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Contact Dermatitis and Patch Testing:

An Update for the Allergist

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

AAAAI

2802 Hands-On Workshop

Saturday, February 23, 2013: 04:45 PM - 06:00 PM

Disclosure

Research and Educational Grants

• AAAAI ArTrust

• Genentech

• Dyax

• Baxter

Speaker’s Bureau

• Baxter

AAAAI

Objectives

1. Discuss the clinical correlation of the patch test

results

2. Develop a current understanding of allergic

contact dermatitis and patch testing to

cosmetics, medical devices and other allergens

3. Demonstrate the technique of application and

interpretation of non standardized allergens as in

personal products

Patterns of Cosmetic Contact Allergy

Facial cosmetic dermatitis

• Bilateral

• Patchy

Eyelid

Neck

• “run-off” pattern

• Cosmetics applied to face, scalp or hair often initially affect

the neck

• Most affected site of ACD from nail varnish is the neck

Lips

• Consort/Connubial Dermatitis:

primarily fragrance

Typical contact allergens tend to be clustered in a

few important classes

• Fragrances

• Preservatives

• Excipients

• Glues

• Sun blocks

The Science of Cosmetics

Fragrance

Contact Allergen of 2007

Most common cause of ACD from cosmetic

> 2800 fragrance ingredients used routinely in cosmetics

• ~100 are known allergens

~10-25% of PT are positive to fragrance chemicals

• 1.7- 4% of general population

• predominantly women

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 population over a 17 year period. Br J Dermatol 2000;142:203-4

Contact Dermatitis 2003 Dec;49(6):287-9

Fragrance

Fragrance Mix I

Balsam of Peru

Myroxylon pereirae

Fragrance Mix II

Cinnamic alcohol 1% Cinnamic acid Coumarin 2.5%

Cinnamic aldehyde 1% Benzoyl Cinnamate Hydroxyisohexyl 3-cyclohexene

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%

Other fragrance sensitizers: Lyral, jasmine, lavender, sandalwood, tea

tree oil , ylang ylang oil, lemongrass oil, jasmine, Narcissus

Fragrance


Standard fragrance mix: Fragrance mix I & Balsam

of Peru

• pick up 60-70% of all ACD to fragrances at best

(-) PT to FM I

• ~ 35% had (+) PT to FM II

(+) PT to FM II

• ~1/3 had (+) PT to FM I

Buckley DA et al. The frequency of fragrance allergy in a patch-test population over a 17 year period. Br J Dermatol 2000;142:203-4

Albert MR et al. Concomitant positive reactions to allergens in the patch testing standard series from 1988-1997. Am J Contact Dermat 1999. 10:219-223

Devos SA et al. Relevance of Positive Patch-Test Reactions to Fragrance Mix. Dermatitis, Vol 19, No 1 January/February), 2008: 43–47

Fragrance Mix Patch Test

Low specificity

• Mild Irritant potential, caution with weak positive reactions

Increased probability of a relevant FM patch-test

• Increased strength of test reaction

• Repeated (+) reaction on retest

• (+) to one of its ingredients

Devos SA et al. Relevance of Positive Patch-Test Reactions to Fragrance Mix. Dermatitis, Vol 19, No 1, 2008: 43–47

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 other than 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

Food-related contact dermatitis

Myroxilon pereirae, Fragrance Mix, Cinnamic Aldehyde

Myroxilon pereirae (Balsam of Peru) (2nd)

Fragrance mix (4th)

Cinnamic aldehyde (6th)

• Relatively specific (not very sensitive) marker for spice

allergy

• Flavoring in gums, mouthwashes, toothpaste

• Sensitization to BOP in topical products may cause systemic

CD from foods with BOP

Warshaw E M et al. Contact Dermatitis Associated with Food: Retrospective Cross-Sectional Analysis of North American Contact Dermatitis Group Data,

2001–2004

Bauer A, Geier J, Elsner P. Type IV allergy in the processing industry: sensitization profiles in bakers, cooks and butchers. Contact Dermatitis 2002;46:228–

35.

