Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

OBJECTIVES: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. METHODS: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. RESULTS: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. CONCLUSION: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

The clinical features of juvenile dermatomyositis: A single-centre inception cohort.

INTRODUCTION: Juvenile Dermatomyositis (JDM), a severe and rare autoimmune disease, is the most common idiopathic inflammatory myopathy in children. We describe the clinical features of a large single-centre cohort. METHODS: We studied an inception cohort (0-18 years old) referred for diagnosis to the JDM clinic at The Hospital for Sick Children (SickKids), between January 1989 and September 2017. Probable or definite diagnosis of JDM was done according to the 2017 ACR/EULAR Criteria. We excluded children who had treatment started at another hospital. The data were collected retrospectively from clinical charts and the SickKids JDM database. RESULTS: 172/230 (74.8%) patients were included. They were most often female (female:male = 1.8:1); the age at diagnosis was 8.5±4.3 years. There was a positive family history for autoimmune disease in 52%, mainly rheumatoid arthritis. No patient died. The most common signs at inception were muscle weakness (85.5%), nailfold capillary abnormalities (83.4%), Gottron papules (78.5%), heliotrope rash (66.3%), abnormal gait (55.8%), and malar/facial rash (54.7%). The prevalence of Gottron papules, heliotrope rash, facial/malar rash, nailfold capillary abnormalities, Raynaud phenomenon, dysphonia/dysphagia (a frequent cause of hospitalization), mouth ulcers, calcinosis, eye problems, joint involvement, acanthosis nigricans and lipodystrophy increased during follow-up. Muscle enzymes, namely CK, ALT, AST, were often normal or only slightly raised despite active muscle disease; conversely LD was often high. Anti-Nuclear Autoantibodies were positive in 49.7% of patients at diagnosis. The course of the disease was: 29.1% monocyclic, 5.3% polycyclic, 33.1% chronic. The course of 56 patients (32.5%) was not classifiable due to length of follow-up. Corticosteroids were used as treatment in almost all our patients and 30% required intravenous therapy due to the severity of the presentation; methotrexate was added in 64%, more often in recent years. Unresponsive patients were treated mostly with intravenous immunoglobulins (IVIG). CONCLUSIONS: The information obtained from this relatively large number of patients adds to the growing knowledge base of this rare disease. TRIAL REGISTRATION: SickKids Research Ethics Board approved the study.

Early Abnormal Nailfold Capillary Changes Are Predictive of Calcinosis Development in Juvenile Dermatomyositis.

OBJECTIVE: The long-term outcomes of juvenile dermatomyositis (JDM) are more favorable in recent years. However, calcinosis is still among the complications that can cause serious functional impairment. Little is known about the pathogenesis and risk factors of calcinosis. The aim of this study is to determine risk factors for the development of calcinosis in JDM. METHODS: This was a single-center, retrospective cohort study. All patients were diagnosed and followed at the multidisciplinary JDM clinic of The Hospital for Sick Children, from January 1, 1989, until May 31, 2018. To investigate predictors of incident calcinosis, Cox regression analysis was performed. RESULTS: A total of 172 patients met inclusion criteria, with a median age at diagnosis of 7.7 years (IQR 4.9-12.1), and a median follow-up of 8.5 years (IQR 3.4-12.6, range 0.1-28.3). The only risk factor significantly associated with the development of calcinosis in the univariate analysis was nailfold abnormality at baseline (hazard ratio [HR] 4.86, P = 0.03). In multivariable analysis, including nailfold abnormality, age of diagnosis, sex, and duration from onset to diagnosis, the only statistically significant risk factor for calcinosis was the presence of nailfold abnormalities (HR 4.98, P = 0.03). Further, calcinosis was significantly increased in patients with a chronic course (chi-square 25.8, P < 0.001). CONCLUSION: The presence of abnormal nailfold capillary changes at baseline is predictive for the development of calcinosis in children with idiopathic inflammatory myopathies.

Paediatric-to-adult transition experience in vasculitis: report of a model of care and outcomes.

