ArticlePDF AvailableLiterature Review

Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention

Authors:
  • University of New England (USA) College of Medicine

Abstract and Figures

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics). To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population. This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high–nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.
Content may be subject to copyright.
POLICY STATEMENT Organizational Principles to Guide and Dene the Child Health
Care System and/or Improve the Health of all Children
Nickel Allergic Contact Dermatitis:
Identication, Treatment,
and Prevention
Nanette B. Silverberg, MD, FAAP, FAAD,aJanice L. Pelletier, MD, FAAP,b,c Sharon E. Jacob, MD, FAAP, FAAD,d,e
Lynda C. Schneider, MD, FAAP,fSECTION ON DERMATOLOGY, SECTION ON ALLERGY AND IMMUNOLOGY
abstractNickel is a ubiquitous metal added to jewelry and metallic substances for its
hardening properties and because it is inexpensive. Estimates suggest that at least
1.1 million children in the United States are sensitized to nickel. Nickel allergic
contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type
hypersensitivity reaction worldwide. The incidence among children tested has
almost quadrupled over the past 3 decades. The associated morbidities include itch,
discomfort, school absence, and reduced quality of life. In adulthood, individuals
with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD
in children has been postulated to result from early and frequent exposure to
metals with high amounts of nickel release (eg, as occurs with ear piercing or with
products used daily in childhood such as toys, belt buckles, and electronics).
To reduce exposure to metal sources with high nickel release by prolonged
and direct contact with human skin, Denmark and the European Union
legislated a directive several decades ago with the goal of reducing high nickel
release and the incidence of Ni-ACD. Since then, there has been a global
reduction in incidence of Ni-ACD in population-based studies of adults and
studies of children and young adults being tested for allergic contact
dermatitis. These data point to nickel exposure as a trigger for elicitation of
Ni-ACD and, further, provide evidence that legislation can have a favorable
effect on the economic and medical health of a population.
This policy statement reviews the epidemiology, history, and appearances of
Ni-ACD. Examples of sources of high nickel release are discussed to highlight
how difcult it is to avoid this metal in modern daily lives. Treatments are
outlined, and avoidance strategies are presented. Long-term epidemiological
interventions are addressed. Advocacy for smarter nickel use is reviewed. The
American Academy of Pediatrics supports US legislation that advances safety
standards (as modeled by the European Union) that protect children from
early and prolonged skin exposure to highnickel-releasing items. Our nal
aim for this article is to aid the pediatric community in developing nickel-
avoidance strategies on both individual and global levels.
aDepartments of Dermatology and Pediatrics, Mt Sinai Hospital and
Icahn School of Medicine at Mt Sinai, New York, New York; bNorthern
Light Health, Bangor, Maine; cCollege of Medicine, University of New
England, Biddeford, Maine; dDepartment of Dermatology, Loma Linda
University, Loma Linda, California; eDepartments of Medicine and
Pediatrics, University of California, Riverside, California; and
fDepartment of Pediatrics, Boston Childrens Hospital and Harvard
Medical School, Boston, Massachusetts
Policy statements from the American Academy of Pediatrics benet
from expertise and resources of liaisons and internal (AAP) and
external reviewers. However, policy statements from the American
Academy of Pediatrics may not reect the views of the liaisons or the
organizations or government agencies that they represent.
Drs Silverberg, Pelletier, Jacob, and Schneider fully participated in the
conceptualization, drafting, and revision of this manuscript, and all
authors approved the nal manuscript as submitted.
The guidance in this statement does not indicate an exclusive course
of treatment or serve as a standard of medical care. Variations, taking
into account individual circumstances, may be appropriate.
All policy statements from the American Academy of Pediatrics
automatically expire 5 years after publication unless reafrmed,
revised, or retired at or before that time.
This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors have led
conict of interest statements with the American Academy of
Pediatrics. Any conicts have been resolved through a process
approved by the Board of Directors. The American Academy of
Pediatrics has neither solicited nor accepted any commercial
involvement in the development of the content of this publication.
DOI: https://doi.org/10.1542/peds.2020-0628
To cite: Silverberg NB, Pelletier JL, Jacob SE, et al. AAP
SECTION ON DERMATOLOGY, SECTION ON ALLERGY AND
IMMUNOLOGY. Nickel Allergic Contact Dermatitis:
Identication, Treatment, and Prevention. Pediatrics.
2020;145(5):e20200628
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INTRODUCTION
Nickel Is a Common Cutaneous
Allergen
Recent estimates suggest that 1.1
million children in the United States
are potentially sensitized to nickel
1
;
however, this may be a gross
underestimate given that nickel
allergic contact dermatitis (Ni-ACD) is
found in approximately one-quarter
of children who undergo patch
testing. Nickel is present in metallic
items that are common in childrens
environments, including earrings,
watches, toys, and fasteners on
clothing and belts. Chronic exposure
to nickel increases risk for Ni-ACD.
Nickel has become the most common
metallic cause of allergic dermatitis
and was named the Contact Allergen
of the Yearin 2008 by the American
Contact Dermatitis Society.
Determining the presence of Ni-ACD
in those with allergic dermatitis can
be difcult and elusive, with patch
testing being a crucial tool used to
help differentiate Ni-ACD from other
forms of dermatitis.
2
The risk of Ni-
ACD increases when ears are
pierced.
3
Nickel Exposures Are Common
Nickel is a ubiquitous metal, being the
fth most common element in the
world. Worldwide use of nickel in the
production of hardened metal items
has been increasing since World War
II.
4
The process by which nickel use
shifted from coins and military
purposes to daily use products, such
as clothes and electronics, was
strongly inuenced by metal use in
the postWorld War II era. Among
adults who were screened in
Massachusetts General Hospital from
1996 to 2006, Ni-ACD was found in
22.1% of those 20 to 40 years of age
but in only 10.1% of those older than
60 years, suggesting that Ni-ACD is
a problem of younger individuals
(those raised or those who had their
ears pierced after World War II).
5
Today, nickel has continued to be
a leading production metal in home
and personal goods. Over time, Ni-
ACD evolved from an occupational
eczema of electroplaters to a common
form of allergic contact dermatitis
(ACD) among both adults and
children, currently affecting as many
as 20% of Americans. Historically, Ni-
ACD has been linked to a wide range
of exposures, including suspenders in
the 1950s1960s; zippers, buttons,
and rivets in the 1970s; and ear
piercing in the 1980s.
4
Environmental
nickel present in oxides and suldes
is not as allergenic as the free nickel
present in metal ttings found in
industry.
4,6
Nickel Allergy Has Signicant
Symptomatology
Virtually any site of the body can be
affected by Ni-ACD, but some of the
more commonly affected areas are
the eyelids (transfer from hands),
face, neck, wrists, ngers and hands,
periumbilical area, and thighs.
7
Symptoms and signs of Ni-ACD range
from mild dermatitis with pruritus, to
deep erythema with oozing and
papulation, to a systemic reaction
with generalized idiopathic
hypersensitivity.
6,7
Although Ni-ACD
is a delayed-type hypersensitivity,
symptoms can occur within the rst
30 minutes of exposure through
a complex cascade of inammatory
mediators generated after
sensitization.
8
KEY POINTS IN THE EVOLUTION OF
NICKEL ALLERGY AS A SERIOUS
ALLERGEN
Introduction of Nickel Into the
Manufacturing of Metals
Nickel was rst identied as an
element in 1751 by a Swiss chemist
named Axel Cronstedt. In the 1800s,
nickel was introduced into the
manufacturing of metal alloys with
copper and zinc. As an alloy, its high
value is related to many inherent
qualities: high strength, lengthy life,
anticorrosion, heat resistance, low
cost, and minimal maintenance. In the
mid-1800s, coins in the United States
were alloyed with copper. In the late
1800s, steel production accelerated
because of the strength of steel
products. During the 20th century,
nickel gained a solid place in industry
as part of manufactured stainless
steel alloy (along with chromate and
iron). Today, two-thirds of nickel
production in the world is devoted to
the manufacture of stainless steel,
20% is for other specialized steel
alloys (for military and aerospace),
9% is for plating, and the remainder
is for various uses, including
batteries, coins, and electronics.