Fragrance Systemic Contact Dermatitis

Foods to Avoid in Balsam-Restricted Diet

• Citrus fruits: oranges, lemons, grapefruit, tangerines

• Flavoring agents: pastries, bakery goods, candy, gum

• Spices: cinnamon, cloves, vanilla, curry, allspice, anise, ginger

• Spicy condiments: ketchup, chili sauce, barbecue sauce, chutney,

• Perfumed or flavored tea & tobacco

• Chocolate

• Certain cough medicines & lozenges

• Ice cream

• Cola, spiced soft drinks such as Dr Pepper

• Tomatoes & tomato-containing products

• Possible cross reactivity with Compositae (‘‘natural’’ & ‘‘organic’’)

containing sesquiterpene lactones (chamomile, echinacea)

~ half of patients with (+) PT to MP who followed a low BOP 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

Paulsen E. Contact sensitization from Compositae-containing herbal remedies and cosmetics. Contact Derm 2002;47:189–198.

Paulsen E, Andersen KE. Colophonium and Compositae mix as markers of fragrance allergy: cross-reactivity between fragrance terpenes,

colophonium and compositae plant extracts. Contact Derm 2005;53:285–291.

Summary for Fragrance Allergy

Wash on/wash off products: ? Relevance of brief exposure

• Concentration of fragrance left on fabric is below

threshold induction levels

Testing to FM I & BOP picks up 60-70% of fragrance allergy*

Many FM I PT reactions are weak, perhaps irritant & hard to

reproduce

Advising patients to avoid all fragranced products on the

basis of a very weak (+) PT (? irritant) may deprive them of

one of life's pleasures

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

Preservatives

945 PT patients at Mayo

• 68.4% had at least 1 (+) reaction

• 47.3% had at least 2 (+) reactions

• 49.4% reacted to at least 1 preservative

• 31.2% reacted to at least 1 fragrance/botanical

additive

Older individuals were 3.7x more likely to have (+)

PT to common preservatives than children

J Am Acad Dermatolol. 2010 Nov; 63(5)789-98

Cosmetic Preservatives

Formaldehyde (+) PT Non Formaldehyde (+) PT

Formaldehyde* 8.4 % Methyldibromoglutaronitrile

(Euxyl K 400)

5.8 %

Quarternium 15* 9.3% MCI/MI 2.3 %

Diazolidinyl urea* (Germall II) 3.2 % Parabens* 0.5 %

Imidazolidinyl urea* (Germall) 3.0 % Chloroxylenol 0.8 %

Bromonitropropane

(Bronopol)

3.3 % Iodopropynylbutylcarbamate

0.4%

DMDM Hydantoin (Glydant) 2.6 %

Paraben, quarternium-15 & formaldehyde preservatives are frequently

combined & cosensitize ***

*Antigen present in the T.R.U.E. Test

** % Prevalence PT reaction based on NACDG or TT

***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

Formaldehyde

Most common potential source of exposure

Cosmetics

• Rarely 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

Formaldehyde Resins

•Dermatitis pattern in areas where clothing fit tightly

• posterior neck

• upper back

• lateral thorax

• anterior & posterior axillary folds (spares axillary vault)

• waistband (spares undergarment areas)

• flexor

•Importance of pressure, friction, heat, perspiration

Subacute and chronic dermatitis

Formaldehyde testing alone identifies only ~70% of

formaldehyde resin allergic patients

• PT with resins as well

Slow resolution of dermatitis even with careful avoidance

• As much as 50% still had constant dermatitis *

Occasional exposure to ‘‘Dress clothes’’ on weekends is

enough to maintain 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.

