Contact dermatitis


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Contact dermatitis

Presented by Planee Vatanasurkitt, MD.


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Contact dermatitis

  1. 1. Contact dermatitis : role of immune response in allergic contact dermatitis<br />Planeevatanasurkitt,MD<br />
  2. 2. outline<br />Immune cells in contact dermatitis<br />Classification of contact dermatitis<br />Investigation in contact dermatitis<br />Data of patch testing in contact dermatitis Thailand study<br />Common allergen in contact dermatitis<br />treatment<br />
  3. 3. introduction<br />Contact dermatitis CD is one of the most common inflammatory skin disease<br />CD represents majotity 79-90% annually of skin related occupational complaints<br />CD can be divide into four cattegories base on etiology<br />
  4. 4. pathophysiology<br />In1935 studies of 2,4-dinitrochlorpbenzene DNCB sensitization guinea –pigs<br />Electrophilic component of hapten and nucleophilic side chain of target protein in skin<br />Chemical that are not normally electrophilic can converted to properties of hapten by air oxidation or cutaneous metabolism<br />Contact dermatitis 2005;53:189-200<br />
  5. 5. ACD 20%<br />prototype of type IV cell-mediated hypersensitivity reaction<br />ICD 80%<br />nonimmunologic, multifactorial, direct tissue reaction<br />T cells activated by nonimmune, irritant, or innate mechanisms release proinflammatory cytokines<br />dose-dependent inflammation <br />ACD and ICD frequently overlap because many allergens at high enough concentrations can also act as irritants<br />Pathophysiology<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  6. 6.
  7. 7. histology<br />Spongiosis: predominant histologic feature of CD<br />
  8. 8. Antigen presenting cell in contact dermatitis<br />Langerhans cells<br />keratinocytes<br />
  9. 9. Langerhans cells<br />At steady state 90% LC exhibited relatively little mobility<br />After application hapten dendrite surveillance extension and retraction cycling habitude [dSEARCH] and lateral migration of LC<br />The amplification of dSEARCH is mediated by IL-1α and TNF-α ,cytokine produced by keratinocytes<br />
  10. 10. Langerhans cell<br />LC exhibit increase expression of <br />CD 83 ,marker for LC maturation<br />ICAM-1,adhesion molecule<br />CD 40,B7-1[CD80] B7-2 [CD86], co- stimulation molecule<br />Expression of these marker is specific to hapten-exposed LC, dermal irritants trigger LC migration but not result in LC surface marker changes<br />
  11. 11. Cytokine in LC migration in response to hapten<br />TNF-αand IL-1β signals are required for LC migration <br />during the initiation phase of ACD<br />
  12. 12. Langerhan cell<br />Immature LC express CCR5 and CCR6<br />In response to hapten exposure LC upregulate CCR7<br />CCR7-CCL 19,21 targeting LC to lymph node<br />CCL19 CCL21 express in lymph node paracortex<br />CCL21 expressed by afferent lymphatic endothelial cell <br />
  13. 13. keratinocytes<br />KC are the source of cutaneous TNF-α expression after hapten exposure<br />Express IL-1 receptors which response to LC –derived IL 1 β,leading to expression of TNF-α<br />KC also express ICAM-1 in the presence of IFN-γ<br />T cell ,source of IFN-γ, express CD11a which bind to ICAM-1 on keratinocyte<br />
  14. 14. keratinocytes<br />In the absence of CD80/CD86,antigen presentation in the context of MHC class II leads to clonalanergy and tolelence<br />
  15. 15. keratinocytes<br />KC can express IL 10 particularly in response to hapten exposure<br />KC express IL-16,only first appears 6 h after hapten exposure with maximal expression at 24 h after exposure during elicitation<br />KC express high level of RANKL [receptor activator of NF-κB ligand ] this molecule interacts with its receptor RANK on Langerhans cells leading to upregulation cell surface marker including CD205 and CD86,CD205 associated with induction of CD4+ CD25+<br />
  16. 16.
