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CASE REPORT
Topical Selenium Sulfide for the Treatment
of Hyperkeratosis
Philip R. Cohen .Caesar A. Anderson
Received: August 13, 2018
ÓThe Author(s) 2018
ABSTRACT
Hyperkeratosis presents as thickened skin. It can
be congenital or acquired. Typically, it affects
the palms and soles; the distribution of epider-
mal involvement is either diffuse, focal, or
punctate. Microscopically, the pathologic sig-
nature of hyperkeratosis is marked orthoker-
atosis of the stratum corneum. Topical
treatments provide the mainstay of therapy for
hyperkeratosis. These include keratolytics (such
as urea, salicylic acid, and lactic acid) and reti-
noids; physical debridement, topical corticos-
teroids, and phototherapy (using topical
psoralen and ultraviolet A phototherapy) are
other local therapeutic modalities. Selenium is a
non-metallic essential element; its water-insol-
uble salt, selenium sulfide, is an active ingredi-
ent that is used (in either a foam, lotion, or
shampoo) to treat not only seborrheic der-
matitis but also tinea versicolor. Three
individuals with hyperkeratosis involving their
palms and/or soles are described; the hyperker-
atosis was successful treated with topical sele-
nium sulfide in either a 2.5% lotion/shampoo
or a 2.75% foam. The response to topical sele-
nium sulfide was not only rapid but also com-
plete and sustained; none of the patients
experienced any adverse events secondary to
the therapy. In conclusion, we recommend that
topical selenium sulfide be added to the thera-
peutic armamentarium for congenital or
acquired hyperkeratosis—particularly for those
patients with involvement of their palms and
soles.
Keywords: Foot; Hand; Hyperkeratosis;
Keratoderma; Palm; Plantar; Selenium; Soles;
Sulfide; Topical
INTRODUCTION
Hyperkeratosis presents as thickening of the
skin. Selenium sulfide is an agent that is topi-
cally used for the management of seborrheic
dermatitis and tinea versicolor. Three individ-
uals with hyperkeratosis of their plantar feet,
whose thickened skin was successfully treated
with topical selenium sulfide, are described.
Informed consent was obtained from the par-
ticipants for inclusion in the study.
Enhanced Digital Features To view enhanced digital
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P. R. Cohen (&)
San Diego Family Dermatology, National City, CA,
USA
e-mail: mitehead@gmail.com
C. A. Anderson
University of California San Diego Hyperbaric
Medicine and Wound Healing Center, Encinitas,
CA, USA
Dermatol Ther (Heidelb)
https://doi.org/10.1007/s13555-018-0259-9
CASE REPORTS
Case 1
A 38-year-old African American woman pre-
sented for treatment of plantar hyperkeratosis.
Her past medical history was significant for
spina bifida. However, she was otherwise
healthy.
Four years earlier, she was seen for evalua-
tion and management of a left trochanteric
pressure ulcer. At that time, her cutaneous
examination revealed scaling and ulcers on her
feet. She also had an ulcer overlying the left
trochanter. In addition, she had bilateral lower
extremity edema.
Her leg edema was successfully managed
with lower extremity dynamic compression
therapy. The pressure ulcer on her left tro-
chanter completely healed. The ulcers on her
feet underwent serial debridement; during these
treatments, she also required a brief course of
oral antibiotics. In addition, weekly topical
management of the foot ulcers included
antimicrobial dressings along with white pet-
roleum moisturizer. Also, antifungal cream was
applied twice daily to her toes. Subsequently,
the ulcers on her feet healed; however, the
hyperkeratosis on her feet persisted.
Four years after her initial presentation, she
returned for treatment of her plantar hyperker-
atosis. She also had calluses on her palms that
developed secondary to the use of her manual
wheelchair. Cutaneous examination of the
plantar surface of her bilateral feet showed
thickening of the skin (Fig. 1).
Initially, her feet were treated with salicylic
acid ointment 3% applied topically twice daily.
There was no improvement. The salicylic acid
topical therapy was discontinued and she began
daily treatment with selenium sulfide foam
2.75%.
She was instructed to apply the selenium
sulfide foam onto her feet and continue to rub
the area so that the selenium sulfide was in a
lather form. The foam remained present on her
feet for 10 min prior to being rinsed off. She also
continued to apply Aquaphor ointment daily,
as she had previously done.