Reich H &Warshaw E. Allergic Contact Dermatitis from Formaldehyde Textile Resins. Dermatitis, Vol 21, No 2, 2010: pp 65–76

Formaldehyde in Textile Resin

Treatment for Formaldehyde Resin Allergic

Contact Dermatitis

Use 100% silk, polyester, acrylic, nylon

• Linen & denim if soft & wrinkle easily

Avoid ‘‘easy care,’’ ‘‘permanent press,’’ or

‘‘wrinkle free’’

Some experts also recommend avoidance of

formaldehyde-releasing preservatives in

personal products*

AVOID FORMALDEHYDE RESINS AT ALL

TIMES. Even exposure once a month is

enough to cause a rash to continue

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.

SCD in formaldehyde-sensitive patients after ingesting

aspartame (artificial sweetener) in food, medicaments, vitamins

• Monteleukast chewable tablets (contain aspartame)

– granule does not

Aspartame metabolized to phenylalanine, aspartic acid, &

aspartic acid methyl ester methanol transported to liver

Liver: methanol oxidized formaldehyde

Matiz and Jacob: Systemic Contact Dermatitis Pediatric Dermatology Vol. 28 No. 4 July ⁄ August 20

Jacob SE, Stechschulte S. Formaldehyde, aspartame, and migraines: a possible connection. Dermatitis 2008;19:E10–E11.11

Food-related Contact Dermatitis

Formaldehyde Allergy & Aspartame

Quarternium 15

Most common cosmetic preservative allergen

Most sensitization is caused by formaldehyde releaser

Most Q 15 allergic patients are also allergic to formaldehyde


Paraben

Most commonly used cosmetic ingredient 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

• Foods: paraben is usually less than 1%

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


Erin M. Warshaw et al. Positive Patch Test Reactions to Lanolin: Cross-Sectional Data from the North American Contact Dermatitis Group, 1994 to

2006. Dermatitis. April 2009. 20;2:79-88

Most common sources: moisturizer, creams,

cosmetics & topical medications

Male sex, atopic dermatitis, & co-reactivity to other

allergens were higher in lanolin-positive patients

Complex mixture therefore test actual lanolin used

Lanolin Paradox:

• sensitivity low in normal skin

• moderate in atopic

• high in stasis eczema & ulcers

Cosmetic vehicles, emulsifiers & additives

Lanolin (Wool wax alcohols)

Most common patterns of dermatitis in PG (single reactors)

• Dermatitis on the face

• Scattered or generalized dermatitis

Uses

• solvent, vehicle, emulsifier or humectant

• thickening agent in many foods (concentration may be too

low to cause skin reactions)

Most common source of allergy

• Personal care products

• Topical medicaments, especially topical CS

PROPYLENE GLYCOL

Food-related irritant and allergic contact dermatitis

Specific Allergens: Propylene Glycol

Used in food colorings, foods thickening agent in cake mixes, salad dressings, soft drinks, popcorn

Concentration in foods is likely too low to cause a reaction

• but there are reports of flares from ingestion of foods containing propylene glycol by sensitized patients

• flares following oral provocation (15 mL of propylene glycol)

Warshaw E M et al. Contact Dermatitis Associated with Food: Retrospective Cross-Sectional Analysis of North American Contact Dermatitis Group Data,

2001–2004

Bauer A, Geier J, Elsner P. Type IV allergy in the processing industry: sensitization profiles in bakers, cooks and butchers. Contact Dermatitis 2002;46:228–

35.

Permanent Hair Dye

• Theoretically, does not cause reaction if fully oxidized

• In reality, it is likely that PPD is never completely

oxidized

P-phenylenediamine (PPD)


New Route of Exposure

Body painting & temporary tattooing (until stratum corneum is shed)

Clinical course

(1) acute intense eczematous response within 1-2

days of tattooing

(2) subacute response: lichenoid eruptions within 1- 2

week

– Most likely causative agent is PPD

PPD sensitization is likely lifelong; may react to first

attempts at hair coloring

Leo V. p-Phenylenediamine Dermatitis Volume 17, Issue 02, June 2006, Pages 53-55 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

