Update on Juvenile Spondyloarthritis.

Spondyloarthritis (SpA) is a blanket term encompassing entities such as enthesitis-related arthritis, nonradiographic axial SpA, and ankylosing spondylitis. These diseases share many clinical features, including a predilection for inflammation of the entheses and the sacroiliac joints. The nomenclature is based on the evolution of the classification of the disease and the age of the patient. SpA has a prevalence of approximately 1% of the population of the United States, with 10% to 20% of patients experiencing the onset during childhood. Children with onset of arthritis before age 16 years are classified as having juvenile idiopathic arthritis. Children with enthesitis and/or sacroiliitis are further classified as belonging to the enthesitis-related arthritis subtype of juvenile idiopathic arthritis. The initial manifestations can be subtle and will usually include a peripheral pattern of arthritis and enthesitis. It may take several years for axial disease to develop in children. Except for an association with the human leukocyte antigen (HLA-B27) serotype, there are no laboratory markers for the disease, and the radiographic findings are often negative. A careful clinical evaluation for evidence of inflammation in the entheses and the joints and a search for comorbidities are required. Magnetic resonance imaging facilitates the early detection of sacroiliitis, an important feature that may be clinically silent. Because recent studies indicate that earlier introduction of therapy can help achieve better outcomes, rapid identification and treatment of children with SpA is essential.

Procalcitonin Differs in Children With Infection and Children With Disease Flares in Juvenile Idiopathic Arthritis.

BACKGROUND/OBJECTIVE: Patients with juvenile idiopathic arthritis (JIA) often present with signs and symptoms suggestive of serious bacterial infection (SBI). Procalcitonin (PCT) is a biomarker that is elevated in SBI. We conducted a comparative cohort study to test the hypothesis that PCT levels will differ between active JIA, quiescent JIA, and bacteremic patients and healthy controls. METHODS: From October 2016 to May2018, consecutive children 6 months to 18 years of age with (a) active untreated JIA, (b) quiescent JIA, and (c) healthy elective presurgical candidates were recruited from clinics at a musculoskeletal specialty hospital. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Clinical data and serum samples meeting the same criteria were included from a prior study. Consecutive bacteremic patients were identified over the same period. Procalcitonin and other common measures of inflammation were measured. Descriptive statistics and univariate logistic analyses were performed. RESULTS: Ninety-two study subjects were recruited. Erythrocyte sedimentation rate, C-reactive protein (CRP), and PCT levels were all elevated in bacteremic patients in comparison to the other groups. Erythrocyte sedimentation rate and CRP both had wide ranges that overlapped between groups; however, the PCT concentration was 0.15 µg/mL or greater in 1 of 59 patients with JIA, whereas it was 0.15 µg/mL or less in only 1 bacteremic patient. CONCLUSIONS: Our study indicates that serum erythrocyte sedimentation rate, CRP, and PCT levels are all biomarkers that can be used to distinguish SBI versus active JIA at presentation. However, PCT is the most accurate, with the least overlap between patients with infection and noninfectious inflammatory arthritis. This finding can help clinicians direct therapy.

PROMIS Computer Adaptive Tests and Their Correlation With Disease Activity in Juvenile Idiopathic Arthritis.

BACKGROUND/OBJECTIVE: The importance of patient-reported outcomes, like the Patient-Reported Outcomes Measurement Information System (PROMIS) measures, is increasingly recognized both in clinical care and in research. While "short forms" have been studied in juvenile idiopathic arthritis (JIA), study of PROMIS computer adaptive tests (CATs) in JIA is limited. This cross-sectional study evaluates whether PROMIS CATs correlate with disease activity in patients with JIA. METHODS: A convenience sample of patients with JIA (N = 44) was recruited from a single center. Patients and parents completed pediatric and parent proxy PROMIS CATs. Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71) and the Childhood Health Assessment Questionnaire (CHAQ). Correlation of the CAT T scores with disease activity was assessed using Spearman correlation coefficients. RESULTS: Forty-four of 80 eligible subjects (29 patients and 15 parents) completed all or some PROMIS CATs. Pain interference and mobility CATs correlated moderately with JADAS-71. Nearly all correlations with the JADAS-71 were weakened when the patient global was removed. Pain interference, mobility, and fatigue were strongly correlated with the CHAQ. Among parent proxy CATs, only mobility and depressive symptoms correlated strongly with the CHAQ. CONCLUSIONS: Only pain interference and mobility PROMIS CATs showed strong correlation with standard disease activity measures in JIA, and nearly all correlations were weakened when the patient global was removed. Correlations of the CATs with the CHAQ were stronger than correlations with the JADAS-71, indicating that although the CHAQ is no longer routinely used it may be a better measure of health-related quality of life in routine clinical care.

Urine biomarkers of chronic kidney damage and renal functional decline in childhood-onset systemic lupus erythematosus.

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.

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.

Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis.

