Scabies-2017-The Journal of Dermatology

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 through sexual contact, communal living and other activities,
DIAGNOSIS AND TREATMENT OF SCABIES which makes it virtually impossible to eliminate the parasite
(THIRD EDITION) completely.
Therefore, it is important to make prompt and accurate
Scabies is caused by an infestation with Sarcoptes scabiei (S. diagnosis of scabies, and to provide appropriate treatment,
scabiei var. hominis), upon whose extermination, scabies is resulting in a cure. Dermatologists are the leading physicians
cured. However, infection from person to person persists 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: [email protected]
*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. are skin lesions and itching arising from allergic reactions to the
Thus, this guideline was created. body, excretion, exuviae and other parts of the parasite.3–7
BACKGROUND OF CREATING THE GUIDELINE ECOLOGY OF S. SCABIEI (SCABIES MITE)

Scabies has been a problem for humans since the dawn of his- Sarcoptes scabiei, which is responsible for scabies, is approxi-
tory. Towards the middle of the 19th century, scabies began to mately oval in its shape.8 The mature female mite is larger at
be managed primarily by dermatologists. However, until approximately 400 lm in length and approximately 325 lm in
recently, no markedly effective drug for oral or topical treat- width, while the mature male mite is approximately 60% of the
ment had been officially approved, so a variety of therapies female size. The mites molt and grow through repeating the
and folk remedies were used for the treatment of this disease cycle of egg, larvae, nymph and mature form. The hatching of
in Japan. Recently, drugs effective against scabies were offi- eggs takes 3–5 days, and the life cycle is approximately 10–
cially introduced for clinical use. 14 days.9–11 Larvae, nymphs and mature male mites walk
The Japanese Dermatological Association previously cre- around on the surface of human skin or hide in small burrows
ated a guideline for the diagnosis and treatment of scabies in created within the keratinous layer of the skin or in hair follicles.
20051 and 2007.2 As phenothrin topical use is now approved It is therefore difficult to locate this mite on the host. Mature
under the National Health Insurance (health insurance) (August female mites create small burrows suitable for laying eggs and
2014), the third edition of the guideline was thought to be wait there for males. Males seek females to mate. After mating,
necessary. The third edition was created through a series of mature female mites advance through the keratinous layer, cre-
discussions by the Executive Committee and Board of Direc- ating a burrow, and continue burrowing for the remainder of their
tors for the guideline. Public comment was invited, and the life (4–6 weeks) while laying 2–4 eggs every day. As S. scabiei is
guideline was published with the approval of the Executive not a blood-sucking mite, exudate, tissue fluid and other sub-
Committee and Board of Directors of the Japanese Dermato- stances in the keratinous layer are thought to serve as sources
logical Association. 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-
POSITION OF THE GUIDELINE
ture and are completely inactive at temperatures below 16°C.
This guideline shows the standard diagnosis and treatment pro- It is estimated that the infectivity of S. scabiei decreases within
tocol for scabies in Japan at present. However, the pathology of several hours once this mite is detached from the skin. This
scabies is not fully understood, the clinical picture is diverse and mite cannot tolerate high temperatures and dies if exposed to
the severity of symptoms varies. Furthermore, there are few a temperature of 50°C for 10 min.12
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,
DISEASE TYPING
and simply adopting the measures set out in this guideline does Based on clinical symptoms13,14 and the number of infested
not exempt physicians from liability. Additionally, this guideline is mites, scabies is usually divided into two types: scabies (com-
not intended to discourage physicians from adopting a treatment mon scabies, classical scabies) and crusted scabies. (Note:
strategy not described in this guideline (third edition), and such This type is also known as Norwegian scabies [synonymous
actions cannot be regarded as negligence. 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
CONFLICT OF INTEREST
used in this guideline.)
The Japanese Dermatological Association covered all the costs Clinical symptoms will be described in the next section. In
required to formulate this guideline, and no support was common scabies, the number of mature female mites found is
received from specific bodies, enterprises or pharmaceutical five or fewer in half of all cases (in healthy individuals), but there
companies. Furthermore, members of the guideline Executive are cases where more parasites are found. Namely, there may
Committee involved in the development of related pharmaceu- be a larger number of parasites, even in infections with common
ticals were not involved in determining the degree to which the scabies, in people with reduced immunity, including patients
respective treatment should be recommended. Apart from the taking steroids or immunosuppressants, patients with malignant
above, no conflicts of interest should be declared by each tumors or diabetes, those on dialysis and elderly people.
committee member regarding the formulation of this guideline. In crusted scabies, 1–2 million mature mites (occasionally
>5 million) are seen per patient,15,16 and the infectivity is very high.
DEFINITION OF SCABIES
Scabies is caused by infection with S. scabiei var. hominis,
ROUTE OF INFECTION
which is a mite parasitic to the keratinous layer (horny layer, stra- The mite is transmitted primarily by direct skin contact. After a
tum corneum) of human skin. Major symptoms of this infestation symptom-free incubation period of approximately 1–2 months
992 © 2017 Japanese Dermatological Association

Guideline for scabies in Japan
(sometimes several months in elderly individuals), clinical the wrinkles on the fingers.24–29 This type of eruption is often
symptoms, such as skin eruption, appear.17,18 not elevated.26,29 When observed with a magnifying glass, the
There is no published work that clearly describes the route mite is sometimes visible as a dark-brown triangle, which cor-
of transmission during the incubation period. Additionally, the responds to the head (capitulum) and two pairs of forelimbs of
number of S. scabiei during this period is small, so there is lit- the mite. Sites where this feature may be found are several
tle risk of infecting another person. millimeters ahead of the vesicle at the tip of the burrow or at
Both common scabies and crusted scabies are infestations the tip of a linear wake-like eruption. Wiping the area around
caused by the same agent, S. scabiei, however, the infectivity the scabies burrow once with an alcohol swab makes detec-
and the means of spreading infection differ significantly. tion of S. scabiei easier, and detection is even easier using a
In common scabies, there are only a small number of dermoscope (see the section on dermoscopy). The scabies
S. scabiei parasites per patient.19 The longer the parasite is burrow itself is itchy, but the itching sensation is sometimes
detached from the host, the infectivity of S. scabiei absent in elderly patients. Second, erythematous small
decreases.12 The circumstances in which mites can be trans- papules accompanied by an intense itching sensation are
mitted from a patient with common scabies include activities scattered through the umbilical region, abdomen, thoracic
such as sharing the same bed, using bedding used by the region, axillae, medial aspect of the thigh, and flexor surface
patient and holding hands for an extended period.20 Transmis- of the upper arm. The itching sensation intensifies at night,
sion is limited to intense contact; therefore, there is little risk of sometimes disrupting sleep. This itching sensation is consid-
infection with short periods of contact, or through fomites such ered as an allergic reaction after sensitization to the feces,
as clothing or bed linen. exuviae and other waste products from the S. scabiei during
In crusted scabies, the keratinous layer of the skin contains the approximately 1-month incubation period. It is rare to
a large number of S. scabiei. In such cases, infection can be detect mites or eggs from the area affected by this type of
established not only through direct skin contact but also papule. Third, red-brown nodules the size of small beans, pri-
through the spread of the mite as the detached keratinous marily affecting the external genitalia of men, and they are also
layer is dispersed or attaches to other surfaces. Therefore, seen in the axillae, olecranon and buttocks. This type of erup-
infection can spread through short, direct skin contact, such tion is uncommon, seen in only approximately 7–30% of all
as when visiting the affected person, and via indirect contact, cases of scabies, and it causes a very intense itching sensa-
such as via bed linen where there is no direct skin contact with tion. Nodules are also attributable to allergic reactions to the
the infected person. This can result in mass infection.21 The mite. Burrows are sometimes seen, even in freshly formed
parasites can also be transmitted via staff working in hospital nodules, and in such cases, it may be possible to detect
facilities, and other factors.22 The incubation period for crusted S. scabiei from the burrows.
scabies is sometimes shorter (4–5 days) due to infestation with Eruptions including vesicles, blisters, pustules and crust
a large number of S. scabiei. 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-
CLINICAL SYMPTOMS
losis of infancy may also been seen in children where vesicles
Common scabies and small pustules appear on the palms and soles of the feet
There are roughly three kinds of skin symptoms in scabies.6 during infestation with scabies and after the scabies has been
First, the burrow type, which often develops on the flexural cured.30
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, Crusted scabies
dorsum pedis, olecranon, nipples (in women), genitalia (partic- This type of scabies tends to occur in individuals with poor
ularly in males), buttocks, axillae and so forth. The scabies condition or severe underlying disease, individuals in an
burrow is a type of skin eruption unique to scabies, and it immunocompromised state due to steroid or immunosuppres-
serves as the path through which the mature female mite sive treatment, and elderly individuals with these back-
advances through the keratinous layer while laying eggs. Thus, grounds.31 Crusted scabies may also affect individuals with
mites and eggs are frequently detected in the burrow. The bur- disorders of the nervous system or severe systemic skin dis-
row is elevated slightly above the skin surface, appearing as a ease, and individuals who have erroneously used topical ster-
linear eruption, following a tortuous arrangement with a whitish oids for common scabies.32
appearance. The width is approximately 0.4 mm (approxi- Symptoms in crusted scabies can be characterized by
mately equivalent to one pattern of fingerprint), and the length hyperkeratosis, presenting as an accumulation of gray to yel-
is often approximately 5 mm, although it can vary depending low-white, rough and thickened, oyster shell-like keratinous tis-
on the length of time since the start of digging. Scales are sue at sites on the skin prone to friction, including the hands,
seen on the side invaded by the mite, while vesicles are some- feet, buttocks, olecranon and patella, as well as in other sys-
times seen at the frontier of digging.23 In elderly patients, the temic areas, including those areas unlikely to be affected by
eruption sometimes assumes the appearance of the “wake” common scabies, such as the head, neck and auricular
sign (resembling the wake of a ship, broadening toward the region.33 Eruption is sometimes accompanied by systemic red-
end after a ship has passed) along the wrists, the palms and ness, which may become erythroderma. Similar hyperkeratosis