Prevention

Home test appear to be predictive and could provide

secondary prevention if properly used

New hair dyes (semipermanent) contain FD & C and D & C

dyes that appear to have very low cross reactivity with PPD

• Elumen Hair Color

– (Goldwell cosmetics Linthicum Heights, MD)

• Clairol Basic Instincts-Loving Care

– (The Proctor & Gamble Company, Cincinnati, OH)

Krasteva et al. Contact Sensitivity to hair dye can be detected by the consumer open test. Eur J Dermatol 2002;12:322-6

Fautz R et al. Hair dye sensitized hairdressers: the cross reaction pattern with new generation hair dyes. Contact Dermatitis 1999;46:319-24

Cocoamidopropyl betaine

Contract Allergen of 2004

Second most common allergen in shampoo

Less irritating than older surfactants (sodium lauryl

sulfate) but more sensitizing

Positive PT are often clinically relevant

Areas of Involvement

• Face: 30.2%

• Neck: 14.3%

• Hands: 12.7%

• Eyelids: 9.5%

• Scalp: 4.8%

• Scattered: 23.8%

Fowler JF. Cocamidopropyl Betaine. Dermatitis 2004;15:3-4

Shampoos

Typically composed of 10-30 ingredients

Matthew Zirwas and Jessica Moe Shampoos. Dermatitis, Vol 20, No 2 (March/April), 2009: pp 106–110

Only 5 products in the Walgreens database were truly fragrance free

Of 9 with no fragrance, 4 had fragrance related ingredients, 3 had botanical ingredients, 1 had

benzyl alcohol)

Emergent and Unusual Allergens in Cosmetics

ACD from cosmetics is a common problem, the formulation of cosmetic products is constantly changing

• Shellac (lacca or gomme-laque): found in pump or aerosol hair sprays, shampoos, eyeliners, mascaras, nail lacquers, lipsticks

• Lipsticks

– Various D&C dyes & inorganic pigments in D&C yellow 11 and D&C red 7

– Oily base: Castor oil (ricinus oil): suspends pigment

– Additives (ie. emollients), antioxidants (ie gallates), sunscreens

Old allergens learn new tricks while new allergens emerge to challenge our quest for a definitive diagnosis

Pascoe D et al. Emergent and Unusual Allergens in Cosmetics Dermatitis Vol 21 No 3 2010 127-137

Issues with Contact Dermatitis

History not always accurate

Physician’s guess is almost always wrong

Changing landscape of cosmetics

NEW Products (New fragrance chemicals constantly introduced )

• New bottles of old products

• New and improved products

• Natural products can cause allergies

Poor Regulation of cosmetics industry

• fragrance formulas are “trade secrets”

• Some manufacturers do not consider essential oils to be fragrance (Tree tea oil , Ylang-ylang oil, Jasmine , Peppermint , Lavender, Citrus oil)

• “Covert fragrances”- used for other than for aroma (i.e. preservatives)

Labels difficult to read or Incomplete

Cross-reactivity and Co-reactivity

Test for personal products especially for facial, eyelid and lip dermatitis

Clinical Campus of Stony Brook University School of Medicine

Nickel in Biomedical Devices

Reports of dermatitis to biomedical devices lead to:

Consults regarding safety of medical devices in nickel-sensitized patients

High variability of care in terms of testing & recommendations

• differences within and between countries

Increased health care costs

Medicolegal concerns contribute to testing

Selection of more expensive & less durable option

As nickel allergy incidence increases, this problem will also increase

Kornik R and Zug K. Dermatitis2008;19(1):3-8 Clinical Campus of Stony Brook University School of Medicine

Pathophysiology of Metal Allergy and Implant Failure

Metal tissue

Deposition

Watari F et al. J. R. Soc. Interface 2009;6:S371-S388

Cunningham et al. The effect of spinal instrumentation particulate wear debris : an in vivo rabbit model and applied clinical study of retrieved instrumentation

cases. The Spinal Journal. 2003; 3:1. 19–32

Basko-Plluska, J et al. Cutaneous and Systemic Hypersensitivity Reactions to Metallic Implants. Dermatitis, 2011. 22: 65–79

