Titanium Dioxide in Toothpaste Causing Yellow Nail Syndrome
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Titanium Dioxide in Toothpaste
Causing Yellow Nail Syndrome
Ting-Yuan Hsu, MD,a Chun-Chen Lin, MD,a,b,c Ming-Dar Lee, MD,a,b Brian Pin-Hsuan Chang, MD,a,b,d Jeng-Daw Tsai, MDa,b,d,e
Yellow nail syndrome (YNS) is an uncommon disorder, the classic triad of abstract
which consists of yellow nails, lymphedema, and respiratory symptoms.
Few pediatric cases have been reported. We report a 9-year-old girl
with yellowish nail discoloration for 1 year accompanied by respiratory
symptoms, including chronic cough, recurrent pneumonia, bronchiectasis,
and chronic sinusitis. The patient was diagnosed with YNS. Knowing that
a relationship between YNS and titanium has been reported, we collected aDepartment of Pediatrics, MacKay Children's Hospital,
her nail clippings and detected titanium in them by energy dispersive Taipei, Taiwan; bDepartment of Medicine, MacKay Medical
College, Taipei, Taiwan; cMacKay Junior College of Medicine,
radiograph fluorescence. This patient’s titanium exposure may have come
Nursing, and Management, Taipei, Taiwan; dDepartment
from her habit of swallowing children’s toothpaste. With meticulous of Pediatrics, Taipei Medical University Hospital, Taipei,
avoidance of swallowing toothpaste, she had amelioration of her yellow Taiwan; and eDepartment of Pediatrics, School of Medicine,
College of Medicine, Taipei Medical University, Taipei,
nail discoloration as well as diminution of her respiratory symptoms. We Taiwan
reevaluated her nail clippings for titanium 3 years later, and no titanium
Dr Hsu conceptualized and designed the study and
was detected. This observation suggests that avoiding titanium exposure drafted the initial manuscript; Dr Lin contributed
could alleviate the symptoms of YNS. This is the first report of YNS in to the acquisition of data and reviewed and revised
a pediatric patient that demonstrates a relationship between YNS and the manuscript; Drs Lee and Chang contributed to
the interpretation of data and reviewed and revised
titanium. We review the previous reports of pediatric patients with YNS. the manuscript; Dr Tsai examined the patient,
contributed to analysis and interpretation of data,
and critically reviewed and revised the manuscript,
and approved the final manuscript as submitted;
Yellow nail syndrome (YNS), first with chronic cough and recurrent
and all authors approved the final manuscript
described by Samman and White pneumonia. Dystrophic yellow nails as submitted and agree to be accountable for all
in 1964,1 is an uncommon disorder were noted. YNS was diagnosed aspects of the work.
characterized by the classic triad and additional respiratory imaging DOI: 10.1542/peds.2016-0546
of yellow and dystrophic nails, studies were evaluated. Titanium was
Accepted for publication Aug 31, 2016
lymphedema, and respiratory detected in the patient’s nail clippings.
Address correspondence to Jeng-Daw Tsai, MD,
symptoms. It mainly affects people The association between titanium and
Department of Pediatrics, MacKay Children’s
40 to 60 years of age and is rare the development of YNS may provide a Hospital, No. 92, Section 2, Chung-Shan North Rd,
in the pediatric population.2 Its new way to manage this condition. Taipei 10449, Taiwan. E-mail: tsaijd@yahoo.com.tw
pathophysiology and etiology remain PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
unknown. In 2011, Berglund and 1098-4275).
Carlmark3 described the relationship CASE PRESENTATION Copyright © 2017 by the American Academy of
between YNS and titanium in adults. Pediatrics
Our research was reviewed and
All of their patients with YNS had a FINANCIAL DISCLOSURE: The authors have
approved by the MacKay Memorial
history of exposure to titanium (by indicated they have no financial relationships
Hospital institutional review board. relevant to this article to disclose.
implants in the teeth or elsewhere) Informed consent was obtained from
FUNDING: No external funding.
or titanium dioxide (by ingestion the patient's mother. The patient is a
of drugs and confectionaries), POTENTIAL CONFLICT OF INTEREST: The authors
9-year-old girl who presented with a
have indicated they have no potential conflicts of
and titanium was detected in the spiking fever for 2 days and chronic interest to disclose.