N. Ishii et al.
may also be seen in the nail plate (nail scabies), presenting scabies by means of microscopic examination of the kerati-
with clinical symptoms resembling tinea unguium.34 Nail sca- nous layer. Microscopic detection of the mite is covered by
bies occurs when S. scabiei are present within, under or on health insurance as a microbial test.
top of the nail plate, and the condition may also be compli-
cated by tinea unguium. Dermoscopy
In recent years, there has been a tendency toward an Scabies can also be diagnosed through detection of the mite
increase in cases where eruption is confined to the palms, feet via dermoscopy.23,29,40,45 The female mite, approximately
or nails, or occasionally confined to the auricular region, neck, 0.4 mm in size, and its dark-brown head, two pairs of fore-
head and so forth. There are also cases where only small limbs and almost transparent round body can be
amounts of mica-like scales are seen in the extremities, but observed.29,45,46 This can be usually found at the tip of the
numerous mites and eggs are detected in the scale. There is curved, shiny, whitish burrow. Dermoscopic examination is not
no particular itching tendency in these cases, and itching may covered by health insurance in Japan.
be completely absent.
Crusted scabies may also occur concurrently with condi- Hematology
tions such as secondary bacterial infection or kidney failure,35– It is not possible to make a definitive diagnosis of scabies
37
which may be fatal, so early treatment is essential. 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
TESTS
cases with nodules.47,48 No practical IgE test specific to
Tests for detection of S. scabiei S. scabiei has been developed. There is also data indicating a
At present, microscopy and dermoscopy are available methods crossover of the human S. scabiei antigen with the Der-
for detecting mites. However, to increase the efficiency of matophagoides farinae and Dermatophagoides pteronyssinus
S. scabiei detection, it is vital to improve these existing tech- antigens.49
niques, to develop new alternatives and to confirm their
validity.38
EPIDEMIOLOGICAL STATUS OF DISEASE
OUTBREAK
Microscopy
Sarcoptes scabiei are collected for microscopy from burrows, Usually, the onset of scabies in two or more individuals within
fresh papules, nodules and so forth by means of: (i) resec- the same ward or unit during a 2-month period is regarded as
tion with ophthalmic scissors; (ii) scratching with a scalpel; a mass outbreak. When making such a judgment, the status of
(iii) scrape with small tweezers; (iv) collection of mites with a mass outbreak in neighboring communities is also taken into
sterile needle using a dermoscope or under magnification account,50–52 and individuals suspected of having scabies are
with a loop, and other such techniques. In cases where the to be adequately interviewed to determine contact with scabies
keratinous layer is thick, as in cases of crusted scabies, the patients.
keratinous layer is collected with ophthalmic scissors, tweez-
ers or other such implements. The samples thus collected
DIAGNOSIS OF SCABIES
are observed under a microscope at a magnification of
9100, similar to the procedure for the observation of myco- Diagnosis of scabies is based on a general assessment of: (i)
sis. The mite body, trunk, limbs, eggs, exuviae, feces and so clinical symptoms; (ii) results of microscopy, dermoscopy and
forth are checked. Fecal pellets dissolve easily with potas- so forth for detection of the mite; and (iii) epidemiological sta-
sium hydroxide and can be stained with chlorazol black E.39 tus of the outbreak (including information about the chance of
At present, there is no established method for differentiating contact with scabies patients). If S. scabiei has been detected
whether the mite is alive or dead.40,41 Even in cases of by microscopy, dermoscopy or other such means, a definitive
eruption associated with scabies, the mite detection rate diagnosis can be made. In cases where microscopy and/or
with microscopy varies widely, ranging 10–70%,17,42–44 so it dermoscopy yields negative results but the possibility of sca-
is essential to improve the techniques of detection and to bies cannot be ruled out in view of clinical symptoms and/or
frequently repeat the test at different sites on the body. For epidemiological status of an outbreak, it is necessary to per-
efficient detection of S. scabiei, the mite burrows must be form microscopy or dermoscopy again at a later time. In cases
magnified with a dermoscope and the tips of the burrows of common scabies, the number of mites is small;15,16 thus,
examined. In elderly individuals, it is important to not over- this type requires repeated tests for detection of the mite to
look the palms and the soles of the feet and to look for make a definitive diagnosis.
V-shaped wake-like scales.26,29 The mite detection rate is
low in papules on the body trunk.
TREATMENT OF SCABIES
With crusted scabies, there are innumerable mites of all
stages, ranging from the eggs to the mature form, and these Basic concept of treatment
are detectable in the hyperplastic keratinous layer. Therefore, Treatment of scabies53 is performed on patients definitively
detection of the mite is easy in suspected cases of crusted diagnosed as having scabies based on S. scabiei detection or

patients showing evident clinical symptoms of scabies after Reference text: There is little clear scientific evidence on the
coming into contact with patients definitely diagnosed as hav- efficacy of sulfur, but it may be used.
ing scabies. Recommendation level: C1 (use of the treatment may be
At present, the only preparations for the treatment of sca- considered, but there is insufficient evidence).
bies (scabicides) covered by health insurance in Japan are Explanation: According to reports based on randomized
phenothrin (Sumithrinâ; Kracie Pharma, Tokyo, Japan) lotion, controlled trials (RCT) on scabies, patients with 50 subjects per
topical sulfur preparation and ivermectin (Stromectolâ; Merck, group, topical application of 10% sulfur for 7 consecutive days
Kenilworth, NJ, USA) (Table 1). Crotamiton (Euraxâ; GSK CHJ- had equivalent efficacy and safety as topical application of
Novartis, Tokyo, Japan) cream is not covered by health 0.3% c-BHC for 7 days consecutively.56 Additionally, accord-
insurance, but a notification has been issued by the Social ing to a report based on an RCT on scabies patients with 69–
Insurance Medical Fee Payment Fund to the effect that “if cro- 89 subjects per group, topical application of sulfur (unknown
tamiton is usually prescribed for scabies, then it will be concentration) in the morning and evening for 3 days consecu-
approved after examination of the usage case in question” tively had an equivalent efficacy and safety as topical applica-
(dated 21 September 2007). Benzyl benzoate is a special for- tion of 25% benzyl benzoate lotion in the morning and evening
mulation containing a combination of reagent and vehicle, and for 3 days consecutively.57 Another report indicated a cure rate
is used at the discretion of physicians in the absence of effec- of approximately 85% with 6–10% precipitated sulfur ointment
tive topical preparations, although its efficacy and safety have applied every evening repeatedly for 3 days.58 In Japan, there
not yet been fully evaluated. No topical permethrin preparation are few topical medicines covered by health insurance. Only
is approved in Japan, as the preparations contain the stabilizer sulfur powder can be used as a prescription drug, and this
formaldehyde as a component. drug is prepared as a hospital preparation in each hospital.
c-Benzene hexachloride (c-BHC; lindane) is subject to regu- Manufacture of the over-the-counter (OTC) sulfur, salicylic acid
lation by the Stockholm Convention relating to persistent and thianthol ointment has been discontinued, and only prepa-
organic pollutants, so it is now unavailable (lindane was added rations containing thianthol 30% are available. Treatment was
to the list of Class I Specified Chemical Substances in the Act effective in all patients who used sulfur camphor lotion (6%
on the Evaluation of Chemical Substances and Regulation of sulfur mixture), which is commonly used for acne, for 7 days.
Their Manufacture, and so forth in April 2010), so it can no However, this is simply a case series, and there is little sup-
longer be used in Japan. porting evidence.59
Long-term use or overdose of scabicides may induce emer-
gence of drug-resistant S. scabiei.54 There are only a small Crotamiton
number of different types of scabicides available, so the drugs CQ: Is crotamiton effective for treating scabies?
must be correctly administrated to prevent the emergence of Reference text: The efficacy of crotamiton monotherapy is
drug-resistant S. scabiei. not highly evaluated, but it is effective depending on the
patient.
Collecting evidence on therapeutic drugs Recommendation level: C1 (use of the treatment may be
Databases used for the collection of data were PubMed, Japan considered, but there is insufficient evidence).
Medical Abstracts Society Web (Ichushi) and Cochrane Data- Explanation: Crotamiton topical preparation has been used
base of Systematic Reviews (2010). in Japan on scabies patients since the end of the 1970s, but
Regarding the search period, the aforementioned Cochrane the usage method is not standardized, and most cases use
database was available in PubMed, so we searched the avail- this preparation in combination with other drugs.
able published work between January 2009 and May 2014 Two RCT (overnight application,60 application for 2 nights
(search entry: drug name AND human AND scabies). Important consecutively nights)61 were conducted comparing crotamiton
new published work was added as needed. For Ichushi, we 10% cream with permethrin 5% cream in 194 scabies patients.
searched the available published work up to May 2014 (search The cure rate after 4 weeks was 60% versus 89% in the former
entry: drug name AND human AND scabies AND excluding trial and 88% versus 98% in the latter trial, indicating that cro-
conference proceedings). Important new published work was tamiton had inferior efficacy. Crotamiton also had higher persis-
added as needed. tence of itching sensation after 4 weeks (24% vs 11%) and a
higher incidence of secondary infection (38% vs 15%) than per-
Evidence level and criteria for classification of methrin.60 There was no significant difference in terms of effi-
degree of recommendation cacy and safety in an RCT on 100 scabies patients comparing
The criteria adopted by the Guideline for the Diagnosis and crotamiton 10% cream and 1% c-BHC.61 A report in Japan indi-
Treatment of Skin Cancer, edited by the Japanese Dermato- cated a cure rate of 61.6% in children and 100% in adults after
logical Association was referenced (Table 2).55 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
Summary of clinical questions (CQ) on treatment
monotherapy is not used in definitive cases of scabies, but effi-
Sulfur cacy is seen in cases in the early stage of scabies infestation
CQ: Is sulfur effective for treating scabies? and in cases in the incubation period.63 Therefore, in cases

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 been used for a long time as a treatment not covered by health
recommendation level (referencing the criteria adopted by the insurance, including in the preparation of reagents. The usage
guideline for the diagnosis and treatment of skin cancer, edited method varies, and depends on the preparation method (e.g.
by the Japanese Dermatological Association) lotion, mixed with crotamiton), the concentration (6–35%), the
Classification of evidence level number of doses and dosing intervals. The timing for determin-
I Systematic review/meta-analysis ing efficacy is also not fixed. The efficacy of benzyl benzoate
II One or more randomized controlled trials has been described in an RCT with 181 subjects, comparing
III Non-randomized controlled trial benzyl benzoate 25% or 12.5% lotion with a single dose of
IV Analytical epidemiological study (cohort study, ivermectin. The treatment was effective with two doses.64 In an
case–control trial) RCT with 30 subjects, benzyl benzoate lotion (adult 25%, chil-
V Descriptive study (case report, case series)
dren 12.5%) had an equivalent efficacy to aloe pulp.65 Con-
VI Opinions of specialist committee, specialist individual†
versely, another report, albeit a report of poor quality, showed
Classification of recommendation level‡
A Use of the treatment is strongly recommended that c-BHC 1% ointment is effective but benzyl benzoate 6%
(there is at least one level I or good quality and crotamiton ointment is ineffective.66 Benzyl benzoate can
level II evidence demonstrating efficacy) also cause irritant dermatitis as an adverse drug reaction.
B Use of the treatment is recommended (there is at least Thus, based on the above information, this drug should be
one or more inferior quality level II, good quality used when no other option is available.
level III or extremely good quality level IV evidence
demonstrating efficacy) c-BHC, lindane
C1 Use of the treatment may be considered, but there is CQ: Can c-BHC be used to treat scabies?
insufficient evidence§ (inferior quality level III–IV, a
Reference text: On 1 April 2010, c-BHC was designated in
number of good quality level V or a
Annex A of the Stockholm Convention relating to persistent
committee-approved level VI)
C2 Use of the treatment cannot be recommended, as organic pollutants, so its use is now prohibited.
there is no evidence§ (no evidence of efficacy or Recommendation level: D (recommended not to use the
evidence of ineffectiveness) treatment).
D Recommended to not use the treatment (there is good Explanation: c-BHC has historically been a highly effective
quality evidence demonstrating that the treatment is topical treatment for treating scabies, but it is not approved by
ineffective or harmful) insurance; hence, it was prescribed as a hospital preparation.
While there is evidence of its efficacy,66 there is also evidence
†
Data based on basic experiments and theory guided by that data of extremely severe adverse effects.67 There is also a report of
would correspond to this level.
‡
There may be levels of recommendation in this text that do not always the concentration of c-BHC in the brain increasing to several
match the criteria in the above table. This is because there are sections times that of the blood due to its lipid solubility and delayed
where the grade of recommendation level was decided based on the degradation.68 Accumulation of c-BHC in the environment is a
consensus of the Executive Committee, which was based on considera-
tions that there is a lack of evidence on this condition internationally,
serious problem, so despite it being possible to prescribe this
given that overseas evidence cannot always be applied without change drug as a clinically effective and highly safe therapeutic agent,
to the situation in Japan, and further considering the practical applica- this drug should not be used based on the harmful effect of
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.
Permethrin
CQ: Is permethrin effective for treating scabies?
Reference text: Permethrin is superior for treating scabies in
where scabies has been definitively diagnosed and scabies terms of both efficacy and safety, and it can be used in infants
cases presenting with clinically typical symptoms, topical appli- aged 2 months and older, as well as in pregnant and lactating
cation of phenothrin or oral ivermectin, which have a strong women.
insecticidal effect, are recommended. However, crotamiton Recommendation level: C1 (use of the treatment may be
monotherapy may be effective depending on the patient. considered, but there is insufficient evidence)
Explanation: Permethrin belongs to the pyrethroid insecti-
Benzyl benzoate cide family, and contains pyrethrum active ingredients and
CQ: Is benzyl benzoate effective for treating scabies? derivatives. Permethrin 5% cream and lotion is used overseas
Reference text: The treatment method differs depending on as a drug to treat scabies. There is little percutaneous absorp-
the referenced article, and while it is difficult to determine the tion, with low toxicity to humans. The drug rapidly degrades
efficacy and safety of this treatment clearly, it is effective to a after taking effect, so it has no effect on the environment. Its
degree, so it may be used. safety in infants aged over 2 months of age and in pregnancy
Recommendation level: C1 (use of the treatment may be has been reported and it is used as a first-line drug in many
considered, but there is insufficient evidence). countries.69,70 According to the 2010 guideline for treatment of
Explanation: In some countries, benzyl benzoate is a first- infection prepared by the Centers for Disease Control and
line topical treatment for scabies, and in Japan as well, it has Prevention, USA, permethrin may be used in infants and in

