Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database.

BACKGROUND: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. OBJECTIVES: We examined the incidence of serious infection and infection mortality in patients with psoriasis. METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). RESULTS: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. CONCLUSION: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.

Incidence, Prevalence, and Mortality of People with Psoriasis and Psoriatic Arthritis in Taiwan: A Nationwide Cohort Study.

There is a recognized need to better understand changes in the epidemiology of psoriasis and psoriatic arthritis (PsA) over time in Asia. Using the Taiwan National Health Insurance claim records this population-based study examined changes in the prevalence, incidence, and mortality rates in patients with psoriasis or psoriatic arthritis in Taiwan over 12 years. Patients with ≥1 diagnosis code for psoriasis or psoriatic arthritis, recorded either by dermatologists or rheumatologists, were identified. Annual age- and sex-standardized prevalence and incidence rates were calculated using the Taiwan general population as reference. To investigate mortality, each patient in the incident cohort was matched to 10 comparators from the general population by sex and age (at diagnosis). The risk of mortality between study cohorts and comparators was analysed by Cox proportional hazard regression. The prevalence of psoriasis (0.18-0.86%) and psoriatic arthritis (0.01-0.08%) increased steadily between 2006 and 2017. The incidence rates, however, remained stable (psoriasis: 62-65 per 100,000 person-years; psoriatic arthritis: 6-5 per 100,000 person-years). The risk of all-cause mortality for patients with psoriasis (hazard ratio 1.16; 95% confidence interval: 1.13-1.19) was higher than the general population, despite a decreasing trend over time in the all-cause mortality rates for both groups. The steady increase in the prevalence of psoriasis despite stable incidence rates suggests that improvements in life expectancy may be the key determinant of this increase.

Cardiovascular Risk Associated with Methotrexate versus Retinoids in Patients with Psoriasis: A Nationwide Taiwanese Cohort Study.

PURPOSE: Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids. PATIENTS AND METHODS: We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination. RESULTS: We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76-0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71-1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89-1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66-0.85). Similar results were found in as-treated analyses. CONCLUSION: In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.

Capsaicin attenuates imiquimod-induced epidermal hyperplasia and cutaneous inflammation in a murine model of psoriasis.

Psoriasis is one of the most common chronic inflammatory diseases that is characterized by well-defined erythematous plaques, with typical histopathological findings of lymphocytic infiltration and epidermal hyperplasia. Topical treatments of psoriasis are either associated with limited response or with side effects. Up to date, topicals targeting neuroimmune axis in psoriasis or psoriasiform dermatitis have not been explored. Here, we investigated whether percutaneous delivery of capsaicin could attenuate the pathological change of psoriasiform inflammation. Imiquimod-induced psoriasis-like murine model was used to evaluate therapeutic effects from topical application of capsaicin. An additional model of psoriasiform dermatitis induced by direct IL-23 injection was used to identify the level of action from capsaicin in this neuroimmune axis. Cutaneous inflammation was assessed by erythema level and ear thickness change. Key cytokines, infiltrating cells in the skin, and draining lymph node cells were investigated. The results showed that capsaicin administration obstructed the activation of IL-23/IL-17 pathway induced by imiquimod, presenting with significantly reduced psoriasiform dermatitis both in gross appearance and microscopic features. Tissue gene expression of psoriatic core cytokines induced by imiquimod (including IL-23, IL-17A, IL-22, TNF-α, and IL-6) were greatly decreased by capsaicin application. This protective effect from capsaicin could be hampered by direct intradermal injection of IL-23. CONCLUSION: Epicutaneous delivery of capsaicin on imiquimod-treated murine skin could significantly decrease expression of multiple inflammatory cytokines and the severity of prototypic change of psoriasiform inflammation. The beneficial effect imposed by capsaicin reinforces the neuroimmune contribution towards psoriasiform inflammation and provides a potential non-steroidal therapeutic alternative for topical treatment of psoriasiform dermatitis.

Network meta-analysis-based comparison of first-line steroid-sparing adjuvants in the treatment of pemphigus vulgaris and pemphigus foliaceus.

BACKGROUND: Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials. OBJECTIVE: To determine the best first-line steroid-sparing adjuvants for pemphigus treatment. METHODS: Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose. RESULTS: Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, -11,830.5 mg (95% CI, -14,089.48 to -9571.52), -3032.48 mg (-4700.74 to -1364.22), and -2469.54 mg (-4128.42 to -810.66), respectively. LIMITATIONS: The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons. CONCLUSION: Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.

All-Cause and Cause-Specific Mortality in Patients with Psoriasis in Taiwan: A Nationwide Population-Based Study.

