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Contact dermatitis

Contact dermatitis

Contact dermatitis

Presented by Planee Vatanasurkitt, MD.




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    Contact dermatitis Contact dermatitis Presentation Transcript

    • Contact dermatitis : role of immune response in allergic contact dermatitis
    • outline
      Immune cells in contact dermatitis
      Classification of contact dermatitis
      Investigation in contact dermatitis
      Data of patch testing in contact dermatitis Thailand study
      Common allergen in contact dermatitis
    • introduction
      Contact dermatitis CD is one of the most common inflammatory skin disease
      CD represents majotity 79-90% annually of skin related occupational complaints
      CD can be divide into four cattegories base on etiology
    • pathophysiology
      In1935 studies of 2,4-dinitrochlorpbenzene DNCB sensitization guinea –pigs
      Electrophilic component of hapten and nucleophilic side chain of target protein in skin
      Chemical that are not normally electrophilic can converted to properties of hapten by air oxidation or cutaneous metabolism
      Contact dermatitis 2005;53:189-200
    • ACD 20%
      prototype of type IV cell-mediated hypersensitivity reaction
      ICD 80%
      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 concentrations can also act as irritants
      J Allergy ClinImmunol 2010;125:S138-49.
    • histology
      Spongiosis: predominant histologic feature of CD
    • Antigen presenting cell in contact dermatitis
      Langerhans cells
    • Langerhans cells
      At steady state 90% LC exhibited relatively little mobility
      After application hapten dendrite surveillance extension and retraction cycling habitude [dSEARCH] and lateral migration of LC
      The amplification of dSEARCH is mediated by IL-1α and TNF-α ,cytokine produced by keratinocytes
    • Langerhans cell
      LC exhibit increase expression of
      CD 83 ,marker for LC maturation
      ICAM-1,adhesion molecule
      CD 40,B7-1[CD80] B7-2 [CD86], co- stimulation molecule
      Expression of these marker is specific to hapten-exposed LC, dermal irritants trigger LC migration but not result in LC surface marker changes
    • Cytokine in LC migration in response to hapten
      TNF-αand IL-1β signals are required for LC migration
      during the initiation phase of ACD
    • Langerhan cell
      Immature LC express CCR5 and CCR6
      In response to hapten exposure LC upregulate CCR7
      CCR7-CCL 19,21 targeting LC to lymph node
      CCL19 CCL21 express in lymph node paracortex
      CCL21 expressed by afferent lymphatic endothelial cell
    • keratinocytes
      KC are the source of cutaneous TNF-α expression after hapten exposure
      Express IL-1 receptors which response to LC –derived IL 1 β,leading to expression of TNF-α
      KC also express ICAM-1 in the presence of IFN-γ
      T cell ,source of IFN-γ, express CD11a which bind to ICAM-1 on keratinocyte
    • keratinocytes
      In the absence of CD80/CD86,antigen presentation in the context of MHC class II leads to clonalanergy and tolelence
    • keratinocytes
      KC can express IL 10 particularly in response to hapten exposure
      KC express IL-16,only first appears 6 h after hapten exposure with maximal expression at 24 h after exposure during elicitation
      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+
    • Tolerance mechanism
    • lymphocyte
      T cells
      B cells
      NKT cells
      T reg cells
      NK cells
    • T cell
      Primary effector cell of ACD are CD8+ cell
      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
      In the absence of CD8+ T cell, CD4+T cells are capable of mediating the CHS to trinitrophenyl
      J Interferon Cytokine Res 2002;22:407-12
    • T cell
      Invitro studies indicated that hapten-specific CD8+ T cell induce Fas-mediated apoptosis of CD 4+ T cells
      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
      Expert Rev ClinImmunol 2005;1:75-86
      J Immunol 2004:173:3178-3185
    • T cell
      Cytokines involved in T helper cell type 1 proliferation/activation are consider important during development of CHS responses
      Contact allergen triggered KC produce IL12 leading to proliferation of T cell into Th1 phenotype
      Scand J immunol 2004 ;59:385-394
    • T cell
      In vitro studies demonstrated that both initiation and elicitation phases of DNFB-mediated ACD were significantly blocked by IL-12 neutralizing antibodies
      Conclusion IL-12 is important in the pathogenesis of ACD
      J Immunol 1996;156:1799-1803
    • T cell
      IFN-γ classically produced by Th1 CD4+T cell
      IFN- γi n CHS shown to be produced by CD8+ T cells
      IFN- γis important in the pathogenesis of cellular infiltration associated with CHS while cutaneous edema is IFN-γ independent
      J Exp Med 1996;183:1001-1012
    • B cell
      Initial hapten exposure B-1 proliferate and produce IgM while B-2 cell remain at pre-exposure levels
      IgM antibody activates complement
      C5a trigger inflamation through binding to C5a receptor on mast cell and platelet leading to recruitment of effector T cells
      J Exp Med 2002;196:1277-1290
      Trends Immunol 2004;25:441-449
    • NKT cells
      Characterizes by expression CD 161 and α /β chains of T cell receptor
      TCR on invariant NKT cell bind highly conserved glycolipids in the context of CD1d
      The production of IL-4 by iNKT cells shown to be toll-like receptor dependent
    • Treg cells
      Express CD25, cytotoxic T lymphocyte-associated antigen-4 [CTLA-4] ,and forkhead box P3 [Foxp3]
