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Skin
Therapy
Letter
Management of Scabies
Articles
Gentiane Monsel, MD1 and Olivier Chosidow, MD, PhD2
Volum e 17 - 1Department of Dermatology, Saint Louis Hospital, Paris, France
2012 Article s
2Universit
Paris-Est Crteil Val de Marne and Assistance Publique-Hpitaux de Paris,
Volum e 16 -
2011 Article s
Department of Dermatology, Henri Mondor Hospital, Crteil, France
Volum e 15 -
2010 Article s
Volum e 14 -
AB S T RAC T
2009 Article s
Scabies is a common contagious parasitic dermatosis. Transmission of the mite Sarcoptes scabiei var
Volum e 13 -
hominis generally occurs by skin-to-skin contact, but with crusted scabies it may also occur through
2008 Article s
fomites, such as infected clothing or bedding. Diagnosis is usually clinical. A 2010 updated Cochrane
Volum e 12 -
review concluded that management of scabies is based on topical scabicides, mainly 5% permethrin.
2007 Article s
However, oral ivermectin, although not licensed in many countries, may be useful, particularly for
Volum e 11 -
patients who cannot tolerate or comply with topical therapy and in institutional scabies epidemics.
2006 Article s
Patients should also receive detailed information about the infestation to limit further spreading.
Volum e 10 -
Cases resulting from close physical or sexual contact, even without symptoms, should be
2005 Article s
systematically treated. Hygienic measures should be taken after treatment is completed. Patients
Volum e 9 -
should be followed to confirm cure, including resolution of itching, which may take up to 4 weeks or
2004 Article s
longer.
Volum e 8 -
2003 Article s
Key Words: benzyl benzoate, ivermectin, permethrin, scabicides, scabies
Volum e 7 -
2002 Article s
Volum e 6 - Scabies is a common parasitic infection caused by the mite Sarcoptes scabiei var hominis, arthropod of the
2001 Article s order Acarina. The worldwide prevalence has been estimated at about 300 million cases annually, although
Volum e 5 -
this may be an overestimate.1 In general, transmission occurs by direct skin-to-skin contact. In crusted
2000 Article s
scabies, transmission may also occur through infected clothing or bedding. Skin eruption with classical scabies
Volum e 4 -
is attributable to both the infestation and a hypersensitivity reaction to the mite. Moreover, because the
1999 Article s
eruption is usually itchy, prurigo and superinfection are common.
Volum e 3 -
1998 Article s
The main symptom is pruritus that typically worsens at night, and it is often associated with itching
Volum e 2 -
experienced by other family members in the household or amongst people in close physical contact with an
1996-97
infested individual. The lesions are commonly located in the finger webs, on the flexor surfaces of the wrists,
Article s
on the elbows, in the axillae, and on the buttocks and genitalia. The elementary lesions are papules, burrows,
STL Family and nodules. In crusted scabies, clinical signs include hyperkeratotic plaques, papules and nodules,
Practice particularly on the palms of the hands and the soles of the feet, although areas such as the axillae, buttocks,
Edition
scalp, and genitalia in men, and breasts in women may also be affected.1
Volum e 7 -
2011 Article s The definitive diagnosis relies on the identification of mites. Multiple superficial skin samples should be
Volum e 6 - obtained from characteristic lesions by scraping with a scalpel. The specimens are examined under a
2010 Article s microscope, looking for mites, eggs, empty eggs, and scybala. Failure to find a mite is common and does not
Volum e 5 - rule out scabies.1 New methods such as dermoscopy or adhesive tape test may increase the sensitivity of
2009 Article s
skin scraping tests and limit false-negative results.2,3 However, comparing the accuracy of different tests for
Volum e 4 -
2008 Article s
diagnosing scabies remains elusive without a criterion standard.4
Volum e 3 -
2007 Article s
Scabies may be endemic in indigenous communities with a high rate of superinfection, which implies the need
Volum e 2 -
for specific management. Here, we describe the management of scabies in Western countries.
2006 Article s
US Volum e Indication for Therapy
1 - 2006
Article s
People with scabies and their close physical contacts, even without symptoms, should receive treatment at
Volum e 1 -
the same time. Prescriptions must be provided for all household members and sexual partners.
2005 Article s

Medical Patient Education

Treatments
Patients should receive detailed verbal and written information about scabies infestation.5 Infested
Acne individuals should be advised to avoid close physical contact until they and their sexual partners have
Tre atm e nt completed treatment.
C old Sore s
Tre atm e nt Treatment Options
Ecze m a
Topical and oral products are available, although rigorous studies to guide their use are lacking. Whether oral
Tre atm e nt
or topical treatment is more advantageous for improved efficacy, tolerance or convenience remains
Fungal
unknown.6-9 Table 1 summarizes the doses and side effects of common agents used in scabies management.
Tre atm e nt
Topical treatment includes permethrin, lindane, benzyl benzoate, esdpalltrine (bioallethrin), crotamiton, and
Psoriasis
precipitated sulfur. Topical scabicides have neurotoxic effects on mites and larvae. Despite the varied
Tre atm e nt
methodological quality of trials, a recent meta-analysis suggested that topical permethrin is the most
Psoriatic
Arthritis effective.6 Oral ivermectin interrupts the gamma-aminobutyric acid-induced neurotransmission of many
Tre atm e nt parasites (including mites). However, oral ivermectin is not licensed in most countries. It must be given at 200
R osace a g/kg as a single dose in patients >2 years of age and >15 kg. A second dose is necessary 2 weeks later due
Tre atm e nt to the lack of ovicidal action of the drug.1,10 Because ingestion of food increases the bioavailability of
Sk in C ance r ivermectin by a factor of 2,11 taking it with food might enhance the penetration of the drug into the epidermis.
Tre atm e nt Finally, topical permethrin is reasonable as first-line therapy. If permethrin is not available (e.g., in France),
Sk in C are benzyl benzoate may be used. Oral ivermectin is a good but more expensive alternative; however, this agent
Tre atm e nts may be preferred for patients who cannot tolerate topical therapy or are unlikely to adhere to such a
Bacte rial
therapeutic regimen.1,10 In classical scabies, the combination of topical therapy and oral ivermectin has never
Infe ction
been compared with either treatment alone. Table 2 presents strategies of treatment according to the clinical
Tre atm e nt
picture.
Lice
Tre atm e nt
Treatment
He rpe s Treatment Dosage Contraindication Advantages Disadvantages Comments
Regimen
Tre atm e nt
Lupus Permethrin 5% cream Rinsed off Effective, well Itching and Second
after 8-12 tolerated, stinging on application
Tre atm e nt
hrs safe application often
W art routinely
Tre atm e nt prescribed 1
week after
Doctor's the first
Toolbox application
A-De tails
Lindane 1% lotion Rinsed off Pregnant Effective, Cramps, Withdrawn
De rm atology or cream after 6 hrs women, infants, inexpensive dizziness, in the
R e vie w seizure seizures in European
Me e tings disorders children Union
because of
and
neurotoxicity
Proce e dings concerns
C ME / C HE
Benzyl 25% Rinsed off Pregnant Effective, Can cause Not currently
Derm News benzoate ointment after 24 women and inexpensive severe skin available in
Archives hrs (once infants (limit irritation Canada,
or several duration of use approved in
De rm atology times) to 12 hrs) Europe
Ne ws 2007
De rm atology Esdpalltrine 0.6% Rinsed off People with
(bioallethrin) aerosol after 12 asthma
Ne ws 2006
hrs