Asian population-based data evaluating all-cause mortality and cause-specific mortality in patients with psoriasis are limited. This study aimed to evaluate the risk of all-cause mortality (stratified according to onset status, disease severity, and concomitant psoriatic arthritis) and cause-specific mortality in patients with psoriasis. Our study cohort consisted of 80,167 patients with newly diagnosed psoriasis between 2001 and 2012 in the National Health Insurance Database. Vital status and cause of death were ascertained from the National Death Registry of Taiwan. All-cause and cause-specific crude mortality rates and standardized mortality ratios were estimated. A total of 7,198 deaths were identified during the follow-up period (508,505 person-years). The standardized mortality ratios were 1.53 for severe psoriasis (95% confidence interval = 1.45-1.60), 1.47 for early-onset psoriasis (95% confidence interval = 1.34-1.61), and 1.47 for patients with psoriatic arthritis (95% confidence interval = 1.36-1.58). In the cause-specific mortality analysis, the absolute and excess risks of death were highest for malignancies (3.6 and 1.57 deaths per 1,000 patient-years, respectively) and circulatory system diseases (3.0 and 1.44 deaths per 1,000 patient-years, respectively). Patients with severe psoriasis, early-onset psoriasis, and psoriatic arthritis had higher all-cause mortality risks. In particular, patients with psoriasis had higher excess risks of mortality from malignancies and circulatory system diseases.

Risks of hypertension associated with cyclosporine, nonsteroidal anti-inflammatory drugs, and systemic glucocorticoids in patients with psoriasis: a nationwide population-based nested case-control study in Taiwan.

PURPOSE: Patients with psoriasis and/or psoriatic arthritis (PsA) are known to have increased cardiovascular morbidity and mortality. Hypertension, an important risk factor for cardiovascular disease, is highly prevalent in patients with psoriasis and/or PsA. The effects of anti-psoriatic medications - including cyclosporine, nonsteroidal anti-inflammatory drugs, and glucocorticoids - on hypertension remain unclear. We examined whether such medication exposure was associated with hypertension in psoriasis patients. METHODS: This population-based, nested case-control study analyzed data from an inception psoriasis cohort identified from Taiwan's National Health Insurance Research Database, 2000-2010. A total of 1530 patients with newly diagnosed hypertension and 4542 age- and gender-matched controls were included in the analysis. Conditional logistic regressions were applied to estimate the effects of drug of interest on hypertension. RESULTS: After adjusting for potential confounders, patients with current use of cyclosporine [odds ratio (OR) = 7.13; 95% confidence interval (CI) 1.85-27.49], nonsteroidal anti-inflammatory drugs (OR = 2.2; 95% CI 1.95-2.49), or systemic glucocorticoids (OR = 1.42; 95% CI 1.23-1.64) showed an increased risk of hypertension as compared to those not exposed to these drugs. Moreover, an increasing dose or combined use of nonsteroidal anti-inflammatory drugs and glucocorticoids was associated with increased hypertension risk. The risk of hypertension associated with glucocorticoids, or combined use was greatest among patients aged 49 years or less. CONCLUSIONS: The use of cyclosporine, nonsteroidal anti-inflammatory drugs, or glucocorticoid was associated with hypertension in patients with psoriasis and/or PsA. These study results inform physicians on the importance of early identification of hypertension during therapy with such medication.

High Serum Uric Acid Levels Are Associated with All-Cause and Cardiovascular, but Not Cancer, Mortality in Elderly Adults.

OBJECTIVES: To estimate the all-cause, cardiovascular, and cancer mortality risks associated with serum uric acid levels in elderly adults. DESIGN: Cohort study. SETTING: The Annual Geriatric Health Examination Program database from 2006 to 2010. PATICIPANTS: Community-dwelling Taipei citizens aged 65 and older (N = 77,541). MEASUREMENTS: Stratified according to sex, serum uric acid levels were analyzed in quartiles and as normal versus high categories. Mortality was determined by matching cohort identifications with national death files. RESULTS: Men had significantly higher uric acid levels than women (P < .001), and mean levels increased with age (P < .001). Serum uric acid levels (normal vs high) were an independent risk factor for all-cause and cardiovascular mortality in men and women, with the strongest association found for cardiovascular mortality. The association between serum uric acid levels and cardiovascular mortality was independent of other cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia, and glomerular filtration rate levels. When levels were analyzed as quartiles, men with levels in the second quartile had the lowest hazard ratios for all-cause and cardiovascular mortality. CONCLUSION: High serum uric acid levels are associated with greater risk of all-cause and cardiovascular mortality but not cancer mortality in elderly adults. Further studies are warranted to investigate the prognostic implications and potential utility in the monitoring of therapy.

Efficacy and adverse events of high-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis.

