Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan.

BACKGROUND: A link between rosacea and inflammatory bowel disease (IBD) has been proposed with unknown mechanisms. Epidemiologic evidence of this association needs to be examined. METHODS: In this nationwide cohort study, a total of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 were identified in the Taiwanese National Health Insurance Research Database. Cumulative incidences of IBD were compared between these 2 cohorts. Frailty Cox proportional hazard model was used and subgroup analyses were conducted to examine the risk factors for IBD. RESULTS: The 15-year cumulative incidences of IBD were 0.036% (95% confidence interval [CI] 0.00%-1.57%) and 0.019% (95% CI 0.00%-0.83%) in rosacea and nonrosacea cohorts, respectively (P = .05). Rosacea (adjusted hazard ratio 1.94, 95% CI 1.04-3.63, P = .04) and male gender (adjusted hazard ratio 3.52, 95% CI 2.03-6.11, P < .01) were independently associated with IBD, after adjustment for major comorbidities. Multivariate subgroup analyses revealed consistent results. The incidence rates of IBD decreased with increasing antibiotic use in patients with rosacea, but without statistical significance. LIMITATION: Information related to lifestyle, diet, alcohol, and smoking was not included in the database. CONCLUSION: Patients with rosacea may have an increased risk of IBD.

Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. Inflammation plays a prominent role in atherosclerosis and its complications. OBJECTIVE: We sought to investigate the associations of rosacea with cardiovascular disease risk factors and cardiovascular diseases from a nationwide population-based database. METHODS: A total of 33,553 patients with rosacea and 67,106 age- and gender-matched control subjects were identified from the National Health Insurance Research Database in Taiwan from 1997 to 2010. Multivariate logistic regressions were performed to compare the odds of comorbidities between the 2 groups. RESULTS: Dyslipidemia (odds ratio 1.41; 95% confidence interval 1.36-1.46), coronary artery disease (odds ratio 1.35, 95% confidence interval 1.29-1.41), and hypertension (odds ratio 1.17, 95% confidence interval 1.12-1.21) were significantly associated with rosacea. Coronary artery disease remained independently associated with rosacea after adjustment for hypertension, diabetes mellitus, and dyslipidemia. Male patients with rosacea had higher risks for all comorbidities than female patients with rosacea. LIMITATIONS: The National Health Insurance Research Database does not contain information regarding rosacea subtypes or disease severity, or laboratory data. CONCLUSION: Patients with rosacea are more likely to have dyslipidemia and hypertension. They are also at increased risk of coronary artery disease after adjustment for cardiovascular disease risk factors.

Autoimmune disease comorbidities in patients with atopic dermatitis: a nationwide case-control study in Taiwan.

BACKGROUND AND OBJECTIVES: Atopic dermatitis (AD) is a chronic relapsing dermatitis of unknown etiology. It is thought that abnormal regulation of Th1 and Th2 is not only the major cause of AD, but also the vital pathogenesis of many autoimmune diseases. To date, no large-scale studies have been performed on the relationship between AD and autoimmune disease. By conducting a nationwide population-based study with case-controls in Taiwan, we sought to clarify the association of AD with other autoimmune diseases to obtain a better understanding of its pathogenesis. METHODS: Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan from 1997 to 2010. In total, 41950 patients with AD and 167800 age- and gender-matched controls were enrolled. RESULTS: Patients with AD tended to have a high risk of associated lupus erythematosus (LE) (OR: 1.94, 95% CI: 1.48-2.54). The risk of LE was higher in female AD patients (OR: 2.05, 95% CI: 1.53-2.76) than in male AD patients (OR: 1.48, 95% CI: 0.76-2.85). Juvenile patients younger than 18 yrs with AD had higher risk of LE (OR: 3.02, 95% CI: 1.30-7.03) than adult patients with AD (OR: 1.68, 95% CI: 1.26-2.24). CONCLUSIONS: Our study confirmed the association between AD and LE. Early survey for LE in juvenile patients with AD is recommended.

