To assess the attitudes and strategies of pediatric rheumatology clinicians toward withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA).
Members of the ...Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision making and approaches for withdrawing medications for inactive nonsystemic JIA. Data were analyzed using descriptive statistics.
Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision making for withdrawing medications were the duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of rheumatoid factor-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6-12 months of inactive disease before stopping methotrexate (MTX) or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children receiving combination MTX-biologic therapy, 63% of respondents preferred stopping MTX first. Most clinicians reported using imaging only seldom or sometimes to guide decision making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation.
Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes.
Telehealth is an extraordinary advancement of modern medicine. It has increased access to care for underserved populations and, in the case of pediatric rheumatology, has expanded the reach of a ...limited work force. During the Coronavirus Disease 2019 (COVID-19) pandemic, telehealth has radically changed the way healthcare workers have been able to deliver care while maintaining social distance. In addition to the infectious havoc of COVID-19, the pandemic has further altered the psychosocial milleu of our society which directly impacts the wellness and safety of our pediatric rheumatology patients. These psychosocial factors may be difficult to assess and triage solely using telehealth. The objective of this short review is to educate practitioners on the psychosocial concerns exacerbated by the COVID-19 pandemic and to discuss the possible hurdles in utilization of telehealth to care for our vulnerable patient population.
The clinical relevance of different antiphospholipid antibody (aPL) profiles, including low level anticardiolipin (aCL) and anti-β
-glycoprotein-I (aβ
GPI) antibodies, is ill-defined in the pediatric ...population. Our purpose is to describe the demographic, clinical, and laboratory characteristics of aPL positive pediatric patients based on different aPL profiles.
In this single center retrospective cohort study, based on the screening of our pediatric (age ≤ 18) rheumatology electronic medical records (2016-2022), we identified patients who had at least one "positive" aPL (lupus anticoagulant LA, aCL IgG/M, or aβ
GPI IgG/M) result. Patients were grouped into high- (LA positive and/or aCL/aβ
GPI IgG/M > 40U ELISA) and low-risk (LA negative and aCL/aβ
GPI IgG/M 20-39U) aPL profiles; those with persistently positive aPL were descriptively analyzed for demographic and clinical characteristics. Of 57 included patients, 34 (59%) had initial high- and 23 (40%) had initial low-risk profiles. Based on subsequent aPL results available in 42/57 (74%) patients, 25/27 (93%) in the high-, and 7/15 (47%) in the low-risk groups remained still positive. Of these 32 patients with persistently positive aPL, moderate-to-large vessel or microvascular thrombosis occurred in nine (28%) patients with high-risk and in none with low-risk aPL profiles; non-thrombotic aPL-related manifestations were reported in 15 (47%) patients with persistent aPL positivity.
An initial high-risk aPL profile was persistent in approximately 90% of our cohort, a third of whom had thrombosis, and half had non-thrombotic aPL manifestations. Our results underscore the need for a large-scale effort to better characterize aPL-related manifestations in pediatric patients with persistent high-risk aPL-profiles.
Vascular pathologies associated with SARS-CoV-2 infection are poorly understood. Color and sensory changes to the extremities, often referred to as “COVID toes” or chilblains-like lesions, have been ...widely reported in children and adolescents since the onset of the pandemic, raising the concern that they could be a vasculitis secondary to the infection. However, it is unclear if the lesions are a result of the infection or an epiphenomenon. Most literature focuses on adults, and while there are reports on children and adolescents, many of them are small. This review will help medical care providers better understand the epidemiology, etiology, outcomes, and potential treatments for chilblains-like lesions seen in children and adolescents during the pandemic.
Women with SLE have higher rates of persistent human papilloma virus (HPV) infections and precancerous lesions than healthy women. HPV vaccine is safe and effective in healthy females aged ...9-26 years. There are limited data on the safety and immunogenicity of HPV vaccine in females with SLE, and none in adolescents with SLE. Our study evaluates the safety and immunogenicity of recombinant quadrivalent HPV vaccine, Gardasil, in adolescents and young women with SLE.
