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Recent Patents on Inflammation & Allergy Drug Discovery 2017, 11, 2-11
REVIEW ARTICLE
Cutaneous Larva Migrans
Inflammation
& Allergy
Drug Discovery
Discovery
 1,* 2 3
Alexander K.C. Leung , Benjamin Barankin and Kam L.E. Hon

1
Department of Pediatrics, The University of Calgary, Alberta Children’s Hospital,
2
Calgary, Alberta, Canada; Toronto Dermatology Centre, Toronto, Ontario, Canada;
3
Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong
& Allergy Drug
ART IC LE H I ST O RY

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.
Recent Patents on Inflammation
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 – 16 th 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 course leads 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
2212 -2710/17 $100.00+.00 © 2017 Bentham Science
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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.
Fig. (1). A 35-year-old man with cutaneous larva migrans on the left leg. Note the serpiginous tracks.

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, affected indi-
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].
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-nancy and 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 CO 2 laser passes to 3
to 4, and noted no further larval migration. At the end of the 4-week follow-up period, all CO 2 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 skin lesions 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 financial relationship.

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.

REFERENCES
[1] Benardon S, Ramoni S, Boneschi V, Cusini M, Veraldi S. Multifo-cal perigenital cutaneous larva migrans. G Ital Dermatol
Venereol 2014; 149(4): 477-9.
[2] Dhanaraj M, Ramalingam M. Cutaneous larva migrans masquerad-ing as Tinea corporis: A case report. J Clin Diagn Res
2013; 7(10): 2313.
[3] Lee R. Case of creeping eruption. Trans Clin Soc Lond 1974; 8: 44-5.
[4] Crocker HR. Diseases of The Skin. 2nd ed. Philadelphia: The Blakiston Company 1893; pp. 926-7.
[5] Meotti CD, Plates G, Nogueira LL, da Silva RA, Paolini KS, Nunes EM, et al. Cutaneous larva migrans on the scalp:
Atypical presenta-tion of a common disease. An Bras Dermatol 2014; 89 (2): 332-3.
[6] Morrone A, Franco G, Fazio R, Valenzano M, Calcaterra R. Bullous cutaneous larva migrans. Acta Dermatovenerol Croat
2011; 19(2): 120-1.
[7] Sugathan P, Bhagyanathan M. Cutaneous larva migrans: Presenta-
tion at an unusual site. Indian J Dermatol 2016; 61(5): 574-5.
[8] Caumes E, Danis M. From creeping eruption to hookworm-related cutaneous larva migrans. Lancet Infect Dis 2004; 4: 659-
60.
[9] Feldmeier H, Schuster A. Mini review: Hooked worm related cuta-neous larva migrans. Eur J Clin Microbiol Infect Dis 2012;
31: 915-8.
[10] Tekely E, Szostakiewicz B, Wawrzycki B, Kadziela-Wypyska G, Juszkiewicz-Borowiec M, Pietrzak A, et al. Cutaneous larva
mi-grans syndrome: A case report. Postep Derm Allergol 2013; 30(2): 119-21.
[11] Padmavathy L, Rao L. Cutaneous larva migrans - a case report. Indian J Med Microbiol 2005; 23(2): 135-6.
[12] Heukelbach J, Jackson A, Ariza L, Feldmeier H. Prevalence and risk factors of hookworm-related cutaneous larva migrans in
a rural community in Brazil. Ann Trop Med Parasitol 2008; 102(1): 53-61.
[13] Lederman ER, Weld LH, Elyazar IR, von Sonnenburg F, Loutan L, Schwartz E, et al. Dermatologic conditions of the ill
returned trav-eler: An analysis from the GeoSentinel Surveillance Network. Int J Infect Dis 2008; 12(6): 593-602.
[14] Jelinek T, Maiwald H, Nothdurft HD, Loscher T. Cutaneous larva migrans in travelers: Synopsis of histories, symptoms, and
treat-ment of 98 patients. Clin Infect Dis 1994; 19(6): 1062-6.
[15] Sunderkotter C, von Stebut E, Schofer H, Mempel M, Reinel D, Wolf G, et al. S1 guideline diagnosis and therapy of
cutaneous larva migrans (creeping disease). J Dtsch Dermatol Ges 2014; 12(1): 86-91.
