Contact dermaititis (irritant and allergic).pdf

Contact
dermatitis
F1 Chaloemchai Chumsaengchotsakul
24th May 2024

Focus
Allergic
Contact
dermatitis

Contact dermatitis
• Introduction
• Epidemiology
• Common allergen
• Pathogenesis
• Clinical manifestation
• Investigation and Treatment

Introduction
• Contact dermatitis is a common inflammatory, noninfectious skin disease
that occurs after direct or indirect contact with substances that are harmful
to the skin.
• Skin disease accounts for 30% of all occupational disease in industrialized
nations, of which 90% is due to contact dermatitis
Middleton's Allergy: Principles and Practice, Ninth Edition

Introduction
• Contact dermatitis may be subdivided into
• Irritant contact dermatitis (ICD)
• Allergic contact dermatitis (ACD)

Epidemiology
Prevalence
• The most common form of CD is ICD, accounting for 80% of cases
• Common irritants include soap, degreasing agents, cosmetics, dust, foods
and solvents
Nat Rev Dis Primers. 2021 May 27;7(1):38.

Epidemiology : irritant contact dermatitis
Irritant contact dermatitis account 17% of all patients with occupational illness.
(second most common follow from musculoskeletal disorders)
Incidence
• 50-70 cases / 100,000 workers / year , in US
• 10.2% from employee survey
Bolognia J et al. Dermatology 4th ed; 2018

Prevalence of ACD
•North American Contact Dermatitis Group (NACDG)
• 5,597 patients referred for assessment of contact allergy
• 66.6% had at least one positive reaction to a patch test
• 50.2% had a final, primary diagnosis of ACD
European countries -> 3,119 people from five European countries
• 27% of individuals had a positive patch test and therefore had contact allergy.
Meta-analysis
• The prevalence of contact allergy was consistently ~20%.
• The prevalence in children is not known, but rates of positive patch test results from children
referred with suspected ACD range from 27% to 95.6%.

Risk factor for ACD
• Underlying inflammatory skin diseases such as ICD and stasis dermatitis
• Occupation -> hairdressers, health-care workers, beauticians, construction
workers, metal workers and those in the foodservice industry
• Innate
Genetic susceptibility, such as mutations in the gene encoding filaggrin
Ethnicity • Darker skin types have a lower risk of ACD than individuals with lighter
skin types

Risk factor for ACD
Women > men
Starts at a younger age in women (20–29 years old) than in men (50–59 years old)
Atopic dermatitis
• The results from different studies have been conflicting
• The association of ACD with atopic dermatitis is likely multifactorial, with
impaired skin barrier function and sensitization to products used in the
treatment of atopic dermatitis being relevant.

Contact Dermatitis. 2021;84:34-40.

North American
Contact Dermatitis
Group

Epidemiology
The most common allergens in the pediatric population are
• nickel, cobalt, neomycin, Myroxylon pereirae (MP; balsam of Peru), lanolin,
fragrance, bacitracin, carmine, p-phenylenediamine, quaternium 15,
propolis, and formaldehyde

J Am Acad Dermatol. 2021 Feb;84(2):235-244.
North America
Contact dermatitis
group in children

Common allergen
• Metals: Nickel, cobalt, chromium
• Fragrances
• Preservatives
• Paraphenylenediamine (PPD)
• Rubber
• Topical steroids
• Acrylate

Nickel
• Most frequently patch test-positive allergen
worldwide
• More common in women
• Ear piercing = significant risk factor (atopy,
sweat, heat, friction)
• Site of contacts
• Earrings , Necklaces, Backs of watches, Mid
abdomen , Eyelid dermatitis from metal eyelash
curlers or eyeglasses.

Nickel
• Facial dermatitis from cellular phone
• Co-sensitization with cobalt ( due to
frequency of combined )
• Dimethylglyoxime test
• Protection: Heavy-duty vinyl gloves
• Accessory : Stainless steel , Platinum or gold
but not white gold (Have nickel 25%)

Nickel sources
Nickel-rich foods
•Chocolate
•Legumes
•Shellfish
•Grains
•Nuts
•Canned food
Contact Dermatitis. 2019;81:227–241.

The EU Nickel directive states
“products which come into direct and prolonged contact with the skin
should not release more than 0.5 mcg nickel/cm2/week, and piercing
posts not more than 0.2 mcg nickel/cm2/week.”
Dimethylglyoxime (DMG) spot test
• Detect the release of nickel >0.5 μg/cm2/week
• Pink precipitate on a white cotton swab
• Sensitivity of 59%, specificity of 97.5%
Contact Dermatitis. 2019;81:227–241.