This is a prospective, open-label study. Exclusion criteria included disease exacerbation within past 30 days; rituximab or cyclophosphamide within 6 months; pregnancy. Vaccine was administered at months 0, 2, and 6. Physical examination, SLEDAI scores and laboratory studies were performed at months 0, 2, 4, 6 and 7. Each patient's SLEDAI scores and laboratory profile in the year prior to vaccine administration were used as controls for that patient. Primary outcome measures were change in SLEDAI and mean HPV antibody titers.
27 patients, 12 to 26 years, were enrolled; 20 completed the study. Nine had mild/moderate lupus flares. Mean SLEDAI scores decreased from 6.14 pre-vaccination to 4.49 post-vaccination (p = 0.01). Of 12 patients with lupus nephritis, two experienced worsening renal function during/after the study and progressed to renal failure within 18 months of the study. Both had Class IV lupus nephritis with high chronicity scores (≥ 8) on renal biopsies performed within one year prior to study entry. Seropositivity post-vaccine was >94% for HPV 6, 11, 16 and 18.
Quadrivalent HPV vaccine seems generally safe and well tolerated in this series of adolescents and young women with SLE, with no increase in mean SLEDAI scores. Progression to renal failure in two patients was most likely secondary to pre-existing severe renal chronicity and not secondary to HPV vaccination. Immunogenicity to the quadrivalent HPV vaccine was excellent, with the seropositivity rate >94% in all four HPV types.
Objective
To identify novel heterozygous LPIN2 mutations in a patient with Majeed syndrome and characterize the pathomechanisms that lead to the development of sterile osteomyelitis.
Methods
Targeted ...genetic analysis and functional studies assessing monocyte responses, macrophage differentiation, and osteoclastogenesis were conducted to compare the pathogenesis of Majeed syndrome to interleukin‐1 (IL‐1)–mediated diseases including neonatal‐onset multisystem inflammatory disease (NOMID) and deficiency of the IL‐1 receptor antagonist (DIRA).
Results
A 4‐year‐old girl of mixed ethnic background presented with sterile osteomyelitis and elevated acute‐phase reactants. She had a 17.8‐kb deletion on the maternal LPIN2 allele and a splice site mutation, p.R517H, that variably spliced out exons 10 and 11 on the paternal LPIN2 allele. The patient achieved long‐lasting remission receiving IL‐1 blockade with canakinumab. Compared to controls, monocytes and monocyte‐derived M1‐like macrophages from the patient with Majeed syndrome and those with NOMID or DIRA had elevated caspase 1 activity and IL‐1β secretion. In contrast, lipopolysaccharide‐stimulated, monocyte‐derived, M2‐like macrophages from the patient with Majeed syndrome released higher levels of osteoclastogenic mediators (IL‐8, IL‐6, tumor necrosis factor, CCL2, macrophage inflammatory protein 1α/β, CXCL8, and CXCL1) compared to NOMID patients and healthy controls. Accelerated osteoclastogenesis in the patient with Majeed syndrome was associated with higher NFATc1 levels, enhanced JNK/MAPK, and reduced Src kinase activation, and partially responded to JNK inhibition and IL‐1 (but not IL‐6) blockade.
Conclusion
We report 2 novel compound heterozygous disease‐causing mutations in LPIN2 in an American patient with Majeed syndrome. LPIN2 deficiency drives differentiation of proinflammatory M2‐like macrophages and enhances intrinsic osteoclastogenesis. This provides a model for the pathogenesis of sterile osteomyelitis which differentiates Majeed syndrome from other IL‐1–mediated autoinflammatory diseases.
Objectives
To delineate urine biomarkers that reflect kidney structural damage and predict renal functional decline in pediatric lupus nephritis (LN).
Methods
In this prospective study, we evaluated ...kidney biopsies and urine samples of 89 patients with pediatric LN. Urinary levels of 10 biomarkers adiponectin, ceruloplasmin, kidney injury molecule-1, monocyte chemotactic protein-1, neutrophil gelatinase-associated lipocalin, osteopontin, transforming growth factor-ß (TGFß), vitamin-D binding protein, liver fatty acid binding protein (LFABP), and transferrin were measured. Regression analysis was used to identify individual and combinations of biomarkers that determine LN damage status NIH-chronicity index (NIH-CI) score ≤ 1 vs. ≥ 2 both individually and in combination, and biomarker levels were compared for patients with vs. without renal functional decline, i.e., a 20% reduction of the glomerular filtration rate (GFR) within 12 months of a kidney biopsy.
