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Treatment of Cutaneous Larva Migrans


Eric Caumes

From Service des Maladies Infectieuses et Tropicales,


Hopital Pitie-Salpetrie`re, Paris, France

Cutaneous larva migrans is the most frequent skin disease


among travelers returning from tropical countries [1]. It is now
easy to treat with new oral antihelmintic agents, which are both
well tolerated and effective.
Cutaneous larva migrans is caused by the larvae of animal
hookworms, of which Ancylostoma braziliense is the species
most frequently found in humans [2, 3]. These hookworms
generally live in the intestines of domestic pets such as dogs
and cats and shed their eggs via feces to soil (usually sandy
areas of beaches or under houses). Humans are infected in
tropical and subtropical areas of endemicity by contact with
contaminated soil. The hookworm larva burrows through intact skin but remains confined to the upper dermis, since humans are incidental hosts.
Larval migration through the skin is marked by an intensely
pruritic, linear, or serpiginous track (figure 1, left) known as a
creeping eruption. Note that creeping eruptions occur in many
other human skin diseases. Hookworm folliculitis is an uncommon form of cutaneous larva migrans, marked by pustular
folliculitis of the buttocks (figure 1, right) [4].
Cutaneous larva migrans usually heals spontaneously within
weeks or months. In a series of 25 patients treated with a placebo, 12% healed by the end of the first week and 36% by the
end of the fourth week; the longest period required for spontaneous healing was 11.2 weeks in this series [5], but the larvae
have been known to migrate for up to 1 year [3].
Complications include impetigo and local or general allergic
reactions. For example, edema and vesiculobullous reactions
were reported in, respectively, 6% and 9% of 67 French patients
[1] and 17% and 10% of 60 Canadians [6]. In the largest series
Received 22 November 1999; electronically published 18 May 2000.
Reprints or correspondence: Dr. Eric Caumes, Hopital Pitie-Salpetrie`re,
Service des Maladies Infectieuses et Tropicales, 47 Boulevard de lHopital,
75013 Paris, France (egcaumes@cybercable.fr).
Clinical Infectious Diseases 2000; 30:81114
q 2000 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2000/3005-0012$03.00

of cutaneous larva migrans, involving 98 German patients, 20%


of the 40 patients tested had hypereosinophilia (defined as an
eosinophil proportion 17% of the total leukocyte count); the
mean eosinophilia level was 5%, and the range was 0%37%
[7].
These potential complications, together with the intense pruritus and the duration of the disease, make treatment mandatory. However, optimal management is controversial: in 1
study, 22 German patients with cutaneous larva migrans had
received 12 different treatments, including surgery and French
brandy, before they were referred to a specialized center [7].
The most effective treatment is topical or oral administration
of antihelmintic agents, such as albendazole, thiabendazole,
and ivermectin.

Topical Treatments
Freezing. Freezing the leading edge of the skin track with
ethylene chloride spray, solid carbon dioxide, or liquid nitrogen
rarely works, as the larva is usually located several centimeters
beyond the visible end of the trail. In 1 series, cryotherapy
(repeated applications of liquid nitrogen) was unsuccessful for
6 patients and resulted in severe blistering or ulceration in 2
patients [7]. In another series, none of 7 patients treated with
liquid nitrogen was cured [6]. Because this method is both ineffective and painful, it should be avoided.
Thiabendazole. Topical application of a 10%15% thiabendazole solution/ointment to the affected area was shown
decades ago to be efficacious [8, 9]. In a large study of 53
Canadian patients, in which 15% thiabendazole cream in a
water-soluble base was applied to the affected area 2 or 3 times
a day for 5 days, all but 1 of the patients were cured [6]. The
thiabendazole cream was prepared by crushing 500-mg tablets
of thiabendazole in a water-soluble base. In most patients the
pruritus ceased and larval track migration halted within 48 h
of treatment. In the largest such study (98 German patients),
thiabendazole ointment (15% thiabendazole and 3% salicylic

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Cutaneous larva migrans caused by the larvae of animal hookworms is the most frequent
skin disease among travelers returning from tropical countries. Complications (impetigo and
allergic reactions), together with the intense pruritus and the significant duration of the disease,
make treatment mandatory. Freezing the leading edge of the skin track rarely works. Topical
treatment of the affected area with 10%15% thiabendazole solution or ointment has limited
value for multiple lesions and hookworm folliculitis, and requires applications 3 times a day
for at least 15 days. Oral thiabendazole is poorly effective when given as a single dose (cure
rate, 68%84%) and is less well tolerated than either albendazole or ivermectin. Treatment
with a single 400-mg oral dose of albendazole gives cure rates of 46%100%; a single 12-mg
oral dose of ivermectin gives cure rates of 81%100%.

