Patch Test

By H.Eshaghi M.D

IRRITANT CONTACT DEMATITIS

Non-immunologic inflammatory reaction of the skin due to an external agent

Varied morphology Clinical types

Chemical burns Irritant reactionsAcute irritant contact dermatitisChronic irritant contact dermatitis

Irritant Contact dermatitis :

Acute irritant dermatitis → severe eczematous reaction Single overwhelming exposure Few brief exposures to strong irritants or a caustic agent

Chronic (cumulative) irritant dermatitis → eczematous changes that develop upon repeated exposure to weaker irritants:

water, soaps, detergents, solvents, weak acids or alkalis, low humidity, heat, air, and dusts

Allergic Contact Dermatitis Delayed type IV hypersensitivity reaction

SENSITIZER: chemical agent with low molecular weight which is able to sensitize certain individuals and induce cell mediated immune reaction that end with dermatitis only in previously sensitized persons.

Pathogenesis: Induction (sensitization) phase: 18-24 daysElicitation phase: 2-4 days

Antigen binds Langerhan’s cells in the epidermis or macrophages in the dermis

Interaction with CD4+ T lymphyocytes at the regional lymph nodes causes release of inflammatory cytokines

Mechanism

Specific immune phenomenon that is the result of

a T cell mediated immune response to a defined

allergen resulting in eczema or the exacerbation of

a pre-existing dermatitis

Common allergens

ChromateRubber chemicals PreservativesNickelFragrancesEpoxy resins Phenol-formaldehyde resins

Contact dermatitis of the hands in a dental technician

Patch testing to be allergic to the Thiuram chemicals (accelerator in gloves)

Theoretical basis of patch testing

Patch test was first devised by

Jadassohn(1895) and described in practical detail by Bloch (1929) immunological basis of the patch test is the type IV.

Hypersensitive Reactions

1. Type I Hypersensitivity

2. Type II Hypersensitivity

3. Type III Hypersensitivity

4. Type IV Hypersensitivity

Components and cells in Type I hypersensitivity

Allergen ： pollen 、 dust mite 、 insects, etc

selectively activate CD4+Th2 cells and B cells

Allergen（ IgE） and its production

IgE ： mainly produced by mucosal B cells in the lamina prapria

special affinity to the same cell

IL-4 is essential to switch B cells to IgE production

High affinity receptor of the IgE on mast cell and basophil

Type I hypersensitivity

Type I hypersensitivity

Skin allergy

Systemic anaphylaxis:

1) Anaphylactic drug allergy ： penicillin

2) Anaphylactic serum allergy ：

Respiratory allergic diseases :

1) Allergic asthma 2) Allergic rhinitis

Gastrointestinal allergic diseases :

The lack of Serum IgA protein hydrolase Undigested protein Allergen

Common disease of type I hypersensitivity

Allergen

Stimulate

Antibody

A. Opsonic phagocytosis

D. ADCC of NK

C. Effect of complement

Combined opsonic activities

Cell injury ways of type II hypersensitivity

Cell

Antigen or hapten on cell

Antibody (IgG, IgM)

Activate complement

Lyse target cell

Opsonic phagocytosis NK , phagocyte Stimulate / block

Destroy target cell ADCC

Target cell injury Change the function ofTarget cell

Mechanism of Type II hypersensitivity

Mechanism of type III hypersensitivity

Formation of the intermediate immune complex

Deposition of the intermediate immune complex

Tissue injury by the immune complex

common disease of type III hypersensitivity

1. Local immune complex disease

Arthus reaction ：Experimental local reaction,

Necrotic vasculitis Ulcer

Human local reaction: insulin-dependent diabetes mellitus (IDDM)

2. Acute systemic immune complex disease

serum sickness

Anti-serum → Ab+Ag → systemic tissue injury ,fever, arthritis, skin rash

Pinicillin 、 Sulfanilamide

Acute immune complex glomerulonephritis : Streptococcus infection

3. Chronic immune complex disease:

SLE

Rheumatoid arthritis ：RF+IgG → Deposit on synovial membrane

Type IV hypersensitivity

characteristics of type IV hepersensitivity

mechanism of type IV hepersensitivity

common diseases of type IV hepersensitivity

Characteristics

Interaction of primed T cells and associated antigen

Infiltration of Mononuclear Cells, Inflammatory response

Mechanism of type IV hypersensitivity Formation of effector and memory T cells

Inflammation and cytotoxicity caused by effector T cells

1) Inflammation and tissue injury mediated by CD4+Th1

Release chemokines and cytokines

Immune injury mainly caused by infiltration of mononuclear

cells and lymphocytes

2) Cytotoxicity of CD8+

Common disease of type IV hypersensitivity

Infectious delayed type hypersensitivity

OT( Old Tuberculin ) test

Contact dermatitis

Acute rejection of allogenic transplantation

Same disease (SLE), multiple immune injury ,hypersensitivity

involved

Same drug (penicillin), several types of hypersensitivity

Sensitized T lymphocytes have secondary contact with

the antigen (hapten)

