Contact dermatitis

Content
 Introduction
 Epidemiology
 Common allergen
 Pathophysiology
 Clinical manifestation
 Source and causative allergen
 Differential diagnosis
 Investigation
 Management

 Common inflammatory, noninfectious skin disease
 Occur after direct or indirect contact with substance the
harmful to skin
 Subdivided into
1. Irritant contact dermatitis
2. Allergic contact dermatitis
3. Contact urticaria
Middleton's Allergy: Principle and Practice 8th Edition

 Twice frequent in women > men
 Often start at a young age
 The Odense Adolescence Cohort Study 1501 school children
(12 to 16 years of age)
 prevalence 15%
 most common contact allergens nickel (8.6%) clinically relevant
69%, fragrance mix (1.8%) clinically relevant 29%

3 most common contact allergens
1. Nickel
2. Thimerosal
3. Fragrance mix
 Other: cobalt, chromium, p-phenylenediamine (PPD), and
methylisothiazolinone/methylchloroisothiazolinone (MI/
MCI) were prevalent allergens in many studies

Common Contact Allergens in US

 to determine the frequency of contact allergy in patients with
eczematous dermatitis in Thammasat University Hospital,
Prathumthani, Thailand
 From June 1, 2008 to June 30, 2009
 157 patients : 23 standard allergens patch tested Positive in
70 patients (44.6%)
1. Nickel sulfate (26.8%)
2. cobalt chloride (7.6%)
3. p-phenylenediamine (7.0%)
4. fragrance mix (7.0%)
 Contact allergy to fragrance mix was significantly more frequent
in patients who had personal history of atopy (p = 0.04).

 Prevalence is higher in women than in men
 17.1% (3.9% to 38.8%) vs 3.0% (0.7% to 6.8%)
 Pierced ears: a significant risk factor
 One of most common allergens cause systemic CD
 Ectopic CD: transferred to eyelids by fingers
 Europe: European Union (EU) restricted nickel use in consumer
products in 1994 -> decrease nickel allergy among young adults
 United States: not limit nickel exposure in consumer products

 Non-formaldehyde releaser in preservative
 Cosmetic, vaccine
 There is a single case report of generalized pruritic MP rash
attributed to thiomerosal in an Influenza vaccine
Kelso et al. Adverse reactions to vaccines practice parameter 2012 update

1. Fragrance mix I (FM I) use for screening fragrance allergy
(more common used than FM 2)
 8 ingredients: cinnamyl alcohol, cinnamal, amyl cinnamal,
geraniol, hydroxycitronellal, eugenol, isoeugenol, and oakmoss
absolute (Evernia prunastri)
2. Myroxylon pereirae (MP) (balsam of Peru)
3. Fragrance mix 2 (FM 2)
 7 ingredients: HICC ( hexene carboxaldehyde, also known as
lyral), citral, citronellol, coumarin, farnesol, α-hexyl-cinnamal,
and Myroxylon pereirae resin

 Prevalence for sensitization to FM I: 2.3% (women 1.7%, men
1.3%)
 Myroxylon pereirae (MP) (formerly known as balsam of
Peru): 1.1% (women 1.4%, men 0%)
 Prevalence in school children 12 to 16 years of age: 1.8% to
FM I and 0.6% to MP

 Occupational problem
 ACD
 Source: exposure to wet cement -prevalence as high as 17%
 EU regulated the content of chromium in cement
 Other sources: leather tanned with salts containing
Chromium

 Oxidative hair dye ingredients
 Prevalence 0.2% to 2.5% European population
 Prevalence up to 20% of hairdressers
 Extremely important risk factor for sensitization to PPD is
the use of temporary black “henna” tattoos

Irritant contact dermatitis (ICD)
 Phototoxic dermatitis
Allergic contact dermatitis (ACD)
 Photo contact dermatitis
 Contact urticaria (CU)

 Most common form of contact dermatitis
 Complex, multifactorial disease
 Usually the result of non immunologic, direct tissue reaction
 Intrinsic factors: genetic susceptibility (atopic skin disease
or genetically related skin barrier dysfunction)
 Extrinsic factors: nature of irritant (sufficient concentration/
time), environment
 Most frequent part: hands

