Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening state of immune hyperactivation that arises in the setting of genetic mutations and infectious, inflammatory, or neoplastic ...triggers. Sustained, aberrant activation of cytotoxic CD8+ T cells and resultant inflammatory cytokine release are core pathogenic mechanisms. Key clinical features include high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. HLH is likely under-recognized, and mortality remains high, especially in adults; thus, prompt diagnosis and treatment are essential. Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation. HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A. In other forms of HLH, addressing the underlying trigger is essential. There remains a pressing need for more sensitive, context-specific diagnostic tools. Safer, more effective therapies will arise with improved understanding of the cellular and molecular mechanisms of HLH.
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.
Objective
To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile ...idiopathic arthritis (JIA).
Methods
In this multinational, multicenter study, pediatric rheumatologists and hemato‐oncologists entered patient data collected retrospectively into a web‐based database.
Results
A total of 362 patients, 22% of whom had MAS at the onset of systemic JIA, were included in the study by 95 investigators from 33 countries. The most frequent clinical manifestations were fever (96%), hepatomegaly (70%), and splenomegaly (58%). Central nervous system dysfunction and hemorrhages were recorded in 35% and 20% of the patients, respectively. Platelet count and liver transaminase, ferritin, lactate dehydrogenase, triglyceride, and d‐dimer levels were the sole laboratory biomarkers showing a percentage change of >50% between the pre‐MAS visit and MAS onset. Evidence of macrophage hemophagocytosis was found in 60% of the patients who underwent bone marrow aspiration. MAS occurred most frequently in the setting of active underlying disease, in the absence of a specific trigger. Nearly all patients were given corticosteroids, and 61% received cyclosporine. Biologic medications and etoposide were given to 15% and 12% of the patients, respectively. Approximately one‐third of the patients required admission to the intensive care unit (ICU), and the mortality rate was 8%.
Conclusion
This study provides information on the clinical spectrum and current management of systemic JIA–associated MAS through the analysis of a very large patient sample. MAS remains a serious condition, as a sizeable proportion of patients required admission to the ICU or died.
Youth with chronic medical illness, such as juvenile myositis (JM), require specialized behavioral health care. However, access to such care is challenging due to the youth mental health crisis, ...which impacts accessibility of mental health services in the community, as well as challenges accessing behavioral health care above and beyond the demands of care related to their JM management. In this paper we describe an embedded behavioral health care model, including the establishment and implementation of such a model, at a pediatric hospital where youth with JM receive medical care in a Center of Excellence (CoE). We describe a unique partnership with a philanthropic organization; the challenges and benefits of delivering care within this model; as well as recommendations for maximizing its effectiveness. Ultimately, we provide an example of a successful embedded behavioral health care program for youth with rare disease, which may be applied to other institutions providing similar care.
Objective Maternal infection has been posited as a risk factor for childhood autoimmune disease such as type I diabetes. Given that similar studies in JIA are scant, our objective was to evaluate the ...association between Juvenile Idiopathic Arthritis (JIA) and maternal infection. Methods This case-control study used an existing database that included 1290 JIA cases and 6072 controls matched on birth year. Maternal infection information was obtained from Washington State birth records. JIA diagnosis and categories were confirmed through chart review. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Results JIA was not associated with maternal infection (OR = 1.02, 95%CI: 0.8-1.3). There was no association between JIA and maternal infection for persistent oligoarticular, RF negative polyarticular, or enthesitis-related JIA. There was suggestive evidence of an increased association of maternal infection with JIA in females in sex-stratified analysis. Conclusions We did not observe an increased risk of JIA in children exposed to maternal infection. Suggestive evidence of differential sex-specific results warrants further study. Keywords: Juvenile arthritis, Pregnancy, Risk factors
The use of telemedicine in pediatric rheumatology has been historically low. The current COVID 19 global pandemic has forced a paradigm shift with many centers rapidly adopting virtual visits to ...conduct care resulting in rapid expansion of use of telemedicine amongst practices. BODY: This commentary discusses practical tips for physicians including guidance around administrative and governance issues, preparation for telemedicine, involving the multidisciplinary care team, and teaching considerations. We also outline a standard proforma and smart phrases for the electronic health record. A proposed variation of the validated pediatric gait arms legs spine examination (pGALS) called the video pGALS (VpGALS) as a means of conducting virtual pediatric rheumatology physical examination is presented.
This commentary provides a starting framework for telemedicine use in pediatric rheumatology and further work on validation and acceptability is needed.
We present two cases of Nodular Regenerative Hyperplasia (NRH) associated with Juvenile Dermatomyositis (JDM).
Case 1: A nine-year-old Caucasian male with refractory JDM and anti-NXP2 autoantibodies ...was diagnosed at age two. Over seven years, he developed arthritis, dysphagia, dysphonia, severe calcinosis, and colitis. Complications included recurrent cellulitis, infections, and hepatosplenomegaly. Multiple medications were chronically used, including prednisone, methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, rituximab, tacrolimus, etanercept, abatacept, infliximab, and tocilizumab. Case 2: A 19-year-old Asian female with chronically active JDM and anti-MDA5 autoantibodies was diagnosed at age 15. Symptomatology included ulcerative skin lesions, Raynaud's phenomenon with digital ulcers, arthritis, interstitial lung disease with pulmonary hypertension, and calcinosis. Medications included chronic use of prednisone, methotrexate, abatacept, cyclophosphamide, mycophenolate mofetil, rituximab, tofacitinib, and sildenafil. In both patients, clinical symptomatology was not suggestive of liver disease or portal hypertension, but laboratory studies revealed elevated serum transaminases with progressive thrombocytopenia and no active liver-associated infections. The first patient's liver ultrasound showed coarse hepatic texture with mild echogenicity, splenomegaly, and portal hypertension. The second patient's liver ultrasound was normal, but elastography indicated increased stiffness. Liver biopsy confirmed NRH in both patients.
It is difficult to recognize NRH in JDM, as it often presents with elevated transaminases which may be mistaken for JDM muscle flare, corticosteroid-related fatty liver, or medication-related transaminitis. NRH has been associated with several medications used to treat JDM, including methotrexate, azathioprine, and cyclophosphamide, which should be discontinued if NRH develops. Providers should consider NRH in JDM patients with severe, refractory disease who have persistently elevated transaminases and persistent thrombocytopenia.
Objective
The scope of clinical practice of pediatric rheumatology has been difficult to define. The lack of definition prevents an accurate understanding of the knowledge and skills required of ...practicing pediatric rheumatologists. A practice analysis process was used with the goal of establishing a precise definition of clinical pediatric rheumatology practice. The definition of practice will improve training and the creation of relevant certification examinations.
Methods
A practice analysis approach used meetings with a representative panel of pediatric rheumatologists to create a practice analysis document (PAD) and a test content outline (TCO). Panel experience, entrustable professional activities, and the current TCO were used to guide the process. Surveys were administered to fellowship program directors (PDs) and a broader group of practicing pediatric rheumatologists to revise and validate the content of the documents.
Results
A PAD was created, including 14 categories of conditions diagnosed or managed by pediatric rheumatologists and eight domains of practice, with the tasks, knowledge, and skills required to perform these tasks. The survey of PDs (n = 10) indicated that the PAD content is important and useful. A TCO was created and consists of 18 domains used to define content areas to be assessed on certifying examinations. The survey of practicing pediatric rheumatologists (n = 127) indicated that the TCO domains are relevant.
Conclusion
A practice analysis process produced valuable resources for defining the clinical practice of pediatric rheumatology. The PAD and TCO can be used to develop more specific training curricula and to create relevant certification examinations.
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