ISSUE
12
JUNE
2015
all things contact dermatitis
™
NEWS & NOTES
in thi s i ssue
Gold Nuggets P1
Positive Patch Test Reactions—Now What? P3
Gold Nuggets
G
Dear Reader,
Have you ever patch tested a patient with
gold—only to discover that the ensuing
positive reaction persists…and persists…
and persists? Or had a patient who had a
positive reaction to gold but you couldn’t
establish its clinical relevance despite conducting an investigation that would have
made Sherlock Holmes proud? Or received
a concerned phone call a couple of weeks
after you did the last reading of a patient’s
patch test because suddenly a reaction had
developed? If so, you are not alone. As you
will discover in this issue, any and all of these
occurrences are normal when patch testing
with gold—and they are no cause for alarm!
Part of the challenge of patch testing with
gold or with any other allergen, for that
matter, is navigating the tricky business of
patient education about allergen avoidance.
Patch testing means little if patients are
unable to avoid products and substances
that contain their allergen. It helps even
more if patients know not only what to avoid
but which products they actually can use
without worry. Fortunately, there are plenty
of resources to help you communicate
with your patients effectively—both from
their perspective and from that of the busy
practitioner. And as always, we are here to
help you achieve your patch testing goals—
we’re only a phone call away.
Sincerely,
Dr. Curt Hamann
President & CEO, SmartPractice
old is an allergen surrounded by considerable controversy.
Its clinical relevance has been questioned, concerns about
the risk of sensitizing patients have been expressed, and how
reaction patterns to gold should be interpreted has been debated.
Yet, in 2001 when the American Contact Dermatitis Society (ACDS)
selected gold as their Allergen of the Year, expert patch tester, Dr. Joseph
Fowler, wrote that gold should perhaps not only be the allergen of the year but
the allergen of the millennium! This year Chen and Lampel have revisited the ongoing debate
about gold in a thoughtful review. It is clear that many mysteries remain about this fairly
common sensitizer.
Elicitation of symptoms has been linked to gold in jewelry, occupational exposure to gold,
dental hardware, gold-plated intracoronary stents, eyelid implants, and a homeopathic medication containing gold. In particular, contact allergy to gold strongly correlates with medical
and dental applications of gold. For example, the frequency of gold allergy is high in patients
with gold in the oral cavity. Contact allergic gastritis has even been attributed to dental gold.
Patients with contact allergy to gold have developed localized dermatitis after receiving gold
eyelid implants, and the dermatitis has resolved when the gold was removed. Patients also
have developed flare ups at old sites of clinical contact dermatitis after systemic provocation
with ionic gold. In an unusual case, a woman taking a homeopathic medicine that contained
gold for heart disease developed systemic contact dermatitis that disappeared after she discontinued use of the drug. Finally, gold-coated coronary stents have been associated with an
increased frequency of restenosis and contact allergy to gold. In vivo corrosion of bare-metal
stents has been associated with the release of heavy metal ions into adjacent tissue, with ensuing vasculitis and restenosis.
The clinical relevance of gold as an allergen, however, has been questioned. The primary
reason is that some patients have a positive patch test reaction to gold sodium thiosulfate
(GST), the salt often preferred for patch testing in North America, but no reaction to jewelry
made from gold. That, however, a contact allergic reaction to the gold salt is more common
than allergic contact dermatitis to elemental gold or its alloys is not surprising. Metallic gold
is mostly inert and not that easy to solubilize. Specific conditions may need to be present to
encourage the formation of gold ions. For example, the sulfa-containing amino acid cysteine
enhances the release of gold in artificial body fluids. Microabrasives in cosmetic powders
such as titanium dioxides may abrade jewelry and help transfer gold ions to the face. And
low-karat gold alloys, for instance, those with a relatively high copper content, release more
gold than higher-karat alloys. The finding suggests that lower-karat gold may elicit more
intense reactions than higher-karat gold. Furthermore, although many patients do not exhibit
dermatitis at the site of contact with gold jewelry, their dermatitis has cleared after they
stopped wearing gold jewelry. Finally, more than half a century ago, a colloidal gold stain was
developed to identify Langerhans cells in the skin, clearly demonstrating that physiological
binding of gold is possible.
