doi: 10.1111/1346-8138.

13896 Journal of Dermatology 2017; 44: 991–1014

GUIDELINE
Guideline for the diagnosis and treatment of scabies in Japan
(third edition)
Executive Committee of Guideline for the Diagnosis and Treatment of Scabies*
The Japanese Dermatological Association, Tokyo, Japan

ABSTRACT
In the current work, we present our new guideline for the diagnosis and treatment of scabies which we, the Exec-
utive Committee convened by the Japanese Dermatological Association, developed to ensure proper diagnosis
and treatment of scabies in Japan. Approval of phenothrin topical use under the National Health Insurance in
August 2014 led to this action. Permethrin, a topical anti-scabietic medication belonging to the same pyrethroid
group as phenothrin, is already in use worldwide. In this guideline, we introduce criteria for a proper diagnosis of
scabies, treatment algorithm for common and crusted (hyperkeratotic) scabies, and prevention. The major change
from our second edition is the treatment algorithm. As phenothrin is now available, the first-line therapy for com-
mon scabies is either topical phenothrin lotion or oral ivermectin. The second-line option for topical treatment is
sulfur-containing ointments, crotamiton cream or benzyl benzoate lotion. c-Benzene hexachloride ointment is no
longer provided for clinical use. In an immunosuppressed patient, the treatment option is still the same, but with
close follow up. If the symptoms persist, diagnosis and treatment must be reassessed. For hyperkeratotic scabies
and nail scabies, removal of thick crust, cutting of nails and occlusive dressing are additionally required. The
safety and effectiveness of combined treatment with topical and oral medications are not yet confirmed. Further
assessment is needed. In addition to appropriate treatment, it is essential to educate patients and health-care
workers and to conduct epidemiological studies to prevent further spread of the disease through effectively utiliz-
ing available resources including manpower, finance, logistics and time.
Key words: guideline, ivermectin, Japan, phenothrin, scabies.

AIM OF PREPARING THE GUIDELINE FOR THE
DIAGNOSIS AND TREATMENT OF SCABIES
(THIRD EDITION)
Scabies is caused by an infestation with Sarcoptes scabiei (S.
scabiei var. hominis), upon whose extermination, scabies is
cured. However, infection from person to person persists
through sexual contact, communal living and other activities,
which makes it virtually impossible to eliminate the parasite
completely.
Therefore, it is important to make prompt and accurate
diagnosis of scabies, and to provide appropriate treatment,
resulting in a cure. Dermatologists are the leading physicians
for dealing with this condition. Furthermore, it is essential that

Correspondence: Norihisa Ishii, M.D., Ph.D., Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama,
Tokyo 189-0002, Japan. Email: norishii@nih.go.jp
*Executive Committee of the guideline for the diagnosis and treatment of scabies the Japanese Dermatological Association: Norihisa Ishii, Leprosy
Research Center, National Institute of Infectious Diseases, Tokyo; Toshiya Asai, Asai Dermatology Clinic, Yokohama; Akihiko Asahina, Jikei Uni-
versity School of Medicine, Tokyo; Akira Ishiko, Faculty of Medicine, Toho University, Tokyo; Hidekazu Imamura, Imamura Dermatology and
Plastic Surgery Clinic, Ube; Toyonori Kato, Department of Pharmacy, Hokuto Hospital, Okazaki; Nobuo Kanazawa, Wakayama Medical Univer-
sity, Wakayama; Yumiko Kubota, Fukuoka Sanno Hospital, Fukuoka; Hitomi Kurosu, Infection Control, Department of Nursing, Ebara Hospital,
Tokyo; Takeshi Kono, Nippon Medical School Chiba Hokuso Hospital, Inzai; Masayo Komoda, Faculty of Pharmaceutical Sciences, School of
Medical Safety, Tokyo University of Science, Noda; Mari Sekine, Ebara Hospital, Tokyo; Masaru Tanaka, Medical Center East, Tokyo Women’s
Medical University, Tokyo; Hiroko Taniguchi, Kudanzaka Hospital, Tokyo; Yuichiro Tsunemi, Tokyo Women’s Medical University, Tokyo;
Masaru Natsuaki, Hyogo College of Medicine, Nishinomiya; Takashi Hirota, Biopharmaceutics, Department of Pharmacy, Tokyo University of
Science, Noda; Kuniko Makigami, Tsubasa Home Care Clinic, Funabashi; Tomoko Matsuda, Matsuda Tomoko Dermatology Clinic, Fukuoka;
Junko Yoshizumi, Yoshizumi Dermatology Clinic, Tokyo; Rie Yotsu, National Sanatorium Suruga/Center Hospital of the National Center for
Global Health and Medicine, Gotemba/Tokyo; Yasuo Wada, Ako City Hospital, Ako.
This is the English version of the Guideline for the diagnosis and treatment of scabies (third edition) (Jpn J Dermatol 2015; 125: 2023–2048) developed
by the Executive Committee organized by the Japanese Dermatological Association.
Received 16 March 2017; accepted 23 March 2017.

© 2017 Japanese Dermatological Association 991

N. Ishii et al.
dermatologists prevent mass infection and educate the public.
Thus, this guideline was created.
BACKGROUND OF CREATING THE GUIDELINE
Scabies has been a problem for humans since the dawn of his-
tory. Towards the middle of the 19th century, scabies began to
be managed primarily by dermatologists. However, until
recently, no markedly effective drug for oral or topical treat-
ment had been officially approved, so a variety of therapies
and folk remedies were used for the treatment of this disease
in Japan. Recently, drugs effective against scabies were offi-
cially introduced for clinical use.
The Japanese Dermatological Association previously cre-
ated a guideline for the diagnosis and treatment of scabies in
20051 and 2007.2 As phenothrin topical use is now approved
under the National Health Insurance (health insurance) (August
2014), the third edition of the guideline was thought to be
necessary. The third edition was created through a series of
discussions by the Executive Committee and Board of Direc-
tors for the guideline. Public comment was invited, and the
guideline was published with the approval of the Executive
Committee and Board of Directors of the Japanese Dermato-
logical Association.
POSITION OF THE GUIDELINE
This guideline shows the standard diagnosis and treatment pro-
tocol for scabies in Japan at present. However, the pathology of
scabies is not fully understood, the clinical picture is diverse and
the severity of symptoms varies. Furthermore, there are few
drugs covered by health insurance. Therefore, detailed strate-
gies for the management of this disease should be devised by
individual physicians based on the features of individual cases,
and simply adopting the measures set out in this guideline does
not exempt physicians from liability. Additionally, this guideline is
not intended to discourage physicians from adopting a treatment
strategy not described in this guideline (third edition), and such
actions cannot be regarded as negligence.
CONFLICT OF INTEREST
The Japanese Dermatological Association covered all the costs
required to formulate this guideline, and no support was
received from specific bodies, enterprises or pharmaceutical
companies. Furthermore, members of the guideline Executive
Committee involved in the development of related pharmaceu-
ticals were not involved in determining the degree to which the
respective treatment should be recommended. Apart from the
above, no conflicts of interest should be declared by each
committee member regarding the formulation of this guideline.
DEFINITION OF SCABIES
Scabies is caused by infection with S. scabiei var. hominis,
which is a mite parasitic to the keratinous layer (horny layer, stra-
tum corneum) of human skin. Major symptoms of this infestation
992
are skin lesions and itching arising from allergic reactions to the
body, excretion, exuviae and other parts of the parasite.3–7
ECOLOGY OF S. SCABIEI (SCABIES MITE)
Sarcoptes scabiei, which is responsible for scabies, is approxi-
mately oval in its shape.8 The mature female mite is larger at
approximately 400 lm in length and approximately 325 lm in
width, while the mature male mite is approximately 60% of the
female size. The mites molt and grow through repeating the
cycle of egg, larvae, nymph and mature form. The hatching of
eggs takes 3–5 days, and the life cycle is approximately 10–
14 days.9–11 Larvae, nymphs and mature male mites walk
around on the surface of human skin or hide in small burrows
created within the keratinous layer of the skin or in hair follicles.
It is therefore difficult to locate this mite on the host. Mature
female mites create small burrows suitable for laying eggs and
wait there for males. Males seek females to mate. After mating,
mature female mites advance through the keratinous layer, cre-
ating a burrow, and continue burrowing for the remainder of their
life (4–6 weeks) while laying 2–4 eggs every day. As S. scabiei is
not a blood-sucking mite, exudate, tissue fluid and other sub-
stances in the keratinous layer are thought to serve as sources
of nourishment for the mite, although details are unknown.
Sarcoptes scabiei cannot endure dryness. They become
less active at temperatures lower than human body tempera-
ture and are completely inactive at temperatures below 16°C.
It is estimated that the infectivity of S. scabiei decreases within
several hours once this mite is detached from the skin. This
mite cannot tolerate high temperatures and dies if exposed to
a temperature of 50°C for 10 min.12
DISEASE TYPING
Based on clinical symptoms13,14 and the number of infested
mites, scabies is usually divided into two types: scabies (com-
mon scabies, classical scabies) and crusted scabies. (Note:
This type is also known as Norwegian scabies [synonymous
with hyperkeratotic scabies]. These scabies were named as
such because they were first reported by a Norwegian scien-
tist, but the name is now deemed discriminatory, and is not
used in this guideline.)
Clinical symptoms will be described in the next section. In
common scabies, the number of mature female mites found is
five or fewer in half of all cases (in healthy individuals), but there
are cases where more parasites are found. Namely, there may
be a larger number of parasites, even in infections with common
scabies, in people with reduced immunity, including patients
taking steroids or immunosuppressants, patients with malignant
tumors or diabetes, those on dialysis and elderly people.
In crusted scabies, 1–2 million mature mites (occasionally
>5 million) are seen per patient,15,16 and the infectivity is very high.
ROUTE OF INFECTION
The mite is transmitted primarily by direct skin contact. After a
symptom-free incubation period of approximately 1–2 months
© 2017 Japanese Dermatological Association