 Skin exposure to irritant -> disruption of the skin barrier (direct
injury) and release of proinflammatory mediators by
keratinocytes, induce expression of TNF-α IL-1α IL-1β
 Identified irritants: wet work
 Other irritants: soaps, detergents, shampoos, solvents, oils,
cleaning agents, disinfectants, acids and alkalis, dusts, fiberglass,
plants
 Physical and environmental irritants: heat, sweating under
occlusion, friction, such as from handling paper, manual
handling, and low humidity

 First signs: dry and slightly scaly
skin, with increasing redness and
lichenification after prolonged or
repeated exposure to an irritant
followed by formation of fissures
“rhagades”
 Predominant areas: web spaces
initially, dorsal of hands and
fingers, forearms -> then palms

 Different from ACD lesions
 Limited to exposure sites
 Secondary spread to other areas typically does
not occur
 Itching is not as severe as in ACD

 Atopic eczema (because of changes in skin barrier function)
 loss-of-function of Filaggrin gene associated with chronic ICD
 Frequent hand washing (repetitive of wetting and drying),
long periods of occlusive glove use
 “Wet work” defined as
 expose liquids >2 hours/day, or
 use occlusive gloves > 2 hours/day or
 clean the hands very often (20 times/day, or less often if the
cleaning procedure is aggressive)

 Mediated by exposure to UV radiation, not
have an immunologic basis
 Systemic agents: medications (eg.
furosemide, HCTZ, NSAIDs, doxycycline,
tetracycline, amiodarone, chlorpromazine)
 Topical agents: plants containing
furocoumarins (eg. celery, carrot, and citrus
fruits)
Classic example: skin exposure to lime juice in a tropical
environment, causing a characteristic angulated, streaky erythema
on the areas of exposure, which is followed by marked
hyperpigmentation

Delayed hypersensitivity reaction
 Allergens penetrate skin and combine with MHC class II on
epidermal dendritic or Langerhans cells
 LC activate, mature, and migrate to lymph nodes, required IL-
1β, TNF-α, and GM-CSF within 24 hr
 In LN, naive CD4+ T cells (TH0 cells) activated, proliferate and
generate hapten-specific CD4+ CD25+regulatory and
CD8+effector clones, which subsequently become either
memory or effector cells
 CD4 regulatory/effector and CD8 effector cells then “home” to
the original induction skin site
Fonacier et al. Practice parameter. ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY 2006. Vol 97

 T cells attracted to locus of inflammation by keratinocyte-
derived CCL27, binds to their CCR10
 Primed T-cell disseminate throughout skin, and thereafter
stay in the skin for long periods
Reexposure to a contact allergen
 Activated T cells produce cytokines such as IFN γ, IL-2, and
IL-17
 T cells have an apoptotic effect because of their FasL and
perforin expression
 lead to spongiosis (predominant histology of CD) and an
intense perivascular inflammatory infiltration, maximum
after 18 - 48 hours
Kostner et al. ACD. Immunol Allergy Clin N Am 37 (2017) 141–152

Photo contact dermatitis
 Exposure to UVA causes certain chemicals transform to allergenic and thus photoallergens
 Although rare, most common photoallergens are sunscreen, such as benzophenone
 affects face, ‘‘V'' of the anterior neck, dorsal hands, forearms
 spares upper eyelids, upper lip, submental and postauricular areas
 Differential diagnosis : phototoxic drug eruption, photo-allergic drug eruption, SLE before
diagnosis
Fonacier et al. Practice parameter update. J Allergy Clin Immunol Pract 2015;3:S1-S39

 Acute: marked itching,
possibly vesiculation or
frank blistering, and
swelling, redness, scaling,
blistering, formation of
papules or pustules,
exudation, and excoriation
 Chronic: fissures,
lichenification, and
hyperkeratosis

 Common site: hands, eyelids (preservative in a shampoo or face
cream) and neck (nail polish)
 other sites: axillae (fragrance in a deodorant), dorsal aspect of the feet
(patient allergic to chromate in leather sandals)

