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Cutaneous Larva Migrans
Article  in  Recent Patents on Inflammation & Allergy Drug Discovery · January 2017
DOI: 10.2174/1872213X11666170110162344
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Recent Patents on Inflammation & Allergy Drug Discovery 2017, 11, 2-11
REVIEW ARTICLE 
Cutaneous Larva Migrans 
 2212-2710/17 $100.00+.00 © 2017 Bentham Science Publishers
Alexander K.C. Leung1,*, Benjamin Barankin2 and Kam L.E. Hon3
1Department of Pediatrics, The University of Calgary, Alberta Children’s Hospital, Calgary, Alberta, Canada; 2Toronto 
Dermatology Centre, Toronto, Ontario, Canada; 3Department of Paediatrics, The Chinese University of Hong Kong, 
Shatin, Hong Kong 
A R T I C L E H I S T O R Y
Received: December 20, 2016 
Revised: January 1, 2017 
Accepted: January 9, 2017 
DOI: 
10.2174/1872213X11666170110162344
Abstract: Background: Cutaneous larva migrans is one of the most common skin diseases reported in 
travelers returning from tropical regions. Western physicians, however, are often not familiar of this 
condition. 
Objective: To review in depth the epidemiology, pathophysiology, clinical manifestations, complica-
tions, and treatment of cutaneous larva migrans. 
Methods: A PubMed search was completed in Clinical Queries using the key term “cutaneous larva 
migrans”. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. 
Patents were searched using the key term “cutaneous larva migrans” from www.google.com/patents, 
www.uspto.gov, and www.freepatentsonline.com. 
Results: Cutaneous larva migrans is a zoonotic infestation caused by penetration and migration in the 
epidermis of filariform larva of different kinds of animal hookworms through contact with feces of 
infected animals. Cutaneous larva migrans is endemic in tropical and subtropical regions. Clinically, 
cutaneous larva migrans is characterized by an intensely pruritic erythematous migrating tortuous or 
serpiginous, slightly raised track. The diagnosis is mainly clinical, based on the history of travel to an 
endemic area and exposure to contaminated soil/sand and the characteristic serpiginous track. Treat-
ment options as well as recent patents related to the management of cutaneous larva migrans are also 
discussed. Compared with oral antihelminthics, topical treatment over the affected area is less effec-
tive. Oral ivermectin is the treatment of choice.
Conclusion: The pruritic serpiginous track is pathognomonic. Oral ivermectin is the treatment of choice. 
Keywords: Ancylostoma braziliense, Ancylostoma caninum, cats, dogs, hookworm, pruritus, serpiginous track. 
1. INTRODUCTION 
 Cutaneous larva migrans is a zoonotic infestation caused 
by penetration and migration in the epidermis of filariform 
larva of different kinds of animal hookworms through con-
tact with feces of infected animals, mostly dogs and cats [1- 
3]. Clinically, cutaneous larva migrans is characterized by a 
pruritic erythematous migrating tortuous or serpiginous, 
slightly raised track [1]. The condition was first described by 
Lee, a British physician, in 1874 [3]. The term "cutaneous 
larva migrans" was coined by Crocker in 1893 [4]. Syno-
nyms include creeping eruption, sandworm disease, beach 
worm disease, ground itch, linear serpiginous dermatitis, 
dermatitis serpiginosus, migrant helminthiasis, migrant linear 
epidermatitis, epidermatitis linearis migrans, creeping ver-
minous dermatitis, duck hunter's itch, and plumber's itch 
*Address correspondence to this author at The University of Calgary, Al-
berta Children’s Hospital, #200, 233 – 16th Avenue NW, Calgary, Alberta, 
Canada T2M 0H5; Tel: (403) 230 3300; Fax: (403) 230-3322; 
E-mail: aleung@ucalgary.ca 
[5-7]. Although some authors use the term "cutaneous larva 
migrans" and "creeping eruption" interchangeably, Caumes 
et al. rightly pointed out that cutaneous larva migrans is a 
syndrome whereas creeping eruption is a clinical sign which 
can be caused by various parasites [8]. Suffice to say, hook-
worm-related cutaneous larva migrans is the most common 
cause of a creeping eruption [9]. 
 Cutaneous larva migrans is one of the most common skin 
diseases reported in travelers returning from tropical regions 
[10]. Western physicians, however, are often not familiar of 
this condition. As a matter of fact, the initial diagnosis is 
only correct in less than 55% of cases. Misdiagnosis of 
courseleads to inappropriate or delayed treatment. A review 
of the topic is therefore in order and is the purpose of the 
present communication. 
2. EPIDEMIOLOGY 
 Cutaneous larva migrans affects millions of people 
worldwide [11]. The condition is common in individuals 
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Cutaneous Larva Migrans Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 3
residing in tropical and subtropical regions, especially in 
developing countries [9]. In a rural community in Brazil, 
approximately 4.4% of the general population and 15% of 
children have been found to be infested [9, 12]. 
 Cutaneous larva migrans is the most common ectoparasi-
tosis acquired by travelers returning from tropical and sub-
tropical regions [6]. In one study, cutaneous larva migrans 
accounted for approximately 10% of dermatological diagno-
ses in sick travelers returning from tropical regions [13]. In 
another study, 1463 of 13,300 patients who attended a travel-
related-disease clinic during a period of 4 years had skin 
symptoms [14]. Of the 1463 patients, 98 (6.7%) patients had 
cutaneous larva migrans [14]. Prevalence is high in geo-
graphic regions with a warm and humid climate where indi-
viduals tend to walk barefoot and come in contact with feces 
of dogs and cats [15]. This is especially so in rainy season 
when the risk of infestation may be 15 times higher [9, 16]. 
