Allergic Contact Dermatitis vs Irritant Contact Dermatitis


ACD_vs_ICD.png

ICD Diagnostic Criteria
Major
Minor
  • Macular erythema, hyperkeratosis, or fissuring predominating over vesiculation
  • Glazed, parched, or scalded appearance of the epidermis
  • Healing begins promptly on withdrawal offending agent
  • Patch testing negative
  • Sharp circumscription of the dermatitis
  • Evidence of gravitational influence (dripping effect)
  • Less tendency for dermatitis to spread (than in ACD)
  • Morphologic changes suggest small differences in concentration or contact time producing large differences in skin damage



Systemic Contact Dermatitis (SCD)

  • Localized or generalized dermatitis in contact-sensitized individuals re-exposed to the allergen orally, transcutaneously, internally (e.g. from implants), intravenously, or by inhalation.
    • Presentation
      • Dermatitis occurs at the site of exposure, at previously sensitized sites (eg, an old lesion or the site of a positive patch test response), or in previously unaffected areas
      • For SCD to implants, patients may present with joint loosening, joint pain, and/or rash beginning weeks-months after implantation; the rash is often erythema, induration, papules or vesicles above site of implantation
        • Consequences of implanting a device with a component that the patient has a positive patch test to is unclear, but a shorter lifespan of the implant has been observed in patients with positive patch testing to metals and bone cement components and history of metal hypersensitivity
    • Common causes:
      • The two most common allergens are nickel and Balsam of Peru
      • Biomedical devices - orthopedic implants, stents, pacemakers, pectus bar, dental implants, contraceptive implants
      • Metals - cobalt, copper, chromium, gold, mercury, nickel, and zinc
      • Medications - corticosteroids, antihistamines (diphenhydramine, ethylenediamine, hydroxyzine, and doxepin), miconazole, terbinafine, neomycin, gentamicin, erythromycin, pseudoephedrine, cinchocaine, benzocaine, tetracaine, oxycodone, IVIG, aminopenicillins, 5-aminosalicylic acid, naproxen, allopurinol, mitomycin C, 5-fluorouracil, and suxamethonium
      • Other - ragweed, chamomile, feverfew (Tanacetum parthenium), Arnica species, marigold, Echinacea species, mugwort, cinnamon oil, vanilla oil, and Balsam of Peru
    • In drug-induced SCD the clinical picture is frequently a symmetric intertriginous and flexural exanthema
      • Criteria for diagnosis
        • Exposure to a systemic drug at first or repeated dosing (contact allergens excluded)
        • Erythema of the gluteal/perianal area, V-shaped erythema of the inguinal/perianal area, or both (Baboon syndrome)
        • Involvement of at least 1 other intertriginous/flexural localization
        • Symmetry of affected areas
        • Absence of systemic signs and symptoms


Approach to SCD to Implants

  • 5% of patients with orthopedic implant sensitivity and up to 21% of patients with preop metal sensitivity may develop cutaneous reactions on re-exposure to the same metal


Orthopedic Metal Implant Algorithm
Orthopedic Implant SCD algo.png
*metals: Aluminium, Chromium, Cobalt, Iron, Manganese, Molybdenum, Nickel, Niobium, Phosphorus, Silicon, Tantalum, Titanium, Tungsten, Vanadium, Zirconium


Combined Metal Implant Algorithm
Implant SCD algo.png
Series allergens outlined in


  • General notes
    • Fonacier: the need for patch testing is controversial because it is poorly reliable in predicting or confirming implant reaction
      • Preimplantation patch test: consider if strongly suspect metal allergy
      • Post-cutaneous reaction (months - years post implant): patch testing can be done with the appropriate series of metals
      • Negative patch test is reassuring for absence of delayed hypersensitivity
      • Positive patch test does not prove that the metal is causative, however if relevant allergens are identified and corticosteroid therapy is insufficient to clear the eruption, removal of implant may be considered
    • Management ultimately ends in implant removal vs. implant replacement with non-allergenic alloy vs. coating implant with teflon; if replacement is not feasible then a 21 day prednisone taper is recommended



ACD with Scattered Generalized Distribution

  • Difficult diagnostic and therapeutic challenge: lacks the characteristic distribution of ACD that gives a clue to the etiology
  • 49% with scattered generalized dermatitis had a positive patch test at least possibly relevant to their dermatitis
  • Prevalence higher with history of AD
  • Two most common allergens: Nickel, Balsam of Peru

Contact Antigens


Common Contact Allergens

  • More than 3700 substances have been identified as contact allergens, but fewer than 40 allergens produce most cases of allergic contact dermatitis.
Top_30_contact_allergens.png



Pediatric Contact Allergens

  • Although rare in the first years of life (<10 years), the occurrence of ACD in older children attains and even exceeds that observed in adults.
Top_10_pediatric_contact_allergens.png