She achieved an excellent result with the
selenium sulfide therapy; there was complete
resolution of her plantar hyperkeratosis within
2 weeks (Fig. 1). Subsequently, she was instruc-
ted to taper the selenium sulfide therapy—every
other day for 3 weeks and then as needed if the
hyperkeratosis reappeared. She continued to use
Aquaphor ointment daily.
Her feet remained clear of the hyperkeratotic
skin. Therefore, she decided to discontinue the
Aquaphor ointment and began topical treat-
ment with ammonium lactate cream 12%. The
plantar hyperkeratosis recurred; she stopped the
ammonium lactate cream 12% and treated her
feet with the selenium sulfide foam 2.75%.
Promptly, the plantar hyperkeratosis resolved.
Case 2
A 32-year-old Caucasian man presented for
evaluation and treatment of congenital hyper-
keratosis with fissures on his palms and soles.
His sister also had a similar congenital palmo-
plantar hyperkeratosis; correlation of the clini-
cal history and lesion morphology established a
diagnosis of Unna–Thost disease. In addition,
the patient’s past medical history was signifi-
cant for poorly controlled diabetes mellitus and
severe coronary artery disease with several prior
myocardial infarctions and placement of coro-
nary stents.
Cutaneous examination of the plantar sur-
face of his feet showed hyperkeratosis with
multiple fissures (Fig. 2). Prior unsuccessful
topical therapies had included salicylic acid
ointment, urea cream, ammonium lactate
cream, and high-potency corticosteroid creams
and ointments. Therefore, a decision was made
to implement selenium sulfide shampoo 2.5%.
He applied the shampoo daily and rubbed it
into his feet until it was in a lather form. Then
he allowed the shampoo to remain present for
10 min prior to rinsing it off. He also applied
Aquaphor ointment daily.
He had excellent results. There was complete
resolution of the plantar hyperkeratosis within
2 weeks after initiating therapy (Fig. 2).
Prompted by the effectiveness of the topical
selenium sulfide treatment after 1 week of
Dermatol Ther (Heidelb)
application to his feet, he began to apply it for
30 min daily not only to his feet, but also to his
hyperkeratotic hands. He tolerated this regimen
and noted significant improvement. Therefore,
the following week, he kept the shampoo lather
on his hands for up to 2 h.
Follow-up examination revealed that his
palmar hyperkeratosis had also almost com-
pletely resolved. The patient enthusiastically
discussed that none of his prior treatments had
worked this well. He was instructed to use the
selenium sulfide 2.5% shampoo on an as-nee-
ded basis and to continue to apply Aquaphor
ointment daily.
Case 3
An 80-year-old African American man pre-
sented for evaluation and treatment of exten-
sive hyperkeratosis of his lower legs and feet.
His past medical history was significant for
chronic bilateral lymphedema of his distal
lower extremities. He also had ongoing issues
with compliance to medical therapy.
Three and one-half years earlier, he was ini-
tially seen for his lower extremity lymphedema
and associated numerous verrucous keratoses
on his distal legs and feet. His management
required bilateral lower extremity compression
therapy—including manual lymphatic drainage
massage therapy—coupled with extensive
debridement of the hyperkeratotic scaly skin of
both legs. These interventions proved useful in
managing the lymphedema along with achiev-
ing a marked improvement in the extent of
papillomatous skin lesions of legs and feet.
The application of white petroleum prior to
each compression wrap to his legs was contin-
ued weekly. However, follow-up examination
showed that the hyperkeratosis of his legs and
feet persisted. Yet, most of the hyperkeratosis
responded to weekly labor-intensive superficial
curette debridement of the skin, which resulted
in the shedding of a substantial amount of
scales.
Subsequently, two and one-quarter years
ago, he was again evaluated for the manage-
ment of his lower-extremity hyperkeratosis.
