contact dermatitis
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Contact dermatitis Presented by Planee Vatanasurkitt, MD. 20111007TRANSCRIPT
CONTACT DERMATITIS : ROLE OF IMMUNE RESPONSE IN ALLERGIC CONTACT DERMATITIS Planee vatanasurkitt,MD
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 treatment
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 etiologyIrritant contact
dermatitis non immunological
Photocontact dermatitis Chemical require light –induced in UV spectrum to cause skin response
Contact urticaria IgE mediated
Allergic contact dermatitis
Complex Immune mechanism : induction and elicitation
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
Electrophilic component
nucleophilic
Aldehydes, ketone,amide metal ion
Lysine,cyctein ,histidine
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
PATHOPHYSIOLOGY
J Allergy Clin Immunol 2010;125:S138-49.
HISTOLOGY
Spongiosis: predominant histologic feature of CD
ANTIGEN PRESENTING CELL IN CONTACT DERMATITIS
Langerhans cells keratinocytes
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-α Via TNFR2
IL-1 family IL-1α, IL-1β ,IL18 IL1β rapidly produced by LC and act through IL1RI to produce TNF-α
TNF-α and 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 clonal anergy 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 Clin Immunol 2005;1:75-86J 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- γ is 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,the Treg 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
CauseMetal (cobalt, copper, chromium, gold, mercury, nickel, and zinc)
Medications corticosteroids, 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 medicineJ Allergy Clin Immunol 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 areasabsence of systemic signs and symptoms
J Allergy Clin Immunol 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 guidelinesANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006
INVESTIGATION: PATCH TESING
Indicated in patients with chronic,pruritic eczematous,or lichenified 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 allergensT.R.U.E test serve as screening tool in
allergist practice
J Allergy Clin Immunol 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 Clin Immunol 2010;125:S138-49.
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006
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
Chulalongkorn U. Siriraj Thammasat U
129 patient 323 patient 157 patient
34 standard patch test
European standard International patch test series
23 Europeanstandard
June 2003-2004 Jan 2004-Dec2006 June 2008-2009
Positive patch test 72.13 %nickel sulfate 18.6%Cobalt chloride 17%P-phynylenediamine 1.55%Fragrance mix 14.73 %
Positive patch test nickel sulfate 26.6%Cobalt chloride 16.4%P-phynylenediamine 10.3%Fragrance mix 20.7%
Positive patch test 44.6%nickel sulfate 26.8%Cobalt chloride 7.6%P-phynylenediamine 7%Fragrance mix 7%
J Med Asso Thai vol 93 supl 7 2010
area agent
Face and eyelid Only eyelid :Gold ,fragrances, preservative,nickel,thiuram,cocamidopropyl betain,amidoamine[shampoo] tosylamide formaldehyde resin[nail polish]Mixed facial and eyelid dermatitis: nickel,kathon,fragrance
hand Patch test in hand eczema :Rubber element,nickel sulfate,potassium dichromateEntire hands :thiuram mix PPD, chromate balsam of peruFinger and digital spaces: nickel, cobalt
feet Most common positive patch test with ACD exclusive on feet : rubber compound
ALLERGEN
nickel jewelry
neomycin Topical antibiotic
Balsam of Peru fragrance
Thimerosal Otic opthalmic ,antiseptic
Chromate Leather products
Thiuram Rubber accelerants
Lanolin emollients
Formaldehyde preservative
Paraphenylenediamine Permanent hair dye, Henna
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
definite Suspected item positive
probable Antigen could present in skin contact and clinical consistant
possible Skin contact with materials contain allergen was likely
INVESTIGATION Repeat open application test (ROAT)
Improving reliability of interpreting tests for leave-on products
suspected allergens are applied to antecubital fossa 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 Clin Immunol 2010;125:S138-49.
SELECTED CONTACT ALLERGENS
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
J Allergy Clin Immunol 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 Clin Immunol 2010;125:S138-49.
COSMETICS 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 contains allergens found in 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 reactionJ Allergy Clin Immunol 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 reportedJ Allergy Clin Immunol 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 Clin Immunol 2010;125:S138-49.
CAPB ( Cocoamidopropyl betaine ) 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 Clin Immunol 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,and paromomycin
J Allergy Clin Immunol 2010;125:S138-49.
MEDICATIONS
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
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 Clin Immunol 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 fibroproliferative restenosis
J Allergy Clin Immunol 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
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY, VOLUME 97, SEPTEMBER, 2006
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 Clin Immunol 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 Clin Immunol 2010;125:S138-49.