Schalock1, et al Hypersensitivity reactions to metallic implants – diagnostic algorithm & suggested patch test series for clinical use. Contact Dermatitis, 66, 4–19

Metal Corrosion Tissue Reactions

Necrosis Foreign body

Phagocytosis giant cells

Immunologic Level • Endothelial cell exposure induce intercellular adhesion molecule1 expression

• Cutaneous reactions above implant are primarily T cell-mediated type IV rxns

• Tissues adjacent to implant in metal sensitive patients have elevated immune

cells/markers (CD3þ T lymph, CD4þ cells, CD11cþ macrophages/dendritic cells & cells with abundant MHC class II)

Orthopedic Implant Allergy

5% of orthopedic implant & up to 21% of patients with preop

metal sensitivity may develop cutaneous allergic reactions on

reexposure to the same metal

Clinical manifestations

• Cutaneous

– localized: eczematous reaction overlying implant

(urticaria & vasculitis reported)

– generalized

– both

Non Cutaneous Reactions

• Implant Failure

Basko-Plluska JL, Thyssen, JP & Schalock PC. Cutaneous & Systemic Hypersensitivity Reactions to Metallic Implants.Dermatitis, 2011.22:65–79

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

Prospective Longitudinal Studies and Reviews

Study Pt Conclusions

Carlsson &

Mo ller 1989

18 Metal allergic pts with confirmed allergy to metal in their device prior to

stainless steel orthopedic implants had no issues (6-yr ff-up)

Thyssen et al,

2009

356 Risk of surgical revision not increased in patients with metal allergies

Carlsson A, Mo ller H. Implantation of orthopaedic devices in patients with metal allergy. Acta Derm Venereol 1989;69:62–6

Thyssen JP, Jakobsen SS, Engkilde K, et al. The association between metal allergy, total hip arthroplasty, and revision. Acta Orthop 2009;80:646–52

Merritt K, Rodrigo JJ. Immune response to synthetic materials.Sensitization of patients receiving orthopaedic implants. Clin Orthop 1996;326:71–9

Niki Y et al. Screening for symptomatic metal sensitivity: a prospective study of 92 patients undergoing total knee arthroplasty. Biomaterials 2006;26:1019–26.

Eben R et al. Contact allergy to metals and bone cement components in patients with intolerance of arthroplasty. Dtsch Med Wochenschr 2010;135:1418–22.

Thomas P, et al. Increased metal allergy in patients with failed metal-on-metal hip arthroplasty & 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.

Niki et al 2006 92 26% had (+) LST tests to at least one metal (Ni, Co, Cr, Fe)

5% of total study developed cutaneous allergic reactions

In metal (+) prior to implant: 21% developed dermatitis at site of implant

(some widespread)

Study Pt Conclusions

Carlsson &

Mo ller 1989

18 Metal allergic pts with confirmed allergy to metal in their device prior to stainless

steel orthopedic implants had no issues (6-yr ff-up)

Thyssen et al,

2009

356 Risk of surgical revision not increased in patients with metal allergies




(some widespread)

Eben et al

2010

92 66/92 had sx (pain, reduced motion, swelling)

Rates of allergy: nickel: 24.2% vs 3.8% (no Sx); cobalt: 6.1%; vs 3.8%

Symptomatic (31.8%) had allergic reaction to bone cement components




(some widespread)

Eben et al

2010




Braathen et al 16 81% of failed metal-on-metal implants had metal sensitivity (PT &/or LTT)




(some widespread)

Eben et al

2010




Braathen et al 16 81% of failed metal-on-metal implants had metal sensitivity (PT &/or LTT)