N. Ishii et al.
pregnant and lactating women.71 The transfer of permethrin no malathion RCT in existence.78,79 On the other hand, an alert
into breast milk is unknown. However, less than 2% of the has been issued regarding the purity of malathion.79
drug is absorbed into the body with a single application.72,73 Malathion inhibits the action of cholinesterase, and inhibits
The efficacy of permethrin in treating scabies is better than the degradation of acetylcholine, a neurotransmitter at nerve
ivermectin, c-BHC, benzyl benzoate, crotamiton and sulfur, endings; thus, this drug can produce acetylcholine hyperstimu-
and the cure rate after one application ranges 89–98%. There lation-like symptoms.80
are reports that two applications 1 week apart has a cure rate Malathion is used in countries such as England, but it can-
of between 85% and 100%.74,75 It is used in Japan through not be obtained for medical use in Japan.
individual importation of the drug,74 but it is not covered by
health insurance in Japan. As it contains formaldehyde as a Ivermectin
preservative, there is no plan to approve the drug (there is now CQ: Is oral ivermectin effective for treating scabies?
also a product available that does not contain formaldehyde). Reference text: Ivermectin is effective for treating scabies.
Given that it is not possible to obtain permethrin in Japan Recommendation level: A (use of the treatment is strongly
unless it is privately imported, it is not covered by health insur- recommended).
ance, and considering that this guideline is essentially a guide- Explanation: Ivermectin is an anthelmintic collected and iso-
line for Japan, the recommendation level is set at C1. lated from the soil in Japan. However, ivermectin was
approved for the indication of scabies despite no clinical trials
Phenothrin being conducted globally on scabies with this product. There
CQ: Is phenothrin effective for treating scabies? are no RCT in Japan. Additionally, as there are many options
Reference text: Based on clinical data and the data on per- for effective topical medications available overseas, only a lim-
methrin, phenothrin is superior in terms of efficacy and safety. ited number of countries have approved ivermectin as a drug
Recommendation level: A (use of the treatment is strongly to treat scabies.81 However, an RCT was conducted in Mexico
recommended, Executive Committee determination). with 55 subjects, using a single dose of 200 lg/kg. The cure
Explanation: Clinical trials on phenothrin 5% lotion have rate in the ivermectin group was reported to be 74%, com-
been completed, being approved by health insurance, and the pared with 15% in the placebo group, demonstrating the effi-
product entered the market on 22 August 2014, so the only cacy of ivermectin, and no adverse reactions were seen.82
data available is that from the clinical trials. In a clinical trial There is a wealth of usage experience with ivermectin in the
with 96 subjects where phenothrin was applied topically twice treatment of animal scabies or non-scabies parasitosis in
at 1-week intervals, the drug had an efficacy rate of 92.6%. It humans. There are also a number of RCT comparing the effi-
was effective in 88 subjects, ineffective in seven subjects and cacy of ivermectin with that of other drugs in the treatment of
indeterminate in one subject. Adverse drug reactions were human scabies. Ivermectin is currently widely used in Japan as
seen in eight subjects (7.8%). The main adverse reactions were the only oral drug for human scabies and the results of post-
dermatitis (n = 2, 2.0%), elevated aspartate aminotransferase marketing surveillance of all 807 patients have been published
(n = 2, 2.0%) and elevated alanine aminotransferase (n = 2, (the evidence level is low, but the number of cases is high).83
2.0%), but the reactions were mild and improved at an early Considering these results, ivermectin is strongly recommended
stage. for use in the treatment of scabies.
This drug is highly effective with few adverse reactions. Phe-
nothrin belongs to the same pyrethroid family as permethrin. Ivermectin and c-BHC
The 50% lethal doses (lg/cm2) of phenothrin and permethrin CQ: Is ivermectin more effective than c-BHC in treating
for D. farinae and Tyrophagus putrescentiae, which are similar scabies?
mites to S. scabiei, are less than 0.01 and 0.045, respectively, Reference text: Ivermectin is more effective in the treatment
for D. farinae, and 0.46 and 1.9, respectively, for T. putrescen- of scabies than c-BHC.
tiae. Thus, phenothrin has been reported to have equivalent or Recommendation level: A (use of the treatment is strongly
superior miticide action to that of permethrin.76 Therefore, as recommended).
the concentration of both drugs is 5%, it was determined that Explanation: Meta-analysis demonstrates that ivermectin is
they are effective against scabies. Because there is only data significantly more superior in terms of efficacy than
from clinical trials, we are awaiting the results of the drug use c-BHC.81,84,85 There is no difference in the incidence of
survey. adverse events. Currently, c-BHC cannot be used in Japan
(see c-BHC CQ section). Given these considerations, use of
Malathion ivermectin rather than c-BHC in the treatment of scabies is
CQ: Is malathion effective for treating scabies? strongly recommended.
Reference text: There are no results that demonstrate the
efficacy of malathion. Permethrin and c-BHC
Recommendation level: C2 (use of the treatment cannot be CQ: Is permethrin more effective than c-BHC in treating
recommended, as there is no evidence). scabies?
Explanation: Despite it being more than 30 years since the Reference text: Permethrin is more effective in the treatment
trial that initially claimed the efficacy of malathion,77 there are of scabies than c-BHC.

Recommendation level: C1 (use of the treatment may be Crotamiton

considered, but there is insufficient evidence). Pharmacological action, pharmacokinetics: The action mecha-
Explanation: There are RCT61,86–89 and meta-analysis81 nism is unknown, but this product was developed as an insec-
which demonstrate that permethrin is significantly superior to ticide, and it is used to treat scabies.
c-BHC in terms of efficacy and antipruritic action. However, Usage method: Crotamiton topical preparation is not cov-
permethrin is not covered by health insurance in Japan, and ered by health insurance, but use is permitted with insurance
considering that this guideline is essentially a guideline for review. Crotamiton 10% cream is usually washed off 24 h after
Japan, the recommendation level is set at C1. 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
Permethrin and ivermectin applied for approximately 10–14 days. It has been reported that
CQ: Is permethrin more effective than ivermectin in treating frequent use of crotamiton induces methemoglobinemia in chil-
scabies? dren,7 so continuous use requires caution. Crotamiton is added
Reference text: Permethrin is more effective in the treatment to a variety of drugs as a solubilizing agent or an absorption
of scabies than ivermectin. enhancer for the main agent,92 and it can induce contact der-
Recommendation level: C1 (use of the treatment may be matitis,93,94 so it should be used with caution. Many crotamiton
considered, but there is insufficient evidence). preparations contain steroids (e.g. Eurax H cream),92 and these
Explanation: There are RCT70,75,90,91 and meta-analysis81 preparations should not be used as scabicides.
which demonstrate that permethrin is significantly superior to It is advisable to avoid high doses or prolonged use of
ivermectin in terms of efficacy. Permethrin has almost no the drug over wide areas in pregnant women, infants and
adverse effects. However, permethrin is not covered by health children.60,95
insurance in Japan, and considering that this guideline is
essentially a guideline for Japan, the recommendation level is Benzyl benzoate
set at C1. Pharmacological action, pharmacokinetics: The action mecha-
nism and pharmacokinetics are unknown.
Detailed exposition of drugs used to treat scabies Usage method: Benzyl benzoate is prepared in hospitals as
(pharmacological action, pharmacokinetics, usage a special formulation in the form of 6–35% lotion (blemish balm
method) lotion, prepared immediately before use). In Western countries,
The drugs currently available to treat scabies are shown in 25% lotion is used for adults and lotions with lower concentra-
Table 1, but this section describes the drugs available for use tions, such as 10%, are used for children. This kind of lotion
in Japan. sometimes uses a flammable vehicle (e.g. ethanol). In these
cases, it is preferable to apply the lotion under the supervision
Sulfur of a doctor. The lotion is washed off 24 h after application.
Pharmacological action: On the skin surface, sulfur gradually There are various regimens for using this lotion, including repe-
becomes hydrogen sulfide, polythionic acid, and particularly tition of cycles of 2–3 days of treatment followed by a 4–5-day
pentathion, producing an antibacterial action that successfully break or three doses every other day. This drug is intensely irri-
treats parasitic skin diseases. The –SH base, which is said to table and can cause conjunctivitis when exposed to the eyes.
have a relationship with skin keratinization, changes to S–S, Adverse reactions of the central nervous system have also
thus producing a keratin-softening action. The smaller the sul- been reported. Therefore, particular care is needed when
fur particles become, the more the chemical change of sulfur applying the lotion to the face or neck, ensuring contact with
is promoted. Therefore, when colloidal sulfur is used, the the eyes is avoided.96 This drug can also induce side-effects
aforementioned actions are particularly notable. When sulfur including blister formation and itching sensation. It is recom-
is combined with alkaline drugs, the keratin-softening, mended to stop breast-feeding when using this drug for lactat-
antibacterial and antiparasitic action intensifies. Sulfur and ing women.97 It must not be used during pregnancy or in
sulfides destroy the scabies burrows and kills the mite bodies children younger than 2 years of age.97,98
and eggs. When using this drug, procedures are to follow the “Guideli-
Pharmacokinetics: No data. nes on the preparation and use of in-hospital formulations”,
Usage method: 5–10% precipitate sulfur ointment (prepared the approval of the in-hospital ethics review board is to be
in the hospital as a special preparation) is available for use. obtained, written consent is to be obtained from the patient (or
The ointment is washed off 24 h after application, and this pro- guardian) after the efficacy and safety of benzyl benzoate has
cess is repeated for 2–5 days or for 7 days.7 been fully explained, and then the drug is to be used under the
Mixtures of sulfur with bleaching powder, potassium chlo- responsibility of the attending physician. Combination of benzyl
rate or potassium permanganate are explosive. Toxicity is low benzoate with alkaline drugs is contraindicated as it undergoes
and this therapy can be used on pregnant women and small hydrolysis under alkaline conditions.99 Benzyl benzoate may
children, but the ointment is odorous and causes skin irritabil- become unstable when mixed with crotamiton cream,100 which
ity. It is essential to be aware that it tends to cause asteatotic contains weakly basic additives, so it is preferable to mix
eczema. immediately before use.

