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.

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.

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.

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.

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.

Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

Depression and Insomnia in Patients With Psoriasis and Psoriatic Arthritis Taking Tumor Necrosis Factor Antagonists.

Psoriasis patients with moderate to severe disease often present with depression and insomnia. Treatment targeting both psoriasis and psychological comorbidities is needed to improve the quality of life of these patients.In this nationwide cohort study, a total of 980 patients with psoriatic arthritis or psoriasis who had received nonbiological disease-modifying antirheumatic drugs and biologics therapy between 2009 and 2012 were identified. The prevalence rates of patients taking medications for depression and insomnia were compared before and after biologics therapy. Logistic regression method was used to investigate the risk factors for depression and insomnia. Further stratified analyses were performed to examine the prevalence of use of medications for depression and insomnia among different patient subgroups.The prevalence of patients taking regular antidepressants before starting biologics therapy was about 20%. There was a more than 40% reduction in this prevalence after biologics therapy for 2 years. Age higher than 45 years, female sex, presence of comorbidities, and psoriatic arthritis were independently associated with depression and insomnia. Further stratified analyses revealed a more rapid and significant reduction in depression/insomnia in those undergoing continuous biologics therapy, younger than 45 years, without psoriatic arthritis and not taking concomitant methotrexate, when compared with their counterparts.The results suggest that biologics therapy may be associated with reduced rates of depression and insomnia, and a reduced rate of regular antidepressants use in psoriasis patients.

Risk of fractures in vitiligo patients treated with phototherapy-A retrospective population-based cohort study.

BACKGROUND: Phototherapy might increase bone mineral density. However, it is unknown whether phototherapy can reduce the risk of fractures in patients with vitiligo. OBJECTIVES: To investigate the effect of phototherapy on fracture risks in vitiligo patients aged 40 or older. METHODS: This population-based cohort study used the 2000-2010 Taiwan National Health Insurance Research Database (NHIRD) to identify 3863 patients newly diagnosed with vitiligo between 2003 and 2009 at age ≥40 years. Study subjects were classified into three cohorts: (1) frequent phototherapy; (2) infrequent phototherapy; and (3) no phototherapy. Patients were followed until the first hip or vertebral fracture or 31 December 2010. Data were analysed using Cox regression models and also stratified by age and gender. RESULTS: Frequent phototherapy decreased the fracture risks (adjusted hazard ratio (aHR)=0.32, p=0.009) in vitiligo patients. Stratification by age and gender confirmed the fracture prevention effect of frequent phototherapy in patients aged 40-64 years (aHR=0.14, p=0.016) and in female patients (aHR=0.31, p=0.024). CONCLUSIONS: This study provides the first evidence that frequent phototherapy can reduce the risk of fractures among middle-aged and among female vitiligo patients.

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.

The risk of cancer in patients with rheumatoid arthritis taking tumor necrosis factor antagonists: a nationwide cohort study.

INTRODUCTION: The association between cancer and use of biologic therapy among rheumatoid arthritis (RA) patients remains controversial. We aimed to compare the relative risk of cancer development between RA patients taking tumor necrosis factor α (TNFα) antagonists and those taking nonbiologic disease-modifying anti-rheumatic drugs (nbDMARDs). METHODS: We conducted a nationwide cohort study between 1997 and 2011 using the Taiwan National Health Insurance Research Database. The risk of newly diagnosed cancer was compared between patients starting TNF-α antagonists (biologics cohort) and matched subjects taking nbDMARDs only (nbDMARDs cohort). Cumulative incidences and hazard ratios (HR) were calculated after adjusting for competing mortality. Standardized incidence ratio (SIR) was calculated for cancer risk. Multivariate analyses were performed using Cox proportional hazards model. RESULTS: We compared 4426 new users of TNF-α antagonists and 17704 users of nbDMARDs with similar baseline covariate characteristics. The incidence rates of cancer among biologics and nbDMARDs cohorts were 5.35 (95% confidence interval (CI) 4.23 to 6.46) and 7.41 (95% CI 6.75 to 8.07) per 1000 person-years, respectively. On modified Cox proportional hazards analysis, the risk of cancer was significantly reduced in subjects in biologics cohort (adjusted HR 0.63, 95% CI 0.49 to 0.80, P < .001), after adjusting for age, gender, disease duration, major co-morbidities, and prior use of DMARDs and corticosteroids. However, there was an increased risk for hematologic cancers in biologics cohort, yet without statistical significance. The effect of biologics was consistent across all multivariate stratified analyses and the association between biologics use and cancer risk was independent of dosage of concomitant nbDMARDs. CONCLUSION: These findings suggested that RA patients taking TNF-α antagonist are associated with a lower risk of cancer, but not for hematologic cancers, than RA patients taking nbDMARDs alone.

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.

EGb-761 prevents ultraviolet B-induced photoaging via inactivation of mitogen-activated protein kinases and proinflammatory cytokine expression.