 Autotransfer: nail lacquer located on the eyelids or on the
neck (transfer by fingers)
 Heterotransfer: transfer to another person, mainly partner,
also known as connubial ACD
 Airborne ACD: transport of allergen by air (dust particles,
vapors, or gasses; eg, from wall paint or pollen), typically
clinical lesions on uncovered areas
 most notorious example is Parthenium dermatitis found in
India

Airborne ACD
(Parthenium)
Parthenium hysterophorus
with white flower heads
• affects face, especially eyelids, neck, V
of the chest, and cubital and popliteal
fossae
• start as an acute eczema
• usually in spring and summers,
improves during winters
• In sensitized individuals, within 24
hours of exposure, may be up to 2-3
days or longer in milder cases
Sharma VK, Verma P. Parthenium dermatitis in India: Indian J Dermatol Venereol Leprol 2012;78:560-8.

 exposed to allergens from routes other than skin: oral, IV, or
inhalation
 Clinical manifestation flare-ups of dermatitis in previous
sites/ positive patch test site as well as vesicular hand
eczema
 “baboon syndrome”: well-demarcated rash on the buttocks,
genital area, and thighs from metals such as nickel, cobalt,
chromate, gold, and mercury

Allergens
associated
with
systemic CD

Contact urticaria
 Immediate hypersensitivity reaction
 itchy, erythematous, transient eruption
 Common causes: latex, ammonium persulfate or
hairdressing bleach, food proteins in food handlers
 Repeated episodes of contact urticaria can lead to protein
contact dermatitis, appears eczematous and cannot be
differentiated from ICD or ACD

Source Substance
Cosmetics • Fragrances
• Balsam of Peru (BOP)
ectopic transfer
resulting in eyelid
and periorbital
dermatitis
• Methyl methacrylate
(artificial nails)
• Tosylamide/ formaldehyde
(nail polish)
• Airborne pollen (Compositae)
Topical ophthalmic
medicines
• Neomycin sulfate
• Thimersol
Hard contact lens
solution
• cocamidopropyl betaine
(CAPB)
Face

Source Substance
Jewelry Nickel (most common)
Cosmetic quaternium-15, FM, BOP
Hair dye P-phenylenediamine (PPD)
Hair permanent
wave solutions
Glyceryl thioglycolate
Nail enamel
products
Tosylamide and/or formaldehyde resin
Nail product
adhesive
Methyl methacrylate
Shampoo fragrances
preservatives that are formaldehyde releasers
(quaternium-15, imidazolidinyl urea)
CAPB- Cocoamidopropyl betaine in eye and
facial cleaners, shampoo
Scalp and neck

Source Substance
• Oral hygiene products
(toothpastes, mouthwashes,
flavorings, compounds used for
dental impressions)
• Cosmetics
• lip products
Fragrance
Balsam of Peru (BOP)
Lip balm propolis produced by bees,
lanolin, coconut oil, almond oil,
peppermint oil, and vitamin E
Dentifrices and chewing gum Cinnamon and peppermint
flavorings
Lips: Allergic contact cheilitis
most common sources for ACC
• female = lipsticks and lip balms
• male = toothpaste, flavoring - mint derivatives: spearmint, menthol, peppermint, carvone,
cinnamal, anethole
often involve lip vermillion border with concomitant perioral dermatitis, spare adjacent
oral mucosa

Source Substance
• ICD >ACD eg.
Cosmetic, glove
• ACD >ICD
Occupational (hair
dresser, health care)
• Preservative: quaternium-15 (16.5%),
formaldehyde (13.0%)
• Nickel sulfate (12.2%)
• FM (11.3%)
• thiuram mix (10.2%)
• BOP (9.6%)
• carba mix (7.8%) used in rubber
products,
• neomycin sulfate (7.7%), bacitracin
(7.4%)
Hands
Chronic hand eczema: patch testing is highly recommended in all patients

