Pharmacology and therapeutics

Treatment of larva migrans cutanea (creeping eruption): acomparison between albendazole and traditional therapy

Giancarlo Albanese, MD, Caterina Venturi, MD, and Giuseppe Galbiati, MD

Abstract

Background Creeping eruption (CE), which is characteristic of tropical and subtropical

regions, is being increasingly frequently observed in Italy. The presence on the beaches of

stray animals infected by nematodes of the Ancylostoma species favors contact between

human skin and the larva-infested soil.

Materials and methods Our experience with 56 patients (13 cryotherapy, one

thiabendazole together with cryotherapy, six thiabendazole, two albendazole with

cryotherapy, and 34 albendazole) is described.

Results A prompt and de®nitive cure was achieved in all 56 patients. The therapeutic

effectiveness of the various methods used is therefore equivalent.

Conclusions We believe that albendazole should be considered the ®rst choice for

treatment. It is extremely well tolerated and patient compliance is good.

Introduction

Creeping eruption (CE) is a parasitosis, featuring creeping

cutaneous lesions, endemic to hot, humid, tropical and

subtropical areas (Fig. 1), but also increasingly evident in

other areas due to frequent tourist and business travel to

exotic places.1±7 It is mainly caused by Ancylostoma

braziliense, a helminth that normally lives in the intestines

of dogs, cats, and wild animals. Less frequently other

species may result in the same clinical picture: Ancylosto-

ma caninum, Uncinaria stenochepala, Bunostomun phle-

botomun, or the human larvae of Necator americanus and

Ancylostoma duodenale.3±5,8,9

The life-cycle of the various nematodes is thus very

similar. The eggs of parasites, expelled by the infected

animals with the feces in sandy soil, mature into larvae

which are initially rhabditiform, then strongyloid, and

then, within 5±7 days, develop into the infective ®lariform

type.3,4,8

If humans come into contact with contaminated soil,

the larvae can cross unbroken skin or, even more

frequently, enter via the hair follicles, sweat glands, or

damaged skin.3,4 After a variable length of time,

proceeding at about 2±5 cm/day, they start to migrate

into the epidermis, especially at night, giving rise to an

initial erythematous, papular, aspeci®c itching lesion,

more frequently located on the feet, buttocks, and

thighs. A moderately in¯amed, winding, usually raised,

erythematous, swollen cutaneous lesion appears, varying

in color between pink and dark red, 2±3 mm thick, with

a ¯uid serous content, along which there may be

nodules or blisters. Sometimes the clinical picture is

represented only by folliculitis.1±5,8±11

Patients, often bathers, but also gardeners, farmers,

hunters, or people who lay water pipes, etc., complain of

intense itching, which is often the cause of insomnia and

violent scratching, and sometimes of a burning sensation.

Infective or allergic complications are possible. Sometimes

a Loef¯er syndrome may coexist.1,4,5,8,9,11

Diagnosis of this parasitosis is typically based on clinical

anamnesis. Because the parasite itself is often located

beyond the visible lesions, it is extremely dif®cult to isolate

it via skin biopsy. Hematochemical tests sometimes reveal

hypereosinophilia or an increase in the immunoglobulin E

(IgE) rate. Some authors recently proposed examining the

lesion under epiluminescent microscopy for diagnostic

con®rmation, while others suggest searching for speci®c

IgG with enzyme-linked immunoabsorbent assay (ELISA)

methods.4±6,8

This dermatosis requires differential diagnosis from

other parasitoses, e.g. larva migrans viscerale, eruptions

of Strongyloides stercoralis, subcutaneous nodules or

granulomas due to other species, and different pictures of

From the Divisione Dermosi®lopatica,

Micologia e Dermatologia Tropicale,

Ospedale S. Gerardo, Monza (MI),

Italy

Correspondence

Giancarlo Albanese, MD

Divisione Dermosi®lopatica, Micologia

e Dermatologia Tropicale

Via Donizetti, 106

20052 Monza (MI)

Italy

Drug names

albendazole: Albenza (USA), Zentel

(Italy)

ã 2001 Blackwell Science Ltd International Journal of Dermatology 2001, 40, 67±71

