World Allergy Organization
December, 2011
Cancun, Mesxico
New Horizons Session on Skin Diseases
Contact Dermatitis
Luz Fonacier MD, FACAAI, FAAAAI
Section Head of Allergy
Program Director, Allergy and Immunology
Winthrop University Hospital
Professor of Clinical Medicine
SUNY at Stony Brook
Long Island, New York
Disclosure
 Research and Educational Grants:
• AAAAI ART Grant
• Genentech
• Dyax
• Lev
 Speaker’s Bureau
• Baxter
Long Island, New York
Objectives WAO
Upon completion of this workshop, participants should be
able to:
1. Recognize important contact allergens
2. Be familiar with the clinical correlation of the results of the
patch test
Long Island, New York
Dermatitis Contact Allergens of the Year
2011: Dimethyl Fumarate
Bruze M, Zimerson E. Dermatitis 2011,Vol 22,No 1
2010: Neomycin
Sasseville D. Dermatitis 2010, Vol. 21, No 1
2009: Mixed Dialkyl Thioureas Anderson B, Dermatitis 2009, Vol. 20, No. 1
2008: Nickel 2008
Komik R. Zug K Dermatitis 2008 Vol. 19, No. 1
2007: Fragrance
Storrs F. Dermatitis 2007 Vol.28, No. 1
2006: P-Phenylenediamine
DeLeo V. Dermatitis 2006 Vol. 17, No. 2
2005: Corticosteroids
Isaksson BM. Dermatitis 2005 Vo. 16, No. 1
2004: Cocoamidopropyl Betaine Fowler J. Dermatitis 2004 Vol 15, No.1
2003: Bacitracin
Sood A, Taylor J. Dermatitis 2003 Vol 14, No. 1
2002: Thimerosal
Belsito D. Dermatitis 2002 Vol.13, No.1
2001: Gold
Fowler J Dermatitis 2001 Vol.12, No.1
2000: Disperse Blue Dyes
Storrs F Dermatitis 2000 Vol. 11, No. 1
Long Island, New York
Dimethyl Fumarate
Contact Allergen of 2011
Furniture-Related Dermatitis
• Common sites were trunk, limbs,
buttocks, face
• Blistering, lichenoid, contact
urticaria
Shoe Related Dermatitis
Textile Related Dermatitis
Photo from: Bruze M, Zimerson E. Dermatitis 2011,Vol 22,No 1
Long Island, New York
Neomycin
Contact Allergen of 2010
 Fifth most common allergen in NA (ACDS
database)
 Higher rate of sensitization due to availability
of antibiotic in OTC: ‘‘triple antibiotic’’
 High risk groups: stasis dermatitis, leg ulcers,
anogenital dermatitis & otitis externa
Long Island, New York
Patch Test with Neomycin
 In T.R.U.E. Test: 20% in petrolatum
• False (-) may occur in 10% of cases *
• If strongly suspected, ROAT with commercial
preparation or PT with 20% aqueous solution
 Intradermal tests: 1% solution of neomycin
 Patch-test slow to appear, peaking at day 4 or even
at day 7**
 Similar to gold, (+) reactions may persist for days to
weeks
*Epstein E. Contact dermatitis to neomycin with false negative patch tests: allergy established by intradermal and usage tests.
Contact Dermatitis 1980;6:236–7
**Bjarnason B, Flosado´ ttir E. Patch testing with neomycin sulfate. Contact Dermatitis 2000;43:295–302
Long Island, New York
Neomycin Cross Reactivity






90% for paromomycin & butirosin
70% for framycetin
60% for tobramycin & kanamycin
50% for gentamicin
4% for streptomycin
Concomitant sensitizations: neomycin and
bacitracin
Long Island, New York
Neomycin in vaccines
 Vaccines contain 25 mg of neomycin
 Reactions are minimal, local or transient
 The Committee on Infectious Diseases of the
American Academy of Pediatrics no longer
considers contact hypersensitivity to neomycin a
contraindication to vaccination
Kwittken PL, Rosen S, Sweinberg SK. MMR vaccine and neomycin allergy. Am J Dis Child 1993;147:128–9
Long Island, New York
Mixed Dialkyl Thioureas
Contact Allergen of 2009
 Mixture of diethylthiourea (DETU) & dibutylthiourea (DBTU)
 Applications and Uses
• Adhesive manufacturing
• Anticorrosive agents
• Paint & glue removers
• Pesticides & fungicides
• Photocopy paper (diazo copy paper)
• Photography, as an antioxidant
• Rubber accelerator (especially neoprene)
• Synthetic resins
• Textile and dye industry
1.1% + PT reaction rate and of highest relevance rate in NACD
Anderson B. Mixed Dialkyl Thioureas. Dermatitis 20:1 pp 3-5. 2009
Long Island, New York
Nickel: Contact Allergen of 2008
 10% of population are nickel allergic
 Increasing incidence of allergic
sensitization to nickel in North America
• New sources of nickel ACD: cell
phones
 New insight was offered into the possible
genetics of nickel contact allergy
Long Island, New York
Dietary Nickel
 Evidence support the contribution of dietary
nickel to dermatitis such as vesicular hand
eczema
 Meta-analysis of systemic contact dermatitis
following oral exposure to nickel estimated that:
• 1% of nickel allergic patients would have
systemic reaction to nickel content of a normal
diet
• 10% would react to 0.55 - 0.89 mg of nickel *
Kornik R & Zug K. Dermatitis2008;19(1):3-8
* Jensen CS, Menné T, Johansen JD. Systemic contact dermatitis after oral exposure to nickel: a review with a modified metaanalysis Contact Dermatitis 2006;54:79–86