Plant DermatitisToxicodendron_range_US.jpg

  • Toxicodendron (Rhus) dermatitis
    • Also known as poison ivy, oak, or sumac
    • Caused by urushiol found in the saps of the Anacardiaceae plant family
      • Urushiol is also contained in mango skin, cashew nut oil, ginkgo (female) leaves, Japanese lacquer, and Indian marking ink.
    • Identified by its streak-like or linear papulovesicular presentation (isomorphic Koebner reaction). The dermatitis is similar whether caused by poison ivy, poison oak, or poison sumac.
    • Symptoms develop 4-96 hours after exposure and peak between 1-14 days. New lesions can present up to 3 weeks later in previously unexposed individuals.
    • Patch testing is not indicated for Toxicodendron dermatitis, because the dermatitis is self-limiting, readily diagnosable, and there is a danger of exacerbating ACD.
    • Although Anacardiaceae causes most cases, other plants that are common sensitizers are listed below:


Non_rhus_plant_contactants.png
  • Non-rhus plant dermatitis
    • Alstroemeria (Peruvian lily) dermatitis due to alpha-methylene-gamma-butyrolactone (aka tulipalin A) that is present in the flowers and bulbs
      • Most frequent cause of hand eczema in flower workers
      • Allergen can penetrate latex and vinyl gloves
      • Classic finding is an eczematous and intensely pruritic eruption that affects the first 3 fingers and exposed areas of dorsal hands, forearms, the V-region of the neck and the face.
      • Recurrent summertime flares during plant growing seasons and winter remissions are typical
  • Pollen dermatitis
    • Seasonal recurrence of ACD on exposed skin surfaces may be due to repeated exposure to oleoresins in airborne pollen. Reported particularly for ragweed pollen, but ACD to tree and grass pollen also occur.


Contact Allergens Associated with Foods

  • Nickel sulfate
    • Foods may naturally contain Ni
    • Metal utensils leach Ni into foods
    • Evidence support the contribution of dietary nickel to vesicular hand eczema
  • Myroxilon pereirae (Balsam of Peru)
    • Found in toothpaste, mouthwash, flavors
    • Sensitization to balsam of Peru in cosmetics may lead to future systemic ACD flares from foods containing balsam of Peru
  • Propylene glycol
  • Fragrance mix
  • Compositae mix
  • Cinnamic aldehyde
  • Potassium dichromate
  • Sesquiterpene lactone mix



Corticosteroid-induced Contact Dermatitis


Steroid structural groups.png
Structural class
Class A:
Hydrocortisone type
Class B:
Triamcinolone acetonide type
Class C:
Betamethasone type
Class D1:
Betamethasone dipropionate type
Class D2:
Betamethasone dipropionate type
Cross-reactions
Cross-reacts with D2
Budesonide specifically cross-reacts with D2


Cross-reacts with class A and budesonide
Patch Test Substance
Tixocortol-21-pivalate
Budesonide
Triamcinolone acetonide

Clobetasol-17-propionate
Hydrocortisone-17-butyrate
  • Budesonide and tixocortol-21-pivalate found in T.R.U.E. patch test
  • Refer to topical corticosteroids for steroids found in each structural class



Differential Diagnosis

  • Contact dermatitis is an eczematous disease with lesions that range from red clustered papules to vesicles and bullae. Scaling and pruritus are prominent features.
Major Conditions That May Be Investigated in the Differential Diagnosis of Contact Dermatitis
Primary Skin Diseases
Systemic Diseases
  • Atopic dermatitis
  • Lichen simplex dermatitis
  • Neurodermatitis; prurigo nodularis----------------
  • Nummular dermatitis
  • Dyshidrotic dermatitis
  • Seborrheic dermatitis
  • Psoriasis
  • Dermatophytosis
  • Polymorphous light eruption
  • Impetigo
  • Acne rosacea
  • Factitial dermatitis
  • Intertrigo
  • Erythrasma
  • Lichen planus
  • Scabies
  • Pyoderma gangrenosum
space
  • Wiskott-Aldrich syndrome
  • X-linked agammaglobulinemia
  • Phenylketonuria
  • Acrodermatitis enteropathica
  • Hurler syndrome
  • Chronic granulomatous disease
  • Hyper-IgE syndrome
  • Drug reactions
  • Dermatophytid ID reaction
  • Connective tissue diseases (SLE, dermatomyositis)--------
  • Porphyria cutanea tarda
  • Mycosis fungoides