      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
      Treg are involved in ACD suppression and hapten tolerance
    • NK cells
      NK cell have ability to acquire hapten specific memory and mediated CHS
    • Clinical evaluation
      Diagnosis of allergic contact dermatitis from clinical presentation and possible exposure to contact allergen
    • Systemic contact dermatitis
      localized or generalized inflammatory skin disease in contact-sensitized individuals exposed to hapten orally, transcutaneously, intravenously, or by means of inhalation
      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, mitomycin C, 5-FU
      Herbal medicine
      J Allergy ClinImmunol 2010;125:S138-49.
    • Drug induced SCD
      Symmetric drug-related intertriginous and flexural exanthema
      Criteria for diagnosis :
      exposure to systemic drug at first or repeated dosing (contact allergens excluded)
      erythema of gluteal/perianal area, V-shaped erythema of inguinal/perianal area, or both
      involvement of at least 1 other intertriginous/flexural localization
      symmetry of affected areas
      absence of systemic signs and symptoms
      J Allergy ClinImmunol 2010;125:S138-49.
    • Occupational contact dermatitis
      4 of 7 criteria must be positive to conclude OCD
      clinical appearance is consistent with CD
      cutaneous irritants 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
      nonoccupational exposures 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
    • Investigation: Patch tesing
      Indicated in patients with chronic,pruriticeczematous,orlichenified dermatitis in whom ACD is suspected
      Affected by oral corticosteroid [>20 mg of prednisolone /day or equivalent] cancer chemotherapy,immunosuppressive drug
      Topical corticosteroid should be discontinued for 5-7 days before patch testing
    • Investigation
      Sources of allergens
      T.R.U.E. TEST :not US FDA approved
      But recommended by CD experts
      Numbers of allergens
      ideal number remains controversial
      T.R.U.E. Test contains 29 allergens
      higher false-negative reactions to neomycin, thiuram mix, balsam of Peru, fragrance mix, cobalt, and lanolin
      NACDG series range from 65 to 70 allergens
      T.R.U.E test serve as screening tool in allergist practice
      J Allergy ClinImmunol 2010;125:S138-49.
    • Patch test technique
      applied to upper or middle back areas (2.5 cm lateral to midspinal reference 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
      J Allergy ClinImmunol 2010;125:S138-49.
    • diagnosis
      Clinical presentation of rash with history of exposure agent confirmed with possible patch test result
    • Current opinion in pediatrics 2009,21;491-498
    • Standard patch test
    • CD in thailand : patch test result
    • J Med Asso Thai vol 93 supl 7 2010
    • Allergen
    • Common combination
      PPD and benzocaine
      Thiuram mix carba mix mercapto mix
      Quaternium 15 and paraben
      Cobalt and nickel
      Patients older than 40 years are prone to multiple sensitivities
      Repeat open application test might confirm the presence or absence of ACD
    • Determining clinical relevance
    • Investigation
      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
      J Allergy ClinImmunol 2010;125:S138-49.
      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
      J Allergy ClinImmunol 2010;125:S138-49.
    • 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.
    • Cosmetics
      Common allergens in these products include fragrances, preservatives, excipients, glues, and sun blocks
      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
      J Allergy ClinImmunol 2010;125:S138-49.
    • 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 : Paraben most 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.
    • 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.
    • CAPB ( Cocoamidopropylbetaine )
      amphoteric surfactant 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, thioglycolates might 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.
    • Medications
      Antibiotics and antiseptics
      Neomycin and nitrofurazone are potent sensitizers
      Neomycin sulfate can cross-sensitize with gentamicin, kanamycin, streptomycin, spectinomycin, tobramycin,andparomomycin
      J Allergy ClinImmunol 2010;125:S138-49.
    • Medications
      Patients with worsening of previous dermatitis or initial improvement followed by deterioration of dermatitis after application of corticosteroids should be evaluated
      Patch test should inclulde groups of simultaneously or cross reacting corticosteroid,vehicle and preservative
      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, include pateint’s own product
      30% of ACD to corticosteroids be missed if delayed 7-day reading not done
      J Allergy ClinImmunol 2010;125:S138-49.
    • CD Due to Surgical Implant Devices
      use of nickel in biomedical devices,led to increasing concern about safety in suspected nickel-sensitized patients
      Presently,high variability 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
      J Allergy ClinImmunol 2010;125:S138-49.
    • CD Due to Surgical Implant Devices
      criteria for diagnosis of cutaneous implant–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
    • Treatment
      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 hand washing should be discouraged in hand dermatitis, and nonirritating or sensitizing moisturizers must be used after washing
      J Allergy ClinImmunol 2010;125:S138-49.
    • Treatment
      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
      J Allergy ClinImmunol 2010;125:S138-49.