Long Island, New York
Nickel Pyramid
>50 mcg
Soybean, Boiled ~ 1 cup: 895mcg
Cocoa, 1 tbsp: 147 mcg
Cashew, ~ 18 nuts:143 mcg
Figs ~5: 85 mcg
Lentils ½ cup cooked: 61 mcg
Raspberry: 56 mcg
20-50 mcg
Vegetables, canned½ cup: 40 mcg
Lobster 3 oz: 30 mcg
Peas Frozen, ½ cup: 27 mcg
Asparagus, 6 spears: 25 mcg
Oat Flakes 2/3 cup: 25 mcg
Pistaccios, 47 nuts: 23 mcg
Strawberries, 7 med: 9 mcg
Bread wheat, 1 slice: 5 mcg
Poultry, 3.5 oz: 5 mcg
Carrots, 8 sticks: 5 mcg
Apple, 1 med: 5 mcg
Cheese 1.5 oz:3 mcg
Yogurt, 1 cup:3 mcg
Mineral water, 8 fl oz: 3 mcg
Mushroom raw, ½ cup: 2 mcg
Corn Flakes, 1 cup: 2mcg
<20mcg
Nickel in Biomedical Devices
Reports of dermatitis to biomedical devices lead to:
• Consultation requests from orthopedic surgeons & orthodontists
regarding safety of permanent or semipermanent metal medical
devices in suspected nickel-sensitized patients
• High variability of care in terms of testing & recommendations
• Increased health care costs
• Medicolegal concerns contribute to testing consultations
• In some instances of joint replacement, selection of a more
expensive & less durable option
As nickel allergy incidence increases, this problem also presumably will
increase
Kornik R and Zug K. Dermatitis2008;19(1):3-8
Long Island, New York
METAL IMPLANT “ALLERGY”
Often suspected but rarely documented
 Nickel: 10% of population are nickel allergic
• 25% of nickel sensitive patients are also cobalt sensitive
 5% of orthopedic implant patients & up to 21% of patients with
preoperative metal sensitivity may develop cutaneous allergic
reactions upon reexposure to the same metal*
 Clinical manifestations
• Cutaneous
– localized
– generalized: mostly eczematous
(urticaria & vasculitis reported)
• Implant Failure
Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous &Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis,
2011. 22;2: 65–79
*Niki Y, Matsumoto H, Otani T, et al. Screening for symptomatic metal sensitivity: a prospective study of 92 patients
undergoing total knee arthroplasty. Biomaterials 2006;26:1019–26.
Long Island, New York
Metals and Alloys Used in Implants
Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous &Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis,
2011. 22;2: 65–79
Long Island, New York
Knee replacements
 Incidence of sensitivity for all types of orthopedic
implants is probably < 0.1%
• includes static orthopedic implants (higher
probability of sensitization than dynamic prostheses)
 Rare partly because modern knee prostheses are
metal-on-plastic, as opposed to metal-on-metal
 Other components that very rarely cause sensitization
• bone cement (methyl methacrylate)
• polyethylene (plastic spacer)
Merritt K, Rodrigo JJ. Immune response to synthetic materials. Clin Orthop Relat Res 1996;(326):71–9
Long Island, New York
Prospective Longitudinal Studies and Reviews
Study
Total Pts
Conclusions
Carlsson &
Mo¨ller 1989
18
Metal allergic pts with confirmed allergy to one of the metals in their device
prior to stainless steel orthopedic implants had no issues (6-yr ff-up)
Merritt &
Rodrigo1996
22
1% develop cutaneous vs 20–25% develop implant-induced metal
sensitivity without any allergic skin manifestations
Niki et al,
2006
92
26% of screened pts had (+) lymphocyte stimulation tests to at least one
metal (Ni, Co, Cr, Fe).
In metal (+) prior to implant, 21% (5/24) developed cutaneous dermatitis at
the site of implant;(some widespread dermatitis)
5% of the total study developed cutaneous allergic reactions.
Thyssen et
al, 2009
356
Risk of surgical revision was not increased in patients with metal allergies
Risk of metal allergy was not increased in patients who were operated on,
in comparison with controls.
Eben et al,
2010
92
66/92 had sx (pain, reduced motion, swelling)
Rates of allergy: nickel: 24.2%; cobalt:6.1%; chromium: 3.0%
Symptomatic (31.8%) had allergic reaction to bone cement components
(gentamicin 23.8%, benzoyl peroxide 10.6%, hydroquinone 4.5%)
Sensitization rates in symptom-free patients: 3.8% for nickel,
cobalt, chromium; 15.4% for gentamicin
Carlsson A, Mo¨ller H. Implantation of orthopaedic devices in patients with metal allergy. Acta Derm Venereol 1989;69:62–6
Merritt K, Rodrigo JJ. Immune response to synthetic materials.Sensitization of patients receiving orthopaedic implants. Clin Orthop 1996;326:71–9..
Niki Y, Matsumoto H, Otani T, et al. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials
2006;26:1019–26.
Thyssen JP, Jakobsen SS, Engkilde K, et al. The association between metal allergy, total hip arthroplasty, and revision. Acta Orthop 2009;80:646–52.
