Association Between Pruritus and Fibromyalgia: Results of a Population-Based, Cross-Sectional Study.

Fibromyalgia is a common musculoskeletal condition that affects up to 3% of the worldwide population. Its pathogenesis is not entirely clear but is thought to involve neurogenic inflammation as well as aberrations in peripheral nerves and central pain mechanisms. It is believed that the same mechanism that causes hypersensitivity and pain in patients with fibromyalgia also predisposes them to pruritus.

Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients.

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA and extracutaneous/systemic CLA memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB).

Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood.

Background: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.

Objective: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls.

The pathogenetic role of Th17 immune response in atopic dermatitis.

Purpose Of Review: As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment.

CLA+ memory T cells in atopic dermatitis.

Circulating skin-homing cutaneous lymphocyte-associated antigen (CLA) T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are associated with the CLA T cell mechanisms in atopic dermatitis patients. The function of CLA T cells corresponds with the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases.

High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.

Background: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available.

The erythema Q-score, an imaging biomarker for redness in skin inflammation.

Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with inter-rater reliability and variability in the setting of higher Fitzpatrick skin types make visual erythema assessment unreliable. We developed and validated a computer-assisted image-processing algorithm (EQscore) to reliably quantify erythema (across a range of skin types) in the dermatology clinical setting.

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood.

Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored.

Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects.

Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4/CD8 T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA) versus systemic/CLA T cells.

The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.

Objective: To analyze blood inflammatory proteins of early pediatric AD.

Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.

Atopic dermatitis endotypes and implications for targeted therapeutics.

Recent research advancements indicate that atopic dermatitis (AD) is a complex disease characterized by different subtypes/phenotypes based on age, disease chronicity, ethnicity, filaggrin and IgE status, and underlying molecular mechanisms/endotypes. This heterogeneity advocates against the traditional "one-size-fits-all" therapeutic approaches still used to manage AD. Precision medicine approaches, striving for targeted, tailored, endotype-driven disease prevention and treatment, rely on detailed definitions of the disease's variability across different phenotypes.

Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.

Background: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA) T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo.

Objective: We sought to measure cytokine production by circulating skin-homing (CLA) versus systemic (CLA) "polar" CD4/CD8 ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects.

Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients.

Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature.

Ichthyosis molecular fingerprinting shows profound T17 skewing and a unique barrier genomic signature.

Background: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy.

Objective: We sought to profile the molecular fingerprint of the most common orphan ichthyoses.

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.

The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4/CD8 and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations.

Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial.

Background: Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems.

Objective: To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD).

Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations.

Background: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA ) vs systemic (CLA ) "polar" CD4 and CD8 and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood.

Methods: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4 and CD8 T cells.

The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain mutations: Immunophenotyping and response to ustekinumab.

Background: The immune abnormalities underlying the ichthyoses are poorly understood.

Objective: To determine the immunophenotype of an ichthyosis resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin gene (DSP) and target therapy on the basis of molecular pathogenesis.

Methods: Immunophenotyping was performed by using the blood and skin of a girl with SR6 region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy.

Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march.

Skin barrier abnormalities have been suggested to play an essential role in initiation of early atopic dermatitis (AD). Antigen penetration through a compromised barrier likely leads to increased innate immune responses, antigen-presenting cell stimulation, and priming of overt cutaneous disease. In a T2-promoting environment, T-cell/B-cell interactions occurring in regional lymph nodes lead to excessive IgE switch.

An Update on the Pathophysiology of Atopic Dermatitis.

Atopic dermatitis (AD) is increasingly recognized as a complex, inflammatory skin disease involving interplay of multiple elements. This article notes key advances in understanding of immune dysregulation, skin barrier dysfunction, environmental, genetic, and microbial influences orchestrating disease pathogenesis, and the relevance of therapeutic interventions in each area. Accumulating evidence and the discovery of new T-cell subsets has matured AD as a multiple-cytokine-axes-driven disorder, evolved from the widely held belief of it being a biphasic Th1/Th2 disease.