Eczema and dermatitis • •Allergic contact dermatitis •Irritant contact dermatitis •Atopic dermatitis •Microbial eczema •Seborrheic dermatitis Allergic contact dermatitis • makes 5 – 15% of all dermatoses • •¨ prevalence – 1,5-3% •¨ incidence – 5-10 / 1000 per year •¨ Hypersensitive reaction of the • IVth type according Coombs & Gell • Allergic contact dermatitis •¨ contact allergens – molecules smaller than • 500 D – penetration through the skin barrier • •¨ binding of the molecule – hapten - to pt‘s own proteins in the skin forms an antigen – • with the molecular weight at least 5000 D • • the conjugation of haptens with proteins takes place in LC (antigen presenting cells) • Allergic contact dermatitis • • Induction phase ® penetration of allergen through the stratum corneum ® interaction with APC • ® phagocytosis of antigen ® • subsequent expression of antigen on the surface • of LC ® migration to regional lymphatic nodes and presentation of the antigen to naive • T–lymphocytes Allergic contact dermatitis •Elicitation phase – in case of sensitization ® proliferation of specific •Clone of effector T–lymfophocytes ® migration • to the site of allergen penetration • ® cytotoxic effect of T–lymphocytes releasing cytokines leading to inflammation • ® allergic contact dermatitis • Shortest time to sensitization: 5-14 days • migration of LC to regional LN takes about 5-24 hours • proliferation of T-lymphocytes – 5-10 days) Patophysiology of the late-type hypersensitivity • macrophages • IFNγ • MHCII TCR IL-2 • LC Th1 Tc1 TNFα • (IFNγ) β • Ag • • • IL-1β ê perforine • NK • granzymes • • IL-12 • • Eo • • Allergic contact dermatitis •Factors influencing the ease of sensitisation: ¨Chemical structure of allergens ¨Patient – skin barrier status (fissures, maceration) • localisation (eyelids x soles) • age ¨ ·Duration of hypersensitivity • - survival time of memory T-lymphocytes • - character of allergens European Standard Series • •Potassium dichromate O,5 % pet. •Neomycin sulphate 20 % pet. •Thiuram mix 1% pet. •Paraphenylenediamine 1% pet. •Cobalt chloride 1% pet. •Caine mix 10% pet •Formaldehyde 1% aq. •Colophony 20% pet. •Hydroxyethyl metacrylate 2% pet. •Balsam of Peru 25 % pet. •N-isopropyl-N-phenyl-4-phenylenediamine 0,1% pet. •Wool alcohols 20% pet. •Mercapto mix 2% pet. •Epoxy resin 1% pet. •Paraben mix 16% • European Standard Series •pet.4-t- butylphenol formaldehyd resin 1% pet. •Fragrance mix 8% pet. •Quaternium 15 1% pet. •Nickel sulphate 5% pet. •Kathon CG 0,01% aq. •Mercaptobenzothiazole %pet. •Sesquiterpenlactone mix 0,1% pet. •Propolis 10% pet. •Tixocortol-21-pivalate 0,1% pet. •Budesonide 0,01% pet. •Methyldibromoglutaronitrile (1,2-dibromo-2,4-dicyanobutane)* •Fragrance II 14% pet. •Lyral 0,5 % pet. •Methylisothiazolinone 0,02% aq •Textile dye mix 6,6% pet. • Metal watch Metal glasses 4cd945fcd702a Allergic contact dermatitis – nickel Metal button Metal ring 4cd7e90f74ba0.jpg 4cd7e92b4c271.jpg ACD to chromium from leather boots ACD- IPPD, antioxydant of black rubber Rubber boot Obrázek59 Obrázek60 Tonometer, stethoscope (nurse) Obrázek61 ACD to PPD from hair dyes 098 099 nik26425 nik26426 nik13845 nik13846 ACD to fragrance (eau de toilette) nik14881 21 CH2OH • 20 C O … OH 17 13 D 16 15 14 C 18 CH3 12 11 9 8 7 6 5 1 4 2 3 HO 19 CH3 A B 10 O Corticosteroids A - type Hydrocortison: D kruh nesubstituovaný, C 20, C 21 nesubstituovaný nebo C 17, C 21 krátký řetězec (acetáty nebo estery), event. C 21, thioester B - type Triamcinolon acetonid: C 16, C 17 cis-ketal struktura nebo diol struktura C - type Betametason: C 16 methyl substituce D - type Hydrocortison butyrát: C 17, a/nebo C 21 dlouhé esterové řetězce, event. C 16 metyl substituce Budesonide - Apulein ung, crm, liq, Pulmicort aer inh, Pulmicort, Turbuhaler plv inh, Rhinocort spr nas Patch test– contact allergy to Budesonide Obrázek70 Obrázek71 Obrázek72 Nik_20203 Drug eruption in patient sensitized to topical CS after systemic exposure to - Prednisone tbl Obrázek73 Obrázek74 Obrázek75 Obrázek76 Fragrances •v Cinnamic aldehyde •v Cinnamic alcohol •v