[16] Veraldi S, Persico MC, Francia C, La Vela V. Appearance of a reservoir of hook-worm-related cutaneous larva migrans in
Brit-tany? G Ital Dermatol Venereol 2012; 147(6): 649-52.
[17] Shahmoradi Z, Abtahi-Naeini B, Pourazizi M, Meidani M. Creep-ing eruption of the hand in an Iranian patient: Cutaneous
larva mi-grans. Adv Biomed Res 2014; 3: 263.
[18] Weller PF, Leder K. Hookworm-related cutaneous larva migrans. In: Post TW, Ed. Waltham, MA: UpToDate ® [Accessed on
De-cember 9, 2016].
[19] Beattie PE, Fleming CJ. Cutaneous larva migrans in the west coast of Scotland. Clin Exp Dermatol 2002; 27(3): 248-9.
[20] Diba VC, Whitty CJ, Green T. Cutaneous larva migrans acquired in Britain. Clin Exp Dermatol 2004; 29(5): 555-6.
[21] Klose C, Mravak S, Geb B, Bienzle U, Meyer CG. Autochthonous cutaneous larva migrans in Germany. Trop Med Int Health
1996; 1(4): 503-4.
[22] Malik M, Walker SL. Foreign travel and hookworm-related cuta-neous larva migrans. Br J Dermatol 2015; 172: 819.
[23] Morrone A, Paradisi M, Paradisi A, Valenzano M, Fazio R, Fornari U, et al. Autochthonous creeping eruption in an Italian
child. Am J Clin Dermatol 2008; 9(3): 205-6.
[24] Patterson CR, Kersey PJ. Cutaneous larva migrans acquired in England. Clin Exp Dermatol 2003; 28(6): 671-2.
[25] Roest MA, Ratnavel R. Cutaneous larva migrans contracted in England: A reminder. Clin Exp Dermatol 2001; 26(5): 389-90.
[26] Zimmermann R, Combemale P, Piens MA, Dupin M, Le Coz C. Cutaneous larva migrans, autochthonous in France. Apropos
of a case. Ann Dermatol Venereol 1995; 122(10): 711-4.
[27] Karthikeyan K, Thappa D. Cutaneous larva migrans. Indian J Der-matol Venereol Leprol 2002; 68: 252-8.
[28] Baple K, Clayton J. Hookworm-related cutaneous larva migrans acquired in the UK. BMJ Case Rep 2015.
[29] Kudrewicz K, Crittenden KN, Himes A. A case of cutaneous larva migrans presenting in a pregnant patient. Dermatol Online
J 2015; 21(1): 14.
[30] Siddalingappa K, Murthy SC, Herakal K, Kusuma MR. Cutaneous larva migrans in early infancy. Indian J Dermatol 2015;
60(5): 522.
[31] Quashie NB, Tsegah E. An unusual recurrence of pruritic creeping eruption after treatment of cutaneous larva migrans in an
adult Ghanaian male: A case report with a brief review of the literature. Pan African Med J 2015; 21: 285.
[32] Eichelmann K, Tomecki KJ, Martinez JD. Tropical dermatology: Cutaneous larva migrans, gnathostomiasis, cutaneous
amebiasis and trombiculiasis. Semin Cutan Med Surg 2014; 33: 133-5.
[33] Aljasser M, Lui H, Zeng H, Zhou Y. Dermoscopy and near-infrared fluorescence imaging of cutaneous larva migrans.
Photodermatol Photoimmunol Photomed 2013; 29: 337-8.
[34] Le Joncour A, Lacour SA, Lecso G, Regnier S, Guillot J, Caumes E. Molecular characterization of Ancylostoma braziliense
larvae in a patient with hookworm-related cutaneous larva migrans. Am J Trop Med Hyg 2012; 86: 843-5.
[35] Prickett KA, Ferringer TC. What's eating you? Cutaneous larva migrans. Cutis 2015; 95(3): 126-8.
[36] Kincaid L, Klowak M, Klowak S, Boggild AK. Management of imported cutaneous larva migrans: A case series and mini-
review. Travel Med Infect Dis 2015; 13: 382-7.