9,10
Early Reporting of Nickel Allergy
Weston et al
11
rst reported Ni-ACD
in young pediatric patients in 1984.
Until that point, it was unclear
whether cutaneous immune function
in infants was mature enough to
mount such responses. After the
report of this phenomenon by Weston
et al,
11
more attention to allergic
reactions in infants and young
children made it clear that contact
allergy to nickel can begin in infancy,
with some authors indicating
increasing incidence after the age of
5 years.
1216
Nickels place as a cause
of contact dermatitis in pediatrics
was solidied by these early reports.
Ni-ACD can cause systemic
hypersensitivity in children, and this
was elucidated in 2 articles in 2002.
Silverberg et al
16
reported a group of
30 children with clinical features of
Ni-ACD manifested by persistent
umbilical or wrist dermatitis. In that
cohort, all children had positive
results on patch testing for nickel;
furthermore, 50% had an idiopathic
hypersensitivity reaction,
a hypersensitivity response
characterized by the presence of
inammatory papules on the extensor
surfaces of the extremities in sites not
exposed to nickel.
17
A similar article
from Sharma et al
17
reviewed 38
children with periumbilical papules
consistent with Ni-ACD, all of whom
demonstrated an idiopathic
reaction.
18
Systemic contact
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dermatitis has been dened as a
generalized ACD rash from systemic
administration of a drug, chemical, or
food to which the patient previously
experienced ACD.There is no known
general population-based prevalence
of systemic nickel hypersensitivity,
neither for kids nor for adults.
Strongly positive ($3 papular) nickel
patch test results in these patients
suggest that severe reactions
correlate with systemic disease.
17
Pathophysiology and Genetics of
Nickel Allergic Sensitization
Nickel-contact allergy is a delayed-
type (type IV) cutaneous
hypersensitivity reaction that
develops through a biphasic process:
an induction phase is followed by an
elicitation phase. In the induction
phase, there are repeat exposures to
free nickel that are beyond a minimal
threshold. During this initial phase, an
antigen is presented by the skins
dendritic cells to T cells (T helper 1
and T helper 17 cells), which causes
the skin to develop a set of memory
T cells that specically recognize
nickel. During the elicitation phase,
there is amplication of the allergy
through subsequent repetitive
exposures that result in the
manifestations of ACD.
4,6,18
Ni-ACD is inuenced by
a combination of genetic and
environmental factors, the latter
being more important, according to
leading experts.
4
Filaggrin mutations
are associated with increased Ni-ACD
risk. Another genetic determinant
that may increase risk for Ni-ACD is
HLA antigen expression.
19,20
Staphylococcal biolms may promote
the development of Ni-ACD in the
setting of atopic dermatitis.
21
Menné and Holm
22
showed a twin
concordance rate of 29% in patients
with Ni-ACD, conrmed from
a population-based survey. Half of the
pediatric patients with severe Ni-ACD
with additional idiopathic reactions
had a parent with Ni-ACD in the
Silverberg et al
16
cohort, a statistic
that is higher than that in the general
population.
Product Properties That Contribute
to Allergenicity
The amount of nickel released to the
skin from contact with a metal object
(not the presence of nickel)
determines the potential for causing
Ni-ACD. The development of Ni-ACD
from contact with a nickel-containing
object is promoted in a 3-step
process: 1) the nickel in the material
must be corroded, 2) the resulting
nickel compounds must be
solubilized, and 3) the nickel ions
must be absorbed by the skin to
cause a reaction.
23,24
Other
contributory factors include the use
of products under occlusion (eg,
piercing holes) or prolonged contact
with the skin such that sweat may
erode or release nickel (eg, underside
of the thighs against a chair).
Rising Prevalence of Nickel Allergy
The prevalence of nickel allergy in
North America has increased
signicantly since the 1980s in both
adults and children. Data on
prevalence in the United States are
derived from patch testing, that is,
epicutaneous allergy testing, which
reveals contact sensitization but not
relevance of the allergy, outcomes,
and/or associated disabilities. The
North American Contact Dermatitis
Group (NACDG) reported that nickel
sensitization rates increased steadily
between 1970 and 2002 in a mixed
group of adults and children from
11% to 16.9%.
25
Pediatric-specic
data from Peltonen
26
revealed
a prevalence of Ni-ACD of 2.5% in
1981, and the NACDG series from
2001 to 2004 demonstrated 28.3% of
children with positive patch test
results were nickel allergic, showing
an increase even more substantial in
childhood than in adulthood.
27
One
series revealed that although not all
children with Ni-ACD have disabling
symptoms, for those who undergo
a patch test series, Ni-ACD represents
a common relevant allergen, being
detected in as many as 36.8% of
children and adolescents tested and
having an 80.4% relevance (ie, being
identied as contributing to
dermatitis activity).
28
Population-based screening on
individuals (including adults)
referred for patch testing have
highlighted the pervasive issue of Ni-
ACD in the United States. In 1978,
a population-based study of 1158
people identied 9% of individuals
with Ni-ACD,
1
and approximately
50% of those who were nickel allergic
had never sought medical care.
26
In
a recent meta-analysis of 5 ACD
studies representing 1507 pediatric
subjects, 22.9% had Ni-ACD.
29
The
current estimate of Ni-ACD in
children with suspected ACD who are
patch tested is 28.3% according to
the NACDG.
27
Data from Denmark are the most
revealing when evaluating European
Union (EU) nickel directives because
Denmark introduced the directives in
1990, 14 years before widespread EU
adoption. The Nickel Directive states
that consumer items intended to be
in direct and prolonged contact with
the skin were not allowed to release
more than 0.5 mcg nickel/cm
2
/week.
This legislation was intended to
reduce Ni-ACD but not eliminate
disease. The venture has been
successful in reducing Ni-ACD in
young women with ear piercings who
are patch tested. One particular
outcome has been reduced severity of
reaction on epicutaneous patch
testing to nickel, which suggests less
severity of disease. On the other hand,
because the sale of nickel-laden
agents is not criminalized, sales of
items with nickel release persist in
Europe, especially in outdoor ea
markets.
3,30
Before EU legislation, the percentage
of female rst-year college students
in Finland in 1995 with Ni-ACD was
39%, suggesting that the rate may
continue to increase further in the
United States if no population-based
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restrictions are enacted.
29,31,32
Population-based data on true nickel
allergy in adolescents derived from
survey data in Sweden reported in
2008, 7 years after EU legislation was
put into action, revealed that 14.8%
of 6095 adolescents polled believed
they had Ni-ACD, with conrmation in
9.9%, revealing how EU nickel
directives may be beneting
adolescents.
33
Data from a Danish
pediatric contact dermatology
database reveal ongoing reduction in
nickel sensitization, with ACD rates of
9.7% in those tested (252 of 2587)
from 2003 to 2011 and 7% (107 of
1540) from 2012 to 2016 (adjusted
odds ratio, 0.69; 95% condence
interval, 0.550.88). Predominance of
girls in the Ni-ACD group persisted in
this study, as with previous
studies.
33,34
Piercings and Jewelry Are Leading
Sources of Nickel Sensitization
Piercings, costume jewelry, watches,
belt buckles, and clothing fasteners
(grommets, buttons, studs, and
toggles) are leading sources of
epicutaneous nickel sensitization in
countries without legislation
controlling nickel release.
6
The same
1995 Finnish study of rst-year
college students revealed that
piercings in female students were
associated with a rate of 42% nickel
allergy, compared withs 14% for
female students without piercings.
31
A study of 960 girls 8 to 15 years of
age in Sweden (published in 1985)
with piercings revealed that 13%
were nickel allergic, compared with
1% of girls without piercings.
23
In
patch testing of school-aged girls for
Ni-ACD from 1999 to 2000, older girls
who had piercings before Danish
regulations were implemented were 4
to 5 times as likely as those who had
piercings after regulations to be
allergic to nickel (17.1% vs 3.9%,
respectively). A Norwegian pediatric
contact allergy study of 7- to 12-year-
old schoolchildren, published in 1994,
identied a rate of 30.8% nickel
allergy in children with piercings,
compared with 16.3% in children
without piercings.
35,36
Nickel allergy
in girls with pierced ears has
dramatically decreased in Denmark
over the last 3 decades since strict
nickel-release legislation was
enacted.
