CONTACT DERMATITIS Oktay Taşkapan,MD

Ekzema-Dermatit Polimorf inflamasyon paterni Kontakt dermatit: Derinin ekzematöz reaksiyonuyla kendini gösteren inflamatuar bir intolerans (irritasyon / allerji) İKD daha sık, (etken belirlenmezse) AKD’nin prognozu daha kötü KD insidansı %0,79 ve en az bir allerjene duyarlanma %15-16 * KD, dermatolojik konsültasyonların % 4-7’sinde saptanır *Brasch J ve ark. JDDG 2007.

Contact Dermatitis A spectrum of inflammatory skin reactions induced by exposure to external substances Contact dermatitis represents the vast majority (79–90% annually) of skin-related occupational complaints A common skin problem. Nearly eight million physician visits per year (2000, USA) More than 85 000 chemicals, almost 3000 of the may act as contact allergens When avoidance and appropriate treatment isn’t achieved, the condition may become chronic and lead to a major impairment in quality of life It is a major health concern for patients and has a major impact on the economy

A lifetime incidence of “hand eczema” is 17 % (Danish studies) For contact dermatitis without further etiologic definition, i.e. irritant and allergic combined, an incidence of 7.9 per 1000 population per year was observed Incidences in selected professions are significantly higher

In contrast to ACD, there is no specific recognition of a foreign substance in ICD, but a reaction of the immune system towards skin damage Even in ICD, inflammatory mediators released in the framework of a complex network by cells of the epidermis and dermis as well of the immune system play a central role Routine tests such as histology do not allow differential diagnosis between ICD and ACD.

Acute stage: Erythematous papules, edema, and vesiculation Subacute stage: The vesicles rupture  oozing and eroded skin  crusting and scaling As the papulovesicular lesions disappear, ACD enters into chronic stage (lichenification, further scaling, fissuring and pigmentation) Secondary bacterial infections may occur

Irritant contact dermatitis (ICD) Allergic contact dermatitis (ACD) Photocontact dermatitis (phototoxic / photoallergic)

Irritant contact dermatitis: lesions limited to sites of contact, spectrum ranges from erythema to necrosis, clinical picture dependent on acuteness and agent Allergic contact dermatitis: spread from primary site of contact is typical. Location and configuration of lesions can be indicative of causative agent Airborne contact dermatitis: dermatitis on exposed skin without overt allergen contact (wall paints, flowering plants, others) Photo contact dermatitis: occurs primarily on light-exposed skin. Previous contact not necessary for irritants, but definitely for photoallergens Asteatotic dermatitis: dry, “fissuring” skin with red fissures especially in aged and overly stressed skin (wrong skin care, excessive washing).

Airborne contact dermatitis (due to parthenium hysterophorus)

Photocontact dermatitis

Allerjik kontakt dermatit Antijene özgüllük gösteren efektör T hücrelerinin rol oynadığı bir deri inflamasyonu Yaşam boyu prevalansı yaklaşık %15 (Brasch J ve ark. JDDG 2007) Kaşıntı, vezikülasyon ve papül oluşumu daha belirgin İlk ortaya çıkan lezyonlar, temas bölgesinde sınırlıdır, ancak uzak yayılım da gelişebilir

Allergic contact dermatitis can occur anywhere on the body There may be extreme pruritus and the lesions may spread beyond the areas of initial contact The appearance of the lesion in ACD often corresponds to the stage Edema predominates if areas of loose tissue, such as eyelids or genitalia, are affected The vesicles may coalesce into bullae

Yama testi: IPPD: (++) Yama testi: Potasyum dikromat, kolofoni, karba miks ve tiuram miks (++)

Allerjik kontakt el ekzeması

İrritan kontakt dermatit Derinin irritanlara karşı geliştirdiği non-immünolojik / non-spesifik reaksiyon Genellikle yüksek dozda irritan maddeyle karşılaşan hemen herkeste, özellikle atopik bireylerde görülür Kuaförler, besin sektöründe çalışanlar ve sağlık çalışanlarında İKD gelişme olasılığı yüksektir Doğrudan doku yıkımıyla birkaç dakika ile birkaç saat içinde ortaya çıkar, genellikle keskin sınırlıdır Akut evrede kaşıntıdan çok yanma, batma, acıma ve ağrı belirgindir Kronik evrede hiperkeratoz ve fissürler görülür

Akut İKD (dilüe edilmemiş alkali temizleyiciye bağlı) Akut İKD (Monokloroasetik asite bağlı) İKD (bromoasetik aside bağlı) Akut İKD (diklofenak jel kullanımına bağlı) Akut İKD (ağdaya bağlı) Yüzde HTİKD (taş tozuna bağlı)

