Orandi, Amir B.

ABSTRACTBackgroundBlau syndrome is a rare, autosomal dominant granulomatous disease caused by mutations in the NOD2/CARD15 gene. While the classic triad of arthritis, dermatitis, and uveitis is well known, the full range of cutaneous manifestations remains underexplored.ObjectiveTo expand the understanding of cutaneous findings in Blau syndrome, correlate these findings with NOD2 variants, and evaluate treatment outcomes across organ systems.MethodsA retrospective review of medical records from January 1999 to January 2024 identified 14 patients with Blau syndrome supported by the presence of NOD2 variants. Clinical data on dermatological features, genetics, and treatment responses were analyzed and categorized into specific and non‐specific cutaneous findings.ResultsOf the 14 patients with Blau syndrome, 85% (12/14) demonstrated skin involvement. Specific findings included lichenoid or granulomatous papules and nodules (50%, 6/12), while non‐specific findings (83%, 10/12) were more diverse, including dermatitis (6/10), chronic urticaria (5/10), ichthyosiform eruptions (4/10), vasospastic disorders (5/10), and oral/genital ulcers (2/10). Skin biopsies in three patients with specific findings revealed non‐caseating granulomas. Genetic analysis identified multiple NOD2 variants, though no clear genotype–phenotype correlation was observed. TNF‐alpha inhibitors demonstrated efficacy in controlling ocular and joint disease.ConclusionBlau syndrome presents with a broader spectrum of cutaneous findings than previously recognized. These findings highlight the importance of dermatological evaluation and a multidisciplinary approach to optimize diagnosis and management.

Abstract Background Prolonged and recurrent fevers in pediatric outpatients often require specialist consultations, presenting a challenge in accurately triaging to the correct pediatric subspecialty. This study aims to develop an artificial intelligence (AI)-based model to accurately direct pediatric patients to appropriate subspecialties.Table 1.Patient characteristics and the department confirming the final diagnosis Table 1. Patient characteristics and the department confirming the final diagnosis Methods A retrospective study was conducted at the Mayo Clinic, Rochester, from December 1, 2020, to January 1, 2023, involving pediatric patients aged 0 to 18 referred for recurrent fever or fever of unknown origin. Six machine learning models, including gradient boosting, random forest, support vector machines (SVM), k-Nearest Neighbor (KNN), logistic regression (LR) and decision tree, were developed using 7 variables (demographics, chief complaints, referral sources, departments of same-day initial visit, and lab tests results within 30 days before initial visits). Data were extracted from external electronic health records (EHR) using Mayo Data Explorer and Lab Information Management Systems. Precision, Recall, F1 Score, and area under the curve (AUROC) were selected to measure the performance.Table 2.Performance of six machine learning models Table 2. Performance of six machine learning models Results The study evaluated 87 pediatric patients with a median age of 10.2 years (IQR: 4.6-13.8), including 43 (49%) females (Table 1). External provider referrals were noted in 40 (46%) patients. Musculoskeletal pain was the most common chief complaint, identified in 29 (33%) patients, in addition to prolonged or recurrent fever. Infectious disease and rheumatology divisions jointly saw 43 (49%) patients during the initial visit. Sub-optimal performance was observed in six machine learning models (Table 2). The random forest model showed the best results (Accuracy=0.39, Precision=0.34, Recall=0.39, F1 Score=0.35, AUROC=0.60) (Figure).Figure.ROC curves for various models Figure. ROC curves for various models Conclusion This study demonstrates the potential of AI-based models for outpatient triage prediction in pediatric patients with recurrent fever, using EHR data to optimize health resource utilization. This data serves as the groundwork to expand and refine this AI triage tool. Disclosures All Authors: No reported disclosures

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.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1,152 patients have been evaluated with an overall solve rate of 14.1% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Background: Many health care organizations offer pediatric infusions in outpatient infusion centers or, as in our organization, in a hospital-based outpatient Pediatric Infusion Therapy Center (PITC). When restrictions related to the COVID-19 pandemic decreased our PITC appointment capacity by 40%, other patient and family satisfaction issues were exacerbated. We implemented a new approach to pediatric infusions with the aim of improving patient and family satisfaction and reducing the amount of time in an appointment itinerary without negatively affecting patient safety. Methods: Our team used a phased approach to pilot the administration of short chemotherapy infusions in the same outpatient clinic examination rooms where consultation and routine office visits were conducted. Patients saw their specialist for an examination and, if clinically indicated, their infusion was administered in the same room. Appointment itineraries were then completed. The team tracked efficiency, satisfaction, and safety metrics related to the new process. Results: All efficiency metrics improved. No harm came to the 49 unique patients who received a total of 184 infusions. Patient appointment itineraries were shortened by an average of 1.03 hr. Satisfaction survey responses indicated a clear preference (93%) for the new process. Discussion: The novel approach of offering short infusions in outpatient clinic examination rooms provides an opportunity to ease capacity constraints and further increase patient and family satisfaction. This method may be especially helpful for health care organizations when external influences (e.g., lack of physical space, challenging patient volumes, and pandemics) necessitate a change.

AbstractTumor necrosis factor‐alpha inhibitor therapy for inflammatory bowel disease may be associated with paradoxical cutaneous adverse events, most commonly psoriasiform eruptions. We present the case of a pediatric female patient with Crohn's disease who developed multiple concurrent cutaneous eruptions while on infliximab treatment, including morphea, psoriasiform dermatitis, and genital lichen sclerosus. Although refractory to skin‐directed treatments, all three conditions resolved upon discontinuation of infliximab, supporting their development as a paradoxical reaction to infliximab therapy.

Objective To characterize the incidence and prevalence of childhood‐onset systemic lupus erythematosus (SLE), and to estimate the proportion of patients who are diagnosed with SLE during childhood. Methods A cohort of patients with incident childhood‐onset SLE from 1976 to 2018 from an 8‐county region in the US were identified based on comprehensive medical record review. All patients met the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE or the ACR SLE classification criteria from 1997 at or before age 18 years. Incidence rates were estimated using Poisson methods. We estimated the childhood‐onset SLE point prevalence for January 1, 2015. Results were sex and age adjusted to the US 2000 population. Among all the SLE patients living in the 8‐county region on January 1, 2015, the proportion of patients diagnosed at ≤18 years was estimated. Results A total of 13 children were diagnosed with childhood‐onset SLE during the study period (using the EULAR/ACR definition; mean age at diagnosis 15.1 years, 85% female, 69% White). Childhood‐onset SLE overall adjusted incidence rate was 0.7 (95% confidence interval [95% CI] 0.2–1.1) per 100,000 children. The incidence rate in girls was 1.2 (95% CI 0.5–1.9) per 100,000 children, while in boys it was 0.2 (95% CI 0.0–0.5) per 100,000. The adjusted prevalence of childhood‐onset SLE was 1.1 (95% CI 0.0–3.1) per 100,000 children. The proportion of patients with SLE diagnosed as children was 9% (95% CI 6–13%). Conclusion In this population‐based study, both the incidence and prevalence rates of childhood‐onset SLE were ~1 per 100,000 children. One in 10 adults with SLE was diagnosed in childhood. More studies are needed to further characterize the epidemiology of childhood‐onset SLE in minorities.