Despite variations in test substances, test doses, and study designs, large patch testing series
support the clinical relevance of gold as an allergen. In their 2001-2002 study period, the North
Continued on next page
1
Gold Nuggets…continued
American Contact Dermatitis Group (NACDG) found that 10.2% of
4,900 patients tested positive for gold sodium thiosulfate (GST), and
the relevance of 10% of the reactions was deemed probable. In their
2003-2004 study period, the rate of positive reactions to GST had
dropped but was still a substantial 8.7%. Thereafter, the NACDG
dropped GST from their standard series in favor of aimed patch
testing to sidestep concerns about delayed reactions and persistent
reactions. In an NACDG patch test study stratified by age, adults
between 19 and 64 years had the highest frequency (10%) of positive
reactions to 0.5% GST compared to adults older than 64 (7.3%) years
and to children 18 years or younger (6.1%). Of the 19- to 64-year-old
group, 4.1% of the positive reactions were deemed relevant. Women
are also more likely to test positive than men, a finding that has been
attributed to their potentially greater exposure to gold in the form of
wearing jewelry. In a patch test study of metal allergens conducted by
Mayo Clinic, positive responses were seen in 23% of patients tested
with 2% GST and in 18% tested with 0.5% GST. The percentage of
relevant allergic responses was almost 24% and 40%, respectively. In
a subsequent study from Mayo Clinic using their standard series of 71
allergens, the allergen with the highest percentage of positive allergic
responses (17%) was 2% GST, almost 20% of which were deemed relevant. As recently as 2013, the ACDS opted to include GST in their
Core Series.
Our understanding of gold as an allergen may be further impeded,
as Chen and Lampel noted, because sensitivity to gold can be overlooked. Late reactions are well known; consequently, reading a patch
test to gold only on Day 3 risks missing patients with reactions that
develop later. Some expert patch testers recommend a final patch
test reading as long as 3 weeks after patch removal to minimize missing positive reactions.
Persistent reactions are another common feature of patch testing
with GST that concerns many clinicians. Prolonged reactions to gold
have been reported in 26% of patients with no known allergies. Such
reactions, which can persist for weeks or months, should alarm neither
patients nor clinicians. Although reactions to gold have been reported to persist as long as about 3 months, there have been no serious
clinical repercussions. Patients sensitive to gold may be most likely to
have a prolonged reaction. Possible explanations for persistent test
reactions to GST include slow elimination of the allergen at the reaction site or a tendency to elicit chronic inflammation. Patients should
be informed that they might develop a persistent or a late reaction,
but neither is reason to avoid patch testing with GST. If patients
develop an uncomfortable persistent reaction, an over-the-counter
topical steroid may provide relief until the response dissipates.
Many patch testers, however, prefer aimed testing. The ACDS has
noted that patch testing to gold may be particularly worthwhile in
individuals with facial or eyelid dermatitis and in those with long-term
exposure from oral gold. Fingers and earlobes also may be involved.
Careful questioning of patients may yield clues, such as a potential
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As with any allergen, many complicated factors are involved in interpreting the clinical relevance of patch test reactions to gold. Currently, our
ability to identify gold allergies is limited because the appropriateness
of screening agents, concentrations, and time course is still largely
undetermined. However, strategies for establishing clinical relevance
include careful questioning of the patient to determine past and present reactions and exposures (i.e., occupational and nonoccupational)
to the allergen as well as further testing as deemed necessary. For
example, different dilutions of the same gold salt or different gold
salts altogether may need to be tested to identify patch-test positive
patients. The ACDS has stated that patients who have a positive reaction to gold but who have no dermatitis or who lack exposure to gold
can be considered to have an irrelevant sensitization.
Patients who are deemed allergic to gold must avoid products that
list any of the following names in the ingredients, material safety data
sheet, label or package insert: gold sodium thiosulfate; gold trisodium
bis(thiosulphate); thiosulfuric acid, gold(1+) sodium salt (2:1:3); and
thiosulfuric acid (H2S2O3), gold(1+) sodium salt (2:1:3). Patients should
avoid working with products that contain gold and wear protective
or utility gloves made of natural or synthetic rubber or vinyl if occupational contact is unavoidable. Patients should inform their doctors
about the test result. They can discuss with their dentist whether existing gold fillings or crowns should be removed. However, data suggest that it is unnecessary to remove crowns or fillings unless sores
are present in areas of the mouth in contact with the gold. Although
definitive answers to all the questions remaining about gold as a
sensitizer await further research, Fowler as well as Chen and Lampel
encourage continued patch testing with gold and a multidisciplinary
approach to understand its clinical relevance.