Hallab N, et al

2001

Accumulated reports in total hip arthroplasty: prevalence of metal allergy

~ 25% in well-functioning vs. ~ 60% in failed/poorly functioning implant

Allergic Contact Dermatitis from bone cement components

Common causes of failure:

infection, recurrent dislocation, aseptic osteolysis, fractures

*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

Common Bone Cement Allergen

in Total Joint Arthroplasties

Use Approx % (+)

Reaction

N,N-dimethyl-p-toluidine (DPT) Reaction initiator 10

Polymethyl methacrylate (MMA) Cement Base 25

Benzoyl Peroxide Activator 8-10

Hydroquinone MMA Stabilization 5

Gentamycin Antibiotic 17-24

Reported in 24.8% of patients (n = 239)*

Study Positive Findings Negative Findings

Köster R,

et al 2000

Prospective

study

Coronary in-stent

restenosis 6 mos post

stent & PT 2 mo after

angioplasty

(+) PT in 10/131 (8%)

- All 10 (100%) had in-stent

restenosis

However, 57% of (-) PT

had ISR

Gold-plated stents (thought to be inert), subsequently showed that gold in

cardiac stents was a strong risk factor for ISR, especially in those with prior

gold allergy *

Endovascular stent &

In-stent restenosis

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 et al. The impact of metallic allergy on stent implantation: metal allergy & recurrence of in-stent restenosis Int J Cardiol 2005;104:319–25 Thyssen J P et al. G H No association between metal allergy and cardiac in-stent restenosis in patients with dermatitis – results from a linkage study. Contact Dermatitis 2011: 64: 138–141. *Svedman C et al. A correlation found between contact allergy to stent material and restenosis of the coronary arteries. Contact Dermatitis 2009: 60: 158–164


Köster R,

et al 2000

Prospective

study

Coronary in-stent



angioplasty

(+) PT in 10/131 (8%)


restenosis


had ISR

Iijima R,

et al 2005

Prospective

study

174 stented patients

-109 (initial placement)

- 65 (restenosis)

Recurrence of ISR: higher (+)

PT to metals (39% vs.12%; p =0.02)

Predictors of recurrent restenosis:

(+) patch test (OR 4.39, p =0.02)

Initial stent implantation

not significantly

different between with or

w/o restenosis (10% vs 9%)


Köster R,

et al 2000

Prospective

study

Coronary in-stent



angioplasty

(+) PT in 10/131 (8%)


restenosis


had ISR

Iijima R,

et al 2005

Prospective

study

174 stented patients

-109 (initial placement)

- 65 (restenosis)

Recurrence of ISR: higher (+) PT

to metals (39% vs.12%; p =0.02)

Predictors of recurrent restenosis:

(+) patch test (OR 4.39, p =0.02)

Initial stent implantation

not significantly different

between with or w/o

restenosis (10% vs 9%)

Thyssen,

et al 2012

Linkage Study

149/18,794 (0.8%) PT

prior to metal stent

placement

14% (21/149) had ISR

- Only 11.8% (2 /21) had

metal allergy

Pacemakers/Defibrillators

Majority of reactions are infections

Allergic complications rare: ~30 cases reported in

literature

• Ti alloy shell: most frequent

• Manifestations:

– dermatitis localized above implant

– impaired wound healing

– generalized or remote dermatitis

(uncommon)

Schalock et al Hypersensitivity reactions to metallic implants – diagnostic algorithm and suggested patch test series for clinical use. Contact Dermatitis, 66, 4–19

HonariG, et al. Hypersensitivity reactions associated with endovascular devices. Contact Dermatitis 2008: 59: 7–22

Hallab N J, Jacobs J J. Biologic effects of implant debris. Bull NYU Hosp Jt Dis 2009: 67: 182–188

Oprea M L, Schn oring H, Sachweh J S, Ott H, Biertz J, Vazquez-Jimenez J F. Allergy to pacemaker silicone compounds: recognition and surgical management.