Diagnosis


History and Physical Exam

  • Although history can strongly suggest the cause of ACD, experienced physicians accurately predict the sensitizer in 10%-20% of patients when relying solely on the history and physical exam.
    • Most common occupations associated with ACD are health professions, food processors, beauticians, hairdressers, machinists, and construction workers.
    • Most common hobbies and nonwork activities include gardening, macrame, painting, ceramic work, carpentry, and photography
    • History of animal exposure: pet dander, products used on pets, and traces of outdoor allergens all can cause ACD
Clues from Physical Exam
Location
Eyes/Eyelids
Ocular contact dermatitis
  • Differential diagnosis: ACD (63.5%), irritant contact dermatitis (15%), AD (<10%), seborrheic dermatitis (4%)
    • Main factors in history for diagnosis: 4 eyelid inolvement (suggests ACD), onset of symptoms within 2-6 months of visit (ICD), onset >6 months from visit and history of atopy (AD)
  • May present as rash over the eyelids, tearing, redness, itching, stinging/burning sensations, and a sensation of fullness in the eye when swelling is involved. The eyelid may appear thickened, red, and sometimes ulcerated. When the conjunctiva is involved, vasodilatation, chemosis, watery discharge, and sometimes papillae can be observed.
  • Common allergens include:
    • In 72% with only eyelid dermatitis, gold was the most common allergen.
      • Fragrances, preservatives, nickel, thiuram (rubber), cocamidopropyl betaine (CAPB) and amidoamine (shampoos), and tosylamide formaldehyde resins (nail polish) are also frequent.
    • Topical drugs and antibiotics (anesthetics, neomycin, antivirals, pilocarpine, timolol)
    • Preservatives in ophthalmic solutions (thimerosol, benzalkonium chloride, chlorobutanol, chlorhexidine, EDTA)
    • Cosmetics (eye and lip glosses containing waxes, fats, and dyes)
    • Perfumes, sunscreens containing PABA
    • Fingernail products (containing acrylates, formaldehyde resins and sulfonamide derivatives)
    • Hair products (dyes, permanent solutions)
    • Adhesives including acrylates (false eyelashes, artificial nails)
    • Nickel (eyelash curlers and eyeglass frames)
    • Irritant plants (poison ivy, sumac, oak)
    • Latex (gloves)
    • Soaps, detergents, bleach, and solvents
    • Soft contact lenses (acrylates)
  • In patients with mixed facial and eyelid dermatitis, nickel, Kathon, and fragrance are the most frequently positive patch tests

Ectopic contact dermatitis
  • Occasionally personal care products and cosmetics will manifest the contact allergy lesions in locations distant from the original skin sites
  • Typical causes are toluene sulfonamide formaldehyde resin in nail polish, which may cause an eyelid dermatitis yet leave the periungual skin and distal fingers clear
  • Cocamidopropyl betaine, a surfactant in shampoo and facial cleansers, can present with eyelid dermatitis without concurrent dermatitis on the scalp, neck, and ears
Face
  • Cosmetics (including vehicles and preservatives)
  • Fragrances
  • Cell phones (Ni)
  • Cigarettes - allergens from filters, paper, tobacco, including menthol (mint, peppermint), licorice, colophony, formaldehyde
  • In children, may occur due to contact with maternal hair dye (paraphenylenediamine)
Scalp
  • Paraphenylenediamine (found in hair dyes)
  • Cocamidopropyl betaine (surfactant found in shampoos, cleansers)
  • Glycerol thioglycolate (permanent wave solutions)
Lips/mouth
  • Cosmetics, balms applied to lips
  • Cinnamon and peppermint flavorings from oral care products and chewing gum
  • Nail polish, cigarette paper, various essential oils,
  • Foods - oranges, lemons, grapefruits, carrots, celery, parsnips; mangoes (in urushiol-sensitive patients)
  • Cigarette
  • Dental composite resins, dentures containing acrylates
Hands
Neck/Back
Vehicles, preservatives, drippings from permanent wave preparations, hair dyes, shampoos, conditioners, fragrances, and nickel in jewelry
Axilla
Contact to topically applied agents may involve the entire axillary vault, whereas allergy due to clothing usually spares the apex of the vault.
Anogenital
Topical medications, suppositories, douches, latex condoms and diaphragms, spermaticides, lubricants (used during coitus), sprays, and anogenital cleansers
Lower extremities
  • Shaving agents, moisturizers, and, rarely, stocking materials or dyes
  • Topical medications used to treat venous stasis
Feet
  • ACD more common than ICD, usually located on the dorsum of the feet and toes (especially the hallux) but can also involve the sole and calcaneus. The interdigital areas are rarely involved
  • Most common positive patch test reactions in patients with ACD exclusively on the feet are rubber compounds (mercaptobenzothiazole mix, thiuram mix, carba mix, and PPD mix), with some patients sensitive to more than 1 of the agents. Other chemicals in footwear (eg, leather, adhesives, glues, and dyes) or in topical agents used for treatment (eg, creams, ointments, and antiperspirants) can cause ACD. Chemical agents used in the tanning and dyeing processes of leather (chrome), glues (colophony) used in soles and insoles, and nickel sulfate used in footwear buckles, eyelets, and ornaments can be sensitizing agents.
Sun-exposed areas
  • Involves sun exposed areas such as face, V of neck, dorsal hands and forearms; spares upper eyelids, upper lip, submental areas, postauricular areas
Rash appearance
Streak-like or linear papulovesicular rash
  • Toxicodendron dermatitis (e.g. poison ivy)
Patient history
Recent surgical implant
Criteria for diagnosis of a cutaneous implant–induced reaction are:
  1. Dermatitis (localized or generalized) appearing after implant surgery
  2. Persistent dermatitis that is resistant to appropriate therapies
  3. A positive patch test result proven history to a metallic component of the implant or to commonly used acrylic glues
  4. Resolution of the dermatitis after removal of the implant
  • Patch test kits may be available from the manufacturer of the implant to screen patients pre-op or diagnose patients with problems post-op
Rash worsening with topical medications
  • Suspect ACD to component(s) of topical medications:
    • Corticosteroids
    • Lanolin (Amerchol) - found in Aquaphor
    • Para-aminobenzoic acid - sunscreens
    • Neomycin sulfate
    • Bacitracin
    • Topical anesthetics (benzocaine, tetracaine, dibucaine)
    • Thimerosal - preservative
    • Propylene glycol - preservative
    • Iodochlorhydroxyquin (aka clioquinol) and chlorquinaldol (quinolone mix) - antimicrobial
Health professional with hand dermatitis
  • DDx includes ACD, ICD, IgE-mediated contact urticaria
  • Typically due to rubber accelerants (In one study, 13% were sensitized to thiurams, 3.5% to dithiocarbamates, 3% to mercaptobenzothiazole and/or derivatives, 0.4% to thioureas, 3% to 1,3-diphenylguanidine) and epoxy resins (e.g. bisphenol-A)



