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.

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.

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.

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).

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.

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.

Drug-induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan.

BACKGROUND & AIMS: Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. METHODS: We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. RESULTS: A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P < .003). Chronic kidney disease with high-dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol-induced DILI with SCAR. The HLA-B*5801 was associated with a high risk and mortality of allopurinol-induced DILI with SCAR. Likewise, the HLA-B*1502 was closely related to carbamazepine-induced DILI with SCAR. CONCLUSIONS: DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA-B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol-induced DILI with SCAR.

Infantile infection and antibiotic exposure in association with pediatric psoriasis development: A nationwide nested case-control study.

BACKGROUND: Microbiol dysbiosis and antibiotic exposure have been implicated in the pathogenesis of pediatric inflammatory diseases. OBJECTIVES: To investigate the impacts of infantile infection and antibiotic exposure on pediatric psoriasis development. METHODS: This is a nationwide nested case-control study. From the National Health Insurance Research Database of Taiwan, a total of 1527 patients with pediatric psoriasis were identified and matched with 15,270 reference individuals without psoriasis, for the period of 2000 to 2017. Demographic characteristics and comorbidities were compared. Conditional stepwise logistic regression analysis was conducted to examine the associations. RESULTS: The mean ages were 9.9 ± 3.7 years in both groups. Atopic dermatitis (adjusted odds ratio [aOR], 2.07; 95% confidence interval [CI], 1.84-2.32) and family history of psoriasis, especially of the mother (aOR, 9.86; 95% CI, 6.89-14.10) or other first-degree relatives (aOR, 5.49; 95% CI, 3.91-7.70), were independently associated with pediatric psoriasis on multivariate analyses. Skin viral and bacterial infections (aOR, 1.35; 95% CI, 1.13-1.62) and fungal infections (aOR, 1.71; 95% CI, 1.44-2.04) in the first 2 years of life were significantly associated with pediatric psoriasis. Systemic antibiotic exposure was not. These results were consistent at different time periods across sensitivity analyses. LIMITATION: Information about diet and lifestyle was not available. CONCLUSION: Skin infections at an early age were associated with pediatric psoriasis development.

Obesity, but Not Metabolic Diseases, Is Associated with Risk of Psoriasis: A Population-Based Cohort Study in Taiwan.

BACKGROUND: Obesity and metabolic diseases including diabetes, hyperlipidemia, and hypertension are reportedly associated with an increased risk of psoriasis. However, few prospective studies have investigated the association of obesity and metabolic diseases with the risk of psoriasis. OBJECTIVE: To examine whether obesity or metabolic diseases increase the risk of psoriasis. METHODS: Participants were collected from 4 rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident cases of psoriasis were identified from the National Health Insurance database. Participants were followed from the time of the National Health Interview Survey interview until December 31, 2017, or until a diagnosis of psoriasis was made or the participant died. The Cox regression model was used for the analyses. RESULTS: Of 60,136 participants, 406 developed psoriasis during 649,506 person-years of follow-up. Compared to participants with a BMI of 18.5-22.9, the adjusted hazard ratios (aHR) of psoriasis were 1.34 (95% CI 1.05-1.71) for a BMI of 25.0-29.9 and 2.70 (95% CI 1.95-3.72) for a BMI ≥30. Neither individual nor multiple metabolic diseases were associated with incident psoriasis. Participants with a BMI ≥30 were at significantly higher risk of both psoriasis without arthritis (aHR 2.60; 95% CI 1.85-3.67) and psoriatic arthritis (aHR 3.96; 95% CI 1.45-10.82). CONCLUSION: Obesity, but not metabolic diseases, significantly increased the risk of psoriasis.

Effect of energy per atom (E/n) on the Ar gas cluster ion beam (Ar-GCIB) and O2+ cosputter process.

Gas cluster ion beam (GCIB) is a promising technique for preserving molecular structures during ion sputtering and successfully profiling biological and soft materials. However, although GCIB yields lower damage accumulation compared with C60+ and monoatomic ion beams, the inevitable alteration of the chemical structure can introduce artifacts into the resulting depth profile. To enhance the ionization yield and further mask damage, a low-energy O2+ (200-500 V) cosputter can be applied. While the energy per atom (E/n) of GCIB is known to be an important factor influencing the sputter process, the manner through which E/n affects the GCIB-O2+ cosputter process remains unclear. In this study, poly(ethylene terephthalate) (PET) was used as a model material to investigate the sputter process of 10-20 kV Ar1000-4000+ (E/n = 2.5-20 eV per atom) with and without O2+ cosputter at different energies and currents. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) with Bi32+ as the primary ion was used to examine surfaces sputtered at different fluences. The sputter craters were also measured by alpha-step and atomic force microscopy in quantitative imaging mode. The SIMS results showed that the steady-state cannot be obtained with E/n values of less than 5 eV per atom due to damage accumulation using single GCIB sputtering. With a moderate E/n value of 5-15 eV per atom, the steady-state can be obtained, but the ∼50% decay in intensity indicated that damage cannot be masked completely despite the higher sputter yield. Furthermore, the surface Young's modulus decreased with increasing E/n, suggesting that depolymerization occurred. At an E/n value of 20 eV per atom, a failed profile was obtained with rapidly decreased sputter rate and secondary ion intensity due to the ion-induced crosslink. With O2+ cosputtering and a moderate E/n value, the oxidized species generated by O2+ enhanced the ionization yield, which led to a higher ion intensity at steady-state in general. Because higher kinetic energy or current density of O2+ led to a larger interaction volume and more structural damage that suppressed molecular ion intensity, the enhancement from O2+ was most apparent with low-energy-high-current (200 V, 80 µA cm-2) or high-energy-low-current (500 V, 5 µA cm-2) O2+ cosputtering with 0.5 µA cm-2 GCIBs. In these cases, little or no intensity drop was observed at the steady-state.

Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study.

BACKGROUND: Alcohol consumption and smoking have long been suspected of increasing the risk of developing psoriasis. Most evidence to date has derived from cross-sectional or case-control studies. OBJECTIVE: We sought to investigate the effects of alcohol and smoking on incident psoriasis. METHODS: Alcohol consumption, smoking status, and other covariates were collected from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident psoriasis was identified from the National Health Insurance database. Cox regression model was used for the analysis. RESULTS: Of 60,136 subjects, 242 (0.40%) developed psoriasis. After controlling for demographics and comorbidities, alcohol consumption was not significantly associated with psoriasis risk. Conversely, psoriasis risk was higher for current smokers than never smokers (adjusted hazard ratio 1.47 [95% confidence interval 1.04-2.07]). The risks were higher among subjects who smoked >25 cigarettes per day and for >20 pack-years. In subgroup analysis, current smoking was significantly associated with risk of psoriasis without psoriatic arthritis but not psoriatic arthritis alone. LIMITATIONS: Alcohol consumption was not assessed based on the number of drinks consumed. CONCLUSION: Current smoking increased the risk of psoriasis, particularly augmented for individuals who smoked >25 cigarettes per day and for >20 pack-years, while alcohol consumption was not significantly associated with psoriasis development.

Albumin levels and cause-specific mortality in community-dwelling older adults.

To investigate the association between serum albumin levels and cause-specific mortality among community-dwelling older adults. This cohort study was based on data obtained from the government-sponsored Annual Geriatric Health Examination Program for the older adults in Taipei City between 2006 and 2010. The study sample consisted of 77,531 community-dwelling Taipei citizens (≥65 years old). Mortality was determined by matching the participants' medical records with national death files. Serum albumin levels were categorized into <3.6, 3.6-3.7, 3.8-3.9, 4.0-4.1, 4.2-4.3, and ≥4.4 g/dL. Cox proportional hazards regression models were used to evaluate the association between albumin levels and cause-specific mortality. Spline regression was used to calculate the risk of mortality associated with albumin levels, modeled as continuous variables. Community-dwelling older adults had a mean albumin level of 4.3 g/dL, which significantly reduced by age. Compared to albumin levels ≥4.4 g/dL, mildly low albumin levels (4.2-4.3 g/dL) were associated with an increased mortality risk (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.05-1.28 for all-cause mortality), and albumin levels <4.2 g/dL were associated with significantly higher rates of all-cause, cancer, cardiovascular, and respiratory mortalities. In the spline regression, the curve of mortality risk was relatively flat at an albumin level ≥4.4 g/dL, and the mortality risk gradually increased as the albumin level declined. Albumin levels ≥4.4 g/dL were associated with better survival among community-dwelling older adults, and mortality risk increased as the albumin level decreased.

Violaceous Nodules on the Right Leg and Foot.

A patient with a history of bullous pemphigoid treated with oral prednisolone presented with multiple round, dark brown to violaceous-colored firm nodules on the right leg and 2 nodular masses with hemorrhagic crusts on the right foot. Complete blood cell count and creatinine and liver function test results were normal, and results of HIV antibody testing were negative. What is the diagnosis and what would you do next?

The risk of autoimmune connective tissue diseases in patients with atopy: A nationwide population-based cohort study.

BACKGROUND: The relationship between autoimmune connective tissue disease (ACTD) and atopy is controversial. OBJECTIVES: To investigate the risks of ACTDs in patients with atopic triad diseases, including atopic dermatitis, allergic rhinitis, and asthma, by using a nationwide data base. METHODS: A cohort of 155,311 patients newly diagnosed with atopic dermatitis, allergic rhinitis, or asthma in 2002-2011 was obtained from the Taiwan National Health Insurance Research Database. An age- and sex-matched control group was selected from the same data base. The association between atopy and ACTD was investigated by using Cox proportional hazards regression analyses. RESULTS: Atopic dermatitis, allergic rhinitis, and asthma were present in 12.1, 78.6, and 26.3%, respectively, of the patients with atopy. The presence of atopic diseases increased the overall risk of ACTDs (incidence rate ratio 1.85 [95% confidence interval {CI}, 1.52-2.25]). The hazard ratio (HR) for ACTDs remained higher after adjusting for age, sex, urbanization level, socioeconomic status, and comorbidities. Individual risks of systemic lupus erythematosus (HR 1.58 [95% CI, 1.06-2.37]), rheumatoid arthritis (HR 1.74 [95% CI, 1.31-2.33]), and Sjögren syndrome (HR 2.49 [95% CI, 1.71-3.63]) were also higher. The coexistence of atopic triad diseases increased the risk of ACTDs from 1.80 (95% CI, 1.48-2.21) for one atopic disease to 3.29 (95% CI, 1.22-8.88) for three atopic diseases. CONCLUSION: The presence of atopic triad diseases is significantly associated with risks of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome, and their coexistence exacerbates this risk. To our knowledge, this was the first study that reported an increased risk of Sjögren syndrome among patients with atopy.