References
Andersen KA, Jensen CD: Long-lasting patch reactions to gold sodium thiosulfate occurs
frequently in healthy volunteers. Contact Dermatitis 56: 214-217, 2007
Chen JK, Lampel HP. Gold contact allergy: Clues and controversies. Dermatitis 2015; 26(2): 69-77
Davis MDP, Wang MZ, Yiannias JA, et al: Patch testing with a large series of metal allergens: Findings from more than 1,000 patients in one decade at Mayo Clinic. Dermatitis 2011; 22(5):256-271
Fowler JF Jr. Gold remains an important allergen. Dermatitis 2015; 26(2):67-68
Fowler JF Jr. Gold. Am J Contact Derm 2001; 12(1):1-2
Pratt MD, Belsito DV, DeLeo VA et al: North American Contact Dermatitis Group Patch-Test
Results, 2001-2002 Study Period. Dermatitis 2004; 15(4):176-183
Schalock PC, Dunnick CA, Nedorost S: American
Contact Dermatitis Society Core Allergen Series.
Dermatitis 2013; 24(1):7-9
Wentworth AB, Yiannis JA, Keeling JH:
Trends in patch-test results and allergen
changes in the standard series: A
Mayo Clinic 5-year retrospective review
(January 1, 2006, to December 31, 2010).
J Am Acad Dermatol 2014; 70:269-275
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occupational exposure, that support the presence of a gold allergy.
Provocation by an intramuscular injection of gold sodium thiomalate
for the treatment of rheumatoid arthritis has even been associated
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Positive Patch Test Reactions — Now What?
A
s challenging as it can sometimes be to identify the allergen(s) underlying a patient’s contact dermatitis, many practitioners might
agree that the hardest part follows the diagnosis—helping patients
to avoid further exposure. Given the multitude of allergens and
how ubiquitous so many allergens are in our occupational, home,
and recreational environments, the task can indeed be daunting.
Nonetheless, it is also a crucial task. Otherwise, patients’ dermatitis
might not only recur or fail to improve, it may actually worsen—even
to the point of becoming systemic. Only complete avoidance of a
known allergen will allow patients to live free of allergic contact dermatitis—not cured—but in remission.
Counseling, of course, requires clinicians to help their patients with
Type IV hypersensitivities to understand the rudiments of the clinical
aspects of their disease—how sensitization occurs, how it can occur
at any time after an exposure, and how they must avoid the identified
allergen(s) to prevent outbreaks. Once, the primary tool physicians
used to help patients grapple with the latter issue was an information sheet about the substances they needed to avoid. Typically, such
sheets contain alternative names for the allergen(s) in question and
lists of products that might contain the culprits. The onus was then
on the patients to read the tiny print of product labels to look for the
welter of confusing names. Such information, of course, is necessary
and can be obtained online free to both clinicians and consumers. Still
the need for consumers to read every label, to recall every chemical
variant of an allergen, and to recognize substances that could cause
cross-reactions is unrealistic, and even the most diligent patients are
bound to make a mistake once in a while inadvertently placing themselves at risk.
Fortunately, valuable digital resources are now available to help ensure
a successful clinician-patient partnership on the lifelong endeavor of
allergen avoidance. One such application was developed by Dr. James
Yiannis, who recounts an exchange that eventually prompted the
development of the Contact Allergen Replacement Database (CARD).
Not long after completing his residency, Dr. Yiannis was dismayed
to discover a skin product in his father’s bathroom that contained
lanolin—the very substance to which his father had patch tested positive. Dr. Yiannis rebuked his father for his negligence, and his father
responded: “Dear God, man! Can’t you just create a computer program to tell me what I can use, instead of…scolding me for making
the wrong choices?”
Although he failed to act on his father’s request for a few years,
Dr. Yiannis’s repeated encounters with confused patients eventually spurred him to design just such a database. His efforts began by
learning Microsoft’s database software, Access. He built the rudiments
of the database while taking a course to learn the software. Despite
initial limitations such as an inability to deal with cross reactors or
synonyms, the program was constructed so that both products and
ingredients could be added as could allergens that might be recognized in the future.
Development continued and in 2011 CARD was licensed to Preventice,
an IT company in Rochester, Minnesota, to introduce a mobile phone
application that consumers could use real-time while shopping. At
the time of its launch in 2011, the downloadable app offered data
on more than 8,000 ingredients in more than 5,500 skin products.