Atopic diathesis in patients with Kawasaki disease.

OBJECTIVE: To determine the association between Kawasaki disease (KD) and atopic diathesis (atopic dermatitis [AD], allergic rhinitis, and asthma) in children younger than 5 years of age. STUDY DESIGN: In this nationwide study, we aimed to analyze the association and temporal relationship between KD and atopic diathesis. Data were obtained from the National Health Insurance Research Database of Taiwan from 1997 to 2010. In total, 200 patients with KD younger than 5 years of age and 800 age- and sex-matched control subjects were enrolled. RESULTS: In the whole study population, an increased risk of any concomitant atopic diseases was observed in patients with KD (OR 1.61, 95% CI 1.15-2.26). The risk of AD was increased in male patients between 1 and 5 years of age (OR 3.02, 95% CI 1.22-7.50). More than 60% of the patients developed atopic diseases after the diagnosis of KD. CONCLUSION: There appears to be an association between KD and risk of AD. Most of the atopic diseases occurred after the episode of KD.

Increased risk of sexual dysfunction in male patients with psoriasis: a nationwide population-based follow-up study.

INTRODUCTION: An association between psoriasis and sexual dysfunction (SD) has been explored. However, the risk of SD after the diagnosis of psoriasis relative to the age-matched general population remains unknown. Aim. To clarify the risk of developing SD in male patients with psoriasis. METHODS: From 2000 to 2001, we identified 12,300 male patients with newly diagnosed psoriasis and 61,500 matching controls from National Health Insurance Database in Taiwan. MAIN OUTCOME MEASURES: The two cohorts were followed up until 2008, and we observed the occurrence of SD by registry of SD diagnosis in the database. Stratified Cox proportional hazard regressions were used to calculate the 7-year SD risk for these two groups. RESULTS: Of the 73,800 sampled patients, 1,812 patients (2.46%) experienced SD during the 7-year follow-up period, including 373 (3.03% of patients with psoriasis) in the study group and 1,439 (2.34% of patients without psoriasis) in the comparison group. The hazard ratio (HR) for SD for patients with psoriasis was 1.27 times (95% confidence interval [CI], 1.11-1.46; P = 0.001) as high as that for patients without psoriasis after adjusting for age, monthly income, number of health-care visits, systemic treatment, and other comorbidities. Stratified analysis showed that the risk of SD was higher in patients older than 60 years old (HR: 1.42, 95% CI: 1.12-1.81) and patients with psoriatic arthritis (HR: 1.78, 95% CI: 1.08-2.91). However, the risk of SD was not significantly elevated in patients receiving systemic treatment, including retinoid, methotrexate, and cyclosporine. CONCLUSIONS: Male patients with psoriasis are at increased risk of developing SD. Physicians should pay attention to the impact of psoriasis on psychosocial and sexual health, especially in old-aged patients.

Cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in Taiwan.

It has long been a debate that whether atopy is a risk factor or protective factor for cancer. However, no large-scale study of different cancers in patients with atopic diseases has been conducted among Asians. Here, we conducted a nationwide study to evaluate the cancer risk in patients with allergic rhinitis (AR), asthma and atopic dermatitis (AD). Drawing on Taiwan's National Health Insurance Research Database, 225,315 patients with AR, 107,601 patients with asthma and 34,263 patients with AD without prior cancers were identified in the period from 1996 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. Although the overall cancer risks in patients with atopic symptoms were not increased, the risks were slightly elevated in female patients with AR or asthma (SIR: 1.13 and 1.08, AR and asthma, respectively) and slightly decreased in males patients with AR. Those aged 20-39 years-old possessed the highest risk. A higher risk of developing brain cancer was found in patients with atopic diseases, and patient with AR or asthma also had an elevated risk of developing cancer of kidney and urinary bladder. In contrast, the risk of nonmelanoma skin cancer was lower in patients with AR and asthma. Compared to patients with only one atopic disease, those with more than one atopic disease had lower cancer risks. Our data suggests that the association between atopy and cancer is site-specific.