Cutaneous larva migrans is endemic in Central and South 
America, Mexico, Caribbean, Africa, Southeast Asia, Medi-
terranean regions, the southeastern parts of the United States, 
and other tropical areas [15-18]. The exact prevalence among 
returning travelers is not known, but it is bound to increase 
in parallel with the popularity of travel to subtropical and 
topical areas. The disease is very rarely acquired in temper-
ate areas [16]. Notwithstanding this, autochthonous cases in 
persons without a history of foreign travel have rarely been 
reported in European countries such as the United Kingdom, 
Germany, France, and Italy, presumably because of global 
warming [19-26]. 
 There is no racial or sex predilection because the disease 
depends on exposure [13]. The condition is more common in 
children than in adults [13, 18, 27]. Individuals whose hob-
bies and occupations bring them in contact with contami-
nated soil or sand are at risk for cutaneous larva migrans; 
these individuals include travelers, swimmers, sunbathers, 
hunters, plumbers, miners, carpenters, farmers, gardeners, 
fishermen, and pest exterminators [18]. Poor hygiene and 
poor sanitation are important predisposing factors [11, 27]. 
3. CAUSATIVE ORGANISMS 
 Cutaneous larva migrans is caused by the filariform lar-
vae of animal (notably dogs and cats) hookworms. The most 
common causative larva is Ancylostoma braziliense (hook-
worm of wild and domestic dogs and cats) followed by An-
cylostoma caninum (dog hookworm) [7, 18]. Other causative 
larvae are Uncinaria stenocephala (dog hookworm), 
Bunostomum phlebotomum (cattle hookworm), and Ancy-
lostoma ceylonicum (dog and cat hookworm) [2, 7, 28-30].
Ancylostoma caninum and Uncinaria stenocephala have, 
occasionally, been isolated from foxes [28]. 
 The adult hookworms infest the intestines of the definite 
host animals [29, 31]. Their eggs are excreted in their feces 
and contaminate the surrounding soil or sand. Under optimal 
environmental conditions (moisture, shade, and warmth), the 
embryonated eggs hatch in the superficial layer of the soil 
within two days [31, 32]. The released rhabditiform larvae 
feed on the bacteria in the soil and/or feces [31, 32]. These 
larvae mature and molt twice in 5 to 10 days to become fi-
lariform larvae which are infective [18]. The filariform lar-
vae can survive a few weeks to even a few months under 
optimal conditions [9, 10, 18]. The larva of Ancylostoma 
braziliense, the most common causative larva, on average, 
measures approximately 6.5 mm long and has a diameter of 
0.5mm [33-35]. 
4. DISEASE TRANSMISSION 
 Humans are accidental hosts and become infected when 
the filariform larvae come into direct contact and penetrate 
the stratum corneum. The larvae usually live in the superfi-
cial layer of the sand/soil, within inches of where the eggs 
are deposited [27]. Beaches are a common reservoir for the 
filariform larvae. Human infection typically occurs after 
walking barefoot or with open-type shoes or lying undressed 
on the sand/soil, especially sandy beaches, contaminated by 
feces of infected dogs and cats [29, 36]. The larvae can also 
be found in sandpits, and loose soil at construction sites, gar-
dens, fields, or under houses [30, 37]. Simultaneous infesta-
tion with larvae of other hookworm species may also occur 
[15]. 
5. PATHOPHYSIOLOGY 
 Because of the proteases and hyaluronidase that they 
secrete, the filariform larvae can penetrate fissures, hair fol-
licles, sweat glands and even intact skin by digesting the 
keratin in the epidermis [29-31]. After penetrating the skin, 
the filariform larvae shed their cuticle [38]. Until then, the 
larvae do not have functioning mouth parts [38]. After the 
cuticle has been shed, the larvae start migration in approxi-
mately 7 days [39]. The larvae lack the collagenase enzyme 
and therefore cannot penetrate the basement membrane to 
invade the dermis and reach blood or lymphatic vessels to 
ultimately reach the intestine and complete their life cycle, as 
they would do so in an appropriate animal host [9]. As such, 
the larvae remain confined to the epidermis. The larvae creep 
or wander aimlessly within the epidermis in a serpiginous 
route at a rate of 2mm to 2cm per day [7, 18]. The speed of 
migration varies depending on the species of the larva, but 
generally does not exceed 1cm a day [15, 18, 35, 40, 41]. 
The larvae usually die in the subcutaneous tissue in 2 to 8 
weeks without being able to complete their life cycle in the 
human body [18, 32, 35, 36, 42]. In other words, humans are 
a dead-end host for the larvae. In spite of this, migration to 
internal organs has, very rarely, been reported [29, 43, 44]. 
6. CLINICAL MANIFESTATIONS 
 A stinging or tingling sensation may be experienced 
within 30 minutes of the larva penetrating the skin [6, 30]. A 
few hours later, an itchy reddish-brown papule or nonspe-
cific eruption may be noted at the site of penetration [6, 45]. 
The incubation period is about 5 to 15 days, with a range of a 
few minutes to 165 days; during which time the larvae lie 
dormant [39, 40, 46-49]. After the incubation period, the 
larva start migrating and wandering freely in the epidermis, 
resulting in the formation of an erythematous, slightly raised, 
tortuous, winding, serpiginous or, less often, linear track 
extending from the reddish-brown papule - the site of larval 
penetration [28, 39]. The pruritic serpiginous track is 
pathognomonic (Fig. (1)) [15]. Papular and vesicular lesions 
may be present in conjunction with the track [41]. The width 
of the track ranges from 1 to 4mm [1, 50]. The length is 
4 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 Leung et al. 
highly variable and may reach 20cm in length [10, 16, 40]. 