812

Caumes

CID 2000;30 (May)

acid in unguentum alcoholum lanae) was successful in 96 cases


(cure rate, 98%) within 10 days. In the other 2 cases, treatment
was successful after 2 weeks in 1 case and after 4 weeks in the
other [7].
The main advantage of topical treatments is the absence of
systemic side effects. Their main disadvantages are that they
have limited value for multiple lesions and hookworm folliculitis and that they require multiple daily applications for several days.

Oral Treatments
Thiabendazole. Thiabendazole is the drug with which there
has been the most experience in the oral treatment of cutaneous
larva migrans [5, 912] (table 1). Thiabendazole is poorly effective when given as a single dose. For example, only 68% of
28 patients in 1 series were cured by a single dose of 50 mg/kg
[5]. The cure rate improved to 77% after 2 consecutive days,
87% after 34 consecutive days, and 89% after 4 weekly doses
(table 1).
Thiabendazole is less well tolerated than either albendazole
or ivermectin. In a study of 138 patients treated with thiabendazole (1.252.5 g/d for 12 days) for various indications, the
following adverse effects occurred: giddiness (13%54%), nausea (49%), vomiting (2%16%), and headache (7%) [13].
Albendazole. Albendazole is a third-generation heterocyclic
antihelmintic drug. It has been used for about a decade to treat
intestinal helminthiases, such as ascaridiasis, enterobiasis, ancylostomiasis, trichuriasis, and strongyloidiasis. Trials of albendazole in the treatment of cutaneous larva migrans have
yielded conflicting results with respect to the optimal dosage.
Cure rates of 100% have been obtained after treatment with a
single dose of 400 mg and with the same dose given for 3 and
5 consecutive days (table 2). Albendazole has also been used

with success at higher daily doses (800 mg for 3 consecutive


days). However, in the largest trial of albendazole in cutaneous
larva migrans (involving 26 Italian tourists), treatment with 400
mg for 5 consecutive days failed for 2 patients [18]. In addition,
in a study of 11 French tourists, a single 400-mg dose failed in
6 cases [19].
Differences in the study populations may account for the
different cure rates (46%100%) observed in these studies. It is
interesting that 3 of the 4 studies with a 100% cure rate involved
inhabitants of regions of endemicity, in whom it is difficult to
distinguish between relapse and reinfection. In 2 of the 3 studies
involving tourists, albendazole failed for 2 of 26 Italian patients
[18] and 6 of 11 French patients [19], while the duration of
follow-up was not given in the third study [14]. These findings
suggest that for tourists with cutaneous larva migrans who are
treated with albendazole, the regimen should be 400800 mg/d
for 35 days.
Albendazole was well tolerated in trials involving patients
with cutaneous larva migrans. However, 27% of 30 patients
with gastrointestinal strongyloidiasis complained of gastrointestinal pain and diarrhea after receiving 800 mg of albendazole by mouth on 3 consecutive days [20]. Other publications
Table 1. Treatment of cutaneous larva migrans with oral thiabendazole (50 mg/kg/d).
Reference

No. of patients

Treatment

[11]
[10]
[5]

17
51
28

[12]

25

2 days
34 days
1st dose
a
2d dose
a
3d dose
a
4th dose
1st dose
a
2d dose

One dose of 50 mg/kg per week.

Patients healed,
no. (%)
13
44
19
21
22
24
21
23

(77)
(87)
(68)
(75)
(79)
(89)
(84)
(92)

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Figure 1. Left, A cutaneous serpiginous track characteristic of cutaneous larva migrans. Right, Hookworm folliculitis, an uncommon clinical
form of cutaneous larva migrans.

