1. Contact dermatitis Boonthorn 23 June 2010

2. Definition Classification Epidemiology Pathology & Pathophysiology Clinical presentation & Differential diagnosis Investigation Special exposure associated with CD management Outline

3. Common inflammatory skin disorder Most common recognized as eczematous inflammation Allergic or irritant skin reaction caused by an external agent Definition J Allergy ClinImmunol 2010;125:S138-49. Allergy 2009:64:1669-1714.

4. Allergic contact dermatitis (ACD) (20%) inflammation caused by allergen-specific T lymphocytes. rapid development of dermatitis occurs following re-exposure to low concentrations of allergen, not cause lesions in non-sensitized individuals Irritant contact dermatitis (ICD) (80%) develop following prolonged and repeated exposure to irritants inflammatory cells have role in development of dermatitis allergen-specific lymphocytes not involved in pathogenesis prior sensitization is not necessary Classification www.worldallergy.org

5. In U.S. (2004) overall prevalence rate 24,400 /100,000 people Cohort population-based studies in Europe prevalence rates 0.7% - 18.6% for ACD Incidence of OCD in other countries 1.3 - 19 cases per 10,000 All age groups are affected with slight female preponderance prevalence increases with age decreased prevalence in patients >70 years Epidemiology J Allergy ClinImmunol 2010;125:S138-49.

6. Pathology epidermal hyperplasia with spongiosis and mounds of parakeratosis. There is superficial, perivascular infiltrate of lymphocytes and eosinophils with exocytosis

7. inflammation in epidermis and superficial dermis Acute superficial perivascular infiltration with lymphocytes, monocytes and small number of eosinophils increased intercellular spaces between keratinocytes (spongiosis):predominant histologic feature of CD Chronic thickening of epidermis, irregular elongation of the rete ridges and vertical thickening of collagen of papillary dermis Pathology WWW.worldallergy.org

8. ACD prototype of type IV cell-mediated hypersensitivity reaction ICD nonimmunologic, multifactorial, direct tissue reaction T cells activated by nonimmune, irritant, or innate mechanisms release proinflammatory cytokines dose-dependent inflammation ACD and ICD frequently overlap because many allergens at high enough oncentrationscan also act as irritants Pathophysiology J Allergy ClinImmunol 2010;125:S138-49.

9. Pathophysiology (ACD) Allergy 2009: 64: 1699–1714.

10. Pathophysiology (ACD) Allergy 2009: 64: 1699–1714.

11. Keratinocytes play key role in development of both ACD and ICD synthesize and release pro-inflammatory cytokines, in particular interleukins IL-1, 6 and 8, TNF-α and GM-CSF These cytokines play important part in recruitment and homing of inflammatory cells and can be induced and released from keratinocytes by both irritants and allergens role of keratinocyte

12. Langerhans cells are primary APCs of epidermis cell surface expression of CD1a and presence of intracytoplasmicBirbeckgranules process protein Ag by cleaving them into peptides and present fragments in peptide-binding groove of their surface located MHC class II Hapten-conjugated LC migrate to local LN where they present allergen to T lymphocytes T lymphocytes must then home to inflamed skin Antigen presentation: The role of Langerhanscell

13. Homing is process whereby circulating cells migrate to relevant sites This process relies on linkage between adhesion molecules expressed on endothelial cells and their ligands expressed on lymphocytes homing receptor on T lymphocytes probably "cutaneous lymphocyte antigen" (CLA), ligandfor E-selectin Additional adhesion molecule ICAM-1 interacts with LFA-1 VCAM-1 interacts with VLA-4 Homing of T lymphocytes

14. Classic presentation pruritic, eczematous plaque localized to site of allergen exposure redness, edema,papules, vesiculation, weeping, crusting Geometric or linear patterns or involvement of unusual focal skin areas, eg. earlobes, or weight-bearing areas of feet may suggest contact cause Chronic ACD (i.e. nickel and fragrances) can be insidious and present as localized lichenification or with more generalized reactions Clinical presentation ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