Patch Testing (Occlusive)

  • Patch testing is the gold standard for identification of a contact allergen.
  • Procedure:
    • Determine if patient is a good candidate:
      • Patient's dermatitis must be under control
      • Patients should not be taking high-dose systemic corticosteroids (low dose 20 mg/day, may be acceptable) and should avoid potent topical corticosteroids and calcineurin inhibitors to avoid false negative reactions.
    • Perform test:
      • When possible, use upper back (concentration of standard allergens were determined for back skin), and avoid midline of back (ideally place patches 2.5 cm lateral to the midspinal column); shave back hair if needed
      • Clean skin with plain water (no alcohol or soap) and dry before application of patches
      • Allergens are placed in Finn chambers and affixed to the back with tape
        • Quantity of allergen to place in chamber is 5 mm ribbon of petrolatum based or 1 drop of liquid in filter paper disc
      • Patients need to abstain from bathing or heavy exercises/sweating while the patches are in place.
    • Interpret test:
      • The tape is kept in place for 48 hours at which point the patient returns to the office for the initial reading, and also in 96 h for the final reading. Since 30% of reactions are negative at 48 hours, additional reading(s) should be performed at 3 or 4 and sometimes 7 days after the initial application, depending on the allergen.
        • Ideally, read tests 30 minutes after removal of the patch to allow erythema, due to occlusion of the tape and/or chamber to resolve
        • Irritant reactions tend to disappear by 96 hours
        • Delayed reading after 5 days may be necessary for allergens like metals (gold, potassium dichromate, nickel, cobalt), topical antibiotics (Neomycin, Bacitracin), topical corticosteroids, and p-phenylenediamine; 30% of negative tests at 48 h may be positive on delayed (96 h) readings
      • Score test:Patch_test_scoring.png
        Patch_test_reading.png
      • Reactions graded as 2+ and 3+ strongly suggest the presence of prior or present sensitization to an allergen. The greatest source of misinterpretation is due to questionable or non-reproducible reactions in the equivocal +/- or 1+ categories
      • A negative patch test has good NPV
      • Common cause of false positives:
        • Use of irritant substances, which often appear sharply demarcated (confined to disc area), shiny (often with blister), burning or painful sensation, and the severity may decrease between 1st and 2nd reading
        • Pustular patch reactions are common in atopics, minimal pruritus noted, commonly caused by nickel, copper sulfates, arsenic trioxide, mercuric chloride
        • Angry back syndrome - false positive reactions adjacent to large true positive ones that induce contiguous skin inflammation and irritability (i.e. marked 2+ or 3+ patch surrounded by milder positive responses)
        • Excited skin syndrome - suspected if there are >5 positive reactions
        • If false positives suspected repeat the patch test with greater separation of allergens if the initial reactions are not clinically relevant, as the false positive reactions are not reproducible when the triggering allergens are removed
      • ? and+ reactions are more likely to be truly allergic if redness/pruritus develops by 96 h; common causes are formaldehyde, potassium dichromate, wool wax alcohol, fragrance, paraben, nickel, chlorhexidine, gluteraldehyde
        • Can clarify by repeat testing or by the "use" test (aka repeated open application test or ROAT, see below)



Chemotechnique Diagnostics Patch Test




T.R.U.E. Test

  • Thin Layer Rapid Use Epicutaneous Test - commercially available FDA approved patch test
  • Negative aspects of T.R.U.E. Test
    • Of the top 30 contact allergens reported in 2005-2006, 10 were not included in the T.R.U.E. test
      • Only 25-30% of patients with allergic contact dermatitis are diagnosed
      • 50% of allergens causing occupational dermatitis are missed
    • Although patch testing beyond the TRUE Test does not have FDA approval, many dermatology referral centers routinely use an expanded allergen series of 50 to 80 allergens, such as the NACDG Screening Series. In addition, smaller series are added depending on an individual patient’s exposures, such as a baker, dental hygienist, hairdresser, or nail technician.