The lesion is intensely pruritic [42]. The track created by the 
migrating larva desiccates with time after the death of the 
parasite and is covered with a scab [10]. 
 Sites of predilection include the ankles, feet, legs, but-
tocks, and thighs [1, 2, 35]. Basically, any part of the body 
which has direct contact with the contaminated soil/sand can 
be affected. Unusual sites include the face [51], scalp [5], 
upper extremities [52], trunk [52], abdomen [11, 42], breast 
[30], oral cavity [30], genitalia [1, 7, 53], and the perineal 
areas [54]. Lesions are usually unilateral and solitary [35], 
but may be bilateral and multiple [30]. Most affected indi-
viduals have one to three lesions [18]. Rarely, affectedindi-
viduals have hundreds of lesions [27]. 
 Follicular cutaneous larva migrans, also known as hook-
worm folliculitis, is a clinical variant and accounts for less 
than 5% of cases [18]. In contrast to the classical form, this 
variant is more common in adults than in children [50]. The 
condition is characterized by numerous (20 to 100), intensely 
pruritic, erythematous, follicular papules that are sometimes 
surmounted or topped with vesicles or pustules with or with-
out a serpiginous or linear track [18, 38, 50, 55]. The track, if 
present, is usually short [18]. Characteristically, a hair shaft 
is generally not seen in the center of the papule [56]. Nodular 
lesions have also been described [50, 57, 58]. Sites of predi-
lection include the buttocks, inguinal regions, forearms, ab-
domen, back, flanks, and thighs [10, 29, 50]. It is believed 
that the condition is due to invasion of the larva through the 
hair follicular canal and the folliculitis results from an aller-
gic reaction to the larva [55, 59]. Follicular cutaneous larva 
migrans is more resistant to treatment because the larva is 
located deep in the hair follicle [50, 60]. 
Bullous cutaneous larva migrans is another clinical vari-
ant which is quite rare [6, 61-64]. The bulla occurs along a 
track, contains a clear serous fluid, and may reach several 
centimeters in diameter [50, 61, 63]. Presumably, bullae may 
result from a delayed hypersensitivity or contact dermatitis 
(be it irritant or allergic) to larval antigens or lytic enzymes 
released by the larva [6, 62, 63]. 
7. DIAGNOSIS 
 The diagnosis is mainly clinical, based on the history of 
travel to an endemic area and exposure to contaminated 
soil/sand and the characteristic serpiginous track. Unfortu-
nately, the initial diagnosis is correct in less than 50% of 
cases [65, 66]. 
8. DIAGNOSTIC STUDIES 
 The diagnosis can be aided by dermoscopy which typi-
cally shows translucent, brownish, structureless areas in a 
segmental arrangement corresponding to the body of the 
larva and red-dotted vessels corresponding to an empty bur-
row [35, 67]. However, dermoscopy fails to identify the 
larva in a significant number of cases [33]. Near-infrared 
fluorescence imaging of the lesion gives a better yield [33]. 
Confocal scanning laser microscopy may also be used to 
detect the highly refractile larva and a dark disruption in the 
normal honeycomb epidermis corresponding to the burrow 
[35, 68]. Laboratory investigations such as eosinophil count 
in the peripheral blood and serum IgE levels are usually not 
helpful in making the diagnosis [29, 56]. Biopsy is usually 
not necessary or helpful as the larva is usually 1 to 2cm 
ahead of the advancing end of the visible serpiginous track 
[18, 35, 42]. Should a biopsy be obtained 1 to 2cm ahead of 
the visible serpiginous track and the larva (PAS-positive) be 
found, the larva is usually seen residing in a hair follicle, or 
more often, in a suprabasalar burrow within the epidermis 
along with an eosinophilic infiltrate, spongiosis, and intra-
epidermal vesiculation with necrotic keratinocytes [30, 59, 
69]. Suffice to say, a skin biopsy has low sensitivity and it is 
difficult to identify the larva in a biopsy specimen [40]. In 
one study, the larvae were found in 8 of 300 biopsy speci-
mens [70]. As such, the species of animal hookworm causing 
the cutaneous larva migrans in individual cases is usually 
unknown. 
9. DIFFERENTIAL DIAGNOSIS 
 The differential diagnosis includes larva currens 
(strongyloidiasis), migratory (creeping) myiasis, loiasis, cer-
carial dermatitis, gnathostomiasis, dirofilariasis, dracunculia-
sis, tungiasis, scabies, herpes zoster; tinea corporis, contact 
dermatitis, and bacterial folliculitis [2, 45, 71-76]. 
 Larva currens (strongyloidiasis), caused by Strongyloides 
stercoralis, is characterized by a rapidly migrating urticarial 
or maculopapular, pruritic, linear or serpiginous, eruption 
[40]. The eruption usually starts in the perineum and then 
spreads to the buttocks and thighs [40]. The larva migrates at 
a rate of 5 to 15 centimeters per hour, hence the name "run-
ning" larva [18, 77-79]. In contrast, the dog or cat hookworm 
larva seen in cutaneous larva migrans typically migrates 
much less quickly at a rate of 2mm to 2cm per day, depend-
ing on the species of the larva [2, 40, 41]. 
Fig. (1). A 35-year-old man with cutaneous larva migrans on the 
left leg. Note the serpiginous tracks. 