Fig. 1 The right plantar foot of a 38-year-old African
American woman. There is prominent hyperkeratosis on
the medial aspect of the plantar foot (top). Complete
resolution of the plantar hyperkeratosis is observed 2 weeks
after the initiation of daily treatment with selenium sulfide
foam 2.75% (bottom). The foam was applied to the area
for 10 min prior to being rinsed off; after rinsing,
Aquaphor ointment was also applied daily
Dermatol Ther (Heidelb)
Ammonium lactate cream 12% was recom-
mended; however, the patient was unable to
tolerate the cream because of extensive burning.
When the dosage was reduced to 5%, he had the
same problem and had to discontinue the
treatment with ammonium lactate. After
2 weeks, he also complained of burning with
the 5% version.
He resumed daily Aquaphor ointment
application to his legs. In addition, he contin-
ued his maintenance compression therapy.
However, during the subsequent 2 years, the
hyperkeratotic lesions recurred on his legs and
prompted further debridement.
Cutaneous examination showed extensive
hyperkeratosis on his legs and feet (Fig. 3). Daily
application of selenium sulfide shampoo 2.5%
was started. He applied the shampoo to both
legs and feet daily in a lather form. The sham-
poo was allowed to remain present for
10–20 min each day prior to rinsing it off.
Afterwards, he continued to apply Aquaphor
ointment daily to his lower extremities.
He achieved excellent results. There was
complete resolution of his bilateral lower
extremity hyperkeratosis (Fig. 3). The daily
application of selenium sulfide shampoo 2.5%
has become part of his maintenance routine; in
addition, he has not required any debridement
of hyperkeratosis. However, he continues to
struggle with lymphedema management, and
the verrucous skin changes correlate inversely
with his edema control: more lesions are pre-
sent when his lymphedema control is worse.
DISCUSSION
Hyperkeratosis, also often referred to as kerato-
derma, can be an acquired condition or an
inherited disorder. It frequently affects the
palms and soles. It typically presents as thick-
ening of the skin; fissures and ulceration may
develop [1,2].
The classification of hyperkeratosis may be
determined by its manifestations of epidermal
Fig. 2 The left plantar foot of a 32-year-old Caucasian
man who had Unna–Thost syndrome and congenital
hyperkeratosis of his palms and soles. There is confluent
hyperkeratosis of the mid and distal plantar foot (top).
There is complete resolution of the plantar hyperkeratosis
within 2 weeks after initiating daily topical therapy with
selenium sulfide shampoo 2.5% (bottom). The shampoo
remained on the foot for 10 min after it had been rubbed
into the foot and was in a lather form; it was then rinsed
off and Aquaphor ointment was applied
Dermatol Ther (Heidelb)
involvement: diffuse or focal or punctate. Cat-
egories of acquired palmoplantar hyperkeratosis
include chemically induced, dermatoses-re-
lated, drug-related, idiopathic, infection-re-
lated, keratoderma climactericum, malignancy-
associated, malnutrition-associated, and sys-
temic-disease-related. Hereditary palmoplantar
keratoderma may be limited to persistent
thickening of the palms and soles or may be
associated with syndromes characterized by
additional extracutaneous manifestations, such
as cardiomyopathy, deafness, inborn errors of
metabolism, internal organ involvement,
mucosal lesions, or sexual development disor-
ders [1,2].
Hyperkeratosis is histologically defined by
marked orthokeratosis: an increased thickness
of the stratum corneum. Other epidermal
pathologic changes that may be present include
parakeratosis (demonstrated by retained nuclei
in the stratum corneum), acanthosis (in which
there is thickening of the entire epidermis) and
hyperplasia of the granular layer and stratum
spinosum; a perivascular lymphocytic infiltrate
may also be seen in the dermis. Congenital
hyperkeratosis can also have additional changes
in the epidermis, such as epidermolysis of the
granular layer [1,2].
The initial treatment of acquired hyperker-
atosis (particularly of the palms and soles) is to
identify and treat the underlying cause of the
associated condition. For those individuals with
idiopathic acquired hyperkeratosis and patients
with hereditary hyperkeratosis, there are several
potential conservative treatment options that
have each been associated with variable success
for any given individual; they include topical
keratolytics (such as urea, salicylic acid, and
lactic acid), repeated physical debridement,
topical retinoids, topical psoralen and ultravio-
let A phototherapy, and topical corticosteroids.