a-amyl-cinnamic aldehyde •v Eugenol •v Isoeugenol •v Geraniol •v Hydroxycitronellal •v Oak moss absolute (Akranorin) • Sorbitan sesquioleate • (emulgator) •Frequency of sensitization: •worldwide 4,7-13,3% Fragrance mix I Allergic contact dermatitis– fragrance – cosmetic cream Patch tests – contact allergy to fragrance and cinnamic alcohol Obrázek79 Obrázek80 Obrázek81 Fragrances •Fragrance mix II •Lyral,Citral,Farnesol,Citronellol, •hexyl cinnamic aldehyde,Coumarine • •Fragrance mix III • yasmine absolute 2,0 % vaz.Amylcinnamaldehyde 2,0 % vaz.Musk ketone 1,0 % vaz.Sandalwood oil 2,0 % vaz.Musk moskene 1,0 % vaz.Ylang-ylang 2,0 % vaz.Cananga oil 2,0 % vaz.Vanilin 10,0 % vaz.Jasmine synthetic 2,0 % vaz.Geranium oil Bourbon 2,0 % vaz.Musk xylene 1,0 % vaz.Lavaner absolute 2,0 % vaz.Rose oil 2,0 % vaz.Narcissus absolute 2,0 % vaz.Methyl anthranilate 5,0 % vaz.Benzyl salicylate 2,0 % vaz.Benzyl alcohol 1,0 % vaz. • •Balsam of Peru •Propolis • Propolis •natural product – is a resinous mixture that honey bees collect from tree buds, sap flows, or other botanical sources. The chemical composition of propolis varies depending on season, bee species and geographic location. Propolis has approximately 50 constituents, primarily resins and vegetable balsams (50%), waxes (30%), essential oils (10%), and pollen (5%). Propolis has antibacterial, fungicidal, antipruritic and antiinflammatory effects and promotes epithelisation Allergic contact dermatitis– propolis (folk medicine preparations) Obrázek82 Obrázek83 Allergic contact dermatitis– propolis (folk medicine preparations) Obrázek84 Obrázek85 „new“ allergens •Ketoprophene – nonsteroidal antiinflammatory drug •Derivative of propionic acid • •Ketoprophene – topical systemic • Fastum Ketoprofen tbl,sup • Profenid gel Ketonal cap,sup amp i.m. • Ketonal crm Ketonal forte tbl • and others Ketonal ret tbl • Profenid cap,tob,sup amp • Profenid 100 mg pro inf • Toprec tbl •Allergy potenciated by sun exposure – photocontact allergy Photocontact allergy - ketoprophene - generalizace (Fastum gel) Photocontact allergy - ketoprophene (Fastum gel) Patch test - alergická reakce na Fastum gel Patch test - alergická reakce na ketoprophene Obrázek66 Obrázek67 Obrázek68 Obrázek69 Tea Tree Oil ¨source: leaves of the tea tree (Melaleuca • alternifolia) • ¨ occurence: Australia, Spain, Portugal ¨ use: folk /traditional/ medicine ¨ effects: antiseptic • antifungal • antibacterial • Components of Tea Tree Oil •Mixture of mono and sesquiterpens • •v Terpinen-4-ol 30-45% v 1,8 Cineol 0-15% •v g-Terpinen 10-28% v d-Cadinen stopa-8% •v a-Terpinen 5-13% v Aromadendren stopa-7% •v a-Terpineol 1,5-8% v Sabinen stopa-3,5% •v a-Terpinolen 1,5-5% v Globulol stopa-3% •v a-Pinen 1-6% v Viridiflorol stopa-1,5% •v r-Cymene 0,5-12% v d 3-Caren stopa-0,2% •v d-Limonen 0,5-4% • Allergic contact dermatitis – tea tree oil (cosmetic preparations) Patch tests – contact allergy to tea tree oil and other etheric oils Obrázek86 Obrázek87 Plant extracts family of Compositae main allergens - sesquiterpenolaktons Extr. Chamomillae - chamomile Extr. Calendulae - marigold Extr. Arnicae - arnica others: Sunflower - Heliantus annuus, Chrysanthemum, Cynia, Astra etc. nik4950 ACD to marigold in the terrain of atopic dermatitis nik4310 ACD to marigold (extr. Calendulae) Eczema contactum - chloramphenicol, extr. Chamomillae Eczema atopicum et contactum - extr. Chamomillae Eczema contactum - Neomycin, extr. Chamomillae Obrázek88 Obrázek89 Obrázek90 Irritant contact dermatitis •Nonallergic reaction •Dose dependent •Exposition to exogenous more or less toxic agent •More common than allergic contact dermatitis Irritant contact dermatitis •Causes: •chemical agents: •alkaline & acid solutions •Organic solvents (toluene…) •Detergents •Disinfectants •Food stuffs (fruit acids, mustard…) •Even water • •physical agents: UV radiation, heat, cold, mechanical factors • Clinical picture •Lesion sharply bordered •Intensity depends on the toxicity of the subsance (more toxic.. more acute reaction) •Toxic agents: •redness – swelling - blisters - necrosis • •Less toxic agents – chronic ICD •Redness, scales, lichenification, hyperkeratosis • • • Acute ICD alergo 019 Chronic ICD alergo 018 Treatment of ACD & ICD •Topical corticosteroids •Class I - low potency CS • HCT acetate (HCT ung.), DXM acetate (DXM crm.) •Class II mid-potent CS • HCT butyrate (Locoid crm.,lotio), TMC acetonid (TMC crm.), alclomethason (Afloderm crm, ung.) • prednikarbate (Dermatop crm., ung.) • methylprednisolon aceponate (Advantan crm.) •Class III - potent CS • betamethasone dipropionate (Beloderm,Diprosone crm.) • fluocinolone acetonide ( Gelargin gel,ung.) • momethason furoate ( Elocom crm., ung., lotio) •Class IV – very potent CS • clobethasol propionate (Dermovate crm., ung) •Antihistamines, systemic corticosreroids – short courses • Atopic dermatitis •strongly pruritic chronic or chronically relapsing non-infectious dermatitis with variable morphology and clinical course, usually starting during early childhood • •often associated with positive personal or family history in terms of allergic rhinitis, conjunctivitis and bronchial asthma. •genetic predisposition •In about 80% associated with IgE levels • • Atopic dermatitis -epidemiology •Incidence in population: 0,5 - 5% •(higher incidence – scandinavian countries) • • infants 16% • children under 2 y 14% • children under 14 y 12% • adults 2% • Atopic dermatitis • two forms, same clinical picture • • extrinsic 80% elevated IgE • sensitization to airborne • and/or food allergens (sIgE) • - association with allergic • rhinoconjunctivitis and/or • allergic asthma • • • intrinsic 20% normal levels of IgE skin barrier disturbace Etiology of AD: unknown basis = genetic predisposition 1) skin barrier disturbance 2) hyperreactivity of the skin environmental triggers: 1) irritant substances, allergens 2) stress 3) many others …. I. skin barrier disturbance •Genetically conditioned: •Filaggrin: null mutation of FLG R501X and 2282del4 alleles lead to increased permeability of skin barrier and they are • associated with AD (in about 50% cases), as well as with ichtyosis vulgaris •Claudin- 1, corneodesmosin •Increased activity of serin proteases Genes involved in AD geny AE skin barrier disturbance •Defective synthesis of ceramides • (takes place in lamellar bodies in granular layer of epidermis) • ß • decreased ability to bind water in the skin • skin barrier disturbance AD and skin barrier •Defective structure and function of skin • barrier • Þ insufficient hydration (TEWL ) • ß • dryness - xerosis • ß • increased irritability of the skin • possibility of contact sensitization II: Immunological abnormalities in AD biphasic model of AD (Th2 à Th1 shift) •Ag IL-2 , IFNg • IgE Th1h1 48 h • IL-12 • FeεRI IL-12 • • LB • • TCR • MHCII IL-4, IL-13 • Ag • Th2 B-ly IgE • • • • • IL-5 MBP 24 h • • Eo ECP • EDN III. Staphyloccus aureus and AD •colonization of AD lesions in 74 - 96% atopic patients, 30 - 56% even on „healthy“ skin • •Mechanisms: •Defective skin barrier with „naked“ laminin and fibronectin • enables SA binding the skin • •Decreased defensive mechanisms:Ldefective signallization via • TLR 2 • ¯b2 defensine a kathelicidine • ¯ production of IFN g • •1) Toxic effect: staphylococcal exfoliatine a •2) Stimulation of sIgE production (sIgE à stimulation of basophils à histamine) •3) superantigens: SEA- SEE a TSST-1 • • • • - without previous processing by LC • - able to bridge V b chain of TC Receptor, • - not necessary exact conformity of all 5 • subunits of the receptor • 1000x stimulation • - non-specific but huge stimulation of Tly • (1 SA even 20% of circulating lymph.) • • Grafika2 Staphyloccus aureus and AD Triggering and mainaining factors of AD •Allergy ( house dust mites, pollen, pets, • molds, foods – milk, eggs, wheat, soya, nutts, fish) •Microbes – Staphylococcus aureus •Irritant substances (water,detergents etc.) •- climatic (temperature, wind, low humidity ..) •Psychological stress • Clinical picture of AD •AD in infants • •Exudative form – acute eczema •(oozing, crusting) • • ¨ location - periorally • - periorbitally • • ¨ possibility