Risk factors for haemodynamic compromise in multisystem inflammatory syndrome in children: a multicentre retrospective study.

OBJECTIVES: To identify predictors of a severe clinical course of multisystem inflammatory syndrome in children (MIS-C), as defined by the need for inotropic support. METHODS: This retrospective study included patients diagnosed with MIS-C (according to the CDC definition) in nine Israeli and one US medical centre between July 2020 and March 2021. Univariate and multivariate regression models assessed odds ratio (OR) of demographic, clinical, laboratory and imaging variables during admission and hospitalization for severe disease. RESULTS: Of 100 patients, 61 (61%) were male; mean age 9.65 (4.48) years. Sixty-five patients were hypotensive, 44 required inotropic support. Eleven patients with MIS-C fulfilled Kawasaki disease diagnostic criteria; 87 had gastrointestinal symptoms on admission. Echocardiographic evaluation showed 10 patients with acute coronary ectasia or aneurysm, and 37 with left ventricular dysfunction. In a univariate model, left ventricular dysfunction was associated with severe disease [OR 4.178 (95% CI 1.760, 9.917)], while conjunctivitis [OR 0.403 (95% CI 0.173, 0.938)] and mucosal changes [OR 0.333 (95% CI 0.119, 0.931)] at admission were protective. Laboratory markers for a severe disease course were low values of haemoglobin, platelets, albumin and potassium; and high leukocytes, neutrophils, troponin and brain natriuretic peptide. In multivariate analysis, central nervous system involvement and fever >39.5°C were associated with severe disease. Mucosal involvement showed 6.2-fold lower risk for severe disease. Low haemoglobin and platelet count, and elevated C-reactive protein and troponin levels were identified as risk factors for severe disease. CONCLUSION: Key clinical and laboratory parameters of MIS-C were identified as risk factors for severe disease, predominantly during the disease course and not at the time of admission; and may prompt close monitoring, and earlier, more aggressive treatment decisions. Patients presenting with a Kawasaki-like phenotype were less likely to require inotropic support.

Adherence to medication by adolescents and young adults with childhood-onset systemic lupus erythematosus.

Background: Approximately 20% of all cases systemic lupus erythematous (SLE) are juvenile onset. Children and adolescents with SLE usually present with more severe illness and have a higher mortality rate compared to adults with SLE. Adherence to medications in children and adolescents has a major impact on disease control as well as short- and long-term outcomes. Improved understanding of adherence rates, risk factors for non-adherence, and barriers to adherence are essential in order to increase patient adherence with medication regimens. The aim of our study was to evaluate adherence to medications among children and young adults with pediatric-onset SLE and identify barriers for non-adherence by utilizing several adherence evaluation methods.Methods: Adherence to medications of patients aged 12-25, with childhood-onset SLE was assessed as follows: (1). The brief medication questionnaire (BMQ): self-report tool for screening adherence and barriers to adherence. (2). Mycophenolic acid (MPA) serum level. (3). Medication possession ratio (MPR): data assessing 90-day refills and dispense prior to patient's enrollment was collected.Results: Of the 38 patients who were enrolled in the study, 65% were found to be non-adherent according to at least 1 measurement method. Forty-four percent of patients were found to be non-adherent based on the self-reported questionnaire (BMQ). Of those taking MMF, 33% had an MPA level < 1 mcg/mL and were defined as non-adherent. Seventeen percent of patients were found to be non-adherent according to pharmacy refills rate. Forty-six percent of patients stated that their medications caused side effects, 33% of patients indicated difficulty remembering to take the medications, and 25% reported difficulty paying for medications. The disease activity index (SLEDAI) score of the "adherent group" at diagnosis was significantly lower compared to the "non-adherent" group. Patients with private insurance had more access barriers to obtaining medications compared to patients with public insurance.Conclusion: Non-adherence to medications is highly prevalent among cSLE patients. Higher SLEDAI score is a risk factor for non-adherence. Adherence to medications should be routinely evaluated among adolescence and young adults with cSLE and barriers to adherence need to be addressed to decrease morbidity and improve patient outcomes.

Fulminant myocarditis and atrial fibrillation in child with acute COVID-19.

COVID-19 has manifested with ventricular dysfunction and cardiac arrhythmias, most commonly atrial fibrillation (AFib), in adults. However, very few pediatric patients with acute COVID-19 have had cardiac involvement. AFib, an exceedingly rare arrhythmia in otherwise healthy children, has not been reported in children with COVID-19. We report a 15 year-old girl with acute COVID-19, fulminant myocarditis and AFib.

Mucosal-associated Lymphoid Tissue (MALT) Lymphoma in Association With Pediatric Primary Sjogren Syndrome: 2 Cases and Review.

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.

Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory disease in children (MIS-C) is a condition typically seen 3 to 6 weeks after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Believed to be a postinfection hyperinflammatory response, the clinical manifestation of this viral sequelae can vary significantly in severity and symptomatic presentation. Clinical prodrome includes persistent fever and dysfunction of at least two organ systems. Often developing after asymptomatic or mildly symptomatic coronavirus disease 2019 (COVID-19) infection, MIS-C is a diagnosis of exclusion that requires evaluation for other infectious or noninfectious etiology for symptoms. Vital sign instability, including fever, tachycardia, and hypotension; laboratory studies demonstrating elevated inflammatory markers and elevated cardiac markers; and positive SARS-CoV-2 polymerase chain reaction, SARS-CoV-2 antibodies, or exposure to someone with confirmed COVID-19 infection 4 to 6 weeks before clinical presentation are used to diagnose this condition. Skin and mucosal involvement, gastrointestinal symptoms, and neurologic manifestations are also commonly seen. An echocardiogram is indicated to evaluate for cardiac dysfunction, including but not limited to coronary artery enlargement, left ventricular dysfunction, arrythmias, or atrioventricular block. [Pediatr Ann. 2023;52(3):e114-e121.].

Multicenter Study of Utility and Acceptability of Depression and Anxiety Screening in Adolescents and Young Adults With Childhood-Onset Systemic Lupus.

OBJECTIVE: To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE) in the pediatric rheumatology setting. METHODS: AYA with cSLE, ages 12-21 years, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with postscreening surveys completed by AYA and parents. Chi-square and Wilcoxon rank sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. RESULTS: Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% for suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference and moderately correlated with increased pain severity, decreased mobility, and decreased peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. CONCLUSION: Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.

The clinical spectrum of juvenile idiopathic arthritis in a large urban population.

Urban populations present particular challenges for medical providers. Patients are extremely diverse, with varied socioeconomic, cultural, and ethnic backgrounds. Physicians caring for children with juvenile idiopathic arthritis must be prepared to interact effectively with many types of families who bring with them varied experiences and expectations. Pediatric rheumatologists should be familiar with patient characteristics that can influence disease outcomes. Access to care is affected by place of residence, referral delays, parental education, and the child's insurance status. Patients of different ethnic backgrounds vary in their trust of physicians and health systems. Understanding of risk in medical decision making is influenced by ethnicity as well. Adherence also varies by ethnic group, with African American patients reporting lower adherence than Caucasian patients. Issues of doctor­ patient communication and use of complementary and alternative medicine are also affected by cultural factors. Especially for physicians working in a large metropolitan area, an understanding of societal factors influencing patient behavior is essential to provide optimal care for children with juvenile idiopathic arthritis.

The Role of Anti-IL-1 Medications in Autoinflammatory Disease.

The interleukin (IL) -1 family of cytokines are involved in different aspects of inflammation with IL-1 beta being the best known and most powerful proinflammatory cytokine. Dysregulation of IL-1 beta and other family members results in autoinflammatory conditions such as systemic juvenile idiopathic arthritis and familial Mediterranean fever. The growing understanding and knowledge of the pathophysiology of many autoinflammatory diseases have led to the development and use of IL-1 blocking medications for many chronic and disabling diseases. In this article, we present the anti-IL-1 agents and their major indications in pediatric rheumatology. [Pediatr Ann. 2022;51(2):e72-e76.].

Juvenile Fibromyalgia in Patients With Juvenile Idiopathic Arthritis: Utility of the Pain and Symptom Assessment Tool.

OBJECTIVE: To evaluate the proportion of children with juvenile idiopathic arthritis (JIA) who met criteria for comorbid juvenile fibromyalgia (FM) using the Pain and Symptom Assessment Tool (PSAT), and to identify clinical and demographic differences among JIA patients with and without juvenile FM. METHODS: Patients ages 11-17 years with JIA were recruited from 4 North American pediatric rheumatology centers. Each patient completed the PSAT. Additional clinical and disease activity measures included pain visual analog scale, patient global assessment of disease activity (PtGA) and physician global assessment of disease activity (PhGA), the Functional Disability Inventory (FDI), and the Pain Catastrophizing Scale in children. RESULTS: Of 129 patients, 11 met criteria for juvenile FM. FDI scores were markedly higher in patients who tested positive for juvenile FM, with a mean of 24.8 compared to 6.9 in patients without juvenile FM (P < 0.001). Pain catastrophizing scores were also significantly higher, by ~14 points, in patients with juvenile FM. There was a significant tendency for patients to give higher disease activity scores than physicians, which was more marked among patients with juvenile FM. In patients with juvenile FM, PtGA scores exceeded PhGA scores by a mean of 3.7, compared to a mean of 0.7 among patients without juvenile FM (P < 0.001). CONCLUSION: A minority of JIA patients (8.5%) met criteria for juvenile FM. This group demonstrated markedly more functional impairment. PtGA scores were strikingly higher than PhGA scores among patients with JIA who met juvenile FM criteria, suggesting that providers might consider a more expansive approach to chronic pain and non-musculoskeletal symptom assessment and treatment in JIA patients.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

Pilot Study of the Juvenile Dermatomyositis Consensus Treatment Plans: A CARRA Registry Study.