N. Ishii et al.
Phenothrin generated. When phenothrin is applied to the skin to treat sca-

Phenothrin (Sumithrin) is a topical preparation belonging to the bies, the unchanged drug demonstrates miticidal action, but if
pyrethroid family, as is permethrin. Phenothrin was approved any drug is absorbed into the body, it is thought to undergo
for manufacture in 1976 as a drug to target household insects, rapid metabolization (detoxification). Clinical data on phenothrin
and it is sold as a treatment for head lice and pubic lice. The lotion showed that the phenothrin in the applied lotion pene-
concentration in OTC drugs is 0.4%. trates into the keratinous layer.102 Any phenothrin that is
The phenothrin structure consists of chrysanthemic acid and absorbed from the keratinous layer into the body is rapidly
3-phenoxybenzyl alcohol ester. Permethrin has an extremely metabolized and excreted, with only a minute amount found in
similar structure, with only a substitution of the dichloro group the plasma and urine. The drug almost completely disappears
on the end of the chrysanthemic acid (permethrin) replacing 7 days after application. The concentration of phenothrin in the
the dimethyl (phenothrin) (Table 3). Phenothrin has superior keratinous layer is almost the same 24 h after application as it
safety in the event of acute toxicity with both drugs, which is at the time of application, but the concentration rapidly decli-
could be attributable to this substitution (Table 3). nes after the drug is washed off.
Phenothrin 5% lotion (Sumithrin lotion 5%) can now be Usage method: Normally, 30 g per dose is applied to the
used for medical purposes based on the indications and skin below the neck at 1-week intervals, and then the drug is
effects for scabies (Table 1). Similarly, the concentration of the washed off and removed in the bath or shower at least 12 h
pyrethroid insecticide permethrin in topical preparations is 5%. after application. The lotion must be applied at least twice.
To date there has been no published work on phenothrin topi- However, there is little experience with the use of phenothrin in
cal preparation, and the comparison between this drug and Japan, so it is essential to take adequate precautions regard-
ivermectin based on clinical data and so forth is described in ing the efficacy and safety of this drug and carefully monitor
Table 4. the progress of the patient. There may be temporary itching
Pharmacological action: Pyrethroid insecticides containing after the initial application. In Japan, there is no usage experi-
phenothrin act upon the Na+ channels of nerve cells. Pheno- ence in children (safety is not established), and as children
thrin demonstrates its insecticidal action via repetitive depolar- have smaller body surface areas, the amount applied in a sin-
ization or interruption of nerve conduction through delayed gle application should be reduced accordingly. There is no
closure of Na+ channels. experience of use in pregnancy in Japan, so safety is not
Pharmacokinetics: Pyrethroid insecticides containing phe- established. Thus, phenothrin should only be used when the
nothrin are more easily degraded by light, air and heat than treatment benefits outweigh the risks. Phenothrin may be
other insecticides, and their efficacy and toxicity rapidly disap- excreted in the breast milk of lactating women,103 so it is
pears, with little residual effect. In the bodies of mammals, pyr- preferable to avoid use. If use is unavoidable, breast-feeding
ethroid insecticides are metabolized (degraded) through rapid should be stopped until 7 days after application when the
ester hydrolysis, oxidation action and conjugation, so it tends plasma concentration falls below detectable levels.
not to accumulate in body tissues.101 The main metabolite is The use of phenothrin must be carefully examined, and the
3-phenoxybenzoic acid (3-PB) and related metabolites are also characteristics of the drug should be fully explained to the
patient and their family.
Phenothrin-resistant head lice have been confirmed both
Table 3. Acute toxicity of phenothrin and permethrin in rats† overseas and in Japan.104 Care must be taken to not use high
and their structural formulae
doses and frequent treatments of phenothrin randomly to treat
Oral Transcutaneous Inhalation scabies, to ensure that phenothrin-resistant S. scabiei do not
Drug name LD50 (mg/kg) LD50 (mg/kg) LD50 (mg/m3) appear.
Phenothrin >5000 >5000 >2100 (4 h)
Permethrin 430–470 >2500 >685 (3 h) 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
† cell membrane permeability and hyperpolarization of nerve or
Household insecticides and pyrethroid: Usage and safety, Japanese
Industry Association of Household Insecticides, Osaka 2007. muscle cells, leading to the paralysis and death of the para-
LD50, lethal dose 50 (50% lethal dose). sites. In particular, ivermectin is thought to interact with other

Table 4. Action and usage instruction for topical Phenothrin and oral Ivermectin
Non-proprietary name Phenothrin Ivermectin

Brand name Sumithrinâ lotion 5% Stromectolâ tablets 3 mg
Antimicrobial agent Synthetic pyrethroid Semisynthetic oral anthelmintic derived from
Pyrethroid is the collective name for the active avermectin†
ingredient contained in pyrethrum, and it is used
as an insecticide
Major action Acts on receptors on the nerve cells of insects, Selectively binds with a high affinity to the
amphibians, and reptiles. It is a neurotoxin that glutamatergic chloride channels present in
causes depolarization by continuously opening the muscle cells and nerve cells of
Na+ channels. Has only a weak effect on invertebrates, increases cell membrane
receptors in mammals and birds 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
Current indications Scabies Scabies, intestinal strongyloidiasis
Concentration in the keratinous 24 h after initial application, the mean Reaches peak level approximately 8 h after
layer concentration of unchanged drug is dosing, tends to decrease after 24 h
3.567 µg/cm2. This rapidly declines after
washing
Concentration in the plasma The concentration of unchanged drug after initial Reaches peak plasma level 4–5 h after
application is less than 10 ng/mL. The drug dosing, and half-life is approximately 18 h
almost completely disappears after 7 days
Administration method One dose (30 g) is applied to the skin from the Taken with water on an empty stomach (if this
neck down at 1-week intervals, and then the drug is taken after a high-fat meal, the blood
drug is washed off and removed in the bath or drug concentration may increase)
shower at least 12 h after application. The lotion
must be applied at least twice
Precautions at administration Avoid application to ulcerations or broken skin. Wait 1 week before re-dosing
Do not use on the eyes or on mucosa The itching sensation may intensify
temporarily in the initial stage of treatment
Administration to the elderly Elderly individuals usually have complications, or Elderly individuals usually have complications,
are often taking other medications, so this drug or are often taking other medications, so this
should be used with caution drug should be used with caution
Administration to pregnant Should only be used when the treatment benefits Should only be used when the treatment
women outweigh the risks. There is no experience of benefits outweigh the risks. Safety in
use in pregnancy, so safety is not established pregnancy is not established. Teratogenicity
has been proven in animals
Administration to lactating Breast-feeding should be stopped for at least Breast-feeding should be stopped. The drug
women 1 week transfers into breast milk and has been
detected in breast milk up to 14 days after
dosing
Administration to children Safety in children is not established (no usage Safety is not established in children weighing
experience). Children have smaller body surface <15 kg (usage experience is limited)
areas, so the amount applied in a single
application should be reduced accordingly
Adverse drug reactions Dermatitis, elevated aspartate aminotransferase Liver dysfunction, jaundice, reduced platelet
and alanine aminotransferase etc. 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 in mammals, ivermectin has a poor affinity with specific binding
c-aminobutyric acid (GABA), a neurotransmitter. In terms of the sites in the brains of mammals, and avermectins do not easily
safety margin of this class of compounds in humans, the safety cross the blood–brain barrier in mammals such as rats.106
of ivermectin is considered to be assured. Given that the pres- It has been reported that ivermectin has a p-glycoprotein
ence of glutamatergic chloride channels has not been reported (p-Gp) substrate.107 Therefore, reports indicate that

N. Ishii et al.
combination of ivermectin with drugs that inhibit p-Gp in sheep reactions relating to kidney function.112 Almost all the metabo-
inhibits gastrointestinal p-Gp, increasing the absorbed amount lites are excreted in the feces, and it takes 12 days or more for
(resulting in elevated plasma concentration),107 so care should 95% or more of the drug to be eliminated.106
be taken in humans. The brain/blood concentration ratio during Dosing method: The drug is taken with water on an empty
p.o. administration of ivermectin to rats and mice was small, stomach at a dose of 200 lg/kg. Safety is not established in
suggesting that ivermectin has poor permeability of the blood– children weighing less than 15 kg. Teratogenicity has been
brain barrier. Tests also show that the transfer of ivermectin proven in animals, so this drug should not be used during
B1a into the cerebrospinal fluid of female dogs is extremely pregnancy. The maximum concentration was distributed in
low. However, it should be considered that when used in com- breast milk 4 h after administration of 12 mg ivermectin to
bination with other drugs that similarly inhibit p-Gp, the excre- breast-feeding women (maximum concentration, 7.6 ng/mL),
tory function of p-Gp at the blood–brain barrier is inhibited, and ivermectin was detected in breast milk 14 days after dos-
which may result in the distribution of ivermectin into the ing.106 Therefore, it is preferable to stop breast-feeding when
brain.106 using this drug and to resume breast-feeding once a sufficient
Pharmacokinetics: Oral absorption of ivermectin is relatively period of time has elapsed since dosing.
rapid. When 6–15 mg ivermectin tablets are administrated to Studies suggest that ivermectin may enhance the action of
healthy adults, the maximum plasma concentration peaks in 4– GABA, an inhibitory system neurotransmitter.113,114 Therefore,
5 h (12 mg dose is ~30 ng/mL), and subsequently disappears particular care is essential when using this drug in combination
with a half-life of 10–20 h.106 Within this dosage range, the with drugs that reinforce the activity of GABA, such as barbitu-
pharmacokinetics are dose dependent and there is almost no rates, benzodiazepines and sodium valproate, as it can lead to
racial or sex differences.106 Ivermectin is a fat-soluble drug, augmented activity.
and there are reports showing that absorption increases There can be temporary intensification of the itching sensa-
approximately 2.57 times after consumption of a high-fat tion and eruptions in the initial stages of treatment with iver-
meal.108 Therefore, it is preferable to take this drug on an mectin. The reason for this is presumed to be due to a
empty stomach. Ivermectin has high transitivity to tissues (vol- temporary release of a high volume of mite body components
ume of distribution, 4–5 L/kg),106 and data from non-clinical tri- due to ivermectin killing the mites, which intensifies the allergic
als suggest that the drug is distributed to the liver in high reaction. This allergic reaction may persist for a number of
concentrations. Therefore, liver function tests should be imple- months after the mites have died, so the drug is not to be hap-
mented as needed in patients with liver dysfunction and in hazardly administrated again due to symptoms such as itching
elderly patients. or erythema, unless new characteristic eruptions appear and
The transitivity of ivermectin to the skin is as described surviving mites are identified.105
below.109 A single oral dose of ivermectin 12 mg was adminis- There have been reports of adverse drug reactions including
trated to five patients hospitalized with scabies, and the con- liver dysfunction, jaundice, reduced platelet count, toxic epi-
centration of ivermectin was measured in the scales, sebum dermal necrolysis and Stevens–Johnson syndrome. Therefore,
and sweat at seborrheic zones (forehead, behind the auricle of appropriate measures should be taken such as monitoring skin
the ear) and non-seborrheic zones (index finger, dorsum of the symptoms after dosing, and conducting blood biochemistry
hand, axilla and abdomen). Ivermectin was detected in all the tests 1 week after dosing.
samples. The highest concentration was in the forehead, and A report has shown that ivermectin tablets can easily be
the concentration was 23 11 ng/g in four patients with suspended in warm water at 55°C (simple suspension method),
asteatotic eczema and 110 ng/g in one patient with seborrheic enabling effective administration via a gastric tube.115 How-
skin. Tmax was seen after 8 h in almost all the samples. The ever, ivermectin is sparingly soluble in water, and most of the
drug concentration in the skin was investigated in a patient drug precipitates in suspension. Hence, the dose may be
with onchocerciasis administrated a single oral dose of iver- reduced by close to half depending on the technique used for
mectin 150 lg/kg.110 The skin and plasma concentration 4 h tubal administration. When administrating ivermectin suspen-
after dosing was 90.9 ng/g and 46 ng/mL, respectively, sion via a gastric tube, infusing the drug with the angle of the
decreasing to 66.6 ng/g and 24 ng/mL 48 h after dosing. After alimentary syringe perpendicular or sloping downward, and
72 h, the skin concentration was 41.4 and 64.9 ng/g in two infusing the remaining precipitate in the syringe with rewashing
patients. Based on the aforementioned two published works, can keep the dose loss to 10% or less.116 When administrating
transfer to the skin reaches the maximum level 4–8 h after dos- the drug with a nasogastric tube, if the bed is in a 30° upright
ing, and is thought to decrease steadily thereafter. A higher position and a technique similar to that used with the syringe
concentration of the drug transfers to seborrheic zones. The is employed, it has been confirmed that there is no loss of iver-
minimum lethal dose for S. scabiei has not been clarified. mectin dose.117
Metabolites are mainly formed via oxidation or desorption of
glucose, and cytochrome P450 3A4 (CYP3A4) is presumed to Phenothrin and ivermectin combination therapy
be involved in part of the metabolic reaction.106 Only a very Safety: Phenothrin primarily undergoes ester hydrolysis, and 3-
small amount is excreted in the urine, so it is not necessary to PB is produced as the main metabolite. 3-PB is mainly metab-
reduce the dose in patients with renal disorders or on dialy- olized by cytochrome P450 2E1.118 The involvement of
sis.111 However, there are a number of reports of adverse CYP3A4 in the metabolism of ivermectin has been clarified,119