İrritan el ekzeması Kronik İKD (temizlik işçisi) Kronik İKD (metal işçisi) İKD (Aşırı el yıkamaya bağlı) Kronik İKD (hemşire) Kronik İKD (basımevi işçisi) Kronik İKD Kronik İKD Kronik İKD (numuler tip)

A specific diagnostic test to identify irritant contact dermatitis is not available The diagnosis of irritant contact dermatitis is made on the basis of history and clinical findings after excluding a causative contact sensitization, and can indirectly be confirmed by successive healing after stopping exposition to the noxious agent DD: Atopic dermatitis, fungal infections, cutaneous T-cell lymphoma or special forms of psoriasis

AKD’de Lezyonların yerleşimi ve tanısal ipuçları Lezyonların dağılımı Olası allerjen kaynakları Saç sınırı, saçlı deri ve kulak arkaları Saç ürünleri (boya, şampuan, saç kremi, jöle vb.) Göz kapakları Havayla taşınan, sürülen ya da başka yerlerden taşınan ürünler (kozmetikler, tırnak boyaları, tırnak sertleştiriciler, kokular, saç boyaları, ele uygulanan krem ve losyonlar, dokunulan cisimlerdeki metal parçacıkları) Kulak memeleri, boyun Metal takılar, kokular Aksiller çukur Deodoranlar Aksilla (çukur dışındaki alanlar) Tekstil boyaları Peri/infraumbilikal bölge Metal düğmeler, kemer tokaları vb. Ekstremitede çizgisel lezyonlar Zehirli sarmaşık / sumak, fitofotodermatit Ayak dorsal yüzü Deri, kauçuk, boya vb. Ayağın ağılık taşıyan bölümleri Ayakkabı tabanı yapımında kullanılan ürünler Lee PW ve ark. Curr Opin Pediatr 2009.

Asteatotic (xerotic) eczema

Nummular Dermatitis and Dyshidrotic Dermatitis

ACD Pathogenesis

CD4+ or CD8+ T cells play critical roles in ACD Langerhans cells, NKT cells, NK cells, B cells, and Treg cells Although most environmental agents are too large to penetrate the skin layers, some are of sufficiently low molecular weight to penetrate the stratum corneum Hapten exposure duration and the host immune response are crucial components in the development of ACD.

ACD: Histopathology A pattern of subacute chronic dermatitis or acute dermatitis may be seen The inflammatory infiltrate in the dermis predominately contains lymphocytes and other mononuclear cells Epidermal edema (ie, spongiosis and microvesicle formation) may be seen Chronic stage: Thickening of the epidermis (acanthosis) with hyperkeratosis and parakeratosis

Epidermal spongiosis and edema Epidermotropism of mononuclear cells Dermal inflammatory cellular infiltrate

Differential diagnosis

ACD: Differential diagnosis ICD Asteatotic eczema Atopic dermatitis Seborrheic dermatitis Nummular dermatitis Dyshidrotic dermatitis Photocontact dermatitis Intertrigo Tinea corporis Tinea cruris / pedis Dermatomyositis Lichen simplex chronicus Cutaneous T-cell lymphoma Perioral dermatitis Stasis dermatitis Cellulitis

Differential diagnosis of acute ACD Acute ICD Erysipelas Acute SLE Dermatomyositis Angioedema Herpes zoster (early phase)

Severe edema of the face 2 days after dyeing the hair at home (a) Severe edema of the face 2 days after dyeing the hair at home (a). The patient was referred by the emergency physician as erysipelas because she had slight fever, nausea, and lymphadenopathy. Close inspection revealed eczematous lesions at the hairline and on the scalp (b).

Allergens

Allerjen Kaynak Yerleşim Nikel Takılar, düğme, toka, gözlük, anahtar, para, cep telefonları, ortodontik ürünler Yüz / göz kapakları, kulak memeleri, boyun, bilek, sub / periumbilikal, el (SKD) Neomisin Antibiyotikli pomatlar Yüz / göz kapakları Peru balsamı / fragrans miks Parfüm ve kozmetikler, tatlandırıcılar, diş macunları, pastiller Yüz / göz kapakları, ağız, dudaklar, boyun, eller Timerosal Aşılar, kremler, losyonlar, antiseptikler, kozmetikler, otik /oftalmik solüsyonlar, rimeller Periorbital bölge Kobalt Takılar, düğmeler, tokalar, seramik, çimento, B12 Kulak memeleri, periorbital bölge, boyun, umbilikal bölge, eller / bilekler Krom Tabaklanmış deri, kibrit, çimento, boyalar Eller, umbilikal bölge Tiuram Elastik bileklikler, çoraplar, eldivenler, mayolar, ayakkabılar, pestisitler Bilekler, eller, ayaklar, gövde Lanolin Nemlendiriciler, sabunlar, pomatlar Eller, nemlendirici uygulanan bölgeler Formaldehit / f.salan ürünler Şampuan, losyon, kozmetikler, giysiler Yüz, kulaklar, eller, gövde PPD Saç boyaları, yazıcı mürekkepleri, kına Saç sınırı, kulaklar, eller, dövme alanları Lee PW ve ark. Curr Opin Pediatr 2009.