nails of each patient. Until now, cough for 6 months. One month
the relationship between YNS and before presentation, she was admitted
titanium had never been reported in to another hospital with lobar To cite: Hsu T, Lin C, Lee M, et al. Titanium Dioxide
in Toothpaste Causing Yellow Nail Syndrome.
children. In this report, we describe pneumonia and was treated with oral
Pediatrics. 2017;139(1):e20160546
a 9-year-old girl who presented antibiotics after discharge. However,
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PEDIATRICS Volume 139, number 1, January 2017:e20160546 CASE REPORT
FIGURE 2
Chest computed tomographic demonstrating
bronchiectasis in the right middle lobe, left
lingula, and bilateral lower lobes. R, right side;
L, left side.
nails for additional evaluation. FIGURE 3
Nail clippings analyzed by energy Waters’ view shows bilateral maxillary sinusitis.
R; right side.
dispersive radiograph fluorescence
showed an elevated level of
DISCUSSION
titanium (11.48 μg/g−1). Titanium
was not found in the nails of her YNS is an uncommon disorder. More
family and 6 other healthy people. than 300 cases have been reported
FIGURE 1 in literature. In 1964, Samman1
Toenails and fingernails show typical features
We therefore obtained a detailed
of YNS. exposure history of titanium. The described 13 patients, all of whom
patient had no history of orthopedic had thickened and slow-growing
her productive cough and purulent or dental implants. Her parents also yellow nails, and 10 of whom also
nasal discharge did not improve. denied a history of long-term use had lymphedema. This was the
Physical examination was notable for of antibiotics or other drugs, but first reported case series of YNS.
coarse breath sounds with crackles she took antibiotics intermittently In 1966, Emerson4 added pleural
in both lower lung fields. Chest effusion as a frequent feature of YNS.
for pneumonia in the last month.
radiograph disclosed pneumonia in In 1979, Runyon et al5 described
There was no history of massive
the lower lobes bilaterally. the classic triad of YNS: yellow
consumption of confectionaries or
nails, lymphedema, and pleural
chewing gum. However, we surmised
On admission, we noticed yellowish effusion. Later, bronchochiectasis,
discoloration and thickening of nail that when our patient brushed her
rhinosinusitis, recurrent
plates in all of her fingernails and teeth, she had a habit of swallowing
pneumonia, and chronic cough
toenails (Fig 1). This manifestation a significant amount of children’s were also recognized as frequent
was first noted 1 year previously, toothpaste that contained titanium manifestations of YNS.6 Current
and the growth of her nails had been dioxide, which may be the source opinion supports the replacement
slow. High-resolution computerized of titanium detected in her nail of pleural effusion with respiratory
tomography revealed bronchiectasis clippings. manifestations as the third criterion.
in the right middle lobe, left lingula, The clinical features of YNS are
and lower lobes bilaterally (Fig In addition to optimal control of variable among individuals and can
2). Bilateral air-fluid levels in a sinusitis and bronchiectasis with vary over time. Only 27% of YNS
Waters’ view of the maxillary sinuses antibiotics and bronchopulmonary patients have all 3 classic symptoms
suggested bilateral maxillary sinusitis hygiene measures, we encouraged simultaneously.7,8 Hiller et al6
(Fig 3). the patient to avoid the habit of suggested the diagnosis of YNS can
swallowing toothpaste. The yellow be made when a patient presents
Because the patient had yellow nails
discolored nails gradually detached with 2 of the 3 classic symptoms
and respiratory manifestations,
from the nail bed in 2 to 3 months, at any given time without another
the diagnosis of YNS was made.
and new nails grew in normally explanation.