15. Differentiation between ICD and ACD J Allergy ClinImmunol 2010;125:S138-49.

16. J Allergy ClinImmunol 2010;125:S138-49.

17. Exogenous causes of ICD in Occupational Dermatology Clinic, Skin and Cancer Foundation, Australia (total 621 patients over the period 1993–2002) Australasian Journal of Dermatology (2008) 49, 1–11

18. Differential diagnosis ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

19. Differential diagnosis Best practice

20. Physical examination Current Opinion in Pediatrics 2009, 21:491–498

21. Patch tests gold standard for identification of contact allergen occlusive patch testing is most common technique Patch testing a patient with active AD more likely to produce “angry back” reaction, resulting in a false-positive reading affected by oral corticosteroids (>20 mg of prednisone per day or its equivalent) cancer chemotherapy, or immunosuppressive drugs Topical corticosteroids should be discontinued for 5 to 7 days before patch testing not affected by antihistamines Investigation J Allergy ClinImmunol 2010;125:S138-49.

22. Sources of allergens T.R.U.E. TEST :not US FDA approved But recommended by CD experts No. of allergens ideal number remains controversial T.R.U.E. Test contains 29 allergens higher false-negative reactions to neomycin, thiurammix, balsam of Peru, fragrance mix, cobalt, and lanolin NACDG series from 65 to 70 allergens use of FDA-certified antigen panel available in US can fully evaluate ~ 25- 30% of ACD Investigation J Allergy ClinImmunol 2010;125:S138-49.

23. Current Opinion in Pediatrics 2006, 18:385–390

24. applied to upper or middle back areas (2.5 cm lateral to midspinalreference point) free of dermatitis and hair kept in place for 48 hours read 30 minutes after removal of patches second reading should be done 3 to 5 days after initial application Metals , topical antibiotics , topical orticosteroids, and PPD can elicit positive reactions after 7 days Nonstandardized patch tests tested at 1:10 to 1:100 dilutions Patch test technique J Allergy ClinImmunol 2010;125:S138-49.

25. ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

26. Repeat open application test (ROAT) Improving reliability of interpreting tests for leave-on products suspected allergens are applied to antecubitalfossa twice daily for 7 days and observed for dermatitis absence of reaction makes CD unlikely If eyelid dermatitis is considered, ROAT can be performed on back of ear dimethyl-glyoximetest for nickel identification of allergens Skin biopsy Distinguishing CD from morphologically similar diseases Investigation J Allergy ClinImmunol 2010;125:S138-49.

27. localized or generalized inflammatory skin disease in contact-sensitized individuals exposed to hapten orally, transcutaneously, intravenously, or by means of inhalation Cause Metal (cobalt, copper, chromium, gold, mercury, nickel, and zinc) Medicationscorticosteroids, antihistamines (diphenhydramine, ethylenediamine, hydroxyzine, and doxepin), miconazole, terbinafine, neomycin,gentamicin, erythromycin, pseudoephedrine, benzocaine, tetracaine, oxycodone, IVIG, aminopenicillins, 5-aminosalicylic acid, naproxen, allopurinol, mitomycinC, 5-FU Herbal medicine Systemic contact dermatitis J Allergy ClinImmunol 2010;125:S138-49.

28. Symmetric drug-related intertriginous and flexural exanthema Criteria for diagnosis : exposure to systemic drug at first or repeated dosing (contact allergens excluded) erythemaof gluteal/perianalarea, V-shaped erythemaof inguinal/perianalarea, or both involvement of at least 1 other intertriginous/flexural localization symmetry of affected areas absence of systemic signs and symptoms Drug induced SCD J Allergy ClinImmunol 2010;125:S138-49.