(sometimes several months in elderly individuals), clinical
symptoms, such as skin eruption, appear.17,18
There is no published work that clearly describes the route
of transmission during the incubation period. Additionally, the
number of S. scabiei during this period is small, so there is lit-
tle risk of infecting another person.
Both common scabies and crusted scabies are infestations
caused by the same agent, S. scabiei, however, the infectivity
and the means of spreading infection differ significantly.
In common scabies, there are only a small number of
S. scabiei parasites per patient.19 The longer the parasite is
detached from the host, the infectivity of S. scabiei
decreases.12 The circumstances in which mites can be trans-
mitted from a patient with common scabies include activities
such as sharing the same bed, using bedding used by the
patient and holding hands for an extended period.20 Transmis-
sion is limited to intense contact; therefore, there is little risk of
infection with short periods of contact, or through fomites such
as clothing or bed linen.
In crusted scabies, the keratinous layer of the skin contains
a large number of S. scabiei. In such cases, infection can be
established not only through direct skin contact but also
through the spread of the mite as the detached keratinous
layer is dispersed or attaches to other surfaces. Therefore,
infection can spread through short, direct skin contact, such
as when visiting the affected person, and via indirect contact,
such as via bed linen where there is no direct skin contact with
the infected person. This can result in mass infection.21 The
parasites can also be transmitted via staff working in hospital
facilities, and other factors.22 The incubation period for crusted
scabies is sometimes shorter (4–5 days) due to infestation with
a large number of S. scabiei.
CLINICAL SYMPTOMS
Common scabies
There are roughly three kinds of skin symptoms in scabies.6
First, the burrow type, which often develops on the flexural
side of the wrist, the palms, finger webs and the sides of the
fingers. This is sometimes seen also on the soles of the feet,
dorsum pedis, olecranon, nipples (in women), genitalia (partic-
ularly in males), buttocks, axillae and so forth. The scabies
burrow is a type of skin eruption unique to scabies, and it
serves as the path through which the mature female mite
advances through the keratinous layer while laying eggs. Thus,
mites and eggs are frequently detected in the burrow. The bur-
row is elevated slightly above the skin surface, appearing as a
linear eruption, following a tortuous arrangement with a whitish
appearance. The width is approximately 0.4 mm (approxi-
mately equivalent to one pattern of fingerprint), and the length
is often approximately 5 mm, although it can vary depending
on the length of time since the start of digging. Scales are
seen on the side invaded by the mite, while vesicles are some-
times seen at the frontier of digging.23 In elderly patients, the
eruption sometimes assumes the appearance of the “wake”
sign (resembling the wake of a ship, broadening toward the
end after a ship has passed) along the wrists, the palms and
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
the wrinkles on the fingers.24–29 This type of eruption is often
not elevated.26,29 When observed with a magnifying glass, the
mite is sometimes visible as a dark-brown triangle, which cor-
responds to the head (capitulum) and two pairs of forelimbs of
the mite. Sites where this feature may be found are several
millimeters ahead of the vesicle at the tip of the burrow or at
the tip of a linear wake-like eruption. Wiping the area around
the scabies burrow once with an alcohol swab makes detec-
tion of S. scabiei easier, and detection is even easier using a
dermoscope (see the section on dermoscopy). The scabies
burrow itself is itchy, but the itching sensation is sometimes
absent in elderly patients. Second, erythematous small
papules accompanied by an intense itching sensation are
scattered through the umbilical region, abdomen, thoracic
region, axillae, medial aspect of the thigh, and flexor surface
of the upper arm. The itching sensation intensifies at night,
sometimes disrupting sleep. This itching sensation is consid-
ered as an allergic reaction after sensitization to the feces,
exuviae and other waste products from the S. scabiei during
the approximately 1-month incubation period. It is rare to
detect mites or eggs from the area affected by this type of
papule. Third, red-brown nodules the size of small beans, pri-
marily affecting the external genitalia of men, and they are also
seen in the axillae, olecranon and buttocks. This type of erup-
tion is uncommon, seen in only approximately 7–30% of all
cases of scabies, and it causes a very intense itching sensa-
tion. Nodules are also attributable to allergic reactions to the
mite. Burrows are sometimes seen, even in freshly formed
nodules, and in such cases, it may be possible to detect
S. scabiei from the burrows.
Eruptions including vesicles, blisters, pustules and crust
may also be seen. Eruption is usually absent from the head
and face, although it is exceptionally visible in infants, small
children and elderly patients. A condition known as acropustu-
losis of infancy may also been seen in children where vesicles
and small pustules appear on the palms and soles of the feet
during infestation with scabies and after the scabies has been
cured.30
Crusted scabies
This type of scabies tends to occur in individuals with poor
condition or severe underlying disease, individuals in an
immunocompromised state due to steroid or immunosuppres-
sive treatment, and elderly individuals with these back-
grounds.31 Crusted scabies may also affect individuals with
disorders of the nervous system or severe systemic skin dis-
ease, and individuals who have erroneously used topical ster-
oids for common scabies.32
Symptoms in crusted scabies can be characterized by
hyperkeratosis, presenting as an accumulation of gray to yel-
low-white, rough and thickened, oyster shell-like keratinous tis-
sue at sites on the skin prone to friction, including the hands,
feet, buttocks, olecranon and patella, as well as in other sys-
temic areas, including those areas unlikely to be affected by
common scabies, such as the head, neck and auricular
region.33 Eruption is sometimes accompanied by systemic red-
ness, which may become erythroderma. Similar hyperkeratosis
993
N. Ishii et al.
may also be seen in the nail plate (nail scabies), presenting
with clinical symptoms resembling tinea unguium.34 Nail sca-
bies occurs when S. scabiei are present within, under or on
top of the nail plate, and the condition may also be compli-
cated by tinea unguium.
In recent years, there has been a tendency toward an
increase in cases where eruption is confined to the palms, feet
or nails, or occasionally confined to the auricular region, neck,
head and so forth. There are also cases where only small
amounts of mica-like scales are seen in the extremities, but
numerous mites and eggs are detected in the scale. There is
no particular itching tendency in these cases, and itching may
be completely absent.
Crusted scabies may also occur concurrently with condi-
tions such as secondary bacterial infection or kidney failure,35–
37
which may be fatal, so early treatment is essential.
TESTS
Tests for detection of S. scabiei
At present, microscopy and dermoscopy are available methods
for detecting mites. However, to increase the efficiency of
S. scabiei detection, it is vital to improve these existing tech-
niques, to develop new alternatives and to confirm their
validity.38
Microscopy
Sarcoptes scabiei are collected for microscopy from burrows,
fresh papules, nodules and so forth by means of: (i) resec-
tion with ophthalmic scissors; (ii) scratching with a scalpel;
(iii) scrape with small tweezers; (iv) collection of mites with a
sterile needle using a dermoscope or under magnification
with a loop, and other such techniques. In cases where the
keratinous layer is thick, as in cases of crusted scabies, the
keratinous layer is collected with ophthalmic scissors, tweez-
ers or other such implements. The samples thus collected
are observed under a microscope at a magnification of
9100, similar to the procedure for the observation of myco-
sis. The mite body, trunk, limbs, eggs, exuviae, feces and so
forth are checked. Fecal pellets dissolve easily with potas-
sium hydroxide and can be stained with chlorazol black E.39
At present, there is no established method for differentiating
whether the mite is alive or dead.40,41 Even in cases of
eruption associated with scabies, the mite detection rate
with microscopy varies widely, ranging 10–70%,17,42–44 so it
is essential to improve the techniques of detection and to
frequently repeat the test at different sites on the body. For
efficient detection of S. scabiei, the mite burrows must be
magnified with a dermoscope and the tips of the burrows
examined. In elderly individuals, it is important to not over-
look the palms and the soles of the feet and to look for
V-shaped wake-like scales.26,29 The mite detection rate is
low in papules on the body trunk.
With crusted scabies, there are innumerable mites of all
stages, ranging from the eggs to the mature form, and these
are detectable in the hyperplastic keratinous layer. Therefore,
detection of the mite is easy in suspected cases of crusted
994
scabies by means of microscopic examination of the kerati-
nous layer. Microscopic detection of the mite is covered by
health insurance as a microbial test.
Dermoscopy
Scabies can also be diagnosed through detection of the mite
via dermoscopy.23,29,40,45 The female mite, approximately
0.4 mm in size, and its dark-brown head, two pairs of fore-
limbs and almost transparent round body can be
observed.29,45,46 This can be usually found at the tip of the
curved, shiny, whitish burrow. Dermoscopic examination is not
covered by health insurance in Japan.
Hematology
It is not possible to make a definitive diagnosis of scabies
based on hematological findings. Increased eosinophils and/or
elevated immunoglobulin (Ig)E are not indicative of a scabies
infestation, however, there is a tendency of elevated IgE in
cases with nodules.47,48 No practical IgE test specific to
S. scabiei has been developed. There is also data indicating a
crossover of the human S. scabiei antigen with the Der-
matophagoides farinae and Dermatophagoides pteronyssinus
antigens.49
EPIDEMIOLOGICAL STATUS OF DISEASE
OUTBREAK
Usually, the onset of scabies in two or more individuals within
the same ward or unit during a 2-month period is regarded as
a mass outbreak. When making such a judgment, the status of
mass outbreak in neighboring communities is also taken into
account,50–52 and individuals suspected of having scabies are
to be adequately interviewed to determine contact with scabies
patients.
DIAGNOSIS OF SCABIES
Diagnosis of scabies is based on a general assessment of: (i)
clinical symptoms; (ii) results of microscopy, dermoscopy and
so forth for detection of the mite; and (iii) epidemiological sta-
tus of the outbreak (including information about the chance of
contact with scabies patients). If S. scabiei has been detected
by microscopy, dermoscopy or other such means, a definitive
diagnosis can be made. In cases where microscopy and/or
dermoscopy yields negative results but the possibility of sca-
bies cannot be ruled out in view of clinical symptoms and/or
epidemiological status of an outbreak, it is necessary to per-
form microscopy or dermoscopy again at a later time. In cases
of common scabies, the number of mites is small;15,16 thus,
this type requires repeated tests for detection of the mite to
make a definitive diagnosis.
TREATMENT OF SCABIES
Basic concept of treatment
Treatment of scabies53 is performed on patients definitively
diagnosed as having scabies based on S. scabiei detection or
© 2017 Japanese Dermatological Association