14
Although piercings have
been linked to nickel sensitization,
occurrence of Ni-ACD is also common
in children without piercings;
therefore, reduction of nickel release
is needed across all costume jewelry
types.
6
A recent review of NACDG
data revealed that of 1894 pediatric
patients who were patch tested,
23.7% had nickel contact dermatitis
and 36.4% had a pattern of skin
disease consistent with all types of
jewelry as the source of the nickel.
37
The High Cost of Nickel Allergy in the
United States
The 2004 estimates in the United
States suggest that contact dermatitis,
which includes nickel sensitization,
accounted for $1.918 billion in health
care costs (including direct medical
costs and lost productivity costs) and
affected 72.29 million people. Given
that nickel-contact sensitization is
noted in approximately one-quarter
of patients, it is likely that nickel
allergy contributes heavily to this
burden.
24
Recent data from the
American Academy of Dermatology
reveal that contact allergy costs more
than $1.5 billion in 2013.
38
Given that
nickel allergy is the number one
allergen nationwide in all age groups,
nickel allergy is costly.
Other Sources of Nickel-Contact
Sensitization
Contact with commonplace nickel
alloy metallic products, such as toys,
can lead to nickel release that
deposits on a childs skin.
39,40
In
a recent radiograph uorescence
spectroscopy study of US jewelry, 79
of 96 samples released nickel.
41
In
a case series of children and
adolescents from Brazil, the source of
nickel exposure in the setting of Ni-
ACD included jewelry piercings; metal
clothing appliques on garments,
accessories, and shoes; nail clippers;
razor blades; and cosmetics.
1
Newer
nickel sources reported to cause
dermatitis include devices such as
metallic cell phone cases (a persistent
plaque on the hollow of the cheek),
laptop cases and handheld device
cases (ngertip, hand, lap, and
periocular dermatitis), makeup
applicators and ferrules (site of
application), eye makeup, dog tag
necklaces, and lip balm containers
(lip and perioral).
4248
Table 1
contains a brief compendium of items
of daily use linked to nickel exposure
and allergy.
4,6
Many of these newer
nickel sources are more difcult to
diagnose because the site of allergy
can be areas not in direct contact, for
example, the eyes.
43
The timing and
type of nickel exposures throughout
life are important. Ni-ACD was shown
to be much less common when ear
piercing occurred after placement of
metal dental braces, compared with
when piercing occurred before
exposure to braces. So, less nickel
sensitization may occur if placement
of braces occurs rst and piercing
later.
44
This phenomenon may be
analogous to the enteral tolerance
that develops to lessen peanut allergy
and may be akin to reasoning
forwarded by the Learning Early
About Peanut Allergy study.
49
THE CLINICAL APPEARANCE OF NICKEL
CONTACT DERMATITIS IS PROTEAN
Ni-ACD commonly is diagnosed on
the basis of the appearance of itchy,
persistent, erythematous, and/or
lichenied papules and plaques that
appear to conform to the area
matching the exposure pattern of the
metal object with the skin, for
example, a circular erythematous
plaque on the extensor wrist at the
site of exposure to the backside of the
wristwatch. Ni-ACD can also be
caused by a child playing with
a nickel-releasing object and then
transferring the nickel to other
sites.
1,45,46
Ni-ACD has also been
described with nail polish from
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a bottle with nickel metal balls
included.
47
This itchy rash is often
diffuse and can occur on other less
common areas, such as the scalp and
eyelids.
Other jewelry-related patterns of
appearance include a plaque over the
upper back at the site of a necklace
clasp pressed against the skin,
periumbilical plaques at the site of
belt buckle or button y skin contact,
midback plaques where bra hooks
press against the skin, and earring
plaques and/or nodules at the site of
piercing because of exposure to
highnickel-releasing earring
posts.
16,17,48
Dental amalgams are
rarely high nickel releasing, but they
still can cause oral lesions such as
persistent oral lichenoid reactions
near the amalgam, anesthetic
sensation, and/or systemic lesions.
52
When the source of nickel shifts
against the skin, (eg, chair nail heads,
belt buckles, and coins in the pocket),
the contact dermatitis may be more
papular and/or diffuse, making the
source less obvious. Furthermore,
patients with atopic dermatitis may
have background disease activity that
prevents the margins of the Ni-ACD
from being clearly
distinguished.
4,16,17,53
In adults,
nickel has been identied as a contact
allergen that can worsen
palmoplantar or scalp psoriasis.
54
Idiopathic reactions, or diffuse
hypersensitivity reactions, to nickel
can occur. These may be associated
with dietary or complementary
supplements as the source of nickel
ingestion,
55
creating generalized
pruritus and exacerbating pruritus at
the site of cutaneous nickel exposure,
or they may come from a generalized
idiopathic hypersensitivity reaction
triggered by ongoing cutaneous
exposures (a type of systemic contact
dermatitis), the latter of which is
manifested by extensor papules and
lichenoid (at-topped) papules and
plaques over extensor surfaces.
Idiopathic reactions (also called
dermatophytid) are similar to those
seen in some patients with tinea
capitis when starting oral griseofulvin
therapy.
4,6
Dental amalgams, caps, and braces
that contain or release nickel in
higher concentration are associated
with perioral Ni-ACD as well as Ni-
ACD in eccentric sites such as ears,
the waist, and wrists. Ni-ACD may
precede or be caused by dental
devices containing nickel.
Furthermore, such Ni-ACD can be
associated with lip swelling and
a burning oral sensation.
52,5658
Although most allergic reactions to
nickel are of a type IV delayed-type
hypersensitivity, rare reports have
appeared in the literature of
individuals with systemic nickel
hypersensitivity of a type I or
immediate-type hypersensitivity.
Other types of allergic reactions to
nickel may occur after oral nickel
exposure, causing symptoms as minor
as ares of earlier nickel-allergic
eczema sites, to a generalized
maculopapular or vasculitislike rash,
to more severe symptoms, including
urticaria, headache malaise, diarrhea,
fever, and arthralgia.
59,60
Skin prick
testing has been performed in rare
cases but remains
controversial.
52,59,60
It is still most
likely, even in such settings, that the
reaction to nickel is a delayed-type
hypersensitivity because rapid
TABLE 1 Sources of Nickel Exposure in
Children
Sources
Artwork
White metal statues
Cleaners and detergents
Steel wool
Coins
Cooking
Pans
Pots
Stainless steel cookware used to cook acidic
foods
Utensils (eg, silverware, spatula, and tongs)
Electronics
Batteries
Cell phone cases and electric shavers
a
Mobile phones
a
Laptops
a
Tablets
a
Foods (Mislankar and Zirwas
50
and Sharma
51
)
Especially canned food
Seafood
Beans
Chocolate
Furniture
Brushed-metal furniture
Metal ttings and studs
Grooming
Nail clippers
Razors
Hair clips
Bobby pins
Metal brushes
Curling irons
Implants
Cardiac
Dental
Orthopedic
Keys
Makeup
Eyelash curlers
Ferrules
Lip balm containers
Musical instruments
Horns
Wind instrument mouthpieces
Occupational
Metal workers
Miners
Hospital cleaning staff
Ornamentation
Accessories
Ball and chain necklaces
a
Belt buckles and/or belts
a
Button ies
a
Glasses
Grommets
Jewelry (costume, white gold, and low-karat
gold)
a
Earrings
a
Necklaces
a
Rings
a
Watches
a
TABLE 1 Continued
Sources
Overalls
Rivets
Snaps
Zippers
Scissors
Tools
Toys
Adapted from Jacob SE, Goldenberg A, Pelletier JL,
Fonacier LS, Usatine R, Silverberg N. Nickel allergy and
our childrens health: a review of indexed cases and
a view of future prevention. Pediatr Dermatol. 2015;32(6):
77978 and Tuchman M, Silverberg JI, Jacob SE, Silver-
berg N. Nickel contact dermatitis in children. Clin Der-
matol. 2015;33(3):320326.
a
The most commonly identied nickel-allergy sources in
clinical practice.
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reactions as fast as 10 to 30 minutes
can be described in Ni-ACD delayed
type.
61
The data on these cases are
extremely limited, and no
recommendation can be made until
additional broad-based population
data become available for testing.
