We describe the clinical evolution of a patient with tumoral calcinosis due to a pathogenic variant in the GALNT3 gene presented with a large mass overlying her left hip associated complicated by ...inflammatory flares. Therapy (sevelamer, acetazolamide, and probenecid) was unsuccessful in preventing tumour surgeries, therefore, interleukin-1β monoclonal antibody therapy was added; this was successful in the prevention of tumour re-growth. This case highlights the importance of assessing and treating the inflammatory aspect of calcinotic tumour.
Objective
To assess whether children with juvenile idiopathic arthritis (JIA) in clinical remission show pathologic findings on either gray‐scale or power Doppler ultrasound of their joints.
Methods
...Children with JIA were eligible if they were in clinical remission for at least 3 months, as defined by the absence of clinically active joints and serologic markers of inflammation. Gray‐scale as well as power Doppler ultrasonography of the wrist, knee, and ankle were carried out on previously affected joints and unaffected contralateral joints. Images were read by 2 independent readers. Findings were categorized as 1) structural abnormalities in the case of synovial thickening or increased joint fluid on gray‐scale ultrasound or 2) power Doppler positive in the case of an abnormal power Doppler signal.
Results
The study cohort consisted of 28 patients. Eight of 14 patients with previous wrist involvement had pathologic gray‐scale findings, and 3 of these 14 patients also had pathologic Doppler findings in the wrist. None of the 20 patients with past knee involvement had pathologic gray‐scale or Doppler findings in the knee. Six of 15 patients with previous ankle involvement had pathologic gray‐scale findings and 1 of the 15 patients had pathologic Doppler findings in the tibiotalar joint.
Conclusion
This study demonstrates that some patients who meet clinical criteria for remission continue to show ongoing pathology on joint ultrasound, which may be suggestive of persistent inflammation.
ABSTRACT Rates of pediatric inflammatory bowel disease and biologic therapy use continue to rise. Consequently, specialists and generalists should recognize potential complications and side effects. ...We report the unique case of an adolescent with ulcerative colitis (UC) on vedolizumab presenting with severe abdominal pain, hematochezia, and subsequent purpura. After extensive investigation and a complex clinical course, diagnosis of atypical immunoglobulin A vasculitis was made. This is the first pediatric case of vasculitis in a patient with UC on vedolizumab and only the second reported case overall in UC. This case illustrates the emerging diagnostic challenge of distinguishing inflammatory bowel disease treatment complications from other common pediatric conditions.
To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments.
Children newly diagnosed with JIA at 16 ...Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan-Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments.
In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46-57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA.
Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.
(1) To evaluate the spectrum of serum autoantibodies in pediatric-onset systemic lupus erythematosus (pSLE) with a focus on ethnic differences; (2) using cluster analysis, to identify patients with ...similar autoantibody patterns and to determine their clinical associations.
A single-center cohort study of all patients with newly diagnosed pSLE seen over an 8-year period was performed. Ethnicity, clinical, and serological data were prospectively collected from 156/169 patients (92%). The frequencies of 10 selected autoantibodies among ethnic groups were compared. Cluster analysis identified groups of patients with similar autoantibody profiles. Associations of these groups with clinical and laboratory features of pSLE were examined.
Among our 5 ethnic groups, there were differences only in the prevalence of anti-U1RNP and anti-Sm antibodies, which occurred more frequently in non-Caucasian patients (p < 0.0001, p < 0.01, respectively). Cluster analysis revealed 3 autoantibody clusters. Cluster 1 consisted of anti-dsDNA antibodies. Cluster 2 consisted of anti-dsDNA, antichromatin, antiribosomal P, anti-U1RNP, anti-Sm, anti-Ro and anti-La autoantibody. Cluster 3 consisted of anti-dsDNA, anti-RNP, and anti-Sm autoantibody. The highest proportion of Caucasians was in cluster 1 (p < 0.05), which was characterized by a mild disease with infrequent major organ involvement compared to cluster 2, which had the highest frequency of nephritis, renal failure, serositis, and hemolytic anemia, or cluster 3, which was characterized by frequent neuropsychiatric disease and nephritis.
We observed ethnic differences in autoantibody profiles in pSLE. Autoantibodies tended to cluster together and these clusters were associated with different clinical courses.
We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, ...parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.
Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r
, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development.
Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile.
Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.
Objective
Adrenal suppression (AS), a glucocorticoid (GC) side effect with potentially significant morbidity, is poorly understood. The purpose of our study was to determine frequency, duration, and ...predictors of AS following a gradual taper of GC in children with rheumatic conditions.
Methods
A prospective, observational cohort study was conducted. All patients ages ≤16 years ready to discontinue GC after >4 weeks of therapy were included. Morning cortisol was tested 4 weeks after GC taper to physiologic doses and then repeatedly until normalization. GCs were subsequently discontinued and a low‐dose adrenocorticotropic hormone stimulation test was performed.
Results
The study was completed by 31 of 39 patients. The median age was 12.9 years and median duration of GC therapy was 39.6 weeks. Seventeen patients (54.8%) had AS. Of the patients with AS, 50% showed recovery by 7 months. Two patients had persistent AS at 12 months and 1 patient at 2 years. A higher maximum GC dose was a significant predictor for the development of AS.
Conclusion
More than 50% of our patients had AS after GC discontinuation, despite a gradual taper of GC. Stress steroids should be considered in children treated with long‐term GC, even after steroid discontinuation, to prevent possible adrenal crisis.
Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders.
This work aims to evaluate the incidence and predictors of osteoporotic ...fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders.
Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping.
A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9).
VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.
To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare.
We ...studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression.
1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare.
In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.
Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of ...Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories.
We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P < 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended (<60%; 157). Localized patients more often maintained their baseline patterns (P < 0.05 for five groups by permutation test) than nonlocalized patients (P < 0.05 for three groups by permutation test) over a five-year follow-up period. We modelled time to zero joints in the discovery cohort using a multivariate Cox proportional hazards model considering joint pattern, degree of localization, and ILAR subtype. Despite receiving more intense treatment, 50% of nonlocalized patients had zero joints at one year compared to six months for localized patients. Overall, localized patients required less time to reach zero joints (partial: P = 0.0018 versus localized by log-rank test; extended: P = 0.0057). Potential limitations include the requirement for patients to be treatment naïve (except NSAIDs), which may skew the patient cohorts towards milder disease, and the validation cohort size precluded multivariate analyses of disease trajectories.
Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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