Ann Thorac Surg 2009: 87: 1275–1277

Dental Implants & Orthodontic Devices

Potential allergen groups

• Ni–palladium &/or Ti alloys

• CoCrMo alloys

• Epoxy & epoxy-acrylate preparations

• Anesthetics & flavorings

Flexible titanium-nickel arch wires release more nickel

compared to stainless steel

• Nickel: most common contact allergen to

orthodontics

Schalock1, et al Hypersensitivity reactions to metallic implants – diagnostic algorithm and suggested patch test series for

clinical use. Contact Dermatitis, 66, 4–19

Gynaecological devices

Mostly from contraceptive devices

• contain copper

Reports of systemic allergic dermatitis

resolving with IUCD removal

Contraindication to placement

• Copper allergy in Copper IUCDs (Paragard)*

• Ni allergy in Nitinol (Essure)**

*Paragard. Product description. Available at: http://www.paragard.com/hcp/aboutparagard/product-description (last

accessed 3 December 2010).

** Essure. Instructions for use. Available at:http://www.essuremd.com/portals/essuremd/PDFs/TopDownloads/L3002%

2009_09_09%20smaller.pdf (last accessed 28 January 2011).

Should allergy screening be performed?

Patients with no history of metal hypersensitivity need not be

screened prior to implantation

Pre-implantation PT identifies metal-allergic individuals*

• Screening prior to surgery is recommended for those with

history of metal sensitivity of a magnitude sufficient to cause

concern to the patient or healthcare provider **

Post-implantation PT: joint pain, implant loosening, or

unexplained cutaneous reaction at the implant site with a

question of metal hypersensitivity

Schalock1, et al. Hypersensitivity reactions to metallic implants – diagnostic algorithm & suggested patch test series for clinical use. Contact Dermatitis, 66, 4–19

*Reed K B, et al. Retrospective evaluation of patch testing before or after metal device implantation. Arch Dermatol 2008: 144: 999–1007

**ThyssenJP,Menn e T, Schalock P C, Taylor J S, Maibach H I. Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic

orthopaedic implants before and after surgery. Br J Dermatol 2011: 164:473–478

What is the benefit of the medical history?

An alternative view

The validity of self reported nickel allergy*

• Sensitivity : 37–82%

• Specificity: 77–87%

Suggests that patient’s history is not sufficiently predictive

to warrant PT & that the prevalence of reactions is high

enough to warrant pre-implant evaluation **

*Schalock et al Hypersensitivity reactions to metallic implants – diagnostic algorithm & suggested patch test series for clinical use. Contact Dermatitis, 66, 4–19

* Fors R, et al. Nickel allergy – prevalence in a population of Swedish youths from patch test and questionnaire data. Contact Dermatitis 2008: 58: 80–87

*Fleming C J et al. Accuracy of questions related to allergic contact dermatitis. Am J Contact Dermat 2000: 11: 218–221.

* Dotterud L K, Falk E S. Metal allergy in north Norwegian schoolchildren and its relationship with ear piercing and atopy. Contact Dermatitis 1994: 31: 308–313.

**Kieffer M. Nickel sensitivity: relationship between history and patch test reaction. Contact Dermatitis 1979: 5: 398–401.

“…requires all patient who will undergo pectus surgery to be tested for allergies

to the metallic component of the implanted surgical stainless steel pectus bar”

http://www.chkd.org/

Patch Testing vs. Lymphocyte Transformation Test

Measures lymphocyte proliferation (stimulation index) after 7

days incubation +/- allergen

• Limited allergens, availability & rapid decay of T cells

(rapid transportation) *

? LTT better reflect immune reactions within the body,

whereas PT reflects cutaneous reactivity

May be useful in questionable cases

• 54/56 patients with Ti implants, (-) PT & (+) Ti LTT whose

systemic symptoms resolved after implant removal

Needs Validation

*(MELISA test: Health Diagnostics and Research Institute, South Amboy, NJ)

Muller K E, Valentine-Thon E. Hypersensitivity to titanium: clinical & laboratory evidence. Neuro Endocrinol Lett 2006: 27: 311–313