29. Second most common type of occupational disease In 1999, incidence rate of occupational skin disorders was 49 cases per 100,000 most common occupations associated with OCD are health professionals (especially nurses), food processors, beauticians and hairdressers, machinists,andconstruction workers Occupational contact dermatitis ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

30. 4 of 7 criteria must be positive to conclude OCD clinical appearance is consistent with CD cutaneousirritants or allergens are present in workplace anatomic distribution of dermatitis is consistent with skin exposure to chemicals in course of various job tasks temporal relationship between exposure and onset of symptoms is consistent with CD nonoccupationalexposures are excluded as probable causes of dermatitis dermatitis improves away from work exposure and reexposure causes exacerbation there are positive-reaction and relevant patch tests performed according to established guidelines Occupational contact dermatitis ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

31. Toxicodendron dermatitis (poison ivy) is most common form of ACD and can be readily identified by its streak-like or linear papulovesicularpresentation caused by urushiol, which is found in saps of this plant family Urushiol contained in mango skin,cashewnut oil, ginkgo (female) leaves, Japanese lacquer, and Indian marking ink Plant dermatitis ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

32. Allergic contact dermatitis to poison ivy (toxicodendronradicans). Note the linear lesions induced by contact with branches www.worldallergy.org

33. Current Opinion in Pediatrics 2006, 18:385–390

34. Current Opinion in Pediatrics 2009, 21:491–498

35. Metals Nickel NACDG reported 18.7% of patients evaluated for ACD had positive patch test reaction to nickel Female sensitization to nickel higher because of increased ear piercing 1% of nickel allergy have systemic reactions to nickel content of normal diet Foods with higher nickel content include soybean, fig, cocoa, lentil, cashew, nuts, and raspberry SELECTED CONTACT ALLERGENS J Allergy ClinImmunol 2010;125:S138-49.

36. Allergic contact dermatitis to nickel in watchband

37. Allergic contact dermatitis to nickel in earring

38. Allergic contact dermatitis to nickel in belt buckle Current Opinion in Pediatrics 2006, 18:385–390

39. Gold NACDG reported that 389/4101(9.5%) had positive patch test reactions to gold hands (29.6%); face, with seborrheic distribution (19.3%); and eyelids (7.5%) mostly used for fashion appeal, anti-inflammatory medication, used in electroplating industry, part of dental appliances (present with oral symptoms) J Allergy ClinImmunol 2010;125:S138-49.

40. Common allergens in these products include fragrances, preservatives, excipients, glues, and sun blocks Fragrance most common cause of ACD from cosmetics results in positive patch test reactions in 10.4% of patients ‘‘unscented’’ and ‘‘Fragrance-free’’ Fragrance mix I containsallergensfoundin 15% to 100% of cosmetic products and might detect ~85% of subjects with fragrance allergy positive patch test reaction to fragrance must correlate with distribution of dermatitis and evaluation of clinical relevance, eg. positive ROAT reaction Cosmetics J Allergy ClinImmunol 2010;125:S138-49.

41. Preservatives and excipients Lanolin : common component of consumer products It is weak sensitizer on normal skin but a stronger sensitizer on damaged skin stasis dermatitis, are at higher risk of lanolin sensitivity Cosmetic preservatives Formaldehyde releasers non–formaldehyde releasers : Parabenmost commonly used preservative in cosmetics, as well as in pharmaceutical and industrial products Type I immediate hypersensitivity reactions (contact urticaria) and SCD from ingestion of paraben-containing medications or foods have been reported J Allergy ClinImmunol 2010;125:S138-49.

42. Hair products Second most common cause of cosmetic allergy PPD(Paraphenylenediamine) is most common cause of CD in hairdressers In hair dye users the dermatitis often spares the scalp and usually involves the face near the hairline, eyelids, and neck PPD cross-reacts with COX-2 inhibitor (celecoxib), sunscreens, and antioxidants used in manufacture of rubber products New hair dyes that contain FD&C and D&C dyes have very low levels of cross-reactivity with PPD J Allergy ClinImmunol 2010;125:S138-49.

