onset in infancy (SAVI), and another by additive loss-of-function mutations in proteasome genes causing the proteasome-associated autoinflammatory syndromes (PRAAS) (also, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures [CANDLE]), presented with chronically elevated interferon (IFN) signatures, suggesting a pathogenic role for type-I IFN in autoinflammatory diseases (2, 3). Type-I IFN was first discovered as a soluble antiviral factor over 50 years ago, and a role in sterile inflammation was proposed in patients with systemic lupus erythematosus (4). However, the discovery of genetic mutations that cause the autoinflammatory type-I interferonopathies CANDLE (2, 5), SAVI (3, 6-8), and Aicardi-Goutières syndrome (AGS) (9, 10) have shed light on pathomechanisms that drive chronic IFN signaling, and recent studies blocking IFN signaling validate a critical role for type-I IFNs (11). AGS-causing loss-of-function mutations in nucleases impair self-nucleic acid homeostasis, SAVI-causing

BACKGROUND: Childhood-onset systemic lupus erythematosus (c-SLE) is a complex autoimmune disease that requires systemic immunosuppressive therapy. Infections are the second leading cause of death in these patients, with invasive pneumococcal infections being a major preventable cause of morbidity and mortality. Pneumococcal vaccination is recommended in this population; however, vaccination rates remain low. METHODS:The plan-do-study-act method of quality improvement was applied. We calculated baseline vaccination rates for pneumococcal conjugate and pneumococcal polysaccharide vaccines in patients with c-SLE in the rheumatology clinic from January 2015 to August 2016. We developed an age-based algorithm to simplify the vaccination guidelines. The clinical pharmacist and nurses performed weekly previsit planning to update vaccine records, make targeted recommendations, and ensure vaccine availability. The primary outcome measure was the percentage patients with of c-SLE seen per month who had received age-appropriate pneumococcal vaccination. RESULTS:The percentage of children receiving at least 1 pneumococcal vaccine increased from 24.9% to 92.7% by 12 months. By 18 months, the compliance rate with both pneumococcal vaccines increased from 2.5% to 87.3%, with sustained results. No serious adverse events or disease flares were reported.CONCLUSIONS: By identifying the major barriers to pneumococcal vaccination in our population with c-SLE, we significantly improved vaccination rates while decreasing time burden on providers. We attribute our success to a teambased quality improvement approach and plan to implement alerts in the electronic health record to streamline the process.

Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates [PRs]), as well as barriers/facilitators to fertility counseling and fertility preservation.

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.

Objective Patients with systemic lupus erythematosus (SLE) have altered bone metabolism and are at risk of osteoporosis. The aim of this study was to examine bone turnover markers in relation to vitamin D, disease activity, and clinical risk factors in patients with established SLE. Methods Clinical registry and biorepository data of 42 SLE patients were assessed. Serum samples were analyzed for osteocalcin as a marker of bone formation, C-terminal telopeptide of type 1 collagen (CTX) as a marker for bone resorption, and 25-hydroxy vitamin D. Results Patients with a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI) score of 3 or greater had a lower median osteocalcin level (P = 0.02) and lower 25-hydroxy vitamin D levels (P = 0.03) than those with a score of less than 3. No significant differences in bone turnover markers were observed between patients dichotomized into subgroups using a 25-hydroxy vitamin D cut-off of 30 ng/mL or by a daily prednisone dose greater than or 5 mg or less. Osteocalcin levels were negatively correlated with SLEDAI scores (P = 0.034), and were positively correlated with the CTX index (a ratio of measured CTX value to the upper limit of the normal value for age and gender) (P < 0.01). No association between the CTX index and SLEDAI scores was found. Conclusion SLE disease activity may have direct effects on bone formation, but no effects on bone resorption in this cohort of established SLE patients, probably related to the inflammation-suppressing effects of glucocorticoids, thereby inhibiting cytokine-induced osteoclast activity. A fine balance exists between disease control and the use of glucocorticoids with regard to bone health.

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 Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, and drug formularies or other third-party analyses that cite ACR guidelines should state this. These recommendations cannot adequately convey all uncertainties and nuances of patient care.

for the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Antineutrophil Cytoplasmic Antibody-Associated Vasculitis WorkgroupObjective. There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibodyassociated vasculitis (AAV). Because of the rarity of pediatric AAV, randomized trials have not been feasible. The present study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) was undertaken to establish consensus treatment plans (CTPs) for severe pediatric AAV to enable the future study of comparative effectiveness and safety.Methods. A workgroup of CARRA members (rheumatologists and nephrologists) formed the AAV Workgroup. This group performed a literature review on existing evidence-based treatments and guidelines for the management of AAV. They determined that the target population for CTP development was patients <18 years of age with new-onset granulomatosis with polyangiitis (GPA), microscopic polyangiitis, or renal-limited AAV (eosinophilic GPA was excluded), with presentation confined to those with severe disease (i.e., organ-or life-threatening). Face-to-face consensus conferences employed nominal group techniques to identify treatment strategies for remission induction and remission maintenance, data elements to be systematically collected, and outcomes to be measured over time.Results. The pediatric AAV Workgroup developed 2 CTPs for each of the remission induction and remission maintenance of severe AAV. A glucocorticoid-weaning regimen for induction and maintenance, a core data set, and outcome measures were also defined. A random sample of CARRA membership voted acceptance of the CTPs for remission induction and remission maintenance, with a 94% (75 of 80) and 98% (78 of 80) approval rate, respectively.Conclusion. Consensus methodology established standardized CTPs for treating severe pediatric AAV. These CTPs were in principle accepted by CARRA-wide membership for the evaluation of pragmatic comparative effectiveness in a long-term registry.

Objective The goal was to characterize short‐term kidney status and describe variation in early care utilization in a multicenter cohort of patients with childhood‐onset systemic lupus erythematosus (cSLE) and nephritis. Methods We analyzed previously collected prospective data from North American patients with cSLE with kidney biopsy‐proven nephritis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from March 2017 through December 2019. We determined the proportion of patients with abnormal kidney status at the most recent registry visit and applied generalized linear mixed models to identify associated factors. We also calculated frequency of medication use, both during induction and ever recorded. Results We identified 222 patients with kidney biopsy–proven nephritis, with 64% class III/IV nephritis on initial biopsy. At the most recent registry visit at median (interquartile range) of 17 (8–29) months from initial kidney biopsy, 58 of 106 patients (55%) with available data had abnormal kidney status. This finding was associated with male sex (odds ratio [OR] 3.88, 95% confidence interval [95% CI] 1.21–12.46) and age at cSLE diagnosis (OR 1.23, 95% CI 1.01–1.49). Patients with class IV nephritis were more likely than class III to receive cyclophosphamide and rituximab during induction. There was substantial variation in mycophenolate, cyclophosphamide, and rituximab ever use patterns across rheumatology centers. Conclusion In this cohort with predominately class III/IV nephritis, male sex and older age at cSLE diagnosis were associated with abnormal short‐term kidney status. We also observed substantial variation in contemporary medication use for pediatric lupus nephritis between pediatric rheumatology centers. Additional studies are needed to better understand the impact of this variation on long‐term kidney outcomes.