so it is unlikely that competitive inhibition will occur in the 3–5 days, so the drugs should be administrated taking into
metabolic enzymes. Guidelines for treating scabies in northern consideration the life cycle of the mites.
Australia and in the USA recommend combining permethrin There are topical treatments and oral treatments.
and ivermectin for the treatment of crusted scabies, and no
serious adverse events have been reported through using Topical treatment. Phenothrin (recommendation level A) is rec-
these two drugs in combination.70 There were no reports of ommended as the first-line drug, and it should be applied at
serious adverse events when topical permethrin and oral iver- least twice with a 1-week interval between applications. The
mectin were used in combination in four subjects in a clinical topical medication is washed off in the bath or shower at least
study report in Japan.74 12 h after application. There is limited experience with phe-
Efficacy: Phenothrin acts upon Na+ channels in the nerve nothrin use, so it should be administrated while checking effi-
cells of invertebrates, exciting and killing parasites through the cacy and safety.
depolarization of nerve cells or by interrupting neurotransmis- Second-line drugs are crotamiton (C1), sulfur (C1) and ben-
sion. On the other hand, ivermectin acts upon the glutamater- zyl benzoate (C1).
gic chloride channels present in the nerve cells of
invertebrates, causing hyperpolarization of nerve cells, and par- Oral treatment. Ivermectin (A) is administrated on an empty
alyzing and killing parasites. While the action site differs, the stomach at a dose of 200 lg/kg. The patient is requested to
induced effect is excitation of the nerve cells and paralysis, so come back after 1 week, and if S. scabiei are detected with a
it cannot be ruled out that using these two drugs simultane- microscope or dermoscope, or if new formation of the charac-
ously may affect efficacy. However, in overseas guidelines, no teristic scabies eruption (e.g. scabies burrows) is seen, then
mention is made of the dosing timing of the two drugs.70 The ivermectin is re-administrated. Liver function tests should be
“Safety and efficacy when used in combination with other conducted as necessary for patients with liver dysfunction or
drugs for treating scabies” was incorporated into the post-mar- elderly patients. Normally, the scabies are cured in approxi-
keting drug risk management plan for phenothrin lotion.120 mately 1 month with two doses.121
Usage method: At present, the usage method for topical When insufficient response is seen with topical treatment
phenothrin is removal of the lotion at least 12 h after applica- or oral treatment, consider changing the treatment method
tion, by washing in a bath or shower. Ivermectin is to be taken after checking treatment compliance with the patient.
with water on an empty stomach, so dosing is conducted in Patients on steroids or those taking immunosuppressants,
accordance with these procedures. However, further investiga- patients with malignant tumors and diabetes, those on dialy-
tion with more cases should be conducted to examine drug sis and elderly patients may have a reduced immune status,
interactions, efficacy and safety when the two drugs are used which may prolong the treatment period. For such cases,
in combination. combined treatment with topical and oral medication should
be considered.122
Actual treatment method
The treatment algorithm is shown in Figure 1. Crusted scabies
With common scabies, the usage method for topical agents The basic treatment is: (i) removal of the hyperkeratotic
is application of the medication over the entire body below the layer; and (ii) topical, oral, or a combination of topical and
neck, including areas free of eruption. Ensure all areas are oral treatment. As there is no experience in Japan of com-
coated, including behind the ears, between the fingers, the bining phenothrin lotion and ivermectin, careful consideration
external genitalia and the buttocks. With children and elderly should be given to drug interactions, efficacy and safety
patients, ensure the entire body is coated, including the face when using these drugs in combination. As a measure to
and the head, even with cases of common scabies. prevent the spread of infection, the patient needs to be iso-
With crusted scabies, the entire body is to be coated, lated in a private room for 1–2 weeks after obtaining consent
including the face and the head. for this procedure.
With sulfur, crotamiton and benzyl benzoate, the topical The topical phenothrin lotion is applied to the entire body.
agents are to be washed off in a bath or shower 24 h after An occlusive dressing is applied over the lotion using Vase-
application. The same process applies to phenothrin 12 h or line containing salicylic acid or zinc oxide to soften the
more after application. Consider wearing gloves and socks thickened keratinous layer and crust. After the keratinous
as needed to prevent the medication entering the mouth. layer has softened, it is loosened by bathing and subsequent
Treatment is completed once S. scabiei is no longer removal with a brush or other such implement. This skin
detected, or no new formation of eruptions characteristic of treatment procedure is repeated every day, including days
scabies, such as the scabies burrows, occurs. However, be when phenothrin lotion is not applied. The patient must
aware of itching sensation, eruptions, reinfestation and relapse always be checked for the presence of nail scabies. Iver-
after scabies treatment. mectin is used as oral therapy.
Microscopy is performed once a week and treatment meth-
Common scabies ods should be considered after checking for the presence of
Virtually none of the existing scabicides kills the eggs, includ- S. scabiei and for new eruptions characteristic of scabies, such
ing phenothrin and ivermectin. The eggs of S. scabiei hatch in as scabies burrows. Some reports claim that the number of

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

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, consideration 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.

N. Ishii et al.
Reinfestation and/or relapse even with epidemiological studies, it is often impossible to

It is not uncommon for scabies to be judged “cured” after identify the crusted scabies that are the source of
treatment, only to be diagnosed again a few months later (rein- infection.44,134,135 Patients with crusted scabies are often in
festation/relapse).127,131 In such cases, reinfestation or relapse poor general health, and may leave the affected group before
is determined by examining the patient, confirming treatment diagnosis due to death or hospital transfer, so the affected
compliance and making inquiries about or examining the skin person may be absent at the time the mass outbreak is recog-
condition of people in the patient’s immediate vicinity, such as nized. In these situations, the patient first diagnosed with com-
roommates, family, friends and acquaintances. Genetic testing mon scabies may be erroneously regarded as the source of
of the mite infesting the person may also be considered to infection.
make a judgment on reinfestation and relapse.132 However, at Even if infection prevention measures are adopted, new
present, there is no practical application of testing methods to scabies patients may appear, but this does not always mean
differentiate between different mite infestations. that the respective measures are inadequate. This is because
Reinfected/relapsed scabies still respond to treatment,54,127 the patient might have been infested prior to implementation of
so at present, it is not necessary to consider drug resistance the preventative measures, and the infestation became symp-
when treating reinfected or relapsed cases. However, resis- tomatic after the incubation period. The incubation period is
tance to ivermectin has already been reported in the veterinary long, so new cases may be seen after a number of months. It
field.133 There has also been a report of two human cases is recommended to continue with the minimum required mea-
overseas where in vitro-resistant S. scabiei were confirmed,54 sures that can be implemented without exhausting people in
so caution is now essential. the workplace, based on the understanding of the differences
between common scabies and crusted scabies (Table 6).
PREVENTION OF INFESTATION Mass outbreak

For the prevention of scabies infestation, it is necessary to Even with a mass outbreak, conditions can vary, depending on
adopt measures based on the ecology of S. scabiei. Medical factors such as the number of affected patients. Namely, the
personnel, as well as the directors and managers of facilities, risk of infection differs depending on: (i) the potency of the
patients and patient families should all be adequately educated infection in the index case; (ii) the period of time the index case
on the clinical condition, diagnosis, treatment and prevention came into contact with others before preventative measures
of scabies, which will prevent panic in the event of a mass out- were in place; and (iii) group characteristics (age, underlying
break, and will also serve as a preventative measure. diseases, immunity and behavior). The measures required to
mitigate that risk will differ depending on the extent of available
Basic concept of scabies prevention funds and the burden of effort. The aforementioned conditions
If a scabies patient is confirmed in an area of communal living, will differ for each individual mass outbreak, so there is no
including hospitals, facilities for the elderly, facilities for the dis- fixed standard for measures that should be adopted. There-
abled, children’s nursery school and so forth, first checks are fore, it is necessary to examine measures to suit the circum-
to be made to rule out other scabies patients. The infectivity of stances of each particular facility.
common scabies is not very strong, so the risk of infestation is 1. The infectivity of scabies patients differs depending on the
low without close contact with the affected patient. Typical number of mites infesting the patient. The infectivity of
examples of persons in close contact would be someone shar- crusted scabies is also thought to differ depending on the
ing a bed with the affected person, but shared bedding or extent of hyperkeratosis, and there have been attempts to
walking hand-in-hand with someone for a prolonged period of grade risks based on clinical findings.122 Establishment of
time also poses a risk of infestation. infection will also be affected by the immunity of the person
If two or more scabies patients are found within the same who came into contact with the patient, and particular care
group within a few months, it would be considered a mass out- is needed with individuals using immunosuppres-
break. Crusted scabies should be considered as a source of sants.136,137
infection, so efforts must be made to locate the patient with 2. Cases differ significantly depending on the timeframe from
crusted scabies. onset in the first patient (sometimes it may not be possible
When taking measures to prevent scabies infestation, it is to identify this person), until a mass outbreak is recognized
important to ensure early diagnosis and early treatment without and measures are started.42 The longer this period of time,
overlooking any potential scabies patients.42 Medical examina- the longer the period where people are exposed to the
tion days should be adjusted based on consideration of the source of infection without any measures in place, and the
incubation period. Drugs used to treat scabies are miticides, larger the scale of the mass outbreak. Group behavior pat-
and treatment of the patient will reduce the number of living terns, including the frequency of close contact, will also
S. scabiei on the surface of the patient’s skin, thus reducing change the way in which the infection spreads. There have
infectivity. been reports of cases where staff nursing and caring for
Common scabies do not have a strong degree of infectivity. bedridden patients with crusted scabies become infested
With the exception of special circumstances, the source of and the infestation then spreads to other patients and fam-
infection in a mass outbreak will be crusted scabies. However, ily members via the infected staff members.138,139

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

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
1008
N. Ishii et al.
Table 6. (continued)
Measure Common scabies Crusted scabies

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

3. It is essential to have a leader to take command of infec- Is there any significance of adopting a “border
tion prevention during a mass outbreak. That person should strategy” for scabies?
conduct an epidemiological survey, ascertain any changes Scabies is a disease that spreads through human-to-human
in the number of patients and the response to treatment, contact, so living in groups presents a risk for infection. In
and explain the situation to concerned parties. They must other words, the risk is considered to be higher in patients
also decide how much effort should be expended and how who are transferred from another hospital or facility, than in
much financial burden is needed for the infection preven- patients who are admitted to the hospital or placed into facili-
tion measures. ties from their own home. However, scabies is a disease with
4. There are occasions when patients with crusted scabies a long incubation period, so the incidence of scabies is low in
must be put into isolation. Isolation is a restriction of patients transferred from hospitals or facilities. Therefore,
human rights. Therefore, it is necessary to obtain informed implementing measures such as requesting a negative diagno-
consent for this procedure and to limit the period of isola- sis certificate or implementing prophylaxis across the board is
tion to the required minimum. not recommended.143 It is important to observe the individual
for a certain period of time.
Prophylaxis Mass outbreak of scabies in children