OBJECTIVE: To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA). METHODS: In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose, with adjustments. Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity (i.e., decreased levels of D-dimer and myeloid-related proteins [MRPs]) were also evaluated. RESULTS: Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white and female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from the start of the study were 78.3%, 60.9%, and 34.8%, respectively; these responses were generally maintained over the study duration. Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study, and in 22 of 23 patients, the prednisone dose was decreased or prednisone therapy was discontinued. No serious treatment-related adverse events were observed. CONCLUSION: Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated.

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus.

The autoimmune disease lupus erythematosus (lupus) is characterized by photosensitivity, where even ambient ultraviolet radiation (UVR) exposure can lead to development of inflammatory skin lesions. We have previously shown that Langerhans cells (LCs) limit keratinocyte apoptosis and photosensitivity via a disintegrin and metalloprotease 17 (ADAM17)-mediated release of epidermal growth factor receptor (EGFR) ligands and that LC ADAM17 sheddase activity is reduced in lupus. Here, we sought to understand how the lupus skin environment contributes to LC ADAM17 dysfunction and, in the process, differentiate between effects on LC ADAM17 sheddase function, LC ADAM17 expression, and LC numbers. We show through transcriptomic analysis a shared IFN-rich environment in non-lesional skin across human lupus and three murine models: MRL/lpr, B6.Sle1yaa, and imiquimod (IMQ) mice. IFN-I inhibits LC ADAM17 sheddase activity in murine and human LCs, and IFNAR blockade in lupus model mice restores LC ADAM17 sheddase activity, all without consistent effects on LC ADAM17 protein expression or LC numbers. Anti-IFNAR-mediated LC ADAM17 sheddase function restoration is associated with reduced photosensitive responses that are dependent on EGFR signaling and LC ADAM17. Reactive oxygen species (ROS) is a known mediator of ADAM17 activity; we show that UVR-induced LC ROS production is reduced in lupus model mice, restored by anti-IFNAR, and is cytoplasmic in origin. Our findings suggest that IFN-I promotes photosensitivity at least in part by inhibiting UVR-induced LC ADAM17 sheddase function and raise the possibility that anifrolumab ameliorates lupus skin disease in part by restoring this function. This work provides insight into IFN-I-mediated disease mechanisms, LC regulation, and a potential mechanism of action for anifrolumab in lupus.

Increase in pediatric recurrent fever evaluations during the first year of the COVID-19 pandemic in North America.

The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019-29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020-28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (p < 0.001). Our findings showed that the first year of the COVID-19 pandemic was associated with a higher number of evaluations by pediatric subspecialists for recurrent fevers. Further research is needed to understand the reasons behind these findings and to explore non-infectious triggers for recurrent fevers in children.

Corrigendum: Increase in pediatric recurrent fever evaluations during the first year of the COVID-19 pandemic in North America.

[This corrects the article DOI: 10.3389/fped.2023.1240242.].

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS: This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS: This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION: Application of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

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.

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.

Lyme disease presenting as persistent severe photophobia.

Long-term photophobia in children that has no obvious cause is uncommon and presents a diagnostic dilemma. It may produce significant discomfort and result in social isolation and school absence. We present the case of a 5-year-old boy who presented with chronic photophobia due to interstitial keratitis that was the result of Lyme disease.

The value of the patient global health assessment in polyarticular juvenile idiopathic arthritis: a nested cohort study.

OBJECTIVE: The objectives were: 1) to explore the discordance between the Patient Global Health Assessment (PtGA) scores, the Physician Global Health Assessment (PhGA) scores, and Pain scores; and 2) to explore whether the PtGA during disease remission is associated with future disease flare in pJIA. METHODS: Data from an NIH funded clinical trial (NCT00792233) evaluating flare were used (N = 137). PtGA, PhGA, and Pain scores were assessed. Flare was defined as any active arthritis. Spearman's correlation coefficients were calculated, and multivariable logistic regression was performed. RESULTS: 122 patients had records of flare status, of which 63 developed flare, and 42 of these patients had a visit immediately prior to flare. For study subjects with a visit immediately prior to flare, the PtGA, pain scores, and PhGA all increased at time of flare. For every unit increase in PtGA and Pain scores, there was a 9% and 23% higher odds of developing flare, respectively (p = 0.76, p = 0.40). For every unit increase in the PhGA score, there was a substantially lower odds of developing flare (p = 0.05). CONCLUSION: Our results demonstrate that the PtGA and Pain scores are strongly correlated with each other and increased at the visit prior to flare, while the PhGA scores are not. Further, the PtGA and Pain score have some predictive value for flare, while the PhGA does not. These findings highlight the value of patient input in medical care and decision-making, and support the development and use of more sophisticated PROs in the care of JIA patients.

Novel Majeed Syndrome-Causing LPIN2 Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis.

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-1ß 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/ß, 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.

Glitches in the utilization of telehealth in pediatric rheumatology patients during the COVID-19 pandemic.

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.