patients showing evident clinical symptoms of scabies after
coming into contact with patients definitely diagnosed as hav-
ing scabies.
At present, the only preparations for the treatment of sca-
bies (scabicides) covered by health insurance in Japan are
phenothrin (Sumithrinâ; Kracie Pharma, Tokyo, Japan) lotion,
topical sulfur preparation and ivermectin (Stromectolâ; Merck,
Kenilworth, NJ, USA) (Table 1). Crotamiton (Euraxâ; GSK CHJ-
Novartis, Tokyo, Japan) cream is not covered by health
insurance, but a notification has been issued by the Social
Insurance Medical Fee Payment Fund to the effect that “if cro-
tamiton is usually prescribed for scabies, then it will be
approved after examination of the usage case in question”
(dated 21 September 2007). Benzyl benzoate is a special for-
mulation containing a combination of reagent and vehicle, and
is used at the discretion of physicians in the absence of effec-
tive topical preparations, although its efficacy and safety have
not yet been fully evaluated. No topical permethrin preparation
is approved in Japan, as the preparations contain the stabilizer
formaldehyde as a component.
c-Benzene hexachloride (c-BHC; lindane) is subject to regu-
lation by the Stockholm Convention relating to persistent
organic pollutants, so it is now unavailable (lindane was added
to the list of Class I Specified Chemical Substances in the Act
on the Evaluation of Chemical Substances and Regulation of
Their Manufacture, and so forth in April 2010), so it can no
longer be used in Japan.
Long-term use or overdose of scabicides may induce emer-
gence of drug-resistant S. scabiei.54 There are only a small
number of different types of scabicides available, so the drugs
must be correctly administrated to prevent the emergence of
drug-resistant S. scabiei.
Collecting evidence on therapeutic drugs
Databases used for the collection of data were PubMed, Japan
Medical Abstracts Society Web (Ichushi) and Cochrane Data-
base of Systematic Reviews (2010).
Regarding the search period, the aforementioned Cochrane
database was available in PubMed, so we searched the avail-
able published work between January 2009 and May 2014
(search entry: drug name AND human AND scabies). Important
new published work was added as needed. For Ichushi, we
searched the available published work up to May 2014 (search
entry: drug name AND human AND scabies AND excluding
conference proceedings). Important new published work was
added as needed.
Evidence level and criteria for classification of
degree of recommendation
The criteria adopted by the Guideline for the Diagnosis and
Treatment of Skin Cancer, edited by the Japanese Dermato-
logical Association was referenced (Table 2).55
Summary of clinical questions (CQ) on treatment
Sulfur
CQ: Is sulfur effective for treating scabies?
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
Reference text: There is little clear scientific evidence on the
efficacy of sulfur, but it may be used.
Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence).
Explanation: According to reports based on randomized
controlled trials (RCT) on scabies, patients with 50 subjects per
group, topical application of 10% sulfur for 7 consecutive days
had equivalent efficacy and safety as topical application of
0.3% c-BHC for 7 days consecutively.56 Additionally, accord-
ing to a report based on an RCT on scabies patients with 69–
89 subjects per group, topical application of sulfur (unknown
concentration) in the morning and evening for 3 days consecu-
tively had an equivalent efficacy and safety as topical applica-
tion of 25% benzyl benzoate lotion in the morning and evening
for 3 days consecutively.57 Another report indicated a cure rate
of approximately 85% with 6–10% precipitated sulfur ointment
applied every evening repeatedly for 3 days.58 In Japan, there
are few topical medicines covered by health insurance. Only
sulfur powder can be used as a prescription drug, and this
drug is prepared as a hospital preparation in each hospital.
Manufacture of the over-the-counter (OTC) sulfur, salicylic acid
and thianthol ointment has been discontinued, and only prepa-
rations containing thianthol 30% are available. Treatment was
effective in all patients who used sulfur camphor lotion (6%
sulfur mixture), which is commonly used for acne, for 7 days.
However, this is simply a case series, and there is little sup-
porting evidence.59
Crotamiton
CQ: Is crotamiton effective for treating scabies?
Reference text: The efficacy of crotamiton monotherapy is
not highly evaluated, but it is effective depending on the
patient.
Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence).
Explanation: Crotamiton topical preparation has been used
in Japan on scabies patients since the end of the 1970s, but
the usage method is not standardized, and most cases use
this preparation in combination with other drugs.
Two RCT (overnight application,60 application for 2 nights
consecutively nights)61 were conducted comparing crotamiton
10% cream with permethrin 5% cream in 194 scabies patients.
The cure rate after 4 weeks was 60% versus 89% in the former
trial and 88% versus 98% in the latter trial, indicating that cro-
tamiton had inferior efficacy. Crotamiton also had higher persis-
tence of itching sensation after 4 weeks (24% vs 11%) and a
higher incidence of secondary infection (38% vs 15%) than per-
methrin.60 There was no significant difference in terms of effi-
cacy and safety in an RCT on 100 scabies patients comparing
crotamiton 10% cream and 1% c-BHC.61 A report in Japan indi-
cated a cure rate of 61.6% in children and 100% in adults after
daily application of crotamiton 10% cream for 3 weeks in 39
children aged 3–5 years and in 12 adults.62 In cases of mass
outbreaks in elderly resident facilities, crotamiton 10% cream
monotherapy is not used in definitive cases of scabies, but effi-
cacy is seen in cases in the early stage of scabies infestation
and in cases in the incubation period.63 Therefore, in cases
995
 996
Table 1. Drugs available for treatment of scabies

Health insurance Non-proprietary Usage Pharmacological Adverse drug Suitability for Suitability in
N. Ishii et al.

coverage name Brand name concentration action Toxicity† reactions children pregnancy
Oral Covered by Ivermectin Stromectolâ 200 µg/kg Primarily acts on LD50 11.6–40 Liver Safety not Safety not
health tablet 3 mg (dose) nerve cell mg/kg (mouse, dysfunction, established in established
insurance Cl channels oral) jaundice, children in pregnancy
reduced weighing (teratogenicity
platelet count, <15 kg in animals)
toxic epidermal
necrolysis,
Stevens–Johnson
syndrome
Topical Covered by Phenothrin Sumithrinâ 5% Primarily acts on LD50 >5000 Dermatitis, elevated Safety not Safety not
health lotion 5% nerve cell Na+ mg/kg (rat, AST, elevated established (no established
insurance channels oral)§ ALT, etc. usage (no usage
experience) experience)
Sulfur Sulfur powder 5–10% Demonstrates LD50 >8437 Asteatotic eczema Indicated Indicated
Organic Sulfur Thianthol 10–30% direct and indirect mg/kg (rat,
(OTC drug germicidal and oral)§
only) insecticidal effect
Not covered Crotamiton Euraxâ 10% Unknown LD50 1600 Feeling hot, Extensive Large doses
by health cream 10% mg/kg (mouse, irritation application to or prolonged
insurance‡ oral)§ symptoms, be avoided extensive
contact dermatitis application
to be
avoided
Informed Benzyl Benzyl 6–35% Unknown LD50 1400 Central nervous Do not use in Refrain
consent of benzoate benzoate mg/kg (mouse, system disorders, children from use
patient is oral)¶ skin irritation, etc. ≤2 years
necessary for
special
formulation
Unavailable Permethrin Elimiteâ 5% Primarily acts on LD50 383 mg/kg Contact dermatitis, Safety and Indicated
in Japan Cream etc. nerve cell Na+ (rat, oral)§ etc. efficacy not
channels established in
children
<2 months

†
LD50: lethal dose 50 (50% lethal dose).
‡
Not covered by health insurance, but allowed after insurance review.
§
Japan Poison Information Center (ed). Acute Toxicity Treatment Manual [3rd Edition]. Jiho, 1999.
¶
Merck Index: An encyclopedia of drugs, Chemicals and Biologicals, 1996.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; OTC, over-the-counter.

© 2017 Japanese Dermatological Association


Table 2. Evidence level and criteria for classification of
recommendation level (referencing the criteria adopted by the
guideline for the diagnosis and treatment of skin cancer, edited
by the Japanese Dermatological Association)
Classification of evidence level
I Systematic review/meta-analysis
II One or more randomized controlled trials
III Non-randomized controlled trial
IV Analytical epidemiological study (cohort study,
case–control trial)
V Descriptive study (case report, case series)
VI Opinions of specialist committee, specialist individual†
Classification of recommendation level‡
A Use of the treatment is strongly recommended
(there is at least one level I or good quality
level II evidence demonstrating efficacy)
B Use of the treatment is recommended (there is at least
one or more inferior quality level II, good quality
level III or extremely good quality level IV evidence
demonstrating efficacy)
C1 Use of the treatment may be considered, but there is
insufficient evidence§ (inferior quality level III–IV, a
number of good quality level V or a
committee-approved level VI)
C2 Use of the treatment cannot be recommended, as
there is no evidence§ (no evidence of efficacy or
evidence of ineffectiveness)
D Recommended to not use the treatment (there is good
quality evidence demonstrating that the treatment is
ineffective or harmful)
†
Data based on basic experiments and theory guided by that data
would correspond to this level.
‡
There may be levels of recommendation in this text that do not always
match the criteria in the above table. This is because there are sections
where the grade of recommendation level was decided based on the
consensus of the Executive Committee, which was based on considera-
tions that there is a lack of evidence on this condition internationally,
given that overseas evidence cannot always be applied without change
to the situation in Japan, and further considering the practical applica-
tions of treatment (after demonstrating the evidence level).
§ c-BHC on humans.
Evidence refers to findings based on clinical studies and/or epidemio-
logical studies.
where scabies has been definitively diagnosed and scabies
cases presenting with clinically typical symptoms, topical appli-
cation of phenothrin or oral ivermectin, which have a strong
insecticidal effect, are recommended. However, crotamiton
monotherapy may be effective depending on the patient.
Benzyl benzoate
CQ: Is benzyl benzoate effective for treating scabies?
Reference text: The treatment method differs depending on
the referenced article, and while it is difficult to determine the
efficacy and safety of this treatment clearly, it is effective to a
degree, so it may be used.
Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence).
Explanation: In some countries, benzyl benzoate is a first-
line topical treatment for scabies, and in Japan as well, it has
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
been used for a long time as a treatment not covered by health
insurance, including in the preparation of reagents. The usage
method varies, and depends on the preparation method (e.g.
lotion, mixed with crotamiton), the concentration (6–35%), the
number of doses and dosing intervals. The timing for determin-
ing efficacy is also not fixed. The efficacy of benzyl benzoate
has been described in an RCT with 181 subjects, comparing
benzyl benzoate 25% or 12.5% lotion with a single dose of
ivermectin. The treatment was effective with two doses.64 In an
RCT with 30 subjects, benzyl benzoate lotion (adult 25%, chil-
dren 12.5%) had an equivalent efficacy to aloe pulp.65 Con-
versely, another report, albeit a report of poor quality, showed
that c-BHC 1% ointment is effective but benzyl benzoate 6%
and crotamiton ointment is ineffective.66 Benzyl benzoate can
also cause irritant dermatitis as an adverse drug reaction.
Thus, based on the above information, this drug should be
used when no other option is available.
c-BHC, lindane
CQ: Can c-BHC be used to treat scabies?
Reference text: On 1 April 2010, c-BHC was designated in
Annex A of the Stockholm Convention relating to persistent
organic pollutants, so its use is now prohibited.
Recommendation level: D (recommended not to use the
treatment).
Explanation: c-BHC has historically been a highly effective
topical treatment for treating scabies, but it is not approved by
insurance; hence, it was prescribed as a hospital preparation.
While there is evidence of its efficacy,66 there is also evidence
of extremely severe adverse effects.67 There is also a report of
the concentration of c-BHC in the brain increasing to several
times that of the blood due to its lipid solubility and delayed
degradation.68 Accumulation of c-BHC in the environment is a
serious problem, so despite it being possible to prescribe this
drug as a clinically effective and highly safe therapeutic agent,
this drug should not be used based on the harmful effect of
Permethrin
CQ: Is permethrin effective for treating scabies?
Reference text: Permethrin is superior for treating scabies in
terms of both efficacy and safety, and it can be used in infants
aged 2 months and older, as well as in pregnant and lactating
women.
Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence)
Explanation: Permethrin belongs to the pyrethroid insecti-
cide family, and contains pyrethrum active ingredients and
derivatives. Permethrin 5% cream and lotion is used overseas
as a drug to treat scabies. There is little percutaneous absorp-
tion, with low toxicity to humans. The drug rapidly degrades
after taking effect, so it has no effect on the environment. Its
safety in infants aged over 2 months of age and in pregnancy
has been reported and it is used as a first-line drug in many
countries.69,70 According to the 2010 guideline for treatment of
infection prepared by the Centers for Disease Control and
Prevention, USA, permethrin may be used in infants and in
997
N. Ishii et al.
pregnant and lactating women.71 The transfer of permethrin
into breast milk is unknown. However, less than 2% of the
drug is absorbed into the body with a single application.72,73
The efficacy of permethrin in treating scabies is better than
ivermectin, c-BHC, benzyl benzoate, crotamiton and sulfur,
and the cure rate after one application ranges 89–98%. There
are reports that two applications 1 week apart has a cure rate
of between 85% and 100%.74,75 It is used in Japan through
individual importation of the drug,74 but it is not covered by
health insurance in Japan. As it contains formaldehyde as a
preservative, there is no plan to approve the drug (there is now
also a product available that does not contain formaldehyde).
Given that it is not possible to obtain permethrin in Japan
unless it is privately imported, it is not covered by health insur-
ance, and considering that this guideline is essentially a guide-
line for Japan, the recommendation level is set at C1.
Phenothrin
CQ: Is phenothrin effective for treating scabies?
Reference text: Based on clinical data and the data on per-
methrin, phenothrin is superior in terms of efficacy and safety.
Recommendation level: A (use of the treatment is strongly
recommended, Executive Committee determination).
Explanation: Clinical trials on phenothrin 5% lotion have
been completed, being approved by health insurance, and the
product entered the market on 22 August 2014, so the only
data available is that from the clinical trials. In a clinical trial
with 96 subjects where phenothrin was applied topically twice
at 1-week intervals, the drug had an efficacy rate of 92.6%. It
was effective in 88 subjects, ineffective in seven subjects and
indeterminate in one subject. Adverse drug reactions were
seen in eight subjects (7.8%). The main adverse reactions were
dermatitis (n = 2, 2.0%), elevated aspartate aminotransferase
(n = 2, 2.0%) and elevated alanine aminotransferase (n = 2,
2.0%), but the reactions were mild and improved at an early
stage.
This drug is highly effective with few adverse reactions. Phe-
nothrin belongs to the same pyrethroid family as permethrin.
The 50% lethal doses (lg/cm2) of phenothrin and permethrin
for D. farinae and Tyrophagus putrescentiae, which are similar
mites to S. scabiei, are less than 0.01 and 0.045, respectively,
for D. farinae, and 0.46 and 1.9, respectively, for T. putrescen-
tiae. Thus, phenothrin has been reported to have equivalent or
superior miticide action to that of permethrin.76 Therefore, as
the concentration of both drugs is 5%, it was determined that
they are effective against scabies. Because there is only data
from clinical trials, we are awaiting the results of the drug use
survey.
Malathion
CQ: Is malathion effective for treating scabies?
Reference text: There are no results that demonstrate the
efficacy of malathion.
Recommendation level: C2 (use of the treatment cannot be
recommended, as there is no evidence).
Explanation: Despite it being more than 30 years since the
trial that initially claimed the efficacy of malathion,77 there are
998
no malathion RCT in existence.78,79 On the other hand, an alert
has been issued regarding the purity of malathion.79
Malathion inhibits the action of cholinesterase, and inhibits
the degradation of acetylcholine, a neurotransmitter at nerve
endings; thus, this drug can produce acetylcholine hyperstimu-
lation-like symptoms.80
Malathion is used in countries such as England, but it can-
not be obtained for medical use in Japan.
Ivermectin
CQ: Is oral ivermectin effective for treating scabies?
Reference text: Ivermectin is effective for treating scabies.
Recommendation level: A (use of the treatment is strongly
recommended).
Explanation: Ivermectin is an anthelmintic collected and iso-
lated from the soil in Japan. However, ivermectin was
approved for the indication of scabies despite no clinical trials
being conducted globally on scabies with this product. There
are no RCT in Japan. Additionally, as there are many options
for effective topical medications available overseas, only a lim-
ited number of countries have approved ivermectin as a drug
to treat scabies.81 However, an RCT was conducted in Mexico
with 55 subjects, using a single dose of 200 lg/kg. The cure
rate in the ivermectin group was reported to be 74%, com-
pared with 15% in the placebo group, demonstrating the effi-
cacy of ivermectin, and no adverse reactions were seen.82
There is a wealth of usage experience with ivermectin in the
treatment of animal scabies or non-scabies parasitosis in
humans. There are also a number of RCT comparing the effi-
cacy of ivermectin with that of other drugs in the treatment of
human scabies. Ivermectin is currently widely used in Japan as
the only oral drug for human scabies and the results of post-
marketing surveillance of all 807 patients have been published
(the evidence level is low, but the number of cases is high).83
Considering these results, ivermectin is strongly recommended
for use in the treatment of scabies.
Ivermectin and c-BHC
CQ: Is ivermectin more effective than c-BHC in treating
scabies?
Reference text: Ivermectin is more effective in the treatment
of scabies than c-BHC.
Recommendation level: A (use of the treatment is strongly
recommended).
Explanation: Meta-analysis demonstrates that ivermectin is
significantly more superior in terms of efficacy than
c-BHC.81,84,85 There is no difference in the incidence of
adverse events. Currently, c-BHC cannot be used in Japan
(see c-BHC CQ section). Given these considerations, use of
ivermectin rather than c-BHC in the treatment of scabies is
strongly recommended.
Permethrin and c-BHC
CQ: Is permethrin more effective than c-BHC in treating
scabies?
Reference text: Permethrin is more effective in the treatment
of scabies than c-BHC.
© 2017 Japanese Dermatological Association

Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence).
Explanation: There are RCT61,86–89 and meta-analysis81
which demonstrate that permethrin is significantly superior to
c-BHC in terms of efficacy and antipruritic action. However,
permethrin is not covered by health insurance in Japan, and
considering that this guideline is essentially a guideline for
Japan, the recommendation level is set at C1.
Permethrin and ivermectin
CQ: Is permethrin more effective than ivermectin in treating
scabies?
Reference text: Permethrin is more effective in the treatment
of scabies than ivermectin.
Recommendation level: C1 (use of the treatment may be
considered, but there is insufficient evidence).
Explanation: There are RCT70,75,90,91 and meta-analysis81
which demonstrate that permethrin is significantly superior to
ivermectin in terms of efficacy. Permethrin has almost no
adverse effects. However, permethrin is not covered by health
insurance in Japan, and considering that this guideline is
essentially a guideline for Japan, the recommendation level is
set at C1.
Detailed exposition of drugs used to treat scabies
(pharmacological action, pharmacokinetics, usage
method)
The drugs currently available to treat scabies are shown in
Table 1, but this section describes the drugs available for use
in Japan.
Sulfur
Pharmacological action: On the skin surface, sulfur gradually
becomes hydrogen sulfide, polythionic acid, and particularly
pentathion, producing an antibacterial action that successfully
treats parasitic skin diseases. The –SH base, which is said to
have a relationship with skin keratinization, changes to S–S,
thus producing a keratin-softening action. The smaller the sul-
fur particles become, the more the chemical change of sulfur
is promoted. Therefore, when colloidal sulfur is used, the
aforementioned actions are particularly notable. When sulfur
is combined with alkaline drugs, the keratin-softening,
antibacterial and antiparasitic action intensifies. Sulfur and
sulfides destroy the scabies burrows and kills the mite bodies
and eggs.
Pharmacokinetics: No data.
Usage method: 5–10% precipitate sulfur ointment (prepared
in the hospital as a special preparation) is available for use.
The ointment is washed off 24 h after application, and this pro-
cess is repeated for 2–5 days or for 7 days.7
Mixtures of sulfur with bleaching powder, potassium chlo-
rate or potassium permanganate are explosive. Toxicity is low
and this therapy can be used on pregnant women and small
children, but the ointment is odorous and causes skin irritabil-
ity. It is essential to be aware that it tends to cause asteatotic
eczema.
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
Crotamiton
Pharmacological action, pharmacokinetics: The action mecha-
nism is unknown, but this product was developed as an insec-
ticide, and it is used to treat scabies.
Usage method: Crotamiton topical preparation is not cov-
ered by health insurance, but use is permitted with insurance
review. Crotamiton 10% cream is usually washed off 24 h after
application to the entire body. While it is said to be sufficient to
repeat application for 5 days, in reality, this drug needs to be
applied for approximately 10–14 days. It has been reported that
frequent use of crotamiton induces methemoglobinemia in chil-
dren,7 so continuous use requires caution. Crotamiton is added
to a variety of drugs as a solubilizing agent or an absorption
enhancer for the main agent,92 and it can induce contact der-
matitis,93,94 so it should be used with caution. Many crotamiton
preparations contain steroids (e.g. Eurax H cream),92 and these
preparations should not be used as scabicides.
It is advisable to avoid high doses or prolonged use of
the drug over wide areas in pregnant women, infants and
children.60,95
Benzyl benzoate
Pharmacological action, pharmacokinetics: The action mecha-
nism and pharmacokinetics are unknown.
Usage method: Benzyl benzoate is prepared in hospitals as
a special formulation in the form of 6–35% lotion (blemish balm
lotion, prepared immediately before use). In Western countries,
25% lotion is used for adults and lotions with lower concentra-
tions, such as 10%, are used for children. This kind of lotion
sometimes uses a flammable vehicle (e.g. ethanol). In these
cases, it is preferable to apply the lotion under the supervision
of a doctor. The lotion is washed off 24 h after application.
There are various regimens for using this lotion, including repe-
tition of cycles of 2–3 days of treatment followed by a 4–5-day
break or three doses every other day. This drug is intensely irri-
table and can cause conjunctivitis when exposed to the eyes.
Adverse reactions of the central nervous system have also
been reported. Therefore, particular care is needed when
applying the lotion to the face or neck, ensuring contact with
the eyes is avoided.96 This drug can also induce side-effects
including blister formation and itching sensation. It is recom-
mended to stop breast-feeding when using this drug for lactat-
ing women.97 It must not be used during pregnancy or in
children younger than 2 years of age.97,98
When using this drug, procedures are to follow the “Guideli-
nes on the preparation and use of in-hospital formulations”,
the approval of the in-hospital ethics review board is to be
obtained, written consent is to be obtained from the patient (or
guardian) after the efficacy and safety of benzyl benzoate has
been fully explained, and then the drug is to be used under the
responsibility of the attending physician. Combination of benzyl
benzoate with alkaline drugs is contraindicated as it undergoes
hydrolysis under alkaline conditions.99 Benzyl benzoate may
become unstable when mixed with crotamiton cream,100 which
contains weakly basic additives, so it is preferable to mix
immediately before use.
999
N. Ishii et al.
Phenothrin
Phenothrin (Sumithrin) is a topical preparation belonging to the
pyrethroid family, as is permethrin. Phenothrin was approved
for manufacture in 1976 as a drug to target household insects,
and it is sold as a treatment for head lice and pubic lice. The
concentration in OTC drugs is 0.4%.
The phenothrin structure consists of chrysanthemic acid and
3-phenoxybenzyl alcohol ester. Permethrin has an extremely
similar structure, with only a substitution of the dichloro group
on the end of the chrysanthemic acid (permethrin) replacing
the dimethyl (phenothrin) (Table 3). Phenothrin has superior
safety in the event of acute toxicity with both drugs, which
could be attributable to this substitution (Table 3).
Phenothrin 5% lotion (Sumithrin lotion 5%) can now be
used for medical purposes based on the indications and
effects for scabies (Table 1). Similarly, the concentration of the
pyrethroid insecticide permethrin in topical preparations is 5%.
To date there has been no published work on phenothrin topi-
cal preparation, and the comparison between this drug and
ivermectin based on clinical data and so forth is described in
Table 4.
Pharmacological action: Pyrethroid insecticides containing
phenothrin act upon the Na+ channels of nerve cells. Pheno-
thrin demonstrates its insecticidal action via repetitive depolar-
ization or interruption of nerve conduction through delayed
closure of Na+ channels.
Pharmacokinetics: Pyrethroid insecticides containing phe-
nothrin are more easily degraded by light, air and heat than
other insecticides, and their efficacy and toxicity rapidly disap-
pears, with little residual effect. In the bodies of mammals, pyr-
ethroid insecticides are metabolized (degraded) through rapid
ester hydrolysis, oxidation action and conjugation, so it tends
not to accumulate in body tissues.101 The main metabolite is
3-phenoxybenzoic acid (3-PB) and related metabolites are also
Table 3. Acute toxicity of phenothrin and permethrin in rats†
and their structural formulae
Oral Transcutaneous Inhalation
Drug name LD50 (mg/kg) LD50 (mg/kg) LD50 (mg/m3)
Phenothrin >5000 >5000 >2100 (4 h)
Permethrin 430–470 >2500 >685 (3 h)
† cell membrane permeability and hyperpolarization of nerve or
Household insecticides and pyrethroid: Usage and safety, Japanese
Industry Association of Household Insecticides, Osaka 2007.
LD50, lethal dose 50 (50% lethal dose).
1000
generated. When phenothrin is applied to the skin to treat sca-
bies, the unchanged drug demonstrates miticidal action, but if
any drug is absorbed into the body, it is thought to undergo
rapid metabolization (detoxification). Clinical data on phenothrin
lotion showed that the phenothrin in the applied lotion pene-
trates into the keratinous layer.102 Any phenothrin that is
absorbed from the keratinous layer into the body is rapidly
metabolized and excreted, with only a minute amount found in
the plasma and urine. The drug almost completely disappears
7 days after application. The concentration of phenothrin in the
keratinous layer is almost the same 24 h after application as it
is at the time of application, but the concentration rapidly decli-
nes after the drug is washed off.
Usage method: Normally, 30 g per dose is applied to the
skin below the neck at 1-week intervals, and then the drug is
washed off and removed in the bath or shower at least 12 h
after application. The lotion must be applied at least twice.
However, there is little experience with the use of phenothrin in
Japan, so it is essential to take adequate precautions regard-
ing the efficacy and safety of this drug and carefully monitor
the progress of the patient. There may be temporary itching
after the initial application. In Japan, there is no usage experi-
ence in children (safety is not established), and as children
have smaller body surface areas, the amount applied in a sin-
gle application should be reduced accordingly. There is no
experience of use in pregnancy in Japan, so safety is not
established. Thus, phenothrin should only be used when the
treatment benefits outweigh the risks. Phenothrin may be
excreted in the breast milk of lactating women,103 so it is
preferable to avoid use. If use is unavoidable, breast-feeding
should be stopped until 7 days after application when the
plasma concentration falls below detectable levels.
The use of phenothrin must be carefully examined, and the
characteristics of the drug should be fully explained to the
patient and their family.
Phenothrin-resistant head lice have been confirmed both
overseas and in Japan.104 Care must be taken to not use high
doses and frequent treatments of phenothrin randomly to treat
scabies, to ensure that phenothrin-resistant S. scabiei do not
appear.
Ivermectin
Ivermectin was approved in 2002 as a drug to treat intestinal
strongyloidiasis. In August 2006, the indication of scabies was
added, making it the only oral medication approved for scabies
(Tables 1,4). Ivermectin contains 90% or more of ivermectin
B1a and less than 10% of ivermectin B1b, so ivermectin B1a
is considered the main ingredient that elicits pharmacological
effect.105
Pharmacological action: Ivermectin is a broad-spectrum
antiparasitic drug; it belongs to the avermectin group, and has
a characteristic action mechanism. Ivermectin selectivity binds
with high affinity to the glutamatergic chloride channels in the
muscle and nerve cells of invertebrates. This results in elevated
muscle cells, leading to the paralysis and death of the para-
sites. In particular, ivermectin is thought to interact with other
© 2017 Japanese Dermatological Association
 Guideline for scabies in Japan