OBJECTIVES: Transitioning from paediatric to adult care can be challenging. Whereas transition models of care have been shared in some rheumatological conditions, reported experience in vasculitis is lacking. METHODS: Retrospective chart review of adolescents aged 16-18 years assessed at the vasculitis transition clinic by paediatric and adult rheumatologists, and then scheduled for follow-up at the Adult Vasculitis Clinic (Toronto, Canada) from January 2013 until May 2020. RESULTS: Twenty-eight patients were seen at the transition clinic and included. Mean age at transition was 17 years and 11 (± SD 2) months, with a mean follow up from diagnosis of 32 (± 24) months. Most patients had ANCA-associated vasculitis (N=19, 39%), followed by Takayasu's arteritis (N=4, 14%); all but one were in remission at the time of transition. Twenty-six (93%) patients showed up for their first booked adult visit (two did not, were called and rebooked), after a mean of 4 (± 2) months after transition clinic. Subsequently, two patients missed 1 appointment, and three missed ≥ 2 appointments; only one (4%) stopped coming, while in remission for >2 years post-transition. Five (18%) patients were identified to have medication non-adherence after transition. With a mean follow up post-transition of 32 (± 25) months, 7 (25%) patients had minor and five (18%) had major relapses, at a mean of 17 (± 9) and 25 (± 15) months post-transition, respectively (compared to 12 (43%) and 9 (32%) prior to transition). At their last visit, all were in remission, 18 (64%) off glucocorticoids, and damage had remained stable. CONCLUSIONS: This model of care of vasculitis transition clinic resulted in favourable outcomes, as reflected by continuity of follow-up, and no increased risk of relapse.

Tibia stress injury and the imaging appearance of stress fracture in juvenile dermatomyositis: six patients' experiences.

BACKGROUND: Tibial stress injuries are frequent injuries of the lower extremity and the most common causes of exercise-induced leg pain among athletes and military recruits. They sometimes occur in patients with pathological conditions of bone metabolism such as osteoporosis or rheumatoid arthritis, but there are previously no cases reported in juvenile dermatomyositis (JDM). Here we report 6 JDM patients who presented with shin pain, and the imaging appearance of tibial stress fractures or stress reactions. CASE PRESENTATION: All 6 patients with JDM presented with shin pain or tenderness in the anterior tibia without any evidence of excessive exercise or traumatic episode. They were diagnosed with tibial stress injuries based on a combination of radiographs, three-phase bone scans, and magnetic resonance imaging (MRI), and 5 out of 6 patients had been treated with prednisone and/or methotrexate at onset of tibial stress injuries. In one patient, we could not find any abnormalities in his radiograph, but the subsequent MRI showed tibial stress reaction. In all 6 patients, the tibial stress injuries improved with only rest and/or analgesics. CONCLUSION: We experienced 6 children with JDM who presented with shin pain, and who were diagnosed with tibial stress fractures or stress reactions. Their underlying disease and weakness, treatment with glucocorticoid and methotrexate, or inactivity may have resulted in these tibial injuries, and made these patients more predisposed than other children. In addition to preventing JDM patients from getting osteoporosis, we need to consider stress reactions when children with JDM complain of sudden shin pain.

Correlation of a Modified Disease Activity Score (DAS) with the Validated Original DAS in Patients with Juvenile Dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare disease in children that is treatable, but patients may suffer from long-term effects. Clinical trials are needed to find better treatments for affected patients. Among validated tools for evaluating disease activity clinically is the Disease Activity Score (DAS), but it is not routinely collected in all clinics. We developed a modified DAS (DASmod), which can be scored using data routinely collected by our clinical staff and has been used in previous studies. The aim of this study was to determine if our DASmod correlates with the validated DAS in patients with JDM. METHODS: In this study, we used DASmod (scored 0-12) and DAS (scored 0-20) scores for patients with JDM in our clinic. We analyzed the correlation between the DASmod and the validated DAS. RESULTS: For 51 patients seen in our JDM clinic, the median (IQR) DASmod score was 2.0 (0-4.0) and the DAS score was 3.0 (0-5.5). Scores on the 2 tools were highly positively correlated (r = 0.94, P < 0.001, 95% CI 0.89-0.96). The linear regression was significant [R2 = 0.88, F (1, 49) = 357.60, P < 0.001] and in this dataset, the tools can be used interchangeably with the regression equation: DAS score = -0.26 + 1.5*DASmod. CONCLUSION: If the regression equation from this dataset is successfully tested against future datasets, then further research collaborations between centers that collect different data related to disease activity in children with JDM will be facilitated.

Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener's granulomatosis.

OBJECTIVE: Wegener's granulomatosis (WG) is a devastating small-vessel vasculitis in children. Standard treatment consists of immunosuppressive medications with cyclophosphamide potentially associated with significant infectious side effects, including Pneumocystis jiroveci pneumonia (PCP). Recently, rituximab, a monoclonal antibody against B cells, has successfully been used in refractory disease. METHODS: We describe the first pediatric patient with refractory WG with sinus and lung disease who developed PCP 6 months after treatment with rituximab, while being treated with methotrexate and prednisone. This 9-year-old child had no CD20+ B cells at time of infection, with normal lymphocyte and CD4 counts. RESULTS: This study provides a review of the published literature, including current protocols, which suggest chemoprophylaxis only in WG patients receiving T cell-targeted immunosuppression such as cyclophosphamide. However, clinical and laboratory evidence points toward a possible role of B cells in the defense against PCP. CONCLUSION: Routine PCP chemoprophylaxis should be strongly considered in patients with WG treated with rituximab.