67

myiasis, but also from simpler and more common

pathologies, such as allergic contact dermatitis, urticaria

factitia, other types of dermatitis, and pyoderma.3,5,8

Although CE normally disappears by itself within

anything from 1 to 6 months or, rarely, longer, the intense

itching, the unpleasant sensation felt by the patient of the

larva slowly creeping below the skin, and the possible

complications suggest that treatment should be given that

can reduce the length of the disease, even if different

therapeutic options turn out to be somewhat ineffective or

dif®cult to put into practice.1±3

Cryotherapy, for instance, which is painful for the

patient, can only be applied for a limited number of lesions

and is unlikely to solve the problem due to the dif®culty in

identifying the exact position of the parasite, which can

anyway withstand low temperatures.1±4,9,11

Thiabendazole for topical use requires repeated treat-

ment throughout the day, sometimes leads to local

irritating reactions, can only be applied if lesions are

neither numerous nor widespread, and is often followed by

recurrence.2±5,7,8,10,11

Some authors have suggested the topical use of cream

with 2% gammexane, ointment with 25% piperazine, or

metriphonate.3,5

The systemic use of thiabendazole, 25±50 mg/kg once or

twice a day for 2±5 days, or in a single 50 mg/kg dose, may

be effective in the case of widespread lesions, but is

contraindicated due to its possible poorly tolerated

side-effects. What's more, this drug is not available in

Italy.2±5, 7±11

Figure 1 Endemic areas for creeping

eruption

Figure 2 Distribution of the cases by year

Table 1 Seaside resorts visited by our patients

Country Number of patients

Central America 29 (52%)

Jamaica 12

Mexico 9

Cuba 3

S Domingo 2

Barbados 1

Grenada 1

Caribbean 1

Africa 10 (18%)

Kenya 6

Tunisia 1

Tanzania 1

Senegal 1

Egypt 1

South America 8 (14%)

Brazil 6

Venezuela 2

Asia 7 (12%)

Malaysia 3

Indonesia 1

Thailand 1

Maldives 1

Middle East 1

Europe 2 (4%)

Italy (Apulia, Sardinia) 2

Pharmacology and therapeutics Treatment of larva migrans cutanea Albanese, Venturi, and Galbiati

International Journal of Dermatology 2001, 40, 67±71 ã 2001 Blackwell Science Ltd

68

Another possibility is a single 150±200 mg/kg dose of

ivermectin, a drug capable of eradicating the parasite with

minimum or no side-effects, but which still needs more

thorough research, and which we only use in a veterinary

context.2,4,5,7,10,11

Flubendazole (200 mg/day for 5 days), currently at an

experimental stage, would appear to offer good prospects

for the future.4

Materials, methods, and results

In our experience, a valid alternative to conventional

treatment is albendazole, recommended in the case of CE at

adoseof400±800 mg/dayforaperiodthatmayvaryfrom1to

7 days. It is an anthelminth which is effective against eggs,

larvae, and the adult stage of numerous helminths.1±4,7±11

Exactly how it works is still not completely clear. It may

reduce or block the uptake of glucose, thus determining the

depletion of glycogen reserves with a decrease or cessation in

the production of adenosine triphosphate (ATP). It may

inhibit fumarate-reductase or maleate-dehydrogenase, de-

couple oxidative phosphorylation, or induce the degenera-

tion of the cytoplasmatic microtubules with the death of the

parasitebyautolysis. Finally, someauthorsbelieve that it acts

Figure 3 Distribution of our survey by

continent

Figure 4 Sites most affected by the parasitic disease

Figure 5 Clinical view of a patient before treatment

Albanese, Venturi, and Galbiati Treatment of larva migrans cutanea Pharmacology and therapeutics

ã 2001 Blackwell Science Ltd International Journal of Dermatology 2001, 40, 67±71

69

by inhibiting microtubule polymerization via the com-

pound's speci®c and highly selective link to b-tubulin. It is

particularly resistant to inactivation, little absorbed in the

intestine, and therefore usually well tolerated if administered

for a short length of time. In the long term, it can lead to an

increase in liver enzymes or rarely to alopecia, allergic

reactions, leukopenia, and thrombocytopenia. It has proved

to be teratogenic and embryotoxic in rats and rabbits, but

does not appear to be mutagenic or carcinogenic.1±4,9±11

Our experience concerns 56 patients of both sexes (21

female (37%) and 35 male (63%)), aged between 2 and

60 years (average, 30.43 years), who came to our

attention with suspected CE between March 1987 and

December 1999 (Fig. 2). All had been on recent trips to

seaside resorts for their holidays (Fig. 3), mainly (95%)

in endemic areas for this parasitosis (Table 1). Further

information about patient characteristics is given in

Table 2. The dermatosis was mainly found on the feet,

while some patients had cutaneous alterations distrib-

uted as shown in Fig. 4.

The patients were treated using various procedures,

according to whatever was available at the time of

diagnosis. In detail, 13 patients (23%), among the ®rst to

come to our attention, were treated with physical therapy

because there were no speci®c low toxicity drugs for

systemic use for this parasitosis on the market at that time.