Cutaneous Larva Migrans Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 5
 Migratory (creeping) myiasis is caused by larvae of the 
horse (Gasterophilus intestinalis) and cattle (Hypoderma 
ovis and Hypoderma lineatum) bot flies [80, 81]. Migratory 
myiasis caused by G. intestinalis presents with a superficial 
serpiginous track. Compared to cutaneous larva migrans, 
migratory myiasis moves more slowly and the serpiginous 
track is less widespread [81, 82]. Migratory myiasis caused 
by H. ovis and H. lineatum is deeper and presents with tender 
subcutaneous nodules in the absence of a serpiginous track 
[45, 81]. 
 Loiasis, caused by the filarial nematode Loa loa, is 
transmitted to humans through the bites of deerflies of the 
genus Chrysops [83]. Clinically, loiasis may present as visi-
ble movement of the adult worm under the conjunctiva of the 
eye (hence the name "eye worm") and migratory angioedema 
known as Calabar swellings [84, 85]. Calabar swellings, pre-
sumably due to a hypersensitivity reaction to the migrating 
larva, occur predominately on the legs and arms and are of-
ten associated with localized and/or generalized pruritus [83, 
84]. The swellings can last from hours to several days [78]. 
 Cercarial dermatitis (swimmer's itch) follows penetration 
of the human skin by cercariae of nonhuman schistosome 
flukes [86]. Clinically, cercarial dermatitis presents as an 
intensely pruritic maculopapular rash within hours to a day 
after exposure to water contaminated with schistosomes re-
leased from infected snails. Typically, the rash is non-
migratory which helps to distinguish it from cutaneous larva 
migrans [45]. 
 Gnathostomiasis, also known as larva migrans profundus, 
is caused by the infective third stage larva of Gnathostoma 
species, notably G. spinigerum and G. bispidum [32, 87]. 
Humans acquire the infestation after consuming inadequately 
cooked fish, shellfish or amphibians that contain the infec-
tive larvae [32, 88]. The cutaneous variant presents with in-
termittent migratory cutaneous or subcutaneous swellings or 
nodules [87]. In contrast to cutaneous larva migrans, the le-
sions are usually deeper and may involve muscles [89]. 
 Dirofilariasis is caused by the zoonotic filarial worms of 
the Dirofilaria species, notably D. repens and D. tenuis; the 
natural hosts of which are dogs and wild canines [90]. When 
mosquitoes feed on the infected animal, the microfilariae are 
ingested with the blood meal [91]. Humans acquire the infec-
tion via bites from mosquitoes carrying the infective microfi-
lariae [91]. The larva wanders in the subcutaneous tissue and 
produces an asymptomatic, non-migratory, subcutaneous 
nodule [90]. Sites of predilection include the extremities, 
head, and neck [90]. 
 Dracunculiasis, also known as guinea-worm disease, is 
caused by drinking water contaminated with parasite-
infected water-fleas (Cyclops species) that have ingested 
guinea-worm larvae (Dracunculus medinensis). After matu-
ration into adult worms and copulation, the male worms die 
and the female worms migrate in the subcutaneous tissue 
towards the skin surface [92]. Clinically, subcutaneous 
dracunculiasis presents as a painful papule, most commonly 
on the lower extremities but may occur on the genitalia and 
buttocks. Worms may emerge from the papule. 
 Tungiasis is an ectoparasitic infestation caused by the 
penetration of the gravid female sand flea Tunga penetrans
into the skin [93]. Both female and male fleas are hemato-
phagous[93]. The male flea dies after copulation while the 
female flea burrows into the human epidermis where it 
grows as large as 10mm in diameter as its fertilized eggs 
mature. Clinically, the condition presents as a non-migratory 
papule or nodule with a central black dot. The latter repre-
sents the ano-genital opening of the female flea through 
which she expels feces and passes eggs [93]. The lesion can 
be asymptomatic, painful, or pruritic [93, 94]. The majority 
of the lesions are located on the feet. 
 Scabies is a skin infestation caused by the parasite mite 
Sarcoptes scabiei var hominis. Clinically, scabies is charac-
terized by burrows, an erythematous papular eruption, and 
intense pruritus [76]. Burrows, which are pathognomonic of 
the disease, appear as serpiginous grayish, whitish, reddish, 
or brownish lines several millimeters long in the upper epi-
dermis [76]. Sites of predilection include the interdigital web 
spaces and flexor aspects of wrists. 
 Occasionally, cutaneous larva migrans, especially the 
bullous variant, can mimic herpes zoster [88, 95]. Clinically, 
herpes zoster is characterized by a painful, unilateral vesicu-
lar eruption in a restricted dermatomal distribution. Herpes 
zoster has a predilection for areas supplied by the cervical 
and sacral dermatomes in young children and the lower tho-
racic and upper lumbar dermatomes in adults [72, 73, 75]. 
On the other hand, the eruption seen in cutaneous larva mi-
grans is intensely pruritic rather than painful, is more com-
mon in the lower extremities and buttocks, does not follow 
any dermatome, and progresses in an unpredictable manner 
resulting in the formation of a serpiginous track. 
 Tinea corporis refers to a superficial fungal infection of 
the skin most often caused by Trichphyton rubrum, T. ton-
surans, and Microsporum canis [74]. Typically, tinea cor-
poris presents as a sharply circumscribed, well-demarcated, 
annular, erythematous plaque with a raised leading edge and 
scaling [74]. The border can be papular, vesicular, or pustu-
lar. The lesion spreads centrifugally and clears centrally to 
form the characteristic lesion commonly known as “ring-
worm” [74]. Tinea corporis tends to be asymmetrically dis-
tributed. When multiple lesions are present, they may be-
come coalescent. Mild pruritus is common. 