OVERLAP WITH ATOPIC DERMATITIS
The NACDG demonstrated that 34%
of children with a positive contact
allergy result on testing had
concurrent atopic dermatitis.
62
In
children with atopic dermatitis, Ni-
ACD can trigger severe exacerbations
of pruritus.
6
In the setting of atopic
dermatitis, Ni-ACD overlap is
associated with more extensive atopic
dermatitis and greater difculty in
diagnosing Ni-ACD.
7
Because the
background population data on nickel
allergy does not differ in prevalence,
Ni-ACD can only be viewed as an
aggravating or obscuring factor and
not necessarily as a cause of disease.
MANAGEMENT OF NI-ACD
The broad goals of medical therapy in
Ni-ACD are as follows:
1. identication and avoidance of
nickel;
2. treatment of skin inammation;
and
3. restoration of the skin barrier and
skin protection.
Identication and Avoidance of
Nickel
Identifying sources of nickel requires
investigation of personal adornments,
hobbies (eg, instruments played), and
jobs (eg, leisure-time activities and
review of everyday device usage).
Patients should be asked about
garments or uniforms worn at work
or school. Avoidance of nickel can be
enhanced through testing objects for
nickel content (see Avoidance of
Nickel Exposure in Childhood
section). Using Table 1 as a guide,
pediatricians can ask patients
targeted questions to determine
nickel sources hidden in daily
activities.
One of the hallmarks of good clinical
care in ACD is education on how to
avoid allergen-laden goods. Such is
the case in Ni-ACD. Patients with Ni-
ACD can be counseled to recognize
objects that may be high-release
nickel, to test such objects, and to
protect the skin from prolonged and
direct contact with the objects.
Table 2 is a handout that can be used
to help educate parents and children
and adolescents about nickel
avoidance. In general, piercing with
nickel-free earrings can minimize risk
of Ni-ACD, as can use of low-release
nickel, but the latter still results in
some release of nickel. Sterling silver
(which is 92.5% pure silver), 18-karat
yellow gold (which is 75% gold) or
more-pure gold, platinum, titanium,
and plastic earrings are alternatives
that have low or no nickel content.
Silver that is not sterling, such as
nickel silver, 800 silver (80% silver),
and German silver (which contains no
silver at all; an alloy of nickel and
zinc), are not ideal for the patient
with Ni-ACD.
Treatment of Skin Inammation
Inammatory symptoms, including
eczematous changes and pruritus, are
the main symptoms of Ni-ACDinduced
inammation. There is no US Food
and Drug Administrationapproved
therapy for Ni-ACD; however, Ni-ACD
is a steroid-responsive dermatosis,
and therefore topical corticosteroids
may be helpful in conjunction with
prevention of retriggering of
dermatitis through avoidance of
suspected sources of nickel exposure
and with therapeutics to aid in
pruritus or itch reduction. Although no
specic regimen of topical
corticosteroids has been endorsed by
any organization for Ni-ACD, the
American Academy of Pediatrics
recommends choosing the
corticosteroid class on the basis of the
site of application and severity. Like in
atopic dermatitis, off-label use of
topical calcineurin inhibitors (eg,
pimecrolimus and tacrolimus) can be
effective in steroid-resistant Ni-ACD
cases.
63,64
These topical therapies are
used in combination with nickel
avoidance, which is the cornerstone of
treatment of Ni-ACD. Prevention is
TABLE 2 Handout for Patients
Nickel is a metal that is added to many metal objects to harden them. Nickel can be found in almost all
costume jewelry (including earrings, necklaces, watch backs, rings, and bracelets), some belt
buckles, and such jewelry as ball and chain necklaces, dog tags, metal tabs, grommets, and button
ies.
When you sweat, the nickel is released from the metal, even if it is only a small amount or percentage of
the metal. Stainless steel is a stronger white metal and does not release nickel as easily.
If you are allergic to nickel, your rash will keep returning until you avoid nickel completely. There are
many steps required to avoid nickel completely. It is not easy, but it is necessary to make you feel
better.
1. Remove all nonessential metal from your clothing; replace button ies with plastic buttons and
wear a belt that ties or has a plastic buckle.
2. For metal that you cannot remove, such as grommets on the side pockets of your jeans or the back
of your watch, coat with 2 coats of clear nail polish every week or after washings.
3. Avoid sitting in shorts on metal chairs or plastic chairs with metal tabs.
4. Do not cook acidic foods in stainless steel cookware. Avoid stainless steel cookware if you can.
5. Tucking in your shirt does not prevent you from reacting to the nickel in your belt buckle or button
y.
6. Avoid ear piercing, especially if dental work, such as braces, is expected.
7. Sources of nickel in jewelry include costume jewelry, including earring posts that are not stainless
steel, white gold, and all low-karat gold jewelry. Sterling silver and high-karat yellow gold jewelry
are expected to have a low content of nickel but are not generally nickel free.
8. Tests to look for nickel released from household metals can be found at the following Web sites:
https://nonickel.com/collections/nickel-test-kit-for-jewelry-and-meteorites and https://www.
delasco.com/spot-test-for-nickel/. More information can be found at https://athenaallergy.com/
pages/how-to-test-for-nickel-using-nickel-alert-dimethylglyoxime-test.
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paramount because there is no cure
for Ni-ACD and because the disease
is lifelong.
65
In recalcitrant cases or
in the setting of severe Ni-ACD and
severe pruritus or for those with
widespread lesions, oral steroids
for several days and then tapered,
together with antihistamines for
pruritus, can aid in symptomatic
resolution.
66
Restoration of the Skin Barrier and
Skin Protection
Emollients can be used to enhance
the skin barrier in children with
atopic dermatitis and may benet
children with Ni-ACD and concurrent
dermatitis symptoms. Skin protection
can be achieved through thick
physical blockage of nickel-containing
metal objects, for example, cell phone
cases, backing button ies in denim,
or replacing metal buttons with
plastic buttons. Thin fabrics and
strategies such as tucking in ones
shirt may not be fully protective.
4,53
Conrmation of Suspected Ni-ACD
When a typical pattern of Ni-ACD
appears on the wrist or periumbilical
region, no conrmatory testing is
needed.
16,17,67
In some cases in which
suspicion is harder to conrm, patch
testing, otherwise known as
epicutaneous skin testing, is a form of
testing in which a dilute version of
the allergen is placed in
a hypoallergenic well (sometimes
called a Finn chamber) and applied to
the back. Contact time with the skin
of the upper back or inner upper
arms is up to 48 hours. After this
period, the patches are removed, and
the test results are read. The patches
are read again at a delayed point
between 72 and 120 hours after
placement. Interpretation of results is
based on the appearance of redness
and/or papules and/or a plaque in
the shape of the chamber. Papular
($3 severity) reactions at the site of
testing are common in nickel allergy
in children, and they can be
associated with idiopathic systemic
hypersensitivity. If the testing result
is negative but clinical history
supports Ni-ACD, a late reading
should be considered 7 to 10 days
after the patch test application. There
is a US Food and Drug
Administrationapproved series of 36
patches (T.R.U.E. Test; SmartPractice,
Phoenix, AZ) that contains nickel at
200 mg/cm
2
nickel sulfate, which
corresponds to 160 mg of nickel per
patch. In pediatrics, standardized
comprehensive patch testing is often
custom tailored by history, and
testing is performed with nickel
sulfate hexahydrate 2.5% in
petrolatum, as would be found in the
American Contact Dermatitis Society
Core series.
4,53
Broad-metal contact
allergy screening should be
performed when multiple metals are
suspected as the potential source of
contact dermatitis. This screening can
be accomplished by using an
epicutaneous metal contact allergy
panel containing nickel, gold,
titanium, copper, cobalt, zinc, and
more than a dozen other metals.
Although children with obvious nickel
allergy usually do not need
conrmatory patch testing for nickel,
they may need testing for other metal
allergens when metal appliances for
dental work or implants are
needed.
68,69
In particular, the Nuss
procedure, which is a placement of
metal rods for the repair of pectus
excavatum, has been associated with
complications in patients with metal
allergy, especially to nickel.
Consequences include extensive
granulation tissue formation,
localized edema, dermatitis,
lymphadenopathy, pleural effusion,
and inammation and/or infection,
which may require removal of
stainless steel rods in some cases.