Results
Adiponectin, LFABP, and osteopontin levels differed significantly with select histological damage features considered in the NIH-CI. The GFR was associated with NIH-CI scores Pearson correlation coefficient (
r
) = − 0.49;
p
< 0.0001 but not proteinuria (
r
= 0.20;
p
> 0.05). Similar to the GFR area under the ROC curve (AUC) = 0.72;
p
< 0.01, combinations of osteopontin and adiponectin levels showed moderate accuracy AUC = 0.75;
p
= 0.003 in discriminating patients by LN damage status. Renal functional decline occurred more commonly with continuously higher levels of the biomarkers, especially of TGFß, transferrin, and LFABP.
Conclusion
In combination, urinary levels of adiponectin and osteopontin predict chronic LN damage with similar accuracy as the GFR. Ongoing LN activity as reflected by high levels of LN activity biomarkers heralds renal functional decline.
Key messages
• Levels of osteopontin and adiponectin measured at the time of kidney biopsy are good predictors of histological damage with lupus nephritis.
• Only about 20% of children with substantial kidney damage from lupus nephritis will have an abnormally low urine creatinine clearance.
• Continuously high levels of biomarkers reflecting lupus nephritis activity are risk factors of declining renal function.
Objective
There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the ...diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies.
Methods
Case‐based surveys were administered to CARRA members to identify prevailing treatments for new‐onset systemic JIA. A 2‐day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Followup surveys were employed to refine the plans and assess clinical acceptability.
Results
The initial case‐based survey identified significant variability among current treatment approaches for new‐onset systemic JIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed 4 consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The 4 treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra, or tocilizumab, with or without glucocorticoids. This approach was approved by >78% of the CARRA membership.
Conclusion
Four standardized treatment plans were developed for new‐onset systemic JIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of systemic JIA.
Mucosal-associated lymphoid tissue (MALT) lymphoma is rare in the pediatric population, but primary Sjogren syndrome is a well-established risk factor for this malignancy. This report describes 2 ...cases of MALT lymphoma in children with Sjogren syndrome. A 15-year-old girl developed MALT lymphoma of the parotid gland as the presenting symptom of Sjogren syndrome. In the second case, a 15-year-old boy with known Sjogren syndrome presenting mainly with arthritis was diagnosed with MALT lymphoma, also of the parotid gland. With early diagnosis and treatment, outcomes in pediatric MALT lymphoma are generally encouraging. Pediatric oncology specialists should be aware of the association of MALT lymphoma with Sjogren syndrome and have a high index of suspicion for this malignant complication.
Systemic juvenile idiopathic arthritis (SJIA) is a rare disease with distinct features not seen in other categories of juvenile idiopathic arthritis. In recent years, advances in the understanding of ...disease immunopathogenesis have led to improved targeted therapies with significant improvement in patient outcomes. Despite these advances, there remain subsets of SJIA with refractory disease and severe disease-associated complications. This review highlights existing options for treatment of refractory SJIA and explores potential future therapeutics for refractory disease.
Key Points:
Despite targeted Interleukin IL-1 and IL-6 inhibitors a subset of SJIA remains refractory to therapy. About 1 in 7 SJIA patients will be refractory to targeted IL-1 or IL-6 therapy.
There is no current agreed upon definition for refractory SJIA and we propose in this review that refractory SJIA is presence of active systemic or arthritic features despite treatment with anti-IL-1 or anti-IL-6 therapy or disease requiring glucocorticoids for control beyond 6 months.
SJIA disease associated complications include presence of associated macrophage activation syndrome (MAS), interstitial lung disease (ILD) or amyloidosis and management of each differs.
Refractory SJIA treatment options currently include additional conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), biologic (bDMARDS), combination biologic therapy, targeted synthetic (tsDMARDS) or other immunomodulatory therapies.
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