treatment of cutaneous larva migrans and toxocara infection
TRANSCRIPT
O R I G I N A L
A R T I C L E
Treatment of cutaneous larva migransand Toxocara infection
Eric CaumesService des Maladies Infectieuses et Tropicales, Hopital Pitie-Salpetriere, 47/83 Bld de l’Hopital, 75651 Paris Cedex 13,
France
C U T A N E O U S L A R V A M I G R A N S
The most common treatment for cutaneous larva
migrans (CLM) remains topical thiabendazole, although
new oral antihelmintic agents are well tolerated and
efficient [1].
Topical treatments
Freezing
Freezing the leading edge of the cutaneous trail with
carbon dioxide snow, ethylene chloride spray, or liquid
nitrogen rarely works, because the larvae are usually
located several centimeters beyond the leading edge.
In one series of eight patients, repeated application of
liquid nitrogen was unsuccessful in six cases and resulted
in severe blistering or ulceration in two [2]. Likewise,
liquid nitrogen was ineffective in another series of seven
patients [3]. Cryotherapy is no longer recommended,
being painful, risky and rarely effective. Other less
traumatic treatments are now available [1].
Topical tiabendazole
Topical application of 10–15% tiabendazole to the
affected areas is a well-known and effective treatment
[4,5]. In one study, 52 of 53 Canadian travelers were
cured after treatment with 15% tiabendazole cream
applied to the affected area two to three times a day for
5 days [3]. The cream was prepared by crushing 500-mg
tiabendazole tablets in a water-soluble base. Pruritus
resolved and larval migration ceased in most cases after
48 h of treatment. In a series of 98 German travelers,
therapy with tiabendazole ointment (15% tiabendazole
and 3% salicylic acid in unguentum alcoholum lanae)
was successful within 10 days in 96 cases. The other
two patients were cured after 2 and 4 weeks of treatment
[2].
The main advantage of topical treatment is its good
tolerability, with only rare cases of contact dermatitis.
However, topical treatment has a number of drawbacks,
such as multiple daily application (especially in patients
with multiple lesions), relatively lengthy treatment, and
lack of efficacy in hookworm folliculitis.
Oral treatments
Tiabendazole
Tiabendazole is the oral drug with which we have much
experience in the treatment of CLMs, having been tested
in more patients than any other agent. Single-dose
tiabendazole therapy is poorly effective. In one series,
only 68% of 28 American patients were cured by a single
dose of 50 mg/kg [6]. The cure rate rises to 77% with
treatment for two consecutive days [7], 87% for three to
Keywords
albendazole,
cutaneous larva migrans,
ivermectin,
tiabendazole,
toxocariasis
Received 4 November 2002;
revised 25 November 2002;
accepted 20 January 2003
Correspondence and reprints:
A B S T R A C T
The treatment of cutaneous larva migrans and Toxocara infection relies on
antihelminthic agents such as thiabendazole, albendazole and ivermectin. The
efficacy of these agents varies according to the helminthic disease.
� 2003 Blackwell Publishing Fundamental & Clinical Pharmacology 17 (2003) 213–216 213� 2003 Blackwell Publishing Fundamental & Clinical Pharmacology 17 (2003) 213–216
four consecutive days [8], and 89% after four weekly
doses [6].
Tiabendazole is poorly tolerated. In a series of
138 patients treated for various indications with 1.25–
2.5 g/day tiabendazole for 1–2 days, 13–54% complained
of giddiness, 49% of nausea, 2–16% of vomiting, and 7%
of headache [9].
Albendazole
Albendazole has been used over the past decade to treat
various intestinal helminthiases, such as ascaridiasis,
enterobiasis, ancylostomiasis, trichuriasis and strongylo-
idiasis. Clinical trials of albendazole therapy for CLMs
have failed to establish the optimal dosage regimen.
Cure rates of 100% have been reported with a single
dose of 400 mg [10], 400 mg/day for three [11] and
five [12] consecutive days, and 800 mg/day for three
consecutive days [11,13]. However, in the largest study,
400 mg/day albendazole for five consecutive days failed
in two of 26 Italian tourists [14]. In addition, in a study
of 11 French tourists, a single albendazole dose of
400 mg failed in six cases [15]. Differences in the study
populations (tourists vs. residents) may account for the
wide range of reported cure rates (46–100%) [1]. Indeed,
three of the four studies yielding 100% cure rates
involved inhabitants of endemic regions, in whom it is
difficult to distinguish between relapse and reinfection.
These findings suggest that albendazole should be given
at a dose of 400–800 mg/day for 3–5 days when
treating CLMs in travelers [1].
Albendazole therapy is well tolerated by patients with
cutaneous larva migrans.
Ivermectin
Ivermectin has the dual advantages of being well
tolerated and highly effective as a single oral dose of
12 mg. Single-dose ivermectin cured all patients with
CLMs enrolled in two open studies published in 1992: in
one, eight Cameroonian patients received 150 lg/kg
[16] and in the other, 12 French tourists received
200 lg/kg [17].
The efficacy of single-dose ivermectin has since been
confirmed in larger studies, in which the cure rate
ranged from 77% [18] to more than 94% [19,20].
