ABSTRACT
Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.
Subject(s)
Dermatitis, Atopic/immunology , Interleukin-13/metabolism , Organ Specificity/genetics , Psoriasis/immunology , RNA/genetics , Skin/metabolism , Th2 Cells/immunology , Cohort Studies , Dermatitis, Atopic/genetics , Gene Expression Profiling , Humans , Interleukin-13/genetics , Interleukin-4/metabolism , Psoriasis/genetics , RNA, Long Noncoding/genetics , Sequence Analysis, RNA , Signal Transduction , Skin/pathology , TranscriptomeSubject(s)
Abnormalities, Multiple/classification , Abnormalities, Multiple/pathology , Darier Disease/classification , Darier Disease/pathology , Erythema/pathology , Eyebrows/abnormalities , Facial Dermatoses/pathology , Melanosis/pathology , Adolescent , Child, Preschool , Diagnosis, Differential , Erythema/classification , Eyebrows/pathology , Facial Dermatoses/classification , Humans , Male , Melanosis/classificationABSTRACT
Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease/genetics , Genotype , Myocardial Infarction/genetics , Polymorphism, Single Nucleotide/genetics , Psoriasis/genetics , Aged , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Female , Germany , Humans , Incidence , Insurance Benefits/statistics & numerical data , Insurance, Health/statistics & numerical data , Longitudinal Studies , Male , Middle Aged , Myocardial Infarction/epidemiology , Prospective Studies , Psoriasis/complications , Risk Factors , Severity of Illness IndexABSTRACT
Primary cutaneous CD4+ small to medium-size pleomorphic T-cell lymphoma (PCSM-TCL) is a rare disease that has been added as a provisional entity to the World Health Organization European Organization for Research and Treatment of Cancer (WHO-EORTC) classification of lymphomas with primary cutaneous manifestations. Patients commonly present with a solitary nodule or plaque on the head or upper trunk, but are usually otherwise in good health. The prognosis is favorable, but the optimal treatment has not been defined. Recent publications have described the expression of programmed death-1 in PCSM-TCL and T-cell pseudolymphoma, suggesting a diagnostic value of this marker in the differential diagnosis of PCSM-TCL in contrast to other types of cutaneous T-cell lymphoma. We present the case of a 12-year-old girl with a tumor of the right supraorbital area. She was treated as an outpatient four times with intralesional triamcinolone acetonide at intervals of 3 to 4 weeks. In addition to the case history, this report includes the clinical and histologic findings and a review of the current literature.