of spreading - erythroderma • • Atopic dermatitis – Infant AD Obrázek1a Infant AD Obrázek6 Obrázek5 Clinical picture of AD •AD in children and adolescents • •Decrease of exudation - lichenification • • ¨ most often – flexural eczema • - facial eczema • ¨ less often - erythroderma • Atopic dermatitis – flexural eczema Obrázek1b Obrázek1c Atopic dermatitis – erytrodermic form Obrázek Obrázek9 Obrázek10 Obrázek11 Clinical picture of AD •AD in adults •(about 15% of cases appear after puberty) • •¨ flexural •¨ prurigininous •¨ neurodermitic •¨ erythrodermic • chronic course acute flares possible Adult AD – pruriginous form Obrázek12 Obrázek13 Obrázek14 Obrázek15 Adult AD – neurodermitic form Obrázek16 Obrázek17 Obrázek18 Adult AD – erythrodermic form Obrázek19 Obrázek20 AD in adults •¨ atypical forms - nummular, dyshidrotic, • hyperkeratotic forms • •¨ minimal forms - cheilitis sicca, stomatitis • angularis, pulpitis sicca, • intertrigo retroauricularis, aj. • Adult AD - dyshidrotic form Obrázek21 AD eyelid dermatitis, lip dermatitis Obrázek24 Obrázek25 Obrázek26 AD retroauricular dermatitis Obrázek27 Obrázek28 Complications of AD •¨ bacterial - impetiginization (St. aureus) •¨ viral – herpetication-HSV, warts, mollusca •¨ fungal (Tr. rubrum, Pityrosporum ovale) •¨ contact sensitization (nickel, fragrances, KS…) • • • • •¨ association: • alopecia areata • ichtyosis vulgaris • vitiligo 1-895a I~000023 Eczema atopicum herpeticatum Obrázek29 Obrázek30 Obrázek31 Obrázek32 Treatment of AD • mild form of AD (30-40% of patients): • education of pacient ( or parents) • identification of triggering factor • and their elimination • emmolients and baths • topical corticosteroids • pimecrolimus • antihistamines during flares Treatment of AD • mid-severe form of AD (40-50% of patients): • treatment similar as in mild form • + tacrolimus • or • hospitalization – lab. and clinical tests (triggers) • traditional topical treatment /tar/ • or • phototherapy (UVB 311nm, UVA-1) • • Tacrolimus (PROTOPIC oinment) Protopic 001 • Topical Immunomodulator • Blocks calcineurin • antiinflammatory • antipruritic • Long - term treatment • No skin atrophy Treatment of AD • severe form of AD (5-10% patients): • phototherapy (PUVA, UVA-1) • systemic corticosteroids (short courses) • imunosupressives: cyclosporine A, MMF, AZT,MTX • imunomodulants: IFN g (?) • experimental terapie: i.v. Ig • JAK, PDE ihibitors • biologicals (dupilumab....) Microbial eczema •Allergy of IVth type to bacterial allergens – • mostly to Staph. aureus • appears mostly secondary: • in pyodermas, scabies, atopic dermatitis, ICD • around fistulas, stomias, in varicous terrain on legs • around sites of inflamamtion (chronic rhinitis, otitis) • variant: nummular dermatitis (coin shaped • patches and/or plaques) usually in patients with focal bacterial infection (tooth gfranuloma, chronic tonsillitis, chronic urogenital infections etc. Microbial eczema Microbial eczema Obrázek91 Obrázek92 nik_00035 Microbial eczema in patients with CVI = varicous eczema nik_00041 Microbial eczema in a patient with chronic otitis nik_00042 Microbial eczema in a patient with scabies Treatment of microbial eczema •Acute phase: •Drying compresses •Topical zinc preparations •Topical corticosteroids in lotion base •Subacute and chronic phase: •ATB paste, endiaron paste, tar preparations •Combination with topical CS (TMC-E, Belogent, Fucicort Systemic ATBs • • Seborrheic dermatitis §localisation: seborrheic predilection sites § §etiology: genetic predisposition • dysseborrhea – altered composition of sebum • Malassezia furfur = pityrosporon ovale • immunodeficiency - AIDS • depletion of zinc •Clinical picture: erythematoous scaly lesions •In typical sites: scalp, eyebrows, nasolabial folds, •midchest region, around umbilicus, groins & axillae §Subjective complaints: itching, burning nik_00045 nik_00046 Treatment of seborrheic dermatitis § • §Topical imidazole antifungals + topical corticosteroids §Topical imidazole antifungals §Topical preparation with zinc §zinc supplementation •(Systemic antifungals) •