Pruritus resolved after an average of 3 days (range
1–7 days) and the creeping eruption ceased after 9 days
(range 4–30 days) [18].
Ivermectin has been compared with oral albendazole
in an open, randomized trial involving 21 patients
with CLMs [15]. Ten patients received ivermectin and
11 received albendazole. All the patients who received
ivermectin responded, and none relapsed (cure rate
100%). All but one of the patients receiving albendazole
responded, but five relapsed after a mean of 11 days
(cure rate 46%) (P ¼ 0.017). No major adverse effects
were observed in either group. Thus, a single 12-mg dose
of ivermectin was more effective than a single 400-mg
dose of albendazole for the treatment of CLMs.
A second, and sometimes a third course of ivermectin,
1 week apart, may be necessary if pruritus persists or if
the larva continues to migrate 1 week after the previous
dose [18].
Our experience with ivermectin in the treatment of
hookworm folliculitis is somewhat different. Only two of
five patients with hookworm folliculitis and CLM were
cured by a single dose of ivermectin (12 mg), while two
patients required two doses 1 week apart, and the fifth
patient required three doses at 1-week intervals [21].
Treatment was only stopped when the pruritus dis-
appeared, indicating parasite death. The folliculitis took
longer to resolve than the creeping eruptions.
Ivermectin is well tolerated by patients with CLMs. The
only major adverse effects were reported in patients with
filariasis, as a result of the immune response to killed
microfilariae [22].
T O X O C A R I A S I S
The decision to treat human Toxocara infection can be
difficult. Toxocariasis is most often subclinical or self-
limited, but treatment is required for symptomatic
patients. Among the drugs potentially effective on
toxocariasis, only benzimidazoles (albendazole, meben-
dazole and tiabendazole) and diethylcarbamazine have
been tested in controlled studies.
Albendazole is the most commonly used drug,
although other benzimidazole compounds have shown
some efficacy [23]. Overall, the cure rate ranges from 30
to 50%, but treatment efficacy is difficult to evaluate,
symptoms being diverse and non-specific. Laboratory
markers of treatment efficacy are disappointing [24],
with the possible exception of specific anti-Toxocara
IgE levels [25]. Whatever the drug, eosinophilia rises
within a week after treatment initiation, followed by an
improvement in clinical symptoms and signs; eosino-
philia and antibody titers decline over a period of at least
4 weeks [23].
Two comparative studies have been published in this
setting. Between 1986 and 1988, 34 patients with
visceral or ocular larva migrans were randomly assigned
214 E. Caumes
� 2003 Blackwell Publishing Fundamental & Clinical Pharmacology 17 (2003) 213–216
to receive a 5-day course of thiabendazole 25 mg/kg
twice a day (15 patients) or albendazole 5 mg/kg twice a
day (19 patients) [24]. Tolerability, assessed on the fifth
day of treatment, was good or excellent in six patients
(40%) receiving thiabendazole and 11 patients (58%)
receiving albendazole. Efficacy was assessed after
30 weeks on average (range 6–56 weeks). Four patients
in the thiabendazole group (27%) and six patients in the
albendazole group (32%) were clinically cured. There was
no significant difference in treatment efficacy between
thiabendazole and albendazole. Because of its better
tolerability, the authors recommended albendazole for
the treatment of visceral and ocular larva migrans, with a
minimum dose of 10 mg/kg daily for 5 days. Treatment
may have to be repeated, depending on the biological and
clinical response. A larger controlled study is required to
confirm these results. A single course of albendazole has
been recommended for patients with eosinophilia and at
least moderately positive serological results [23].
Albendazole is usually combined with corticosteroids
for the treatment of ocular and neurological manifesta-
tions. The efficacy of albendazole (adults: 800 mg bid;
children: 400 mg bid) combined with a steroid has been
evaluated in five immunocompetent patients with Toxo-
cara canis uveitis [26], on the basis of visual acuity,
inflammatory responses, adverse effects, and toxicity.
Treatment improved visual acuity in every case. Uveitis
never recurred during follow-up (average: 13.8 months;
range: 3 days to 24 months).
The efficacy of diethylcarbamazine and mebendazole
was recently compared in an open randomized study, in
39 and 41 patients, respectively, all exhibiting clinical
and biological features of toxocariasis and Western blot
positivity [25]. The clinical impact of the disease was
quantified using a 20-item scoring system. Post-treat-
ment follow-up included clinical evaluations, eosinophil
counts, total and specific anti-Toxocara IgE assay, and
Western blot. All the patients attended the control visit
1 month after the end of treatment. The results showed a
similar good efficacy of diethylcarbamazine and meben-
dazole on the clinical score and the eosinophil count.
Mebendazole therapy was slightly more effective on the
kinetics of specific anti-Toxocara IgE, while mean total
IgE titers were not affected by either diethylcarbamazine
or mebendazole. Patients in the diethylcarbamazine
group reported a significantly higher rate of adverse
reactions, most of which were attributed to parasite lysis.
The authors recommended treating human toxocariasis
with mebendazole, on account of its better tolerability
and efficacy on specific anti-Toxocara IgE levels.
Ivermectin showed no significant efficacy in an open
study of a dozen cases of visceral larva migrans caused
by Toxocara canis or cati [27].
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