T.R.U.E. Test Allergens
Panel 1.1 Allergens
Potential Allergen Sources:
1
Nickel Sulfate

---------------------------------------------------------
  • Nickel and nickel-plated objects; tools; metal machine parts and equipment
  • Cell phones
  • Nickel catalysts, powders and pigments
  • Metalworking fluids and oils
  • Costume jewelry; keys, coins and utensils
  • Metal clothing fastener
  • Foods such as legumes, nuts, grains, fish, chocolate, and potatoes.
2
Wool Alcohol
  • Personal care products such as cosmetics and cleansers
  • Pet care products
  • Metalworking fluids
3
Neomycin Sulfate
  • Topical medications containing neomycin
  • Other substances to which the patient may react
    • Topical antibiotics: gentamicin, bacitracin, framycetin
    • Injectable antibiotics: kanamycin, mycifradin, sisomycin, paromomycin,
      streptomycin, butirosin, spectinomycin, fradiomycin
  • Vaccination with neomycin-containing preparations poses very little risk of systemic contact dermatitis (due to very small quantity in vaccine)
  • Although bacitracin and neomycin are chemically unrelated, the two often co-react during patch testing, probably due to patients being exposed to both medications through combination ointments
4
Potassium Dichromate
  • Industrial, construction and home repair products such as cement, concrete, wood preservatives
  • Leather and hide glues
  • Metal working, welding and plating with chrome alloys; cutting oils, corrosion inhibitors, drilling muds
  • Green dyes and metallic pigments; inks and paints
  • Chromic surgical gut sutures
  • Orthopedic and dental implants or prosthesis.
5
Caine Mix
  • Benzocaine
  • Tetracaine hydrochloride
  • Dibucaine hydrochloride
  • Topical medications containing anesthetic
6
Fragrance Mix
  • Geraniol
  • Cinnamaldehyde
    Hydroxycitronellal
  • Cinnamyl alcohol
  • Eugenol
  • Isoeugenol
  • Amylcinnamaldehyde
  • Oak moss
  • Any scented product including foods, medications, cosmetics, lotions, detergents, etc.
  • Fragrances in patch testing have irritant potential, and weak positive reactions must not be regarded as proof of allergic contact sensitization
    • Increased probability of a a relevant fragrance patch test if there is a positive reaction on retest or another patch positive to one of the mix components
7
Colophony (Rosin)
  • Derived from tree sap
  • Wood products, sawdust, wood fillers; glues and adhesives
  • Coatings, polishes, and waxes; waxed thread
  • Industrial lubricants and cutting fluids; soldering products
  • Musical instrument rosin
  • Topical salves
8
Paraben Mix
  • Products for personal care, hygiene, oral hygiene and hair care
  • Most cosmetics
  • Pet care and grooming products
  • Analgesic medications for skin; and hemorrhoid preparations
9
Negative Control

10
Balsam of Peru
  • Resin from Myroxylon pereirae tree
  • Perfumes and colognes; cosmetics; personal care, hygiene, oral hygiene and hair care products
  • Over-the-counter and prescription medicines
  • Pet care products; pesticides
  • Household cleaners, air fresheners and deodorizers; paper products
  • Some foods and flavorings; botanical (herbal) products
  • Metal working fluids and industrial cleaners, deodorizers and masking fragrances
  • Candles, incense and essential oils
11
Ethylenediamine Dihydrochloride
  • Used in the industrial manufacturing of chelating agents, corrosion inhibitors, fuel additives, epoxy curing agents, pharmaceuticals, carbamate-based chemicals, bleach activators, retention and processing aids, plastic lubricants, urethane foam catalysts, printing ink binders, and textile dye-assist compounds.
  • Cross-reactivity may be seen with aminophylline, piperazine-based antihistamines (hydroxyzine, meclizine, etc.) and promethazine
12
Cobalt Dichloride
  • Cement and bricks
  • Cobalt and cobalt alloys; cobalt catalysts; cobalt fumes, powders and pigments
  • Metalworking fluids and oils
  • Metal tools, jewelry and utensils (as with nickel)
  • Paints, inks, glazes and finishes