Table 4. Action and usage instruction for topical Phenothrin and oral Ivermectin

Non-proprietary name Phenothrin Ivermectin

Brand name
Antimicrobial agent
Major action
Current indications
Concentration in the keratinous
layer
Concentration in the plasma
Administration method
Precautions at administration
Administration to the elderly
Administration to pregnant
women
Administration to lactating
women
Administration to children
Adverse drug reactions
Sumithrinâ lotion 5%
Synthetic pyrethroid
Pyrethroid is the collective name for the active
ingredient contained in pyrethrum, and it is used
as an insecticide
Acts on receptors on the nerve cells of insects,
amphibians, and reptiles. It is a neurotoxin that
causes depolarization by continuously opening
Na+ channels. Has only a weak effect on
receptors in mammals and birds
Scabies
24 h after initial application, the mean
concentration of unchanged drug is
3.567 µg/cm2. This rapidly declines after
washing
The concentration of unchanged drug after initial
application is less than 10 ng/mL. The drug
almost completely disappears after 7 days
One dose (30 g) is applied to the skin from the
neck down at 1-week intervals, and then the
drug is washed off and removed in the bath or
shower at least 12 h after application. The lotion
must be applied at least twice
Avoid application to ulcerations or broken skin.
Do not use on the eyes or on mucosa
Elderly individuals usually have complications, or
are often taking other medications, so this drug
should be used with caution
Should only be used when the treatment benefits
outweigh the risks. There is no experience of
use in pregnancy, so safety is not established
Breast-feeding should be stopped for at least
1 week
Safety in children is not established (no usage
experience). Children have smaller body surface
areas, so the amount applied in a single
application should be reduced accordingly
Dermatitis, elevated aspartate aminotransferase
and alanine aminotransferase etc.
Stromectolâ tablets 3 mg
Semisynthetic oral anthelmintic derived from
avermectin†
Selectively binds with a high affinity to the
glutamatergic chloride channels present in
the muscle cells and nerve cells of
invertebrates, increases cell membrane
permeability, generates hyperpolarization in
nerve or muscle cells, to paralyze and kill
parasites. Reports also suggest that
ivermectin may intensify the action
of c-aminobutyric acid, an inhibitory
neurotransmitter
Scabies, intestinal strongyloidiasis
Reaches peak level approximately 8 h after
dosing, tends to decrease after 24 h
Reaches peak plasma level 4–5 h after
dosing, and half-life is approximately 18 h
Taken with water on an empty stomach (if this
drug is taken after a high-fat meal, the blood
drug concentration may increase)
Wait 1 week before re-dosing
The itching sensation may intensify
temporarily in the initial stage of treatment
Elderly individuals usually have complications,
or are often taking other medications, so this
drug should be used with caution
Should only be used when the treatment
benefits outweigh the risks. Safety in
pregnancy is not established. Teratogenicity
has been proven in animals
Breast-feeding should be stopped. The drug
transfers into breast milk and has been
detected in breast milk up to 14 days after
dosing
Safety is not established in children weighing
<15 kg (usage experience is limited)
Liver dysfunction, jaundice, reduced platelet
count, toxic epidermal necrolysis, Stevens–
Johnson syndrome, etc.

†
Nakanishi K. Current status and outlook for antiparasitic drugs – strongyloidiasis and ivermectin. BIO Clinica 1999; 14: 88–92.

ligand-gated chloride channels, albeit weakly, activated by
c-aminobutyric acid (GABA), a neurotransmitter. In terms of the
safety margin of this class of compounds in humans, the safety
of ivermectin is considered to be assured. Given that the pres-
ence of glutamatergic chloride channels has not been reported
in mammals, ivermectin has a poor affinity with specific binding
sites in the brains of mammals, and avermectins do not easily
cross the blood–brain barrier in mammals such as rats.106
It has been reported that ivermectin has a p-glycoprotein
(p-Gp) substrate.107 Therefore, reports indicate that

© 2017 Japanese Dermatological Association 1001

N. Ishii et al.
combination of ivermectin with drugs that inhibit p-Gp in sheep
inhibits gastrointestinal p-Gp, increasing the absorbed amount
(resulting in elevated plasma concentration),107 so care should
be taken in humans. The brain/blood concentration ratio during
p.o. administration of ivermectin to rats and mice was small,
suggesting that ivermectin has poor permeability of the blood–
brain barrier. Tests also show that the transfer of ivermectin
B1a into the cerebrospinal fluid of female dogs is extremely
low. However, it should be considered that when used in com-
bination with other drugs that similarly inhibit p-Gp, the excre-
tory function of p-Gp at the blood–brain barrier is inhibited,
which may result in the distribution of ivermectin into the
brain.106
Pharmacokinetics: Oral absorption of ivermectin is relatively
rapid. When 6–15 mg ivermectin tablets are administrated to
healthy adults, the maximum plasma concentration peaks in 4–
5 h (12 mg dose is ~30 ng/mL), and subsequently disappears
with a half-life of 10–20 h.106 Within this dosage range, the
pharmacokinetics are dose dependent and there is almost no
racial or sex differences.106 Ivermectin is a fat-soluble drug,
and there are reports showing that absorption increases
approximately 2.57 times after consumption of a high-fat
meal.108 Therefore, it is preferable to take this drug on an
empty stomach. Ivermectin has high transitivity to tissues (vol-
ume of distribution, 4–5 L/kg),106 and data from non-clinical tri-
als suggest that the drug is distributed to the liver in high
concentrations. Therefore, liver function tests should be imple-
mented as needed in patients with liver dysfunction and in
elderly patients.
The transitivity of ivermectin to the skin is as described
below.109 A single oral dose of ivermectin 12 mg was adminis-
trated to five patients hospitalized with scabies, and the con-
centration of ivermectin was measured in the scales, sebum
and sweat at seborrheic zones (forehead, behind the auricle of
the ear) and non-seborrheic zones (index finger, dorsum of the
hand, axilla and abdomen). Ivermectin was detected in all the
samples. The highest concentration was in the forehead, and
the concentration was 23  11 ng/g in four patients with
asteatotic eczema and 110 ng/g in one patient with seborrheic
skin. Tmax was seen after 8 h in almost all the samples. The
drug concentration in the skin was investigated in a patient
with onchocerciasis administrated a single oral dose of iver-
mectin 150 lg/kg.110 The skin and plasma concentration 4 h
after dosing was 90.9 ng/g and 46 ng/mL, respectively,
decreasing to 66.6 ng/g and 24 ng/mL 48 h after dosing. After
72 h, the skin concentration was 41.4 and 64.9 ng/g in two
patients. Based on the aforementioned two published works,
transfer to the skin reaches the maximum level 4–8 h after dos-
ing, and is thought to decrease steadily thereafter. A higher
concentration of the drug transfers to seborrheic zones. The
minimum lethal dose for S. scabiei has not been clarified.
Metabolites are mainly formed via oxidation or desorption of
glucose, and cytochrome P450 3A4 (CYP3A4) is presumed to
be involved in part of the metabolic reaction.106 Only a very
small amount is excreted in the urine, so it is not necessary to
reduce the dose in patients with renal disorders or on dialy-
sis.111 However, there are a number of reports of adverse
1002
reactions relating to kidney function.112 Almost all the metabo-
lites are excreted in the feces, and it takes 12 days or more for
95% or more of the drug to be eliminated.106
Dosing method: The drug is taken with water on an empty
stomach at a dose of 200 lg/kg. Safety is not established in
children weighing less than 15 kg. Teratogenicity has been
proven in animals, so this drug should not be used during
pregnancy. The maximum concentration was distributed in
breast milk 4 h after administration of 12 mg ivermectin to
breast-feeding women (maximum concentration, 7.6 ng/mL),
and ivermectin was detected in breast milk 14 days after dos-
ing.106 Therefore, it is preferable to stop breast-feeding when
using this drug and to resume breast-feeding once a sufficient
period of time has elapsed since dosing.
Studies suggest that ivermectin may enhance the action of
GABA, an inhibitory system neurotransmitter.113,114 Therefore,
particular care is essential when using this drug in combination
with drugs that reinforce the activity of GABA, such as barbitu-
rates, benzodiazepines and sodium valproate, as it can lead to
augmented activity.
There can be temporary intensification of the itching sensa-
tion and eruptions in the initial stages of treatment with iver-
mectin. The reason for this is presumed to be due to a
temporary release of a high volume of mite body components
due to ivermectin killing the mites, which intensifies the allergic
reaction. This allergic reaction may persist for a number of
months after the mites have died, so the drug is not to be hap-
hazardly administrated again due to symptoms such as itching
or erythema, unless new characteristic eruptions appear and
surviving mites are identified.105
There have been reports of adverse drug reactions including
liver dysfunction, jaundice, reduced platelet count, toxic epi-
dermal necrolysis and Stevens–Johnson syndrome. Therefore,
appropriate measures should be taken such as monitoring skin
symptoms after dosing, and conducting blood biochemistry
tests 1 week after dosing.
A report has shown that ivermectin tablets can easily be
suspended in warm water at 55°C (simple suspension method),
enabling effective administration via a gastric tube.115 How-
ever, ivermectin is sparingly soluble in water, and most of the
drug precipitates in suspension. Hence, the dose may be
reduced by close to half depending on the technique used for
tubal administration. When administrating ivermectin suspen-
sion via a gastric tube, infusing the drug with the angle of the
alimentary syringe perpendicular or sloping downward, and
infusing the remaining precipitate in the syringe with rewashing
can keep the dose loss to 10% or less.116 When administrating
the drug with a nasogastric tube, if the bed is in a 30° upright
position and a technique similar to that used with the syringe
is employed, it has been confirmed that there is no loss of iver-
mectin dose.117
Phenothrin and ivermectin combination therapy
Safety: Phenothrin primarily undergoes ester hydrolysis, and 3-
PB is produced as the main metabolite. 3-PB is mainly metab-
olized by cytochrome P450 2E1.118 The involvement of
CYP3A4 in the metabolism of ivermectin has been clarified,119
© 2017 Japanese Dermatological Association