70,71
Because of the potential
consequences of undiagnosed Ni-ACD
in such patients, surgeons performing
the procedure often refer patients for
patch testing to nickel and other
metals before the procedure.
72
Stainless steel discs provided by the
manufacturer are suboptimal to
screen for metal allergy and Ni-ACD
in this setting; it is more prudent to
proceed with patch testing by using
the extended metal series.
73
Titanium
bars can be used safely in patients
with Ni-ACD if they are identied
before surgery as having no
previously reported allergic events.
70
PREVENTION OF NI-ACD
Avoidance of Nickel Exposure in
Childhood
Ni-ACD is a threat to pediatric public
health that persists as a problematic
skin disease into adulthood. Ni-ACD is
the most common cutaneous allergy
and involves lifelong hazards that can
affect peoples lives both personally
and professionally.
74
Common
cutaneous nickel-containing items
include earring posts, belt buckles,
jewelry, zippers, snaps, clasps,
grommets, electronics, coins, keys,
paper clips, chairs, braces, and
implants.
2,24,45,7577
To reduce the
risk and severity of Ni-ACD,
avoidance of skin contact with nickel
is critical. According to European
reports, earrings appear to be the
most common source of elicitation of
Ni-ACD, providing credence to take
preventive and economic measures.
The United States should heed the
European lead to reduce nickel
release from common contacts in
children to serve and protect
population health. Using the handout
in Table 2, parents can identify
sources of high-release nickel in their
childrens lives. The purchase of items
with no nickel or with a low release of
nickel can be guided by the use of the
dimethylglyoxime test, which
indicates a pink or red color on
exposure to a nickel-releasing
metallic item. Currently, because of
the lack of labeling of lownickel-
release or nickel-free metal items,
parents can screen metal objects for
nickel release using such test kits,
which can be purchased on medical
Web sites (eg, https://www.delasco.
com/spot-test-for-nickel/ and
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https://athenaallergy.com/pages/
how-to-test-for-nickel-using-nickel-
alert-dimethylglyoxime-test).
78
However, it would be more ideal if
labeling of lownickel-release or
nickel-free items was available for
parents.
Reduction in Dietary Nickel Exposure
Withdrawal diets in children cannot
be recommended because of
inadequate pediatric data and risk of
malnutrition with a limited
diet.
50,79,80
Data on the use of low-
nickel diets in children are
lacking.
51,81,82
Advocacy
Ni-ACD represents a signicant and
preventable pediatric public health
burden. Regulation of nickel release
in materials that comes in contact
with skin can decrease both the high
pediatric prevalence and treatment
costs of the disease. There is a call in
the United States for such regulation
2
given the high number of children
affected by this disease. The
American Academy of Dermatology
has recently accepted a proposal in
support of reduced nickel release in
manufacturing.
82
Adoption of
legislation similar to that in the EU by
the US Congress would represent
a promise for prevention by starting
to reduce the nickel-related health
burden.
A REVIEW OF EU POLICY
Nickel is ubiquitous, and people are
exposed to it primarily via metal
objects throughout their lifetimes.
Preventive models of safer exposures,
or those less likely to trigger Ni-ACD,
have been demonstrated by other
countries to be medically and
economically benecial. The EU
Nickel Directive of 1994 (approved
June 30, 1994, and in full effect June
2001) regulated the method for
measuring nickel release onto human
skin and established regulations for
nickel allowed to be released onto
exposed skin over time, including for
watches, buttons, zippers, and now
mobile phone cases.
83
The EU
directive was born from the original
work in Denmark, where the Nickel
Directive was designed to limit the
maximum release of nickel in contact
with human skin to an amount less
than 0.2 µg/cm
2
per week for posts
inserted into pierced skin and not
more than 0.5 µg/cm
2
per week for
products with prolonged and direct
skin contact.
83,84
The European
standard EN 1811:20111A1:2015 is
a standardized testing system that is
approved by the EU to measure the
potential amount of nickel release
under the conditions of direct and
prolonged contact with the skin.
Articles, such as those used for
earrings in children, should not
release nickel more than 0.2 mg/cm
2
per week (by EN 1811 testing) to
prevent children from becoming
allergic to nickel or having
a dermatitis reaction if they are
already allergic to nickel. This nickel-
release rate is for the parts of
earrings that are in contact with the
skin and within the pierced part of
the ear.
4,83
Germany and Sweden
joined in the legislation and
eventually Korea and China did as
well.
83
Because the rate of release of nickel
(and not nickel content itself) is
important and relevant in
determining whether there is a risk
for Ni-ACD, articles may contain
nickel but not cause a dermatitis
reaction. For example, surgical
stainless steel (grade 316L), which
contains 10% to 15% nickel and does
not release nickel more than 0.2 mg/
cm
2
per week (by using EN 1811
testing), is therefore regarded as
appropriate for use in articles in
direct and prolonged contact with the
skin. The American Section of the
International Association for Testing
Materials Standard Consumer Safety
Specication for Adult Jewelry
(designation: F2999-13) lists surgical
stainless steel (typically containing
10%15% nickel) as one of the
approved materials for adult body-
piercing jewelry.
4,84,85
The effect of the Danish decree was
a drastic decrease in pediatric nickel
sensitization from 24.8% to 9.2%.
85
Reduction in Ni-ACD after Denmarks
Nickel Directive resulted in cost
savings that grew to more than $2
billion (US dollars) over the 2
decades after implementation.
4
The
EU followed the commanding lead of
the Danish dermatologists who
worked with the Danish ministry to
advance this innovative health
directive. In 2006, the Nickel
Directive was incorporated into the
EU regulation of toxins, which is
called Registration, Evaluation,
Authorization, and Restriction of
Chemicals (REACH).
84
After this
regulation, there was a signicant
reduction of Ni-ACD in patients
younger than 30 years studied in
European countries.
83
National
databases involving 180 390 patients
with suspected ACD reveal an
approximately 10% reduction in Ni-
ACD in young women, specically
from the following 4 countries, in the
years 19852010: Denmark,
Germany, Italy, and the United
Kingdom (20042010 only).
REACH is a complex bill that outlines
industry obligations regarding 30 000
chemicals. REACH is far more
reachingthan is the US counterpart,
the Toxic Substances Control Act
(TSCA) of 1975,
86
which regulates
chemicals but does not differentiate
toxic from nontoxic chemicals. The
TSCA was supplanted by the Chemical
Safety for the 21st Century Act,
introduced in the Senate in 2015 and
passed in the House of
Representatives in May 2016.
Although the TSCA required the
Environmental Protection Agency
(EPA) to consider least burdensome
chemical regulations for industry, the
Chemical Safety for the 21st Century
Act tasks the EPA to focus on
unreasonable risk to human health
and the environment; however,
unfortunately, this may not apply to
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jewelry and cosmetics.
8688
Although
the EPA acknowledges the hazards of
nickel as a cause of ACD, no current
ruling restricts nickel exposures in
childhood; however, this regulatory
foundation has room to act to reduce
risk for Ni-ACD in children.
8689
The
United States stands to improve
collective health status and lower
related medical costs if it were to
follow Denmarks lead and the EU
model in protecting the public from
the hazards of high nickel exposure.
Stakeholders may note that the
nonprot organization Nickel
Producers Environmental Research
Association does support the
elimination of high-release nickel
alloys and plating used in products
with dermal contact such as jewelry
and electronics.
7,90
US legislators
should advance evidenced-based
policies to adopt a twofold guideline:
(1) adoption of the EU guidelines on
nickel release in manufacturing and
(2) adoption of a policy to avoid
usage of nickel in plating in
household electronic devices. If the
United States can incorporate safety
directives and sound
recommendations regarding nickel
production and usage, as has been
done in the EU, then the population
can achieve signicant reductions in
Ni-ACD in the next 2 to 3 decades.
RECOMMENDATIONS
The following are recommended to
reduce the US pediatric burden of Ni-
ACD:
1. To minimize nickel-induced ACD
in children, use of nickel in the
manufacture of items that have
direct or prolonged contact with
the skin (eg, jewelry, electronic
devices, toys, etc) should be
limited. Regulations similar to the
EU Nickel Directive that limit the
weekly allowable release of nickel
to less than 0.5 µg/cm
2
/week
should be adopted.
