systemic sclerosis and CREST syndrome, and the concordance between the diagnosis of dystrophic calcification obtained by physical exploration and that obtained by scintigraphy. Patients and methods: A comparative, observational, and transverse study conducted in patients of one and the another gender, between 5 and 17 years of age, with diagnosis of juvenile dermatomyositis, progressive systemic sclerosis, and CREST syndrome to detect dystrophic calcification by physical exploration and scintigraphy. Fisher’s exact test was performed to evaluate the association between the two diagnostic methods, and the Kappa test was used for the level of concordance and analysis of distribution by group and extent of dystrophic calcification. The sensitivity and specificity of scintigraphy in detecting dystrophic calcification in soft tissues, bony protrusions, costal arches and vertebrae were also estimated. Results: The overall incidence of calcinosis was 80%. In 16 patients dystrophic calcification was detected by dermatological physical exploration and in 9 patients by scintigraphy. No association or concordance was found between the findings from physical exploration and scintigraphic findings. The latter have 37.5% sensitivity for detection of dystrophic calcification in soft tissues and 43.8% in bony protrusions, and are suitable for detection in costal arches. Conclusions: Dermatological exploration and scintigraphy are complementary tools for detecting dystrophic calcification.

SP0190 Juvenile Dermatomyositis: Whats New in 2014?

It is increasingly clear that juvenile dermatomyositis (JDM), a rare complex autoimmune disorder that involves autoimmune, vascular and inflammatory mechanisms, is not homogeneous. Rather, the diagnosis of JDM covers a...