Panel 2.1 Allergens
Potential Allergen Sources:
13
p-tert-Butylphenol Formaldehyde Resin
  • Adhesives and glues in leather and rubber shoe manufacturing and repair; neoprene adhesives; glues for furniture and auto upholstery
  • Construction materials such as laminated wood products
  • Manufacture of fiberglass and mineral fiber insulation; modifiers in resin manufacturing
  • Photosensitive coatings
14
Epoxy Resin
  • Two-component paints, protective coatings and adhesives
  • Manufacturing of epoxy composite products including lightweight equipment, tennis racquets, skis, and circuit boards
  • Electron microscopy embedding media
  • Dental bonding agents and dental restorative materials
15
Carba Mix
  • Diphenylguanidine
  • Zincdibutyldithiocarbamate
  • Zincdiethyldithiocarbamate
Used in fungicides, pesticides and the manufacturing of natural rubber, butyl rubber, nitrile or neoprene
16
Black Rubber Mix
  • N-Isopropyl-N’-phenyl
  • paraphenylenediamine
  • N-Cyclohexyl-N’-phenyl
  • paraphenylenediamine
  • N, N’-Diphenyl
  • paraphenylenediamine
Antidegradants used in the manufacture of black rubber
17
Cl+ Me- Isothiazolinone (MCI/MI)
Biocide and preservative used in industrial and consumer products including:
  • Cleaning and laundry products, skin cleansers and shampoos, hair coloring products, hand and body lotions, cosmetics
  • Latex paints, adhesives and glues
  • Industrial metal working fluids
18
Quaternium-15
  • Personal care products (cosmetics, hair and hygiene products)
  • Household cleaning agents and latex paints
  • Industrial polishes, waxes, inks, paints and metal working fluids
19
Mercaptobenzothiazole
Used in the manufacturing of natural rubber, butyl rubber, nitrile or neoprene
20
p-Phenylenediamine
  • Permanent and semipermanent coloring products for hair and facial hair
  • Temporary, paint-on and black henna tattoos
  • Textile and fur dyes
  • Photodeveloping agents and printing inks
  • Black rubber products
21
Formaldehyde
  • Pressed wood construction materials (particleboard, fiberboard, plywood), and urea-formaldehyde resins and foams
  • Durable press ("non-iron") fabrics
  • Personal care products (cosmetics, hair and hygiene products)
  • Metal working fluids, glues, cleaning agents, latex paints, polishes, waxes, inks
  • Embalming and preserving fluids
22
Mercapto Mix
Used in the manufacturing of natural rubber, butyl rubber, nitrile or neoprene
23
Thimerosal
Infrequently used as a preservative in:
  • Some vaccines and ophthalmic, otic and nasal preparations
    • Although many children may have a positive patch test result to thimerosal, these are rarely of clinical significance as children typically can tolerate vaccines containing this preservative
  • Some fluorescent dyes in metal and forensic industries
  • Some thiosalicylic acid-based nonsteroidal anti-inflammatories
24
Thiuram Mix
Used in fungicides, pesticides, seed protectants, animal repellants, Antabuse® and the manufacturing of natural rubber, butyl rubber, nitrile or neoprene

Panel 3.1 Allergens-------------------------------
Potential Allergen Sources:
25
Diazolidinyl urea
  • Products for personal care, hygiene, and hair care
  • Cosmetics
  • Cleaning agents
  • Liquid soaps
  • Pet shampoos
26
Imidazolidinyl urea
  • Products for personal care, hygiene, and hair care
  • Cosmetics
  • Cleaning agents
  • Liquid soaps
  • Moisturizers
27
Budesonide
  • Medications containing budesonide
  • Other substances to which the patient may react:
    • Amcinonide
    • Hydrocortisone
    • Methylprednisolone
    • Prednicarbate
    • Triamcinolone
28
Tixocortol-21-pivalate
  • Medications containing tixocortol
  • Other substances to which the patient may react:
    • Cloprednol
    • Hydrocortisone
    • Prednisolone
    • Fludrocortisone
29
Quinoline mix
  • Clioquinol
  • Clorquinaldol
  • Paste bandages
  • Prescription and non prescription preparations as:
    • topical antibiotics and antifungal creams, lotions, ointments
    • Animal food
    • Bacteriostatic and fungistatic cream (eg. Sterosan Cream)


