Allergic Contact Dermatitis

H M Nadjib Dahlan Lubis

Bag Patologi Anatomi Fak Kedokteran USU / UISU Medan

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Inflammatory Dermatoses

- Urticaria

- Acute Eczematous Dermatitis

- Erythema Multiforme

Acute Excematous Dermatitis

- red, papulovesicular, oozing, & crusted, pruritic (itchy)

- Categories : - allergic contact d

- atopic d

- drug-related eczematous d

- photoeczematous d

- primary irritant d

- pruritic, edematous, oozing plaques, small/large blister

- bact yellow crust (impetiginization)

Acute Excematous Dermatitis

- red, papulovesicular, oozing, & crusted, pruritic (itchy)

- Categories : - allergic contact d

- atopic d

- drug-related eczematous d

- photoeczematous d

- primary irritant d

- pruritic, edematous, oozing plaques, small/large blister

- bact yellow crust (impetiginization)

Morphology

- spongiosis

- >< urticaria: superficial dermis, AED: intercell epid

- ingested drug lcy & eos: deep & superf dermal vessels

- contact Ag superficial

I. Anaphylactic

II. Ab >< Ag: surface, tis componet

- Complement-Dependent Reactions

- Ab-Dependent Cell-med Cytotoxicity

- Ab-Mediated Cellular Dysfunction

III. Imm Complex Mediated

- Generalized

- Localized

IV. Cell Mediated

- Delayed-Type

- T-Cell Mediated Cytotoxicity

Type I ( Anaphylactic )

Ag + Ab ( mast & baso ) * Mast (jar), baso (drh)

2 phases: - Initial : dil, leakage, spasm, 5-10 expos, 60 - Late : - 2-8 hari without expose several days - Eos, net, baso, mon - Destruksi mucosa epitel

Mast & baso : - Ig E Fc receptor - C 5a, C3a (anaphylatoxin) - IL8 (cytokine mac) - Codein, morphine - Mellitin (bee venom) - Phy : heat, cold, sunlight

Type I hypersensitivity

- within minutes after Ag + Ab bound to mast cell allergy

- systemic injection

- local: - skin,

- nasal,

- conjunctiva,

- hay fever,

- bronchial asthma

- allergic gastroenteritis

- immediate/ initial: - vasodilatation

- vasc leakage

- smooth muscle spasm

- glandular secretion

- 5-30’ after exposure, subside in 60’

- late phase reaction

- 2-24 h later, w.o. Additional exposure, last for

several days

- infiltration of eos, net, bas, mon, CD4 T cells

- tissue destruction: mocosa

Central role of Th2

- in response to Ag & other: IL-4 T cells differentiate TH2

- TH2 IL-4 B cell class swithing to IgE

development of additional TH2

IL-5 development & activation of eosinophils

IL-13 IgE

mucous secretion

Alergen APC (Dendritic) CD4 + T : TH2

cytokine

Ig E ( B cell)

Rec Fc Ig E (Mast, Bas)

Reexposure

Mediator

Type II

Mediated by Ab >< Ag: surface of cells other tis. comp

- Complement-Dependent Reactions

- Antibody-Dependent Cell-Mediated Cytotoxicity

- Antibody-Mediated Cellular Dysfunction

Complement-Dependent Reactions

- Transfusion reaction s - Erythroblastosis Fetalis - Autoimm hemolytic anemia, agranolocytosis, thrombocytopenia - Pemphigus Vulgaris - Certain Drug Reactions

Antibody-Dependent Cell-Mediated Cytotoxicity

Antibody-Mediated Cellular Dysfunction

- MyasteheniaGravis - Pemphigus Vulgaris, - Graves diseaase

Type III

Ag-Ab comp activate complement sys damage

Ag: - exogen: foreign protein, bacteria, virus

- endogen: nucl Ag, Ig, Tumor Ag

Can be: - Generalized (Sys Imm Comp dis): Ag >>

- Localized (Arthus Reaction) : Ab >>

Type IV: Cell Mediated Hypersensitivity

Initiated by Ag-activated (sensitized) T L’cyte

Includes: - Delayed-type: by CD4 T-cells

- Direct cell cytotoxicity: by CD8 T-cells

T Cell-Mediated (Type IV) Hypersensitivity

- initiated by ag-activated (sensitized) T lcy, inc: CD4 & CD8

- CD4+ T cell-mediated hypersens - environmental Ag

- sel-Ag

CD4 : - = Helper cell

- Cytokines B cell, NK, M’phage

- destroyed by HIV

Subsets: - TH1 IL-2, IFN Cell-mediated Immunity

- TH2 IL-4, IL-5 Humoral Immunity

Cytokines pathogenesis of Type I inc. Bron. Asthma

CD8 : - like CD4 secrete cytokine

- best: - virus

- tumor cells

Delayed Type

Tuberculin Reaction: Reddening, Induration:

8-12 hrs, peak: 24-72 hrs subside.

Morp: - Mononuclear perivascular cuffing

- Permeability edema, fibrin

- L’cyte is replaced by M’phage: 2-3 wks

- M’phage Epitheloid Cells

- E’loid surrounded by L’cyte Granuloma

Sequence

1. First Exposure CD4 recognize peptides bacilli +

class II mol on surface of M’cyte, Langerhans)

Sen CD4 TH1

2. Inj of Tuberculin memory TH1 + Ag (surface APC) activated, blast transformation, proliferation secrete cytokines IL-12

IFN-

IL-2

TNF-

Common examples:

- Contact dermatitis

- Type I diabetes

- Multiple sclerosis

T Cell-Mediated Cytotoxicity

Sensitized CD8+ T cells (CTL) kill Ag-bearing target cells

Role: - Graft Rejection

- Viral Infection

Viral Peptides + Class I complex on surface

Complex is recognized by TCR of CD8+ T L’cyte

2 mechanisms of CTL killing

1. Perforin-granzyme-dependent killing2. Fas-Fas ligand-dependent killing

Perforin & Granzyme: Mediators in lysosome like granules in CTL

Perforin perforate plasma membrane

Granzyme: protease via pores Apoptosis

Activated CTL Fas-ligand ~ TNF-alpha + Fas (on target cells)

Apoptosis

Reaction of CD4: Delayed-Type Hypersen & Immune Inflammation

- DTH to: - exogen Ag

- self-tissue

- ass. w. - TH1 : activated macrophages

- TH17: neutrophil

Causes

Inside : reaction to an internal circulating antigen food or drug).Outside : application of antigen (such as poison ivy) poison ivy/oak (Rhus toxicodendron),

characterized by pruritic, edematous, oozing plaques, often containing small and large blisters (vesicles and bullae) ( Fig. 25-24A ). prone to bacterial superinfection yellow crust (impetiginization). less “wet” (fail to ooze or form vesicles) , (hyperkeratotic) (acanthosis).