so it is unlikely that competitive inhibition will occur in the
metabolic enzymes. Guidelines for treating scabies in northern
Australia and in the USA recommend combining permethrin
and ivermectin for the treatment of crusted scabies, and no
serious adverse events have been reported through using
these two drugs in combination.70 There were no reports of
serious adverse events when topical permethrin and oral iver-
mectin were used in combination in four subjects in a clinical
study report in Japan.74
Efficacy: Phenothrin acts upon Na+ channels in the nerve
cells of invertebrates, exciting and killing parasites through the
depolarization of nerve cells or by interrupting neurotransmis-
sion. On the other hand, ivermectin acts upon the glutamater-
gic chloride channels present in the nerve cells of
invertebrates, causing hyperpolarization of nerve cells, and par-
alyzing and killing parasites. While the action site differs, the
induced effect is excitation of the nerve cells and paralysis, so
it cannot be ruled out that using these two drugs simultane-
ously may affect efficacy. However, in overseas guidelines, no
mention is made of the dosing timing of the two drugs.70 The
“Safety and efficacy when used in combination with other
drugs for treating scabies” was incorporated into the post-mar-
keting drug risk management plan for phenothrin lotion.120
Usage method: At present, the usage method for topical
phenothrin is removal of the lotion at least 12 h after applica-
tion, by washing in a bath or shower. Ivermectin is to be taken
with water on an empty stomach, so dosing is conducted in
accordance with these procedures. However, further investiga-
tion with more cases should be conducted to examine drug
interactions, efficacy and safety when the two drugs are used
in combination.
Actual treatment method
The treatment algorithm is shown in Figure 1.
With common scabies, the usage method for topical agents
is application of the medication over the entire body below the
neck, including areas free of eruption. Ensure all areas are
coated, including behind the ears, between the fingers, the
external genitalia and the buttocks. With children and elderly
patients, ensure the entire body is coated, including the face
and the head, even with cases of common scabies.
With crusted scabies, the entire body is to be coated,
including the face and the head.
With sulfur, crotamiton and benzyl benzoate, the topical
agents are to be washed off in a bath or shower 24 h after
application. The same process applies to phenothrin 12 h or
more after application. Consider wearing gloves and socks
as needed to prevent the medication entering the mouth.
Treatment is completed once S. scabiei is no longer
detected, or no new formation of eruptions characteristic of
scabies, such as the scabies burrows, occurs. However, be
aware of itching sensation, eruptions, reinfestation and relapse
after scabies treatment.
Common scabies
Virtually none of the existing scabicides kills the eggs, includ-
ing phenothrin and ivermectin. The eggs of S. scabiei hatch in
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
3–5 days, so the drugs should be administrated taking into
consideration the life cycle of the mites.
There are topical treatments and oral treatments.
Topical treatment. Phenothrin (recommendation level A) is rec-
ommended as the first-line drug, and it should be applied at
least twice with a 1-week interval between applications. The
topical medication is washed off in the bath or shower at least
12 h after application. There is limited experience with phe-
nothrin use, so it should be administrated while checking effi-
cacy and safety.
Second-line drugs are crotamiton (C1), sulfur (C1) and ben-
zyl benzoate (C1).
Oral treatment. Ivermectin (A) is administrated on an empty
stomach at a dose of 200 lg/kg. The patient is requested to
come back after 1 week, and if S. scabiei are detected with a
microscope or dermoscope, or if new formation of the charac-
teristic scabies eruption (e.g. scabies burrows) is seen, then
ivermectin is re-administrated. Liver function tests should be
conducted as necessary for patients with liver dysfunction or
elderly patients. Normally, the scabies are cured in approxi-
mately 1 month with two doses.121
When insufficient response is seen with topical treatment
or oral treatment, consider changing the treatment method
after checking treatment compliance with the patient.
Patients on steroids or those taking immunosuppressants,
patients with malignant tumors and diabetes, those on dialy-
sis and elderly patients may have a reduced immune status,
which may prolong the treatment period. For such cases,
combined treatment with topical and oral medication should
be considered.122
Crusted scabies
The basic treatment is: (i) removal of the hyperkeratotic
layer; and (ii) topical, oral, or a combination of topical and
oral treatment. As there is no experience in Japan of com-
bining phenothrin lotion and ivermectin, careful consideration
should be given to drug interactions, efficacy and safety
when using these drugs in combination. As a measure to
prevent the spread of infection, the patient needs to be iso-
lated in a private room for 1–2 weeks after obtaining consent
for this procedure.
The topical phenothrin lotion is applied to the entire body.
An occlusive dressing is applied over the lotion using Vase-
line containing salicylic acid or zinc oxide to soften the
thickened keratinous layer and crust. After the keratinous
layer has softened, it is loosened by bathing and subsequent
removal with a brush or other such implement. This skin
treatment procedure is repeated every day, including days
when phenothrin lotion is not applied. The patient must
always be checked for the presence of nail scabies. Iver-
mectin is used as oral therapy.
Microscopy is performed once a week and treatment meth-
ods should be considered after checking for the presence of
S. scabiei and for new eruptions characteristic of scabies, such
as scabies burrows. Some reports claim that the number of
1003
N. Ishii et al.

Scabies

Common Crusted scabies

scabies
Removal of thick keratinous layer
Recommendation level A
Recommendation level A
(Executive committee
(Executive committee
consensus)
Recommendation level A consensus)

Topical Oral Combined topical and oral therapy

Phenothrin Ivermectin Phenothrin and Ivermectin
However, the efficacy and safety of
combination treatment is unconfirmed

1. Scabies detected
2. New skin lesions
characteristic of scabies
(scabies burrows, etc.)

Neither present 1 and/or 2 are present

End of treatment
Be aware of post-treatment itching sensation,
eruption, reinfestation and relapse
Reinvestigate diagnosis and
treatment
Insufficient treatment
Poor compliance to treatment
Reinfestation, Misdiagnosis
Drug-resistant scabies

Figure 1. Scabies treatment algorithm. This algorithm only describes recommendation level A treatment. Refer to this document for
the usage methods of each drug. This does not preclude the use of other drugs to treat scabies.

doses should be determined based on the severity classifica-
tion of the crusted scabies.123 However, in Japan, there are
few cases, so it is essential to consider this procedure after
more cases have been evaluated. As there is no experience in
Japan of multiple applications of phenothrin lotion, it is vital to
consider the efficacy and safety of applying this lotion more
than three times carefully.
Although the efficacy of ivermectin against nail scabies
has not been evaluated in basic studies, its clinical ineffec-
tiveness against nail scabies has been reported.124,125 Partic-
ularly in cases where mites are found within and above the
nail plate, the drug cannot penetrate into the nail. For this
reason, ivermectin is not used in cases where scabies is
confined to the nails. In such cases, phenothrin lotion
monotherapy should be used as topical therapy, or occlusive
dressing therapy should be used with multilayer coatings of
keratolytic agents such as Vaseline containing salicylic acid
for 24 h. Topical therapy using phenothrin lotion should be
repeated at weekly intervals and topical Vaseline containing
salicylic acid should be applied between applications of phe-
nothrin lotion. In parallel with the topical therapy, physically
scraping off the nail and the thickened keratinous layer and
cutting the nail short will reduce the amount of diseased nail,
reduce the number of mites and improve the penetration of
the drug.
Examples of drugs used for each age group
(Table 5)
In individuals with a bodyweight of 15 kg or more, treatment
for scabies should be used (Figure 1).
Regarding children aged 2 months and older, or with a
bodyweight of less than 15 kg, the safety of phenothrin has
not been established (no usage experience), but phenothrin
(C1) can be used. However, when using the drug, the patient
and guardian (family) should be fully informed that there is no
usage experience in children as it is a new drug. Otherwise,
sulfur (C1) or crotamiton (C1) may be used.
Regarding children younger than 2 months of age, there is
no evidence on therapeutic agents. Phenothrin is highly safe,
but this drug should only be used after the patient’s
guardian (family) has been fully informed and consent
obtained.

