A Case of Painless Elderly-Onset Rheumatoid Arthritis.

Rheumatoid arthritis (RA) has multiple manifestations. Patients present with a variety of symptoms and varying levels of severity. Elderly-onset rheumatoid arthritis (EORA) is described as RA with onset after 60 years of age. EORA can present with different clinical and laboratory findings compared to RA in a younger patient, making awareness of the condition important. Diagnosing inflammatory arthritis can be especially challenging in an elderly population where symptoms are poorly reported and communication is often difficult. We report the case of an elderly patient whose presentation with persistent tachycardia and raised inflammatory markers led to a diagnosis of EORA. This case details an atypical presentation of EORA with convincing diagnostic features for the disease without any joint symptoms reported. Clinicians should be aware of the differences in the typical presentation of EORA versus RA, the challenges of diagnosing inflammatory arthritis in elderly, isolated patients, and the importance of early diagnosis.

An Unusual Presentation of Crohn's Disease in an Elderly Patient: A Report of a Rare Case.

Crohn's disease is a chronic inflammatory bowel disease that primarily affects the terminal ileum and proximal colon. The exact cause is unknown but likely involves genetic factors, environmental triggers, and immune dysregulation. This case report delineates the choice of diagnostics for a 70-year-old patient presenting with symptoms indicative of small bowel obstruction. Initial assessments and imaging suggested a common clinical scenario, yet further investigation uncovered an unexpected diagnosis of Crohn's disease, a condition infrequently encountered in this age demographic.

La artritis reumatoide de inicio en el anciano recibe terapias menos agresivas que la artritis reumatoide de inicio en el adulto en una cohorte argentina / Elderly-onset rheumatoid arthritis receives less aggressive therapies than young-onset rheumatoid arthritis in an Argentinian cohort

Antecedentes y objetivo: Cuando la artritis reumatoide (AR) comienza después de los 60años se denomina artritis reumatoide de inicio en el anciano, y cuando se inicia antes, artritis reumatoide de inicio en el adulto. Son escasos los estudios latinoamericanos que compararon ambos grupos. El objetivo del estudio fue evaluar diferencias en las características clínicas, en la evolución y en la elección terapéutica entre los pacientes con AR de inicio antes o después de los 60años. Materiales y métodos: Estudio observacional de pacientes con AR atendidos en forma consecutiva en cuatro centros de Argentina. Se recolectaron datos sociodemográficos, comorbilidades, manifestaciones clínicas al diagnóstico, presencia de factor reumatoide y/o anti-proteínas cíclicas citrulinadas (PCC) y tratamientos recibidos. En la última visita se registraron las articulaciones tumefactas o dolorosas, la evaluación de la actividad de la enfermedad por el paciente y por el médico, la presencia de erosiones radiográficas y el estado funcional mediante el HAQ-DI. Resultados: Se analizaron 51 pacientes de cada grupo. El grupo de AR del anciano tuvo significativamente mayor proporción de fumadores (58,8% vs 35,3%, p=0,029), de antecedentes cardiovasculares (54,9% vs 21,6%, p=0,001), de inicio abrupto (49% vs 29,4%, p=0,034) o con síntomas similares a la PMR (19,6% vs 0%, p=0,001), menores dosis de metotrexato: 19mg (15-25) vs 21,9mg (20-25) (p=0,0036) y con mayor frecuencia no recibieron FAMEb o FAMEsd. Discusión y conclusiones: Se han descrito los beneficios del tratamiento intensivo en pacientes con AR. En este trabajo, el empleo de FAME en el grupo de AR de inicio en el anciano fue menos intensivo, sugiriendo que la edad avanzada constituye una barrera en la elección terapéutica.(AU)

Objectives: When rheumatoid arthritis (RA) starts after the age of 60 it is called elderly-onset rheumatoid arthritis (EORA) and when it starts earlier, young-onset rheumatoid arthritis (YORA). There are few Latin American studies that compared both groups. The objective of the study was to evaluate differences in the clinical characteristics, evolution and treatment among patients with RA with onset before or after 60years of age. Materials and methods: Observational study of patients with RA attended consecutively in four centers in Argentina. Sociodemographic data, comorbidities, clinical manifestations at diagnosis, presence of rheumatoid factor and/or anti-CCP (cyclic citrullinated peptide) and treatments received were collected. At the last visit, swollen and tender joints, assessment of disease activity by the patient and physician, the presence of radiographic erosions, and functional status using the HAQ-DI were recorded. Results: Fifty-one patients from each group were analyzed. The EORA group had a significantly higher proportion of smokers (58.8% vs. 35.3%, P=.029), cardiovascular history (54.9% vs. 21.6%, P=.001), abrupt onset (49% vs. 29.4%, P=.034) or with symptoms similar to PMR (19.6% vs. 0%, P=.001). Lower methotrexate doses were used in the EORA group: 19mg (15-25) vs. 21.9mg (20-25) (P=.0036) and more frequently did not receive bDMARDs or tsDMARDs. Discussion and conclusions: The benefits of intensive treatment in patients with RA have been described. In this study, the use of DMARDs in the EORA group was less intensive, suggesting that advanced age constitutes a barrier in the therapeutic choice.(AU)

Multiple Ulcers in the Ileum and Lymphadenopathy Following the Usage of Methotrexate in a Patient With Rheumatoid Arthritis: A Case Report.

This case report aims to highlight a rare occurrence of severe anemia and lymphadenopathy secondary to methotrexate (MTX)-induced ileal mucosa damage in a patient with elderly onset rheumatoid arthritis (EORA). We present the case of a 72-year-old female with a history of EORA, treated with MTX, who exhibited hematochezia without accompanying pain, diarrhea, or known infectious contacts. Diagnostic investigations included imaging and endoscopic procedures. The patient's presentation of severe anemia was atypical, given the absence of significant pain or discomfort associated with EORA. The lack of active bleeding observed during endoscopy, coupled with multiple ileal ulcers, suggested a chronic progression of mucosal damage. Laboratory findings, including normal lactate dehydrogenase, soluble interleukin-2 receptor levels, and the absence of malignancy in mucosal biopsies, ruled out MTX-induced lymphoma. The patient's condition improved with the cessation of MTX and the introduction of symptomatic treatment and anemia management. This case underscores the need for vigilant monitoring and comprehensive evaluation in patients with RA, especially the elderly, treated with MTX. It also highlights the importance of considering drug-induced complications in the differential diagnosis of anemia. The case demonstrates the necessity of a personalized approach to treatment, emphasizing regular follow-ups and adjustments based on the patient's response to therapy. This report contributes to the growing body of evidence on the complexities of managing RA in the elderly, particularly regarding the side effects of common medications like MTX.

Elderly-onset rheumatoid arthritis receives less aggressive therapies than young-onset rheumatoid arthritis in an Argentinian cohort.

OBJECTIVES: When rheumatoid arthritis (RA) starts after the age of 60 it is called elderly-onset rheumatoid arthritis (EORA) and when it starts earlier, young-onset rheumatoid arthritis. (YORA). There are few Latin American studies that compared both groups. The objective of the study was to evaluate differences in the clinical characteristics, evolution and treatment among patients with RA with onset before or after 60 years of age. MATERIALS AND METHODS: Observational study of patients with RA attended consecutively in four centers in Argentina. Sociodemographic data, comorbidities, clinical manifestations at diagnosis, presence of rheumatoid factor and/or anti-CCP (cyclic citrullinated peptide) and treatments received were collected. At the last visit, swollen and tender joints, assessment of disease activity by the patient and physician, the presence of radiographic erosions, and functional status using the HAQ-DI were recorded. RESULTS: 51 patients from each group were analyzed. The EORA group had a significantly higher proportion of smokers (58.8% vs. 35.3%, p = 0.029), cardiovascular history (54.9% vs. 21.6%, p = 0.001), abrupt onset (49% vs. 29.4%, p = 0.034) or with symptoms similar to PMR (19.6% vs. 0%, p = 0.001). Lower methotrexate doses were used in the EORA group: 19 mg (15-25) vs. 21.9 mg (20-25) (p = 0.0036) and more frequently did not receive bDMARDs or tsDMARDs. DISCUSSION AND CONCLUSIONS: The benefits of intensive treatment in patients with RA have been described. In this study, the use of DMARDs in the EORA group was less intensive, suggesting that advanced age constitutes a barrier in the therapeutic choice.

Frailty risk and treatment strategy in elderly-onset inflammatory bowel disease. A Norwegian nationwide population-based registry study.

BACKGROUND/AIMS: To determine real-world medical and surgical treatment patterns in elderly-onset inflammatory bowel disease in a nationwide cohort, and to investigate associations between frailty and treatment choices. METHODS: Norwegian health registries were used to identify adult-onset (born 1950-1989) and elderly-onset (born 1910-1949) patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed 2010-2017 (n = 13,006). Patients were classified as no, low and intermediate/high frailty risk after the Hospital Frailty Risk Score. Outcomes included use of medical and surgical treatment. RESULTS: Within five years, elderly-onset patients received less biologics (13% [CD], 7% [UC]) and immunomodulators (24% [CD], 11% [UC]), and major surgery was more frequent (22% [CD], 9% [UC]) than in adult-onset. Respective log rank tests were significant (p < 0.01). Compared to no frailty risk groups, elderly-onset UC with intermediate/high frailty risk had lower probability of starting biologics (4% versus 9%), immunomodulators (7% versus 13%) and 5-aminosalisylic acids (66% versus 84%), and elderly-onset CD with intermediate/high frailty risk had higher probability of starting prednisolone (67% versus 49%). Respective log rank tests were significant (p < 0.05). CONCLUSIONS: Elderly-onset patients received less biologics and immunomodulators and a larger proportion underwent major surgery. Frailty risk in elderly-onset patients was associated with increased use of prednisolone, and less use of 5-aminosalisylic acids, immunomodulators and biologics.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

BACKGROUND: Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. OBJECTIVE: To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. METHODS: We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. RESULTS: Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). CONCLUSIONS: These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

Characteristics of patients presenting with concomitant carpal tunnel syndrome at the initial diagnosis with rheumatoid arthritis.

OBJECTIVE: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). METHODS: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). RESULTS: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. CONCLUSIONS: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA.

Acute Onset Rheumatoid Vasculitis With Polyarthritis and Erythema: A Case Report.

We present the case of a woman in her 70s who was diagnosed with rheumatoid vasculitis (RV) after initially presenting with systemic joint pain and erythema. RV, a rare complication of rheumatoid arthritis, involves inflammation of blood vessels, leading to various skin manifestations. The patient's complaints included fever, generalized joint pain, and skin manifestations that initially resembled erythema multiforme. However, a skin biopsy revealed vasculitis, which guided the RV diagnosis. Although rheumatoid arthritis primarily affects the joints, systemic implications such as RV can arise in rare cases. This case underscores the importance of a holistic and meticulous diagnostic approach, especially in older patients, as early detection and treatment are crucial for managing disease progression and associated complications. Collaborative care involving multidisciplinary teams is vital to achieving optimal outcomes in complex cases.

A case of cryopyrin-associated periodic syndrome due to somatic mosaic mutation complicated with recurrent circinate erythematous psoriasis.

Cryopyrin-associated periotic syndrome (CAPS) is a rare autoinflammatory disease (AID) caused by genetic variants in innate immunity genes. AIDs, including CAPS, mediate proinflammatory cytokines such as interleukin (IL)-1 and IL-18 and result in severe systemic inflammation. A gain-of-function mutation in the NLRP3 gene, which encodes the protein cryopyrin, was identified to be responsible for CAPS in 2001, and since then several additional pathogenic mutations have been found. Moreover, other phenotypes have been identified based on severity and symptomatology, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID)/chronic neurologic cutaneous articular syndrome (CINCA). Prompt diagnosis of CAPS remains challenging, however, due to unspecific, extensive clinical signs, and delayed diagnosis and treatment targeting IL-1 lead to multiorgan damage. Another factor complicating diagnosis is the existence of somatic mosaic mutations in the NLRP3 gene in some cases, resulting in symptoms and clinical courses that are atypical. The frequency of somatic mosaic mutations in CAPS was estimated to be 19% in a systematic review. Psoriasis is a chronic inflammatory skin disease that affects about 3% of the global population. Although no reports have shown complication between CAPS and psoriasis, these diseases have several similarities and potential relationships, for instance activation of Th17 cells in the dermis and increased NLRP3 gene expression in psoriatic skin compared with normal skin. Here we report a case of CAPS due to a somatic mosaic mutation with recurrent circinate erythematous psoriasis.

Elderly-Onset Rheumatoid Arthritis: Characteristics and Treatment Options.

Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.

Newly Diagnosed Type 1 Diabetes in an Elderly Patient.

Type 1 diabetes (T1D) is typically diagnosed in young people; however, it can appear at any age. Its incidence in adulthood is not as well-known as in childhood, particularly if it is diagnosed in geriatric age. T1D diagnosed in adulthood can be explained by the development of antibodies in adulthood or also by the existence of slow-disease progressors. A 71-year-old normal-weight woman presented to the Emergency Department complaining of polyuria, polydipsia, and tiredness. She was identified with hyperglycemia (450mg/dL) and high blood and urine ketone bodies. Her arterial gasometry revealed mild metabolic ketoacidosis. Further laboratory work-up was remarkable for positive anti-GAD and anti-ICA antibodies and her HbA1c was 14.1%. The diagnosis of T1D was established. A urinary infection was also identified. The patient's symptoms in association with metabolic ketoacidosis, in the presence of high titers of more than one positive T1D-related antibody, have helped us to diagnose T1D in this elderly woman. A prompt diagnosis enabled us to establish adequate diabetes treatment. The urinary infection was probably a trigger to the symptomatic phase of diabetes.  T1D can be diagnosed at any age, even in elderly patients. A prompt T1D diagnosis can avoid the misdiagnosis of type 2 diabetes (T2D), enabling the beginning of correct medication earlier.

Glial autoantibody prevalence in Chinese optic neuritis with onset after age 45: clinical factors for diagnosis.

Purpose: As glial autoantibody testing is not yet available in some areas of the world, an alternative approach is to use clinical indicators to predict which subtypes of middle-aged and elderly-onset optic neuritis (ON) have manifested. Method: This study was a single-center hospital-based retrospective cohort study. Middle-aged and elderly-onset ON patients (age > 45 years) who had experienced the first episode of ON were included in this cohort. Single- and multi-parametric diagnostic factors for middle-aged and elderly-onset myelin oligodendrocyte glycoprotein immunoglobulin-associated ON (MOG-ON) and aquaporin-4 immunoglobulin-related ON (AQP4-ON) were calculated. Results: From January 2016 to January 2020, there were 81 patients with middle-aged and elderly-onset ON, including 32 (39.5%) AQP4-ON cases, 19 (23.5%) MOG-ON cases, and 30 (37.0%) Seronegative-ON cases. Bilateral involvement (47.4%, P = 0.025) was most common in the MOG-ON group. The presence of other concomitant autoimmune antibodies (65.6%, P = 0.014) and prior neurological history (37.5%, P = 0.001) were more common in the AQP4-ON group. The MOG-ON group had the best follow-up best-corrected visual acuity (BCVA) (89.5% ≤ 1.0 LogMAR, P = 0.001). The most sensitive diagnostic factors for middle-aged and elderly-onset MOG-ON were 'follow-up VA ≤ 0.1 logMAR' (sensitivity 0.89), 'bilateral involvement or follow-up VA ≤ 0.1 logMAR' (sensitivity 0.95), 'bilateral involvement or without neurological history' (sensitivity 1.00), and 'follow-up VA ≤ 0.1 logMAR or without neurological history' (sensitivity 1.00), and the most specific factor was 'bilateral involvement' (specificity 0.81). The most sensitive diagnostic factors for middle-aged and elderly-onset AQP4-ON were 'unilateral involvement' (sensitivity 0.88), 'unilateral involvement or neurological history' (sensitivity 0.91), and 'unilateral involvement or other autoimmune antibodies' (sensitivity 1.00), and the most specific factor was neurological history (specificity 0.98). Conclusion: Based on our cohort study of middle-aged and elderly-onset ON, MOG-ON is less prevalent than AQP4-ON and Seronegative-ON. Using multiple combined parameters improves the sensitivity and negative predictive value for diagnosing middle-aged and elderly-onset MOG-ON and AQP4-ON. These combined parameters can help physicians identify and treat middle-aged and elderly-onset ON early when glial autoantibody status is not available.

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

INTRODUCTION: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. METHODS: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. RESULTS: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg. CONCLUSION: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

Association of air pollution and genetic risks with incidence of elderly-onset atopic dermatitis: A prospective cohort study.

BACKGROUND: Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. OBJECTIVES: To explore the association between genes and air pollution on incident elderly-onset AD. MATERIAL AND METHODS: This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. RESULTS: 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. CONCLUSION: Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes.

CD8+ Regulatory T Cell Deficiency in Elderly-Onset Rheumatoid Arthritis.

Elderly-onset rheumatoid arthritis (EORA) is associated with higher disease activity and accelerated joint destruction compared with young-onset RA (YORA). However, the underlying immunological mechanism remains unclear. Regulatory T cells (Tregs) are an immunosuppressive T cell subset, and CD4+ Tregs are deficient and/or dysfunctional in RA; however, CD8+ Tregs have not been fully examined in RA. Here, we aimed to determine the role of CD8+ Tregs, particularly in EORA. A total of 40 patients (EORA, n = 17; YORA, n = 23) were cross-sectionally enrolled. Current disease activity and treatment were comparable between the two groups; however, levels of multiple cytokines, including IL-1ß, TNFα, interferon (IFN)-γ, IL-2, and IL-10, were significantly increased in EORA. The number of CD4+ Tregs did not differ between the groups (p = 0.37), but those of CD8+ Tregs were significantly decreased in EORA (p = 0.0033). The number of CD8+ Tregs were inversely correlated with plasma matrix metalloprotease (MMP)-3 levels (r = -0.3331, p = 0.036). Our study results revealed an intrinsic deficiency of CD8+ Tregs in patients with EORA, which leaves synovitis unchecked with excessive MMP-3 release. A therapeutic approach to restore CD8+ Tregs may provide a new avenue for the treatment of EORA.