[37] Traversa D, di Regalbono AF, Cesare AD, Torre FL, Drake J, Pietrobelli M. Environmental contamination by canine geo-
helminths. Parasit Vectors 2014; 7: 67.
[38] Miller AC, Walker J, Jaworski R, de Launey W, Paver R. Hook-worm folliculitis. Arch Dermatol 1991; 127(4): 547-9.
[39] Garcia-Rodrigo CG, Romero FT, Olivo CZ. Cutaneous larva mi-grans, welcome to a warmer Europe. J Eur Acad Dermatol
Venereol 2016; 31: e33-5.
[40] Belizario V Jr, delos Trinos JP, Garcia NB. Cutaneous manifesta-tions of selected parasitic infections in Western Pacific and
South-east Asian regions. Curr Infect Dis Rep 2016; 18(9): 30.
[41] Ghosh SK, Bandyopadhyay D. Dermacase: Can you identify this condition? Cutaneous larva migrans. Can Fam Physician
2009; 55(5): 489-91.
[42] Purkait R, Das S, Patra S. Cutaneous larva migrans on upper ab-domen: An unusual site. J Coll Phys Surg Pak 2015; 25(9):
710.
[43] Albanese G, Caterina V, Giuseppe G. Treatment of larva migrans cutanea (creeping eruption): A comparison between
albendazole and traditional therapy. Int J Dermatol 2001; 40(1): 67-71.
[44] Gandullia E, Lignana E, Rabagliati AM, Penna R. Visceral larva migrans caused by Ancylostoma caninum. Minerva Pediatr
1981; 33(18): 917-23.
[45] Podder I, Chandra S, Gharami RC. Loeffler's syndrome following cutaneous larva migrans: An
uncommon sequel. Indian J Dermatol 2016; 61(2): 190-2.
10 Recent Patents on Inflammation & Allergy Drug Discovery 2017, Vol. 11, No. 1
[46] Archer M. Late presentation of cutaneous larva migrans: A case
report. Cases J 2009; 2: 7553.
[47] Chris RB, Keystone JS. Prolonged incubation period of hookworm-
related cutaneous larva migrans. J Travel Med 2016; 23(2).
[48] Hochedez P, Caumes E. Hookworm-related cutaneous larva mi-
grans. J Travel Med 2007; 14: 326-33.
[49] Siriez JY, Angoulvant F, Buffet P, Cleophax C, Bourrat E. Individ-
ual variability of the cutaneous larva migrans (CLM) incubation
period. Pediatr Dermatol 2010; 27(2): 211-2.
[50] Veraldi S, Persico MC, Francia C, Nazzaro G, Gianotti R. Follicu-
lar cutaneous larva migrans: A report of three cases and review of
the literature. Int J Dermatol 2013; 52: 327-30.
[51] Chiriac A, Chiriac AE, Pinteala T, Podoleanu C, Coros MF,
Moldovan C, et al. Cutaneous larva migrans in a temperate area.
Arch Dis Child 2016; 101: 813.
[52] Patel S, Aboutalebi S, Vindhya PL. What's eating you? Extensive
cutaneous larva migrans (Ancylostoma braziliense). Cutis 2008;
82(4): 239-40.
[53] Rao R, Prabhu S, Sripathi H. Cutaneous larva migrans of the geni-
talia. Indian J Dermatol Venereol Leprol 2007; 73: 270-1.
[54] Grassi A, Angelo C, Grosso MG, Paradise M. Perianal cutaneous
larva migrans in a child. Pediatr Dermatol 1998; 15: 367-9.
[55] Caumes E, Ly F, Bricaire F. Cutaneous larva migrans with follicu-
litis: Report of seven cases and review of the literature. Br J Der-
matol 2002; 146(2): 314-6.
[56] Ezzedine K, Pistone T. Hookworm folliculitis. CMAJ 2013;
185(4): E213.
[57] Ginsburg B, Beaver PC, Wilson ER, Whitley RJ. Dermatitis due to
larvae of a soil nematode, Pelodera strongyloides. Pediatr Derma-
tol 1984; 2: 33-7.
[58] Veraldi S, Bottini S, Carrera C, Gianotti R. Cutaneous larva mi-
grans with folliculitis: A new clinical presentation of this infesta-
tion. J Eur Acad Dermatol Venereol 2005; 19: 628-30.
