Autoimmune comorbid diseases associated with lichen planus: a nationwide case-control study.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disorder with unknown aetiology. The association between LP and various autoimmune diseases has been reported, but nationwide study of the relationship of LP with associated diseases is quite limited. OBJECTIVE: Our study aims to clarify the association between LP and a variety of autoimmune diseases in Taiwanese. METHODS: Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan from 1997 to 2011. In total, 12,427 patients with LP and 49,708 age- and gender-matched controls were enrolled. RESULTS: Among patients with LP, there were significant associations with systemic lupus erythematosus (SLE) (multivariate odds ratio [mOR]: 2.87; 95% CI: 1.97-4.17), Sjögren's syndrome (mOR: 3.75; 95% CI: 2.66-5.28), dermatomyositis (mOR: 6.34; 95% CI: 1.82-22.16), vitiligo (mOR: 2.09; 95% CI: 1.31-3.32) and alopecia areata (mOR: 2.82; 95% CI: 2.20-3.62). On gender-stratified analyses, SLE and alopecia areata were significantly associated with LP in both genders. The association with Sjögren's syndrome was significant only in female patients. The associations with dermatomyositis and vitiligo became insignificant in both genders. CONCLUSION: Lichen planus is associated with various autoimmune diseases. Further study is required to elucidate the possible underlying mechanisms and roles of autoimmunity in the aetiology of LP.

The natural course of early-onset atopic dermatitis in Taiwan: a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) often manifests in early childhood and has variable disease course among individual patients. Previous studies regarding the natural course of AD have usually been of small sample size and were not based on nationwide populations. OBJECTIVES: We aimed to find out the disease duration and remission rate of children with early-onset AD (onset in the first 2 years of life) in Taiwan, and to determine whether the presence of allergic rhinitis (AR) or asthma affects the disease course. METHODS: The patients with early-onset AD in a nationally representative cohort were selected using the National Health Insurance Research Database of Taiwan and were followed from birth to 10 years of age. Kaplan-Meier survival analysis was carried out to analyse the disease duration and remission of AD. Between-group analysis using the log-rank test was carried out to analyse the influence of risk factors on the disease course. RESULTS: Of the 1404 children with early-onset AD, 19.4% had disease duration < 1 year and 48.7% had disease duration < 4 years. During the follow-up, 69.8% of the patients went into remission. Sex, onset age, presence of AR, presence of asthma and presence of respiratory atopy (either AR or asthma) did not show statistically significant influence on disease course. CONCLUSIONS: Children in Taiwan with early-onset AD had disease of variable natural course, and the median disease duration was 4.2 years. About 70% of the patients went into remission eventually. The presence of AR or asthma did not affect the disease course of AD.

Psychiatric comorbidities in patients with alopecia areata in Taiwan: a case-control study.

BACKGROUND: Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported. OBJECTIVES: To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan. METHODS: Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age- and gender-matched controls were enrolled. RESULTS: Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression [odds ratio (OR) 2·23; 95% confidence interval (CI) 1·09-4·54] was found in patients with AA aged < 20years. An increased rate of anxiety (OR 1·43; CI 1·15-1·77) was observed with AA onset between the ages of 20 and 39years. The highest odds of obsessive-compulsive disorder (OR 3·00; CI 1·11-8·12) and anxiety (OR 2·05; CI 1·56-2·68) were observed in patients with AA aged 40-59years. Moreover, about 50% of psychiatric disorders occurred earlier than AA. CONCLUSIONS: AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders.

Genome-wide scan identifies a susceptibility locus for familial primary cutaneous amyloidosis on chromosome 5p13.1-q11.2.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder in South America and Southeast Asia. Most cases of PCA are sporadic but familial aggregation has been reported from South America and Taiwan. The different susceptibility among ethnic groups suggests that genetic factors may play an important role in its pathogenesis. OBJECTIVES: We aimed to perform a genome-wide scan by linkage analysis across 15 families with familial primary cutaneous amyloidosis (FPCA) to map the disease gene(s) for FPCA. PATIENTS AND METHODS: A total of 15 FPCA families including 50 individuals affected with PCA were recruited. Throughout the 22 autosomes, 369 polymorphic microsatellite markers were used initially. Regions showing a LOD score > 1 identified in the initial scan were further analysed with additional markers. Two-point and multipoint linkage analysis were performed by using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: A maximum two-point LOD score of 4.76 for the marker D5S1490 (theta = 0.10, alpha = 0.60) and a multipoint LOD score of 4.50 between D5S822 and D5S623 (alpha = 0.60) were obtained under the assumption of heterogeneity. A peak NPL score of 5.23 (P value = 0.000007) was found from D5S1490 to D5S2076. Further analysis focusing on two major families identifies a common haplotype shared by all affected individuals between D5S1490 and D5S623. To our knowledge, this is the first report of genome-wide analysis of a large number of FPCA pedigrees. CONCLUSIONS: Our study provides evidence for significant linkage to chromosome 5p13.1-q11.2 in a subset of FPCA families.

Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23.

BACKGROUND: There is a high incidence of primary cutaneous amyloidosis (PCA) in South America, South-east Asia and Taiwan. To date, the aetiology of PCA remains unknown, but it is believed to be multifactorial. Although most cases are sporadic, some patients have a family history. Familial aggregation and different susceptibility to PCA among ethnic groups suggest that genetic factors may play an important role in its pathogenesis. However, no genetic loci for familial PCA (FPCA) have been identified so far. OBJECTIVES: In order to identify the susceptibility gene of FPCA, we took a candidate gene approach and performed linkage analysis on chromosome 1q21.3-24.2, including the 1q23.2 region where the gene encoding serum amyloid P component (APCS) is located. PATIENTS AND METHODS: Nine FPCA families including 29 individuals affected with PCA were recruited for this linkage study. Initially, 11 highly polymorphic microsatellite markers spanning the region from 1q21.3 to 1q24.2 were genotyped and revealed a suggestive linkage region. This region was further fine-mapped with seven additional markers. We also re-sequenced the 2.5-kb genomic region of the APCS gene in 29 affected and 42 control individuals. Two-point and multipoint linkage analyses were performed using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: Both two-point and multipoint linkage analysis for all 11 markers generated negative or small positive total lod scores for all nine families. However, when we considered only three families, a maximum two-point total lod score of 2.09 was obtained for the marker D1S2844 at theta = 0.01. A plateau of multipoint total lod score between D1S2768 and D1S2878 with a maximum of 2.48 at the marker D1S2844 was observed. A maximum NPL score of 3.11 (P = 0.008) was also obtained for the marker D1S2878. However, re-sequencing of the APCS gene identified no functional mutation. CONCLUSIONS: Both parametric and nonparametric linkage evidence suggested that a possible susceptibility locus for a subset of FPCA might exist on chromosome 1q23. This is the first report demonstrating suggestive evidence of linkage of FPCA to a locus in this candidate region. No functional sequence variations of the APCS gene were found to be associated with this disease among the study families. Our data imply the existence of at least one additional locus responsible for FPCA in these families, confirming genetic heterogeneity of this skin disorder.

Respiratory function and extraocular muscle paralysis following administration of pancuronium bromide in dogs.

Pancuronium bromide, a neuromuscular blocking agent, was evaluated in canine cataract surgical patients under general anesthesia to determine its effects on respiratory function and globe position. Two paralytic, anesthetic regimes were studied: one using a standard dosage of 0.066 mg kg-1 pancuronium bromide, given intravenously while providing the patient with ventilatory support, and one using a dosage of 0.022 mg kg-1 in which no ventilatory support was provided. Eye position and anterior vitreal position/displacement were recorded by a surgeon who was blinded as to treatment group. Physiological parameters indicative of respiratory function were monitored. Both dosages of pancuronium produced comparable, neutral globe position within 30 s following administration which lasted for 20-30 min. All patients in the standard dose group experienced uneventful anesthetic episodes with physiological parameters well within the normal ranges. Within 5 min after administration, all patients in the low-dose group developed a pronounced respiratory acidosis (mean arterial pH = 7.07 +/- 0.08; mean PaCO2 = 79.8 +/- 10.7 mmHg), which exceeded a set of predetermined safety limits, and subsequently these dogs received ventilatory support. We conclude that 0.022 mg kg-1 pancuronium rapidly produces an unacceptable level of respiratory acidosis and, as a result, patients receiving neuromuscular blocking agents should routinely receive ventilatory support.