43. Allergic dermatitis from black leather watch band. Possible allergens include chromates used to tan leather and paraphenylenediaminedye www.worldallergy.org

44. CAPB ( Cocoamidopropylbetaine) amphotericsurfactant often found in shampoos, bath products, and eye and facial cleaners CAPB allergy typically presents as eyelid, facial, scalp, and/or neck dermatitis Glycerol thioglycolate active ingredient in permanent wave solution Unlike PPD, thioglycolatesmight remain allergenic in hair long after it has been rinsed out skin eruptions can continue for weeks after application of permanent wave solution J Allergy ClinImmunol 2010;125:S138-49.

45. Antibiotics and antiseptics Neomycin and nitrofurazone are potent sensitizers Neomycin sulfate can cross-sensitize with gentamicin, kanamycin, streptomycin, spectinomycin, tobramycin,andparomomycin Medications J Allergy ClinImmunol 2010;125:S138-49.

46. corticosteroid 0.2-6% Patients with worsening of previous dermatitis or initial improvement followed by deterioration of dermatitis after application of corticosteroids should be evaluated Cross-reactivity between groups A and D2 and groups B and D2 also has been reported optimal patch test concentration not worked out for most corticosteroids 30% of ACD to corticosteroids be missed if delayed 7-day reading not done Medications J Allergy ClinImmunol 2010;125:S138-49.

47. Current Opinion in Pediatrics 2009, 21:491–498

48. Allergic contact dermatitis to topical steroid preparation applied to hands. Note massive edema, erythema, and sparing of skin under watch band www.worldallergy.org

49. use of nickel in biomedical devices,ledto increasing concern about safety in suspected nickel-sensitized patients Presently,highvariability of care no large, evidence-based guidelines 10 patients with positive patch test reaction to metal had in-stent restenosis associated with clinical symptoms allergy to metals,plays relevant role in inflammatory fibroproliferativerestenosis CD Due to Surgical Implant Devices J Allergy ClinImmunol 2010;125:S138-49.

50. criteria for diagnosis of cutaneousimplant–induced reaction dermatitis (localized or generalized) appearing after implant surgery persistent dermatitis that is resistant to appropriate therapies positive patch test result proven history to metallic component of implant or to commonly used acrylic glues resolution of dermatitis after removal of implant CD Due to Surgical Implant Devices ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

51. Allergen identification to improve contact avoidance Alternatives and substitutes to cosmetics should be offered to patient to increase compliance supportive care and relief of pruritus, cold compresses with water or saline, Burrow solution , calamine, and colloidal oatmeal baths might help acute oozing lesions Excessive handwashing should be discouraged in hand dermatitis, and nonirritating or sensitizing moisturizers must be used after washing Treatment J Allergy ClinImmunol 2010;125:S138-49.

52. TC is first-line treatment for ACD For extensive(>20% BSA) and severe CD, systemic corticosteroids might offer faster relief (12-24hr) recommended dose is 0.5 to 1 mg/kg daily for 5 to 7 days, and only if patient is comfortable at that time is dose reduced by 50% for next 5 to 7 days Treatment J Allergy ClinImmunol 2010;125:S138-49.

53. topical T-cell selective inhibitors efficacy in ACD or ICD not been established antibiotics should be used for secondary infections of ACD or ICD antihistamines have been used for relief of pruritus associated with ACD, generally ineffective diphenhydraminenot be used in patients with ACD to Caladryl and hydroxyzine hydrochloride in ethylenediamine-sensitive patient Other modes of therapy : UV light treatment and immunomodulating agents, eg.MTX,AZA, and MMF Treatment ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

54. Primary prevention In high-risk industries and professions, preventive surveillance programs are possible, especially for apprentices or newly hired workers Secondary prevention Once diagnosis of ACD or ICD is established, emollients, moisturizers, and/or barrier creams may be instituted Prevention ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006

55. ICD is caused by direct toxicity without prior sensitisation and ACD is delayed hypersensitivity reaction Results in localised burning, stinging, itching, blistering, redness and swelling at area of contact with allergen or irritant. Patch testing may aid identification of offending agent Skin biopsy may also be helpful Treatment involves removal of offending agent, future avoidance of offending agent, topical corticosteroids and/or short course of oral corticosteroids. Conclusion