ObjectiveTo determine factors associated with hydroxychloroquine (HCQ)-induced retinopathy in Puerto Ricans with systemic lupus erythematosus (SLE) and to evaluate determinants of early HCQ-induced retinopathy.MethodsWe conducted a retrospective study of adult Puerto Ricans with SLE. Patients with ophthalmologist-confirmed HCQ-induced retinopathy were compared with those without retinopathy. A subgroup analysis comparing patients with early-onset (≤5 years) versus late-onset (>5 years) retinopathy was also performed. Demographic factors, clinical manifestations, and pharmacologic treatments were analyzed using bivariate methods and logistic regression models adjusted for SLE duration.ResultsA total of 279 patients were included; 41 had HCQ-induced retinopathy, while 238 did not. Among patients with HCQ-induced retinopathy, the mean age (SD) was 45.2 (13.2) years, and 90.2% were women. The mean (SD) SLE duration and HCQ treatment duration were 10.3 (7.7) years and 9.1 (5.8) years, respectively. Patients with HCQ-induced retinopathy were more likely to have higher daily and weight-adjusted HCQ doses and greater damage accrual, but were less likely to have proteinuria, lymphopenia, anti-dsDNA positivity, low complement levels or exposure to mycophenolate mofetil. Among patients with HCQ-induced retinopathy, 13 (31.7%) discontinued HCQ within 5 years of treatment initiation. In multivariable analysis, early-onset toxicity was associated with corticosteroid exposure.ConclusionsIn this cohort of Puerto Rican Hispanics with SLE, HCQ-induced retinopathy occurred in 14.7% of patients, and nearly 32% of those affected developed early-onset retinopathy. Retinopathy was primarily associated with higher daily and weight-adjusted HCQ doses, while early-onset retinopathy was associated with corticosteroid exposure. These findings provide population-specific data that may help optimize HCQ dosing and underscore the importance of regular ophthalmologic screening, even during the early years of therapy.

ObjectiveTo examine the clinical outcomes of systemic lupus erythematosus (SLE) patients with COVID-19 during the Pre-Delta/Delta and Omicron periods.MethodsA retrospective study was conducted in a cohort of adult Puerto Ricans with SLE. Demographic parameters, SLE and COVID-19 manifestations, comorbidities, pharmacologic treatment, SLE exacerbations, hospitalizations, and mortality were determined. SARS CoV-2 infection was confirmed by polymerase chain reaction or antigen tests. Variables were compared between the Pre-delta/Delta and Omicron periods. Also, the proportion of COVID-19 cases and mortality of SLE patients was compared to the general population of Puerto Rico.ResultsOf the entire SLE cohort (n = 347), 169 patients (48.7%) had COVID-19. Twenty-two patients had COVID-19 during the Pre-delta/Delta period and 147 during the Omicron period. The proportion of COVID-19 cases in the SLE cohort was significantly higher when compared to the adult general population of Puerto Rico (25.7%), but no difference in mortality was found. Overall, the clinical outcomes of COVID-19 in the SLE cohort were favorable, with low rates of lupus flares (3.0%), hospitalizations (3.6%), and mortality (0.6%). Patients with COVID-19 during the Pre-delta/Delta period were more likely to have oral ulcers, anti-Smith antibodies, and chronic kidney disease, whereas those during the Omicron period were more likely to have COVID-19 symptoms (rhinorrhea, sore throat, and cough).ConclusionIn summary, is this group of Puerto Ricans with SLE, a high proportion had COVID-19, but disease exacerbation, hospitalization, and mortality rates were low. Few clinical differences were noted in SLE patients when comparing the Pre-delta/Delta and Omicron periods.

