Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

Histocompatibility Leukocyte Antigen-A29-Associated Retinal Vasculitis without Choroidal Lesions: A Report of 4 Cases.

This study describes a cohort of patients presenting with histocompatibility leukocyte antigen (HLA)-A29-associated retinal vasculitis without choroidal lesions that may share clinical features with birdshot retinochoroiditis. The methods include a retrospective chart review of patients presenting with HLA-A29-associated retinal vasculitis without choroidal lesions. The data on the patients were entered retrospectively into a new database and analyzed. Four patients who had HLA-A29-associated retinal vasculitis without choroidal lesions were identified. The median age at presentation was 40 years (range: 14-71); 75% were female. At presentation, all four patients had a visual acuity of 20/50 or better in both eyes. All the eyes had mild vitritis, three eyes (37.5%) had cystoid macular edema, and two eyes (25%) had optic disc edema. All the patients required treatment with systemic steroids and immunosuppressive therapy. HLA-A29-associated retinal vasculitis without choroidal lesions appears to share many clinical features with birdshot chorioretinitis, including the need for systemic immunosuppressive therapy. Whether this entity represents an early form of birdshot retinochoroiditis or a more localized variant of the disease is a topic for additional studies.

HLA-DRB1*15 and Eosinophilia Are Common Among Patients With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Concern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)-1 and IL-6 blocking agents, might be causing adverse drug reactions and lung disease (systemic JIA-LD). Carriage of HLA-DRB1*15 has been reported as a risk factor for adverse drug reactions among patients with systemic JIA. We performed a retrospective chart review to evaluate these factors at our center. METHODS: We reviewed the records of 86 subjects with systemic JIA followed for at least 6 months between 1996 and 2022. HLA typing was performed in 23 of the subjects. We compared characteristics of patients with or without eosinophilia. Among patients with HLA typing, we compared clinical characteristics of subjects with or without DRB1*15 and with or without systemic JIA-LD. RESULTS: Among the 23 patients with HLA typing, 74% carried DRB1*15, and 63% of patients without systemic JIA-LD carried DRB1*15. Seven subjects had systemic JIA-LD, all of whom carried DRB1*15. Patients with systemic JIA-LD were younger at the time of diagnosis and more likely to have had macrophage activation syndrome. Exposure to IL-1 and IL-6 blockers was common, occurring in 95% of patients. Eosinophilia occurred in 39% of patients with systemic JIA, often before IL-1 or IL-6 blockade. Eosinophilia was associated with adverse drug reactions and macrophage activation syndrome. There was 1 death, unrelated to active systemic JIA disease. CONCLUSION: Carriage of DRB1*15 was more common in this cohort of patients with systemic JIA than in the general population. Eosinophilia and systemic JIA-LD were more common among patients with severe systemic JIA complicated by macrophage activation syndrome.

Capturing critical data elements in Juvenile Idiopathic Arthritis: initiatives to improve data capture.

BACKGROUND: Documentation of critical data elements is a focus of the Pediatric Rheumatology Care and Outcomes Improvement Network to aid in clinical care and research for patients with juvenile idiopathic arthritis. We aimed to increase data capture for critical data elements and hypothesized that quality improvement methodology would improve data capture. We also hypothesized that data capture for all critical data elements would be lower for virtual visits compared to in-person visits. METHODS: All visits for patients with JIA between 9/14/2020 and 12/31/2021 at the University of Minnesota were included. We assessed completeness of critical data element capture. Sixteen interventions with providers were conducted, including email reminders, individual discussions, group meetings, and feedback reports. We used statistical process control charts to evaluate change over time. RESULTS: Baseline included 355 patient-visits: 221 (62%) in-person and 134 (38%) virtual with critical data elements entry ranging between 50 and 60%. Post-intervention included 1,596 patient-visits: 1,350 (85%) in-person and 246 (15%) virtual, with critical data elements entry reaching 91%. All providers improved data entry during this study. In-person visits had significantly higher data capture rates than virtual visits for all 4 critical data elements. CONCLUSION: We achieved our aim to increase critical data element documentation by focusing on provider buy-in, frequent reminders, and individualized feedback. We also found that collection of critical data elements occurred significantly less often with virtual visits than with in-person visits. Now that we improved capture of critical data elements, we can shift the focus to efforts aimed at improving outcomes for patients with juvenile arthritis.