Prophylaxis should be considered for people who may have
Historically, scabies is a disease that is prevalent mainly in chil-
been in close contact with crusted scabies patients, even
dren and sexually active young people. There are also many
when the patient was asymptomatic, as that would have been
children affected by scabies in developing countries.144,145
the incubation period. Providing prophylaxis can be expected
In Japan, there have been a number of reports of mass out-
to ensure a “cure” for people who are currently in the incuba-
breaks in nursery schools,20,146,147 and the pattern of the
tion period, thus preventing the onset of scabies. However,
spread of infestation differs depending on the circumstances
even if the onset conditions are investigated epidemiologically,
of the case. Compared with cases in hospitals and elderly care
the source of infection and route of infection may be unknown,
facilities, more cases and suspected cases in the general pop-
and it is often impossible to identify who has been in close
ulation are seen at many different regional dermatological clin-
contact with the affected person. In these circumstances, it is
ics. It is essential to be aware of the difficulty of compiling
not recommended to provide prophylaxis, and instead to moni-
information on treatment, and infection prevention policies.142
tor the person’s progress and treat affected people as they
become symptomatic.
DRUGS USED TO TREAT SCABIES OVERSEAS
Mass prophylaxis The drugs used for scabies overseas and their respective posi-
When the attack rate within a group is high, and when all tioning are shown in Table 7.
members of the group may have had close exposure, prophy-
laxis of all the members of the group may be an option. There
ANIMAL SCABIES
are many reports of mass treatment in hospitals, facilities,
communities and so forth using topical and oral medication.140 Summary
There are reports of mass treatment where permethrin was There are different types of scabies unique to each mammal
applied simultaneously to several hundred people, and the host, including humans, monkeys, dogs, cats, rabbits, cows,
mass outbreak was controlled in a short period of time.141,142 horses and sheep. Scabies where the original host is not
However, there are also reports where all the people who human, but temporarily infests humans, causing skin disease,
came into contact with the affected person were dosed with is known as animal-transmitted scabies.148,149 The incidence of
ivermectin en masse, but they subsequently developed sca- animal-transmitted scabies has increased together with the
bies.51,126 It should be noted that there are limitations with effi- recent boom in pet ownership. As people increasingly live
cacy when embarking on prophylaxis, particularly with mass together with animals, the chance of humans being infested
treatment. with canine and feline scabies has increased.
The main causative mite for animal-transmitted scabies is
Methods of prophylaxis and mass prophylaxis the scabies specific to dogs, Sarcoptes scabiei var. canis. This
When using prophylaxis, informed consent should be obtained type of scabies is a variant of the human S. scabiei and the
from the person being treated regarding the advantages (e.g. two types are morphologically indistinguishable. Canine sca-
possibility of ending mass outbreak, possibility of curing scabies bies can temporarily infest human skin, but they cannot repro-
in the incubation period) and the disadvantages (e.g. cost bur- duce.150 When canine scabies infest dogs, they cause
den, overtreatment, possibility of adverse reactions). However, significant hair loss. The condition can become very serious,
this treatment is not covered by health insurance. There are no much like human crusted scabies, and can even result in
standards on mass prophylaxis, neither is there any information death.
on the scale of a mass outbreak that would necessitate mass Apart from canine scabies, feline scabies, Notoedres cati,
prophylaxis.140 Therefore, a decision must be made based on and canine ear scabies, Otodectes cynotis, can also cause ani-
the information in section “Mass outbreak” 1–4 above. mal-transmitted scabies.

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.

Skin symptoms of animal-transmitted scabies dermatologists and medical personnel pool their knowledge on
The clinical profile of animal-transmitted scabies is similar to diagnosis and prevention, improve existing techniques, and
human common scabies, with multiple erythematous papules adopt a stance of tackling preventative measures as a team.
on the trunk and limbs, associated with an intense itching sen- The general public and medical personnel need to be edu-
sation. Pustules may also form. However, scabies burrows and cated on scabies to deepen the level of understanding, reduce
nodules in the genital regions are normally not seen. The gen- the number of scabies patients, and work towards the eradica-
eral clinical characteristics of animal-transmitted scabies origi- tion of scabies.
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 REFERENCES
commonly occurs in sites that come into contact with the 1 Executive Committee of the Guideline for the Diagnosis and Treat-
affected dog (chest and abdomen, forearms); and (iv) the time ment of Scabies: Guideline for the diagnosis and treatment of sca-
until onset of symptoms ranges from a number of hours to bies. Jpn J Dermatol 2005; 115: 1125–1129. [In Japanese]
2 Executive Committee of the Guideline for the Diagnosis and Treat-
1 month after coming into contact with the affected dog.151–154
ment of Scabies: Guideline for the diagnosis and treatment of scabies
On rare occasions, the scabies mite may be detected from the in Japan (second edition). Jpn J Dermatol 2007; 117: 1–13. [In Japa-
eruption.154,155 nese]; English version available in J Dermatol 2008; 35: 378–393.
With dermoscopy, it is not possible to detect the mite body 3 Hayashi M, Uchiyama M, Nakajima H, Nagai R. The immuno-
histopathologic study of scabies by the PAP method - identifica-
as can be seen with human scabies. However, characteristic
tion of IgE positive mast cells. J Dermatol 1986; 13: 70–73.
findings include curved linear crust in the area where the 4 Burgess I. Sarcoptes scabiei and scabies. In: Baker JR, Muller R,
papules are located.156 eds. Advances in Parasitology, Vol. 33. London: Academic Press,
1994; 235–292.
Diagnosis 5 Hayashi M. Scabies. In: Nagatani T, Miyabayashi T, Yamamoto I,
Hayashi M, eds. The Skin Diseases in the Bedridden Old. Tokyo:
In cases where the clinical findings are similar to scabies, but
Medicalsense Co, 2000; 68–89. [In Japanese]
there is no eruption on the palms or between the fingers, and 6 Ohtaki N, Makigami K, Seki N. Scabies-no Spooky. Tokyo: Iga-
no scabies burrows, it is reasonable to suspect animal-trans- kushoin, 2002; 1–137. [In Japanese.]
mitted scabies. 7 Chosidow O. Clinical practices. Scabies. N Engl J Med 2006; 354:
1718–1727.
The presence or absence of pets or animals the person may
8 Uchikawa K. Biology of Sarcoptes scabiei. Infect Agents Surveill
have come into contact with through their work and the health Rep 2001; 22: 246–247. [In Japanese].
status and skin condition of those animals is to be checked. If 9 Heilesen B. Studies on Acarus scabiei and scabies. Acta Derm
animal-transmitted scabies is suspected, scales from the ani- Venereol 1946; 26(Suppl. 14): 151–153.
mals are collected, and if the scabies mite can be detected 10 Hayashi M. The skin diseases and life conduct – scabies/pediculo-
sis-. Pract Dermatol 1998; 20: 469–475. [In Japanese].
through direct microscopic observation, the diagnosis can be
11 Walton SF, Holt DC, Currie BJ, Kemp DJ. Scabies: new future for
confirmed. a neglected disease. Adv Parasitol 2004; 57: 309–376.
12 Arlian LG, Runyan RA, Achar S, Estes SA. Survival and infectivity
Treatment of Sarcoptes scabiei var. canis and var. hominis. J Am Acad Der-
matol 1984; 11: 210–215.
Avoiding direct contact with the affected animal that is the
13 Epstein E, Orkin M. Scabies: clinical aspects. In: Orkin M et al., eds.
source of infection, and treating the animal are the most impor- Scabies and Pediculosis. Philadelphia: JB Lippincott, 1977; 17–22.
tant measures, as the human eruption will not be cured until 14 Hayashi M. What kind of disease is scabies? In: Nanko H, ed. Sca-
treatment of the animal is completed. Treatment of the animal bies Management Perfect Guide. Tokyo: Shujunsha, 2008; 42–63.
that is the source of infection should be requested from a [In Japanese]
15 Johnson CG, Mellanby K. The parasitology of human scabies. Par-
veterinarian.
asitology 1942; 34: 285–290.
The human eruption is an allergic reaction to the scabies 16 Mellanby K. Biology of the parasite. In: Orkin M et al., eds. Scabies
derived from the animal, and animal scabies will not reproduce and Pediculosis. Philadelphia: JB Lippincott, 1977; 8–16.
in human skin. Thus, it is not necessary to use scabicide. The 17 Tajiri A, Inoue S, Ogata K, Kuroki Y, Aoki Y, Shimonuru Y. Scabies
in geriatrics. Pract Dermatol 1987; 9: 274–278. [In Japanese].
eruption should be treated with topical steroids and oral antihis-
18 Ohtaki N. Spread of scabies. Nishinihon J Dermatol 1978; 40: 668–
tamines should be used for the itching sensation. However, topi- 672. [In Japanese].
cal applications such as crotamiton cream may be used if there 19 Mellanby K. Scabies. Middlesex: EW Classey, 1972; 1–74.
is continued contact with an untreated and uncured animal. 20 Makigami K, Ohtaki N, Ishii N. An outbreak of scabies among chil-
dren in a nursery. Rinsho Derma 2009; 51: 1843–1846. [In Japa-
nese].
CONCLUSION 21 Kubota Y, Ishii N, Tokumaru R, Nakayama J. An outbreak of sca-
bies in the same ward and house after discharge of a scabies
The options for treatment of scabies have broadened with new patient. Jpn J Dermatol 2009; 119: 1569–1577. [In Japanese].
22 Maie O. Scabies infected from others hands and arms. J Vis Der-
topical preparations coming onto the market. The efficacy and
matol 2003; 2: 778–779. [In Japanese].
safety of these drugs will be widely evaluated. We hope there 23 Wada Y. A method for the detection of the scabies mite based on
will be more research and development in this field, resulting in the biology of Sarcoptes scabiei. Jpn J Clin Dermatol 2005; 59
even more new drugs. On the other hand, it is vital that (Suppl.): 66–70. [In Japanese]