Dermatomyositis (DM) and systemic lupus erythematosus (SLE) are chronic rheumatic diseases that can affect multiple organ systems. Both conditions share several similarities, including pathogenic mechanisms, clinical manifestations, and pharmacological treatments. However, the coexistence of DM and SLE is rarely encountered in clinical practice. Here, we present the case of a 42-year-old woman who developed DM, characterized by proximal muscle weakness in the upper and lower extremities, dysphagia, heliotrope rash, periungual erythema, erythematous skin lesions on the neck and arms, elevated serum aldolase and creatine phosphokinase (CPK) levels, and positive anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. A skin biopsy confirmed the diagnosis of dermatomyositis. She was initially treated with high-dose corticosteroids and mycophenolic acid, resulting in early improvement. However, three months after the onset of DM, she presented with persistent DM manifestations and the development of new-onset pancytopenia, arthritis, discoid lesions, positive antinuclear antibodies, and C3 hypocomplementemia, consistent with SLE. Rituximab and tacrolimus were added to her regimen of glucocorticoids and mycophenolic acid, and she responded well to therapy, with resolution of all clinical manifestations by four months after starting rituximab and tacrolimus. At the 18-month follow-up, she remained in complete clinical remission from both DM and SLE. This case underscores the complexity of autoimmune diseases. Although the coexistence of DM and SLE is uncommon, healthcare providers should maintain a high index of suspicion in patients presenting with atypical symptoms or overlapping features. It also emphasizes the challenge of managing multiple autoimmune conditions concurrently.

The Triggering Receptor Expressed on Myeloid Cells-Like Transcript-1 (TLT-1) is a platelet receptor that appears to have a role in inflammation and thrombosis.

Chikungunya fever is a global vector-borne viral disease. Patients with acute chikungunya are usually treated symptomatically. The arthritic phase may be self-limiting. However, many patients develop extremely disabling arthritis that does not improve after months. The aim of this study was to describe the treatment of chikungunya arthritis (CHIKA) patients. A medical records review was conducted in 133 CHIKA patients seen at a rheumatology practice. Patients were diagnosed by clinical criteria and confirmed by the presence of anti-chikungunya IgM. Patients were treated with methotrexate (20 mg/week) and/or leflunomide (20 mg/day) and dexamethasone (0-4 mg/day) for 4 weeks. At baseline visit and 4 weeks after treatment, Disease Activity Score 28 (DAS28) and pain (using a visual analog scale) were ascertained. Five months after the end of treatment, patients were contacted to assess pain, tender joint count, and swollen joint count. The mean age of patients was 58.6 ± 13.7 years, and 119 (85%) were female. After 4 weeks of treatment, mean (SD) DAS28-erythrocyte sedimentation rate (6.0 [1.2] versus 2.7 [1.0], P < 0.001) and pain (81.8 [19.2] to 13.3 [22.9], P < 0.001) scores significantly decreased. A total of 123 patients were contacted 5 months after the end of treatment. Pain score, tender joint count, and swollen joint count significantly declined after 4 weeks of treatment, and the response was sustained for 5 months. In this group of patients with CHIKA, 4-week treatment induced a rapid clinical improvement that was maintained 5 months after the end of therapy; however, the contribution of treatment to these outcomes is uncertain.

OBJECTIVES/GOALS: Cardiovascular disease (CVD) is the most common cause of death in systemic lupus erythematosus (SLE). Genome-wide association studies have identified single nucleotide polymorphisms linked with CVD risk, but the association with SLE is not well established. We aimed to determine associations using machine learning in a multi-ethnic lupus cohort. METHODS/STUDY POPULATION: We will use data from the established SLE cohort study named Genetic Profile Predicting the Phenotype (PROFILE). PROFILE was constituted in 1998 by combining existing cohorts at multiple sites which are also of defined ethnicity (Hispanics of Mexican ancestry and Puerto Rico, African American, and Caucasian). The cohort consists of 3,118 individuals and the database contains socioeconomic–demographic, clinical, laboratory, and genetic variables. Genetic data consist of 196,524 single nucleotide polymorphisms. To detect risk genes and predict an individual’s SLE risk will design a random forest classifier using SNP genotype data. Logistic regression models will be performed with CVD as the outcome, adjusted for age, sex, ethnicity, disease duration, and traditional and nontraditional risk factors for CVD. RESULTS/ANTICIPATED RESULTS: We expect to find several established and new susceptibility genes associated with CVD. DISCUSSION/SIGNIFICANCE: This approach offers an opportunity to characterize distinct genetic risk factors and the relationship of CVD with SLE. These data may be important in the identification of patients at high risk for such events and may allow the design of preventive strategies which may beneficially have an impact on the morbidity and mortality of SLE patients.

