Severe Features of Systemic Juvenile Idiopathic Arthritis in Patients with Congenital Heart Disease.

OBJECTIVE: To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA). METHODS: We conducted a retrospective review of patients diagnosed with CHD and sJIA at our institution. Detailed clinical, laboratory and radiographic data were collected from the medical record and reviewed with each patient's primary medical team. RESULTS: Five patients with sJIA and CHD were identified. Each child had a unique cardiac anatomy but all of the patients required surgical repair during the first year of life. Four children had thymectomies at the time of cardiac surgery. Classic signs of sJIA such as fever (n=5), rash (n=5), and arthritis (n=4) developed after surgical intervention in all of the patients. The individuals in this cohort displayed risk factors associated with severe sJIA, including disease onset before 2 years of age (n=5), elevated IL-18 levels (n=5), baseline eosinophilia prior to initiation of biologic disease modifying anti-rheumatic drugs (bDMARDs) (n=4), and positivity for HLA-DRB1*15:01 alleles (n=4). Macrophage activation syndrome (MAS) occurred in 3 patients and sJIA-associated lung disease (sJIA-LD) was identified in 4 patients. Two children died from complications of their cardiac and/or pulmonary disease. CONCLUSION: We identified an association between CHD and severe forms of sJIA. While these findings will need to be confirmed in larger, multi-center cohorts, the results highlight the importance of considering a diagnosis of sJIA in children with CHD and remaining vigilant for complications such as MAS and sJIA-LD.

Classifying Individuals With Rheumatic Conditions as Financially Insecure Using Electronic Health Record Data and Natural Language Processing: Algorithm Derivation and Validation.

OBJECTIVE: We aimed to examine the feasibility of applying natural language processing (NLP) to unstructured electronic health record (EHR) documents to detect the presence of financial insecurity among patients with rheumatologic disease enrolled in an integrated care management program (iCMP). METHODS: We incorporated supervised, rule-based NLP and statistical methods to identify financial insecurity among patients with rheumatic conditions enrolled in an iCMP (n = 20,395) in a multihospital EHR system. We constructed a lexicon for financial insecurity using data from available knowledge sources and then reviewed EHR notes from 538 randomly selected individuals (training cohort n = 366, validation cohort n = 172). We manually categorized records as having "definite," "possible," or "no" mention of financial insecurity. All available notes were processed using Narrative Information Linear Extraction, a rule-based version of NLP. Models were trained using the NLP features for financial insecurity using logistic, least absolute shrinkage operator (LASSO), and random forest performance characteristic and were compared with the reference standard. RESULTS: A total of 245,142 notes were processed from 538 individual patient records. Financial insecurity was present among 100 (27%) individuals in the training cohort and 63 (37%) in the validation cohort. The LASSO and random forest models performed identically and slightly better than logistic regression, with positive predictive values of 0.90, sensitivities of 0.29, and specificities of 0.98. CONCLUSION: The development of a context-driven lexicon used with rule-based NLP to extract data that identify financial insecurity is feasible for use and improved the capture for presence of financial insecurity with high accuracy. In the absence of a standard lexicon and construct definition for financial insecurity status, additional studies are needed to optimize the sensitivity of algorithms to categorize financial insecurity with construct validity.

Racial and Ethnic Composition of Populations Served by Freestanding Children's Hospitals and Disparities in Outcomes of Pediatric Lupus.