1004 © 2017 Japanese Dermatological Association

 Guideline for scabies in Japan

Table 5. Drugs for treating scabies for different types of There may be temporary intensification of the itching sensa-
patients (Executive Committee consensus) tion in the early stage after ivermectin treatment, and this may
also be prolonged. Oral antihistamines should be used to con-
Recommendation
trol the itching sensation.
Patient classification Recommended drug level
Bodyweight ≥15 kg Topical phenothrin A Treatment for patients with diseases that require
Oral ivermectin A
steroid therapy
Topical sulfur C1
Oral and topical steroid therapies may exacerbate scabies and
Topical crotamiton C1
Topical benzyl C1 prolong the time until the scabies are cured.121 Therefore, it is
benzoate preferable to refrain from steroid therapy when treating sca-
Children 2 months or Topical phenothrin C1‡ bies. However, when a patient has a disease that requires ster-
older, weighing Topical sulfur C1 oid therapy, the attending physician should be consulted
<15 kg† Topical crotamiton C1§ regarding continuing with steroid therapy. When steroid ther-
Children <2 months Topical phenothrin C1¶ apy is essential, the dose should be kept to the minimum
Pregnant women Topical phenothrin C1‡ required dose. If continuing with topical steroid, the patient’s
Topical sulfur C1 condition should be carefully monitored.
Topical crotamiton C1§
Lactating women Topical phenothrin C1††
Reference: Permethrin, which is used overseas (not cov-
† ered by health insurance in Japan), and phenothrin, which is
Benzyl benzoate may be used in children older than 2 years of age (C1).
‡ used in Japan, are both drugs with 5% concentration of pyre-
The safety of phenothrin is not established (no usage experience), so
the drug should be fully explained to the patient and his/her guardian throid. Permethrin may be used in infants 2 months and older,
(family) and consent obtained. and in pregnant and lactating women.
§
Do not use crotamiton over a wide area in children. Avoid using in
large doses or over a wide area for an extended period of time in preg-
nancy.
¶
The safety of phenothrin is not established (no usage experience), so JUDGMENT OF CURED SCABIES AND POST-
the drug should be fully explained to the patient’s guardian (family) and CURE SYMPTOMS, REINFESTATION AND
consent obtained.
††
RELAPSE
The safety of phenothrin is not established (no usage experience), so
the drug should be fully explained to the patient and her family and Judgment of cure
consent obtained. Breast-feeding should be stopped for at least 1 week
Mites are difficult to detect during treatment of scabies, so a
when this drug is used.
judgment of cure is made if no mites are detected in two con-
secutive tests at weekly intervals and no new skin lesions
indicative of scabies (i.e. burrow formation) are visible. Because
Examples of drugs used in pregnant and lactating the incubation period of scabies is approximately 1–2 months, it
women (Table 5) is advisable to make follow up of the patient a few months.
Phenothrin (C1) has low toxicity (Table 3), and the plasma con- In cases treated with ivermectin, relapse of the disease
centration after application is low (Table 4), so it can be admin- 2–4 months later has been reported;126,127 therefore, it is desir-
istrated. However, it is a new drug, and there is no usage able to continue monitoring until several months after the
experience; thus, the patient and their family should be fully judgment of healing.
informed before use. Ultimately, the drug should only be used
when it has been determined that the medical benefits out- Post-cure symptoms
weigh the risks. Otherwise, sulfur (C1) or crotamiton (C1) may After scabies have been cured, the eruption and itching sensa-
also be used. Ivermectin must not be used. tion (post-scabietic pruritus) may persist for a prolonged period
Many drugs, including drugs to treat scabies, are excreted after extermination of the mites.5 When there are significant
in breast milk, so it is recommended to stop breast-feeding clinical symptoms, an eczematoid lesion may be present, and
when using these drugs. rarely, hives and/or nodules (post-scabietic nodule) may
appear.128–130 The skin lesion and itching sensation usually
Treatment of itching sensation persist for 2–3 weeks. However, this varies considerably
Oral antihistamines are administrated to control the itching between individuals, and may persist for 3 months to a year.
sensation. However, first-generation antihistamines have anti- There are differences depending on the affected site as well,
cholinergic action, so they cannot be used in patients with with almost all sites on the trunk and limbs having an itching
benign prostatic hypertrophy, glaucoma, epilepsy or other sensation for approximately 2 weeks, while the itching sensa-
related disorders. In elderly patients and children, considera- tion on affected sites on the hands and feet may persist for
tion must also be given to the adverse reaction of somnolence, 3 months. However, if the skin lesions and itching sensation
reduced work efficiency and the risk of falls. Thus, classical do not resolve, while treatment for scabies is not needed, the
antihistamines should be administrated with adequate care. other symptoms should not be left untreated for an extended
Therefore, it is preferable to use non-sedating second-genera- period. Treatment using moisturizers, topical steroids and anti-
tion antihistamines. histamines should be used as needed.

© 2017 Japanese Dermatological Association 1005

N. Ishii et al.
Reinfestation and/or relapse
It is not uncommon for scabies to be judged “cured” after
treatment, only to be diagnosed again a few months later (rein-
festation/relapse).127,131 In such cases, reinfestation or relapse
is determined by examining the patient, confirming treatment
compliance and making inquiries about or examining the skin
condition of people in the patient’s immediate vicinity, such as
roommates, family, friends and acquaintances. Genetic testing
of the mite infesting the person may also be considered to
make a judgment on reinfestation and relapse.132 However, at
present, there is no practical application of testing methods to
differentiate between different mite infestations.
Reinfected/relapsed scabies still respond to treatment,54,127
so at present, it is not necessary to consider drug resistance
when treating reinfected or relapsed cases. However, resis-
tance to ivermectin has already been reported in the veterinary
field.133 There has also been a report of two human cases
overseas where in vitro-resistant S. scabiei were confirmed,54
so caution is now essential.
PREVENTION OF INFESTATION
For the prevention of scabies infestation, it is necessary to
adopt measures based on the ecology of S. scabiei. Medical
personnel, as well as the directors and managers of facilities,
patients and patient families should all be adequately educated
on the clinical condition, diagnosis, treatment and prevention
of scabies, which will prevent panic in the event of a mass out-
break, and will also serve as a preventative measure.
Basic concept of scabies prevention
If a scabies patient is confirmed in an area of communal living,
including hospitals, facilities for the elderly, facilities for the dis-
abled, children’s nursery school and so forth, first checks are
to be made to rule out other scabies patients. The infectivity of
common scabies is not very strong, so the risk of infestation is
low without close contact with the affected patient. Typical
examples of persons in close contact would be someone shar-
ing a bed with the affected person, but shared bedding or
walking hand-in-hand with someone for a prolonged period of
time also poses a risk of infestation.
If two or more scabies patients are found within the same
group within a few months, it would be considered a mass out-
break. Crusted scabies should be considered as a source of
infection, so efforts must be made to locate the patient with
crusted scabies.
When taking measures to prevent scabies infestation, it is
important to ensure early diagnosis and early treatment without
overlooking any potential scabies patients.42 Medical examina-
tion days should be adjusted based on consideration of the
incubation period. Drugs used to treat scabies are miticides,
and treatment of the patient will reduce the number of living
S. scabiei on the surface of the patient’s skin, thus reducing
infectivity.
Common scabies do not have a strong degree of infectivity.
With the exception of special circumstances, the source of
infection in a mass outbreak will be crusted scabies. However,
1006
even with epidemiological studies, it is often impossible to
identify the crusted scabies that are the source of
infection.44,134,135 Patients with crusted scabies are often in
poor general health, and may leave the affected group before
diagnosis due to death or hospital transfer, so the affected
person may be absent at the time the mass outbreak is recog-
nized. In these situations, the patient first diagnosed with com-
mon scabies may be erroneously regarded as the source of
infection.
Even if infection prevention measures are adopted, new
scabies patients may appear, but this does not always mean
that the respective measures are inadequate. This is because
the patient might have been infested prior to implementation of
the preventative measures, and the infestation became symp-
tomatic after the incubation period. The incubation period is
long, so new cases may be seen after a number of months. It
is recommended to continue with the minimum required mea-
sures that can be implemented without exhausting people in
the workplace, based on the understanding of the differences
between common scabies and crusted scabies (Table 6).
Mass outbreak
Even with a mass outbreak, conditions can vary, depending on
factors such as the number of affected patients. Namely, the
risk of infection differs depending on: (i) the potency of the
infection in the index case; (ii) the period of time the index case
came into contact with others before preventative measures
were in place; and (iii) group characteristics (age, underlying
diseases, immunity and behavior). The measures required to
mitigate that risk will differ depending on the extent of available
funds and the burden of effort. The aforementioned conditions
will differ for each individual mass outbreak, so there is no
fixed standard for measures that should be adopted. There-
fore, it is necessary to examine measures to suit the circum-
stances of each particular facility.
1. The infectivity of scabies patients differs depending on the
number of mites infesting the patient. The infectivity of
crusted scabies is also thought to differ depending on the
extent of hyperkeratosis, and there have been attempts to
grade risks based on clinical findings.122 Establishment of
infection will also be affected by the immunity of the person
who came into contact with the patient, and particular care
is needed with individuals using immunosuppres-
sants.136,137
2. Cases differ significantly depending on the timeframe from
onset in the first patient (sometimes it may not be possible
to identify this person), until a mass outbreak is recognized
and measures are started.42 The longer this period of time,
the longer the period where people are exposed to the
source of infection without any measures in place, and the
larger the scale of the mass outbreak. Group behavior pat-
terns, including the frequency of close contact, will also
change the way in which the infection spreads. There have
been reports of cases where staff nursing and caring for
bedridden patients with crusted scabies become infested
and the infestation then spreads to other patients and fam-
ily members via the infected staff members.138,139
© 2017 Japanese Dermatological Association
 Table 6. Essential points for prevention of scabies†

Measure Common scabies Crusted scabies

Hand washing
Hand washing for each Enforced Enforced
procedure
Physical care
Wearing prophylactic No particular Necessary (only during isolation period)
gowns and gloves infection
Used gown and gloves prevention
to be placed into measures needed
plastic bag or the like
to avoid spread of
scales
Bathing
Bathing care has a high Ordinary method Patient is to take a bath last. The bathtub and bathroom floor to be cleaned with water. The dressing room to
risk of infection not be cleaned with a vacuum cleaner
only from scabies, but

© 2017 Japanese Dermatological Association

also other infections
such as tinea, so
routine care should be
taken with
management of
towels, floor mats, etc.
Arrangement of room and environment
Insecticide applied to Unnecessary Necessary (Pyrethroid insecticide sprayed once at the end of isolation/when leaving the room)
patient’s living area
and areas the patient
has visited
Cleaning Ordinary method After removing the scale with a mop or adhesive sheet, clean with a vacuum cleaner (preferably with a filter)‡
Disinfection of bedding Unnecessary At the end of isolation/when leaving the room, cleaning is performed after one round of thermal drying or
spraying with pyrethroid insecticide (see above)
Wheelchair, stretcher, Ordinary method At the end of patient isolation, cleaned with a vacuum cleaner or sprayed with pyrethroid insecticide
sphygmomanometer
Beds in examination Examination rooms, magnetic resonance imaging and electroencephalogram etc. routinely use disposable sheets on the beds, and these
rooms, testing rooms, are replaced for each patient§
etc.
Control of linens
Exchange of sheeting, Ordinary method Exchanged after each treatment to prevent infection of the household
bedding and clothing
Precautions during Routinely placed in plastic bag for transport to avoid spread of scales even if the scales detach from the laundry§
transport of laundry
Washing Ordinary method Any of the following
Dried in a dryer after normal washing
Heat treated at 50°C for 10 min before washing
Sealed and sprayed with pyrethroid insecticide before washing