Eben R, Dietrich KA, Nerz C, et al. Contact allergy to metals and bone cement components in patients with intolerance of arthroplasty. Dtsch Med Wochenschr
2010;135:1418–22.
Long Island, New York
Allergic contact dermatitis from bone cement components
• Reported in 24.8% of patients (n = 239)*
• Orthopedic bone cements composition:
• methyl methacrylate (MMA)
• N,N-dimethylp- toluidine (DPT)
• may be a significant cause of aseptic loosening
**7 /15 patients with aseptic loosening of a total hip
replacement were DPT allergic
• benzoyl peroxide***
• antibiotics (gentamicin, tobramycin, clindamycin, erythromycin)***
*Thomas P, Schuh A, Eben R, et al. Allergy to bone cement components. Orthopa¨de 2008;37:117–20.
**Haddad FS, Cobb AG, Bentley G, et al. Hypersensitivity in aseptic loosening of total hip replacements. The role of constituents of
bone cement. J Bone Joint Surg Br 1996;78:546–9.
*** Kuehn KD, Ege W, Gopp U. Acrylic bone cements: composition and properties. Orthop Clin North Am 2005;36:17–28.
Long Island, New York
Implant Failure
 16 patients with failed metal-on-metal arthroplastic
implants; 81% had metal sensitivity (PT &/or lymphocyte
transformation test)*
 Accumulated reports in total hip arthroplasty :
• prevalence of metal allergy
– ~ 25% in patients with a well-functioning hip
arthroplastic implant
– ~ 60% among patients with a failed or poorly
functioning implant**
* Thomas P, Braathen LR, Dorig M, et al. Increased metal allergy in patients with failed metal-on-metal hip arthroplasty and periimplant
T-lymphocytic inflammation. Allergy 2009;64:1157–65.
** Hallab N, Merritt K, Jacobs JJ. Metal sensitivity in patients with orthopaedic implants. J Bone Joint Surg Am 2001;83:428–36.
Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous &Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis,
2011. 22;2: 65–79
Long Island, New York
Endovascular stenting procedures & in-stent restenosis
* Retrospective study of coronary in-stent restenosis 6 mos post stainless
steel stent placement & PT 2 months after angioplasty
• 11 (+) PT in 10/ 131 (8%)
– 7 to nickel & 4 to molybdenum
• Clinical history not predictive of a (+) or (-) patch-test result
• All 10 with (+) PT to metal had in-stent restenosis (higher frequency
of restenosis than in patients with no metal allergy)
Conclusion: …suggest that allergy to metals, nickel in particular, plays a
relevant role in inflammatory fibroproliferatory restenosis
**
Prospective study of 174 stented patients
• 109 for initial placement & 65 for in-stent restenosis)
• Patients with recurrence of in-stent restenosis had
significantly higher (+) PT to metals (nickel & manganese)
• No correlation with restenosis after initial stent placement
*Köster R, Vieluf D, Kiehn M, et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis Lancet 2000;356:1895–7
**Iijima R, Ikari Y, Amiya E, et al. The impact of metallic allergy on stent implantation: metal allergy & recurrence of in-stent restenosis
Int J Cardiol 2005;104:319–25
Long Island, New York
Diagnostic Criteria for Metal-Induced
Cutaneous Allergic Reactions
1. Chronic eczema beginning weeks or months after the
implant
2. Eczema most severe around the implant site
3. Absence of other contact allergens or systemic cause
4. Patch tests positive or strongly positive for one of the
metals in the alloy
5. Complete & rapid recovery after total removal of foreign
metal implant
Merle C, Vigan M, Devred D, et al. Generalized eczema from Vitallium osteosynthesis material. Contact Dermatitis 1992;27:257–8.
Long Island, New York
METAL IMPLANT “ALLERGY”
Conclusions
 Most reactions to endovascular, cardiovascular, orthopedic, dental
metal implants are based on anecdotal case reports or on data from
relatively small cohorts
• The temporal & physical evidence before and after removal of
implants leaves little doubt that a considerable number of patients
develop metal sensitivity & cutaneous allergic dermatitis in
association with metallic orthopedic implants
 Conflicting Data: Prospective longitudinal studies are strongly needed
• Recent case study showed that ~ 5% developed eczematous
reactions directly associated with metallic implants*
• Preexisting metal sensitivity with implant containing the offending
metal had a higher rate of cutaneous dermatitis
• proven cases incriminate nickel, cobalt, chromium, copper
Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous &Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis, 2011. 22;2: 65–79
*Niki Y, Matsumoto H, Otani T, et al. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty.
Biomaterials 2006;26:1019–26.
**Merritt K, Rodrigo JJ. Immune response to synthetic materials. Sensitization of patients receiving orthopaedic implants. Clin Orthop 1996;326:71–9.