Malignancies after renal transplantation in Taiwan: a nationwide population-based study.

BACKGROUND: Renal transplantation has been regarded as the treatment of choice for end-stage renal disease. Renal transplantation increases the risk of cancers due to long-term immunosuppression. The types of post-transplantation malignancies may vary among different geographic regions and ethnic populations. To date, large population-based studies of post-transplantation malignancies in Asian renal transplant recipients (RTRs) have rarely been reported. METHODS: To investigate the patterns of post-transplantation malignancies in Chinese RTRs, we performed a nationwide population-based cohort study between 1997 and 2008 based on data from the National Health Insurance Database in Taiwan. Patterns of cancer incidence in RTRs were compared with those of the general population using standardized incidence ratios (SIRs). RESULTS: Among the 4716 RTRs (2475 males and 2241 females; mean age 44.1 ± 12.4 years) and 22 556 person-years of observation, 320 post-transplant cancers were diagnosed. The SIR of all cancers was 3.75 (95% confidence interval 3.36-4.18). Women had a higher risk than men for the development of malignancies (SIR 5.04 for women and SIR 2.88 for men). Renal, bladder and liver cancers were the most common cancers, with SIRs of 44.29, 42.89 and 5.07, respectively. When stratified by age, RTRs of young age at transplant (<20 years) had the highest risk of post-transplantation malignancies. CONCLUSIONS: This study demonstrates different patterns of malignancies after renal transplantation in Chinese RTRs, with higher incidences of kidney and bladder cancers. Physicians should be more vigilant in examining RTRs for post-transplantation malignancies especially in younger patients.

Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study.

BACKGROUND: Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by onset age has rarely been reported. OBJECTIVE: We sought to clarify the role of atopic and autoimmune diseases in AA, thereby better understanding its pathogenesis. METHODS: A total of 4334 patients with AA were identified from the National Health Insurance Database in Taiwan from 1996 to 2008. A national representative cohort of 784,158 persons served as control subjects. RESULTS: Among patients with AA, there were significant associations with vitiligo, lupus erythematosus, psoriasis, atopic dermatitis, autoimmune thyroid disease, and allergic rhinitis. Different ages at onset resulted in disparate comorbidities. Increased risk of atopic dermatitis (odds ratio [OR] 3.82, 95% confidence interval 2.67-5.45) and lupus erythematosus (OR 9.76, 95% confidence interval 3.05-31.21) were found in childhood AA younger than 10 years. Additional diseases including psoriasis (OR 2.43) and rheumatoid arthritis (OR 2.57) appeared at onset age 11 to 20 years. Most atopic and autoimmune diseases were observed at onset ages of 21 to 60 years. With onset age older than 60 years, thyroid disease (OR 2.52) was highly related to AA. Moreover, patients with AA had higher risk for more coexisting diseases than control subjects. LIMITATIONS: We could not differentiate hypothyroidism from hyperthyroidism. CONCLUSIONS: AA is related to various atopic and autoimmune diseases. Different associated diseases in each onset age group of AA can allow clinician to efficiently investigate specific comorbidities.

Insights into the mechanism of Piper betle leaf-induced contact leukomelanosis using C57BL/6 mice as the animal model and tyrosinase assays.