CID 2000;30 (May)

Table 2.
dazole.
Reference
[16]
[17]
[15]
[14]
[18]
[19]

Treatment of Cutaneous Larva Migrans

Treatment of cutaneous larva migrans with oral albenNo. of


patients

Daily
dose, mg

Duration of
treatment, d

8
6
2
5
18
26
11

400
400
800
800
400
400
400

1
3
3
3
5
5
1

Patients healed,
no. (%)
8
6
2
4
18
24
5

(100)
(100)
(100)
(100)
(100)
(92)
(46)

oral ivermectin (12 mg) and oral albendazole (400 mg) in the
treatment of cutaneous larva migrans. Twenty-one patients
were randomly assigned to receive ivermectin (n = 10 ) or albendazole (n = 11). All the patients who received ivermectin
responded, and none relapsed (cure rate, 100%). All but 1 of
the patients receiving albendazole responded, but 5 relapsed
after a mean of 11 days (cure rate, 46%); the difference in
efficacy significantly favored ivermectin (P = .017 ). No major
adverse effects were observed. The investigators concluded that
a single 12-mg dose of ivermectin was more effective than a
single 400-mg dose of albendazole for the treatment of cutaneous larva migrans [19].

Prevention
Because tourists are usually infected by walking or lying on
tropical sandy beaches contaminated by dog feces, the best way
to prevent cutaneous larva migrans is to ban dogs from beaches

Table 3. Treatment of cutaneous larva migrans with a single oral


12-mg dose of ivermectin.
Reference
[23]
[24]
[19]
[25]
[26]
[27]

No. of patients
8
12
10
57
51
59

Patients healed, no. (%)


8
12
10
56
48
48

(100)
(100)
(100)
(98)
(94)
(81)

Figure 2. Top, Prevention of cutaneous larva migrans: no dogs allowed on beaches (Sydney, Australia). Bottom, Avoidance of cutaneous
larva migrans: lie on the part of the beach washed by the tide (Boracay,
Philippines).

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suggest that albendazole is well tolerated unless given at high


dosages or for extended periods, such as those required for
hydatid disease [21].
Ivermectin. Ivermectin, an avermectin B derivative, is active against Onchocerca volvulus and other nematodes, including gastrointestinal helminths. Its mechanism of action is poorly
understood [22]. Single doses of ivermectin resulted in 100%
cure rates among patients with cutaneous larva migrans in 2
open studies published in 1992, in which 8 Cameroonian patients received 150 mg/kg [23] and 12 French tourists received
200 mg/kg [24] (table 3). Since then, the efficacy of ivermectin
has been confirmed in 3 larger studies. One involved 57 French
tourists treated with a single oral dose of 12 mg ivermectin, of
whom 56 (98%) were cured [25].
Another study involved 67 Belgian tourists treated with
a single dose (12 mg) of ivermectin. Fifty-one patients were
assessable and 48 (94%) were cured; 2 patients relapsed, and
treatment failed in an immunodeficient patient [26]. The third
study involved 59 French tourists treated with a single oral
dose of 12 mg; 48 patients (81%) were cured, 9 relapsed, and
treatment failed for 2. These latter 11 patients required a second
(n = 9) or third (n = 2) course of ivermectin. The median intervals until disappearance of the pruritus and lesions were 3
days (range, 17 days) for the patients who received a second
dose, and 9 days (range, 430 days) for those who received a
third dose. Only 2 patients were not cured by ivermectin [27].
Ivermectin has been well tolerated in studies of patients with
cutaneous larva migrans, and no adverse effects have been reported in indications other than filariasis [28]. Almost all the
adverse effects are a result of the patients immune response to
killed microfilariae [22].
An open study [19] compared the efficacy of single doses of

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Caumes

(figure 2, top) [29]. Because this is clearly impossible in developing tropical countries, where dogs are ubiquitous, it is best
to wear shoes when walking in sandy areas. When on tropical
beaches frequented by dogs, it is best to lie on sand washed by
the tide or to use a mattress; avoid lying on dry sand, even on
a towel (figure 2, bottom).

References

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16. Orihuela AR, Torres JR. Single dose of albendazole in the treatment of
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