Source Substance
• Deodorants • fragrance: hydroxyisohexyl-3-cyclohexene
carboxaldehyde, isoeugenol,
hydroxycitronellal, cinnamic aldehyde
• antiperspirants
• Dye • Disperse blue, orange dye
Axilla
• Usually ICD >ACD
• ACD in case of antiperspirants, disperse dye
• In some cases, could be a manifestation of SCD (“the baboon syndrome”)

Source Substance
Cosmetics TCS, fragrances, BOP, nickel
sulfate, cinnamic aldehyde
Medications neomycin sulfate
Feminine hygiene and
contraceptive products
Wet baby wipe Methylisothiazolinone
preservative
Anogenital area

Source Substance
Common rubber allergens
–feet
carbamates, thiurams, and
mercaptobenzothiazole
Children with sole
dermatitis
rubber additives or chromates (from
leather tanning)
Legs dermatitis BOP, FM I, antibacterial agents, CS, and
lanolin
Lower extremities, feet and sole

Patch Testing
Gold standard for allergic contact eczema
Specific allergens
carried on petrolatum-based vehicles
hypoallergenic chambers
Application of a series of allergens on the skin (back)
Immunol Allergy Clin N Am 37 (2017) 141–152

Patch Testing : indication
 Allergic contact dermatitis
 Uncontrolled atopic dermatitis
 Avoid missing a secondary diagnosis of ACD
 AD : greater risk for ACD
 Sensitizers: topical medications (eg, topical corticosteroids)
J Allergy Clin Immunol Pract 2015; 3: 652-8.

Patch Testing : indication
 oral prednisone 20 mg/day
 ultraviolet irradiation
 topical application of high-
and medium-potency
corticosteroids : should
withdrawn 5-7 days before)
• low-dose prednisone
• low-dose cyclosporin
• oral antihistamine
Impact Not Impact

Patch Testing : procedure
 Standard panel
North American Contact Dermatitis Group panel: 70 antigens
T.R.U.E. Test (Smart Practice) : 35 antigens
German Contact Dermatitis Research Group
 Extended standard panels or specialized supplementary panels
 Specific occupations : cosmetologists and machinists
 Specific exposure sources : reactive dye panels in clothing and
topical medications panels
Individually loaded chamber systems: the aluminum Finn chamber, IQ chambers
(Chemotechnique) and allergEAZE (Smart Practice)
Middleton’s Allergy: Principle and Practice 8th Edition

Patch Testing
From history and clinical features  select panels for testing
Obligate irritant : sodium lauryl sulfate 0.25% or nonionic acid 
positive control to check the skin’s irritability at the time of exposure
Bioavailability depends on
Intrinsic penetration capacity
Concentration
Vehicle
Occlusivity of the patch test system and tape
Time of exposure

German
Contact
Dermatitis
Research Group

T.R.U.E. test
• Thin-layer Rapid-Use Epicutaneous Test
• Pre-made patch test/Preload device
• Consists of 35 allergens incorporated
into hydrophilic gels
• Convenience and ease of use

TRUE test
In a recent meta-analysis, the most prevalent allergens
detected using the TRUE Test
1. Nickel : 14.7 %
2. Thimerosal : 5 %
3. Cobalt : 4.8 %
4. Fragrance mix : 3.4 %
5. Balsam of Peru : 3 %
 May miss some important antigens
 Personal products (cosmetics and lotions) : diluted for
specialized patch testing
J Am Acad Dermatol. 2004;51(3):349-353.

Patch test : Interpretation
 Removed at 48 hours
 Read 2 times : 48 hours, 3-7 days
 Wait 30 minutes before reading : allowed nonspecific redness
from occluding pressure or stripping of tape/chamber
 Delayed late reactions >/= 7 days  late patch test reading :
metal antigens, topical antibiotics (neomycin), topical
corticosteroids, glues, and preservatives

Patch test : Interpretation
ACD : Crescendo (increasing reaction)
Irritative cause : Decrescendo (initially positive and subsequently
waning reaction)
Cross reactions : Positive reactions to chemically similar allergens
Angry back/excited skin syndrome : Positive reactions to more
than 5 nonrelated substances  polysensibilization  repeat
testing of selected allergens about 2 months later