Systemic retinoid therapy (such as acitretin) has
also been utilized for patients with severe
hyperkeratosis that does not respond to con-
servative measures. We report our observations
of successful hyperkeratosis management using
topical selenium sulfide [1–4].
Selenium is a member of group IVa of the
periodic table; other elements in this group
include oxygen, sulfur, polonium, and
Fig. 3 The right distal leg of an 80-year-old African
American man with a history of chronic lymphedema of
his lower extremities. There was extensive hyperkeratosis
on the distal right pretibial leg (left). The hyperkeratosis
was completely resolved after 2 weeks of applying selenium
sulfide shampoo 2.5% daily for 10–30 min; after rinsing
off the shampoo, Aquaphor was applied (right)
Dermatol Ther (Heidelb)
tellurium. It is a nonmetallic element that has
four natural oxidative states. However, the
water-soluble selenite and selenate salts are
toxic [5].
Selenium has a role in preventing oxidative
degradation of lipids in polysaturated mem-
branes. Selenium is an essential component of
the antioxidant enzyme glutathione peroxidase.
Indeed, selenium deficiency has been linked to
endemic diseases in the Chinese population:
Keshan disease and Kashin–Beck disease [6,7].
Keshan disease results in cardiac enlarge-
ment, congestive heart failure, cardiogenic
shock, and death. It occurs secondary to mul-
tifocal necrosis of the myocardium. Keshan
disease primarily occurs in children and young
women [6].
The main feature of Kashin–Beck disease is
shortened stature. Multiple focal areas of
necrosis in the tubular bone growth plates cause
it. The endemic chronic osteoarthropathy
results from atrophy, degeneration and necrosis
of cartilage. Kashin–Beck disease has been
observed not only in China, but also in Russia
and Korea [7].
However, excess selenium can be associated
with acute and chronic toxicity. Acute ingestion
of selenious acid (which is usually fatal) results
in garlic odor breath and red pigmentation of
the hair, nails, and teeth [8]. Garlicky breath
and nail changes (transverse ridges), in addition
to a metallic taste in the mouth, have been
observed following inhalation of hydrogen
selenide [9,10]. Residents of geographic areas
with high levels of selenium may develop
chronic selenium poisoning; changes charac-
teristically involve the skin (erythema and red
discoloration, pruritic scalp rash, vesicles, and
secondary infections), hair (which becomes
brittle and breaks easily), and nails (which
become brittle and develop yellowish-white or
red longitudinal lines or transverse streaks) [11].
Selenium sulfide (SeS
2
or Se=S) is a selenium
salt. At room temperature, it is a yellow-orange
tablet or powder. In contrast to the water-sol-
uble selenium salts, selenium sulfide is not only
insoluble in water but also nontoxic when
taken orally. Indeed, it has been found to be safe
in animal studies and not carcinogenic when
applied topically [12–14].
Selenium sulfide is used as a therapeutic
agent in dermatological conditions. It is the
active ingredient in anti-dandruff shampoo
[14–16]. In addition, it is also used to treat tinea
versicolor [14,17,18].
Selenium sulfide can be an effective agent for
the treatment of hyperkeratosis—not only for
the soles of the feet and palms of the hands, but
also for thick skin on the distal legs. Either the
2.5% lotion/shampoo or the 2.75% foam
preparation of selenium sulfide can be used. The
treatment protocol is simple and can readily be
performed by the patient or a caregiver. The
selenium sulfide is applied topically and then
continuously rubbed into the affected area of
skin for at least 10 min; longer treatment dura-
tions—ranging from 20 min to 2 h—can also be
used. Thereafter, the treated area is cleaned with
water and dried. Improvement can be observed
within 2 weeks.
All of our patients had plantar hyperkerato-
sis. One man had congenital hyperkeratosis of
the palms and soles consistent with
Unna–Thost disease [19,20]. The other patients
both had lower extremity edema and acquired
hyperkeratosis; the woman had spina bifida and
hyperkeratosis of her plantar feet whereas the
man’s hyperkeratosis was idiopathic and he had
hyperkeratosis of his hands, feet, and distal legs.
Prior to using topical selenium sulfide for
their hyperkeratosis, all of our patients had tried
several other topical therapies, all of which
failed. Indeed, after initiating treatment with
selenium sulfide, all of the patients had rapid,
complete, and sustained improvement of their
hyperkeratosis. In addition, none of them
experienced any adverse events from the
therapy.