Cobalt
• Often used in conjunction with other metals in order to add
hardness and strength
• Frequently combined with nickel, chromium, molybdenum,
and tungsten
• Sources: Metal (Jewelry, buttons or tools) , cosmetics (hair
dyes), orthopedic implants, Ceramics and enamel
• Co-sensitivity 80% to nickel (women) or chromate (men)
• Poral appearance on patch testing : erythematous to
violcaceous dots -> not allergic reaction
• Cobalt spot test: yellow-orange

Chromium
• Two most common causes of chromate ACD : leather and
cement
• Hexavalent chromate (more sensitizing) : Thai, trivalent
chromate
• Tanning agents for leather (shoes, gloves, furniture)
• Two most affected areas: feet and hands
• Occupation: cement/construction workers, leather
manufacturers, chrome platers

Chromium
Common contact allergens 1st ed; 2020

Fragrance
• Fragrance Mix 1 and 2
• Balsam of Peru
• HICC (Lyral)

Epidemiology
• Fragrance mix I
• is used to screen for fragrance allergy and contains the following eight different
fragrance ingredients (International Nomenclature of Cosmetic Ingredients name):
• cinnamyl alcohol, cinnamal, amyl cinnamal, geraniol, hydroxycitronellal, eugenol,
isoeugenol, and oakmoss absolute (Evernia prunastri)
• Fragrance mix II
• has increased the detection of fragrance allergy.
• This contains HICC (hydroxyisohexyl-3-cyclohexene carboxaldehyde, also known
as lyral), citral, citronellol, coumarin, farnesol, α-hexyl-cinnamal, and Myroxylon
pereirae resin

Fragrance
• Balsam of Peru detect only 50% of fragrance
components
• Fragrance Mix 1 Detection rate 75%
• Add Fragrance mix 2 Increased detection rate
• Unscent products may be use fragrances for mask
unpleasant odor -> Fragrances free
• Balsam of Peru, use as fragrance and preservative or
emollient.

Balsam of Peru
• Myroxylon pereirae
• Most common in allergy to fragrance
• Also found in spices allergy
Contains many potential allergens: benzoic acid, benzyl acetate, benzyl benzoate,
benzyl cinnamate, cinnamic acid, cinnamic alcohol, cinnamic aldehyde, cinnamyl
cinnamate, eugenol, farnesol, isoeugenol, nerolidol, and vanillin
• Foods: citrus, tomatoes, spices (cinnamon, cloves, vanilla, curry, nutmeg)
• Beverage: colas, wine, beer, gin

Pediatric Dermatology 2016;33(2): 213-15.
•12-year-old boy with recalcitrant pruritic cheilitis
•Dry, cracked lips with central sparing where the
plastic soda bottle made protective contact
•Consumed a minimum of 4 L of cola a day,
packaged in plastic bottles
•Patch testing: balsam of Peru 2+, cinnamic alcohol
1+, cinnamic aldehyde 2+, sodium benzoate 1+,
benzoic acid 1+

Preservatives
• Methylchloroisothiazolinone (MCI)/Methylisothiazolinone (MI)[Kathon CG]
• Methylisothiazolinone (MI)
• Formaldehyde
• Formaldehyde-releasing preservatives
• 2-Bromo-2-nitropropane-1,3-diol (Bronopol®)
• Diazolidinyl urea
• Imidazolidinyl urea
• DMDM hydantoin
• Quarternium-15

Methylisothiazolinone (MI)
Preservatives in personal hygiene products
Sanitary, Wipes, Shower bath , Hand soap ,
Hand Dishwashing , Floor care , Bleach
product , Make up removal, Shampoo ,
Lotion, Sunscreen
Sanitary wipes -> Anogenital regions and
hand

Formaldehyde
• Can cause several types of reaction including ICD,ACD, contact urticaria, and
mucous membrane reactions
• Can be found in cosmetics, medications, nail hardeners, textiles , paints ,
cigarette smoke
• Today , rarely use in personal care products
• Associated with other formaldehyde-releasing preservatives

Formaldehyde-releasing preservatives
• 2-Bromo-2-nitropropane-1,3-diol (Bronopol®) , Diazolidinyl urea ,
Imidazolidinyl urea , DMDM hydantoin , Quarternium-15
• Textile dermatitis, Formaldehyde resins -> wash and wear or wrinkle resistant
clothes
• Quaternium – 15 -> shampoos, moisturizers, conditioners and soaps
• Associated with formaldehyde sensitivity and others formaldehyde-releasing
preservatives

P-Phenylenediamine (PPD)
• Permanent hair colorant
• Temporary henna tattoos
(darkens the henna tattoo)
• Reactions may persist up to 30
days
• Angioedema-like reaction

P-Phenylenediamine (PPD)
Actas Dermosifiliogr 2018;109:485-507.
Contact Dermatitis 2017; 77:49–63.