Non-criteria antiphospholipid antibodies and pediatric rheumatic disease: a case series.

BACKGROUND: Non-criteria antiphospholipid antibodies (NC-aPL) are a relatively undefined subgroup of antiphospholipid antibodies (aPL). Knowledge about NC-aPL in adults is limited and even less is known in pediatric patients. Routine tests for antiphospholipid syndrome (APS)-a clinical state marked by the presence of aPL in association with vascular thrombosis-usually include lupus anticoagulant (LAC), anti-cardiolipin (aCL) and -beta-2 glycoprotein I (aß2GPI). LAC is a functional screen for prothrombotic aPL, while the latter tests identify specific autoantibodies. Specific targets of NC-aPL include, but are not limited to, phosphatidylethanolamine, phosphatidylserine, and prothrombin. PRESENTATION OF CASES: We present single-center data from eight pediatric patients with NC-aPL identified during a three-year period. All patients had presenting features raising suspicion for APS. Most patients were female with a primary rheumatic disease. One patient had a stroke. Another patient had alveolar hemorrhage and pulmonary hypertension. Raynaud's phenomenon, rashes involving distal extremities, and headaches were common. Most patients had a positive LAC, yet their routine aPL tests were negative, prompting testing for NC-aPL. CONCLUSIONS: Our findings suggest NC-aPL are associated with typical signs and symptoms of APS in pediatric patients. Pediatricians and pediatric subspecialists should consider NC-aPL when clinical suspicion is high and routine aPL tests are negative, particularly when LAC is positive. While guidelines for NC-aPL do not yet exist for children or adults, these autoantibodies have pathogenic potential. Actionable items could include evaluation for the presence of other (primary) rheumatic diseases, and consultation with hematologists and/or obstetricians regarding anticoagulation/platelet inhibition and thrombosis education. Future guidelines regarding NC-aPL will only be generated by gathering more data, ideally prospectively.

Using quality improvement methodology and tools to reduce patient wait time in a paediatric subspecialty rheumatology clinic.

Our paediatric rheumatology clinic has experienced inefficient patient flow. Our aim was to reduce mean wait time and minimise variation for patients. Baseline data showed that most waiting occurs after a patient has been roomed, while waiting for the physician. Wait time was not associated with a patient's age, time of day, day of the week or individual physician. We implemented a checkout sheet and staggered start times. After a series of plan-do-study-act cycles, we observed an initial 26% reduction in the variation of wait time and a final 17% reduction in the mean wait time. There was no impact on patient-physician contact time. Overall, we demonstrate how process improvement methodology and tools were used to reduce patient wait time in our clinic, adding to the body of literature on process improvement in an ambulatory setting.

Tolerability of mycophenolate mofetil in patients with systemic lupus erythematosus.

OBJECTIVE: To quantify the adverse events (AE) associated with mycophenolate mofetil (MMF) in patients with systemic lupus erythematosus (SLE), to examine the relationship between AE and dosage of MMF, and to assess the overall tolerability of MMF in SLE patients. METHODS: A consecutive cohort of adults with SLE who received MMF between October 1996 and June 1999 was identified. Charts were reviewed for baseline data, AE, MMF dosing characteristics, and clinical response at baseline, 3 months, and at final followup or drug discontinuation. RESULTS: The 54 SLE patients were followed for a mean of 12.4 +/- 7.0 person-months. Baseline characteristics: 92.6% female, 72.2% white, mean age 38.3 years, and a mean of 9.6 years since diagnosis. Twenty-one of 54 patients (38.9%) had a total of 28 gastrointestinal AE. Twenty-four of 54 (44.4%) patients had a total of 37 infections, only one of which required hospitalization. Leukopenia occurred 3 times but never required dose adjustment. AE occurred at a similar rate at all MMF doses. Kaplan-Meier estimates show most drug discontinuation occurred in the first 2.5 months and 73% of patients were still on the drug at 12 months. Sixteen of 54 patients discontinued MMF because of AE (n = 9), lack of efficacy (n = 3), pregnancy (n = 2), and administrative reasons (n = 2). Clinical improvement in patients was noted with significant decreases in disease activity measured by the SLEDAI and prednisone dose at 3 months and at final followup. CONCLUSION: The majority of patients tolerated MMF. A range of doses was tolerated and associated with clinical improvement, suggesting that a flexible dosing schedule should be considered when using MMF in patients with SLE.