Long Island, New York
METAL IMPLANT “ALLERGY”
Conclusion
 Need for patch testing is controversial, poorly reliable in
predicting or confirming implant reaction
• Preimplantation PT: may be considered if suspected of
having a strong metal allergy
• Post cutaneous eruption (months to years after implant): PT
can be done with an appropriate series of metals
 A negative PT is reassuring for absence of delayed
hypersensitivity reaction
 A positive PT does not prove relevance
 If relevant allergens are identified and corticosteroid therapy is
insufficient to clear the eruption, removal of the implant may be
considered
Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous &Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis,
2011. 22;2: 65–79
Long Island, New York
Regulating Nickel
 1992: Danish Ministry of Environment regulated nickel
exposure to products in prolonged contact with the skin
• Danish schoolgirls with ears pierced after 1992
regulations had significantly less nickel sensitization
compared to those pierced prior to the regulations
(5.7% vs 19%)
 1994: European Union
• limited nickel release threshold from objects in
prolonged contact with skin to 0.05 mg/cm2/ week
• nickel content of post assemblies (material inserted into
pierced parts of the body) to a migration limit of 0.2
mg/cm2/week
Laws regulating nickel products, appears to be decreasing
sensitization in the younger population
Kornik R and Zug K. Dermatitis2008;19(1):3-8
Jensen CS, Lisby S, Baadsgaard O, et al. Decrease in nickel sensitization in a Danish schoolgirl population with ears pierced after
implementation of a nickel-exposure regulation Br J Dermatol 2002;146:636–42
Long Island, New York
Cosmetics
 Facial cosmetic dermatitis
• Bilateral
• Patchy
 Eyelid
 Neck
• “run-off” pattern
• Cosmtics applied to face, scalp or hair often initially affect
the neck
• Most afftected site of ACVD from nail varnish is the neck
 Lips
Consort/Connubial Dermatitis: primarily fragrance
Fragrance
Contact Allergen of 2007
 > 2800 fragrance ingredients in database of
Research Institute for Fragrance Materials, Inc
• ~100 are known allergens
 Complex substances containing hundreds of
different chemicals
 Most common cause of ACD from cosmetic
• Patch test 4th in frequency (10.4%)
• 1.7-4.1% of general population have + PT to fragrance mix
Johansen JD. Fragrance contact allergy: a clinical review. Am J Clin Dermatol 2003;4:789-98
Pratt MD et a;. North American Contact Dermatitis Group Patch-test Results 2001-2002 study period. Dermatitis 2004;15:176-83
*Buckley DA et al. The frequency of fragrance allergy in a patch-test polulation over a 17 year period. Br J Dermatol 2000;142:203-4
Long Island, New York
Fragrance Mix Patch test
Test Fragrance Mix I
Balsam of Peru
Myroxylon pereirae
NACD
2009-2010
Fragrance Mix II
Cinnamic alcohol 1%
Cinnamic acid
Coumarin 2.5%
Cinnamic aldehyde 1%
Benzoyl Cinnamate
Hydroxyisohexyl 3cyclohexene carboxaldehyde
(Lyral) 2.5%
a-Amyl cinnamaldehyde
(amyl cinnamal) 1%
Benzoyl Benzoate
Citronellol 0.5%
Hydroxycitronellal 1%
Benzoic acid
Farnesol 2.5%
Geraniol 1%
Vanillin
Citral 1.0%
Isoeugenol 1%
Nerodilol
a Hexyl cinnamic aldehyde
5.0%
Eugenol 1%
Oak moss 1%
Tricky Aspects of Fragrance Allergy
 New fragrance chemicals are constantly introduced
 Regulation of fragrance ingredients in cosmetics exempts fragrance
formulas as “trade secrets”
 Some manufacturers do not consider essential oils to be fragrance
• Tree tea oil (Melaleuca alternifolia)
• Ylang-ylang oil (Cananga odorata)
• Jasmine flower oil (Jasminum officinale)
• Peppermint oil (Mentha piperita)
• Lavander oil (Lavandula angustifolia)
• Citrus oil (limonene)
 “Covert fragrances”- used for purposes other that for aroma (ie
preservatives) can be added to “fragrance free” products
• Bensaldehyde
• Benzyl alcohol
• Bisabolol
• Citrus oil
• Unspecified essential oils
Castanedo-Tardan M & Zug K. Patterns of Cosmetic Contact Allergy. Dermatol Clin 2009 27: 265-280
Long Island, New York
Balsam of Peru
Myroxylon pereirae
 One of 5 most prevalent allergens in TT
 Found in toothpaste, mouthwash scents, flavors of food &
drinks
 Cross react with colophony, wood and coal tar, turpentine,
resorcinol monobenzoate
 Systemic CD to certain fruits in patients sensitive to
fragrance
Long Island, New York
Fragrance
 Leave on fragrances: induce dermatitis at
normally utilized concentrations
 Wash on/wash off products: ? Relevance
of brief exposure
• Concentration of fragrance left on
fabric by laundering was very low &
threshold were below induction levels
-Contact Dermatitis. 2003 Jun;48(6):310-6.
-Contact Dermatitis. 2003 Jun;48(6):324-30.