Metals Nickel is the most common cause of ACD in women High-nickel content jewelry is a redisposing factor Ear piercing is considered to be the principal inducer of nickel CD Hand eczema in nickel sensitive patients is often of the dyshidrotic type and may be aggravated by nickel ingestion Chromate is the most common contact allergen in men Sensitization to it is usually occupational. Occupational exposure is most frequent in construction workers who handle cement Other common sources are chrome-tanned leather, bleaching agents, paints, and printing solutions.

Cosmetics and skin care products Compulsory ingredient labeling of cosmetic products has greatly facilitated the diagnosis and treatment of cosmetic contact dermatitis Positive patch tests are found most frequently to preservatives, perfumes, active or category-specific ingredients, excipients/ emulsifiers and sunscreens The relevance of the positive patch tests is confirmed if the contact dermatitis disappears upon discontinuation of the use of the product Most allergic reactions are caused by cosmetics that remain on the skin: “stay-on” or “leave-on” products

Dermatitis from clothes and shoes Contact dermatitis to clothes is usually located in the axillae Clothing dermatitis from formaldehyde is rare nowadays. Textile dye dermatitis is usually related to disperse dyes Leather articles contain several substances that may cause ACD: chrome, adhesives (paratertiary butyl phenol formaldehyde resin), and dyes A number of accelerators and antioxidants used in the production of synthetic rubber may also cause contact dermatitis.

Drug dermatitis Drug dermatitis may be elicited by the active ingredient of a topical drug, by the vehicle or by a preservative Contact sensitization to antibiotics, antiseptics, and anesthetics is relatively frequent, especially in leg ulcer patients ACD from topical corticosteroids has been reported with increasing frequency Systemic application of a drug to which an individual has been sensitized by a previous cutaneous exposure may cause systemic contact dermatitis

Diagnosis

History and clinical findings are guides to the diagnosis History should include questions on the development of the disease, exposition to allergens and causal relationships and be renewed after the results of patch testing Exposition and clinical findings lead to the suspicion that the dermatitis might be caused by contact with an exogenous agent The diagnosis of ACD is made by demonstrating the causative contact sensitization in patch testing In vitro methods in diagnosing contact allergy have not been validated

Patch testing

Patch testing Patch testing is cost effective and reduces the cost of therapy in patients with severe ACD At the time of patch testing, the patient's dermatitis must be under excellent clinical control The dermatitis cannot be severe or acute, as this may result in the false-positive, ‘angry back’ reaction Ptients should not be taking high-dose systemic corticosteroids (low dose, up to 10–20 mg/day, may be acceptable) It is also advisable to avoid the application of potent topical corticosteroids to the patch test sites

Patch testing Patch testing is required to confirm the diagnosis of ACD and to make a differential diagnosis Patch testing must be performed by health care providers trained in the proper technique Patch testing procedure: Small amounts of appropriate labeled dilutions of chemicals are applied to the skin and occluded for 2 days The patch test must be read not only at 48 hours, when the patch tests customarily are removed, but again between 72-96 hours and 1 week following initial application

İşaretleme ve (dijital) fotoğraf çekimi

Patch test recording method (+) weak positive reaction: erythema, infiltration, possibly papules (++) strong positive reaction: erythema, infiltration, papules, vesicles (+++) extreme positive reaction: intense erythema and infiltration, coalescing vesicles, bullous reaction ? doubtful reaction (weak erythema only) IR irritant reaction of different types NR negative reaction NT not tested

YAMA TESTİ DEĞERLENDİRME ÖLÇÜTLERİ (Uluslararası Kontakt Dermatit Araştırma Grubu) KLİNİK YORUM Reaksiyon yok Kontakt allerji yok +/- Hafif eritem Kuşkulu reaksiyon + Eritem,infiltrasyon ve ödem Olası (ya da yalancı pozitif) kontakt allerji ++ Papüler eritem, infiltrasyon ve vezikülasyon Allerjik kontakt dermatit +++ Vezikülobüllöz reaksiyon Allerjik kontakt dermatit (kesin) IR İrritasyon

Nikel sülfat PPDA PPDA PPDA

Nikel sülfat: (+++)

