AD lect 37 - immune-mediated epithelial diseases-SM.pdf

Atopic Dermatitis = AD Atopic Dermatitis or AD • Type I hypersensitivity response causing chronic skin inflammation • Characterized by dry, intensely itchy skin, a raised red rash, and inability of skin to hold moisture • Mainly affects infants and children, but it may affect adults as well • AD i...

Atopic Dermatitis = AD Atopic Dermatitis or AD • Type I hypersensitivity response causing chronic skin inflammation • Characterized by dry, intensely itchy skin, a raised red rash, and inability of skin to hold moisture • Mainly affects infants and children, but it may affect adults as well • AD is one of many forms of eczema https://images-1.eucerin.com/~/media/eucerin/international/skin-concerns/atopic-dermatitis/atopic-dermatitis-on-face/eucerin-int-scatopic-dermatitis-face-06.jpg?h=170&mw=290&w=290&hash=09875DE7B4DB8693D65CCCC06DB26B7C Predisposition to Development of Atopic Dermatitis Are Filaggrin Mutations & Allergies • Thought to be a form of type I hypersensitivity response since it is prevalent in people with history of allergies/asthma (personal or family) • Believed that there may be an underlying defect – mutation in filaggrin, the structural protein involved in keratinocyte differentiation and barrier functions • Exacerbated by stress and physical damage to skin – e.g., harsh soaps, detergents, wool, dry/cold weather, infection, workplace irritants (fumes, chemicals) • What is the difference between atopic dermatitis and eczema? Often used interchangeably, eczema is a general term for several forms of cutaneous disease (see notes). • Similar triggers for AD and eczema Filaggrin Mutations Compromise Keratin Bundles and Weaken the Skin Barrier Mutations in Filaggrin = Greatest Risk Factor for AD Filaggrin = filament aggregating protein Pathophysiology of AD Process • Stress to skin – e.g., allergen, chemical • Increased permeability of skin, so triggering substance is delivered to resident APCs • APCs process Ag and activate B and CD4 T cells, differentiating to CD4 Th2 • CD4 Th2 cells secrete IL-4/5/13, and provide help to activate B cells • Plasma cell isotype switches to IgE • IgE binds to FcR on mast cell and eos • On next exposure to trigger, mast cells and eos degranulate and release mediators that produce symptoms https://www.jacionline.org/article/S0091-6749(00)80006-8/fulltext Symptoms of Atopic Dermatitis • Believed to affect 15-30% of children and 2-10% of adults in developed countries • Itching followed by recurring red, patchy, raised skin rash (papules) • Other clinical features found in notes • Blisters ooze and crust; may get infected • Chronic atopic dermatitis can lead to tough/thickened skin = “lichenification” https://i0.wp.com/images-prod.healthline.com/hlcmsresource/images/ImageGalleries/lichenification/2638-Lichenification-1296x728-slide1.jpg?w=1155 https://post.medicalnewstoday.com/wpcontent/uploads/sites/3/2020/02/lichenification2-scaled.jpg https://atopicdermatitis.net/wp-content/uploads/2017/07/ad_005.jpg Diagnosis, Prevention, and Treatment of AD Diagnosis • Physical exam https://www.verywellhealth.com/ • History of allergies • Allergy testing Prevention • Avoid agents that trigger the rash (e.g., harsh soaps, food) • Breastfeeding – may boost immune system and maybe prevent atopic dermatitis • Hygiene hypothesis may play a role (early exposure to allergens/pathogens) Treatment • Moisturizing with thick creams or petroleum jelly > lotions • Control scratching – e.g., mittens, socks, etc. on baby’s hands • Antihistamines – e.g., diphenhydramine, hydroxyzine • Topical or oral corticosteroids • Calcineurin inhibitors – e.g., pimecrolimus, tacrolimus; remember calcineurin activates T cells through NFAT cell signaling system • UV light treatment – phototherapy (psoralen + UV-A light – PUVA); may have localized immunomodulatory effect • Vitamin D • Dilute bleach bath