-Contact Dermatitis 2002 Dec;47(6):345-52
-Am J Contact Dermat 1996 Jun;7(2):77-83
Fragrance Systemic Contact Dermatitis
Foods to Avoid in Balsam-Restricted Diet
• Citrus fruits: oranges, lemons, grapefruit, tangerines,
marmalade, juices
• Flavoring agents: pastries, bakery goods, candy, chewing gum
• Spices: cinnamon, cloves, vanilla, curry, allspice, anise, ginger
• Spicy condiments: ketchup, chili sauce, barbecue sauce,
chutney, pickles, pizza
• Perfumed or flavored tea & tobacco
• Chocolate
• Certain cough medicines & lozenges
• Ice cream
• Cola, spiced soft drinks such as Dr Pepper
• Tomatoes & tomato-containing products
~ half of patients with positive PT to MP who followed BOP
reduction diet had significant improvement of their dermatitis
Salam TN, Fowler JF Jr. Balsam-related systemic contact dermatitis J Am Acad Dermatol. 2001 Sep;45(3):377-81
Long Island, New York
Summary on Fragrance Allergy
 Fragrance mix I allergens found in 15- 100% of cosmetic
products (especially deodorants)
• 2nd - 5th most common (+) PT in series around the world
• Testing FM I–allergic patients with ingredients of the mix
is successful only about 50% of the time
 Testing to FM I and BOP picks up 60-70% of fragrance
allergic individuals*
 Many persons have (+) PT to fragrance, but few have
clinical allergies to fragrances (allergic contact dermatitis)
Storrs F J. Fragrance. Dermatitis Volume 18, Issue 01, March 2007, Pages 3-7
*Larsen W et al. Fragrance contact dermatiis: a worldwide multicenter investigation (part III)> Contact Dermatitis 2002;46:141-4
Long Island, New York
P-phenylenediamine (PPD)
Contact Allergen of 2006
Permanent Hair Dye
• Theoretically, does not cause reaction if
fully oxidized
• In reality, it is likely that PPD is never
completely oxidized
• Other reactions: IgE mediated
anaphylaxis & lymphomatoid reactions
Risk Factors & Ethnic Differences
 Aging Population
• 40% of women in America & Europe color their
hair (70% are over 35 y.o.)
 Black men have higher incidence –use darker
shades of dye with higher concentration of PPD
 Occupational: Currently the most common cause
of contact dermatitis in hairdressers
Hesse et al. Contact Dermatitis to hair dyes in a Danish Adult population: an interview based study. Br J of Dermatol 2005; 153:132-5
Dickel H et al. Comparison of patch test with standard series among white and black racial groups. Am J Contact Dermat 2001;12:77-82
Long Island, New York
New Route of Exposure
 Body tattooing has increased among the
youth of many cultures
 Use of black henna tattoo (higher PPD
than in hair color)
 Sensitization to PPD from tattoos is likely
lifelong
• likely see individuals who react to their attempts at hair
coloring as they age (reported in 5.3% who never used
hair dye)
Hesse et al. Contact Dermatitis to hair dyes in a Danish Adult population: an interview based study. Br J of Dermatol 2005; 153:132-5
Dickel H et al. Comparison of patch test with standard series among white and black racial groups. Am J Contact Dermat
2001;12:77-82
De Leo V. p-Phenylenediamine Dermatitis Volume 17, Issue 02, June 2006, Pages 53-55
Long Island, New York
Chemicals that may cross react with PPD
•
•
•
•
•
•
•
•
•
Product Class
Sunscreens
Antiinfectives
Diuretics
Anesthetics
Textile dyes
Antidiabetic
COX-2 inhibitors
Rubber Accelerators
Black Rubber mix
Chemicals
PABA & padimate O
Sulfonamides & p-aminosalicylic acid
Thiazides
Benzocaine and related “caines”
Azo dyes
Sulfonylureas
Celecoxib
N-isopropyl-N’-phenyl-p-phenylenediamine
De Leo V. p-Phephenylenediamine. Dermatitis 2006. 17;2: 53-55
Corticosteroids
Contact Allergen of 2005
 Increase detection probably due to
• Greater awareness
• Expanding market for CS
• Improved testing procedure
 Suspect
• In stasis ulcers & chronic eczema
• When dermatitis fails to respond to CS
• When dermatitis worsens with treatment
SKIN TESTING TO TOPICAL CORTICOSTEROID
* Tixocortol Pivalate (1%) - Class A
* Budesonide (0.1%) - Class B&D
Hydrocortisone (1%)
Hydrocortisone-17-butyrate (0.1%)
Betamethasone-17-valerate (0.12%)
Clobetasol-17-propionate (0.25%)
Prednisolone (1%)
* Triamcinolone (0.1%)
Patient’s commercial steroid
Repeat open application test
* Found in current TRUE Test
Identifies > 91% of CS allergy
Bjarnason et al. Assessment of budesonide patch tests. Contact Dermatitis 1999, 41:211-217
Bofa et al. Screening for corticosteroid contact hypersensitivity. Contact Dermatitis 1995,33: 149-151
Long Island, New York
STRUCTURAL GROUPS OF CORTICOSTEROIDS
Cross reactivity based on 2 immune recognition sitesC 6/9 & C16/17 substitutions
Class A (Hydrocortisone & Tixocortol pivalate: has C17 or C21 short chain ester)
Hydrocortisone, -acetate, Tixocortol, Prednisone, Prednisolone, -acetate,
Cloprednol, Cortisone, -acetate, Fludrocortisone, Methylprednisolone-acetate
Class B (Acetonides: has C16 C17 cis-ketal or –diol additions)
Triamcinolone acetonide, -alcohol, Budesonide, Desonide, Fluocinonide,
Fluocinolone acetonide, Amcinonide, Halcinonide
Class C (non-esterified Betamethasone; C16 methyl group)
Betamethasone sodium phosphate, Dexamethasone, Dexamethasone sodium
phosphate, Fluocortolone
Class D1 (C16 methyl group & halogenated B ring)
Clobetasone 17-butyrate, -17-propionate Betamethasone-valerate, dipropionate, Aclometasone dipropionate, Fluocortone caproate, -pivalate,
mometasone furoate
Class D2 (labile esters w/o C16 methyl nor B ring halogen substitution)
Hydrocortisone 17-butyrate ,-17-valerate,-17-aceponate,-17-buteprate,
methylprednisolone aceponate
Wilkinson SM Corticosteroid cross reactions: an alternative view. Contact dermatitis 2000;42:59-63
Long Island, New York
Cocoamidopropyl betaine
Contract Allergen of 2004
 Second most common allergen in shampoo
 Amphoteric surfactant often found in shampoos,
bath products, eye & facial cleaners
 Less irritating than are older polar surfactants
such as sodium lauryl sulfate but more capable of
allergic sensitization.
