Dermatitis – diff. diagnosis I • eczema x dermatitis •Allergic contact dermatitis •Irritant contact dermatitis •Microbial eczema •Seborrheic dermatitis •------------------------------ •Atopic dermatitis • 1. Allergic contact dermatitis • 5 – 15% of all dermatoses • •¨ prevalence – 1,5-3% •¨ incidence – 5-10 / 1000 per year •¨ Hypersensitive reaction of the • IVth type according to 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 happens in LC (antigen presenting cells) • Allergic contact dermatitis • • Induction phase ® penetration of allergen through 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 III 10% pet •Formaldehyde 1% aq. •Colophony 20% pet. •Hydroxyethylmethacrylate 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% pet. • European Standard Series •P -4-t- butylphenol formaldehyde 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 mix 14% pet. •Lyral 5% pet. •Methylisothiazolinone 0,2% aq. •Textile dye mix 6,6% pet. • Most common contact allergens DVK (2019) •1. nickel sulphate 16,1% •2. balzam of Peru 9,3% •3. Kathon 6,8 •4. methylisothiazolinone 5,7% •5. epoxide resin 5,3% •6. PPD 5,0% • textile dye mix 5,0% • fragrance mix I 5,0% • cobalt chloride 5,0% •10. propolis 3,9% • Metal watch Metal glasses 4cd945fcd702a Allergic contact dermatitis – nickel Metal button Metal ring Nik_0001 Allergic contact dermatitis from cobalt & nickel - coupled allergy 008_rajtrova 4cd7e90f74ba0.jpg 4cd7e92b4c271.jpg ACD to chromium from leather boots Kathon CG •Preservative, mixture of CMI and MI 3:1 -cosmetics and other toiletries (hair cosmetics, soaps, refreshing • towels, toilet paper) since 2015 in the EU allowed only in cosmetic products for short-term skin contact –rinse off, concentration up to 15 ppm - household preparations (washing and cleaning preparations, • polishes) - industry (adhesives, water-based paints, latex paints, cooling • fluids etc. - there is no concentration limitation!) Possibility of group hypersensitivity with isothiazoline derivatives used in industry - benzisothiazolinone, octylisothiazolinone 533e9c0f2203b.jpg Allergic contact dermatitis – Kathon CG (from cosmetic preparations), and to methylizotiazolinone, octylizothiazolinone 5411656584f4e.jpg 541165e5003d9.jpg 541165f16e5cc.jpg 5411653c6e4bb.jpg ACD - IPPD, antioxydant of black rubber Rubber boot Obrázek59 Obrázek60 Tonometer, stethoscope (nurse) Obrázek61 ACD to PPD from hair dyes 098 099 nik26425 nik26426 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 nik13845 nik13846 ACD to fragrance (eau de toilette) nik14881 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 • Jasmine absolute, Amylcinnamaldehyde , Musk ketone, Sandalwood oil Musk moskene , Ylang-ylang , Cananga oil , Vanillin 10,0 %, Jasmine synthetic , Geranium oil Bourbon, Musk xylene, Lavander absolute, Rose oil , Narcissus absolute , Methyl anthranilate , Benzyl salicylate, Benzyl alcohol • •Chemical similarities with: Balsam of Peru • Propolis • Colophony •Shared natural substances (cinnamic alhehyde, alcohol, acid, eugenol…) • Shared components in natural produsts •Balsam of peru •cinnamic alcohol •cinnamic aldehyde •cinnamic acid •eugenol •isoeugenol •PABA •benzylbenzoát •benzaldehyd •benzylalcohol •colophony •limonen •vanillin Fragrance-mix I: •cinnamic alcohol •cinnamic aldehyde •cinnamic acid •eugenol •Isoeugenol • •a-amylcinnamoc aldehyde •hydroxycitronellal •geraniol •oak moos absolute Propolis: •Cinnamic alcohol •Cinnamic acid •Vanillin • • • •Caffeic acid •3-hydroxy-cinnamic acid •3-methoxy cinnamic acid •Dimethyl caffeic acid Tea tree oil: •terpinens •d-limonen •a-pinen •1,8-cineol •d-3-caren 49c8d0017ca96.jpg 48bce9698f01f.jpg 48bce9867e839.jpg Eczema contactum – propolis, balsam of Peru α-amyl-cinnamic aldehyde, colophony Propolis •natural product – 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 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 Hydrocortisone: D ring unsubstituted, C 20, C 21 unsubstituted or C 17, C 21 short chain (acetates or esters), possibly. C 21, thioester B - type Triamcinolone acetonide: C 16, C 17 cis-ketal structure or diol structure C - type Bethametasone: C 16 methyl substitution D - type Hydrocortisone butyrate: C 17, and / or C 21 long ester chains, possibly. C 16 methyl substitution 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 „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 Acrylates •Industry: plastics, plexiglass, synthetic rubber, insulating materials, plasters, acrylic floors, adhesives, UV-cured paints, paints Dentistry: composite fillings, orthodontic appliances Bone cement: endoprostheses, osteosynthesis Medical devices: spectacle frames, patches, hearing aids, insulin pumps… •Cosmetic industry: cosmetic industry acrylic nails, artificial eyelash adhesives Acrylates •Monomers - high sensitizing potential Polymers (cured) do not sensitize but: risk of sensitization by contact with monomers created by secondary depolymerisation • 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 2. 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 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 corticosteroids – short courses • 3. 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 • • 4. Seborrheic dermatitis §localisation: seborrheic predilection sites § §etiology: genetic predisposition, hormonal status • dysseborrhea – altered composition of sebum • Malassezia sp. = pityrosporon ovale • immunodeficiency - AIDS • depletion of zinc, comorbidities •Clinical picture: erythematoous scaly lesions •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 immunomodulators (off label) §Topical imidazole antifungals §Topical preparation with zinc §zinc supplementation •Systemic antifungals •