  17. 17. Tolerance mechanism<br />
  18. 18. lymphocyte<br />T cells <br />B cells<br />NKT cells<br />T reg cells<br />NK cells<br />
  19. 19. T cell<br />Primary effector cell of ACD are CD8+ cell<br />Trinitrophenyl TNP is strong hapten that induced predominantly CD8+ T cell CHS response and can triggered normal CHS response in CD8+ T cell depleted mice<br />In the absence of CD8+ T cell, CD4+T cells are capable of mediating the CHS to trinitrophenyl<br />J Interferon Cytokine Res 2002;22:407-12<br />
  20. 20. T cell<br />Invitro studies indicated that hapten-specific CD8+ T cell induce Fas-mediated apoptosis of CD 4+ T cells<br />During sensitization CD8+T cell trigger apoptosis of CD4+ T cell, there by eliminating hapten-specific CD4+ T cell priming/expansion and ensuring CD8+ T cell are dominant effector cell<br />Expert Rev ClinImmunol 2005;1:75-86<br />J Immunol 2004:173:3178-3185<br />
  21. 21. T cell<br />Cytokines involved in T helper cell type 1 proliferation/activation are consider important during development of CHS responses<br />Contact allergen triggered KC produce IL12 leading to proliferation of T cell into Th1 phenotype<br />Scand J immunol 2004 ;59:385-394<br />
  22. 22. T cell<br />In vitro studies demonstrated that both initiation and elicitation phases of DNFB-mediated ACD were significantly blocked by IL-12 neutralizing antibodies<br />Conclusion IL-12 is important in the pathogenesis of ACD<br />J Immunol 1996;156:1799-1803<br />
  23. 23. T cell<br />IFN-γ classically produced by Th1 CD4+T cell<br />IFN- γi n CHS shown to be produced by CD8+ T cells<br />IFN- γis important in the pathogenesis of cellular infiltration associated with CHS while cutaneous edema is IFN-γ independent<br />J Exp Med 1996;183:1001-1012<br />
  24. 24. B cell<br />Initial hapten exposure B-1 proliferate and produce IgM while B-2 cell remain at pre-exposure levels<br />IgM antibody activates complement<br />C5a trigger inflamation through binding to C5a receptor on mast cell and platelet leading to recruitment of effector T cells<br />J Exp Med 2002;196:1277-1290<br />Trends Immunol 2004;25:441-449<br />
  25. 25. NKT cells<br />Characterizes by expression CD 161 and α /β chains of T cell receptor<br />TCR on invariant NKT cell bind highly conserved glycolipids in the context of CD1d<br />The production of IL-4 by iNKT cells shown to be toll-like receptor dependent<br />
  26. 26. Treg cells<br />Express CD25, cytotoxic T lymphocyte-associated antigen-4 [CTLA-4] ,and forkhead box P3 [Foxp3]<br />In individuals who do not develop ACD to nickel,theTreg cells were able to inhibit effector T cells activation while individuals who exhibit ACD to nickel were unable to suppress nickel-specific effector T cell activation in vitro<br />Treg are involved in ACD suppression and hapten tolerance<br />
  27. 27. NK cells<br />NK cell have ability to acquire hapten specific memory and mediated CHS<br />
  28. 28. Clinical evaluation<br />Diagnosis of allergic contact dermatitis from clinical presentation and possible exposure to contact allergen<br />
  29. 29. Systemic contact dermatitis<br />localized or generalized inflammatory skin disease in contact-sensitized individuals exposed to hapten orally, transcutaneously, intravenously, or by means of inhalation<br />Cause<br />Metal (cobalt, copper, chromium, gold, mercury, nickel, and zinc)<br />Medicationscorticosteroids, antihistamines (diphenhydramine, ethylenediamine, hydroxyzine, and doxepin), miconazole, terbinafine, neomycin,gentamicin, erythromycin, pseudoephedrine, benzocaine, tetracaine, oxycodone, IVIG, aminopenicillins, 5-aminosalicylic acid, naproxen, allopurinol, mitomycin C, 5-FU<br />Herbal medicine<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  30. 30. Drug induced SCD <br />Symmetric drug-related intertriginous and flexural exanthema<br />Criteria for diagnosis :<br />exposure to systemic drug at first or repeated dosing (contact allergens excluded)<br />erythema of gluteal/perianal area, V-shaped erythema of inguinal/perianal area, or both<br />involvement of at least 1 other intertriginous/flexural localization<br />symmetry of affected areas<br />absence of systemic signs and symptoms<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  31. 31. Occupational contact dermatitis<br />4 of 7 criteria must be positive to conclude OCD<br />clinical appearance is consistent with CD<br />cutaneous irritants or allergens are present in workplace<br />anatomic distribution of dermatitis is consistent with skin exposure to chemicals in course of various job tasks<br />temporal relationship between exposure and onset of symptoms is consistent with CD<br />nonoccupational exposures are excluded as probable causes of dermatitis<br />dermatitis improves away from work exposure and reexposure causes exacerbation<br />there are positive-reaction and relevant patch tests performed according to established guidelines<br />ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006 <br />
