Jan 03, 2016
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