Poison of Ivy
•Anacardiaceae family
•Most common cause of
allergic contact
dermatitis due to plant
•Poison ivy and Poison
Oak
•กอกกัน และ สะเดาช้าง

Poison of Ivy
• Urushiol (Oily mixture of organic
compound
• Cashew nuts (Anacardium
occidentale) any part of the tree
except nut can cause dermatitis
• Mango (Mangifera indica)
• The leaves, bark and stems and
fruit contain sensitizing
• Peeling the fruit before eating
typically prevents allergic
contact dermatitis

Poison of Ivy
•Ingestion of both cashews and mangoes has been
shown to cause reactions in patients sensitive to
poison ivy and poison oak, as they are all members
of the Anacardiaceae family

Erythema multiforme – like from Exotic woods
Dermatology 1 July 2000; 200 (1): 59–62.
Contact Dermatitis. 2021; 85: 242–244.
Pao ferro
Guitar maker
Rosewood
ring

Emollient
• Lanolin
• Propylene Glycol
• Cocamidopropyl betaine

Cocamidopropyl betaine
• A surfactant found in shampoos (“no tears”) and other
cleansers
• Composed of a coconut oil derivative in addition to
dimethylaminopropylamine and monochloroacetic acid
• Utilized in personal products, especially those for children
• Presents as dermatitis on the eyelids, face, scalp, and neck
• Can also cause a diffuse dermatitis, especially in patients
with AD

Propylene Glycol
• Used as a softening agent, solvent, moisturizer, preservative or vehicle in many personal
products, medications, and industry
• Personal products: lotion, make‐up, hair products (shampoo, conditioner, hair dye kits),
soap, toothpaste, mouthwash, antiperspirant
• Look for PG in many topical CS
• Foods: flavoring agent, food color solvent (highest in flavorings)
• Packaged foods, salad dressings, cake mixes, soda, food coloring, bread, dairy
• Children: diapers, wipes
• Cause of Systemic Contact Dermatitis: foods, medications

Clinical Manifestations : Modern era

Fitzpatrick's Dermatology, Ninth Edition

J Allergy Clin Immunol Pract. 2020 Jun;8(6):1883-1893.

Pathogenesis of ICD
• Acute Phase
• Direct Cytotoxic damage
to keratinocyte
• Release of mediators
• T cell activation
• Chronic Phase
• Slower damage
• Barrier disrupted (lipid)
• Increase TEWL
Bolognia J et al. Dermatology 4th ed; 2018.
J Invest Dermatol. 2013 Oct;133(10):2311-2314.

Clinical Manifestations of ICD
• The first signs of ICD are dry and slightly scaly skin, with increasing redness and
lichenification after prolonged or repeated irritant exposure.
• This may be followed by formation of fissures, also known as rhagades.
• Itching is generally not as severe as in ACD.
• On the hands, the predominant areas involved include the web spaces initially, the
dorsal aspects of the hands and fingers, as well as exposed portions of the forearms.
• Over the course of disease, the palms may also be involved.
• The eczematous lesions generally remain limited to exposure sites, and secondary
spread to other areas typically does not occur.

Acute phase : Occupational Accidents -> peak
quickly, minutes to hours
•Burning , stinging and soreness
Irritant reaction ICD = wet workers , Frequent
exposure to soap and water
Cumulative ICD
•Pruritus , Lichenification , Hyperkeratosis, Xerosis ,
Erythema, Vesicles

Pathogenesis of ACD
• ACD is caused by a type IV delayed hypersensitivity reaction in the skin
and is initiated by an low molecular weight chemicals and metal allergens
penetrating the skin and combining with major histocompatibility complex
(MHC) class II molecules on epidermal dendritic cells or Langerhans cells.
• The disease pathology is comprised of two distinct phases
Yale J Biol Med. 2020 Dec; 93(5): 699–709.

Pathogenesis of ACD

Clinical Manifestations of ACD
•ACD is caused by a type IV delayed hypersensitivity reaction in the skin
and is initiated by a low molecular weight chemicals and metal allergens
penetrating the skin and combining with major histocompatibility complex
(MHC) class II molecules on epidermal dendritic cells or Langerhans cells.
•The disease pathology is comprised of two distinct phases
Yale J Biol Med. 2020 Dec; 93(5): 699–709.