 Positive reactions to this allergen are often
clinically relevant
Shampoos
Typically composed of 10-30 ingredients




eyelid dermatitis, facial dermatitis, neck dermatitis, scalp
dermatitis, dermatitis of the upper back, or dermatitis in
more than one of these areas, often leading to difficulty in
clinical diagnosis.
Of 9 products with no fragrance, 4 had fragrance related potential allergens; 3
of these 4 had botanical ingredients, & 1 had benzyl alcohol
Thus, only 5 products in database were truly fragrance free & definitely safe
for patients with fragrance allergy.
Matthew Zirwas and Jessica Moe Shampoos. Dermatitis, Vol 20, No 2 (March/April), 2009: pp 106–110
Long Island, New York
Cocoamidopropyl betaine
 Typically presents as eyelid, facial, scalp, and/or neck
dermatitis
• frequent exposure to personal cleansing products
• enhanced ability of “sensitive skin” in these areas to
develop ACD
 3.3% of 975 patients had a + reaction to CAPB (NACDG 2001)
 Found in >600 personal care products (FDA data voluntarily
reported by industry)
 Commercial bulk production of CAPB may result in
contamination of the final product with two chemicals used in
the synthesis of CAPB, namely, amidoamine (AA) and
dimethylaminopropylamine (DMAPA)
Fowler JF. Cocamidopropyl Betaine. Dermatitis 2004;15:3-4
Cosmetic Preservatives
•
•
•
•
•
•
Formaldehyde
Formaldehyde*
Quarternium 15*
Diazolidinyl urea*
(Germall II)
Imidazolidinyl urea*
(Germall)
Bromonitropropane
(Bronopol)
DMDM Hydantoin
(Glydant)
(8.4)
(9.3)
(3.2)
(3.0)
•
•
•
•
•
Non Formaldehyde
Methyldibromoglutaronitrile
(Euxyl K400)
MCI/MI
Parabens*
Chloroxylenol
Iodopropynylbutylcarbamate
(5.8)
(2.3)
(0.5)
(0.8)
(0.4)
(3.3)
(2.6)
Paraben, quarternium-15 & formaldehyde preservatives are
frequently combined & cosensitize ***
(% Prevalence PT reaction based on NACDG or TT)
*Antigen present in the T.R.U.E. Test
***Albert MR et al. Concomitant positive reactions to allergens in the patch testing standard from 1988-1997. Am J Contact
Dermat 1999. 10:219-223
Long Island, New York
Formaldehyde
Most common potential source of exposure
 Cosmetics
• rarely listed on ingredient label, direct use forbidden in
some countries
• Contain formaldehyde releasers
 Permanent press textiles
• Increase strength, prevent shrinking, resist wrinkling
(permanent press) of cellulose and rayon fibers
*Agner et al.Formaldehyde allergy: a follow up study. Am J Contact Dermatitis 1999;10:12-17
Long Island, New York
Formaldehyde & Formaldehyde Releasing
Preservatives
 Difficult to avoid because formaldehyde is present in cleaning
products, biocides
 Cross reactivity varies
• A high cross-reactivity rate between formaldehyde, Bioban
(mixture of 4-(2-nitrobutyl)-morpholine and 4,49-(2-ethyl-2nitrotrimethylene) Dimorpholine), and other formaldehydereleasing agents
• Only half of patients with formaldehyde/ FRP allergies
reacted to 1-2 allergens and only 1% reacted to all 6**
*Anderson B et al Patch-Test Reactions to Formaldehydes, Bioban, and Other Formaldehyde ReleasersDermatitis, Vol 18, No 2 (June), 2007:
pp 92–95.
**Herbert C, Reitschel RL. Formaldehyde and formaldehyde releasers: how much avoidance of cross reacting agents is required? Contact
Dermatiits 2004;50:371-3
Formaldehyde in Textile Resin
 Reactions: irritant & ACD, exacerbation of AD, urticaria,
phototoxic eruptions*
• more subacute and chronic dermatitis
 Testing with formaldehyde alone identifies only ~70% of
patients who are allergic to the formaldehyde resins
• PT with resins as well
 Slow resolution of dermatitis even with careful avoidance
• As much as 50% still had constant dermatitis *
*Hatch KL, Maibach HI. Textile chemical finish dermatitis. Contact Dermatitis 1986;14:1–13. Allergic Contact Dermatitis from Formaldehyde
Textile Resins
Fowler JF Jr, Skinner SM, Belsito DV. Allergic contact dermatitisfrom formaldehyde resins in permanent press clothing: an underdiagnosed
cause of generalized dermatitis. J Am Acad Dermatol .1992;27:962–8.