Relapsing polychondritis (RPC) is an uncommon autoimmune systemic disease characterized by recurrent inflammation of the cartilage tissue. It can occur alone or in association with other autoimmune diseases, vasculitis, or hematologic disorders. However, the association of RPC with dermatomyositis is extremely rare. Herein, we present a case of a 38-year-old man who developed concurrent RPC and clinically amyopathic dermatomyositis (CADM) manifested by auricular chondritis, nasal chondritis, polyarthritis, gottron papules, fingertip papules, skin biopsy consistent with dermatomyositis, and positive antimelanoma differentiation-associated gene 5 (MDA5) antibodies. RPC features resolved with corticosteroids, but CADM manifestations were resistant to corticosteroids, cyclophosphamide, azathioprine, and hydroxychloroquine. Subsequent therapy with rituximab was effective to control CADM manifestations. This case highlights the importance of recognizing CADM as part of the autoimmune diseases linked with RPC and maintaining a high level of awareness to initiate effective therapy to avoid the long-term complications associated with these conditions.

Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.

Objective To determine if SARS-CoV-2 mRNA vaccination has an impact on the clinical course of systemic lupus erythematosus (SLE). Methods Puerto Ricans with SLE who received mRNA COVID-19 vaccines were studied. Demographic parameters, clinical manifestations, disease activity (per Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), disease damage (per Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), emergency room visits, hospitalizations, and pharmacologic therapy were determined. Baseline variables (prior to vaccination) were compared between patients with and without exacerbation after SARS-CoV-2 vaccination. Among those with exacerbation, clinical outcomes were determined up to 1 year after vaccination. Results Of the entire cohort ( n = 247), 14 (5.7%) had post-vaccination exacerbations. Photosensitivity, oral ulcers, anti-Ro antibodies, higher SLEDAI score, and corticosteroids exposure were associated with post-vaccination flares. Among those with post-vaccination flares, 10 (71.4%) had major organ involvement. No significant differences were observed for mean SLEDAI scores, emergency room visits, hospitalizations, disease damage, and exposure to immunosuppressive drugs before and after SARS-CoV-2 mRNA vaccination. At 12 months of follow-up, all patients were fully controlled without evidence of active disease. Conclusion In our group of SLE patients, 5.7% had a disease flare after SARS-CoV-2 mRNA vaccination. Most had exacerbations involving major organs/systems. Mucocutaneous manifestations, anti-Ro antibodies, disease activity, and corticosteroids were associated with flares. Awareness of these factors and the possibility of a major lupus flare after vaccination with COVD-19 vaccines is critical to provide timely and effective therapy.

ObjectiveThe long‐term impact of childhood‐onset systemic lupus erythematosus (SLE) on health‐related quality of life (HRQoL) in adult SLE patients in comparison to those with adult‐onset SLE is unknown. We aim to examine and compare HRQoL trajectories in adults with adolescent‐ and adult‐onset SLE.MethodsPatients enrolled in the LUpus in MInorities: NAture versus Nurture cohort were included. Adolescent‐onset SLE were those diagnosed before 24 years of age, and adult‐onset SLE were those diagnosed otherwise. Sociodemographic, clinical, medications, behavioral/psychological, and functioning data were obtained. Longitudinal trajectories of the physical component summary (PCS) and the mental component summary (MCS) Short Form 36 health survey scores were compared between the groups using a linear mixed model accounting for time‐dependent and independent covariates.ResultsA total of 470 SLE patients were included (95 with adolescent‐onset SLE and 375 with adult‐onset SLE). The mean ± SD age at diagnosis was 19.7 ± 2.8 years in the adolescent group and 39.3 ± 11.0 years in the adult group. The baseline PCS scores were higher (better physical functioning) in adolescent‐onset SLE than in adult‐onset SLE (38.9 versus 34.3, respectively; P < 0.001); however, the baseline MCS scores were comparable between the groups (41.4 versus 40.5, respectively; P = 0.53). The HRQoL improved equally in both groups with no statistically significant difference within and between the groups (last mean PCS and MCS scores 43.9 and 45.3 in adolescent‐onset SLE; 38.1 and 43 in adult‐onset SLE).ConclusionsAdults with adolescent‐onset SLE exhibited better physical functioning than those in the adult SLE group, despite more severe disease; noteworthy, HRQoL was below the general US population, despite clinically meaningful improvement in HRQoL over time in both groups.