Consumers with allergies not only can use the app to create safe
shopping lists, they can create personal journals of reactions, compare
products while shopping and be notified of changes in the formula
of products. Patients and physicians had to pay a subscription fee to
access CARD. The latest advance is a new application called SkinSAFE
(see www.empowher.com), which is based on the original CARD. The
intent is a more consumer-friendly product that is aimed at improving the health of the overall population without necessarily requiring
a physician’s input. A database that is larger than the original CARD
system is planned as is expansion to include other products beyond
the skin care category.
Another useful database, known as the Contact Allergen Management
Program (CAMP), is supported by the ACDS. Initially developed
by Matthew Zirwas, MD, CAMP is currently managed by Andrew
Scheman, MD. Access to CAMP is a benefit of membership of the
ACDS (see www.contactderm.org) and is intended to help guide
clinicians in making recommendations to their patients. Like CARD
it generates a list of products that does not include the allergens of
concern and that can be used by patients with those particular allergies. The allergens or cross-reactors are selected by the physician.
The list can be printed and handed to patients or can be shared with
them electronically. Products can also be searched for based on the
manufacturer, the product type, product name, or brand name.
The ACDS site also includes other information that can be useful
in the process of patient counseling. For example, information is
available on both sterile and nonsterile gloves and includes brands
known to be free of specific accelerators, a common cause of hand
dermatitis. The site also provides avoidance narratives in English
and Spanish. Finally, patients are able to access their reports online
for updates. For its members, the ACDS website provides access to
Cosmetic Ingredient and Manufacturer Information, which consists
of four databases developed by the Personal Care Products Council,
formerly the Cosmetic, Toiletry, and Fragrance Association. Another
database that members can access via the ACDS site is the Research
Institute for Fragrance Materials (RIFM) Monograph Database, which
provides links to fragrance raw materials.
Continued on next page
Despite its flaws, the program generated a list of products that
patients with positive patch tests could safely use. After its introduction in 1998, CARD progressed to a fully Web-based user interface
supported by the Mayo Clinic. In 2001 CARD became available to
members of the American Contact Dermatitis Society (ACDS), and
the database was awarded the Gold Triangle Award by the American
Academy of Dermatology for excellence in public education. CARD
was found to be as effective as traditional approaches to patient counseling, to increase patient satisfaction, and to decrease the amount of
time clinicians need to spend with patients on education.
3
Positive Patch Test Reactions—Now What?
…continued
Free governmental resources are also available. Depending on
patients’ individual allergy, The Household Products Database of
the United States Department of Health and Human Services (see
householdproducts.nlm.nih.gov) may help physicians and patients
determine if products are appropriate choices. This database links
more than 13,000 consumer brands to health effects from Material
Safety Data Sheets provided by manufacturers. The database can
be searched by product category, type of product, ingredients,
and manufacturers to help users identify the chemical ingredients
of different brands, the potential effects of ingredients, and how
to contact the appropriate manufacturer. It is worth keeping in
mind that some components of products can originate overseas. In
such cases it can be difficult to identify the ingredients and hence
potential allergens. Nonetheless, both clinicians and patients
should be aware of this vast database.
Many products simply cannot be manufactured without introducing
potential allergens. Consequently, even with robust digital resources at our fingertips, allergy avoidance is likely to remain a challenge
for patients and their caretakers. Just as clinicians partner with their
patients, our mission is to partner with clinicians to make all aspects
of patch testing—from obtaining the supplies to performing the
tests to counseling and education—as easy as possible. Please feel
free to explore the many patch testing resources that you will find
on our website, smartpracticecanada.com.
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References
call
El-Azhary RA, Yiannias JA. A new patient education approach in contact allergic dermatitis:
The Contact Allergen Replacement Database (CARD). Int J Dermatol 2004; 43(4):278-280
866.903.2671
l
email
[email protected]
Kist JM, El-Azhary RA, Hentz JG, Yiannias JA. The Contact Allergen Replacement Database
and treatment of allergic contact dermatitis. Arch Dermatol 2004; 140(12):1448-1450
Kist J, Yiannias J, El-Azhary RA. Efficacy of Contact Allergen Replacement Database in the
treatment of allergic contact dermatitis. Am J Contact Derm 2001; 12(2):124
Yiannias JA, Miller R, Kist JM. Creation, history, and future of the Contact Allergen
Replacement Database (CARD). Dermatitis 2009; 20(6):322-326
ing
Introduc
Yiannias JA, Johnson J. Electronic solutions for allergen avoidance. The Dermatologist
2014;22(8). www.the-dermatologist.com/content/electronic-solutions-allergen-avoidance.
Accessed April 1, 2015
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