 Contact dermatitis results from either exposure to aller-
gens (allergic contact dermatitis) or irritants (irritant contact 
dermatitis). Typically, the lesion is eczematous and occurs 
only in an area which has been in contact with the irritant or 
allergen agent. It does not have a serpiginous appearance. 
 Follicular cutaneous larva migrans should be differenti-
ated from bacterial folliculitis. Bacterial folliculitis typically 
presents as follicular, erythematous, maculopapules and fol-
licular pustules in a hair-bearing area. A hair shaft may be 
seen at the center of the lesion. The lesions may be painful, 
tender or mildly pruritic. In contrast, follicular cutaneous 
larva migrans is intensely pruritic and a hair shaft is not seen 
in the center of the lesion [56]. Unlike bacterial folliculitis, 
follicular cutaneous larva migrans does not respond to anti-
biotic therapy. 
10. COMPLICATIONS 
 Pruritus may cause sleep disturbance [27, 31]. Repeated 
scratching may lead to excoriation and secondary bacterial 
6 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 Leung et al. 
infection and eczematization [17, 27, 45]. Localized and/or 
generalized allergic reactions are among other complications. 
In previously sensitized individuals, erythema multiforme 
may occur [29]. The psychosocial consequences can be sig-
nificant and may have an adverse effect on the quality of life 
[31, 96]. 
 Rarely, cutaneous larva migrans may be complicated by 
optic disease edema and Löffler syndrome [45, 97]. Löffler 
syndrome is characterized by migratory pulmonary eosino-
philic infiltrates and peripheral blood eosinophilia [98, 99]. 
Affected patients may present with fever, malaise, cough, 
substernal discomfort, and blood-tinged sputum containing 
Charcot-Leyden crystals [98]. Löffler syndrome is consid-
ered as a type 1 hypersensitivity reaction to the larva or its 
soluble antigen [45, 64, 98, 99]. 
11. PROGNOSIS 
 The prognosis is excellent [17, 41]. The disease is self-
limited and usually resolves in weeks to months even with-
out treatment [18, 41]. Rarely, the larva may persist in the 
hair follicle for up to two years [18, 52, 55]. 
12. MANAGEMENT 
 Treatment is often necessary to shorten the course of the 
disease because of the intense pruritus and potential compli-
cations associated with the disease [17]. Untreated, the pruri-
tus may last for 3 months or even longer [100]. Appropriate 
treatment hastens resolution of the lesion and the associated 
symptoms and reduces the likelihood of complications. 
Compared with oral antihelminthics, topical treatment over 
the affected area is less effective since the larva is mobile 
and the exact location of the larva is not precisely known 
[40, 101]. 
12.1. Oral Antihelmintic Agents 
Oral Ivermectin: Ivermectin (Stromectol, Mectizan, 
Revectina, Ivermec), a macrocyclic lactone, is a semisyn-
thetic avermectin derived from the bacterium Streptomyces 
avermitilis [99]. William Campbell and Satoshi Omura were 
credited for the development of avermectin and ivermectin 
and were awarded the Nobel Prize in Medicine in 2015 [102-
104]. The medication works by stimulating excessive release 
of neurotransmitters in the peripheral nervous system and 
increasing the permeability of cell membrane of the 
helminth, resulting in the paralysis and death of the helminth. 
Oral ivermectin in a single dose of 12mg in adults (150 to 
200mcg/kg in children, maximum 12mg) is the treatment of 
choice for cutaneous larva migrans [10, 18, 15, 29, 35]. The 
medication should be given on an empty stomach with water. 
If a single dose does not result in much improvement, a sec-
ond dose should be given [15]. As follicular cutaneous larva 
migrans is more resistant to treatment, adult patients should 
be treated with 12mg (150 to 200mcg/kg in children; 12mg, 
maximum) of ivermectin twice a day for several days [18, 
60]. Side effects include anorexia, nausea, vomiting, ab-
dominal pain, constipation, dizziness, xerosis, burning skin, 
flushing, eye pain, red eye, transient tachycardia, and hy-
potension. Oral ivermectin is contraindicated during preg-
nancy, in children under 5 years of age or less than 15kg, and 
in those with hepatic or renal disease [10, 15, 105]. The 
medication should be avoided in breastfeeding mothers. 
Oral Albendazole: Chemically, albendazole (Eskazole; 
Albenza, Andazol, Alworm, Noworm, Alben-G, ABZ, Cida-
zole, Zentel) is methyl 5-(propylthio)-2-benzimidazole car-
bamate. The medication works by causing degeneration in 
the intestinal cells of the helminth by binding to the colchi-
cine-sensitive cells of tubulin, thereby preventing its polym-
erization into microtubules [27]. This in turn leads to im-
paired uptake of glucose by the helminth, and ultimately, to 
its death [27]. 
 In case oral ivermectin is not available, not tolerated, or 
ineffective, oral albendazole is a treatment option [100]. The 
medication is usually given at a dose of 10 to 15mg/kg (800 
mg, maximum) divided into 2 doses for 3 to 5 days [18, 35, 
100]. The optimal duration of treatment has not been estab-
lished as 1 to 7 days of treatment has also been recom-
mended [10, 28]. Some authors suggest a 7-days course of 
treatment for patients with multiple and extensive lesions 
and for those with Löffler syndrome [35, 106]. The medica-
tion should be taken with meals. Side effects include nausea, 
vomiting, abdominal pain, dizziness, headache, reversible 
thinning of hair or hair loss, fever, rash, increased intracra-
nial pressure, bone marrow suppression, and hepatic dys-
function. Oral albendazole is contraindicated during preg-
nancyand in those with hematologic or hepatic disease [15, 
104]. The medication should be avoided in breastfeeding 
mothers. 