2. Additional safety and toxicity
studies are needed to better
understand the complex
relationship between nickel
exposure and population health.
3. Companies and industries using
metal in products should
voluntarily create labeling for
lownickel-release products and
Web-based resources to identify
those items in the United States
that follow EU legislation
guidelines, allowing individuals
who are nickel allergic to shop
more wisely. Ideally, the
development of trustable
resources for those with Ni-ACD
can be met through physician and
industry partnership to develop
educational resources about nickel
allergy that can be easily
understood and accessed by
children, parents, and teachers.
4. Physicians and other health care
providers can support the
reduction of Ni-ACD by
encouraging parents to request
that posts for piercings in their
childrens ears be made of
surgical-grade steel with low
nickel release, per EU standards. It
is recommended that all
individuals who perform piercing
services mention Ni-ACD as
a potential complication of
piercing.
5. Nickel allergy can be genetic;
therefore, physicians and other
providers should consider
educating at-risk groups to avoid
nickel-based body piercings. There
is further genetic reason to believe
that children from families with
a history of Ni-ACD would benet
from reduced exposure in
childhood through the universal
use of lownickel-releasing
jewelry.
6. It is likely that most children
would benet from lower
exposure to such contact, even in
the absence of family history of Ni-
ACD, because such family history
is only present in approximately
half of cases of documented
disease.
7. If orthodontic metal braces are
anticipated, families should
consider delaying ear piercing
until after dental work is
completed.
8. Until such legislation can be
passed, voluntary manufacturer
reduction of nickel-releasing metal
in childrens clothing and close
contacts, including grommets,
button ies, belt buckles, school
chairs, and tables, aimed for use by
children would reduce Ni-ACD
disease burden. Reporting of
voluntary reduction on labels and
on public Web sites would help
parents of children and
adolescents with Ni-ACD identify
hypoallergenic metal objects,
further enhancing reduction of
disease symptomatology and
burden.
CONCLUSIONS
Ni-ACD is a common chronic
dermatitis with detrimental effects on
children now and as they progress
into adulthood. The burden of
symptoms and cost is high. The
United States can act on EU data
revealing that legislation to limit
exposures in childhood, especially
with earrings, can impact the
prevalence and potentially the
severity of disease. Until and even if
legislation is available, pediatricians
can help patients by identifying the
allergy early and intervening with
a plan of prevention and care of
disease.
LEAD AUTHORS
Nanette B. Silverberg, MD, FAAP, FAAD
Janice L. Pelletier, MD, FAAP
Sharon E. Jacob, MD, FAAP, FAAD
Lynda C. Schneider, MD, FAAP
SECTION ON DERMATOLOGY EXECUTIVE
COMMITTEE, 20182019
Bernard Cohen, MD, FAAP
Kimberly A. Horii, MD, FAAP, Chairperson
Leonard Kristal, MD, FAAP
Sheilagh M. Maguiness, MD, FAAP
Megha Mathakia Tollefson, MD, FAAP
PEDIATRICS Volume 145, number 5, May 2020 9
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Miriam G. Weinstein, MD, FRCPC, FAAP
Teresa S. Wright, MD, FAAP
Albert C. Yan, MD, FAAD, FAAP, Immediate
Past Chairperson
LIAISON
Nicholas V. Nguyen, MD Section on Early
Career Physicians
STAFF
Jennifer Gorlewski, MHA
SECTION ON ALLERGY AND IMMUNOLOGY
EXECUTIVE COMMITTEE, 20182019
Elizabeth C. Matsui, MD, FAAP, Chairperson
John A. Bird, MD, FAAP
Carla McGuire Davis, MD, FAAP
Vivian Pilar Hernandez-Trujillo, MD, FAAP
Jordan S. Orange, MD, PhD, FAAP
Michael Pistiner, MD, MMSc, FAAP
Julie Wang, MD, FAAP
LIAISONS
Todd A. Mahr, MD, FAAP American College
of Allergy, Asthma, and Immunology
Paul V. Williams, MD, FAAP American
Academy of Allergy, Asthma, and Immunology
STAFF
Debra L. Burrowes, MHA
ABBREVIATIONS
ACD: allergic contact dermatitis
EPA: Environmental Protection
Agency
EU: European Union
NACDG: North American Contact
Dermatitis Group
Ni-ACD: nickel allergic contact
dermatitis
REACH: Registration, Evaluation,
Authorization, and Re-
striction of Chemicals
TSCA: Toxic Substances
Control Act
Address correspondence to Nanette B. Silverberg, MD. E-mail: nanette.silverberg@mountsinai.org
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2020 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Dr Jacob has indicated she is the Past President and is serving her last year on the Executive Director Board of the American
Contact Dermatitis Society.
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... Nickel-allergic contact dermatitis is the most common delayed-type (type IV) cutaneous hypersensitivity reaction. 13 In Finland, children with ear piercings were more likely to exhibit a reaction to nickel than those without pierced ears (31% vs 2%, P<.001). 14 Replacement with hypoallergenic earrings, avoidance of nickel-containing products, and application of topical corticosteroids are key to managing symptoms of nickel-allergic contact dermatitis. ...
... 14 Replacement with hypoallergenic earrings, avoidance of nickel-containing products, and application of topical corticosteroids are key to managing symptoms of nickel-allergic contact dermatitis. 13 Auricular perichondritis. Transcartilaginous piercing of the helix, scapha, or antihelix of the ear increases susceptibility to minor infections and perichondritis. ...
Article
Question: Ear piercing is one of the most common forms of body modification seen in children and adolescents presenting to my office. Parents of my younger pediatric patients inquire about potential post-piercing complications and risk factors associated with earlobe infections. What guidance should I give them? Also, are there any specific post-piercing complications to consider for older pediatric patients seeking second piercings in the upper cartilage area? Answer: Piercing the earlobe or auricular cartilage continues to be a popular procedure among children and adolescents. Despite its widespread practice, improper aseptic piercing technique, insufficient training, and trauma to the soft tissue during high-pressure piercing (eg, use of spring-loaded ear-piercing instruments) can increase one's susceptibility to infections, bleeding, and microfractures. Other post-piercing complications include embedded earrings, keloids, hypertrophic scarring, and cutaneous hypersensitivity. Early recognition and treatment of infections and perichondritis secondary to transcartilaginous piercings can prevent the progression of severe ear deformities requiring reconstructive surgical interventions.
... Among the metallic ions released into the oral cavity, nickel raises special health concerns and has been systematically studied [29,[32][33][34][35], including in orthodontics [9,15,[36][37][38][39][40][41][42][43][44][45][46][47][48]. Nickel is a trace element in humans [33], and its participation in important cellular functions has been reported [9]. ...
Article
Full-text available
The purpose of the present study is twofold: (i) to assess the salivary nickel, chromium, and iron concentrations and (ii) to characterize the surface microstructure of the typical commercially available Ni-containing metallic appliances during the first 12-week orthodontic treatment period. A total of 85 unstimulated saliva samples were collected from patients before treatment, after 2 days, and after 1, 4, and 12 weeks. Salivary ion concentrations were determined by inductively coupled plasma optical emission spectroscopy, and data were analyzed with the Statistical Package for Social Sciences (IBM SPSS) software. The recorded mean metal concentrations were in the ranges of 132–175 µg/L for Ni, 171–192 µg/L for Cr, and 826–1023 µg/L for Fe. No statistically significant variations were observed between the different study times, and the null hypothesis (the concentrations of metallic ions in patients’ saliva did not significantly change after the placement of the orthodontic appliances) was accepted (p > 0.05). Mean salivary metallic ions were below toxic levels, and no adverse clinical reactions were registered. The intraoral surface degradation of the fixed components was corroborated by optical microscopy, scanning electron microscopy, and energy dispersive spectrometry. Microstructural analysis after complete orthodontic procedure confirmed different corrosion types, from pitting to biocorrosion.
... Важно объяснить пациенту, что основой профилактики НАКД служит отказ от пирсинга, регулярного ношения бижутерии, в особенности, во время интенсивной физической деятельности, пребывания на солнце и купания. Пациентам с подтвержденными НАКД рекомендуется также ограничить поступление цинка с продуктами питания и водой [65]. ...
