The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-α and interleukin-1β induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27–CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27–CCR10 interactions have a pivotal role in T cell–mediated skin inflammation.

CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.14891

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently predates the development of allergic rhinitis or asthma. It is an important skin condition with significant costs and morbidity to patients and their families; the disease affects more than 10% of children. Recent studies have demonstrated the complex interrelationship of genetic, environmental, skin barrier, pharmacologic, psychologic, and immunologic factors that contribute to the development and severity of AD. The current review will examine the cellular and molecular mechanisms that contribute to AD as well as the immunologic triggers involved in its pathogenesis. These insights provide new opportunities for therapeutic intervention in this common skin condition. (J Allergy Clin Immunol 2000;105:860-76.)

https://www.jacionline.org/article/S0091-6749(00)80006-8/pdf

Atopic dermatitis: New insights and opportunities for therapeutic intervention

The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune-suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1468-3083.2012.04635.x

Guidelines for treatment of atopic eczema (atopic dermatitis) part I.

Atopic dermatitis (AD) is a common pruritic and chronically relapsing inflammatory skin disease. The pathophysiology of AD includes disturbed skin barrier functions, frequent allergic responses against allergens, defects in the antimicrobial immune defense, and a genetic predisposition. In this review we summarize advances in our understanding of the complex interdependent network of members of the rapidly growing protein superfamilies of cytokines and chemokines that lead to the development of AD.

Cytokines and chemokines orchestrate atopic skin inflammation

Background Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. Methods We conducted a randomized, double-blind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate-to-severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. Results After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51...

/pdf/a-short-term-trial-of-tacrolimus-ointment-for-atopic-p91rocuapy.pdf

Francois Daniel

Papers

A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group