Lymphedema was not observed in
our patient, and none of her family after she discontinued swallowing In a previous study, 89% of
members had YNS. The relationship toothpaste. Her respiratory patients with YNS had yellow nail
between titanium exposure and symptoms also improved over time. discoloration.9 Typical abnormalities
YNS had been reported in a recent We reexamined her nails 3 years of the nails included yellow
study,3 so we collected the patient’s later, and no titanium was detected. discoloration, thickening, slow
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e2 HSU et algrowth, transverse ridging, excessive implants. Berglund and Carlmark3 has been reported to be associated
curvature, and onycholysis.10 hypothesized that titanium ions are with other systemic diseases, such as
YNS usually affects all 20 nails. released from titanium implants malignancy,21,22 thyroid disease,9
Improvement of nail symptoms is by galvanic actions with dental nephrotic syndrome,23 rheumatoid
often associated with treatment gold or amalgam implants or by arthritis,20 obstructive sleep disorder,24
of the respiratory syndrome.11 the oxidative action of fluorine. and tuberculosis.25 The possible
Lymphedema usually involves the Removal of gold could alleviate the explanation is that patients with
lower limbs symmetrically, but it symptoms of YNS. After Berglund systemic diseases are more likely
can also affect the upper limbs, face, and Carlmark’s study,3 there have to be taking medicines that contain
and eyelids.12 About 40% of patients been 3 subsequent reports that titanium dioxide.20
with YNS present with pleural support their findings.17–19 All of
By contrast, YNS is rarely reported
effusion. Most of the pleural effusions the reported patients had a history
in children. In reviewing the 19
are bilateral (68.3%), consisting of titanium exposure preceding the
pediatric cases of YNS reported in
of exudates with lymphocytic development of YNS. The titanium
the literature (Table 1), we found
predominance.13 levels from the patients’ fingernails
that 6 of them had a history of family
The pathogenesis of YNS remains were all elevated. Withdrawal
tendency. Yellow nails and recurrent
unknown. Some familial cases have of titanium exposure led to
respiratory infections were the most
been described14; however, most improvement of the symptoms in the
common presentations. Lymphedema
cases are sporadic or acquired. early stage of the disease,18 but did
was present in 12 cases. Pleural
The hypothesized mechanisms of not help in a patient with advanced
effusion was present in 5 cases (4
YNS include anatomic or functional disease.19
at birth and 1 later). Bronchiectasis
lymphatic abnormalities and Another source of titanium exposure was diagnosed only in 4 cases. We
microvasculopathy with protein is by uptake of titanium dioxide from find that there are 2 age peaks in
leakage.9,15,16 However, these the digestive tract. The brightness the incidence of YNS. Most pediatric
mechanisms cannot explain the and high refractive index of titanium cases of YNS presented at birth, and 2
nail abnormality, because patients dioxide have made it widely used affected infants were born to mothers
who have lymphedema of any other as a color additive or coating who had YNS.26,27 Fetal hydrops
etiology do not present with yellow agent in sunscreen, toothpaste, may be the clinical presentation
nail discoloration. medication tablets, chewing gum, of lymphedema in newborns. We
Recently, a relationship between confectionaries, and cosmetics. speculate that titanium may cross
titanium and the development of YNS that is associated with taking through the placenta from mother
YNS was reported. In 2011, Berglund medical tablets containing titanium to baby. Another peak of incidence
and Carlmark3 reported that all of dioxide has been repeatedly of YNS is between 6 and 10 years of
their patients with YNS had a history reported, and symptoms are at age, which may be explained by the
of titanium exposure. In their 34 least partially reversible after fact that children at this age have
patients, 26 had received titanium discontinuing these drug tablets.3,20 had exposure to candy or children’s
implants; the other 8 patients were For our patient, a thorough history toothpastes that contain titanium
exposed to high amounts of titanium of titanium exposure suggested that dioxide.
dioxide either in drug tablets or swallowing of toothpaste was the
Titanium is a widely used material,
in confectionaries. Nail clippings potential cause of her YNS. With
but YNS is a relatively rare syndrome.
of these patients were analyzed meticulous avoidance of swallowing
Only rarely do people exposed to
by energy dispersive radiograph toothpaste, she had amelioration
titanium ever develop YNS. The
fluorescence, and titanium was of her yellow nail discoloration
duration and amount of titanium
detected in all samples (range: and her respiratory symptoms also
exposure, sensitization to titanium
1.1–170 μg/g−1). Titanium was not improved over time. Furthermore,
or titanium dioxide, susceptibility
found in the nails of healthy people, no titanium was detected in the nails
to galvanic erosion, and other
even those exposed to titanium. 3 years later.
coexisting factors may be responsible
Titanium is a lustrous metal with a The hypothesis that YNS is related to for development of YNS. It is likely
silver color, low density, and high titanium exposure may explain some that specific patients may have an
strength. In medical uses, titanium characteristics of this syndrome. underlying genetic or immunologic
can be alloyed with aluminum Most patients with YNS are middle- susceptibility to develop YNS when
or iron, among other elements, aged adults or elderly adults, and exposed to titanium or titanium
to produce strong, lightweight these groups of patients have a dioxide. Additional research
alloys for orthopedic or dental greater prevalence of implants. YNS is warranted to determine the
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PEDIATRICS Volume 139, number 1, January 2017 e3TABLE 1 Pediatric Cases of YNS 5. Runyon BA, Forker EL, Sopko JA.