N. Ishii et al.
24 von Hebra F. On Diseases of the Skin, Including the Exanthemata, 50 Nagakura K, Fukaya Y, Kitaharashou Y. Situation of scabies infes-
Vol. II. London: The New Sydenham Society, 1868; 207. tation at elderly facilities in Kanagawa Prefecture. Jpn J Environ
25 Kaposi M. Diseases of the Skin. London: Tindall and Cox, 1895; 655. Infect 2001; 16: 216–219. [In Japanese].
26 Yoshizumi J. Scabies love creases – follow the “wake” left by the 51 Makigami K, Ohtaki N, Sato Y, Yamaguchi N. Nosocomial outbreak
mite. Pract Dermatol 2006; 28: 343–350. [In Japanese]. of scabies in a psychiatric hospital – epidemiological assessment
27 Wada Y. Was there a “wake sign” description in the past? Pract and prophylaxis with oral ivermectin. Jpn J Hyg 2005; 60: 450–
Dermatol 2006; 28: 1518. [In Japanese]. 460. [In Japanese].
28 Yoshizumi J, Tanaka M. Dermoscopy: a useful technique for mak- 52 Ohtaki N. Scabies – diagnosis, treatment, and prevention. Antibiot
ing a diagnosis of scabies. J Vis Dermatol 2007; 6: 262–263. [In Chemother 2003; 19: 70–74. [In Japanese].
Japanese]. 53 Ohtaki N. Scabies. Rinsho Derma 2003; 45: 1495–1501. [In Japa-
29 Yoshizumi J, Harada T. ‘Wake sign’: an important clue for the diag- nese].
nosis of scabies. Clin Exp Dermatol 2009; 34: 711–714. 54 Currie BJ, Harumal P, McKinnon M, Walton SF. First documenta-
30 Ohtaki N. Bullous or pustular lesion, small bulla or pustule type, tion of in vivo and in vitro ivermectin resistance in Sarcoptes sca-
scabies in infants and small children. Rinsho Derma 2000; 42: biei. Clin Infect Dis 2004; 39: 8–12.
1500–1501. [In Japanese] 55 Executive Committee of the Guideline for the Diagnosis and Treat-
31 Hayashi M, Uchiyama M, Nakajima H, Nagai R. The immuno- ment of Skin Cancer: Guideline for the diagnosis and treatment of
histopathologic findings of Norwegian scabies by means of the skin cancer. http://www.dermatol.or.jp/medical/guideline/skincance
PAP method. Jpn J Dermatol 1985; 95: 509–512. [In Japanese]. r/index.html [In Japanese]
32 Alexander JO. Scabies, Arthropods and Human Skin. Berlin: 56 Singalavanija S, Limpongsanurak W, Soponsakunkul S. A compar-
Springer Verlag, 1984; 227–292. ative study between 10 per cent sulfur ointment and 0.3 percent
33 Nanko H. Skin diseases characterized in elderly person. Scabies. gamma benzene hexachloride gel in the treatment of scabies in
Rinsho Derma 2001; 43(Suppl.): 1371–1377. [In Japanese] children. J Med Assoc Thai 2003; 86: 531–536.
34 Miyachi M, Kubota Y, Matsuo M, Tanigawa O, Nakayama J, Ando 57 Gulati PV, Singh KP. A family based study of the treatment of sca-
T. Clinical investigation of scabies in the elderly over the past bies with benzyl benzoate and sulfur ointment. Indian J Dermatol
5 years in the Nishifukuoka Hospital – take note of the feet, sca- Venereol Leprol 1978; 44: 269–273.
bies in the elderly. Nishinihon J Dermatol 2009; 71: 306–311. [In 58 Fathy FM, El-Kasah F, El-Ahwal AM. Clinical and parasitological
Japanese]. study on scabies in Sirte, Libya. J Egypt Soc Parasitol 2010; 40:
35 Orkin M. Today’s scabies. JAMA 1975; 233: 882–885. 707–731.
36 Scrace M, Koko K. An outbreak of acute post-streptococcal 59 Muso Y, Jomura T, Sakai H, Shirabe H, Takagi K. The trial of use
glomerulonephritis in remote Far North Queensland. Aust J Rural of sulfur and camphor lotion for treatment of scabies. Skin Res
Health 2006; 14: 160–163. 2007; 6: 191–194. [In Japanese].
37 Hoy WE, White AV, Dowling A et al. Post-streptococcal glomeru- 60 Taplin D, Meinking TL, Chen JA, Sanchez R. Comparison of cro-
lonephritis is a strong risk factor for chronic kidney disease in later tamiton 10% cream (Eurax) and permethrin 5% cream (Elimite) for
life. Kidney Int 2012; 81: 1026–1032. the treatment of scabies in children. Pediatr Dermatol 1990; 7: 67–
38 Katsumata K, Katsumata K. Simple method of detecting Sarcoptes 73.
scabiei var. hominis mites among bedridden elderly patients suffer- 61 Amer M, El-Gharib I. Permethrin versus crotamiton and lindane in
ing from severe scabies infestation using an adhesive-tape. Intern the treatment of scabies. Int J Dermatol 1992; 31: 357–358.
Med 2006; 45: 857–859. 62 Ohtaki N, Kurumaji Y, Miyamoto C, Hayashi K. Massive occurrence
39 Uenotsuchi T, Moroi Y, Urabe K, Tsuji G, Takahara M, Furue M. of scabies in two children institutions and its therapeutic experi-
The scybala (fecal pellets) of Sacroptes scabiei var. hominis are ence. Rinsho Derma 1985; 27: 599–603. [In Japanese]
obviously stained with chlorazol black E. J Dermatol 2004; 31: 63 Hayashi M. Statistical analysis of patients with scabies presented
511–512. to Yamagata Prefectural Shinjo Hospital, division of Dermatology
40 Wada Y. Diagnostic methods for the detection of Sarcoptes scabiei for last two years. Rinsho Derma 2010; 52: 199–203. [In Japa-
based on its biology. MB Derma 2005; 101: 51–56. [In Japanese]. nese].
41 Kusunoki T. Strategy for scabies - Knack for detecting mite bodies. 64 Ly F, Caumes E, Ndaw CAT, Ndiaye B, Mahe A. Ivermectin versus
J Vis Dermatol 2005; 4: 1214–1215. [In Japanese]. benzyl benzoate applied once or twice to treat human scabies in
42 Juranek DD. Scabies control in institutions. In: Orkin M, Maibach Dakar, Senegal: a randomized controlled trial. Bull World Health
HI, eds. Cutaneous Infestations and Insect Bites. New York: Marcel Organ 2009; 87: 424–430.
Dekker, 1985; 139–156. 65 Oyelami OA, Onayemi A, Oyedeji OA, Adeyemi LA. Preliminary
43 Ishii N, Miyazawa M, Kawaguchi H, Inami S, Nakajima H. Statistical study of effectiveness of aloe vera in scabies treatment. Phytother
analysis of scabies. STD 1989; 70: 19–21. [In Japanese]. Res 2009; 23: 1482–1484.
44 Lettau LA. Nosocomial transmission and infection control aspects 66 Yoshida K, Suzuki H, Shike K et al. Comparison of effectiveness
of parasitic and ectoparasitic diseases. Part III. Ectoparasites/sum- between 6% benzyl benzoate/crotamiton combination ointment
mary and conclusions. Infect Control Hosp Epidemiol 1991; 12: and 1% c-BHC ointment for scabies. J Jpn Soc Hosp Pharm 2003;
179–185. 39: 439–441. [In Japanese].
45 Yamada N, Iida R, Nakazawa K, Tsukamoto K, Shimada S. Macro- 67 Nolan K, Kamrath J, Levitt J. Lindane toxicity: a comprehensive
scopic feature of scabies burrow. Rinsho Derma 1997; 39: 681– review of the medical literature. Pediatr Dermatol 2012; 29: 141–
682. [In Japanese]. 146.
46 Saruta T. Dermascopy of scabies burrows. In: Nanko H, ed. Sca- 68 Siddiqui MK, Nigam U, Kaul PP, Seth TD. Bioaccumulation of HCH
bies Management Perfect Guide. Tokyo: Shujunsha, 2008; 106– isomers in different tissues of young and old rats: a comparison.
128. [In Japanese] Bull Environ Contam Toxicol 1996; 56: 896–902.
47 Larre gue M, Gombert P, Le vy C, Gallet P, Rat JP. Elevation des 69 Mytton OT, McGready R, Lee SJ et al. Safety of benzyl benzoate
IgE dans la gale chez le nfant. Bull Soc Fr Dermatol Syph 1976; 83: lotion and permethrin in pregnancy: a retrospective matched
54–56. cohort study. BJOG 2007; 114: 582–587.
48 Hayashi M. Study of scabies. Yokohama Igaku 1986; 37: 297–314. 70 Currie BJ, McCarthy JS. Permethrin and ivermectin for scabies. N
[In Japanese]. Engl J Med 2010; 362: 717–725.
49 Falk ES, Dale S, Bolle R, Haneberg B. Antigens common to sca- 71 Recommendations and reports: Scabies. CDC MMWR 2010; 59:
bies and house dust mites. Allergy 1981; 36: 233–238. 89–90.

72 van der Rhee HJ, Farquhar JA, Vermeulen NP. Efficacy and trans- 96 National Institute of Health Science (NIHS). International Chemical
dermal absorption of permethrin in scabies patients. Acta Derm Safety Cards (ICSC). 2005. [In Japanese]
Venereol (Stockh) 1989; 69: 170–173. 97 Rote Liste: Rote Liste 2011, 784.
73 Woolen BH, Marsh JR, Laird WJD et al. The metabolism of cyper- 98 WHO. WHO model list of essential medicines for children. 4th list,
methrin in man: differences in urinary metabolite profiles following 2013. http://www.who.int/medicines/publications/essentialmedicine
oral and dermal administration. Xenobiotica 1992; 22: 983–991. s/en/index.html.
74 Morishita A, Taniguchi H, Takino C, Ohtaki N. Efficacy of perme- 99 Japanese Pharmacopeia 15th Edition Drug Monographs, Ministry of
thrin cream in the treatment of scabies. Jpn J Dermatol 2010; 120: Health, Labour and Welfare 2006; 353–355.
1027–1032. [In Japanese]. 100 Oishi T, Tanabe T, Yamazaki H. Changes in ointment combinations
75 Usha V, Gopalakrishnan Nair TV. A comparative study of oral iver- – changes in combinations of intensive antipruritics and corticos-
mectin and topical permethrin cream in the treatment of scabies. teroid ointments and creams. Med Drug J 1998; 34: 2254–2262. [In
J Am Acad Dermatol 2000; 42: 236–240. Japanese]
76 Nemoto O, Ohno A, Takahashi R. Phase II/III trial of phenothrin 101 Soderlund DM. Toxicology and mode of action of pyrethroid insec-
lotion targeting scabies patients – a general clinical study. J Clin ticides. In Hayes Handbook of Pesticide Toxicology, 3rd edn. 2010;
Therap Med 2016; 32: 119–133. pp. 1665–1686.
77 Hanna NF, Clay JC, Harris JR. Sarcoptes scabiei infestation treated 102 Nemoto O, Ohno A, Takahashi R. A phase I study of phenothrin
with malathion liquid. Br J Vener Dis 1978; 54: 354. lotion: a safety study and a placebo-controlled double-blind com-
78 Burgess I, Robinson RJ, Robinson J, Maunder JW, Hassan Z. Aqu- parative skin exposure study. J Clin Therap Med 2015; 31: 385–
eous malathion 0.5% as a scabicide: clinical trial. Br Med J 1986; 399. [In Japanese].
292: 1172. 103 Sereda B, Bouwman H, Kylin H. Comparing water, bovine milk,
79 Petros S. Malathion poisoning. Trop Doct 1990; 20: 71. and indoor residual spraying as possible sources of DDT and pyre-
80 Japan Society for Clinical Toxicology website: http://jsct-web.umin. throid residues in breast milk. J Toxicol Environ Health A 2009; 72:
jp/ 842–851.
81 Strong M, Johnstone P. Interventions for Treating Scabies (Review). 104 Kasai S, Ishii N, Natsuaki M et al. Prevalence of kdr-like mutations
London: The Cochrane Collaboration, Wiley Publishers, 2010; 1– associated with pyrethroid resistance in human head louse popula-
70. tions in Japan. J Med Entomol 2009; 46: 77–82.
82 Macotela-Ruız E, Pen ~a-Gonza lez G. The treatment of scabies 105 Sasaki I. What kind of drug is ivermectin? In: Nanko H, ed. Scabies
with oral ivermectin. Gac Med Mex 1993; 129: 201–205. [In Management Perfect Guide. Tokyo: Shujunsha, 2008; 124–132. [In
Spanish]. Japanese]
83 Koizumi K, Ohnaka Y, Takeshita Y et al. Post-marketing surveil- 106 Banyu Pharmaceutical. Data on Stromectol tablets 3 mg (iver-
lance of Stromectol Tablets 3 mg (ivermectin) for scabies – use mectin). 2002. http://www.info.pmda.go.jp/shinyaku/P200200036/in
results survey. J New Rem Clin 2010; 59: 924–938. [In Japanese] dex.html (See 2011-04-20) [In Japanese]
84 Chouela EN, Abeldan ~o AM, Pellerano G et al. Equivalent therapeu- 107 Lifschitz A, Entrocasso C, Alvarez L et al. Interference with p-gly-
tic efficacy and safety of ivermectin and lindane in the treatment of coprotein improves ivermectin activity against adult resistant
human scabies. Arch Dermatol 1999; 135: 651–655. nematodes in sheep. Vet Parasitol 2010; 172: 291–298.
85 Madan V, Jaskiran K, Gupta U, Gupta DK. Oral ivermectin in sca- 108 Guzzo CA, Furtek CI, Porras AG et al. Safety, tolerability, and
bies patients: a comparison with 1% topical lindane lotion. J Der- pharmacokinetics of escalating high doses of ivermectin in healthy
matol 2001; 28: 481–484. adult subjects. J Clin Pharmacol 2002; 42: 1122–1133.
86 Hansen RC, Remmers E, Menter MA. A controlled comparative trial 109 Haas N, Lindemann U, Frank K, Sterry W, Lademann J, Katzung
of permethrin 5 percent cream and 1 percent lindane lotion for the W. Rapid and preferential sebum secretion of ivermectin: a new
treatment of scabies. Clin Res 1986; 34: 160. factor that may determine drug responsiveness in patients with
87 Taplin D, Meinking TL, Porcelain SL, Castillero PM, Chen JA. Per- scabies. Arch Dermatol 2002; 138: 1618–1619.
methrin 5% dermal cream: a new treatment for scabies. J Am 110 Baraka OZ, Mahmoud BM, Marschke CK, Geary TG, Homeida
Acad Dermatol 1986; 15: 995–1001. MM, Williams JF. Ivermectin distribution in the plasma and tissues
88 Schultz MW, Gomez M, Hansen RC et al. Comparative study of of patients infected with Onchocerca volvulus. Eur J Clin Pharma-
5% permethrin cream and 1% lindane lotion for the treatment of col 1996; 50: 407–410.
scabies. Arch Dermatol 1990; 126: 167–170. 111 Harada T, Seki M, Nishikido M, Kohno S. New drug infections in
89 Zargari O, Golchai J, Sobhani A. Comparison of the efficacy of various organs. Jpn J Clin Dialysis 2006; 22: 737–746. [In Japa-
topical 1% lindane vs 5% permethrin in scabies: a randomized, nese].
double-blind study. Indian J Dermatol Venereol Leprol 2006; 72: 112 Amano H, Ohashi H, Koizumi K et al. Post-marketing surveillance/
33–36. usage results survey of Stromectolâ tablets 3 mg (ivermectin) for
90 Bachewar NP, Thawani VR, Mali SN, Gharpure KJ, Shingade VP, intestinal strongyloidiasis. J New Rem Clin 2012; 61: 1980–1998.
Dakhale GN. Comparison of safety, efficacy, and cost effective- [In Japanese].
ness of benzyl benzoate, permethrin, and ivermectin in patients of 113 Brownlee DJ, Holden-Dye L, Walker RJ. Actions of the anthelmintic
scabies. Indian J Pharmacol 2009; 41: 9–14. ivermectin on the pharyngeal muscle of the parasitic nematode,
91 Sharma R, Singal A. Topical permethrin and oral ivermectin in the Ascaris suum. Parasitology 1997; 115: 553–561.
management of scabies: a prospective, randomized, double blind, 114 Dawson GR, Wafford KA, Smith A et al. Anticonvulsant and
controlled study. Indian J Dermatol Venereol Leprol 2011; 77: 581– adverse effects of ivermectin analogs in mice are mediated
586. through the c-aminobutyric acidA receptor. J Pharmacol Exp Ther
92 Asai T. Topical prescription medicine containing crotamiton. Pract 2000; 295: 1051–1060.
Dermatol 2009; 31: 375–377. [In Japanese]. 115 Hitani A, Kimura M. Ivermectin in controlling a nosocomial scabies
93 Ishina K, Kaneto K. Contact dermatitis with crotamiton included in outbreak. Clin Parasitol 2004; 15: 68–71. [In Japanese].
loxoprofen sodium hydrate cataplasms. Rinsho Derma 2010; 52: 116 Ohtani M, Yamamoto Y, Sakamaki T et al. Influence of devices
1168–1169. [In Japanese]. and technique of administering a simple suspension on the dosage
94 Horiuchi W. Contact dermatitis syndrome induced by crotamiton in of STROMECTOLâ Tablets. Jpn J Pharm Health Care Sci 2012;
an over-the-counter antifungal drug. Rinsho Derma 2009; 51: 38: 78–86. [In Japanese]
1310–1311. [In Japanese]. 117 Kim Y, Sakamaki T, Yuasa N et al. Influence of using transnasal
95 Novartis. Euraxâ 10% cream Drug Interview Form. 2015. [In Japa- tubes on the dose of STROMECTOLâ Tablets. Jpn J Pharm Health
nese] Care Sci 2014; 40: 515–521. [In Japanese].