 In an open study, Caumes et al. compared the efficacy of 
single doses of oral ivermectin (12mg) and oral albendazole 
(400mg) for the treatment of cutaneous larva migrans [107]. 
Twenty one patients were randomized to receive ivermectin 
(n = 10) and albendazole (n = 11). The authors found that the 
all 10 patients who received oral ivermectin responded and 
none relapsed. On the other hand, 10 of the 11 patients who 
received oral albendazole responded, but 5 of the 10 patients 
who responded to oral albendazole relapsed after a mean of 
11 days (range, 3 to 35 days). Caumes et al. concluded that a 
single oral dose of 12mg of ivermectin is more effective than 
a single oral dose of 400mg of albendazole for the treatment 
cutaneous larva migrans. 
 Oral Thiabendazole: Thiabendazole (Mintezol) is a 
benzimidazole derivative with antihelminthic property. 
Thiabendazole works by inhibiting the helminth-specific 
mitochondrial enzyme fumarate reductase, thereby inhibiting 
the citric acid cycle, mitochondrial respiration and subse-
quent production of ATP, ultimately leading to the death of 
the helminth. Oral thiabendazole at doses of 25 to 
50mg/kg/day (2.5g/day, maximum) given twice daily for 2 to 
5 days is effective in the treatment of cutaneous larva mi-
grans [27, 29, 79]. The tablet formulation must be chewed 
before swallowing and taken after meals. Side effects are 
common and include anorexia, nausea, vomiting, abdominal 
cramps, diarrhea, blurred vision, dizziness, and headaches 
[10]. The medication is contraindicated during pregnancy. 
Because of the high incidence of side effects and poor toler-
ance, the medication is no longer recommended for the 
treatment of cutaneous larva migrans [10, 29, 31]. The medi-
cation has been taken off the market in many countries in-
cluding Canada and the United States. 
Cutaneous Larva Migrans Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 7
12.2. Topical Antihelmintic Agents 
Topical Albendazole: Topical albendazole 10% in a 
lipophilic base applied under occlusion three to four times a 
day for 5 to 10 days may be considered for patients with lo-
calized lesion in whom oral antihelminthics are contraindi-
cated or not tolerated [10, 15]. It is a reasonable alternative 
for young children and pregnant women. Side effects include 
irritant contact dermatitis and skin ulceration. 
 Topical Thiabendazole: Topical thiabendazole 10 to 
15% in a lipophilic base applied under occlusion three to 
four times a day for 5 to 10 days may be considered for pa-
tients with localized lesion in whom oral antihelminthics are 
contraindicated or not tolerated [10, 15]. It is a reasonable 
alternative for young children and pregnant women. Side 
effects include irritant contact dermatitis and skin ulceration. 
12.3. Cryotherapy 
 Prior to the availability of antihelminthics, cryotherapy 
with liquid nitrogen was at one time used for the treatment of 
cutaneous larva migrans. Cryotherapy is not very effective as 
the location of the larva is not precisely known; the larva is 
usually found a few centimeters ahead of the advancing visi-
ble end of the lesion. Also, it has been shown that the larva 
can survive temperatures as low as -21ºC for more than 5 
minutes [27, 31]. In addition, the procedure is painful. As 
such, cryotherapy is no longer routinely recommended for 
the treatment of cutaneous larva migrans except for patients 
in whom oral antihelminthics are contraindicated (e.g., preg-
nancy) or not tolerated [29]. 
12.4. Fractional Carbon Dioxide Laser 
 Recently, it has been shown that a single session of 1 to 4 
passes of fractional carbon dioxide laser up to 1 to 2cm pe-
rimeter around the erythematous portion of the serpiginous 
track is effective in the treatment of cutaneous larva migrans 
[108]. In one study, ten cases (eight patients) with cutaneous 
larva migrans were treated with one session of carbon diox-
ide laser treatment and followed up daily for the first week 
with photographic documentation and then weekly for the 
next 3 weeks to complete a 4 week follow-up period. The 
first case received one to two passes of fractional CO2 laser, 
experienced further larval migration for 2 to 3 days, after 
which no more progression was noted. For the next seven 
cases, the authors increased the number of CO2 laser passes 
to 3 to 4, and noted no further larval migration. At the end of 
the 4-week follow-up period, all CO2 laser-treated areas were 
completely healed [108]. 
 Confocal scanning laser microscopy can be used to detect 
the larva, thereby increases the success rate of fractional car-
bon dioxide laser. Fractional carbon dioxide laser works ei-
ther by destroying the larva directly or that the microthermal 
zones produced by the laser halt the migration of the larva 
[108]. The ideal number of passes of fractional carbon diox-
ide laser required to effectively control cutaneous larva mi-
grans has to be determined. 
12.5. Miscellaneous 
 Systemic antihistamines and topical corticosteroid may 
be considered to provide symptomatic relief of itchiness 
[15]. Secondary bacterial infection may require treatment 
with appropriate antibiotics. 