BACKGROUND: EGb-761 is an antioxidant and anticarcinogen; however, its role as a photoprotector remains unknown. OBJECTIVE: To determine whether EGb-761 photoprotects human dermal fibroblasts and BALB/c mice skin against ultraviolet B (UVB) light irradiation. METHODS: To simulate chronic photodamage, shaved BALB/c mice were exposed to UVB irradiation (90mJ/cm(2)) thrice weekly for 3 months. EGb-761 (2mg/cm(2)) was topically applied 1h before irradiation to evaluate its effect. The mechanisms by which EGb-761 protects the skin from photodamage were evaluated by immunohistochemical analysis, enzyme-linked immunosorbent assay (ELISA), and Western blotting. RESULTS: In BALB/c mice, the signs of photoaging or photodamage, such as coarse wrinkle formation, epidermal hyperplasia, and elastic fiber degeneration, markedly reduced with the topical application of EGb-761. Western blot and ELISA revealed that the activation of MMP-1 in cultured fibroblasts markedly diminished after pretreatment with EGb-761. In addition, EGb-761 inhibited UVB-induced overexpression by the fibroblasts of the proinflammatory cytokines, such as interleukin (IL)-1α, IL-1ß, IL-6, and tumor necrosis factor-α. The phosphorylation of the mitogen-activated protein kinase (MAPK) signal transduction pathway components, including extracellular signal-regulated kinase, C-Jun N-terminal kinase, and p38, which are induced by UV irradiation, was significantly inhibited in vivo and in vitro. EGb-761 also diminished the generation of UVB-induced reactive oxygen species (ROS). CONCLUSIONS: EGb-761 photoprotects mice and cultured fibroblasts, inhibits the UVB-induced phosphorylation of MAPK pathway components, and reduces the expression of the proinflammatory cytokines by suppressing ROS generation. Thus, topically applied EGb-761 may be a promising photoprotective agent.

Senile gluteal dermatosis: a clinical study of 137 cases.

BACKGROUND: Senile gluteal dermatosis (SGD) is a common genital dermatosis but has gained little attention before. A large-scale clinical study of this disease is lacking. MATERIALS AND METHODS: We examined 162 consecutive outpatients with gluteal skin diseases of different causes. Fourteen skin biopsies were performed. Patient's age, gender, body mass index (BMI), way of sitting or lying, treatment response, and underlying systemic diseases were recorded. RESULTS: About 137 (85%) patients could be defined as SGD. These patients, with a mean age of 79.4 ± 40.7 years and a mean BMI of 21.7 ± 10.8, presented with either partial (n = 43, 31%) or full-blown (n = 94, 69%) SGD lesions characterized by the sign of so-called "three corners of a triangle": brownish plaques on the gluteal cleft and each side of the buttocks. Male/female ratio was 130/7. Itching or pain of varying intensity was reported by 50 patients (36%) and 14 patients (10%), respectively. Eighty-six patients (53%) presented with horizontal hyperkeratotic ridges, a characteristic sign of SGD. Most patients spent most of the day sitting but reported no special way of sitting or lying. More than half of patients with SGD claimed no response to topical steroids and/or keratolytics. In comparison with patients with SGD, SGD-free patients were younger (61.3 ± 36 years, P = 0.0005) and heavier (BMI 26.2 ± 15.6, P < 0.0001) but showed no significant difference in the frequency of underlying systemic diseases. CONCLUSIONS: SGD is a common dermatosis, mostly affecting the thinner elderly. Friction, pressures and long hours sitting seemed to be important factors to trigger this dermatosis.

Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study.

PURPOSE: Systemic sclerosis is a life-threatening autoimmune disease characterized by vasculopathy, which results in myocardial involvement in an extremely high percentage of patients. Nevertheless, there have been no large-scale epidemiological studies about the risk of acute myocardial infarction in patients with systemic sclerosis. The aims of this study were to evaluate the hazard ratio (HR) and risk factors of acute myocardial infarction in patients with systemic sclerosis, as well as to compare the risks of acute myocardial infarction among systemic sclerosis patients taking different immunosuppressors. METHODS: The study cohort included 1344 patients with systemic sclerosis and 13,440 (1:10) age-, sex-, and comorbidity-matched controls during the period between 1997 and 2006, from the National Health Insurance Research Database. We compared the risk of acute myocardial infarction between patients with systemic sclerosis and controls and calculated the adjusted HRs for acute myocardial infarction in systemic sclerosis patients taking immunosuppressors and not taking immunosuppressors. RESULTS: The incidence rates of acute myocardial infarction were 535 and 313 cases per 100,000 person-years for systemic sclerosis cohort and reference cohort, respectively (P <.001, unadjusted). After adjusting for age, sex, and underlying medical diseases on Cox proportional hazards model, systemic sclerosis was found to be an independent risk factor for acute myocardial infarction (HR 2.45). Other risk factors included hypertension (HR 2.08) and diabetes (HR 2.14). The multivariate adjusted HR for acute myocardial infarction did not decrease among the systemic sclerosis patients taking systemic steroids, penicillamine, cyclophosphamide, azathioprine, methotrexate, or cyclosporine. CONCLUSION: Systemic sclerosis is independently associated with an increased risk of acute myocardial infarction. Immunosuppressors do not lower the risk of acute myocardial infarction in our study.

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.

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.