BACKGROUND/OBJECTIVES: Steamed piper betle leaves (PBL) were once used by many Taiwanese women to treat pigment disorders on the face. Most women claimed a quick, favourable response at first, only to be overcome with facial leukomelanosis later. METHODS: C57BL/6 mice were randomly assigned to different groups to study if PBL could cause the following effects: contact dermatitis, leukomelanosis, or hair bleaching. Intracellular melanin content was measured by tyrosinase assays. RESULTS: Most steamed PBL-treated mice developed contact dermatitis and postinflammatory hyperpigmentation (PIH) on their shaved backs. About half developed bleached hair to varying extents. The steamed PBL did not only bleach the hairs, but also, unexpectedly, stimulated melanocyte replication, indicated by the fact that the number of functional melanocytes in the tail epidermis increased significantly after treatment (P = 0.007). Using tyrosinase assays PBL extract at the undiluted concentration showed limited inhibition of melanogenesis, probably via melanocytotoxicity. CONCLUSIONS: The leukomelanosis observed in patients might be the consequence of PIH combined with a mixed reaction (hyper- and hypopigmentation), probably due to the different volatile chemicals that surface after steaming the PBL. This conflicting mixed reaction suggests that counteractive ingredients might exist in PBL. PBL, if purified, might be a promising source of a novel bleaching agent.

Prevalence of atopic dermatitis, allergic rhinitis and asthma in Taiwan: a national study 2000 to 2007.

To study the prevalence of atopic dermatitis, allergic rhinitis, and asthma in Taiwan, we analysed the claims data of a nationally representative cohort of 997,729 enrolees from the National Health Insurance register from 2000 to 2007. Overall, 66,446 patients were diagnosed with atopic dermatitis, and 49.8% of them had concomitant allergic rhinitis and/or asthma. The overall 8-year prevalences of atopic dermatitis, allergic rhinitis, and asthma were 6.7%, 26.3% and 11.9%, respectively. Children and adolescents had significantly higher prevalences of these atopic diseases. The prevalence of atopic dermatitis in females was lower than that in males before the age of 8 years, but became higher after that. Patients with atopic dermatitis were more likely to have allergic rhinitis and asthma. Those having both atopic dermatitis and allergic rhinitis possessed an even higher risk for asthma (odds ratio 9.04). The numbers of visits for atopic dermatitis were highest in late spring to mid-summer. These data suggest that atopic diseases are common in Taiwan.

Spotted leucoderma after treatment of facial hyperpigmentation on hemodialysis patients employing 1064-nm Q-switched Nd:YAG laser.

The development of skin hyperpigmentation in patients with end-stage renal disease (ESRD) on hemodialysis (HD) have been well documented. However, the cosmetic concern was neither valued seriously nor treated effectively in the past. We report a female case who suffered from facial hyperpigmentation (FH). She was treated by large-spot sized, 1064-nm Q-switched Nd:YAG laser (QSNYL). A significant improvement was found after three treatment sessions at a fluence of 3.9 J/cm(2) with 8-day intervals, but spotted leucoderma developed at the fourth visit. Neither residual FH nor spotted leucoderma subsequently improved following two additional sessions of 1064-nm QSNYL at a lower fluence with topical hydroquinone and HeNe laser, and it persisted at the 1-year follow-up. This clinically specific round-shaped leucoderma suggested laser-induced damage to melanocytes due to unsuitable application. The 1064-nm QSNYL with a large spot size and an appropriate parameter may become an effective therapeutic modality if properly utilized.

Epidemiological features and costs of herpes zoster in Taiwan: a national study 2000 to 2006.

To analyse the epidemiological characteristics and related costs of herpes zoster in Taiwan, a nationally representative cohort of 1,000,000 individuals from the National Health Insurance register was followed up from 2000 to 2006 and their claims data analysed. Overall, 34,280 patients were diagnosed with zoster (incidence 4.89/1000 person-years) and 2944 patients (8.6%) developed post-herpetic neuralgia 3 months after the start of the zoster rash (incidence 0.42/1000 person-years). People with older age, diabetes, and immunocompromising conditions were at higher risk of developing zoster and post-herpetic neuralgia. The overall hospitalization rate for zoster was 16.1 cases per 100,000 person-years. The cost for each home care case and per hospitalized case were approximately 53.30 euro and 1224.70 euro, respectively. Further research into the cost-effectiveness of zoster vaccine is needed.

Follicular Graft-versus-host Disease: A Rare Manifestation in a Patient with the Overlap Subtype of Chronic Graft-versus-host Disease.

Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Although skin involvement is common, generalized follicular eruption as the major clinical manifestation is rare. However, it is important for clinicians to recognize it at the earliest to initiate an appropriate therapy. We report a case of a patient with multiple myeloma who developed extensive hyperkeratotic, lichenoid folliculocentric papules with perifollicular erythema on day 53 following an allogeneic HSCT. The overall clinical and histological findings were consistent with the overlap subtype of chronic follicular GVHD.

Piperacillin-Tazobactam-Induced Linear IgA Bullous Dermatosis Supported by a T-Cell Activation Assay.

Linear immunoglobulin (Ig) A bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear IgA deposits at the basement membrane zone visualized with direct immunofluorescence (DIF). Most cases of LABD are idiopathic, but some are drug-induced with vancomycin being the most common causative agent. We herein report a patient presenting with blisters and erosive lesions, primarily in the intertriginous and flexor areas, consistent with a diagnosis of piperacillin-tazobactam-induced LABD based on the patient's clinical course and histopathology, DIF, and in vitro T-cell activation assay (TAA) findings. Only one case of piperacillin-tazobactam-induced LABD has been previously reported. In addition to its rarity, our case was also unique in that the skin lesions occurred in the intertriginous and flexor areas, uncommon locations for typical adult patients with LABD, and TAA strongly suggested an association with the causative drug.

Cancer risk in patients with alopecia areata: a nationwide population-based matched cohort study.

Alopecia areata (AA) is an organ-specific autoimmune disorder. Defective immune system related disorders are prone to increase the risk of cancer formation. However, the association among AA and variety of cancer types had never been studied. A nationwide population-based matched cohort study was conducted to evaluate the cancer risk in patients with AA. Records from Taiwan National Health Insurance Research Database were analyzed. Cases of AA from 1997 to 2013 and cancers registered in the catastrophic illness profile from the same time period were collected. The standard incidence ratio (SIR) of each cancer was calculated. In total, 2099 cancers among 162,499 patients with AA and without prior cancers were identified. The overall cancer risks in AA patients were slightly decreased, especially among male subjects (SIR: 0.89). Refer to individual cancer, the cancer risk of nonmelanoma skin cancer (NMSC) (SIR: 0.59), upper GI cancer (SIR: 0.70), liver cancer (SIR: 0.82), uterine, and cervix cancer (SIR: 0.84) were significantly lower in patients with AA. In contrast, AA patients were inclined to have lymphoma, breast cancer, kidney, and urinary bladder cancer with the SIR of 1.55, 2.93, and 2.95, respectively. Age stratified analyses revealed female AA patients younger than 50 years old have even higher risk of breast cancer (SIR: 3.37). Further sensitivity analysis showed similar results after excluding major autoimmune disorders. Cancer risk in AA patients is organ specific, and it is not associated with the underlying autoimmune disorders in patients with AA.

Using desmoglein 1 and 3 enzyme-linked immunosorbent assay as an adjunct diagnostic tool for pemphigus.

BACKGROUND: Pemphigus is an acquired autoimmune intraepidermal blistering disease that is divided into 2 major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating anti-desmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. Recently, a novel commercial enzyme-linked immunosorbent assay (ELISA) against Dsg1 and Dsg3 has been established and found to be extremely sensitive and specific. To date, the usefulness of Dsg1 and Dsg3 ELISA in the diagnosis of pemphigus in the Taiwanese population has never been reported. METHODS: Serum samples were obtained from 143 patients, including 20 patients with PV, 9 patients with PF, 72 patients with bullous pemphigoid, 1 patient with dermatitis herpetiformis and 41 patients with non-autoimmune blistering diseases. They were tested for anti-Dsg1 and anti-Dsg3 reactivity by ELISA. RESULTS: Seventeen of 20 PV sera (85%) exceeded the cut-off value of Dsg3 ELISA, and 9 of 9 PF sera (100%) exceeded the cut-off value of Dsg1 ELISA, while only 1 (0.88%) and 3 (2.6%) of 114 non-pemphigus sera exceeded the cut-off values of Dsg3 and Dsg1 ELISAs, respectively. Thus, the sensitivity and specificity of Dsg3 ELISA were 85% and 99.1%, while the sensitivity and specificity of Dsg1 ELISA were 100% and 97.4%, respectively. The correlation between ELISA scores and disease activity along the time course was examined in 6 PV patients and 1 PF patient, and the result was equivocal. CONCLUSION: Dsg1 and Dsg3 ELISAs provide a simple, highly sensitive and specific method that can serve as a useful adjunct tool for the initial diagnosis of pemphigus.

