Contact dermatitis

Contact dermatitis
F1 Pongsawat Rodsaward

Outline
•Introduction
•Epidemiology
•Pathogenesis
•Clinical features
•Diagnosis and investigation
•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)
• Photocontact dermatitis
• Photoirritant contact dermatitis (PICD, phototoxic dermatitis)
• Photoallergic contact dermatitis (PACD, photoallergy)
• Protein contact dermatitis (PCD)
Nat Rev Dis Primers. 2021 May 27;7(1):38.

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.

• 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
• 22 studies from Europe, 4 from North America and 2 from Asia.
• The prevalence of contac 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%.
Epidemiology

•Prevalence of photocontact dermatitis
• Vary from 5.7% in the United Kingdom to 49.5% in China
•Prevalence of protein contact dermatitis
• Unknown
• PCD constituted 11% of all cases of occupational skin disease between 2005
and 2011 in Finland.
Epidemiology

•Risk factor for ACD
• Acquired
• 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
Epidemiology

•Risk factor for ACD
• Women > men
• Occupation
• 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.
Epidemiology

Common Contact Allergens
in the United States
Allergen Common Source of Exposure Positive Result Rate
in Patch Test
Nickel sulfate Jewelry, metal items, coins 20.1
Fragrance mix I Fragrance 11.9
Methylisothiazolinone Preservative 10.9
Neomycin Topical antibiotic 8.4
Bacitracin Topical antibiotic 7.4
Cobalt chloride Metal 7.4
Myroxylon pereirae (balsam of Peru) Fragrances, spices 7.2
p-Phenylenediamine Permanent hair dye 7.0
Formaldehyde Preservative 7.0
Methylchloroisothiazolinone /
Methylisothiazolinone
Preservative 6.4
Fragrance mix II Fragrance 5.7
Formaldehyde Preservative 5.6
Lanolin alcohol Cosmetics 5.4
Carba mix Rubber accelerators 4.8
Quaternium 15 Preservative 4.8 Middleton's Allergy: Principles and Practice, Ninth Edition

•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
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
Epidemiology

Irritant Contact Dermatitis (ICD)
• Irritant
• soaps, detergents, shampoos, solvents, oils, cleaning agents, disinfectants, acids,
alkalis, dusts, fiberglass, plants, and a number of miscellaneous chemicals.
• Wet work
• Skin is exposed to liquid or occlusive glove use for prolonged periods.
• exposed longer than 2 hours per day, or use occlusive gloves longer than 2 hours per day, or clean their
hands very often (e.g., 20 times per day, or less often if the cleaning procedure is aggressive).
• Is common among healthcare workers and hairdressers.
• The role of physical and environmental irritants has been highlighted, such as heat;
sweating under occlusion; friction, such as from handling paper; manual handling;
and low humidity.

Irritant Contact Dermatitis (ICD)
•Irritant will cause direct injury to the skin in any person, if applied in a
sufficient concentration for a sufficient amount of time, without prior
sensitization or immunologic memory.
•The spectrum of ICD ranges from acute disease, caused by a single
exposure to a severe irritant, to chronic disease caused by repeated
exposure to a mild irritant.
•The concentration of the irritant and duration of exposure determine the
severity of disease with acute exposures.

J Invest Dermatol. 2013 Oct;133(10):2311-2314.

Photoirritant contact dermatitis (PICD)
• is a specific type of irritant or toxic reaction that is mediated by exposure to
ultraviolet radiation.
• Common causes include
• Systemic agents
• Diuretics, NSAIDs, tetracyclines, and phenothiazines
• Topical agents
• Plants containing furocoumarins
• A classic example of this is 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.

Allergic Contact Dermatitis
•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
• the initial sensitization phase
• the elicitation phase
Yale J Biol Med. 2020 Dec; 93(5): 699–709.

Yale J Biol Med. 2020 Dec; 93(5): 699–709.

Photoallergic contact dermatitis (PACD)
•is rare and occurs where UVA exposure causes certain chemicals to
undergo transformation to become allergenic.
•The most common photoallergens are fragrances, topical nonsteroidal
antiinflammatory drugs, and sunscreen agents, such as benzophenones.

Clinical features
•Contact dermatitis is characterized by signs of erythema, vesicles,
papules, scaling, fissures, hyperkeratosis, and symptoms of marked itch
and sometimes pain.
•Typically, contact dermatitis is induced by exogenous factors and often
has its origins in direct or indirect contact with irritant or allergic factors.