13. PREVENTION 
In endemic areas, preventative measures include periodic 
deworming of dogs and cats and banning them from beaches 
and playgrounds, disposing the waste products of dogs and 
cats properly, wearing proper footwear while walking on the 
beach, using towels, mattresses and deckchairs on the beach, 
and avoiding lying or sitting directly on the sand/soil [29, 
79]. Sandpits that children play with should be protected 
from dogs and cats [27]. Gloves should be worn when 
soil/sand is handled. 
CURRENT & FUTURE DEVELOPMENTS 
 Current methods for diagnosis of hookworm infections 
primarily involve microscopic examination of fecal samples, 
either directly in fecal smears or following concentration of 
ova by flotation in density media. Despite this procedure is 
popular and in common use, the methods have significant 
shortcomings. These microscopic methods are time-
consuming, are unpleasant, require specialized equipment, 
and can have low specificity having have to rely heavily on 
the skill and expertise of the operator. Geng and Elsemore 
disclosed methods, devices, kits and compositions for detect-
ing more accurately the presence of hookworm such as Ancy-
lostoma caninum and Ancylostoma braziliense in a fecal 
sample by using one or more antibodies that specifically bind 
to a polypeptide present in hookworm coproantigen [109]. 
These methods would allow early diagnosis and treatment of 
the infected animal and efficient follow-up to determine 
whether the animal has been rid of the infestation after 
treatment has been initiated, thereby minimizing the risk of 
cutaneous larva migrans. 
 The drugs currently used against hookworms have limita-
tions as they are contraindicated during pregnancy, in very 
young children, and in those with certain systemic diseases, 
making new drugs highly desirable. Eickhoff et al. patented 
an invention comprising of pyrazolo-triazine derivatives 
and/or pharmaceutically acceptable salts thereof for the 
treatment of infectious diseases including cutaneous larva 
migrans [110]. The pharmaceutical compositions or formula-
tions comprise at least one compound as an active ingredient 
together with at least one pharmaceutically acceptable (i.e. 
non-toxic) carrier, excipient and/or diluent. The preferred 
preparations are adapted for oral administration. Spangen-
berg disclosed an invention comprising of azepanyl deriva-
tives for the treatment of parasitic diseases including cutane-
ous larva migrans [111]. Pharmaceutical formulations ac-
cording to the invention can be adapted for oral as well as 
topical administration. Levine et al. disclosed a method of 
treating or ameliorating skinlesions as may result from cuta-
neous larva migrans by periodically applying to the skin a 
composition comprising: an effective amount of an appropri-
ate composition of herbal bioactive comprising active(s) of 
one or more of Sambucus nigra, Centella asiatica or Echina-
cea purpurea, and an effective amount of a quaternary am-
monium surfactant [112]. At the moment, it is not sure 
whether these new medications have the same contraindica-
tions as the existing ones. Also, their efficacy and adverse 
8 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 Leung et al. 
effects are not known. Comparative studies on the effective-
ness of drugs in the treatment of cutaneous larva migrans are 
few and they are not randomized, double-blind, and placebo-
controlled. It is hoped that future well-designed, large-
scaled, randomized, double-blind, and placebo-controlled 
studies will provide us with more information on the efficacy 
and optimal regimen of the various antihelminthics including 
the present ones and those in development. 
 The cost of antihelminthics may, to certain extent, limit 
its access to patients especially those in developing coun-
tries. By bringing the production cost down, the medication 
would be made available to more patients. Traditionally, in 
the preparation of albendazole, 2-nitroaniline is thiocyanated 
to obtain 2-nitro-4-thiocyanoaniline, then alkylated with n-
propylbromide in the presence of n-propanol and methyl 
tributyl ammonium chloride or the tetrabutyl ammonium 
bromide as the phase-transfer catalyst and an alkali metal 
cyanide or alkaline metal cyanide to generate 4-propylthio-2-
nitroaniline. 4-Propylthio-2-nitroaniline is reduced by so-
dium sulphide monohydrate in the presence of water to ob-
tain 4-propylthio-O-phenylenediamine. This diamine is fur-
ther reacted with sodium salt of methyl-N-cyano carbamate 
to obtain the albendazole. In this process, phase transfer cata-
lyst as well as an alkali metal cyanide or alkaline metal cya-
nide is used for condensation of 2-nitro-4-thiocyanoaniline 
with n-propylebromide, which adds to the cost of production, 
increases the organic material content in effluent and may 
facilitate the formation of impurity and uses toxic cyanide 
compound. The reduction of 4-propylthio-2-nitroaniline is 
done in the presence of water as a solvent which makes the 
reaction sluggish. Thus it is highly desirable to develop a 
process which overcomes most of the drawbacks of the prior 
process. Rane et al. disclosed a novel, cost-effective and 
environment friendly process for preparation of albendazole 
which overcomes most of the above stated drawbacks [113]. 
The process comprises a) thiocyanating 2-nitroaniline of 
formula VI with ammonium thiocyanated in presence of a 
halogen to obtain 2-nitro-4-thiocyanoaniline of formula V; b) 
propylating 2-nitro-4-thiocyanoaniline of formula V with 
propylbromide in presence of n-propanol and a base in ab-
sence of a phase transfer catalyst to obtain 4-propylthio-2-
nitroaniline of formula III; C) reducing the nitro group of 4-
propylthio-2-nitroaniline prepared in step b) by reacting an 
aqueous alkali metal sulphide or an alkaline metal sulphide 
to obtain 4-propylthio-O-phenylenediamine of formula II; 
and d) condensing 4-propylthio-O-phenylenediamine of for-
mula II with alkali or alkaline earth metal salt of methyl-
cyano carbamate in presence of an acid to form albendazole. 