Common Allergens NOT on T.R.U.E. Test
Allergens
Potential Allergen Sources:
Bacitracin----------------------------------------------
  • Topical antibiotic
  • Although bacitracin and neomycin are chemically unrelated, the two often co-react during patch testing, probably due to patients being exposed to both medications through combination ointments
  • 50 percent of positive bacitracin patch test readings are seen only at the 96-hour reading, indicating a delayed reaction in many patients
Methyldibromoglutaronitrile (MDGN)
  • Also known as dibromodicyanobutane
Preservative used in personal care products (hand lotions, soaps) as well as latex paints, adhesives, and metalworking fluids
2-bromo-2-nitropropane-1,3-diol (BNPD)
  • Also known as bronopol
  • Preservative most commonly used in cosmetics
  • Can also cause occupational dermatitis as a preservative in coolants
  • BNPD is degraded to formaldehyde
  • Because it is an irritant, patch testing should not be done at concentrations greater than 0.5%
Cinnamic aldehyde
  • May be found in T.R.U.E. test fragrance mix and in balsam of Peru resin
  • Flavoring agent and fragrance found in cola beverages, vermouths, chewing gums, mouthwashes, soaps, and toothpastes
  • Cross reactions with balsam of Peru and benzoin can be seen
  • One of the most common causes of allergic stomatitis. If a patient has allergic stomatitis and positive patch test to balsam of Peru, cinnamic aldehyde-containing flavorings should be avoided.
  • May also cause contact urticaria.
Propylene glycol
  • Widely used as a vehicle for topical medications, cosmetics, personal lubricants and body lotions, and especially deodorants
    • Some topical steroids contain propylene glycol as a vehicle so patch testing should be considered in cases of dermatitis not responding/worsening with topical steroids
  • Systemic contact dermatitis can be due to propylene glycol found in foods (salad dressings)
  • Ingredient in brake fluid and antifreeze and as a humectant in tobacco products
  • The NACDG uses a 30% concentration when patch testing propylene glycol which will yield some transient irritant responses. However, using lower concentrations can produce false-negative results.
Dimethylol Dimethyl Hydantoin (DMDMH)
  • Preservative that contains 0.5% to 2% free formaldehyde and over 17% combined formaldehyde, commonly found in cosmetics and topical drugs
  • Although not all patients who are formaldehyde allergic need to avoid all formaldehyde releasers, DMDMH contains a significant amount of formaldehyde and thus should be avoided in all formaldehyde allergic patients
Iodopropynyl butylcarbamate (IPBC)
  • Trade names include Troysan Polyphase, Biodocarb, Glycasil
  • Preservative originally used for wood preservation and before it was approved for use in cosmetics and household products, including moistened toilet tissue, shampoos, lotions, powders, makeup, baby products, and contact lenses
  • A small study has shown possible cross-reactivity between IPBC and thiuram mix.21
Ethylene urea melamine formaldehyde (EMF)
  • EMF resins are used as textile finishes, in tableware, as surface coatings, and in glues in the furniture and wood industries
  • As a textile finish, they are used to make wrinkle-resistant or permanent-press clothing. Any wrinkle-resistant fabric, shrink-proof wool, rayon, or corduroy may contain this allergen
  • Patients allergic to EMF are often also allergic to formaldehyde
Disperse Blue 106
  • Textile dye used in clothing
  • Patients with a positive result need to avoid synthetic fibers in general, not just “blue clothing.”
  • Patients allergic to dyes in shirts often present with dermatitis of the axillary borders, but sparing of the axillary vault. If a patient is allergic to a dye in pants, the anterior thighs will often be affected first, followed by posterior thighs and popliteal fossae.
Amidoamine
  • Contaminant found in the manufacture of cocamidopropyl betaine (CAPB). CAPB is used as a surfactant in many personal care products such as shampoos, contact lens solutions, toothpastes, makeup removers, and liquid soaps
  • CAPB and amidoamine allergy often present as scalp/face or hand dermatitis in hairdressers
  • When patch testing, both allergens should be tested separately since few patients react to both allergens


T.R.U.E. Test Procedure

Before Testing
  1. Provide patients with information sheet about test:
  2. In patients with severe ongoing dermatitis, defer patch testing until acute symptoms subside to avoid eliciting excited skin syndrome and false positives.
  3. 2 weeks prior to patch testing stop using oral steroids and topical steroids on the test area.
  4. Do not expose the test area to sun for at least 3 weeks prior to testing.
  5. Test area should be clean and free of oils, lotions and ointments. Select an area without scars, active dermatitis, skin eruptions or any other condition that may interfere with test interpretation.

Apply Test Panels
  1. Peel open the foil outer sleeve and remove test Panel 1.1.
  2. Remove the protective plastic cover from the test surface of the panel. Take care not to touch the test substances.
  3. Use a medical marking pen to index the test location at the notches found on the panel.
  4. Repeat the process for Panel 3.1 with allergen #25 on the upper left corner.
  5. Instruct patients to keep the panels dry, in place, and protected from direct sunlight for 48 hours.

Interpret Test
  • Remove patches at 48 hours, interpret results at 72 and 96 hours
    • Interpret 48-hour reactions after allowing them to subside for a few minutes.
    • Recall patient at 72 and 96 hours for additional readings. A second reading is essential to reduce false positive and false negative results. Additional readings may be required depending on patient history and results.
      • If neomycin or p-phenylenediamine allergies are suspected, readings at 5-7 days may be needed.
  • More than one-quarter of patients can test positive to one of the T.R.U.E. test allergens. Positive reactions should be confirmed by patient history and symptoms.
  • Negative reactions are common. Patients who test negative may be allergic to other substances not included in T.R.U.E. test and require additional testing.

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Non-standardized Patch Tests

  • Nonstandardized patch tests with the patient’s personal products, allergens from cosmetics, or industrial allergens, might be needed.
    • Leave-on cosmetics (makeup, perfume, moisturizer, and nail polish), clothing, and most foods are tested ‘‘as is’’
    • Wash-off cosmetics (soap and shampoo) are tested at 1:10 to 1:100 dilutions
    • Household and industrial products should only be tested after ascertaining their safety and patch test concentrations in the MSDS information

Nonstandardized Patch Testing Concentrations.png

Nonstandard_cosmetic_patch_tests.png

Repeat Open Application Test (ROAT)

  • For individuals who develop weak or 1+ positive reactions to a chemical found in a leave-on consumer product, ROAT is useful in determining whether the reaction is significant.
    • Procedure: Apply product BID x 1 week to the side of the neck, behind an ear, or to antecubital fossa. If dermatitis does not result, the 1+ reaction likely was not meaningful. Conversely, if the individual develops dermatitis following a few days of repeated application of the product, then the weak patch test reaction is highly relevant.
  • Alternatively, place product on plastic tape (or Finn chamber) that is applied to back or arm for 2 days. If no reaction develops, the product should be safe to use.
    • This method could be used by the patient at home to test new products that could potentially cause a reaction.