OBJECTIVES: To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data. METHODS: A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI). The primary outcome was the proportion of patients achieving moderate improvement at 6 months under each CTP. Statistical methods including multiple imputation and inverse probability of treatment weighting were used to handle missing data and confounding by indication. RESULTS: Patients received MP (n = 13), MMP (n = 18) and MMPI (n = 8). Patients in all CTP had significant improvement in disease activity. Of the 36 patients who remained in our pilot study at 6 months, 16 (44%) of them successfully achieved moderate improvement at 6 months (6/13, 46% for MP; 7/15, 47% for MMP; 3/8, 38% for MMPI). After correcting for confounding, there were no statistically significant pairwise differences between the CTP (P = 0.328-0.88). CONCLUSION: We gained valuable experience and insight from our pilot study that can be used to guide the design and analysis of comparative effectiveness studies using the CARRA registry CTP approach. Our analytical methods can be adopted for future comparative effectiveness studies and applied to other rare disease observational studies.

Arthritis in children with LRBA deficiency - case report and literature review.

BACKGROUND: Lipopolysaccharide (LPS)-responsive and beige like anchor (LRBA) deficiency is categorized as a subtype of common variable immune deficiency (CVID). A growing number of case reports and cohorts reveal a broad spectrum of clinical manifestations and variable phenotype expression, including immune dysregulation, enteropathy and recurrent infections. The association between rheumatic disease and CVID generally has been well established, arthritis has been less frequently reported and minimal data regarding its clinical features and characteristic in LRBA deficiency has been published. This case report and literature review evaluates the characteristics and features of arthritis in LRBA deficiency patients. CASE PRESENTATION AND REVIEW RESULTS: Herein, we describe a unique case of LRBA deficiency first presented with poly articular arthritis. Alongside the report, a literature review focusing on LRBA deficiency, rheumatic disease and arthritis has been conducted. We reviewed 43 publications. Among these, 7 patients were identified with arthritis. Age of first presentation was six weeks to 3 years. Male to female ratio was 4/3. Two patients were diagnosed with polyarticular Juvenile idiopathic arthritis (JIA) and three with oligoarticular JIA. Each patient was found to have different genomic mutation. The treatment was diverse and included corticosteroids, cyclosporine, methotrexate, adalidumab and abatacept. CONCLUSION: Joint involvement is variable in LRBA deficiency, hence it should always be kept in mind as a differential diagnosis for a patient with combination of juvenile arthritis and clinically atypical immune dysregulation and / or immunodeficiency.

Pediatric Autoimmune Inner Ear Disease: A Rare, But Treatable Condition.

Autoimmune inner ear disease (AIED) is a rare, but treatable cause of sudden sensorineural hearing loss in children. Most cases present acutely and involve both ears. The precise mechanism of hearing loss in AIED is not known. Many suspected etiologies have been proposed including infections, vascular abnormalities, and trauma. However, 70% of cases are defined as idiopathic. There are no standardized diagnostic criteria for AIED, and the diagnostic process may be challenging. Positive auto antibodies and response to immunosuppressive therapy support the diagnosis. Treatment may include corticosteroids and steroid-sparing immunosuppressive medications. A high index of suspicion is recommended as the hearing loss may be stabilized or even reversed with early treatment. Long-term medical treatment failures generally have good outcomes with cochlear implantation. [Pediatr Ann. 2019;48(10):e391-e394.].

Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy.

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

An Overview of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by a dysregulated hyperinflammatory response associated with aberrant activation of lymphocytes and macrophages that results in hypercytokinemia. It is classically divided into two types: (1) primary or familial HLH and (2) secondary HLH. Familial HLH is generally an autosomal recessive condition, whereas secondary HLH is usually associated with infectious diseases, autoinflammatory and autoimmune diseases (where it is more commonly known as macrophage activation syndrome), malignancy, immunosuppression, hematopoietic stem cell transplantation, organ transplantation, HIV infection, and metabolic diseases. Although its clinical presentation is often similar to bacterial sepsis or systemic inflammatory response syndrome, HLH can be life-threatening. As such, it is imperative to recognize and diagnose HLH in a timely manner to optimize care. [Pediatr Ann. 2017;46(8):e309-e313.].