Clinical and Laboratory Differences Between Early-Onset and Late-Onset Adult Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) in adults is not uncommon, and its prevalence has been increasing in the recent decades. However, there is a paucity of data about the differences between early-onset and late-onset adult AD. OBJECTIVE: The objective of this study is to investigate the clinical and laboratory characteristics of adult AD, focusing on the differences between early-onset and late-onset adult AD. METHODS: We retrospectively reviewed the medical records and clinical photos of 214 adult AD patients (≥18 years of age) over a 3-year period. We classified the patients into 2 groups: early-onset (first onset of AD before 12 years of age) and late-onset (first onset of AD at 12 years of age or later). RESULTS: Among 214 patients, 151 patients (70.6%) belonged to the early-onset group (mean age 24.5 years), while 63 patients belonged to the late-onset group (mean age 29.5 years). An association with allergic asthma or rhinitis, a family history of atopic disease, elevated total serum IgE, and sensitivity to food allergens were more commonly seen in the early-onset group. The late-onset group had a significant likelihood of nonflexural involvement (38.1% vs 13.2%). There was no significant difference in the mean eczema area severity index score, eosinophil count, and sensitivity to aeroallergens between 2 groups. CONCLUSION: Adult AD shows different clinical and laboratory characteristics depending on the age of onset. This study could help to create awareness about the heterogeneity of AD in adulthood and encourage further studies on clinical outcomes and different therapeutic methods depending on the age of onset.

Identification of loci associated with late-onset psoriasis using dense genotyping of immune-related regions.

BACKGROUND: Chronic plaque psoriasis can be subdivided into two groups according to the age of onset: type 1 (early onset, before 40 years) and type 2 (late onset, at or beyond 40 years). So far, 36 genetic loci have been associated with early-onset psoriasis in genome-wide association studies of white populations, while few studies have investigated genetic susceptibility to late-onset psoriasis. OBJECTIVES: To characterize the genetics underpinning late-onset psoriasis. METHODS: We genotyped 543 cases of late-onset psoriasis and 4373 healthy controls using the Immunochip array, a dense genotyping chip containing single-nucleotide polymorphisms previously associated with autoimmune diseases. Imputation using SNP2HLA and stepwise logistic regression analysis was performed for markers spanning the human leucocyte antigen gene region. RESULTS: Two loci (HLA-C and IL12B) previously associated with early-onset psoriasis showed significant association at a genome-wide threshold in the current study (P < 5 × 10(-8)). Six more loci (TRAF3IP2, IL23R, RNF114, IFIH1, IL23A and HLA-A) showed study-wide significant association (P < 2·3 × 10(-5); calculated using Genetic type 1 error calculator). Additionally, we identified an association at IL1R1 on chromosome 2q13, which is not associated with early-onset disease. CONCLUSIONS: This is the largest study to date of genetic loci in late-onset psoriasis, and demonstrates the overlap that exists with early-onset psoriasis. It also suggests that some loci are associated exclusively with late-onset psoriasis.

Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease.

Neuroinflammation is a pathological hallmark of Alzheimer's disease (AD), and microglia, the brain's resident phagocyte, are pivotal for the immune response observed in AD. Microglia act as sentinel and protective cells, but may become inappropriately reactive in AD to drive neuropathology. Recent Genome Wide Association Studies (GWAS) have identified more than 20 gene variants associated with an increased risk of late-onset AD (LOAD), the most prevalent form of AD [1]. The findings strongly implicate genes related to the immune response (CR1, CD33, MS4A, CLU, ABCA7, EPHA1 and HLA-DRB5-HLA-DRB1), endocytosis (BIN1, PICALM, CD2AP, EPHA1 and SORL1) and lipid biology (CLU, ABCA7 and SORL1) [2-8], and many encode proteins which are highly expressed in microglia [1]. Furthermore, recent identification of a low frequency mutation in the gene encoding the triggering receptor expressed in myeloid cells 2 protein (TREM2) confers increased risk of AD in LOAD cohorts with an effect size similar to that for APOE, until recently the only identified genetic risk factor associated with LOAD [9,10(••)] (Figure 1). The present review summarises our current understanding of the probable roles of microglial genes in the regulation of neuroinflammatory processes in AD and their relation to other processes affecting the disease's progression.