Angry back/Excited skin syndrome

A Practice ParametereUpdate 2015

Patch Testing :
Sensitivity and specificity
 Varies according to the allergen
 Sensitivity and specificity of patch testing : 70-80%
 Nickel sulfate
PT positive only 60% of patients with a positive history (ie,
positive predictive value 60%)
12.5-15% negative history of metal allergy had a positive PT

Limitation of patch testing
Lack of standardization : source and amount of allergens,
variation in materials (chambers, vehicles), variation in the type
of occlusion, the duration of application, reading times, and the
score grading of patch test reactions
Ready-made tests or testing preparations seek to overcome this
problem

Limitation of patch testing
Not all allergens are stable over time
Objectivity in reading and scoring : standardized score
Possibilities to induce or reactivate hypersensitivity in
sensibilized patients
No florid eczema or intense exposition to UV light should
precede the test
No data in pregnancy

MODIFICATIONS OF PATCH TESTING
1. Strip patch testing : increase sensitivity by decreasing the
thickness of the stratum corneum (penetration of the
allergens)
2. Repeated open application test : over a few days
3. Atopy patch testing : aerogenic or alimentary allergens in
patients with atopic history (not yet sufficiently validated)
4. Scratch testing
5. Prick testing : type I allergy (protein contact allergy)

Repeated open application test (ROAT)
Substances with the potential for irritation : cosmetics and
personal care products
Repeated application of a suspected allergen to the antecubital
fossa twice daily for up to 1 to 2 weeks
Observation for the local development of dermatitis at the
application site

Usage test
Product highly suspected of containing a sensitizer
under real world conditions to prove causation
For example : eye mascara daily on 1 eye and not the
other  observe for the development of local dermatitis
at the exposed site
Used when PT with suspected commercial allergens is
negative but highly suspicious

Other TESTING
In Vivo test
For assessing antigen-specific sensitization
Lymphocyte proliferation
cytokine production : ELISA or EliSPOT
Still considered investigation

PHOTO PATCH TEST
5 joules of
UVA light
no
UVA light

Management of
contact dermatitis

Management
Identify and avoid the causative substance
Made aware of irritative or allergic substances  avoid
further exposure to those substances

Counseling
Patient education : Informational leaflet
name of the chemical and synonyms
its common uses
examples of the types of products in which it may be found
risk of cross-reactivity to other related chemicals
Clinics in Dermatology (2014) 32, 116–124
List of products that are free of specific sensitizers
The Contact Allergen Management Program (www.contactderm.org)
Mayo Clinic, the SkinSAFE database
(www. SkinSAFEapp.com)

American Family Physician(2010) 82: 249-255
Management
 Nickel-induced contact dermatitis : cover the metal tab
of jeans with an iron-on patch
 Steroid ointment for patients with allergic to
preservatives in base of steroid creams (Thixocortol
pivalate)
 To prevent irritant contact dermatitis of the hands 
avoid latex gloves

Management
Cool compresses  soothe the symptoms
Antihistamines
Not effective for pruritus associated with allergic contact dermatitis
Commonly used esp. for sedation
J ALLERGY CLIN IMMUNOL PRACT SEPTEMBER/OCTOBER 2015

Topical treatment
Emollients, moisturizers, or barrier creams
Secondary prevention strategies
May associated with increased penetration of occupational allergens
and irritants during working hours
Topical corticosteroids
For localized acute allergic contact dermatitis lesion
Soaking the affected areas before applying  improve penetration and
effectiveness
Insufficient data for irritant contact dermatitis
Topical tacrolimus or pimecrolimus : thinner skin ex. Face

Systemic corticosteroids
Systemic corticosteroids : short term during an acute phase
of an extensive or severe contact dermatitis
Extension > 20 % : systemic steroid therapy ( Prednisolone
0.5-1.mg/kg/day * 5-7 days )  relief within 12-24 hours
No evidence to support the use of long-acting injectable
steroids in the treatment of contact dermatitis

Contact dermatitis

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