  32. 32. Investigation: Patch tesing<br />Indicated in patients with chronic,pruriticeczematous,orlichenified dermatitis in whom ACD is suspected<br />Affected by oral corticosteroid [>20 mg of prednisolone /day or equivalent] cancer chemotherapy,immunosuppressive drug<br />Topical corticosteroid should be discontinued for 5-7 days before patch testing<br />
  33. 33. Investigation <br />Sources of allergens<br />T.R.U.E. TEST :not US FDA approved<br />But recommended by CD experts<br />Numbers of allergens<br />ideal number remains controversial<br />T.R.U.E. Test contains 29 allergens<br />higher false-negative reactions to neomycin, thiuram mix, balsam of Peru, fragrance mix, cobalt, and lanolin<br />NACDG series range from 65 to 70 allergens<br />T.R.U.E test serve as screening tool in allergist practice<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  34. 34. Patch test technique<br />applied to upper or middle back areas (2.5 cm lateral to midspinal reference point) free of dermatitis and hair<br />kept in place for 48 hours<br />read 30 minutes after removal of patches <br />second reading should be done 3 to 5 days after initial application <br />Metals , topical antibiotics , topical orticosteroids, and PPD can elicit positive reactions after 7 days<br />Nonstandardized patch tests tested at 1:10 to 1:100 dilutions<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  36. 36. diagnosis<br />Clinical presentation of rash with history of exposure agent confirmed with possible patch test result<br />
  37. 37. Current opinion in pediatrics 2009,21;491-498<br />
  38. 38. Standard patch test<br />
  39. 39. CD in thailand : patch test result<br />
  40. 40. J Med Asso Thai vol 93 supl 7 2010<br />
  41. 41.
  42. 42.
  43. 43.
  44. 44.
  45. 45.
  46. 46. Allergen <br />
  47. 47. Common combination<br />PPD and benzocaine<br />Thiuram mix carba mix mercapto mix<br />Quaternium 15 and paraben<br />Cobalt and nickel<br />Patients older than 40 years are prone to multiple sensitivities<br />Repeat open application test might confirm the presence or absence of ACD<br />
  48. 48. Determining clinical relevance<br />
  49. 49. Investigation <br />Repeat open application test (ROAT)<br />Improving reliability of interpreting tests for leave-on products<br />suspected allergens are applied to antecubitalfossa twice daily for 7 days and observed for dermatitis<br />absence of reaction makes CD unlikely<br />If eyelid dermatitis is considered, ROAT can be performed on back of ear<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  50. 50. SELECTED CONTACT ALLERGENS<br />Metals<br />Nickel<br />NACDG reported 18.7% of patients evaluated for ACD had positive patch test reaction to nickel<br />Female sensitization to nickel higher because of increased ear piercing<br />1% of nickel allergy have systemic reactions to nickel content of normal diet<br />Foods with higher nickel content include soybean, fig, cocoa, lentil, cashew, nuts, and raspberry<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  51. 51. Gold<br />NACDG reported that 389/4101(9.5%) had positive patch test reactions to gold<br />hands (29.6%); face, with seborrheic distribution (19.3%); and eyelids (7.5%)<br />mostly used for fashion appeal, anti-inflammatory medication, used in electroplating industry, part of dental appliances (present with oral symptoms)<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  52. 52. Cosmetics<br />Common allergens in these products include fragrances, preservatives, excipients, glues, and sun blocks<br />Fragrance<br />most common cause of ACD from cosmetics <br />results in positive patch test reactions in 10.4% of patients<br />‘‘unscented’’ and ‘‘Fragrance-free’’<br />Fragrance mix I containsallergensfoundin 15% to 100% of cosmetic products and might detect ~85% of subjects with fragrance allergy<br />positive patch test reaction to fragrance must correlate with distribution of dermatitis and evaluation of clinical relevance, eg. positive ROAT reaction<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  53. 