Clinical Manifestations of ACD
•Well-demarcated pruritic eczematous eruption (blistering, weeping and/or
edema) or Chronic (Lichenification or scaly plaques)
•Usually localized to the area of contact but aware off rinsed over ex. Shampoos
•The clinical presentation in ACD varies greatly, making allergic and irritant
contact dermatitis difficult to distinguish clinically and histologically.

ACD vs ICD
Middleton's Allergy: Principle and Practice 8th Edition

Airborne contact dermatitis
•ACD or ICD , or overlap with photoallergic
contact dermatitis
•Affected area : eyelids , face, V of the neck ,
arms and legs
•Common are plants and epoxy chemicals
•Patch test

Systemic contact dermatitis
• This reaction generally involves a chemical to which the patient
has had a prior contact allergy
• Systemic exposure to an allergen in a sensitized patient with the
subsequent development of a cutaneous delayed hypersensitivity
reaction
• Route : injection or oral, intravenous or intranasal
• The simplest presentation seen is a localized recall reaction where the
dermatitis occurs at the site of prior topical sensitization.
Fitzpatrick's Dermatology, Ninth Edition

Baboon syndrome
International Journal of Dermatology 2012;51:1131-1144.

•In the proper clinical setting, patch
tests demonstrating a sensitivity to
balsam of Peru or fragrance mixture
can support the diagnosis of a
systemic contact dermatitis due to
balsam-related foods or spices. A diet
avoiding such foods or spices may
result in an improvement of the
dermatitis.

Clin Case Rep. 2021 Apr 10;9(5):e04103.

Chelitis from contact dermatitis

Allergic Contact Hand Dermatitis
•Vesicles
•Favors the fingertips , Nailfold, and dorsum
•Less commonly involve the palm as skin thicker in
this area
Duarte I et al. Am J of Contact Derm 1998 9:216‐23 & Warshaw, EM et al
J Am Acad Dermatol 2007;57:301‐314

Allergic Contact Facial Dermatitis
• Facial dermatitis results from allergens placed directly on
face or transferred from other regions of the body or airborne
• Moisturizers, sunscreens, foundations/powders produce a
bilateral dermatitis
• Nickel allergic patients can react to cell phones, eyelash
curlers & hair curlers
• Scalp skin is relatively resistant to allergens in shampoos and
hair dyes
• “run‐off” patterns of dermatitis on the forehead and lateral face,
eyelids, ears, & neck
Castanedo‐Tardan, MP & KA, Zug. Dermatologic Clinics July 2009. 27(3):265‐80

Investigation
• Patch test
• Repeated open application test
• Histopathology

Patch test
• Standard and most important diagnostic procedure for identifying delayed
type hypersensitivity as the cause of ACD.
• Reproduces exposure to an allergen, creating a localized area of ACD.
• Must be performed in accordance with international guidelines: It is
important that substances be tested appropriately, which often involves
diluting them as prescribed by published data, to avoid both inadvertent
sensitization and irritation.

Patch test
• Test in
1. Distributions that are highly suggestive of ACD; ACD of the hands, feet, face,
and eyelid, as well as unilateral presentations
2. A clinical history that is highly suggestive of ACD
3. High-risk occupations for ACD; health care workers, cosmetologists, and
florists, etc
4. Dermatitis of unknown etiology
5. Worsening of a previously stable dermatitis
6. Dermatitis that is unresponsive to treatment J Am Acad Dermatol 2016;74:1029-40.

Patch test
Not test in
• Acute generalized dermatitis or with extensive eczema on the back
• on immunosuppressant medications
• prednisone (less than 20 mg/day) and cyclosporine may still yield clinically relevant
results
• Topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or ultraviolet radiation
• Topical potent TCS or TCI should not be applied on the test site for 5 to 7 days before
testing
• not to have a suntan or use a sunbed 2-4 weeks before the PT
J Allergy Clin Immunol Pract. Sep-Oct 2015;3(5):669-75.