OBJECTIVE: Health disparities may be driven by hospital-level factors. We assessed whether racial and ethnic composition of populations hospitals serve explain or modify disparities in hospital outcomes of children with systemic lupus erythematosus (SLE). METHODS: In this retrospective cohort study of patients 5 to 26 years old with SLE at 47 children's hospitals in the Pediatric Health Information System (2006-2021), race and ethnicity were assessed at the patient level and hospital level (proportion of total admissions composed of Black or Hispanic patients, respectively). Outcomes included intensive care unit (ICU) admission or adverse renal outcome (end-stage renal disease, dialysis, or transplant) during follow-up. We estimated racial and ethnic disparities, adjusted or stratified by hospital racial or ethnic composition. RESULTS: Of 8,125 patients with SLE, 2,293 (28%) required ICU admission, and 698 (9%) had an adverse renal outcome. Black and non-Hispanic White disparities in ICU admission were observed only at hospitals serving higher proportions of Black patients (odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.04-1.59 vs OR 1.07, 95% CI 0.83-1.38). Larger Black and non-Hispanic White disparities in adverse renal outcomes were observed at hospitals with higher Black racial composition (OR 2.0, 95% CI 1.4-2.8 vs OR 1.7, 95% CI 1.1-2.4). Conversely, Hispanic versus non-Hispanic disparities in renal outcomes persisted after adjustment for hospital-reported Hispanic ethnic composition but were observed only at hospitals with lower proportions of Hispanic patients. CONCLUSION: Worse Black and White disparities in SLE outcomes are observed at children's hospitals serving more Black children, whereas distinct patterns are observed for Hispanic and non-Hispanic disparities. Reporting of hospital characteristics related to populations served is needed to identify modifiable drivers of hospital-level variation.

Racial differences in persistent glucocorticoid use patterns among medicaid beneficiaries with incident systemic lupus erythematosus.

OBJECTIVE: Glucocorticoids ("steroids") are frequently used in systemic lupus erythematosus (SLE). Prolonged use may contribute to racial/ethnic disparities in avoidable adverse outcomes. We examined racial/ethnic differences in longitudinal patterns of steroid use and dose. METHODS: We identified Medicaid beneficiaries 18-65 years with incident SLE who received steroids for 12 months following the index date. Group-based trajectory modeling was used to identify patterns of daily prednisone-equivalent steroid doses. We examined demographic, clinical and healthcare utilization factors during the baseline period and used multinomial logistic regression to estimate the odds of belonging to the higher vs. lowest steroid dose trajectories over time. RESULTS: We identified 6314 individuals with SLE with ≥1 dispensed steroid prescription. The mean (SD) prednisone-equivalent dose was 7 (23) mg/day for Black, 7 (26) for Hispanic, 7 (13) for Asian, and 4 (10) for White individuals. Adjusted multinomial models demonstrated higher odds of belonging to the highest vs. lowest steroid trajectory for Black (OR 2.07, 95% CI 1.65-2.61), Hispanic (OR 1.81, 95% CI 1.38-2.39), and Asian (OR 2.42, 95% CI 1.53-3.83) vs. White individuals. Having >5 outpatient visits during the baseline period was associated with lower odds of being in the persistently high-dose steroid trajectory (OR 0.77; 95% CI 0.60-0.98). CONCLUSION: Black, Hispanic, and Asian (vs. White) individuals had higher odds of persistently high-dose steroid use. Sustained access to outpatient care and the development of standardized steroid-tapering regimens from clinical trials with diverse populations may be targets for intervention to mitigate disparities in steroid-related adverse outcomes.

Social Determinants of Health Documentation Among Individuals With Rheumatic and Musculoskeletal Conditions in an Integrated Care Management Program.

OBJECTIVE: Social determinants of health (SDoH), such as poverty, are associated with increased burden and severity of rheumatic and musculoskeletal diseases. This study was undertaken to study the prevalence and documentation of SDoH-related needs in electronic health records (EHRs) of individuals with these conditions. METHODS: We randomly selected individuals with ≥1 International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) code for a rheumatic/musculoskeletal condition enrolled in a multihospital integrated care management program that coordinates care for medically and/or psychosocially complex individuals. We assessed SDoH documentation using terms for financial needs, food insecurity, housing instability, transportation, and medication access according to EHR note review and ICD-10 SDoH billing codes (Z codes). We used multivariable logistic regression to examine associations between demographic factors (age, gender, race, ethnicity, insurance) and ≥1 (versus 0) SDoH need as the odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: Among 558 individuals with rheumatic/musculoskeletal conditions, 249 (45%) had ≥1 SDoH need documented in EHR notes by social workers, care coordinators, nurses, and physicians. A total of 171 individuals (31%) had financial insecurity, 105 (19%) had transportation needs, 94 (17%) had food insecurity; 5% had ≥1 related Z code. In the multivariable model, the odds of having ≥1 SDoH need was 2.45 times higher (95% CI 1.17-5.11) for Black versus White individuals and significantly higher for Medicaid or Medicare beneficiaries versus commercially insured individuals. CONCLUSION: Nearly half of this sample of complex care management patients with rheumatic/musculoskeletal conditions had SDoH documented within EHR notes; financial insecurity was the most prevalent. Only 5% of patients had representative billing codes suggesting that systematic strategies to extract SDoH from notes are needed.