Photopatch Testing

  • If photosensitization is suspected, photo-patch tests should be performed by a physician with expertise in UV radiation.
    • Procedure: duplicate applications of the suspected photocontactant(s) are placed on each side of the upper back. One side is irradiated with 5 J/cm2 of UV-A light 24-48 hours after initial application and then the test is read 48 hours later.


Patch Test Adverse Effects

  • Although systemic contact dermatitis after patch testing is rare, reactivation of patch test reactions may occur after oral ingestion of related allergens or even by inhalation of budesonide in patients with sensitization to topical steroids.
  • Patch testing can sensitize a patient who had not been previously sensitized to the contactant being tested, particularly to poison ivy/oak and aniline dyes.




Treatment

  • Acute treatment
    • Topical corticosteroids
      • Traditionally, treatment begins with high-potency fluorinated corticosteroids that may be switched to medium or even lower-potency preparations as symptoms improve.
    • Topical calcineurin inhibitors
      • Effectiveness of topical calcineurin inhibitors not established but they can suppress patch test reactivity
      • Practice parameter suggest that a trial of these topical agents could be considered for refractory CD
    • Oral corticosteroids in severe cases (usually with face or genital involvement and/or >20% body surface area involved)
      • Prednisone 0.5–1.0 mg/kg/d (maximum 60 mg/d) tapered over 2–3 weeks to minimize the risk of a rebound flare
        • E.g. 3 week course in an adult: prednisone 60 mg/d the first week, 40 mg/d for 2nd week, 20 mg/d for 3rd week.
        • 14-day courses only rarely result in rebound and may be appropriate if there are concerns about steroid toxicity.
    • Adjunctive therapy
      • Domeboro's or Burow's solution (aluminum acetate)
        • Instructions: dissolve one (1:40 dilution) or two tablets (1:20) in water and stir the solution until fully dissolved. Can be used as a soak (15-30 minutes TID) or a wet dressing/compress (saturate a clean, soft, white cloth in the solution; gently squeeze and apply loosely to the affected area. Re-saturate the cloth in the solution q15-30 minutes and apply to affected area. Discard solution after each use and repeat as often as necessary).
      • Cold compresses
      • Calamine lotion
      • Oatmeal baths
      • Oral antihistamines (primarily for sedation)
        • Diphenhydramine should not be used in patients with ACD to Caladryl (diphenhydramine in a calamine base)
        • Hydroxyzine or other piperazine-based antihistamines should not be used in patients with ACD to ethylenediamine
    • Other modes of therapy include UV light treatment, methotrexate, azathioprine, and mycophenolate mofetil

  • Avoidance of contact allergen - provide patient with avoidance information
    • Chemotechniques/Dormer patient information
    • Online contact allergen product databases
    • Balsam of Peru - about 50 % of patients with a positive patch test to Balsam of Peru who followed a Balsam of Peru reduction diet had significant improvement of their dermatitis
    • Cosmetics and skin care
    • Nickel
      • Dimethylgloxime test (e.g. Allertest Ni) is a practical way to identify metallic objects that contain enough nickel to provoke ACD. The patient may purchase a test kit and test objects at home or at work, particularly jewelry or metallic surfaces.
      • Wear only jewelry made from nickel-free stainless steel, surgical-grade stainless steel, titanium, 18-karat yellow gold, or nickel-free 14-karat yellow gold, sterling silver, copper and platinum. Avoid jewelry with nickel, as well as cobalt and white gold, which may contain nickel. Surgical-grade stainless steel may contain some nickel, but it's generally considered hypoallergenic for most people.
      • Nickel is found in foods and could play a role in exacerbating chronic dermatitis in patients allergic to nickel
        • 1% of patients with nickel allergy would have systemic reactions to the nickel content of a normal diet, 10% would react to exposures of 0.55-0.89 mg of nickel
        • Foods with higher nickel content include soybean, fig, cocoa, lentil, cashew, nuts, and raspberry
    • Plant dermatitis - after a known re-exposure, patients should remove any contaminated clothing and gently wash the skin with mild soap and water as soon as possible.
      • Tecnu skin cleanser is expensive and not likely to be superior to mild soap
    • Hand dermatitis due to gloves



References











TRUE Test Site
Chemotechniques Diagnostics AB Sweden
Dormer.com Patch Test Supplies (Chemotechniques US distributor)
Other patch test suppliers Hermal, Brial