conjugated with a protein and presented on the surface

of an antigen presenting cell (APC).

APCs are the Langerhans’ cells

Presentation of the antigen by :Langerhans’ cell to

CD4+ Th-1 type T lymphocyte

Release of cytokines that produces T cell activation and

the recruitment of other non-antigen specific T cells and

macrophages to the site

inflammatory reaction : peak at 72 hours

clinically patch test reaction: localised area of

eczema

After 3–4 days, immunological mechanisms

downgrade the reaction and it gradually fades

away.

Standard series

All patients are patch tested to a standard of

allergens, such as the International, European,

North

American, or British Contact Dermatitis Group

(BCDG) standard series

British Contact Dermatitis Grouprecommended standard series

• Neomycin sulfate• Thiuram mix 1• Paraphenylenediamine• Cobalt chloride • Formaldehyde• Rosin• Quinoline mix• Balsam of Peru• Isopropyl PPD• Wool alcohols• Mercapto mix• Epoxy resin• Paraben mix• PTBPF resin• Fragrance mix

• Quaternium

• Nickel sulfate

• Methylchloroisothiazolinone Methylisothiazolinone

• Mercaptobenzothiazole

• Primin

• Sesquiterpene lactone mix

• Chlorocresol

• Bronopol

• Cetearyl alcoho

• Fucidic aci

• Tixocortol pivalate

• Budesonide

• Imidazolidinyl urea

• Diazolidinyl urea

• Methyldibromoglutaronitrile

• Ethylenediamine dihydrochl

Contact dermatitis Allergens hazards in selected occupations

Bakers:Flavouring, oil, antioxidantBuilding trade workers:Cement (Cr, Co), rubber,resin, woodCaterers, cooks : fruit, veg,Veg/fruit, cutlery (Ni),rubber gloveCleaners: Rubber glove, nickel,Dental personnel :

acrylate, Rubber, acrylate mercury

Electronics assemblers: Cr, Co, Ni

Patch Test: Materials

Finn chambers (shallow aluminium discs to hold allergens) Hypoallergenic acrylate tape.

Allergens (diluted in various vehicles like petrolatum, water, ethanol, acetone, olive oil, etc.)

India Indian Standard Battery approved by CODFI [Contact and Occupational Dermatoses Forum of India] is usually employed Marker pen

Indications of Patch Test

Allergic Contact Dermatitis Syndrome (ACDS) Atopic dermatitis Nummular dermatitis (nummular eczema) Seborrheic dermatitis presenting episodes of acute

inflammation) Asteatotic eczema Stasis dermatitis Eczematous lesions around leg ulcer Pompholyx and/or dyshidrotic eczema Lichenification

Taking a history

past and present occupation (possible contact with

industria allergenor irritants)

Hobbies (plants,animals)

cosmetics, and current and previous

treatments(potential medicamental hydrocortisone).

Selection of Patients

1 .Taking less : 15 mg of oral steroid)

2 .Not applying topical steroid on back for at least 1 week

3 .Not having active or flared-up dermatitis

4 .Not have been sunburned on back within last 2 weeks

5 .Oral antihistamine can be continued during the process.

follow during the patch test procedure

Not to take bath or wash or wet the back

To avoid tight underclothes

To avoid exercise or activity causing sweating

To avoid friction/scratching

avoid strong sun exposure.