Hilary C. Reich and Erin M. Warshaw Allergic Contact Dermatitis from Formaldehyde Textile Resins . Dermatitis, Vol 21, No 2 (March/April),
2010: pp 65–76
Long Island, New York
Key Diagnostic Criteria for Allergic Contact Dermatitis
from Formaldehyde Textile Resins
1. Characteristic location of eruption corresponding
with contact with clothing
2. Positive PT to formaldehyde
3. Positive PT to suspected fabric
4. Demonstration of free formaldehyde in the
suspected fabric
5. Negative reaction to other potential clothing
allergens (eg, rubber, nickel, dyes)
Reich H & Warshaw E. Allergic Contact Dermatitis from Formaldehyde Textile Resins . Dermatitis. 2010. 21;2:65–76
Long Island, New York
Treatment for Textile Finish/
Formaldehyde Resin Allergic Contact Dermatitis
 Use 100% silk, polyester, acrylic, nylon
• Linen & denim are acceptable if soft & wrinkle easily
 Avoid ‘‘easy care,’’ ‘‘permanent press,’’ or ‘‘wrinkle free’’
 Some experts also recommend avoidance of formaldehydereleasing preservatives in personal products*
 AVOID FORMALDEHYDE RESINS AT ALL TIMES. Even
exposure once a month (‘‘Dress clothes’’ only worn on
weekends) is enough to maintain your dermatitis
Reich H & Warshaw E. Allergic Contact Dermatitis from Formaldehyde Textile Resins . Dermatitis. 2010. 21;2:65–76
*Scheman A, Jacob S, Zirwas M, et al. Contact allergy: alternatives for the 2007 North American Contact Dermatitis Group (NACDG)
standard screening tray. Dis Mon 2008;54:7–156.
Long Island, New York
Quarternium 15
 Most common cosmetic preservative allergen
 Most sensitization is caused by formaldehye
releaser
 Most Quarternium allergic patients are also
allergic to formaldehyde
Castanedo-Tardan M & Zug K. Patterns of Cosmetic Contact Allergy. Dermatol Clin 2009 27: 265-280
Long Island, New York
Paraben
 Most commonly used ingredient in cosmetic next to water (87-93%)
 Average total paraben exposure per person in the US is ~ 76 mg/day
• Cosmetics & personal products: 50 mg per day
– Current concentrations of paraben are generally < 0.3%
• Drugs: 25 mg per day
• Food: 1 mg per day
– paraben in foods is usually less than 1%
 Parabens are weak sensitizers in cosmetics
 Paraben-sensitive individuals often tolerate paraben-containing
cosmetics on normal intact skin but not damaged skin
 “Paraben paradox”: only sites of healed dermatitis flare when
sensitizer is applied
Allison CL, Warshaw EM. Parabens: A Review of Epidemiology, Structure, Allergenicity, and Hormonal Properties. Dermatitis 2005; 16:57-66
Castanedo-Tardan M & Zug K. Patterns of Cosmetic Contact Allergy. Dermatol Clin 2009 27: 265-280
Dermatitis of the Eyelid
 Eyelids particularly sensitive
• thickness (0.55 mm) compared to other facial areas (~2 mm )
• substances applied to scalp or face easily come into contact
with the eyelids
• substances on fingers can also be a source of palpebral
eczematous dermatitis
• airborne pollen and dust usually cause such powerful
palpebral reactions that any absence of eyelid involvement
automatically excludes a diagnosis based on airborne pollen
and dust *
Ayala F et al. Eyelid Dermatitis: An Evaluation of 447 Patients. Dermatitis 2003;14:069-074
* Sher M. Contact dermatitis of the eyelids. S Afr Med J 1979;55:511–513. (PubMed)
Long Island, New York
Dermatitis of the Eyelid
 Allergic contact dermatitis:
55-63.5%
13.4% Fragrance / Balsam of Peru
8.2%
6.0%
Gold sodium thiosulfate
Nickel sulfate
 Irritant contact dermatitis:
 Atopic dermatitis:
 Seborrheic dermatitis:
15%
< 10%
4%
Ayala F et al. Eyelid Dermatitis: An Evaluation of 447 Patients. Dermatitis 2003;14:069-074
Reitschel RL et al. Common contact allergens associated with Eyelid dermatitis: data from the NACDG 2003-2004 study period.
Dermatitis 2007; 18:78-81
Long Island, New York
Dermatitis of the Eyelid
Eyelid dermatitis as only site
13.4% Perfume
7.1% Fragrance Mix
6.3% Balsam of Peru
8.2%
Gold sodium thiosulfate (most common allergen in pure
Mixed facial &
eyelid dermatitis*
Nickel
Kathon
Fragrance
eyelid dermatitis.