Crotamiton 10% Rinsed off Well Questionable Not

ointment after 24 tolerated, efficacy available in
hrs and safe for Canada,
then infants often used
reapplied on scabies
for an nodules in
additional children
24 hrs

Precipitated 2%-10% Rinsed off Safe for Questionable

sulfur precipitate after 24 infants, efficacy, skin
in hrs and pregnant and irritation
 petroleum then breastfeeding
base reapplied women
every 24
hrs for the
next 2
days (with
a bath
taken
between
each
application

Ivermectin Pills 200 g/kg Children <15 Good patient Expensive Not
repeated kg; pregnant or compliance approved in
on day 14 breastfeeding many
women countries

Table 1. Drugs commonly used to treat scabies

Additional Measures

Scabies is considered to be a sexually transmitted disease, therefore, patients should undergo routine
examination for sexually transmitted infection.12

Patients must receive detailed information about scabies infestation and therapeutic options, including the
amount of drug to be used and proper administration. Topical treatment must be applied to the entire skin
surface, including the scalp, all folds, groin, navel, and external genitalia, as well as the skin under the nails.
In adults with classical scabies, treating the face is controversial, but in babies, the face must be treated,
because transmission may occur by breastfeeding. Hands should not be washed during therapy, otherwise
the treatment should be reapplied. If the treatment is applied by someone without scabies, this person
should wear medical gloves during administration.

After the completion of treatment, patients should use fresh, clean bedding and clothing. If possible,
potentially contaminated clothes and bedding should be washed at high temperature (>50C) or kept in a
plastic bag for up to 72 hours, because mites that are separated from the human host will die within this time
period. The use of insecticidal powder or aerosol products should be reserved for materials or objects that

cannot be washed.13

With classical scabies, the time course for the eradication of parasites after treatment is not known, but there
is some concern that patients receiving oral ivermectin may remain contagious longer than those receiving
topical therapies.1,10

Special Treatment Considerations (Table 2)

Impetigo

Scabies complicated by impetigo requires combined antiseptic and antibiotic therapy against Streptococcus
pyogenes and Staphylococcus aureus. Oral ivermectin is preferred if skin is damaged.

Crusted Scabies

Management of crusted scabies generally necessitates admission to the hospital and isolation of the patient
because of the risk of transmission to people in physical contact. Active epidemiological measures to ensure
treatment of all individuals in contact are necessary. Hyperkeratosis is treated with a keratolytic agent. The
nails are cut short and brushed with a scabicidal agent.13 The combination of topical and oral therapy is
advised,14 although evidence is lacking regarding efficacy. Topical treatment may be repeated. Dosing and
frequency of administration is based on the severity of infection. The required number of doses of ivermectin
remains uncertain, but depending on infection severity, 3 to 7 doses have been proposed.10 A test of cure
may be performed for crusted scabies.

Pregnancy or Breastfeeding

Permethrin, benzyl benzoate, and sulphur appear to be safe, although evidence is limited.15 Oral ivermectin is
contraindicated.

Children

Permethrin may be used in infants. Benzyl benzoate and esdpalltrine are safe in children <2 years of age,
but duration of use should be limited to 12 hours. Ivermectin is not approved for children <15 kg.

Institutional Outbreaks
Institutional Outbreaks

Management of institutional outbreaks has never been evaluated. The control of institutional outbreaks relies
on prompt recognition of the index case, formation of an outbreak management team, determining the extent
of the outbreak and risk factors for transmission, immediate implementation of infection control practices,
adequate education of all involved individuals, simultaneous treatment of cases and all exposed people, and
concomitant environmental disinfection.16

Recommended Additional
Clinical Conditions Alternative Therapy Comments
Therapy Measures

Classical scabies Two applications of Two doses of oral People in close

permethrin 5% or ivermectin, 200 physical contact,
benzyl benzoate g/kg (at days 1 even without
and 14) symptoms, should
receive treatment
at the same time

Crusted scabies Several Keratolytic agents Control the spread

applications of must be used of scabies infection
permethrin or
benzyl benzoate
with repeated
doses of oral
ivermectin

Children <2 years Permethrin or Ivermectin is Treat the face, Treat scabies
of age benzyl benzoate contraindicated in except mouth and nodules with
(limit duration of children <15 kg eyes crotamiton
use to 12 hrs)

Pregnancy Permethrin, benzyl Ivermectin is

benzoate (limit contraindicated
duration of use to
12 hrs), and sulfur

Superinfected Oral ivermectin is Antibiotherapy Risk of post-

scabies preferred if skin is (antibiotics) before streptococcal
affected topical treatment glomerulonephritis
and systemic
sepsis

Institutional Treat clinical cases Simultaneously Formation of an

outbreaks as for classical and treat all cases and outbreak
crusted scabies all exposed people management team

Table 2. Treatment of scabies by clinical features or situation

Follow-up

Patients should understand that after treatment is completed, itching may persist for several weeks,
especially in atopic individuals. If itching continues after 4 weeks, the cause should be reinvestigated (Table
3). Symptomatic relief may be achieved with an emollient. A test of cure is not usually required with classical
scabies.

Condition Potential Causes Management

Overtreatment Intensive use of emollient

Cutaneous irritation Eczematization Intensive use of emollient

Contact dermatitis Topical steroid

Poor compliance: inappropriate or

Further scabicide application
insufficient treatment
Treatment failure
Resistance to scabicide Change scabicide

Reinfestation or relapse Further scabicide application

Delusions of parasitosis Psychiatric referral

Psychogenic pruritus
Nonparasitic dermatosis Treat the underlying cause

Table 3. Causes of persistent itching after scabicide therapy and suggested management (table adapted
from reference 13)
Conclusion

Scabies is a frequent, contagious dermatosis. Its management is sometimes complex and updated treatment
guidelines are useful.12,17 Patients and people in close physical contact with infested individuals should
receive detailed information from healthcare providers, because treatment failure is often attributable to poor
compliance or incorrectly carrying out instructions of prescribed therapy. Decision-making for topical or oral
treatment may vary by situation. Randomized controlled trials comparing topical treatment to oral ivermectin
demonstrating a high level of evidence are needed.