 Pruritus due to cutaneous larva migrans can be severe 
resulting in sleep disturbance. Currently, systemic antihista-
mines and topical corticosteroid can be used to provide 
symptomatic relief of pruritus [15]. Zhang et al. disclosed a 
method of treating pruritus, comprising administering a 
therapeutically effective amount of 3-[(3aR,4R,5S,7aS)-5-
[(1R)-1-[3,5-bis (trifluoromethyl) phenyl] ethoxy]-4-(4-
fluorophenyl)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl] cy-
clopent-2-en-1-one (serlopitant) or a pharmaceutically ac-
ceptable salt, solvate or polymorph thereof to a patient in 
need of treatment [114]. The invention provides a method for 
treating chronic pruritus using serlopitant or a pharmaceuti-
cally acceptable salt or hydrate thereof. Serlopitant has pre-
viously been disclosed as a neurokinin-1 (NK-1) receptor 
antagonist, an inhibitor of tachykinin and, in particular, of 
substance P. Compositions for oral and topical administra-
tion are available. Ji et al. disclosed a method of treating 
pruritus resulting from, but not limited to, cutaneous larva 
migrans with superoxide dismuate (SOD) mimetic [115]. 
The SOD mimetic can be a complex of a metal (e.g., manga-
nese) and an organic ligand, with suitable organic ligands 
including porphyrins, polyamines, salens, nitroxides, and 
fullerenes. The invention can be given orally, parenterally, or 
topically. Kaspar and Speaker disclosed methods of treating 
pain and/or itch in a targeted region of a subject [116]. Such 
methods include topically administering a therapeutically 
effective amount of an mTOR pathway inhibitor to the sub-
ject. An mTOR is a serine/threonine kinase that regulates 
translation and cell division. The mTOR inhibitor in this 
invention is rapamycin (Sirolimus) or an analogue thereof. 
Rapamycin is a macrocyclic lactone produced by the organ-
ism Streptomyces hydroscopicus. The investigators claim 
that the invention is effective in the symptomatic treatment 
of intense pruritus associated with cutaneous larva migrans. 
These new anti-pruritic medications will offer readers and 
patients another therapeutic option for the treatment of pruri-
tus. 
 Worldwide, cutaneous larva migrans affects millions of 
individuals. Effective vaccines against hookworms would be 
the best way to lower the abundance of hookworm infesta-
tions. Currently no such vaccines exist. Schwarz et al. dis-
closed a method for preventing or treating a hookworm in-
fection in an animal, comprising administering to the animal 
a composition comprising either an antigen or a nucleic acid 
encoding the antigen, wherein the antigen comprises an 
amino acid sequence comprising at least 10 consecutive 
amino acids encoded by an open reading frame in any one of 
SEQ ID NOS: 1-540 [117]. This invention may be for use in 
manufacturing a vaccine. It is hoped that effective hook-
worm vaccines may be available in the future. 
CONCLUSION 
 Cutaneous larva migrans is a zoonotic infestation caused 
by penetration and migration in the epidermis of filariform 
larva of different kinds of animal hookworms through con-
tact with feces of infected animals, mostly dogs and cats. 
Clinically, it is characterized by a pruritic erythematous mi-
grating tortuous or serpiginous, slightly raised track. The 
condition is common in individuals residing in tropical and 
subtropical regions. It is the most common ectoparasitosis 
acquired by travelers returning from those regions. Because 
of the increasing incidence of foreign travel, cutaneous larva 
migrans is no longer confined to endemic regions. Western 
physicians should familiarize themselves with this condition 
so that a correct diagnosis can promptly be made and treat-
ment initiated. Clinically, the condition is characterized by a 
pruritic erythematous migrating tortuous or serpiginous, 
slightly raised track which is pathognomonic. 
 Compared with oral antihelminthics, topical treatment 
over the affected area is less effective since the larva is mo-
bile and the exact location of the larva is not precisely 
known. Unfortunately, the two available oral antihelminthics
(ivermectin and albendazole) are contraindicated during 
pregnancy and should be avoided in breastfeeding mothers. 
Cutaneous Larva Migrans Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1 9
It is hoped that future medications may circumvent these 
problems. 
CONSENT FOR PUBLICATION 
 Not applicable. 
CONFLICT OF INTEREST 
Prof. Leung, Dr. Barankin, and Prof. Hon disclose no 
relevant financialrelationship.
ACKNOWLEDGEMENTS 
 Prof. Alexander K.C. Leung is the principal author. Dr. 
Benjamin Barankin and Professor Kam Lun Hon are co-
authors who contributed and helped with the drafting of this 
manuscript. The authors would like to thank Dr. Kin Fon 
Leong for providing them with the photo image on his pa-
tient with cutaneous larva migrans.
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https://www.researchgate.net/publication/312302631
	Cutaneous Larva Migrans
	Abstract:
	Keywords:
	INTRODUCTION
	EPIDEMIOLOGY
	CAUSATIVE ORGANISMS
	DISEASE TRANSMISSION
	PATHOPHYSIOLOGY
	CLINICAL MANIFESTATIONS
	DIAGNOSIS
	DIAGNOSTIC STUDIES
	Fig. (1).
	DIFFERENTIAL DIAGNOSIS
	COMPLICATIONS
	PROGNOSIS
	MANAGEMENT
	PREVENTION
	CURRENT & FUTURE DEVELOPMENTS
	CONCLUSION
	CONSENT FOR PUBLICATION
	CONFLICT OF INTEREST
	ACKNOWLEDGEMENTS
	REFERENCES