Understanding Stakeholders' Perspectives to Increase COVID-19 Vaccine and Booster Uptake Among Black Individuals With Rheumatic Conditions.

OBJECTIVE: Disparities in COVID-19 vaccine and booster uptake persist. This study aimed to obtain perspectives from community and physician stakeholders on COVID-19 vaccine and booster hesitancy and strategies to promote vaccine uptake among Black individuals with rheumatic and musculoskeletal conditions. METHODS: We invited community leaders and physicians in greater Boston and Chicago to participate in semi-structured interviews using a moderator guide developed a priori. Participants were queried about how to best address vaccine hesitancy, strategies to target high-risk populations, and factors to identify future community leaders. Interviews were audio recorded, transcribed verbatim, and analyzed thematically using Dedoose. RESULTS: A total of 8 physicians and 12 community leaders participated in this study between November 2021 and October 2022. Qualitative analyses revealed misinformation/mixed messaging and mistrust, with subthemes including conspiracy theories, concerns regarding vaccine development and function, racism and historical injustices, and general mistrust of health care systems as the top cited reasons for COVID-19 vaccine hesitancy. Participants also shared demographic-specific differences, such as race, ethnicity, age, and gender that influenced the identified themes, with emphasis on COVID-19 vaccine access and apathy. Strategies for community-based vaccine-related information dissemination included personal storytelling with an iterative and empathetic approach, while recognizing the importance of protecting community leader well-being. CONCLUSION: To increase vaccine uptake among Black individuals with rheumatic conditions, strategies should acknowledge and respond to racial/ethnic and socioeconomic injustices that engender vaccine hesitancy. Messaging should be compassionate, individually tailored, and recognize heterogeneity in experiences and opinions. Results from these analyses will inform a planned community-based intervention in Boston and Chicago.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA. METHODS: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. RESULTS: There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P = 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease. CONCLUSION: Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.

Pediatric EVALI in the Age of COVID-19/MIS-C: Diagnostic Considerations.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) and e-cigarette or vaping product use-associated lung injury (EVALI) have significant overlap in clinical features, which can contribute to delay in identification and treatment. The objectives of this report were to identify and describe features that are common in both diagnoses and those that may help distinguish EVALI from MIS-C, and to highlight the diagnostic challenges observed at our tertiary medical center. METHODS: We identified adolescents diagnosed with MIS-C who had respiratory or gastrointestinal symptoms and patients diagnosed with EVALI during the same time period. We compared demographics, history, clinical manifestations, laboratory findings, and features of the hospital course to determine areas of overlap between MIS-C and EVALI, as well as distinct features of each diagnosis. Mann-Whitney U test was used to compare continuous variables and Fisher's exact test was used to compare categorical variables. RESULTS: We found that cardiovascular and mucocutaneous findings and thrombocytopenia were more common in MIS-C. EVALI patients had a higher degree of inflammation and history of antecedent weight loss. Providers at our institution were more likely to consider MIS-C than EVALI on the differential diagnosis, including in patients with vaping history and no evidence of previous severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: This study emphasizes the need for a thorough collection of substance use history for all patients and consideration of EVALI in adolescents who present with respiratory compromise or gastrointestinal symptoms and systemic inflammation, particularly in the absence of severe acute respiratory syndrome coronavirus 2 exposure or cardiac findings characteristic of MIS-C.

An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome.

OBJECTIVE: To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG). METHODS: A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts. RESULTS: After the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort (P = 0.02). There was a significant improvement in time to 50% reduction in C-reactive protein level in the post-EBG vs pre-EBG cohorts (log-rank P < 0.01). There were trends toward faster time to MAS-HLH diagnosis, faster initiation of immunosuppressive therapy, shorter length of hospital stay, and more rapid normalization of MAS-HLH-related biomarkers in the patients post-EBG. CONCLUSION: While the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes.