Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study.

BACKGROUND: Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. OBJECTIVE: To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. METHODS: This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. RESULTS: The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P < .001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. LIMITATIONS: Observational study. CONCLUSION: Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.

Association of air quality index (AQI) with incidence of atopic dermatitis in Taiwan: A nationwide population-based cohort study.

BACKGROUND: Air pollutants may aggravate atopic dermatitis (AD). However, the association between Air Quality Index (AQI) and incidence of AD remains unknown. OBJECTIVE: To investigate association between AQI and incidence of AD, using the nationwide cohort in the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We included 21,278,938 participants from the NHIRD not diagnosed with AD before 2008. Long-term average AQI value, obtained from the Taiwan Air Quality Monitoring System Network, before AD diagnosis was calculated and linked for each participant. RESULTS: 199,205 incident cases of AD were identified from 2008 to 2018. Participants were classified into 4 quantiles (Q) by AQI value. With the lowest quantile, Q1, as reference, the AD risk increased significantly in the Q2 group (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.04-1.65), Q3 group (aHR: 4.71, 95% CI: 3.78-6.04), and was highest in the Q4 group (aHR: 13.20, 95% CI: 10.86-16.60). As AQI treated as a continuous variable, an increase of 1 unit of AQI value added 7% of AD risk (aHR, 1.07, 95% CI: 1.07-1.08). LIMITATIONS: The NHIRD lacks detailed information on individual subjects. CONCLUSIONS: The results demonstrated a significant positive association between AQI and incidence of AD with a clear dose-response relationship.

Direct effects of alcohol on gut-epithelial barrier: Unraveling the disruption of physical and chemical barrier of the gut-epithelial barrier that compromises the host-microbiota interface upon alcohol exposure.

The development of alcohol-associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host-environment interface. Emerging evidence has pinpointed the critical role of the intestinal host-microbiota interaction in alcohol-induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first-line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut-epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut-epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium.

Risk of Type 1 Diabetes Mellitus in Patients with Atopic Dermatitis: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Atopic dermatitis (AD) is a disease frequently occurring in children. The immune response is characterized by T-helper (Th)-2-dependent inflammation. Type 1 diabetes mellitus (T1DM) is an autoimmune disease that destroys pancreatic islet beta cells. In contrast, it is mainly mediated by a Th-1-dependent response. An inverted association has been hypothesized between T1DM and AD since Th1 and Th2 responses are mutually inhibitory. METHODS: Data was retrieved from a nationwide healthcare database in Taiwan. A logistic regression model was used to evaluate the association of T1DM in patients with AD within a year. A Cox proportional hazards analysis was used to evaluate the subsequent risk of developing T1DM 1 year after AD diagnosis. RESULTS: We identified 396,461 patients with AD and 1,585,844 age- and sex-matched controls. During the first year of follow-up, after adjusting variates, the association between T1DM and AD showed no statistical differences (odds ratio: 1.40; 95% confidence interval [CI]: 0.83-2.38, p = 0.207). After excluding those T1DM cases within 1 year of AD diagnosis and those with a follow-up duration of less than 1 year, AD did not significantly increase the risk of T1DM (hazard ratio [HR]: 1.02; 95% CI, 0.83-1.25, p = 0.843). CONCLUSIONS: Our study revealed that there was no significant association between AD and T1DM in the first year after AD diagnosis, and there was no increased risk of T1DM in AD patients in the average 5-year follow-up in our study.

Association between vitiligo and risk of retinal detachment: A population-based cohort study in Taiwan.

BACKGROUND: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear. OBJECTIVE: This study examined the risk of RD among vitiligo patients. PATIENTS AND METHODS: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database between 2007 and 2018. A total of 21,132 vitiligo patients were 1:4 matched with non-vitiligo patients by age, sex, and propensity score of comorbidities. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in vitiligo patients. Subgroup analysis was performed. RESULTS: The vitiligo cohort had a significantly higher RD rate than the non-vitiligo cohort (adjusted hazard ratio, 1.44; 95% confidence interval, 1.20-1.72; P-value <0.001). Vitiligo patients who required treatments such as phototherapy, systemic corticosteroids, or immunosuppressants exhibited an even greater risk (adjusted hazard ratio, 1.57; 95% confidence interval, 1.16-2.14; P-value 0.004). CONCLUSION: Our study revealed a 1.44-fold increased risk of RD in vitiligo patients with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remains consistently higher over a 10-year follow-up period.

Multidimensional Super-Resolution Microscopy Unveils Nanoscale Surface Aggregates in the Aging of FUS Condensates.

The intracellular liquid-liquid phase separation (LLPS) of biomolecules gives rise to condensates that act as membrane-less organelles with vital functions. FUS, an RNA-binding protein, natively forms condensates through LLPS and further provides a model system for the often disease-linked liquid-to-solid transition of biomolecular condensates during aging. However, the mechanism of such maturation processes, as well as the structural and physical properties of the system, remains unclear, partly attributable to difficulties in resolving the internal structures of the micrometer-sized condensates with diffraction-limited optical microscopy. Harnessing a set of multidimensional super-resolution microscopy tools that uniquely map out local physicochemical parameters through single-molecule spectroscopy, here, we uncover nanoscale heterogeneities in FUS condensates and elucidate their evolution over aging. Through spectrally resolved single-molecule localization microscopy (SR-SMLM) with a solvatochromic dye, we unveil distinct hydrophobic nanodomains at the condensate surface. Through SMLM with a fluorogenic amyloid probe, we identify these nanodomains as amyloid aggregates. Through single-molecule displacement/diffusivity mapping (SMdM), we show that such nanoaggregates drastically impede local diffusion. Notably, upon aging or mechanical shears, these nanoaggregates progressively expand on the condensate surface, thus leading to a growing low-diffusivity shell while leaving the condensate interior diffusion-permitting. Together, beyond uncovering fascinating structural arrangements and aging mechanisms in the single-component FUS condensates, the demonstrated synergy of multidimensional super-resolution approaches in this study opens new paths for understanding LLPS systems at the nanoscale.

Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations With Implications on Host Gene Dysregulation.

BACKGROUND & AIMS: Hepatocellular carcinogenesis of hepatitis B virus (HBV) infection may arise from integration of viral DNA into the host genome. We aimed to gauge the effect of viral inhibition on transcriptionally active HBV-host integration events and explore the correlation of viral integrations with host gene dysregulation. METHODS: We leveraged data and biospecimens from an interventional trial, in which patients with HBV viremia above 2000 IU/mL and minimally raised serum liver enzyme were randomized to receive tenofovir disoproxil fumarate (TDF) or placebo for 3 years. Total RNA-sequencing was performed on paired liver biopsies taken before and after the 3-year intervention in 119 patients. Virus-host chimeric reads were captured to quantify the number of distinct viral integrations. Dysregulation of a host gene disrupted by viral integration was defined by aberrant expression >2 standard deviations away from samples without viral integration. RESULTS: The TDF (n = 64) and placebo groups (n = 55) were comparable at baseline. Expressed viral integrations were detected in all pre- and posttreatment samples. The number of distinct viral integrations significantly correlated with circulatory biomarkers indicative of viral activities including HBV DNA, RNA, and viral antigens (P < .0003 for all correlations). Moreover, TDF vs placebo achieved a significantly greater reduction in distinct viral integrations, with 3.28-fold and 1.81-fold decreases in the expressed integrations per million reads, respectively (analysis of covariance, P = .037). Besides, viral integrations significantly correlated with host gene dysregulation. CONCLUSION: Inhibition of viral replication reduces the number of transcriptionally active distinct HBV-host DNA integrations in patients with substantial viremia. Given the mutagenic potentials of viral integrations, such treatment effects should be considered in patient management.

Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: a nationwide cohort study.

OBJECTIVES: To compare the risk of psoriatic arthritis (PsA) in psoriasis (PsO) patients treated with acitretin vs disease-modifying antirheumatic drugs (DMARDs). METHODS: This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan-Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and comorbidities. RESULTS: The study included 1,948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P=0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65-1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. CONCLUSION: Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients.

Maskless lithography for large area patterning of three-dimensional microstructures with application on a light guiding plate.

This paper presents a maskless lithography system that can perform three-dimensional (3D) ultraviolet (UV) patterning on a photoresist (PR) layer. After PR developing processes, patterned 3D PR microstructures over a large area are obtained. This maskless lithography system utilizes an UV light source, a digital micromirror device (DMD), and an image projection lens to project a digital UV image on the PR layer. The projected UV image is then mechanically scanned over the PR layer. An UV patterning scheme based on the idea of obliquely scanning and step strobe lighting (OS3L) is developed to precisely control the spatial distribution of projected UV dose, such that desired 3D PR microstructures can be obtained after PR development. Two types of concave microstructures with truncated conical and nuzzle-shaped cross-sectional profiles are experimentally obtained over a patterning area of 160 ×115 mm2. These patterned microstructures are then used for replicating nickel molds and for mass-production of light-guiding plates used in back-lighting and display industry. Potential improvements and advancements of the proposed 3D maskless lithography technique for future applications will be addressed.

Risk of Psychiatric Disorders in Patients with Psoriasis Prescribed Acitretin versus Disease-Modifying Antirheumatic Drugs: A Nationwide Matched Cohort Study.

BACKGROUND: Acitretin has been linked to the development of psychiatric disturbance. OBJECTIVES: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs). METHODS: This is a nationwide matched cohort study. From Taiwan's National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs). RESULTS: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23-1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56-4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75-5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age. CONCLUSIONS: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients.

Risk of Serious Infections in Patients with Bullous Pemphigoid: A Population-based Cohort Study.

Patients with bullous pemphigoid are susceptible to serious infections, which are the leading cause of death in these patients. The aims of this population-based cohort study were to investigate the incidence and spectrum of serious infections in patients with bullous pemphigoid and to identify associated risk factors. The outcome measure was any infection requiring hospitalization. Hazard ratios with 95% confidence intervals were estimated using subdistribution hazard models. In total, 12,300 patients with bullous pemphigoid and 49,200 matched controls were identified through the National Health Insurance Research Database in Taiwan. Within 2 years of bullous pemphigoid diagnosis, 5,006 (40.7%) patients developed serious infections, with an incidence of 385.5/1,000 person-years. Patients with bullous pemphigoid were twice as likely to develop serious infections as controls (adjusted hazard ratio, 2.01; 95% confidence interval 1.92-2.10). Systemic corticosteroid use was the strongest risk factor, resulting in a 2-fold increase in the risk for serious infections. Other independent risk factors were advanced age, female sex, low income, and certain comorbidities. In conclusion, this study demonstrated an increased risk of serious infections following a diagnosis of bullous pemphigoid. Prophylaxis of serious infections through active intervention with the risk factors may be essential in reducing the morbidity and mortality associated with bullous pemphigoid.

Proactive therapeutic drug monitoring of vincristine in pediatric and adult cancer patients: current supporting evidence and future efforts.

Vincristine (VCR), an effective antitumor drug, has been utilized in several polytherapy regimens for acute lymphoblastic leukemia, neuroblastoma and rhabdomyosarcoma. However, clinical evidence shows that the metabolism of VCR varies greatly among patients. The traditional based body surface area (BSA) administration method is prone to insufficient exposure to VCR or severe VCR-induced peripheral neurotoxicity (VIPN). Therefore, reliable strategies are urgently needed to improve efficacy and reduce VIPN. Due to the unpredictable pharmacokinetic changes of VCR, therapeutic drug monitoring (TDM) may help to ensure its efficacy and to manage VIPN. At present, there is a lot of supporting evidence for the suitability of applying TDM to VCR therapy. Based on the consensus guidelines drafted by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), this review aimed to summarize various available data to evaluate the potential utility of VCR TDM for cancer patients. Of note, valuable evidence has accumulated on pharmacokinetics variability, pharmacodynamics, drug exposure-clinical response relationship, biomarkers for VIPN prediction, and assays for VCR monitoring. However, there are still many relevant clinical pharmacological questions that cannot yet be answered merely based on insufficient evidence. Currently, we cannot recommend a therapeutic exposure range and cannot yet provide a dose-adaptation strategy for clinicians and patients. In areas where the evidence is not yet sufficient, more research is needed in the future. The precision medicine of VCR cannot rely on TDM alone and needs to consider the clinical, environmental, genetic background and patient-specific factors as a whole.

Methotrexate did not add skin cancer risk in patients with psoriasis receiving narrow-band ultraviolet B phototherapy: a nationwide retrospective cohort study.

BACKGROUND: In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly employed for patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrow-band ultraviolet B (NB-UVB) has rarely been explored. OBJECTIVES: To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis. METHODS: We conducted a retrospective cohort study of data in Taiwan National Health Insurance Research Database from 1997 to 2013. We performed cumulative incidences and multivariate analysis using competing risk regression model, comparing skin cancer risk between cohorts of combination therapy and using NB-UVB alone, matched by relative confounders. We further conducted sensitivity analysis for those receiving higher MTX dosage. Standardized incidence ratio (SIR) was calculated for skin cancer risk. RESULTS: We enrolled 3203 subjects in each cohort. No significant differences in skin cancers were noted between the two cohorts in the cumulative incidences (log-rank test, p = 0.282) and hazard ratio (HR) (adjusted HR = 0.50, 95% CI 0.15, 1.63, p= 0.247) on the competing risk regression model. There were also no significant differences between those receiving higher dose MTX and UVB alone in the cumulative incidences of skin cancers (p = 0.227) and HR (adjusted HR = 0.29, 95% CI 0.04, 2.21, p = 0.231) in the multivariate analysis. There was no significant difference of SIR between the two cohorts compared to the general population. CONCLUSIONS: MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB in the Taiwanese population.

Association between chronic kidney disease and risk of bullous pemphigoid: a nationwide population-based cohort study.

BACKGROUND: Studies have shown that bullous pemphigoid (BP) occurs in patients with chronic kidney disease (CKD). However, the risk of developing BP in patients with CKD remains inconclusive. OBJECTIVE: To investigate whether CKD increases the risk of BP. METHODS: Participants were recruited from the National Health Insurance Database of Taiwan between 2007 and 2018. Overall, 637,664 newly diagnosed patients with CKD and 637,664 age-, sex-, and comorbidity-matched non-CKD participants were selected. A competing risk model was used to evaluate the risk of development of BP. RESULTS: After adjusting for age, sex, and comorbid diseases in the multivariate model, CKD was a significant risk factor for BP (adjusted hazard ratio [aHR]: 1.29; 95% confidence interval [CI]: 1.17-1.42; p < 0.001). CKD patients were classified into the dialytic or non-dialytic groups and compared to non-CKD participants, and this revealed that patients with dialysis-dependent CKD had the highest risk of BP (aHR 1.75; 95% CI 1.51-2.03), followed by patients with non-dialysis-dependent CKD (aHR 1.20; 95% CI 1.08-1.32). LIMITATIONS: We lacked detailed laboratory data on the severity of CKD. CONCLUSIONS: Compared with individuals without CKD, those with CKD had a 1.3-fold increased risk of BP. Patients with dialysis-dependent CKD had an even higher BP risk (1.8-fold).

Association between early life laxative exposure and risk of allergic diseases A nationwide matched cohort study.

BACKGROUND: The early life microbiome can shape human immunity. Recent studies have revealed gut dysbiosis after laxative administration. OBJECTIVE: To investigate the impact of infantile laxative exposure on subsequent allergic diseases. METHODS: This nationwide matched cohort study was conducted using Taiwan's National Health Insurance Research Database for the period 1997 to 2013. A total of 32,986 patients who had complete information of maternal history and delivery modes were identified. We included 291 children having laxatives for at least 7 days within the first 6 months of life and 1164 reference children not receiving laxatives, matching by sex, propensity score, number of hospital visits, and maternal age at delivery. Demographic characteristics and maternal factors were compared, and cumulative incidences of allergic diseases were calculated. Cox proportional hazard model was used to evaluate associations. RESULTS: The 5-year cumulative incidence of allergic diseases in the laxative cohort was significantly higher than that in the reference cohort (49.81% vs 41.68%; P = .01). Early life laxative exposure (adjusted hazard ratio, 1.61; 95% confidence interval, 1.32-1.97) was independently associated with allergic disease development. Other independent risk factors included preterm, male sex, maternal allergic diseases, and prenatal laxative use. Multivariable stratified analyses verified the association between early life laxative exposure and subsequent allergic disease development in all subgroups of children, including those born to mothers without allergic diseases or prenatal laxative use. CONCLUSION: Early life laxative exposure is associated with allergic disease development.

Risk of malignancy in patients with psoriasis receiving systemic medications: A nested case-control study.

Large-scale, real-world studies on the side effects of systemic therapies (including biologics) in patients with psoriasis are limited. We aimed to calculate the risk of malignancy in patients with psoriasis who were treated with systemic medications. Nested case-control analyses were performed among psoriasis patients without a history of malignancy. We recruited 4188 patients with newly diagnosed psoriasis and successive malignancies, and 8376 matched controls from the National Health Insurance Research Database in Taiwan. The therapy duration was within 5 years before malignancy onset and further stratified into two groups according to the duration of medication usage. Multivariate conditional logistic regression adjusted for potential confounders was used to estimate malignancy risk associated with systemic treatments. Among psoriasis patients, long-term (> 12 months) treatment with cyclosporine increased the risk of malignancy compared with no exposure (odds ratio, 1.57; p = 0.01). Short-term (≤ 12 months) or long-term (> 12 months) use of other systemic treatments, including methotrexate, azathioprine, systemic retinoids, mycophenolate mofetil, sulfasalazine, etanercept, adalimumab, and ustekinumab, was not associated with an increased risk of malignancy in patients with psoriasis. Long-term treatment with cyclosporine increased the risk of malignancy in patients with psoriasis by 1.57-fold.

Long-Term Risk of Autoimmune Diseases other than Systemic Lupus Erythematosus in Cutaneous Lupus Erythematosus-Alone Patients: A 10-Year Nationwide Cohort Study.