None had recurrent episodes with time or remarkable

scars, but many underlined how painful the procedure had

been. A further six patients (11%) were treated with 25±

50 mg/kg/day of thiabendazole for systemic use for two

consecutive days, despite its poor availability in Italy, and

one received both this drug and cryotherapy. There was a

regression of itching and cutaneous lesions in all these

Figure 6 Clinical view of a patient after treatment

Table 2 Characteristics of the patients studied

Characteristic Number of patients

Total patients 56

Age

Median 30.43

Range 2±60

Sex

Male 35 (63%)

Female 21 (37%)

Incubation period

Median < 1.5 months

Range < 1 month±5 months

Type of stay

Tourist 56 (100%)

Business 0 (0%)

Presence of dogs on beach

Yes 45 (80%)

No 5 (9%)

Don't remember 6 (11%)

Type of lesion

Localized 49 (88%)

Widespread 7 (12%)

Unilateral 39 (70%)

Bilateral 17 (30%)

Single 35 (63%)

Multiple 21 (37%)

Sites

Trunk 9 (16%)

Arm 1 (2%)

Scrotum 2 (4%)

Buttock 8 (14%)

Thigh 8 (14%)

Knee 1 (2%)

Shin 2 (4%)

Foot 40 (71%)

Sole 28 (50%)

Instep 19 (34%)

Side 9 (16%)

Treatment

Cryotherapy 13 (23%)

Thiabendazole 6 (11%)

Thiabendazole + cryotherapy 1 (2%)

Albendazole + cryotherapy 2 (4%)

Albendazole 34 (60%)

Pharmacology and therapeutics Treatment of larva migrans cutanea Albanese, Venturi, and Galbiati

International Journal of Dermatology 2001, 40, 67±71 ã 2001 Blackwell Science Ltd

70

cases, although they suffered from nausea, diarrhea, and

dizziness, which appeared while they were taking the

treatment proposed.

Of the 36 patients observed from 1993 to 1999 and

treated with 400 mg/day of albendazole for three con-

secutive days, in two cases associated with cryotherapy,

none reported adverse reactions, despite a prompt and

de®nitive cure. Despite the low dosage used, this drug is

active in a short time: after 24±48 h, larva migration in the

skin was stopped with consequent regression of itching.

Moreover, the low dosage makes reactions to the drug

practically nonexistent and reduces the patient's commit-

ment to a minimum (Figs 5 and 6).

Conclusions

Duetotheincreasedincidenceofthisparasitosis inourclinics,

especially during the summer and Christmas holidayperiods,

and the need for treatment due to the unpleasant symptoms

and signs that accompany the dermatosis, albendazole can

de®nitely be considered the drug of ®rst choice. The painful

and laborious nature of cryotherapy, the numerous, unplea-

santside-effects inducedbythesystemicuseof thiabendazole,

the frequent recurrence and poor compliance with galenical

therapy, and the uncertainties of the new drugs proposed

make albendazole stand out as the only tolerable and fast-

acting solution available on the Italian market.

References

1 Di Carlo A, Vassallo D, Iacovelli P, Leone G. Due casi di

creeping disease: risultati del trattamento con albendazolo.

Chron Dermatol 1995; 5 (2): 225±231.

2 Lavaroni G, Briscik E, Kokelj F. Larva migrans cutanea

trattata con albendazolo. G Ital Dermatol Venereol 1995;

130: 405±407.

3 Canizares O, Harman RRM. Helminthic disease I.

NematodesÐcutaneous manifestations of intestinal

parasites. In: Clinical Tropical Dermatology, 2nd edn.

Cambridge, MA: Blackwell Scienti®c, 1992: 332±334.

4 Celano G, Ruatti P. Larva migrans cutanea (creeping

eruption). Osservazioni su un caso autoctono trattato con

albendazolo. Chron Dermatol 1996; 6 (4): 517±528.

5 Gilles HM. Soil-transmitted helminths (geohelminths).

Cutaneous larva migrans. In: Cook GC, ed. Manson's

Tropical Disease. London: WB Saunders, 1996:

1392±1394.

6 Elsner E, Thewes M, Worret WI. Cutaneous larva migrans

detected by epiluminescent microscopy. Acta Dermatol

Venereol 1997; 77: 487±488.

7 Caumes E, CarrieÁre J, Guermonprez G, et al. Dermatoses

associated with travel to tropical countries: a prospective

study of the diagnosis and management of 269 patients

presenting to a tropical disease unit. Clin Infect Dis 1995;

20: 542±548.

8 Rook A, Wilkinson DS, Ebling FJG. Parasitic worms and

protozoa. In: Textbook of Dermatology, Vol. 2, 5th edn.

Oxford: Blackwell Scienti®c, 1992: 1233±1235.

9 Pauluzzi P, Magaton Rizzi G, Mattighello P. Larva

migrans: report of three cases. Therapeutic advice. J Eur

Acad Dermatol Venereol 1996; 6: 89±91.

10 Loughrey MB, Irvine AD, Girdwood RWA, McMillan JC.

Cutaneous larva migrans: the case for routine oral

treatment. Br J Dermatol 1997; 137: 155±156.

11 Rizzitelli G, Scarabelli G, Veraldi S. Albendazole: a new

therapeutic regimen in cutaneous larva migrans. Int J

Dermatol 1997; 36: 700±703.

Albanese, Venturi, and Galbiati Treatment of larva migrans cutanea Pharmacology and therapeutics

ã 2001 Blackwell Science Ltd International Journal of Dermatology 2001, 40, 67±71

71