53. Preservatives and excipients<br />Lanolin : common component of consumer products<br />It is weak sensitizer on normal skin but a stronger sensitizer on damaged skin<br />stasis dermatitis, are at higher risk of lanolin sensitivity<br />Cosmetic preservatives <br />Formaldehyde releasers <br />non–formaldehyde releasers : Paraben most commonly used preservative in cosmetics, as well as in pharmaceutical and industrial products<br />Type I immediate hypersensitivity reactions (contact urticaria) and SCD from ingestion of paraben-containing medications or foods have been reported<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  54. 54. Hair products<br />Second most common cause of cosmetic allergy<br />PPD (Paraphenylenediamine) is most common cause of CD in hairdressers<br />In hair dye users the dermatitis often spares the scalp and usually involves the face near the hairline, eyelids, and neck<br />PPD cross-reacts with COX-2 inhibitor (celecoxib), sunscreens, and antioxidants used in manufacture of rubber products<br />New hair dyes that contain FD&C and D&C dyes have very low levels of cross-reactivity with PPD<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  55. 55. CAPB ( Cocoamidopropylbetaine )<br />amphoteric surfactant often found in shampoos, bath products, and eye and facial cleaners<br />CAPB allergy typically presents as eyelid, facial, scalp, and/or neck dermatitis<br />Glycerol thioglycolate<br />active ingredient in permanent wave solution<br />Unlike PPD, thioglycolates might remain allergenic in hair long after it has been rinsed out<br />skin eruptions can continue for weeks after application of permanent wave solution<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  56. 56. Medications<br />Antibiotics and antiseptics<br />Neomycin and nitrofurazone are potent sensitizers<br />Neomycin sulfate can cross-sensitize with gentamicin, kanamycin, streptomycin, spectinomycin, tobramycin,andparomomycin<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  57. 57. Medications<br />corticosteroid<br />0.2-6%<br />Patients with worsening of previous dermatitis or initial improvement followed by deterioration of dermatitis after application of corticosteroids should be evaluated <br />Patch test should inclulde groups of simultaneously or cross reacting corticosteroid,vehicle and preservative<br />Cross-reactivity between groups A and D2 and groups B and D2 also has been reported<br />optimal patch test concentration not worked out for most corticosteroids, include pateint’s own product<br />30% of ACD to corticosteroids be missed if delayed 7-day reading not done<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  58. 58.
  59. 59. CD Due to Surgical Implant Devices<br />use of nickel in biomedical devices,led to increasing concern about safety in suspected nickel-sensitized patients<br />Presently,high variability of care <br />no large, evidence-based guidelines<br />10 patients with positive patch test reaction to metal had in-stent restenosis associated with clinical symptoms <br />allergy to metals,plays relevant role in inflammatory fibroproliferativerestenosis<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  60. 60. CD Due to Surgical Implant Devices<br />criteria for diagnosis of cutaneous implant–induced reaction<br />dermatitis (localized or generalized) appearing after implant surgery<br />persistent dermatitis that is resistant to appropriate therapies<br />positive patch test result proven history to metallic component of implant or to commonly used acrylic glues<br />resolution of dermatitis after removal of implant<br />ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006 <br />
  61. 61. Treatment <br />Allergen identification to improve contact avoidance<br />Alternatives and substitutes to cosmetics should be offered to patient to increase compliance<br />supportive care and relief of pruritus, cold compresses with water or saline, Burrow solution , calamine, and colloidal oatmeal baths might help acute oozing lesions<br />Excessive hand washing should be discouraged in hand dermatitis, and nonirritating or sensitizing moisturizers must be used after washing<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
  62. 62. Treatment<br />TC is first-line treatment for ACD<br />For extensive(>20% BSA) and severe CD, systemic corticosteroids might offer faster relief (12-24hr)<br />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<br />J Allergy ClinImmunol 2010;125:S138-49.<br />
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