Patch Test: Methods upper back (excluding vertebra and scapular angle)

deltoid area (for small number of allergens)

Site should be gently cleansed (with water and alcohol) and dried

The top of patch test unit is marked and the protective foil removed

and they are kept with aluminium chambers faced up

The protective foil is fixed longitudinally along the edge of the patch

test unit to facilitate handling

Reading the patch test reactions

fixed on the upper back ; left on for two days. removed, marked, read with another reading atfour days problem in reading patch tests: differentiate

irritantreactions (which have no diagnostic value) from allergic ones

Recording Patch test (la dou)

1 +=Weakreaction, nonvesicular,erythema,mild infiltration

2 + =Strongreaction, erythema, edema,vesicles

3 + =Extreme reaction, spreading ,bullous ,ulcerative

4 =Doubtful, faint erythema only

5 = Irritant reaction

6 =Negative

7 =Excited skin reaction

8 =Not tested

Recording patch test (0D)

+/− doubtful: faint erythema only

+ weak: erythema, maybe papules

++ strong: vesicles, infiltration +++ extreme: bullous

Patch Testing

variety of substances found both in the industrial allergen

Acrylates Adhesives

Chromate Cement

Cobalt Pigment

Epoxy resins

Paints/resins

Ethylenediamine

Formaldehyde Preservatives

Detergents

Nickel Electroplating

jewellery manufacture

Paraphenylenediamine

Phenol formaldehyde

The possible side effects are explainedirritation on the back from the presence of the

patches,

the production of an excessive reaction

worsening of the dermatitis in a number of cases,

and actually sensitised by the process of testing

develop a “late” reaction—for example 1–3 weeks after( Gold

salts cause this)

late reaction develops, often re-patch test after a suitable period

(for example, four weeks)

The management of contact dermatitis is

often difficult: overlapping factors

testing helps identify the allergens involved

useful in dermatitis of the hands, face, feet

Most cases of occupational contact dermatitis: mixed etiology

Elimination of an allergen may not produce full resolution →often irritant /endogenous factors at play as well.

Difficult to eliminate fully all contact with ubiquitous allergens such as nickel or colophony

Prick test

Diagnosis of allergic disease

most important

• History taking

• Physical examination

• Evaluation of causative allergen Skin test : prick, intradermal, patch Serum specific IgE :RAST specific allergen provocation test :nasal, bronchial, oral

Focus of Allergy diagnosis Is the patient atopic?

Does allergy contribute to patient’s symptom?

What are the clinical relevant allergens? →allergen avoidance → environmental control →immunotherapy, desensitization

Allergy History Taking Main dominant symptoms Associated symptomsFrequency and severity of symptoms, impact on

lifestyle Seasonal or perennial ? Triggering factors : allergic or non-allergic factor Occupation, hobbies Food, drug consumption history Possible allergen exposure in home Personal or family history of allergic disease Prior treatment response, side-effects

Skin test • Purpose identification of causative allergens standardization of allergens : allergenic

potency

• Advantages easy to perform, fast not expensive high sensitivity

Skin test : method

•Prick test •Intradermal test

•Scratch test

Skin prick test clean the test skin surface(back, forearm volar surface) with

cotton moistened with 75% alcohol and dry up

place a small drop of each test extract and

positive/negative control solution 3-5cm apart

prick with 25 or 26G needle and lift gently needle tip

upward

read the wheal and flare reaction 15min later-read

Skin prick test : method

Skin prick test

Intradermal test clean the test skin surface(back, forearm volar

surface) with 75% alcohol and dry up intradermal injection of allergen extract with 1ml

syringe and 26G needle (approximately 2-4mm diameter bleb, 0.02ml injection)

perform with positive/negative control solution

read the wheal and flare reaction 15min later

Controls

false positive -dermographism -needle irritation false negative -medication (e.g. antihistamine) -underlying disease -technical error

Factors affecting skin test

• Allergen extract• Area of body -back >> arm -upper back >> lower back -ulnar side of arm >> radial side of arm • Age -significant wheal detect in infants -increase from infancy to adulthood -decline after age of 50• Sex, Race• Seasonal variation

Drugs affecting skin test• H1 antihistamine

• Imipramies, Phenothiazines: > 10days

• Systemic steroid short-term(=1wk) : no effect long-term : possible effect

• H2 blocker, leukotriene antagonist, theophylline, beta-agonist: no clinical significance

Positive criteria Size of wheal and erythema(flare)

prick test:wheal size =3mmflare=10mm → regarded as clinically significant allergy

intradermal test : wheal size =5mm

Interpretation Clinical relevancy positive skin test ≠clinical allergic disease consider asymptomatic sensitization, insignificant cross-reaction (sensitization rate: 30-40% of general population)

Correlation with other allergy diagnostic test

Diagnostic value of skin test:

• inhalant : most cheapest and effective method for respiratory allergy • food : low sensitivity • drug : variable, low sensitivity except penicillin