INTRODUCTION: Theoretically, high-frequency oscillatory ventilation (HFOV) achieves all goals of a lung-protective ventilatory mode and seems ideal for the treatment of adult patients with acute respiratory distress syndrome (ARDS). However, its effects on mortality and adverse clinical outcomes remain uncertain given the paucity of high-quality studies in this area. This meta-analysis was performed to evaluate the efficacy and adverse events of HFOV in adults with ARDS. METHODS: We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials through February 2014 to retrieve randomized controlled trials of HFOV in adult ARDS patients. Two independent reviewers extracted data on study methods, clinical and physiological outcomes and adverse events. The primary outcome was 30-day or hospital mortality. Risk of bias was evaluated with the Cochrane Collaboration's tool. Mortality, oxygenation and adverse effects of HFOV were compared to those of conventional mechanical ventilation. A random-effects model was applied for meta-analysis. RESULTS: A total of five trials randomly assigning 1,580 patients met inclusion criteria. Pooled data showed that HFOV significantly improved oxygenation on day one of therapy (four studies; 24% higher; 95% confidence interval (CI) 11 to 40%; P <0.01). However, HFOV did not reduce mortality risk (five studies; risk ratio (RR) 1.04; 95% CI 0.83 to 1.31; P = 0.71) and two early terminated studies suggested a harmful effect of HFOV in ARDS (two studies; RR 1.33; 95% CI 1.09 to 1.62; P <0.01). Safety profiles showed that HFOV was associated with a trend toward increased risk of barotrauma (five studies; RR 1.19; 95% CI 0.83 to 1.72; P = 0.34) and unfavorable hemodynamics (five studies; RR 1.16; 95% CI 0.97 to 1.39; P = 0.12). CONCLUSIONS: HFOV improved oxygenation in adult patients with ARDS; however, it did not confer a survival benefit and might cause harm in the era of lung-protective ventilation strategy. The evidence suggests that HFOV should not be a routine practice in ARDS and further studies specifically selecting patients for this ventilator mode should be pursued.

Increased risk of diabetes mellitus in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population-based cohort study.

BACKGROUND: The association between psoriasis and diabetes mellitus (DM) has been explored previously. However, no studies have been reported regarding the severity of psoriasis, comorbidities, and concomitant medications on the risks of DM in patients with psoriasis. OBJECTIVE: We sought to evaluate the impact of the severity of psoriasis, comorbidities, and concomitant medications on the risk of type 2 DM in patients with psoriasis. METHODS: We conducted a cohort study with 14,158 adults with psoriasis and adults without psoriasis using data from the Taiwan National Health Insurance Research Database. Cox regression models using time-varying covariates were used. RESULTS: After the comorbidities and concomitant medications were adjusted for, psoriasis was found to be independently associated with an increased risk of DM (severe: hazard ratio, 2.06 [95% confidence interval, 1.58-2.68] vs mild: hazard ratio, 1.28 [95% confidence interval, 1.05-1.55]). Other independent risk factors included age, Cushing disease, and the increased cumulative doses of the thiazide and methotrexate. LIMITATION: The National Health Insurance Research Database did not have information regarding the Psoriasis Area and Severity Index, diet, obesity, body mass index, exercise status, and family history of diabetes. CONCLUSION: Patients with psoriasis have a higher risk of developing DM. The risks vary depending on the severity of psoriasis, comorbidities, and concomitant medications.

The risk of developing non-melanoma skin cancer, lymphoma and melanoma in patients with psoriasis in Taiwan: a 10-year, population-based cohort study.

BACKGROUND: Hospitalized psoriasis patients are known to have a higher risk of malignancy (e.g., nonmelanoma skin cancer [NMSC], lymphoma, and melanoma) than the general population; currently, it is unclear whether this risk is affected by psoriasis severity. The aim of this study was to compare the cancer risk of patients with mild and severe psoriasis and the general population. METHODS: Data for this retrospective population-based cohort study were obtained from the Taiwan National Health Insurance Research Database. This study included 7061 patients with a first-time diagnosis of psoriasis. All study individuals were followed up until the end of 2007. The crude incidence density ratio and standardized incidence ratio (SIR) of NMSC, melanoma, and lymphoma were determined. RESULTS: Among psoriasis patients, the most common cancer was NMSC (density ratio: 7.5); women were at a higher risk of NMSC than men (density ratios: 8.08 vs. 7.0). Psoriasis patients in the south geographic group or in the 50- to 59-year-old age group were most likely to develop NMSC. The NMSC SIR was higher among patients with severe psoriasis than among patients with mild psoriasis (SIR: 3.72 vs. 7.08). The lymphoma and melanoma SIR among patients with severe psoriasis was also high (lymphoma SIR: 4.85; melanoma: 11.01). CONCLUSIONS: Psoriasis carries an elevated risk of NMSC and lymphoma. This effect is modified by the severity of psoriasis, age, gender, and geographic location.