Ref. No. Age at Yellow Lymphedema Respiratory Manifestations Family Pleural-fluid kinetics in a patient
Presentation Nails History of YNS with primary lymphedema, pleural
Pleural Beronchiectasis Recurrent
effusions, and yellow nails. Am Rev
Effusion Infection
Respir Dis. 1979;119(5):821–825
26 Neonate V (fetal V Yes (mother)
hydrops) 6. Hiller E, Rosenow EC III, Olsen
27 Neonate V (fetal V Yes (mother) AM. Pulmonary manifestations of
hydrops) the yellow nail syndrome. Chest.
28 Neonate V V (fetal V No 1972;61(5):452–458
hydrops)
28 Neonate V V (fetal V No 7. Tosti A, Baran R, Dawber R. The nail in
hydrops) systemic diseases and drug-induced
29 Neonate V V (fetal V Siblings changes. In: Baran R, Dawber RPR,
hydrops) deBerker DA, Haneke E, Totsi A, eds.
29 Neonate V Yes (siblings)
Baran and Dawber's Diseases of the
29 Neonate V Yes (siblings)
Nails and Their Management, Third
30 Neonate V V No
31 Neonate V V V Not mentioned Edition. 1994:223–329
32 Neonate V No
8. Maldonado F, Ryu JH. Yellow nail
33 Neonate V V V Not mentioned
syndrome. Curr Opin Pulm Med.
34 Neonate V V V Not mentioned
12 7 mo V V No 2009;15(4):371–375
35 6y V V V V Not mentioned
9. Nordkild P, Kromann-Andersen H,
36 6y V V V Yes (father)
37 7y V V No
Struve-Christensen E. Yellow nail
38 10 y V V V V No syndrome--the triad of yellow nails,
3 15 y ? V Not mentioned lymphedema and pleural effusions.
Our case 8y V V V No A review of the literature and a
V, symptom present; ?, not recorded.
case report. Acta Med Scand.
1986;219(2):221–227
relationship between YNS and ACKNOWLEDGMENT 10. Williams HC, Buffham R, du Vivier
titanium exposure. A. Successful use of topical vitamin
We thank Garefully Technology E solution in the treatment of nail
Our patient presented with Co, Ltd, for their assistance in the changes in yellow nail syndrome. Arch
sinusitis and chronic cough, analysis of the nail sample. Dermatol. 1991;127(7):1023–1028
which are common findings in
11. Szolnoky G, Lakatos B, Husz S, Dobozy
children. Without noting the
A. Improvement in lymphatic function
nail changes, YNS can be easily ABBREVIATION and partial resolution of nails after
overlooked and underdiagnosed complex decongestive physiotherapy in
by a physician. Therefore, we YNS: yellow nail syndrome
yellow nail syndrome. Int J Dermatol.
suggest that the diagnosis of 2005;44(6):501–503
YNS should be considered in
12. Yalçin E, Doğru D, Gönç EN, Cetinkaya
children with chronic respiratory
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PEDIATRICS Volume 139, number 1, January 2017 e5Titanium Dioxide in Toothpaste Causing Yellow Nail Syndrome
Ting-Yuan Hsu, Chun-Chen Lin, Ming-Dar Lee, Brian Pin-Hsuan Chang and
Jeng-Daw Tsai
Pediatrics originally published online December 7, 2016;
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/early/2016/12/06/peds.2
016-0546
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Downloaded from www.aappublications.org/news by guest on September 8, 2021Titanium Dioxide in Toothpaste Causing Yellow Nail Syndrome
Ting-Yuan Hsu, Chun-Chen Lin, Ming-Dar Lee, Brian Pin-Hsuan Chang and
Jeng-Daw Tsai
Pediatrics originally published online December 7, 2016;
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/early/2016/12/06/peds.2016-0546
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
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the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2016
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