Side effect of patch test
• Skin reddening and itching at the application site
• this usually disappears after a few days
• Persistent reaction
• some positive test reactions, for example, to gold, may persist for up to a month.
• Flare of eczema • a positive PT may be accompanied by a flare of existing or previous
eczema.
• Pigment change • an increase or decrease in pigment may be seen at the site of patch
tests; this may last for months or rarely (1 in 1000) is permanent. •
• Infection • this is rare and would need antibiotic treatment.
• Scarring • very rare (1 in 10,000)

Methodology
• Test site -> The upper back is the preferred site, as the concentration of standard
allergens has been determined for the skin of the back only.
• Loading the chambers
• acrylates, fragrances, and allergens in aqueous vehicle
• should be loaded in the chambers and placed on the patient right away
• place a filter paper disk (if needed) and apply a drop of liquid, just sufficient to soak the disk
• allergens on petrolatum base
• may be prepared 24-48 hours before application
• apply a 5 mm ribbon of petrolatum-based antigen to each disk

Timing of Patch test reading
• 1st
• 20-30 minutes after application, if contact urticaria is considered
• 48 hours after their application •
• The tests are read 20-30 minutes after removal of the patches to allow erythema from
the occluding pressure or stripping of the tape and/or the chamber to resolve.
• 2nd
• between 3 and 7 days after application.
• 30% of relevant allergens that were negative at the 48-hour reading became
positive at a 96-hour.

Timing of Patch test reading
• 3rd
• a late reading 7-10 days after PT application if there is a negative early reaction
• Contactants such as metals (nickel sulfate, gold sodium thiosulfate, palladium
chloride, potassium dichromate, cobalt chloride), some antibiotics (neomycin),
TCS (tixocortol-21 pivalate, budesonide), and dyes (para-phenylenediamine)
• Decrescendo effect cry late • irritant reactions that appear within the first 48
hours tend to disappear
• Crescendo effect • allergic reactions tend to increase

Interpretation

False positive reaction
• An “angry back” or “excited skin” syndrome
• False-positive reactions adjacent to large true
positive reactions that induce contiguous skin
inflammation and irritability.
• The underlying mechanisms are not fully
understood.
• More likely to develop in patients with a longer
duration of the primary dermatitis.

False positive reaction
• Irritant reaction
• Marginal (edge)
• A pustular patch reaction is an irritant reaction
and is common in atopic individuals especially
in response to metals such as nickel, copper,
arsenic, and mercuric chloride.
• ~5% cobalt chloride

Repeated open application test (ROAT)
• The repeated application of a suspected allergen to the antecubital fossa
twice daily for up to 7 days and observing for the development of
dermatitis up to 3 weeks.
• To replicate the reactivity of eyelid skin, the ROAT can also be performed
on the back of the ear.
• Although the threshold concentration for a positive reaction for the ROAT
per application was significantly lower than the threshold concentration for
a positive PT, the accumulated ROAT dose was very similar to the PT.

Histopathology
• Similar to that observed in eczematous reactions
• Spongiotic dermatitis
• Typical epidermal changes of spongiosis
• The presence of a dense lymphocytic infiltrate in the upper dermis, with
epidermal exocytosis of lymphocytes
• A greater number of eosinophils may be observed in ACD compared with
ICD

Cytokine assay
BMC Immunol 9, 19 (2008).

Cytokine assay
Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):605-14
• Palladium
hypersensitivity
• Six patients with oral
symptoms associated to
the presence of metal
restorations, and with a
positive patch test to Pd
were selected for this
study.

Treatment
• Avoidance of identified allergens and irritants
• Consistent use of an emollient or moisturizing agent
• Topical corticosteroids

Treatment
• Avoidance of identified allergens and irritants
• The core of the management of contact dermatitis
• Avoiding wet work and mechanical irritation
• Consistent use of an emollient or moisturizing agent
• Preparations ideally should be free of preservatives or fragrances, although oil-
based ointments are often greasy, which may hinder compliance.
• In acute disease -> Dressings, lotions, or creams are used.
• In subacute and chronic stages -> Ointments should be used

Treatment
• Topical corticosteroids
• The choice of vehicle depends on the morphology, the eczema stage, and the
nature of the skin lesions
• The use of topical corticosteroids over longer periods of time should be avoided.
• It is preferable to use a stronger corticosteroid preparation to treat the disease
while the condition is acute, followed by relatively rapid tapering of the drug
• ACD caused by topical corticosteroids is not uncommon and should be
considered when contact dermatitis does not respond to treatment.

Treatment
• Phototherapy
• proved effective in chronic contact dermatitis
• Systemic corticosteroids
• should be reserved for exceptional situations and restricted to short-term
use.
• Alitretinoin
• An agonist of both vitamin A acid receptors
• is approved in Europe for the treatment of severe chronic hand eczema that
does not respond, or responds inadequately, to topical corticosteroids

Thank you
Chaloemchai Chumsaengchotsakul, M.D.

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