What to test with

PT with limited allergens is not recommended as there may be

multiple causes of the dermatitis

Baseline series [NACD, ACDS, European Baseline Series etc]

Extended series & specialty trays

• Extended NA standard series (Chemotechnique or Allergeaze;

SmartPractice, Calgary,AB,Canada)

• International Comprehensive Baseline series (Chemotechnique)

Metals


clinical use. Contact Dermatitis, 2011. 66, 4–19

Mayo Clinic PT Protocol for patients

about to or have undergone device implantation

Rationale:

1. Implanted devices contain metals

• nickel, cobalt, chromium, titanium

2. ~ 10% of the general population have cutaneous metal

hypersensitivity

3. Cutaneous reactions to metal implants have been documented

4. Hip prostheses have a shorter lifespan in patients with

documented sensitization to bone cement

5. Pre implantation PT may guide the choice of the device implanted

Reed, et al, Retrospective Evaluation of Patch Testing Before or After Metal Device Implantation. Arch Dermatol. 2008. 144; 8


clinical use. Contact Dermatitis, 2011, 66, 4–19

Suspect Orthopedic Metal Implant Allergy

Pre Implant

No Concern

for Hyper-

sensitivity

Reaction

No Symptoms

Possible

Hyper-

sensitivity

Reaction

No Testing Baseline Series

Metals: Aluminum, Chromium, Cobalt.

Iron, Manganese, Molybdenum, Nickel,

Niobium, Silicon, Phosphorus,Tantalum,

Titanium, Tungsten, Vanadium Zirconium,

Gold,

Extended Series

Metals

Bone Cement

Implant Disc

LTT?

Extended Series

Metals

Implant Test

Disc

Post Implant

No Hx of Dermatitis Hx of Dermatitis Symptoms

No

Testing


clinical use. Contact Dermatitis, 2011 66, 4–19

Orthopedic Metal Implant Allergy

+ Metal Test

No Intervertion

Options

•Remove Implant

•Replace w/ non allergenic alloy

•Coat metal w/ polytetrafluoroethylene

Is removal safe and reasonable

No surgical intervention

(+) dermatitis: consider 21 day

course of tapered oral

prednisone

Is Device Removal Necessary ?

No Symptoms + Symptoms


clinical use. Contact Dermatitis, 2011 66, 4–19

No

Yes

No Yes

METAL IMPLANT “ALLERGY”

What do we know

Metal implant release metal ions and elicit an immune response

Most reactions to metal implants are based on case reports or

relatively small cohorts

~ 5% developed eczematous reactions directly associated with

metallic implants

• proven cases incriminate nickel, cobalt, chromium, copper

The temporal & physical evidence leaves little doubt that a

considerable number of patients develop metal sensitivity &

cutaneous allergic dermatitis in association with metallic

orthopedic implants

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.


What do we know about Patch Testing

Need for patch testing is controversial, poorly reliable in

predicting or confirming implant reaction

• Preimplantation PT: Consider if history of metal sensitivity is

of sufficient cause of concern to patient or healthcare

provider **

• Post cutaneous eruption PT : consider with an appropriate

series

Basko-Plluska JL et al. 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.



What else do we know

(-) PT is reassuring for absence of delayed

hypersensitivity

A (+) PT does not prove relevance

If relevant allergens are identified & corticosteroid therapy is insufficient to clear eruption, removal of implant may be considered


What we do NOT know about Metal Implant Allergy

Whether risk of allergic reaction to orthopedic implants

increase in metal sensitized individuals

Whether supposed allergies to implanted devices really

cause problems such as loosening or dermatitis

How to identify the subgroup of metal allergic patients with

increased risk of complications from metal implant

Whether PT can truly detect reactions to implanted devices

Patch Testing vs. Lymphocyte Transformation Test

Based on the complex findings, it is difficult to make general

principles for good clinical practice & prospective longitudinal

studies are strongly needed

contact dermatitis and patch testing: an update for the ... · contact dermatitis and patch...

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