Investigators have suggested that the mech-
anism of action of selenium sulfide in the
management of seborrheic dermatitis and tinea
versicolor is secondary to its anti-Pityrosporum
effect [15–17,21]. However, the antiseborrheic
properties of selenium sulfide are also the result
of it significantly reducing the mitotic rate and
cell turnover of the epidermis basal layer due to
a cytostatic effect it has not only on the epi-
dermal cells but also the follicular epithelium,
thereby diminishing the formation rate of the
stratum corneum [22,23]. These latter effects of
Dermatol Ther (Heidelb)
selenium sulfide may, in part, contribute to its
effectiveness in the treatment of hyperkeratosis.
In addition, selenium sulfide has been asso-
ciated with an increased sebum excretion rate
[23,24]. This clinical observation corresponds
to an increase in the size of the existing seba-
ceous glands [23]. However, since the palms and
soles have no sebaceous glands, hyperplasia of
the sebaceous gland and subsequent increased
sebum secretion probably did not play a role in
the resolution of our patients’ hyperkeratosis.
Topical selenium sulfide has also been
demonstrated to effectively treat psoriasis, an
immunologically driven hyperproliferative dis-
order of the epidermis. The researchers treated
more than 100 patients with psoriasis; similar to
our methodology, they applied selenium sulfide
shampoo (25 mg/ml) to the affected sites and
allowed the shampoo to remain on the skin
surface for 15 min before washing it off. There
was prompt and sustained improvement of the
psoriatic plaques—even in those individuals
who had been refractory to topical tar or high-
potency corticosteroids or both [25]. It is rea-
sonable to speculate a similar mechanism of
action of selenium sulfide in our patients who
were treated for hyperkeratosis and those indi-
viduals who were treated for psoriasis.
CONCLUSIONS
Hyperkeratosis can be congenital or acquired.
Clinically it presents as thickened skin, often
affecting the palms and soles. Pathologic chan-
ges in affected skin uniformly show marked
orthokeratosis of the stratum corneum. Cur-
rently, topical treatment options include kera-
tolytics and retinoids; other local therapeutic
modalities that have been initiated are physical
debridement, topical corticosteroids, and pho-
totherapy (using topical psoralen and ultravio-
let A phototherapy). Selenium is a nonmetallic
essential element; deficiency can result in sys-
temic diseases. However, acute and chronic
toxicity have been associated with excess
ingestion. The water-insoluble selenium salt
selenium sulfide is a safe active ingredient in
foam, lotion, and shampoo; it has been used to
treat not only seborrheic dermatitis but also
tinea versicolor. The successful use of topical
selenium sulfide (as a 2.5% lotion/shampoo or a
2.75% foam) to treat either congenital or
acquired hyperkeratosis—particularly of the
palms and/or soles—is described for three
patients. All of these individuals had a rapid,
complete, and sustained response to treatment,
without any adverse events. In conclusion, we
recommend that topical selenium sulfide be
added to the therapeutic armamentarium for
hyperkeratosis, especially of the palms and
soles.
ACKNOWLEDGEMENTS
We thank the participants of the study.
Funding. No funding was received for the
publication of this article. The authors are fully
responsible for all content and editorial deci-
sions, and received no financial support or
other form of compensation related to the
development of this manuscript.
Authorship. All named authors meet the
International Committee of Medical Journal
Editors (ICMJE) criteria for authorship of this
manuscript, take responsibility for the integrity
of the work as a whole, and have given final
approval for the version to be published.
Disclosures. Philip R. Cohen and Caesar A.
Anderson have nothing to disclose with regards
to the publication of this article.
Compliance with Ethics Guidelines. In-
formed consent was obtained from the partici-
pants for inclusion in the study.
Open Access. This article is distributed
under the terms of the Creative Commons
Attribution-NonCommercial 4.0 International
License (http://creativecommons.org/licenses/
by-nc/4.0/), which permits any non-
commercial use, distribution, and reproduction
in any medium, provided you give appropriate
credit to the original author(s) and the source,
provide a link to the Creative Commons license,
and indicate if changes were made.
Dermatol Ther (Heidelb)
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