Irritant Contact Dermatitis
• 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.

Photoirritant contact dermatitis (PICD)
N Engl J Med. 2014 Aug 7;371(6):559.

Irritant Contact Dermatitis

• The clinical presentation in ACD varies greatly, making allergic and irritant contact
dermatitis difficult to distinguish clinically and histologically.
• ACD generally is more acute, however, with marked itching, possibly vesiculation
or frank blistering, and swelling.
• Skin changes include redness, scaling, blistering, formation of papules or
pustules, exudation, and excoriation.
• In chronic disease, findings may include fissures, lichenification, and
hyperkeratosis.
• Unlike in ICD, the borders of the lesions are poorly defined.

•Distribution often relates to the site of allergen exposure.
•Additional lesions can appear on other parts of the body that have not
come into contact with the allergen (a phenomenon known as secondary
spread).

•An airborne pattern of ACD may be seen in persons exposed to an
airborne allergen, often plants, from the Compositae group.
• Differentiated from photoallergy and other photosensitive eruptions
• no sparing of shaded areas, such as behind the ears, on the eyelids, and under the
chin.

Systemic contact dermatitis
•Systemic exposure to an allergen in a sensitized patient with the
subsequent development of a cutaneous delayed hypersensitivity reaction
•The clinical presentation of SCD can be complex with a high degree of
variability.
• The simplest presentation seen is a localized recall reaction where the dermatitis
occurs at the site of prior topical sensitization.
• The other end of the spectrum would be erythrodermic SCD.
Fitzpatrick's Dermatology, Ninth Edition

•Baboon syndrome
• erythema of the buttocks and upper inner thighs was seen resembling the red
rump of baboons
• Mercury, nickel, and ampicillin were the first described causative agents

•Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE)
• more precise term which by definition denotes a specific cutaneous adverse
drug reaction in which previous cutaneous sensitization is not a necessary
condition
• Diagnostic Criteria for SDRIFE
1. Exposure to a systemically administered drug either at the first or repeated dose.
2. Sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the
inguinal/perigenital area.
3. Involvement of at least one other intertriginous/flexural localization.
4. Symmetry of affected areas.
5. Absence of systemic signs or symptoms.

An. Bras. Dermatol. 92 (4). Jul-Aug 2017
JAAD Case Rep. 2018 Dec 14;5(1):89-90.

Systemic Drugs That Can Cause Systemic Reactivation of
RELATED DRUG WITH POTENTIAL TO CAUSE
SYSTEMIC REACTIVATION OF ALLERGIC CONTACT
DERMATITIS
ONTACT ALLERGENa
Aminophylline
Piperazine antihistamines: hydroxyzine, cetirizine,
levocetirizine and meclizine
Ethylenediamine dihydrochloride (stabilizer
infrequently found in skin care products)
Tetraethyl thiuram disulfide (generic name: disulfiram) Thiuram (rubber antioxidant)
Piroxicam Thimerosal (mercury-derived preservative)

Noneczematous Variants of Allergic
Contact Dermatitis
Sites/appearance Common causes
Erythema multiforme-like allergic
contact dermatitis (ACD)
Occur at periphery of allergen
application;
systemic symptoms of erythema
multiforme are absent.
Exotic woods,
medicaments
Purpuric ACD Lower legs Rubber, textile dyes
Lichenoid ACD Commonly oral mucosa Color developers, metallic dyes in
tattoos; dental amalgams (oral
lichenoid ACD)
Pigmented ACD Clothed portions of body, face may
be involved (Riehl melanosis)
Textile dyes, cosmetics, and
fragrances
Lymphomatoid ACD Histologic criteria only Metals, para-phenylenediamine,
dimethylfumarate, para-tert-
butylphenol resin

Contact Dermatitis. 2007 Jun;56(6):362-4.
Contact Dermatitis. 2021 Jun;84(6):484-486.

Dermatitis. Sep/Oct 2018;29(5):264-269.
J Dermat Cosmetol. 2018;2(2):123-124.