1007
Guideline for scabies in Japan
 1008
N. Ishii et al.

Table 6. (continued)

Measure Common scabies Crusted scabies

Control of hospital room
Isolated in a private
room (informed
consent and respect of
human rights needed)
Prophylactic care of
persons who came
into contact with the
patient
Unnecessary Isolated in a private room and treatment started
The patient should be moved together with the bed and bedding
Isolation lasts for 1–2 weeks after start of treatment
Prophylactic care Prophylactic care considered for roommates, irrespective of the presence/absence of symptoms. Prophylactic
considered for care for employees considered depending on the frequency and degree of contact with the patient. (see the
roommates, family main text for details)
members or the
like if they sleep
on the same floor
(see main text for
details)

The prophylactic measures shown in this table do not aim to achieve zero scabies patients in a short timeframe. The reason is that by the time a mass outbreak is recognized, there are already
many people who are infested or in the incubation period. It is also virtually impossible to determine who is in the incubation period.
The incubation period of scabies is long, so the period of time where there may be new patients who emerge from the incubation period extends to a number of months. However, if the affected
person is accurately diagnosed and treated, and the condition is prevented from becoming crusted scabies, then mass outbreaks will definitely come to an end. Implementing excessive infection
prevention measures without exhausting the staff is essential for mass infection.
The measures shown below are based on the premise that treatment has already started. Treatment is the highest priority infection prevention measure for scabies.
There are cases which are difficult to differentiate common scabies and crusted scabies clearly. The measure would also differ depending on the presence or absence of an immunocompromised
individual in the group. The information shown in this table details the basic measures and the concepts that support the measures. Each facility is to examine the detailed measures.
†
Each facility should create a manual tailored to the circumstances in the facility, based on this table.
‡
If there is a large volume of scales and the area is cleaned with a vacuum cleaner, there is a risk that the scales will be dispersed via the vacuum cleaner’s exhaust. Therefore, it is better to first
recover the scales using equipment such as a mop, cloth, or adhesive sheet, and then use a vacuum cleaner.
§
Scabies has a long incubation period, so it is impossible to prevent scabies being “brought into” the facilities completely. It is recommended to have routine measures in place, including linen
control, to enable prevention of the spread of the infestation even if there is a case of crusted scabies.

© 2017 Japanese Dermatological Association


3. It is essential to have a leader to take command of infec-
tion prevention during a mass outbreak. That person should
conduct an epidemiological survey, ascertain any changes
in the number of patients and the response to treatment,
and explain the situation to concerned parties. They must
also decide how much effort should be expended and how
much financial burden is needed for the infection preven-
tion measures.
4. There are occasions when patients with crusted scabies
must be put into isolation. Isolation is a restriction of
human rights. Therefore, it is necessary to obtain informed
consent for this procedure and to limit the period of isola-
tion to the required minimum.
Prophylaxis
Prophylaxis should be considered for people who may have
been in close contact with crusted scabies patients, even
when the patient was asymptomatic, as that would have been
the incubation period. Providing prophylaxis can be expected
to ensure a “cure” for people who are currently in the incuba-
tion period, thus preventing the onset of scabies. However,
even if the onset conditions are investigated epidemiologically,
the source of infection and route of infection may be unknown,
and it is often impossible to identify who has been in close
contact with the affected person. In these circumstances, it is
not recommended to provide prophylaxis, and instead to moni-
tor the person’s progress and treat affected people as they
become symptomatic.
Mass prophylaxis
When the attack rate within a group is high, and when all
members of the group may have had close exposure, prophy-
laxis of all the members of the group may be an option. There
are many reports of mass treatment in hospitals, facilities,
communities and so forth using topical and oral medication.140
There are reports of mass treatment where permethrin was
applied simultaneously to several hundred people, and the
mass outbreak was controlled in a short period of time.141,142
However, there are also reports where all the people who
came into contact with the affected person were dosed with
ivermectin en masse, but they subsequently developed sca-
bies.51,126 It should be noted that there are limitations with effi-
cacy when embarking on prophylaxis, particularly with mass
treatment.
Methods of prophylaxis and mass prophylaxis
When using prophylaxis, informed consent should be obtained
from the person being treated regarding the advantages (e.g.
possibility of ending mass outbreak, possibility of curing scabies
in the incubation period) and the disadvantages (e.g. cost bur-
den, overtreatment, possibility of adverse reactions). However,
this treatment is not covered by health insurance. There are no
standards on mass prophylaxis, neither is there any information
on the scale of a mass outbreak that would necessitate mass
prophylaxis.140 Therefore, a decision must be made based on
the information in section “Mass outbreak” 1–4 above.
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
Is there any significance of adopting a “border
strategy” for scabies?
Scabies is a disease that spreads through human-to-human
contact, so living in groups presents a risk for infection. In
other words, the risk is considered to be higher in patients
who are transferred from another hospital or facility, than in
patients who are admitted to the hospital or placed into facili-
ties from their own home. However, scabies is a disease with
a long incubation period, so the incidence of scabies is low in
patients transferred from hospitals or facilities. Therefore,
implementing measures such as requesting a negative diagno-
sis certificate or implementing prophylaxis across the board is
not recommended.143 It is important to observe the individual
for a certain period of time.
Mass outbreak of scabies in children
Historically, scabies is a disease that is prevalent mainly in chil-
dren and sexually active young people. There are also many
children affected by scabies in developing countries.144,145
In Japan, there have been a number of reports of mass out-
breaks in nursery schools,20,146,147 and the pattern of the
spread of infestation differs depending on the circumstances
of the case. Compared with cases in hospitals and elderly care
facilities, more cases and suspected cases in the general pop-
ulation are seen at many different regional dermatological clin-
ics. It is essential to be aware of the difficulty of compiling
information on treatment, and infection prevention policies.142
DRUGS USED TO TREAT SCABIES OVERSEAS
The drugs used for scabies overseas and their respective posi-
tioning are shown in Table 7.
ANIMAL SCABIES
Summary
There are different types of scabies unique to each mammal
host, including humans, monkeys, dogs, cats, rabbits, cows,
horses and sheep. Scabies where the original host is not
human, but temporarily infests humans, causing skin disease,
is known as animal-transmitted scabies.148,149 The incidence of
animal-transmitted scabies has increased together with the
recent boom in pet ownership. As people increasingly live
together with animals, the chance of humans being infested
with canine and feline scabies has increased.
The main causative mite for animal-transmitted scabies is
the scabies specific to dogs, Sarcoptes scabiei var. canis. This
type of scabies is a variant of the human S. scabiei and the
two types are morphologically indistinguishable. Canine sca-
bies can temporarily infest human skin, but they cannot repro-
duce.150 When canine scabies infest dogs, they cause
significant hair loss. The condition can become very serious,
much like human crusted scabies, and can even result in
death.
Apart from canine scabies, feline scabies, Notoedres cati,
and canine ear scabies, Otodectes cynotis, can also cause ani-
mal-transmitted scabies.
1009
 1010
N. Ishii et al.

Table 7. Position of scabies treatment in various countries

USA† Australia UK‡ France Germany Canada Vietnam Korea§ Japan

Recommended drug/ Permethrin Permethrin Permethrin Permethrin Permethrin Permethrin Diethyl Permethrin Phenothrin
first-line drug Crotamiton Benzyl (applied Benzyl c-BHC phthalate c-BHC Ivermectin
benzoate topically benzoate
(25%) twice) (10%)
Ivermectin Allethrin
Benzyl
benzoate
Crotamiton
Second-line drug Ivermectin Ivermectin Malathion c-BHC Crotamiton Crotamiton Sulfur
(applied Crotamiton
topically Benzyl
twice) benzoate
Substitute drugs Sulfur Crotamiton Ivermectin Crotamiton Benzyl Benzyl
Sulfur benzoate benzoate
Off-label use Crotamiton
Not adopted Benzyl c-BHC c-BHC Ivermectin Ivermectin Ivermectin Permethrin
benzoate Permethrin

Based on information obtained in 2017. Overseas drugs used for treatment includes drugs not covered by health insurance in Japan.
†
(USA) Permethrin is the standard treatment, but ivermectin is used for refractory cases. c-Benzene hexachloride (c-BHC) is not used in many states.
‡
(UK) Ivermectin is used for cases that are refractory with topical treatment only and for crusted scabies.
§
Sexually Transmitted Infections Korea Guidelines KCDC 2016.

© 2017 Japanese Dermatological Association


Skin symptoms of animal-transmitted scabies
The clinical profile of animal-transmitted scabies is similar to
human common scabies, with multiple erythematous papules
on the trunk and limbs, associated with an intense itching sen-
sation. Pustules may also form. However, scabies burrows and
nodules in the genital regions are normally not seen. The gen-
eral clinical characteristics of animal-transmitted scabies origi-
nating from canine scabies include: (i) no eruption between the
fingers or on the palms, and no scabies burrows; (ii) difficulty
to detect S. scabiei from the human eruption; (iii) the eruption
commonly occurs in sites that come into contact with the
affected dog (chest and abdomen, forearms); and (iv) the time
until onset of symptoms ranges from a number of hours to
1 month after coming into contact with the affected dog.151–154
On rare occasions, the scabies mite may be detected from the
eruption.154,155
With dermoscopy, it is not possible to detect the mite body
as can be seen with human scabies. However, characteristic
findings include curved linear crust in the area where the
papules are located.156
Diagnosis
In cases where the clinical findings are similar to scabies, but
there is no eruption on the palms or between the fingers, and
no scabies burrows, it is reasonable to suspect animal-trans-
mitted scabies.
The presence or absence of pets or animals the person may
have come into contact with through their work and the health
status and skin condition of those animals is to be checked. If
animal-transmitted scabies is suspected, scales from the ani-
mals are collected, and if the scabies mite can be detected
through direct microscopic observation, the diagnosis can be
confirmed.
Treatment
Avoiding direct contact with the affected animal that is the
source of infection, and treating the animal are the most impor-
tant measures, as the human eruption will not be cured until
treatment of the animal is completed. Treatment of the animal
that is the source of infection should be requested from a
veterinarian.
The human eruption is an allergic reaction to the scabies
derived from the animal, and animal scabies will not reproduce
in human skin. Thus, it is not necessary to use scabicide. The
eruption should be treated with topical steroids and oral antihis-
tamines should be used for the itching sensation. However, topi-
cal applications such as crotamiton cream may be used if there
is continued contact with an untreated and uncured animal.
CONCLUSION
The options for treatment of scabies have broadened with new
topical preparations coming onto the market. The efficacy and
safety of these drugs will be widely evaluated. We hope there
will be more research and development in this field, resulting in
even more new drugs. On the other hand, it is vital that
© 2017 Japanese Dermatological Association
Guideline for scabies in Japan
dermatologists and medical personnel pool their knowledge on
diagnosis and prevention, improve existing techniques, and
adopt a stance of tackling preventative measures as a team.
The general public and medical personnel need to be edu-
cated on scabies to deepen the level of understanding, reduce
the number of scabies patients, and work towards the eradica-
tion of scabies.
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