N-isopropyl-N-phenyl-p-phenylenediamine IPPD: (++) N-isopropyl-N-phenyl-p-phenylenediamine

IRRITANT REACTIONS

Excited skin syndrome (“angry back”)

Treatment

İrritan kontakt dermatitte tedavi İrritanlardan kaçınma: Su, sabun, deterjan / yağlar, alkali, asit ve solventler İş yerinin ve çalışma koşullarının gözden geçirilmesi Eldiven kullanımı (NRL, PVC, nitril, neoprene vb.) Nemlendirici ve syndet kullanımı Bariyer kremler (“koruyucu kremler”) Topikal kortikosteroidler Topikal immünomodülatörler: Boyun ve yüz bölgesindeki İKD’de pimekrolimus krem çok etkili bulunmuş (Mensing CO ve ark. IJD 2008) Fototerapi (kümülatif İKD’de)

Allerjik kontakt dermatit tedavisi 1. Basamak Neden olan allerjenin saptanması 2. Basamak Kaçınma 3. Basamak Deri bakımı 4. Basamak Topikal kortikosteroidler, topikal antimikrobiyaller 5. Basamak Topikal immünomodülatörler (kalsinörin inhibitörleri) Sistemik steroidler / sistemik antihistaminler (?), sistemik antibiyotikler 6. Basamak Fototerapi 7. Basamak İmmünomodülatörler / immünosupressanlar 8. Basamak Biyolojik ajanlar 9. Basamak Eliminasyon diyetleri, hiposensitizasyon 10.Basamak Diğerleri (hipnoz, psikososyal danışmanlık vb.) Allerjik kontakt dermatit tedavisi

Treatment principles The only available etiologic treatment of ACD is elimination of the contact allergen The patients should be informed about the identity of the offending agent and the possible sources of the sensitizer ,as well as alternative products that are allergen free. Cross-reacting substances should be listed Topical steroids are used in the acute stage and are gradually replaced by ointments and cold creams as the skin lesions withdraw If ACD is widespread and severe, systemic corticosteroids may be indicated for a short period of time.

Topical corticosteroids Topical corticosteroids are the mainstay of therapy in ACD. Basic principles of dermatologic therapy is valid for ACD, AD and all other eczematous lesions: While corticosteroid lotions and creams are chosen in acute eczematous stage, ointments are used in chronic phase. The potency of topical corticosteroids and localization of lesions (face, trunk, palm etc.) should also be considered. In general, it is reasonable to use high potency corticosteroids initially and switch to less potent ones as the disease improves

Potency Classification of Topical Corticosteriods Very potent Moderately Potent Clobetasone butyrate 0.05% (Eumovae) Hydrocortisone butyrate 0.1 % (locoid) Prednicarbate 0.1% (Dermatop) Triamcinolone acetonide 0.1% (Kenacort) Mild Hydrocortisone acetate 0.5% (Hipokort) Prednisolone 0.125 % (prednol) Clobetasol propionate 0.05% (Dermovate) Halcinonide 0.1% (Volog, Betacorton) Potent Betamethasone dipropionate 0.05% (Diprolene) Betamethasone valerate 0.05% (Betnovate, Celestoderm) Diflucortolone valerate 0.1% (Temetex) Fluticasone propionate (Cutivate) Mometasone furoate 0.1% (Elocon)

Topical immunomodulators Tacrolimus (protopic) and pimecrolimus (elidel) have been found to be effective in the treatment of nickel-induced ACD Pimecrolimus cream, twice daily with overnight occlusion was also effective in the treatment for chronic hand dermatitis

Systemic corticosteroids may be used in acute stage of ACD (oral prednisone 0.5–1.0 mg/kg per day, or equivalent) Their use should be confined to severe, resistant and/or widespread cases A short course of oral antibiotic therapy is very effective in secondarily infected ACD Cyclosporin A and azathioprine may be tried in resistant cases Ultraviolet radiation; PUVA, UVB and bath-PUVA may bring benefit in generalized ACD, or in cases of unresponsive to standard therapeutic approaches.

Çocuklarda AKD gelişme olasılığının azaltılması için öneriler Çocuklara topikal olarak uygulanan ürünler irritasyona neden olmamalı, koruyucu ve “fragrance” içermemelidir Hem duyarlanma, hem de direnç gelişme olasılığı dikkate alınarak topikal antibiyotiklerin kullanımı kısıtlanmalıdır On yaşın altındaki çocuklarda kulak deldirme önerilmemelidir Anne babalar ve çocuklarla ilgilenen kişiler, uygun deri bakımı konusunda bilgilendirilmelidir *Kütting B ve ark. Eur J Dermatol 2004.