References

1. Chosidow O. Clinical practice. Scabies. N Engl J Med. 2006 Apr 20;354(16): 1718-27.
2. Dupuy A, Dehen L, Bourrat E, et al. Accuracy of standard dermoscopy for diagnosing scabies. J Am Acad
Dermatol. 2007 Jan;56(1):53-62.
3. Walter B, Heukelbach J, Fengler G, et al. Comparison of dermoscopy, skin scraping, and the adhesive
tape test for the diagnosis of scabies in a resourcepoor setting. Arch Dermatol. 2011 Apr;147(4):468-
73.
4. Albrecht J, Bigby M. Testing a test: critical appraisal of tests for diagnosing scabies. Arch Dermatol.
2011 Apr;147(4):494-7.
5. Scabies fact sheet. Atlanta: Centers for Disease Control and Prevention, 2005. Available at:
http://www.cdc.gov/ncidod/dpd/parasites/scabies/factsht_scabies.htm. Accessed: December 15, 2011.
6. Strong M, Johnstone P. Interventions for treating scabies. Cochrane Database Syst Rev.
2007(3):CD000320.
7. Hu S, Bigby M. Treating scabies: results from an updated Cochrane review. Arch Dermatol. 2008
Dec;144 (12):1638-40.
8. Le Cleach L, Chosidow O. Commentary on "Interventions for treating scabies". Evidence-Based Child
Health: A Cochrane Review Journal. 2011 Nov;6(6): 1865-6.
9. Steer AC, Kearns T, Andrews RM, et al. Ivermectin worthy of further investigation. Bull World Health
Organ. 2009 Oct;87(10):A; author reply B.
10. Currie BJ, Mc Carthy JS. Clinical therapeutics. Permethrin and ivermectin for scabies. N Engl J Med. 2010
Feb 25;362(8):717-25.
11. Guzzo CA, Furtec CI, Porras AG, et al. Safety, tolerability, and pharmacokinetics of escalating high
doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002 Oct;42(10):1122-33.
12. Scott GR, Chosidow O. European guidelines for the management of scabies, 2010. Int J STD AIDS.
2011 Jun;22(6):301-3.
13. Chosidow O. Scabies and pediculosis. Lancet. 2000 Mar 4;355(9206):819-26.
14. Alberici F, Pagani L, Rattu G, et al. Ivermectin alone or in combination with benzyl benzoate in the
treatment of human immunodeficiency virus associated scabies. Br J Dermatol. 2000 May;142(5):969-
72.
15. Mytton OT, McGready, Lee SJ, et al. Safety of benzyl benzoate lotion and permethrin in pregnancy: a
retrospective matched cohort study. Br J Obstet Gynecol. 2007 May;114(5):582-7.
16. Bouvresse S, Chosidow O. Scabies in healthcare settings. Curr Opin Infect Dis. 2010 Apr;23(2):111-8.
17. Workowski KA, Berman S. Centers for Disease Control and Prevention (CDC). Sexually transmitted
diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec;17;59(RR-12):1-110.

In this issue:

1. Management of Scabies
2. Silk Fabrics in the Management of Atopic Dermatitis
3. Update on Drugs and Drug News - March 2012

CUSTOM DERMATOLOGY SEARCH:Loading

All content 2005-2012 SkinThearpyLetter | Last modified: Thursday, 21-Jun-2012 16:53:55 MDT
doi: 10.1111/j.1346-8138.2011.01481.x Journal of Dermatology 2012; 39: 545547

ORIGINAL ARTICLE
Treatment of scabies: Comparison of permethrin 5%
versus ivermectin
Mohamad GOLDUST,1 Elham REZAEE,2 Sevil HEMAYAT3
1
Tabriz University of Medical Sciences, Tabriz, 2Medicinal Chemistry, Shahid Beheshti University of Medical Sciences, and 3Tehran
Azad Medical University of Medical Sciences, Tehran, Iran

ABSTRACT
Scabies is an ectoparasitic, highly contagious skin disease caused by a mite called Sarcoptes scabiei. The insecticides
ivermectin and permethrin are commonly used for treatment of scabies. This study aimed at comparing the efficacy of
oral ivermectin with topical permethrin in treating scabies. Two hundred and forty-two patients with scabies attending
the dermatology outpatient department of Sina Hospital, Tabriz University of Medical Sciences were admitted. Patients
were divided into two groups randomly. The first group and their family contacts received 5% permethrin cream and the
other received oral ivermectin. Treatment was evaluated at intervals of 2 and 4 weeks. A single dose of ivermectin
provided a cure rate of 85.9% at a 2-week interval, which increased to 100% after crossing over to the permethrin group
at a 4-week interval. Twice application of permethrin with a 1-week interval was effective in 92.5% of patients, which
increased to 94.2% after crossing over to the ivermectin group at a 4-week interval. Permethrin-treated patients
recovered earlier. Twice application of permethrin with a 1-week interval is superior to a single dose of ivermectin. The
temporal dissociation in clinical response suggests that ivermectin may not be effective against all the stages in the life
cycle of the parasite.

Key words: contagious, oral ivermectin, permethrin 5%, scabies, skin disease.

INTRODUCTION
Scabies is a common ectoparasitic infection caused by a mite,
Sarcoptes scabiei var. hominis. It causes substantial morbidity
from secondary infections and post-infective complications such
as acute post-streptococcal glomerulonephritis.1 Lesions consist
of tiny gray specks, burrows, or both. Non-specific lesions con-
sist of papules and itchy excoriations and crusts. The lesions are
usually found in interdigital folds of the hands, the flexor aspects
of the forearms, axillary folds, nipple areola and the periumbilical
area.2 Disease control requires treatment of the affected individ-
ual and all people they have been in contact with, but is often
hampered by inappropriate or delayed diagnosis, poor treatment
compliance, and improper use of topical compounds such as
benzyl benzoate.3 In addition to concerns over the toxicity of
such compounds, parasite resistance seems to be increasing.
Treatment of scabies in poor countries needs to integrate drug
treatment programs with efforts to improve the socioeconomic
conditions and education programs to reduce stigma.4 Treatment
options that were formerly available included sulfur, crotamiton
lotion and 25% benzyl benzoate. Sulfur in 510% petrolatum is
relatively cheap, but must be applied on three successive nights
to be effective. It is considered the safest treatment for pregnant
women and very young children.5 For many years, lindane was
the preferred therapy until concern was voiced about its efficacy
and safety. Permethrin, malathion have become treatments of
choice.6 Currently, 5% topical permethrin cream is considered by
many as the drug of choice in the treatment of scabies.7 Per-
methrin is a synthetic pyrethroid and was one of the first thermo-
stable and photostable insecticides developed following the
elucidation of the chemical structures of natural pyrethrins in
1947.8 Permethrin demonstrates extremely low mammalian toxic-
ity, combined with insecticidal activity even higher than natural
pyrethrins. These properties, backed by extensive experience of
safety over 20 years in the veterinary and agricultural industry,
made this compound an ideal candidate for use as a treatment
for scabies.9 Ivermectin is a novel antiparasitic agent effective
against a variety of endoparasites and ectoparasites. With a sin-
gle oral dose, ivermectin is effective against intestinal nematodes
and appears to be a promising treatment for head lice infesta-
tions, which are common co-infections in developing countries.10
It is not yet approved by the US Food and Drug Administration
for the treatment of human scabies.11 Initial reports have high-
lighted the utility of oral ivermectin in the treatment of scabies.
Hence, it was considered worthwhile to generate more data
regarding the human use of ivermectin in the treatment of

Correspondence: Mohamad Goldust, Student Research Committee, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran. Email: drmgol
dust@yahoo.com
Conflict of interest: none.
Received 18 May 2011; accepted 1 December 2011.

 2012 Japanese Dermatological Association 545

M. Goldust and E. Rezaee

scabies, comparing the result with the currently available first- using SPSS ver. 16. To account for statistical differences in the two
line treatment of scabies, permethrin.12 In the present study, we groups, a v2-test or Fishers exact test was used, as appropriate.
compared the efficacy and safety of oral ivermectin with topical Students t-test was used for numerical data. P < 0.05 was
permethrin in the treatment of scabies. considered significant.

METHODS RESULTS
In this clinical trial study, 242 patients aged 284 years (mean A total of 272 patients were studied. Thirty-four patients (18 from
42 14 36) with a diagnosis of scabies participated from April group A and 12 from group B) were not able to return after the
2008 to April 2011. All of the patients younger than 2 years of age, first follow-up examination and were therefore excluded from the
pregnant and lactating women, patients with past history of sei- study. The remaining 242 patients consisted of 132 males (54.5%)
zures, sever systemic disorders, immunosuppression and crusted and 110 females (45.5%). Their ages ranged 378 years (mean age,
scabies (Norwegian) were excluded. Informed consents were 36.24 12.6). Of these 242 patients, 121 were treated with per-
obtained from patients. Patients had not received any topical or methrin 5% and the others with ivermectin. The demography of the
systemic acaricide therapy for 1 month prior to the study. The two treatment groups showed no significant difference (Table 1). On
permethrin dermal cream and oral ivermectin were packaged in entry into the study, the number of patients in each treatment group
identical-appearing boxes, the contents of which were unknown to who were graded as having mild, moderate or severe infestations
the evaluation team. This blinding was maintained throughout the was not significantly different (Table 2). At 2 weeks post-treatment,
study. Similarly, the treatment team members who applied medica- treatment was effective in 112 (92.5%) patients in the permethrin
tions took no part in pretreatment scoring of the severity and extent 5% group and 104 patients (85.9%) in the ivermectin group (Table 3).
of the infestations and played no role in subsequent evaluations. This difference was not significant (P = 0.42). The 26 patients (18
Prior to entry into the study, patients were given a physical examina- male and eight female) who had not improved were crossed over to
tion, and their history of infestations, antibiotic therapy and other the other group. On the next follow up, at 4 weeks post-treatment,
pertinent information was recorded. Age, sex, height and weight seven patients in the permethrin 5% group who showed no
were recorded for demographic comparison. The diagnosis of sca- response at the first follow up and were subsequently treated with
bies was made by the demonstration of eggs, larvae, mites or fecal
material by light microscopy or by the presence of the following
three criteria: demonstration of a burrow and or typical scabietic Table 1. Demographic characteristics of the study population
lesions at the classical sites; nocturnal pruritus; and history of similar Permethrin 5% Ivermectin
symptoms in their families and or close contacts. Patients who (n = 121) (n = 121) P
satisfied the above criteria were divided into two groups randomly.
Age 35.74 17.32 37.12 13.14 0.48
The first group and their family contacts received 5% permethrin Sex
cream (group A) and the other received oral ivermectin (group B). Male 72 60 0.36
The treatment with permethrin 5% consisted of two applications of Female 46 64 0.32
the product with a 1-week interval. Patients were advised to apply Height (cm) 172 32 178 14 0.38
the cream from head to toe on each occasion and to take a shower Weight (kg) 68 36 72 58 0.52
12 h later. Oral ivermectin was given to group B in a single dose of
200 lg kg bodyweight. Clinical evaluations after treatment were
made by experienced investigators without knowledge of the treat-
ments. At all evaluation times, they recorded the sites of lesions on Table 2. Severity of infestation pretreatment of all patients
body diagram sheets. The notations of their appearance and Permethrin 5% Ivermectin
whether or not they were new or residuals of original lesions were Lesions (n = 121) (n = 121) P
determined by comparison with the pretreatment photograph. New
Mild (<50) 21 24 0.62
lesions were also scraped for microscopic examination. Severity of Moderate (50100) 34 27 0.48
infestation pretreatment of all patients was considered as: (i) mild Severe (>100) 66 70 0.64
(<50); (ii) moderate (50100); and (iii) severe (>100). Patients were
treated with the scabicides and then followed up at intervals of 2
and 4 weeks. Cure was defined as the absence of new lesions and
all old lesions healed. Treatment failure was defined as a patient Table 3. Response to treatment after 2 weeks
with microscopically-confirmed new lesions at 1 month and who Group A Group B
was not considered cured at 2 weeks. The term re-infestation was (n = 121) (n = 121) P
applied to the patients who were completely clear at 2 weeks and
Effectively 112 (92.5) 104 (85.9) 0.42
developed new lesions with positive microscopic findings at treated
1 month. In case of treatment failure, the patient was crossed over patients
to the other group. At the end of the fourth week, another evaluation at week 2
was performed. The results of the study were statistically analyzed

546  2012 Japanese Dermatological Association


ivermectin still had severe itching. In contrast, all 17 patients not
responding to ivermectin who were then treated with permethrin
showed improvement in itching and skin lesions. Only nine patients
(six in the permethrin group and three in the ivermectin group) expe-
rienced irritation after application of the drug, but none had allergic
reactions.
DISCUSSION
For the past 50 years, lindane has been the preferred therapy for
scabies. This product has become the most widely used antiscabi-
etic drug in many countries, including Iran.12,13 During recent years,
resistance to lindane seems to be rising and there are reports of
several clusters of patients with lindane-resistant scabies world-
wide.3 Permethrin cream (5%) was introduced in 1989 for the treat-
ment of scabies and seems to be a good substitute for lindane. It is
considered to be the drug of choice in many countries.14 The 5%
permethrin preparation kills the organisms and eggs, and has an
extremely low rate of absorption, making the toxicity potential non-
existent.15 Resistance to permethrin in developed countries was
reported in 1999.16 Ivermectin is a novel antiparasitic agent effective
against a variety of endoparasites and ectoparasites.17 In this study,
two applications of permethrin with a 1-week interval was as
effective as a single oral dose of ivermectin by 2 weeks (P = 42).
This study also concurs with the excellent cure rates (90100%)
observed in the initial studies with permethrin.18 The lack of efficacy
of a single dose of ivermectin in some patients may be due to the
lack of ovicidal action of ivermectin.19 Ivermectin, because of its
specific site of action, may not be effective against the younger
stages of the parasite inside the egg because the nervous system
has not yet developed.20 The concentration achieved in the skin
may also be variable because ivermectin is orally administrated.
These factors could also explain the temporal delay in complete
recovery observed in the ivermectin group. Because ivermectin has
not been proven to be ovicidal, a single dose of 200 lg kg body-
weight may be inadequate to eradicate the different stages of the
parasite, and a higher dose or a second dose may be required
within 12 weeks for higher cure rate.21 In the study carried out by
Usha et al.,22 a higher number of patients showed clearance of
lesions as compared to our results. This could be explained due to
the longer follow up. In the study carried out by Khan et al.,23 a
100% cure was seen in both treatment groups, possibly because
the study was carried out on a smaller number of patients with fol-
low up of 2 weeks, and because ages were 12 years or above when
the activity of sebaceous glands is higher. Regarding side-effects,
permethrin was found to be significantly safer than ivermectin
(P = 0.05). Although ivermectin was as effective as permethrin, it
has few outweighing advantages over topical permethrin. It is cost-
effective and can be given to masses with better compliance with or
without supervision. It can also be given safely to patients of scabies
with secondary eczematization, erosions or ulcers where topical
 2012 Japanese Dermatological Association
Permethrin versus ivermectin in scabies
therapies such as permethrin, lindane and benzyl benzoate can
cause serious cutaneous and systemic side-effects in addition to
the problem of compliance.
REFERENCES
1 Dieng MT, Ndiaye B, Ndiaye AM. Scabies complicated by acute glomeru-
lonephritis in children: 114 cases observed in two years in a pediatric ser-
vice in Dakar. Dakar Med 1998; 43: 201204.
2 Feldmeier H, Jackson A, Ariza L et al. The epidemiology of scabies in an
impoverished community in rural Brazil: presence and severity of disease
are associated with poor living conditions and illiteracy. J Am Acad Der-
matol 2009; 60: 436443.
3 Heukelbach J, Feldmeier H. Scabies. Lancet 2006; 367: 17671774.
4 Scott GR, Chosidow O. European guideline for the management of sca-
bies, 2010. Int J STD AIDS 2011; 22: 301303.
5 Diaz M, Cazorla D, Acosta M. Topical treatment with precipitated sulphur
petrolatum for school aged children scabiesfrom Coro, Falcon state,
Venezuela. Parasitol Latinoam 2006; 61: 7481.
6 Gould D. Prevention, control and treatment of scabies. Nurs Stand 2010;
25: 4246.
7 Chosidow O. Clinical practices. Scabies. N Engl J Med 2006; 354: 1718
1727.
8 Scheinfeld N. Controlling scabies in institutional settings: a review of medi-
cations, treatment models, and implementation. Am J Clin Dermatol
2004; 5: 3137.
9 Albakri L, Goldman RD. Permethrin for scabies in children. Can Fam
Physician 2010; 56: 10051006.
10 Diagnosis and treatment of scabies in 2002: rapid diagnosis and proper
management limit the risk of spread. Prescrire Int 2002; 11: 152155.
11 Burkhart CG, Burkhart CN. Optimal treatment for scabies remains
undetermined. J Am Acad Dermatol 2001; 45: 637638.
12 Paasch U, Haustein UF. Treatment of endemic scabies with allethrin,
permethrin and ivermectin. Evaluation of a treatment strategy. Hautarzt
2001; 52: 3137.
13 Pasay C, Arlian L, Morgan M et al. The effect of insecticide synergists on
the response of scabies mites to pyrethroid acaricides. PLoS Negl Trop
Dis 2009; 3: e354.
14 Buffet M, Dupin N. Current treatments for scabies. Fundam Clin Pharma-
col 2003; 17: 217225.
15 Rebora A. The management of rosacea. Am J Clin Dermatol 2002; 3:
489496.
16 Bigby M. A systematic review of the treatment of scabies. Arch Dermatol
2000; 136: 387389.
17 Burkhart CG, Burkhart CN. Oral ivermectin for Phthirus pubis. J Am Acad
Dermatol 2004; 51: 10371038.
18 Bell TA. Treatment of Pediculus humanus var. capitis infestation in Cowlitz
County, Washington, with ivermectin and the LiceMeister comb. Pediatr
Infect Dis J 1998; 17: 923924.
19 Elmogy M, Fayed H, Marzok H et al. Oral ivermectin in the treatment of
scabies. Int J Dermatol 1999; 38: 926928.
20 Behera SK, Dimri U, Singh SK et al. The curative and antioxidative efficiency
of ivermectin and ivermectin + vitamin E-selenium treatment on canine
Sarcoptes scabiei infestation. Vet Res Commun 2011; 35: 237244.
21 Mapar MA, Mali B. The comparison of oral ivermectin and topical lindane
in the treatment of scabies. Iranian J Dermatol 2008; 11: 147150.
22 Usha V, Gopalakrishnan Nair TV. A comparative study of oral ivermectin
and topical permethrin cream in the treatment of scabies. J Am Acad
Dermatol 2000; 42: 236240.
23 Khan I, Yasmin R. Ivermectin in the treatment of scabies. JPAD 2007; 17:
7883.
547
 The n e w e ng l a n d j o u r na l of m e dic i n e

clinical therapeutics

Permethrin and Ivermectin for Scabies

Bart J. Currie, F.R.A.C.P., and James S. McCarthy, F.R.A.C.P.

This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion
of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies,
the clinical use of this therapy, and potential adverse effects are reviewed. Relevant formal guidelines,
if they exist, are presented. The article ends with the authors clinical recommendations.

In a remote aboriginal community in tropical northern Australia, a mother comes to

the health center with her 4-year-old son, who has multiple sores on the skin of his
arms and legs. He is treated with a single dose of intramuscular penicillin G benza-
thine and with the application of topical 5% permethrin cream over his whole body.
A week later, the pyoderma has substantially resolved, but the boy continues to scratch
his hands and feet. The clinic nurse visits the family house and finds that skin sores
are present on both infants who live in the household, three of the six young children,
and one of the three adolescents. Some also have scratches and small interdigital
excoriations, which are consistent with scabies. An infirm elderly aunt living in the
house is found to have widespread areas of extensively crusted and scaly skin, which
are especially prominent on her hands, elbows, armpits, knees, and buttocks. All the
household members are given topical permethrin, and the aunt is referred to the hos-
pital for oral ivermectin therapy.

The Cl inic a l Probl em

Scabies is an ectoparasitic infection caused in humans by the scabies mite Sarcoptes From the Menzies School of Health Re-
scabiei variety hominis. Infection occurs as a result of direct skin-to-skin contact; fomite search and Northern Territory Clinical
School, Royal Darwin Hospital, Darwin,
transmission from mites attached to clothing, bedding, and towels is uncommon.1 NT (B.J.C.); and the Queensland Institute
Scabies occurs worldwide, although estimates of 300 million cases yearly are of Medical Research and University of
possibly exaggerated.2 The infection is endemic in many impoverished communi- Queensland, Herston, QLD (J.S.M.)
both in Australia. Address reprint re-
ties, but prevalence rates vary widely; seasonal outbreaks and documented peaks quests to Dr. Currie at the Menzies
during times of war3 are probably related to crowding and population movements.4,5 School of Health Research, P.O. Box 41096,
In some industrialized countries, scabies is endemic in economically disadvan- Casuarina, NT 0811, Australia, or at bart@
menzies.edu.au.
taged populations, and outbreaks occur in nursing homes and hospitals.6-8
The classic manifestation of scabies is generalized itching that is more intense N Engl J Med 2010;362:717-25.
at night and that causes discomfort to the patient; however, complications and Copyright 2010 Massachusetts Medical Society.

death can also occur, usually as a result of secondary bacterial pyoderma, common
ly caused by Streptococcus pyogenes or Staphylococcus aureus. Such secondary infection
can lead to complications such as post-streptococcal glomerulonephritis and sys-
temic sepsis.5,9,10

PATHOPH YSIOL O GY A ND EFFEC T OF THER A PY

The life cycle of S. scabiei (Fig. 1) begins when adult mites burrow into the skin of the
human host and mate, and the females lay eggs. Larvae hatch from the eggs and
eventually develop into adult mites, thus completing the life cycle. The skin lesions
of scabies are due both to the burrows of the mites and to more widespread inflam-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Stratum Eggs Egg

Adult female
corneum 0.100.15 mm in length

23 days

Larva

Adult Female
0.300.45 mm in length
12 months

34 days

Nymph Stages
47 days

Adult Male
0.200.25 mm in length

Figure 1. Life Cycle of Sarcoptes scabiei.

COLOR FIGURE

Rev3 22/01/10
matory responses in the skin, caused by a hyper- are often localizedAuthor
to the axillae, groin, and gen-
Dr. Currie
sensitivity reaction to the mites and to their sa- italia, such as the scrotum.
Fig # 21

liva or excreta.2,4,11 In the vast majority of scabies Title

Crusted scabies, formerly called Norwegian
ME
infections, the number of female mites is thought scabies, occurs when mite replication is not con-
to be limited to 10 to 15, and burrows may be DE
trolled by the hosts immuneJarcho system and hyper-
Artist Muller
difficult to identify.4 In this classic presentation, infection develops (Fig. 2). This form of scabies
AUTHOR PLEASE NOTE:
lesions are most often present on the interdigital usually occurs in immunocompromised
Figure has been redrawn and type haspatients
been reset
Please check carefully
finger webs and flexor surfaces of the wrists. El- such as patients with human immunodeficiency
date 02-25-2010
bows, axillae, buttocks, and genitalia are quite virus infection or Issue
those who are receiving im-
frequently involved as well (Fig. 2), as are the munosuppressive therapy.6 Patients with crusted
breast areolae in women. Atypical presentations scabies are highly infectious, can be core trans-
such as involvement of the scalp can occur in mitters in communities and in institutional out-
infants and the elderly. Nodular scabies results breaks, have high rates of death from secondary
from an exaggerated hypersensitivity reaction and bacterial sepsis, and are difficult to treat.10
is characterized by chronic, pruritic nodules that A variety of agents, most of them topical, have

718 n engl j med 362;8 nejm.org february 25, 2010

The New England Journal of Medicine

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Copyright 2010 Massachusetts Medical Society. All rights reserved.
 Clinical Ther apeutics

A B

C D

Figure 2. Manifestations of Scabies.

Interdigital lesions are a typical manifestation of classic scabies (Panel A). A pattern of excoriated pustules in the ax-
AUTHOR
illa is characteristic of scabies with secondary
ICM Currie
bacterial RETAKE
infection (Panel B). Crusted1st
scabies can be manifested as ex-
F FIGURE
REG and 2nd
2a-d C). A case of severe crusted
coriated, lichenified skin on the wrists hands (Panel scabies can result in sloughing
CASE 3rd
of layers of thick, hyperkeratotic skin, with TITLE
fissures that can result in secondary bacterial infection and the potential
Revised
for bacteremia and systemic sepsis EMail Chosidow.2
Line from4-C
(Panel D). Panel A reprinted
Enon ARTIST: mst SIZE
H/T H/T
FILL Combo 33p9
AUTHOR, PLEASE NOTE:
Figure has been redrawn and type has been reset.
been used to treat scabies. These include 5 toPlease
10%check and 5% tea-tree oil
carefully. in combination with benzyl
sulfur in paraffin, an agent used widely in Africa benzoate.13,14
and South America4; 1% lindane, 36208 is no
JOB: which ISSUE: 2-25-10
Permethrin is a synthetic pyrethroid agent
longer used in many Western countries because that is applied as a topical 5% cream for the
of concerns regarding neurotoxicity2,4; 10 to 25% treatment of scabies. It disrupts the function of
benzyl benzoate, which is often used in Europe voltage-gated sodium channels of arthropods,
and Australia; malathion7; 10% crotamiton12; causing prolonged depolarization of nerve-cell

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 The n e w e ng l a n d j o u r na l
membranes and disrupting neurotransmission.15
The selective neurotoxic effect of permethrin on
invertebrates is due to structural differences in
voltage-gated sodium channels between verte-
brates and invertebrates.15 Permethrin 5% cream
was approved for treatment of scabies by the
Food and Drug Administration (FDA) in 1989.
Ivermectin is a semisynthetic macrocyclic
lactone antibiotic agent that is administered oral
ly. It disrupts the function of a class of ligand-
gated chloride ion channels, causing persistent
opening of the channels.16 This interaction is well
studied in nematodes, with both -aminobutyric
acid and glutamate-gated channels identified as
targets.16 However, the target of this drug in the
scabies mite has yet to be identified; only a pH-
gated chloride channel that is sensitive to ivermec
tin has been described.17 Although the selectivity
of ivermectin for invertebrates is incompletely
understood, it may be explained, in part, by the
theory that in vertebrates, drug pumps of the
P-glycoprotein family exclude the drug from its
potential site of action.16 Oral ivermectin has been
approved for the treatment of scabies in France
since 2001. It is not licensed for the treatment of
scabies in the United States, United Kingdom, or
Australia but has increasingly been used off-
label in those countries.
CL INIC A L E V IDENCE
There is a paucity of high-quality studies that
compare various therapies for scabies.12 An as-
sessment of the findings of published studies is
impeded by the relatively small size of the studies
and the lack of standardization of diagnosis and
follow-up.18 A Cochrane review concluded that
there are insufficient data available to compare
the relative efficacies of topical permethrin and
topical benzyl benzoate.12 However, that review
did show that permethrin was more effective than
both crotamiton and lindane (relative risk of
treatment failure with permethrin as compared
with crotamiton, 0.24 in two trials involving 194
subjects, and relative risk with permethrin as
compared with lindane, 0.32 in five trials involv-
ing 753 subjects).18
The Cochrane review also concluded that oral
ivermectin appeared to be more effective than
both lindane and topical benzyl benzoate (rela-
tive risk of treatment failure with ivermectin as
compared with lindane, 0.36 in two trials involv-
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Copyright 2010 Massachusetts Medical Society. All rights reserved.
of m e dic i n e
ing 193 subjects, and relative risk with ivermectin
as compared with benzyl benzoate, 0.50 in three
trials involving 192 subjects).12 However, a recent
study showed that there was a higher rate of
treatment failure with single-dose ivermectin
than with topical benzyl benzoate.19 This find-
ing may reflect the fact that ivermectin does not
sterilize scabies eggs. Therefore, a second dose
of ivermectin is usually administered at least
1 week after the first dose to kill the newly
hatched mites. Further support for this concept
comes from a trial that compared ivermectin
with topical permethrin in 85 patients.20 In that
trial, a single dose of ivermectin was less effec-
tive than topical permethrin (cure rate of 70% vs.
98%), but if a second dose of ivermectin was ad-
ministered to patients who did not have a response
after the first dose, the cure rate with ivermectin
rose to 95%.
There are no comparative studies of the safety
and efficacy of various therapies for scabies in
special groups such as infants, small children,
and the elderly or for cases of crusted scabies.
However, observational studies have shown that
ivermectin regimens are effective after the fail-
ure of topical therapy in patients with crusted
scabies.10,21,22
CL INIC A L USE
Our recommendations for the treatment of vari-
ous scabies syndromes are summarized in Table 1.
For the treatment of classical scabies, permethrin
5% cream is our preferred agent. To ensure a reli-
able cure, the cream should be applied to the
entire surface of the skin except around the eyes.
Although some guidelines suggest that topical
therapy need not be applied above the neck, we
believe that including this area is particularly im-
portant in small children and the elderly, in whom
the infection quite often involves the scalp. Par-
ticular attention should be paid to the areas that
are most often involved, including the areas be-
tween the fingers and toes, under the arms, and
under the fingernails and toenails; the wrists;
the external genitalia; and the buttocks.23 To max-
imize exposure of the mites to the drug, it is
generally recommended that the cream be applied
in the evening and left on overnight. To eradicate
any mites that were not exposed at the time of
the first treatment, it is generally recommended
that a second application be administered 1 to
 Table 1. Therapies for Scabies.
Purpose of Therapy
Treatment for classic scabies
Treatment for crusted scabies
Prevention of infection in
close contacts of patients
with scabies
Management of institutional
outbreak of scabies
Prevention in communities
where scabies is endemic
The New England Journal of Medicine
n engl j med 362;8 nejm.org february 25, 2010
or management of com-
munity outbreak
Copyright 2010 Massachusetts Medical Society. All rights reserved.
* Ivermectin is not approved for this indication by the Food and Drug Administration; there are insufficient data on the safety of ivermectin in pregnancy and in children younger than
5 years of age.
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721
Recommended Therapy
Two applications one on day 1 and one be-
tween day 8 and day 15 of topical per-
methrin 5%, applied in the evening and
left on overnight
Both topical permethrin 5% every 2 to 3 days
for 1 to 2 weeks and oral ivermectin (200 g/
kg/dose), taken with food, administered as
three doses (days 1, 2, and 8), five doses
(days 1, 2, 8, 9, and 15) or seven doses
(days 1, 2, 8, 9, 15, 22, and 29), depending
on severity of infection*
A single application of topical permethrin 5%
applied in the evening and left on overnight
Treat persons with clinic cases as recommended
above for classic and crusted scabies and
treat all potentially exposed residents, staff,
and visitors as recommended above for
contacts
Adopt multifaceted approach that includes edu-
cation and community involvement; treat
clinical cases as recommended above for
persons with classic and crusted scabies and
all family and household members as recom-
mended above for contacts; consider treating
all other community members as recom-
mended above for contacts
Alternative Therapy
Two doses of oral ivermectin (200 g/kg/dose),
taken with food one on day 1 and one
between day 8 and day 15*
Topical benzyl benzoate 25% (with or without
tea-tree oil 5%) instead of permethrin
Oral ivermectin (200 g/kg/dose), taken with
food, administered as a single dose*
For refractory outbreaks, consider treatment
of all residents with oral ivermectin*
Treat persons with classic and crusted scabies,
as well as contacts in the community, as
recommended above
Comments
Keratolytic creams should be used for skin
crusts; maintain vigilance for the develop-
ment of sepsis; apply appropriate measures
to control the spread of scabies infection
Look for core transmitter index cases with
crusted scabies; give attention to planning
and logistics of therapy; apply appropriate
measures to control the spread of scabies
Clinical Ther apeutics
infection
Look for core transmitter index cases with
crusted scabies; give attention to planning
and logistics of therapy; be aware that main-
taining control of scabies requires address-
ing underlying issues of overcrowding and
access to health hardware (e.g., functioning
taps with clean water, sinks, and toilets in
the house), health care, and education
 The n e w e ng l a n d j o u r na l
2 weeks after the first. However, the efficacy of
one application as compared with two applica-
tions has not been formally tested, and the opti-
mal interval between doses has not been precise-
ly defined.
Ivermectin, administered orally at a dose of
200 g per kilogram of body weight, is an effec-
tive alternative treatment. Since ingestion of food
increases the bioavailability of ivermectin by a
factor of two,24 taking the drug with food will
enhance the penetration of the drug into the
epidermis. Since ivermectin is not ovicidal, it is
recommended that two doses, separated by 1 to
2 weeks, be administered for the treatment of
classical scabies. The serum half-life of ivermec-
tin is 18 hours,24 with drug elimination occurring
through metabolism in the liver and excretion of
inactive metabolites through the kidneys. Adjust-
ment of the dose is not necessary in patients
with renal impairment. However, the safety of
administering multiple doses of ivermectin in
patients with severe liver disease has not been
studied.
In the case of crusted scabies, we recommend
more frequent administration of ivermectin, rang-
ing from three to seven doses, depending on the
severity of the infection (Table 1). Patients with
crusted scabies should be treated concomitantly
with a topical scabicide (e.g., permethrin, benzyl
benzoate, or benzyl benzoate with tea-tree oil),
as well as a keratolytic cream to facilitate the
breakdown of skin crusts and improve penetra-
tion of the topical agent.
In the first few days after therapy for scabies
is initiated, a transient exacerbation of pruritus
sometimes occurs as a result of sensitization of
the human host to mite antigens, with a conse-
quent immunologic reaction. Sensitization also
frequently results in delayed resolution of symp-
toms, leading to confusion on the part of clini-
cal staff, patients, and families, who may mis-
interpret the natural course of recovery as a
failure of treatment or as a sign of reinfection.
To avoid this confusion, patients can be provided
with information sheets that explain the treat-
ment, alert them to the fact that resolution of
pruritus may be delayed, and assure them that
repeated treatment is generally unnecessary. Top-
ical, intralesional, or systemic corticosteroid ther-
apy can be considered for persons with nodular
scabies who have persistent symptoms, provided
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of m e dic i n e
that administration of adequate scabicidal ther-
apy has been clearly documented.4,6
There may be a prolonged interval between the
onset of the primary infection, at which time the
patient becomes infectious to others, and the on-
set of clinical manifestations. During this period,
which can be as long as 10 weeks,1 the infection
may be transmitted from asymptomatic hosts to
the hosts contacts. Because of the substantial
probability that subclinical infection will occur
in close contacts of the host and will result in
further transmission of infection from those con-
tacts, all family members and other close physi-
cal contacts should also be treated. Bed linen
and clothing should be washed in hot water, but
no special processing such as autoclaving or
bleaching is required. Shoes and other nonwash-
able items should be placed in a tightly sealed
plastic bag for at least 3 days. Establishing cure
ideally requires follow-up clinical assessment for
at least 1 month. This allows time for lesions to
heal and for any eggs and mites to reach matu-
rity if treatment fails.
The successful control of outbreaks of scabies
in institutional settings such as nursing homes
requires attention to planning and logistics of
therapy.7 Important steps in the control of out-
breaks include coordinating the documentation
of case subjects and their contacts; isolating per-
sons with clinical scabies; educating residents,
families, visitors, and staff; providing therapy for
all residents, staff, and other potential contacts;
and disinfecting objects with which persons with
crusted scabies may have come into contact.7,25-27
Prolonged surveillance may be required to ensure
the eradication of nosocomial scabies.28 The
specific therapy used for scabies in institutional
outbreaks will vary according to availability, cost,
and current drug approvals, but at least for per-
sons with clinical cases, a second treatment dose,
administered 1 to 2 weeks after the first dose, is
recommended (Table 1). Successful models have
included the administration of topical therapy
such as permethrin or benzyl benzoate for all
case subjects and their contacts,26,29 the admin-
istration of oral ivermectin for all residents,30-32
and a combination of topical therapy and oral
ivermectin, with the latter considered to be im-
portant therapy for persons with crusted sca-
bies.8,25,27 In the United States, the average whole-
sale price of a 60-g tube of 5% permethrin cream
 Clinical Ther apeutics
is approximately $30.33 The cost of a 3-mg tablet
of ivermectin is approximately $6, which trans-
lates into a cost of about $30 for a single dose
for a patient weighing 70 kg.33 One study esti-
mated that between 2001 and 2005, the typical
cost of treating an episode of scabies, taking into
account second doses, treatment failures, and of-
fice visits, was approximately $95.34
A DV ER SE EfFEC T S
Permethrin is poorly absorbed through the skin,
and the small percentage that is absorbed is me-
tabolized rapidly, with elimination being virtu-
ally complete after 1 week.35 Owing to theoreti-
cal concerns regarding systemic absorption of
permethrin in infants, it has generally been rec-
ommended that infants be treated with crotami-
ton or a sulfur preparation instead of permethrin.
However, given the efficacy of permethrin,12 it
is increasingly being used in children who are
2 months of age or older.
The source of the most extensive data on the
adverse effects of ivermectin in nonpregnant
adults is the Onchocerciasis Control Program.
Through this program, more than 400 million
treatments have been distributed in Africa, with
some persons having received up to 20 annual
treatments.36 When ivermectin is used to treat
filarial parasites, adverse reactions occasionally
occur, including fever, myalgia, malaise, and pos-
tural hypotension.37 These adverse reactions are
probably related to the intensity of the filarial
infection and the release of parasite antigen.38
More severe complications, including lethargy,
confusion, and coma, were seen when ivermec-
tin was administered in patients in West Africa
who were heavily infected with Loa loa.37 These
complications have also been attributed to the
killing of the parasites rather than to a toxic ef-
fect of ivermectin. To date, the use of ivermectin
to treat scabies has not been conclusively associ-
ated with any serious adverse effects.24 However,
it is recommended that ivermectin not be admin-
istered in children who are younger than 5 years
of age or in those who weigh less than 15 kg
because of the lack of data on safety and theo-
retical concerns regarding potential neurotoxic-
ity (see below). It is also recommended that
ivermectin not be used during pregnancy. Never-
theless, reports that have documented the inad-
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Copyright 2010 Massachusetts Medical Society. All rights reserved.
vertent administration of the drug in pregnant
women have not shown an adverse outcome for
the fetus.39-41
A R E A S OF UNCER TA IN T Y
Drug resistance is an emerging concern with ac-
aricides. Potential mechanisms for resistance to
permethrin include sodium-channel mutations in
the organism that make it less susceptible to
treatment,42 removal of the drug by an enhanced
efflux pump such as P-glycoprotein, and enzy-
matic degradation of the drug.43 Potential mech-
anisms for resistance to ivermectin include chlo-
ride-channel mutations in the organism and
enhanced P-glycoprotein expression. In vitro stud-
ies have shown that susceptibility to permethrin
is progressively reduced with repeated adminis-
tration,13,43 although clinical resistance remains
to be documented. Clinical resistance to ivermec-
tin has been documented, with in vitro confir-
mation, in two persons with crusted scabies in
whom resistance developed after the administra-
tion of repeated regimens of multiple doses of
ivermectin.14
Central nervous system toxicity resulting in
death after treatment with ivermectin is well
recognized in various vertebrates.44 As noted
above, severe neurologic effects in humans in
Africa after the administration of ivermectin
have been attributed to inflammatory respons-
es to the filarial parasites that are the target of
treatment.38 Nevertheless, there is one report of
apparent excess mortality attributed to neuro-
toxicity when ivermectin was used in a nursing
home to control an epidemic of scabies.45 This
report has been subject to criticism on epidemio-
logic grounds.46-48 Nonetheless, the safety of
ivermectin at the extremes of age remains to be
conclusively established, although there are in-
creasing data suggesting that the use of ivermec-
tin in children is safe.49
GUIDEL INE S
The Centers for Disease Control and Prevention
(CDC) provides advice on scabies and informa-
tion on specific therapies for health care providers,
patients, and caregivers at www.cdc.gov/scabies/
hcp/index.html. This 2008 version of the CDC
guidelines has useful information on the general
723
 The n e w e ng l a n d j o u r na l of m e dic i n e

management of scabies, including crusted scabies,
and the management of institutional outbreaks.
Guidelines for the treatment of scabies are also
available in the 2006 CDC Treatment Guidelines
for Sexually Transmitted Diseases.50 These guide-
lines, which are currently being updated, include
advice on the off-label use of ivermectin. The
United Kingdom National Guideline on the Man-
agement of Scabies Infestation from the British
Association of Sexual Health and HIV was up-
dated in 2008 and also includes information on
the off-label use of ivermectin (www.bashh.org/
documents/27/27.pdf). We have developed a spe-
cific guideline for the use of ivermectin in per-
sons with crusted scabies that includes combin-
ing topical therapy with multiple doses of oral
ivermectin, according to severity; this guideline
is available at www.health.nt.gov.au/Centre_for_
Disease_Control/Publications/CDC_Protocols/
index.aspx.
R ec om mendat ions
The case of crusted scabies in the elderly aunt in
the vignette is unusual, and although she has
probably been a core transmitter in this situa-
tion, most physicians will not see cases of crust-
ed scabies in clinical practice. The aunt requires
strict isolation after admission to the hospital in
order to prevent transmission of scabies to the
staff, and we would treat her severe, crusted sca-
bies as noted in Table 1. While the aunt is in the
hospital, all family members and other commu-
nity contacts can be assessed and treated for sca-
bies, and the household linen, mattresses, and
clothing should be washed and aired. Topical 5%
permethrin can be administered in contacts who
weigh less than 15 kg and in pregnant women,
and topical 5% permethrin or oral ivermectin, at
a dose of 200 g per kilogram, administered with
food, can be given to all other contacts. Contacts
who have evident or suspected clinical scabies
should have a second treatment 7 to 14 days after
the first.
Supported by grants from the Australian National Health and
Medical Research Council (NHMRC), the Cooperative Research
Centre for Aboriginal Health, the Government of Queensland
Smart State Program, and a Practitioner Fellowship from the
NHMRC (to Dr. McCarthy).
No potential conflict of interest relevant to this article was
reported. Disclosure forms provided by the authors are available
with the full text of this article at NEJM.org.

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