Uveitis with biopsy-proven sarcoidosis in Chinese--a study of 60 patients in a uveitis clinic over a period of 20 years.

BACKGROUND: The aim of this study was to assess the clinical features of uveitis with biopsy-proven sarcoidosis in Chinese patients. METHODS: This was a retrospective study of uveitis patients with biopsy-proven sarcoidosis who consecutively visited the uveitis clinic of Taipei Veterans General Hospital from 1986 to 2005. Medical records were reviewed to obtain demographic data, initial symptoms, biopsy sites, pulmonary conditions detected by chest X-ray and manifestations of uveitis. From 2002 onwards, patients also received chest computed tomography (CT). RESULTS: A total of 60 uveitis patients with biopsy-proven sarcoidosis were identified. Forty-four patients (73%) were found in the last 4 years. Female predominance with a male-to-female ratio of 1:6.5 was found. The most common initial symptom was uveitis in 41 patients (68%). The most common positive biopsy sites were mediastinal lymph nodes, lung, conjunctiva and skin. Twenty (90.9%) of 22 patients with chest X-ray stage 0 showed >or= stage 1 on CT. The mean age at uveitis onset was 47.7+/-14.7 years (range, 21-76 years), with no gender difference (p=0.913). A peak incidence was found in the 6th decade of life. There was bilateral eye involvement in 54 patients (90%). Frequency of the manifestations of uveitis showed isolated anterior uveitis in 2 patients (3.3%), isolated posterior uveitis in 8 patients (13.3%), intermediate and posterior uveitis (i.e. anterior uveitis sparing) in 16 patients (26.7%), and panuveitis in 34 patients (56.7%). CONCLUSION: A marked increase was noted since 2002. One of the causes is the performance of chest CT. Chest CT is useful to discover mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation in patients with peculiar uveitis features indicative of sarcoidosis. Female predominance and peak incidence of uveitis onset in the 6th decade of life were found. The posterior segment was the most common localization of uveitis in biopsy-proven sarcoidosis in Chinese.

Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan.

Previous studies have proposed the association between pemphigus and several autoimmune diseases, but no large-scale study has been reported. To delineate the association between pemphigus and autoimmune diseases including psoriasis. A total of 1,998 patients with pemphigus and 7,992 control subjects were enrolled from the National Health Insurance Research Database in Taiwan from 1997 to 2010. The odds of comorbidities between these two groups were analysed by multivariate logistic regression. Compared with control subjects, patients with pemphigus were much more likely to have Sjögren's syndrome (odds ratio [OR]: 15.0; 95% confidence interval [CI]: 3.16-71.5), psoriasis (OR: 7.18; 95% CI: 5.55-9.29), systemic lupus erythematosus (OR: 4.46; 95% CI: 1.88-10.6), and alopecia areata (OR: 2.68; 95% CI: 1.26-5.67). According to gender-stratified analyses, however, the association between pemphigus and Sjögren's syndrome or alopecia areata was found to be significant only in the female patients. We confirm the association between pemphigus and some autoimmune diseases, including Sjögren's syndrome, systemic lupus erythematosus, and alopecia areata. In addition, we present the novel finding that patients with pemphigus have an increased risk of psoriasis.