6.0%
3.3%
3.0%
2.2%
1.9%
Nickel sulfate
Neomycin
Methyldibromoglutaronitrile, Quarternium 15
Methylchloroisothiaxolinone
Cobalt Cl, DMDM hydantoin, Amidoamine,
Cocamidopropyl amine, Thiuram mix,
1.5% Bacitracin, Cinnamic aldehyde, Tosylamide
formaldehyde resin, Propylene glycol,
Tixocortol pivalate
Of 268 cases, 33 showed relevant reactions to an allergen not
in the 65 NACDG standard screening allergens
*Valsecchi et al. Eyelid Dermatitis: an evaluation of 150 patients. Contact Dermatitis.1992;27:143-7
Reitschel RL et al. Common contact allergens associated with Eyelid dermatitis: data from the NACDG 2003-2004
study period. Dermatitis 2007; 18:78-81
Gold
Contact Allergen of 2001
 9.5% of 4,101 patch-test were (+) to gold
 Most common sites:
• Hands
29.6%
• Face
19.3%
– Common in head & neck with seborrheic
distribution
• Eyelids
7.5%
 Most common uses:
• Wear it: Fashion appeal
• Drink it: Anti-inflammatory medication
• Smile with it: Dental appliance
• Eat it: Dessert contain 5 g of 24-carat gold)
Fonacier L, Dreskin S, Leung DL. “Allergic Skin Diseases”. 2010 Primer on Allergic and Immunologic Diseases , 6th
Edition. The Journal of Allergy and Clinical Immunology. Volume 125, Issue 2, Supplement 2 (February 2010) S 138-149
Ehrlich A, Belsito DV. Allergic contact dermatitis to Gold. Cutis 2000;65:323-6
Fowler et al. Gold allergy in North America. Am J Contact dermat 2001;12:3-5
McKenna KE et al. Contact allergy to gold sodium thiosulfate. Contact Dermatitis 1995;32:143-6
Long Island, New York
Gold
 Oral symptoms: + Patch test may be clinically relevant in patients
with gold dental appliance
• Increased rate if dental gold has been present for >10 yrs
• Late reacting allergen: >50% + gold test was delayed (1 week)
 Facial dermatitis: subset of patients clear with gold avoidance
• women with titanium dioxide in cosmetics that adsorbs gold
released from hand jewelry or eyeglass frames
 Eyelid dermatitis: 7 of 15 gold allergic patients cleared by not
wearing gold jewelry
Ehrlich A, Belsito DV. Allergic contact dermatitis to Gold. Cutis 2000;65:323-6
Fowler et al. Gold allergy in North America. Am J Contact Dermat 2001;12:3-5
Koch P & Balmer F. Oral lesions and symptoms related to metals in dental restorations. A clinical, allergological and histological
study. J Am Acad Dermatol 1999;41;422-430
Nedorost S, Wagman, A. Positive Patch-Test Reactions to Gold: Patients' Perception of Relevance and the Role of Titanium Dioxide
in Cosmetics. Dermatitis 2005;16:67-70
Long Island, New York
Gold
Trial of gold avoidance may be warranted if with + PT to gold
• Avoidance period required for benefit is long and may only be
partial
• Avoidance of gold earrings did not benefit patients with earlobe
dermatitis ie no correlation between gold earring use and
earlobe dermatitis
• Subset of gold-allergic patients with facial dermatitis who wore
powder, eye shadow, or foundation on affected areas did clear
with total avoidance of gold jewelry on the hands and wrists
Ehrlich A, Belsito DV. Allergic contact dermatitis to Gold. Cutis 2000;65:323-6
Fowler et al. Gold allergy in North America. Am J Contact Dermat 2001;12:3-5
Koch P & Balmer F. Oral lesions and symptoms related to metals in dental restorations. A clinical, allergological and histological
study. J Am Acad Dermatol 1999;41;422-430
Nedorost S, Wagman, A. Positive Patch-Test Reactions to Gold: Patients' Perception of Relevance and the Role of Titanium
Dioxide in Cosmetics. Dermatitis 2005;16:67-70
Long Island, New York
Dermatitis with Scattered Generalized
Distribution
 Difficult diagnostic and therapeutic challenge: lacks the
characteristic distribution that gives a clue to the etiology
 NACDG data: ~ 15% of the patients patch tested only had
scattered generalized dermatitis
• 49% had a positive patch test deemed at least possibly
relevant to their dermatitis
• The prevalence was higher in patients with a history of
atopic dermatitis
• Two most common allergens:
– Nickel
– Balsam of Peru
Zug KA, Rietschel RL, Warshaw EM, et al. The value of patch testing patients with a scattered generalized distribution of dermatitis:
Retrospective cross-sectional analyses of North American Contact Dermatitis Group data, 2001 to 2004. J Am Acad Dermatol
2008;59:426-431
Long Island, New York
TREATMENT OF CONTACT DERMATITIS
 Identify and avoid contact with allergens and irritants
• Give exposure list (synonyms & sources)
 Alternatives & substitutions if possible
– Cover nickel plated objects
– Wash formaldehyde containing garments
– Gloves & barriers




Supportive care: antihistamines
Topical corticosteroids
Oral corticosteroids
Other modalities: UV light
TREATMENT OF CONTACT DERMATITIS
 Prior to PT, may provide patient with “Lo.C.A.L. (Low
contact allergen) Skin Diet (Zug KA); eliminates most
common allergens
 Products devoid of
• Fragrance
• Formaldehyde Releasing Preservatives
• MCI/MI
• MDG/PE
• Lanolin
• CAPB
• Benzophenone-3
Long Island, New York
TREATMENT OF CONTACT DERMATITIS
 Acute Contact Dermatitis (wet, oozing lesions)
• Aluminum sulfate & calcium acetate (Domeboro) in clean
absorbent cloth 20-30 min as compress 2-3 x a day
• or Oatmeal baths (Aveeno) in extensive areas
• Oral corticosteroid if severe
• Fluourinated steroids for 1-2 weeks
 Chronic contact dermatitis
• Emollients to decrease itching
• Low to medium strength topical cs
• Antihistamines to decrease itching
• UV light
• Cyclosporine
• Topical calcineurin inhibitors
Long Island, New York