Photoallergic contact dermatitis (PACD)

Contact urticaria
• is a transient wheal and flare reaction from direct contact with a chemical
or protein agent.
•Lesions appear within minutes to an hour and resolve within hours after
exposure.
•Type
• Nonimmunologic contact urticaria (NICU)
• Immunologic contact urticaria (ICU)
• Contact urticaria of uncertain mechanism

Nonimmunologic contact urticaria (NICU)
•Most common type of contact urticaria
•Remains localized, and is less severe than immunologic contact urticaria
(ICU) reactions
•NOT inhibited by H-1 antihistamines
•oral or topical nonsteroidal anti-inflammatory medications are effective

Nonimmunologic contact urticaria (NICU)
CATEGORIES EXAMPLES
Animals Caterpillars, arthropods, corals
Foods Pepper, mustard, thyme
Fragrances and flavorings Cinnamic aldehyde, balsam of Peru, cinnamic
acid
Medicaments Witch hazel, benzocaine, camphor
Metals Cobalt
Plants Nettles, seaweed
Preservatives and disinfectants Benzoic acid, formaldehyde, sorbic acid
Miscellaneous Butyric acid, pine oil, turpentine

Immunologic contact urticaria (ICU)
• is a type I hypersensitivity reaction mediated by allergen-specific immunoglobulin
E (IgE) and seen in individuals previously exposed to the specific agent.
• Atopic individuals are particularly at risk.
• Contact urticaria from latex gloves is the prototypical example of ICU.
• Foods is the second most common cause of ICU.
• potato, carrot, apple, tomato, shellfish, seafood, and meats are well documented, and
wheat allergens
• Additional causes
• preservatives, fragrances, disinfectants, antibiotics, topical medicaments, epoxy resin
hardeners, formaldehyde in clothing, several woods, and birch pollen

Rietschel RL, Fowler JF: Contact urticaria. In Rietschel RL, Fowler JF,
editors: Fisher’s contact dermatitis, Hamilton, Ontario, 2008, BC Decker, pp 615–634.

Contact urticaria of uncertain mechanism
•This type of reaction may occur with substances that produce a CU and a
generalized histamine-type reaction but lacks a direct or immunologic
basis for the reaction.
•It is most commonly caused by ammonium persulfate in bleaching hair
boosters
•Typically has a sudden onset characterized by erythema, edema, severe
pruritus, urticaria, and occasionally syncope with wheezing and dyspnea.

Protein contact dermatitis
•is a chronic eczema because of immediate hypersensitivity to protein and
not related to haptens.
•Repeated episodes of contact urticaria can lead to protein contact
dermatitis.
Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):117-121.

An. bras. dermatol. 88 (4) . Aug 2013

Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):117-121.

V. DIAGNOSIS AND INVESTIGATION

Diagnosis
•Any patient who presents with an eczematous dermatitis should be
regarded as possibly having ACD.
•Careful medical and environmental exposure history
• A history of skin disease, atopy
• The usage of personal care products (soap, shampoo, conditioner, deodorant,
lotions, creams, medications, hair styling products, etc.)
• The patient’s avocations or hobbies
• Occupations

Investigation
•Patch test
•Repeated open application test (ROAT)
•Histopathology

Patch test
•is the 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.

Path test
• Test in
• patients with AD suspected to have ACD, especially those who do not respond to
treatment, initially improve and then exacerbate, or present with a change of pattern of
dermatitis.
• 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
• 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

Methodology
•Application of the PT
• Clean the back with water and pat dry.
• Do not use alcohol as this could be irritating.
• Applied to the upper or mid-back areas (2.5 cm lateral to a midspinal reference
point, as patches applied to the mid-spinal area frequently become detached),
which must be free of dermatitis and hair.

Timing of the 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 the 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
• irritant reactions that appear within the first 48 hours tend to disappear
• Crescendo effect
• allergic reactions tend to increase

Interpretation

False-positive reactions
•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.
huidziekten.nl

•An “angry back” or “excited skin” syndrome
• Should be suspected in patients with more than 5 reactions in close proximity to
each other
• If suspected, repeat the PT with greater separation of allergens or sequentially if
the initial reactions are not clinically relevant, because false-positive reactions
are not reproducible when the triggering allergens are removed.

•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.
T.R.U.E. test

False-negative reactions
•Occur in up to 30% of patch-tested patients
•Possible causes are due to the antigen, skin reactivity, or methodology.

Photo patch test
•Duplicate samples of photoallergens are used; after 48 hours, one set is
exposed to 5 joules of UVA light.
•Test results are read as usual, at approximately day 4 to 7.

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

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.

•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
Treatment

Contact dermatitis

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