N. Ishii et al.
118 Takaku T, Mikata K, Matsui M, Nishioka K, Isobe N, Kaneko H. In 136 Walton SF. The immunology of susceptibility and resistance to
vitro metabolism of trans-permethrin and its major metabolites, scabies. Parasite Immunol 2010; 32: 532–540.
PBalc and PBacid, in humans. J Agric Food Chem 2011; 59: 137 Walton SF, Oprescu FI. Immunology of scabies and translational
5001–5005. outcomes: identifying the missing links. Curr Opin Infect Dis 2013;
119 Stromectol tablets 3 mg drug interview form, Revised June 2012 26: 116–122.
(15th edition). [In Japanese] 138 Ohtaki N, Irimajiri K, Yamada M. Large outbreaks of scabies in a
120 Sumithrin lotion 5% approval review report 4 March 2014 (Evalua- ward consisting of only private rooms. Rinsho Derma 1988; 30:
tion and Licensing Division, Pharmaceutical and Food Safety 325–328. [In Japanese].
Bureau). [In Japanese] 139 Makigami K, Ohtaki N. Two case studies of scabies outbreak in
121 Sadahira C, Amagai M, Ishiko A. Clinical study of oral ivermectin institutional settings: focused on patterns of patient distribution.
for the treatment of scabies. Jpn J Dermatol 2009; 119: 1845– Clin Parasitol 2006; 16: 97–100. [In Japanese].
1850. [In Japanese]. 140 FitzGerald D, Grainger RJ, Reid A. Interventions for Preventing the
122 Ichikawa M, Tanaka M, Naritomi Y, Furue M. Combined ivermectin Spread of Infestation in Close Contacts of People with Scabies
and topical therapy significantly reduces treatment time in aged (Review). London: The Cochrane Collaboration, Wiley Publishers,
scabietic patients. J Dermatol 2013; 40: 306–307. 2014; CD009943.
123 Davis JS, McGloughlin S, Tong SY, Walton SF, Currie BJ. A novel 141 Buehlmann M, Beltraminelli H, Strub C et al. Scabies outbreak in
clinical grading scale to guide the management of crusted scabies. an intensive care unit with 1, 659 exposed individuals - key factors
PLoS Negl Trop Dis 2013; 7: e2387. for controlling the outbreak. Infect Control Hosp Epidemiol 2009;
124 Ohtaki N, Taniguchi H, Ohtomo H. Oral ivermectin treatment in two 30: 354–360.
cases of scabies: effective in crusted scabies induced by corticos- 142 Stoevesandt J, Carle L, Leverkus M, Hamm H. Control of large
teroid but ineffective in nail scabies. J Dermatol 2003; 30: 411– institutional scabies outbreaks. J Dtsch Dermatol Ges 2012; 10:
416. 637–647.
125 Nakamura R, Taniguchi H, Ohtaki N. A case of crusted scabies 143 Makigami K, Ohtaki N, Yasumura S. A 35-month prospective study
with a bullous pemphigoid-like eruption and nail involvement. on onset of scabies in a psychiatric hospital: discussion on patient
J Dermatol 2006; 33: 196–201. transfer and incubation period. J Dermatol 2012; 39: 160–163.
126 Ohtaki N, Taniguchi H, Makigami K. Efficacy of ivermectin in 144 Green MS. Epidemiology of scabies. Epidemiol Rev 1989; 11: 126–
the treatment of endemic of scabies in a nursing home for 150.
the elderly. Jpn J Clin Dermatol 2005; 59: 692–698. [In 145 Hengge UR, Currie BJ, Ja €ger G, Lupi O, Schwartz RA. Scabies: a
Japanese]. ubiquitous neglected skin disease. Lancet Infect Dis 2006; 6: 769–
127 Makigami K, Ohtaki N, Ishii N et al. Risk factors for recurrence of 779.
scabies: a retrospective study of scabies patients in a long-term 146 Makigami K, Ishii N, Ohtaki N, Yasumura S. An outbreak of scabies
care hospital. J Dermatol 2011; 38: 874–879. among infants in a nursery. Rinsho Derma 2008; 50: 1044–1045.
128 Hashimoto K, Fujiwara K, Punwaney J et al. Post-scabietic nod- [In Japanese].
ules: a lymphohistiocytic reaction rich in indeterminate cells. J Der- 147 Makigami K, Onoda M, Kotake I, Ishii N. An outbreak of scabies in
matol 2000; 27: 181–194. a nursery from a child with crusted scabies. Jpn J Clin Dermatol
129 Murayama J, Taniguchi H, Takino C, Ohtaki N, Kumagai J. Two 2013; 67: 942–947. [In Japanese].
cases of post-scabetic nodules: one case mimics lymphoma. Jpn 148 Ohtaki N. Scabies. In: Tamaki K, ed. Comprehensive Handbook of
J Clin Dermatol 2008; 62: 453–456. [In Japanese]. Clinical Dermatology 16. Tokyo: Nakayamashoten, 2003; 56–63. [In
130 Nishi K, Tsuji H, Nakamura T, Yamamoto A, Iizuka H. Post-sca- Japanese]
betic nodules. Pract Dermatol 2005; 27(Suppl.): 39–42. [In Japa- 149 Ohtaki N. Animal scabies. In: Tamaki K, ed. Comprehensive Hand-
nese] book of Clinical Dermatology 16. Tokyo: Nakayamashoten, 2003;
131 Tjioe M, Vissers WH. Scabies outbreaks in nursing homes for the 64–66. [In Japanese]
elderly: recognition, treatment options and control of reinfestation. 150 Ohyama K, Sonoda K, Maekawa Y. Dermatitis due to Sarcoptes
Drugs Aging 2008; 25: 299–306. scabiei var. canis and Notoedres cati. Pract Dermatol 1987; 9:
132 Walton SF, McBroom J, Mathews JD, Kemp DJ, Currie BJ. 541–544. [In Japanese]
Crusted scabies: a molecular analysis of Sarcoptes scabiei variety 151 Emde RN. Sarcoptic mange in the human. A report of an epidemic
hominis populations from patients with repeated infestations. Clin of 10 cases of infection by Sarcoptes scabiei variety canis. Arch
Infect Dis 1999; 29: 1226–1230. Dermatol 1961; 84: 633–636.
133 Terada Y, Murayama N, Ikemura H, Morita T, Nagata M. Sarcoptes 152 Charlesworth EN, Johnson JL. An epidemic of canine scabies in
scabiei var. canis refractory to ivermectin treatment in two dogs. man. Arch Dermatol 1974; 110: 572–574.
Vet Dermatol 2010; 21: 608–612. 153 Norins AL. Canine scabies in children. “Puppy dog” dermatitis. Am
134 Jimenez-Lucho VE, Fallon F, Caputo C, Ramsey K. Role of pro- J Dis Child 1969; 117: 239–242.
longed surveillance in the eradication of nosocomial scabies in an 154 Takenaka S, Nanko H. Animal scabies. In: Nanko H, ed. Scabies
extended care Veterans Affairs medical center. Am J Infect Control Management Perfect Guide. Shujunsha: Tokyo, 2008; 298–303. [In
1995; 23: 44–49. Japanese]
135 Makigami K. Allies and measures for handling mass infection - 155 Ogura C, Natsuaki M, Miyata A, Yamanishi K. Three cases of
from the perspective of community hygiene. In: Nanko H, ed. Sca- canine scabies in a family. Skin Res 2006; 5: 62–66. [In Japanese].
bies Management Perfect Guide. Tokyo: Shujunsha, 2008; 180– 156 Aydingo € z IE, Mansur AT. Canine scabies in humans: a case report
198. [In Japanese] and review of the literature. Dermatology 2011; 223: 104–106.

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doi: 10.1111/1346-8138.

13896 Journal of Dermatology 2017; 44: 991–1014

© 2017 Japanese Dermatological Association 991

BACKGROUND OF CREATING THE GUIDELINE ECOLOGY OF S. SCABIEI (SCABIES MITE)

992 © 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 993

994 © 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 995

© 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 997

998 © 2017 Japanese Dermatological Association

Recommendation level: C1 (use of the treatment may be Crotamiton

© 2017 Japanese Dermatological Association 999

Phenothrin generated. When phenothrin is applied to the skin to treat sca-

1000 © 2017 Japanese Dermatological Association

Non-proprietary name Phenothrin Ivermectin

© 2017 Japanese Dermatological Association 1001

1002 © 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 1003

Common Crusted scabies

Topical Oral Combined topical and oral therapy

Neither present 1 and/or 2 are present

1004 © 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 1005

Reinfestation and/or relapse even with epidemiological studies, it is often impossible to

PREVENTION OF INFESTATION Mass outbreak

1006 © 2017 Japanese Dermatological Association

Measure Common scabies Crusted scabies

© 2017 Japanese Dermatological Association

Measure Common scabies Crusted scabies

© 2017 Japanese Dermatological Association

Prophylaxis Mass outbreak of scabies in children

© 2017 Japanese Dermatological Association 1009

Table 7. Position of scabies treatment in various countries

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

© 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 1011

1012 © 2017 Japanese Dermatological Association

© 2017 Japanese Dermatological Association 1013

1014 © 2017 Japanese Dermatological Association

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