Article
The article provides basic information about nickel-associated allergic contact dermatitis (NACD). Nickel is a common metal that is commonly used in alloys for jewelry, accessories and household items. Contact with this metal often leads to the development of allergic contact dermatitis in sensitized individuals. The prevalence of NACD among the population is high: up to 19% among adults and about 10% among children and adolescents. It is noted that in female’s sensitization to nickel is observed several times more often than in males. On the risk of developing an allergic reaction to nickel, the integrity of the skin barrier, the frequency of contacts with nickel-containing household items, the presence of piercings, high humidity and hyperhidrosis are of decisive importance. Nickel ions entering the body through the alimentary route are capable of both sensitizing the body and forming tolerance to it. The pathogenesis of NACD is based on the classic delayed-type hypersensitivity reaction. The main clinical forms of this allergic dermatosis, as well as the characteristic features of the course of the disease are presented. The features of the course of NACD in patients with atopic dermatitis (AD) are analyzed in detail. The presented data clearly demonstrate that contact allergy to nickel can not only maintain, but also significantly aggravate the course of AD. The main criteria for the differential diagnosis between simple contact and allergic contact dermatitis are shown schematically. The need for early identification and termination of contact with nickel-containing household items is noted as the initial stage of NACD treatment. The main treatment for NACD is local therapy with topical glucocorticosteroids.
... The best way to reduce the widespread occurrence, is prevention of sensitization to nickel by identifying nickel releasing items and making sure they do not come in contact with skin. [2] The population should, therefore, be protected from nickelreleasing objects. [3] There have been many studies investigating nickel release from a host of metallic objects with direct and prolonged skin contact in a wide variety of global locations. ...
Article
Contact allergy to Nickel is the most prevalent contact allergy in western societies. This has led to regulation for metallic items that come into prolonged and direct contact with the skin, such as buttons on clothing, belt buckles, jewelry and watches. In Europe, the legal provision is based on a test in which there is a limit to the amount of nickel that may be released from the item to an artificial sweat solution (EN 1811). This test is costly and has reproducibility issues. The resulting undertesting of items placed on the market, leads to many nickel releasing non-compliant articles being available in spite of the regulations that are in place. In this study, the performance of the standard release test is compared to the performance of a rapid nickel spot test based on dimethylglyoxime (DMG-test). The data suggest that using the rapid DMG-test for compliance testing is sufficiently equivalent to the current gold standard of EN 1811. Previously published comparisons between the DMG-test and EN 1811 did not consider the effect of accelerated wear and corrosion testing according to EN 12472. This study shows that by applying EN 12472, the number of deviating results between the DMG-test and EN 1811 decreases significantly. Regarding consumer protection, it is necessary for wear and corrosion resistance to be considered.
... For example, Weidenhamer and co-authors [4,5] presented interesting findings in this field: they studied the release of some metals, particularly lead, in low-cost objects used by children. Although this topic has been sufficiently studied and investigated, millions of toys that are dangerous to the safety and health of consumers, and especially children [3,6,7], are seized every day by competent authorities around the world. For example, one of the main causes of this danger could be due to colorful toy cars and dolls: their plastics contain phthalates, some of which are shown to be carcinogenic or show properties which may be hazardous to human health [8,9]. ...
Article
Full-text available
Different plastic toys are on sale in the Italian market: they are sold as souvenirs and/or as toys. Such statuettes, called Gongoli, represent a famous character (a soccer player, a politician, the Pope, etc.). In particular, these products are widely sold, but the material composition is not sufficiently defined. Further, the effect of the release of dangerous compounds on human health is not sufficiently documented. Following this hypothesis, a study on eight different statuettes was carried out both for evaluating the possible presence of heavy metals and for evidencing their release from these objects. Preliminary analysis by means of EDS spectroscopy highlighted the percentage chemical composition of different products, especially the presence of total Cr and Ni. Release tests evidenced the release of Cr, Cu, Ni, and Pb: Pb reached 74 mg kg−1, which is an interesting value even if it is lower than reported in the legislation. This study should be considered preliminary due to its limitations, such as the number of items investigated and the large variability found for some elements, but it highlights a serious problem related to the classification of these products which are marketed as souvenirs but manipulated by children.
Article
Aesthetic perforations are often associated with health issues, such as itching, inflammation, or microbial infection. Accordingly, this work proposed a lacquer to be applied on the adornment accessory forming a film from which a proper drug is released. For this, lacquers were formulated containing three different permeation enhancers (limonene - LIM, propylene glycol - PG, and oleic acid - AO) combined according to a mixture design with a model anti-inflammatory natural drug (naringenin) and a soluble film-former polymer (polyvinyl alcohol). Formulations were characterized by physicochemical tests and in vitro and in vivo skin permeation studies. The lacquers were stable and provided a vectorized drug release. LIM, combined with one of the other permeation enhancers, showed a synergic effect, enhancing topical skin penetration in vitro by 53% while preventing permeation to the receptor medium. The in vivo evaluation of lacquers in rodent models showed these systems could provide higher levels of drug retention in the ear (166.4 ± 14.9 µg per ear for F4 and 174.9 ± 29.3 µg per ear for F5) compared to the control (109.2 ± 16.3 µg) without allowing its permeation into the bloodstream, confirming the local drug delivery. Moreover, the anti-inflammatory activity was achieved in the animal model developed for lacquer application on the earring, obtaining inhibition of ear swelling up to 40.8% ± 2.3 compared to the untreated ear. Thus, such an innovative lacquer proved a promising vehicle for treating affections caused by adornments, enhancing skin permeation while avoiding a systemic effect.
Article
Allergic disease represents one of the most prominent global public health crises of the 21st century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy – including allergic contact dermatitis – are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed – from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described. Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet.
Article
Nickel-induced allergic contact dermatitis (ACD) is a common skin disease. The mechanism by which nickel causes ACD is not clear. There is no treatment for it, only symptomatic therapy. However, due to the lifetime sensitization characteristics, the recurrence rate in patients is high. T lymphocytes play a key role in nickel-induced ACD. Elucidating the potential mechanism underlying nickel-induced T lymphocyte signalling might make it possible to achieve targeted treatment of nickel-induced ACD. In our study, a phosphoproteomic approach based on tandem mass tag (TMT) labelling and LCMS/MS analyses was employed. An animal model of nickel allergy was established. Splenic T lymphocytes were purified for quantitative phosphoproteomic analysis. The numbers of phosphoproteins, phosphopeptides and phosphosites identified in this study were 3072, 7977 and 10,200, respectively. Comprehensive gene ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that nickel can significantly affect the phosphorylation of the mTOR signalling pathway in T lymphocytes. Western blotting analysis was used to detect changes in the expression of autophagy-related proteins (Beclin 1, LC3II, and p62). Nickel allergy changed autophagy-related protein expression (p < 0.05). It has been demonstrated that nickel causes autophagy of T lymphocytes in the spleen. Using autophagy inhibitors to intervene, it was found that Th1 differentiation was inhibited, and the expression of Th1-related inflammatory factors was downregulated. Overall, the identification of relevant signalling pathways yielded new insights into the molecular mechanisms underlying nickel allergy and might help in the discovery and development of mechanism-based drugs.
Chapter
Unintended direct or indirect side effects of orthodontic treatment are well recognised and quite extensively described in the literature. Since some degree of mechanically induced functional restrictions, discomfort and pain are recognised to be an experience for a major part of orthodontic patients, material‐related adverse reactions (toxic/allergic) to orthodontic appliances may be misdiagnosed or go undetected. A considerable number of metals are currently used in orthodontic appliances. Some provide strength, some contribute to ‘elastic’ properties, some are added to improve the resistance to corrosion and some may be used for aesthetic reasons. Soft orthodontic removable appliances are used for different applications, for example, positioners, retainers and so‐called ‘trainers’. The orthodontist and the assisting team should be aware that they are a risk group concerning possible adverse effects derived from the materials they use.