BACKGROUND: Up to 25% of patients with cutaneous lupus erythematosus (CLE) can develop systemic lupus erythematosus (SLE). However, the risk of autoimmune diseases other than SLE in CLE patients who have only skin manifestations (CLE-alone) has rarely been explored. OBJECTIVE: To investigate the long-term risk and independent factors of non-SLE autoimmune diseases among CLE-alone patients. METHOD: A nationwide cohort study using the Taiwanese National Health Insurance Research Database 1997-2013. CLE patients and matched subjects were included. Cumulative incidences of autoimmune diseases after 1 year of CLE-alone diagnosis were compared. Cox proportional hazard model was also performed. RESULTS: A total of 971 CLE-alone patients and 5,175 reference subjects were identified. The 10-year cumulative incidence of autoimmune diseases other than SLE was significantly elevated in the CLE-alone cohort (9.00%, 95% confidence interval [CI] 6.72-11.29) than in the reference cohort (4.20%, 95% CI 3.53-4.87%) (p < 0.001). CLE-alone was independently associated with non-SLE autoimmune diseases (adjusted hazard ratio 1.55, 95% CI 1.10-2.18). Among CLE-alone patients, females and those taking long-term systemic corticosteroids (a proxy for extensive disease) were associated with non-SLE autoimmune diseases after adjusting for the number of repeated autoimmune laboratory tests. CONCLUSION: CLE-alone is independently associated with future non-SLE autoimmune diseases.

Association of Immunosuppressants with Mortality of Patients with Bullous Pemphigoid: A Nationwide Population-Based Cohort Study.

BACKGROUND: Bullous pemphigoid (BP) is a common autoimmune blistering skin disease with substantial mortality. OBJECTIVE: To identify whether the use of immunosuppressants was associated with reduced mortality in BP patients. METHODS: The data for this study were obtained from the National Health Insurance Research Database in Taiwan from January 1, 1997 to December 31, 2013. Those BP patients receiving any immunosuppressant for ≥28 days per month for 3 consecutive months were defined as the immunosuppressant cohort. In total, 452 BP patients on immunosuppressants were matched 1:4 by age, sex, propensity score of comorbidities, and use of tetracycline with 1,808 BP patients taking only corticosteroids. RESULTS: The immunosuppressant cohort had a significantly lower 5-year mortality rate than the corticosteroid cohort (0.57 vs. 0.67). In the multivariable regression analysis adjusted for covariates, the use of immunosuppressants significantly reduced the risk of mortality (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.68-0.90, p < 0.001). Hyperlipidemia also reduced risk of mortality. However, age, diabetes, renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, and dementia were significant risk factors for mortality. In the subgroup analysis, the risk of mortality decreased most substantially in those aged <70 years (HR: 0.45, 95% CI: 0.28-0.72). CONCLUSION: Immunosuppressant use was associated with a 22% reduced risk of BP mortality. The effects were more substantial in those aged <70 years, with a 55% reduced risk of mortality.

Association between sodium-glucose co-transporter 2 inhibitors and risk of psoriasis in patients with diabetes mellitus: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) treatment may exert anti-inflammatory effects by modulating the NOD-like receptor family pyrin domain-containing 3 inflammasome and interleukin-17/23 inflammatory axis, which are both involved in the pathogenesis of psoriasis. However, the relationship between SGLT2i treatment and psoriasis remains unclear. AIM: To investigate the association between SGLT2i treatment and incident psoriasis. METHODS: Using the Taiwan National Health Insurance Database for the period 2007-2018, we matched 103 745 patients with Type 2 diabetes mellitus (T2DM) receiving SGLT2i with a control group of patients with T2DM who did not use SGLT2i, matching them in a 1 : 2 ratio by age, sex, diabetes duration, insulin use and comorbidities, and evaluating the psoriasis risk in both groups. RESULTS: The incident psoriasis risk did not significantly differ between the SGLT2i and control groups [hazard ratio (HR) = 1.24, 95% CI 0.95-1.64] after adjustment for potential confounders. Insulin use (HR = 1.65, 95% CI 1.24-2.19) and chronic liver disease and cirrhosis (HR = 1.34, 95% CI 1.01-1.77) were significantly associated with increased psoriasis risk. A slightly increased psoriasis risk was also detected in certain SGLT2i user subgroups, especially those with renal disease (HR = 2.73, 95% CI 1.45-5.13). CONCLUSION: SGLT2i-mediated protective effects in psoriasis could not be established. SGLT2i treatment increased psoriasis risk by 2.7-fold in patients with T2DM exhibiting renal diseases.