Article
Background Contact allergy is common in children, but may be underdiagnosed. Importantly, the clinical relevance of specific allergies is subject to constant change, and it is therefore important to continuously monitor the trends and changes of contact allergies in the paediatric population. Objectives To identify possible changes in contact allergy and allergic contact dermatitis among Danish children referred for patch testing. Methods A retrospective study was performed based on patch test data from the Danish National Database of Contact allergy. The current data were compared with previously published data on Danish children referred for patch testing. Results Between 2012 and 2016, 1573 children and adolescents were patch tested. Overall, 385 (24.5%) had at least 1 positive patch test reaction. The overall prevalence was similar in boys and girls, across age groups, and in patients with and without atopic dermatitis. Statistically significant increases in contact allergy to fragrances and isothiazoliones were seen, whereas a decrease in nickel allergy was found. Conclusion Allergic contact dermatitis continues to be a common disease in children, and is even significantly increasing for some allergens.
Article
Background: Scalp psoriasis and psoriasis limited to palms and/or soles have been referred to as difficult to control psoriasis. Contact allergy has long been suspected to aggravate existing lesions and cause resistance to therapy in these psoriasis variants. Objectives: The objective of the study was to assess common contact allergens in patients with palmoplantar and scalp psoriasis and the impact of their avoidance on dermatology life quality index (DLQI). Materials and methods: A total of 54 patients with palmoplantar and scalp psoriasis were patch tested with Indian Standard Series. The patch test results were read on day 2 and day 4. DLQI was calculated before patch testing and at 1 month and 3 month in patch test positive patients after instructing allergen avoidance. Results: Sixteen out of fifty-four patients (29.62%) showed positive patch test reactions. Metal antigens like nickel and cobalt were the most common sensitizers identified. Statistically significant improvement in DLQI was observed at 1 month and at 3 month of allergen avoidance. Conclusion: Patch testing is a useful test to determine the triggering or aggravating antigens in patients with palmoplantar and scalp psoriasis and subsequent allergen avoidance should be stressed on.
Article
Background: Nickel is a common allergen responsible for allergic contact dermatitis. Objective: To characterize nickel sensitivity in children and compare pediatric cohorts (≤5, 6-12, and 13-18 years). Methods: Retrospective, cross-sectional analysis of 1894 pediatric patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. We evaluated demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources. Results: The frequency of nickel sensitivity was 23.7%. Children with nickel sensitivity were significantly less likely to be male (P < .0001; relative risk, 0.63; 95% confidence interval, 0.52-0.75) or have a history of allergic rhinitis (P = .0017; relative risk, 0.74; 95% confidence interval, 0.61-0.90) compared with those who were not nickel sensitive. In the nickel-sensitive cohort, the relative proportion of boys declined with age (44.8% for age ≤5, 36.6% for age 6-12, and 22.6% for age 13-18 years). The most common body site distribution for all age groups sensitive to nickel was scattered/generalized, indicating widespread dermatitis. Jewelry was the most common source associated with nickel sensitivity (36.4%). Limitations: As a cross-sectional study, no long-term follow-up was available. Conclusions: Nickel sensitivity in children was common; the frequency was significantly higher in girls than in boys. Overall, sensitivity decreased with age. The most common source of nickel was jewelry.
Chapter
Prosthetic hip and knee implantations rank among the most common elective operations in the United States and Europe. These implants are compositionally complex and have undergone drastic evolutions over the past several decades. Hypersensitivity reactions to hip and knee implant components are well documented in the literature but remain uncommon. They range from localized dermatitis to implant loosening and subsequent failure. Currently, patch testing is the most useful method to evaluate for metal allergy. Preimplantation testing is not necessary unless patients have a significant history of skin rashes after metal contact or previously have experienced device failure. Postoperative complications such as aseptic loosening, chronic pain, or new, unexplained local or regional dermatitis may occasionally benefit from evaluation for metal allergy. Clinical next steps following implantation may be challenging. If the implant is symptomatic, topical or systemic corticosteroids may be tried, but ultimately, the surgeon and patient may need to decide whether replacement with a less allergenic alternative is feasible and safe. Whether pre- or postoperative, clinical decisions should be made by the collaborative efforts of dermatologists, allergists, and surgeons. Prospective trials in this field are still necessary to develop an evidence-based approach to the treatment of patients with allergic reactions to metal, as current clinicians are guided largely by expert opinion.
Article
Complex immunologic pathways, influenced by both genetic and environment triggers, contribute to the development of atopic dermatitis and allergic contact dermatitis. Suppressing mechanisms between the Th1-driven allergic contact dermatitis and the Th2-driven atopic dermatitis conditions were thought to reduce the simultaneous expression of both; however, recent evidence demonstrates pediatric patients with atopic dermatitis area as likely to develop clinically relevant positive patch tests and more likely to react to specific allergens, such as lanolin. We review the potential role of skin barrier defects, such as filaggrin mutations and impaired barrier function, including aberrancies in epidermal pH buffering capabilities, which may promote bacterial biofilms and create an environment favoring sensitization.
Article
Background: Nickel in metallic items has been regulated in Denmark since 1990; however, 10% of young Danish women are still sensitized to nickel. There is a need for continuous surveillance of the effect of regulation. Objectives: To identify current self-reported metallic exposures leading to dermatitis in nickel-allergic patients, and the minimum contact time needed for dermatitis to occur. Methods: A questionnaire was sent to all patients who reacted positively to nickel sulfate 5% pet. within the last 5 years at the Department of Dermatology and Allergy, Gentofte Hospital. Results: The response rate was 63.2%. Earrings were the foremost cause of dermatitis after the EU Nickel Directive had been implemented, followed by other jewellery, buttons on clothing, belt buckles, and wrist watches. Dermatitis reactions within 10 min of contact were reported by 21.4% of patients, and dermatitis reactions within 30 min of contact were reported by 30.7% of patients. Conclusions: Nickel exposures that led to implementation of a nickel regulation seem to persist. The durations of contact with metallic items to fall under the current REACH regulation of nickel correspond well with the results of this study.
Article
Since the publication of the last US national burden of skin disease report in 2006, there have been substantial changes in the practice of dermatology and the US health care system. These include the development of new treatment modalities, marked increases in the cost of medications, increasingly complex payer rules and regulations, and an aging of the US population. Recognizing the need for up-to-date data to inform researchers, policy makers, public stakeholders, and health care providers about the impact of skin disease on patients and US society, the American Academy of Dermatology produced a new national burden of skin disease report. Using 2013 claims data from private and governmental insurance providers, this report analyzed the prevalence, cost, and mortality attributable to 24 skin disease categories in the US population. In this first of 3 articles, the presented data demonstrate that nearly 85 million Americans were seen by a physician for at least 1 skin disease in 2013. This led to an estimated direct health care cost of $75 billion and an indirect lost opportunity cost of $11 billion. Further, mortality was noted in half of the 24 skin disease categories.
Article
Patch testing data indicate that the 5 most prevalent contact allergens out of more than 3700 that are known are: nickel (14.3% of patients tested), fragrance mix (14%), the topical antibiotic neomycin (11.6%), balsam of Peru (used in some perfumes, toiletries, and pharmaceutical items) (10.4%), and the mercury-based vaccine preservative thimerosal (10.4%).
Article
Background: Contact sensitization in children is more common than previously thought, but few studies have been performed on a large population assessed by the same team. The objective was to evaluate contact sensitization in children with suspected contact dermatitis, the relationship with atopic dermatitis (AD), and the most common allergens. Methods: The same team patch tested 2,614 children younger than 11 years old with a standard series of 30 allergens. Results: A total of 1220 children (46.7%) developed at least one positive reaction, 606 of which were clinically relevant (49.7%). The most frequent reactions were to nickel sulfate (22.7%), cobalt chloride (11.1%), potassium dichromate (9.9%), neomycin sulfate (5.2%), thimerosal (4.2%), cocamidopropyl betaine (3.4%), and methylchloroisothiazolinone/methylisothiazolinone (3.2%). The prevalence of contact sensitization was similar in children with (47.3%) and without (46.1%) AD. Children with AD had a higher prevalence of positive reactions to potassium dichromate (p < 0.001), Compositae mix (p = 0.01), and disperse blue (p = 0.03). Conclusions: Contact sensitization is quite common in young children. This study adds some information on the most common contact allergens. A similar prevalence of positive patch test reactions was found in children with and without AD, but children with AD had a greater prevalence of positive patch test reactions to potassium dichromate, Compositae mix, and disperse blue.