[59] Rivera-Roig V, Sanchez JL, Hillyer GV. Hookworm folliculitis. Int
J Dermatol 2008; 47: 246-8.
[60] Vanhaecke C, Perignon A, Monsel G, Regnier S, Bricaire F,
Caumes E. The efficacy of single dose ivermectin in the treatment
of hookworm related cutaneous larva migrans varies depending on
the clinical presentation. J Eur Acad Dermatol Venereol 2014;
28(5): 655-7.
[61] Gupta M. Bullous cutaneous larva migrans - a case report. J Der-
matol Dermatol Surg 2016; 20: 65-6.
[62] Sanchez Fernandez I, Julia Manresa M, Gonzalez Ensenat MA,
Vicente Villa MA. Picture of the month - quiz case. Bullous cuta-
neous larva migrans. Arch Pediatr Adolesc Med 2008; 162(5): 485-
6.
[63] Veraldi S, Arancio L. Giant bullous cutaneous larva migrans. Clin
Exp Dermatol 2006; 31: 613-4.
[64] Wong-Waldamez A, Silva-Lizama E. Bullous larva migrans ac-
companied by Loeffler's syndrome. Int J Dermatol 1995; 34(8):
570-1.
[65] French SJ, Lindo JF. Severe cutaneous larva migrans in a traveler
to Jamaica, West Indies. J Travel Med 2003; 10(4): 249-50.
[66] Supplee SJ, Gupta S, Alweis R. Creeping eruptions: Cutaneous
larva migrans. J Community Hosp Intern Med Perspect 2013; 3(3-
4).
[67] Zalaudek I, Giacomel J, Cabo H, Di Stefani A, Ferrara G,
Hoffmann-Wellenhof R, et al. Entodermatoscopy: A new tool for
diagnosing skin infections and infestations. Dermatology 2008;
216(1): 14-23.
[68] Upendra Y, Mahajan VK, Mehta KS, Chauhan PS, Chander B.
Cutaneous larva migrans. Indian J Dermatol Venereol Leprol 2013;
79(3): 418-9.
[69] Cayce KA, Scott CM, Phillips CM, Frederick C, Park HK. What is
your diagnosis? Cutaneous larva migrans. Cutis 2007; 79(6), 429,
435-6.
[70] Wilson JF. The treatment of larva migrans with Stibanose: A pre-
liminary report. South Med J 1952; 45: 127-30.
[71] Krishna MR. Cutaneous larva migrans. Indian Pediatr 2015; 52:
Leung et al.
[75] Leung AK, Barankin B. Bilateral symmetrical herpes zoster in an
immunocompetent 15-year-old adolescent boy. Case Rep Pediatr
2015; 2015: 121549.
[76] Leung AK, Barankin B, Hon KL. Scabies. Consultant Pediatr 2016;
15: 613-6.
[77] Corte LD, da Silva MV, Souza PR. Simultaneous larva migrans
and larva currens caused by Strongyloides stercoralis: A Case Re-
port. Case Rep Dermatol Med 2013; 381583.
[78] Korzeniewski K, Juszczak D, Jerzemowski J. Skin lesions in re-
turning travellers. Int Marit Health 2015; 66(3): 173-80.
[79] Panés-Rodríguez A, Piera-Tuneu L, López-Pestaña A, Ormaetxea-
Pérez N, Gutiérrez-Támara P, Ibarbia-Oruezabal S, et al. Autoch-
thonous cutaneous larva migrans infection in Guipúzcoa. Actas
Dermosifiliogr 2016; 107(5): 407-13.
[80] Robbins K, Khachemoune A. Cutaneous myiasis: A review of the
common types of myiasis. Int J Dermatol 2010; 49(10): 1092-8.
[81] Solomon M, Lachish T, Schwartz E. Cutaneous myiasis. Curr
Infect Dis Rep 2016; 18(9): 28.
[82] Ting PT, Barankin B. Cutaneous myiasis from Panama, South
America: Case report and review. Cutan Med Surg 2008; 12(3):
133-8.
[83] Kobayashi T, Hayakawa K, Mawatari M, Itoh M, Akao N, Yotsu
RR, et al. Loiasis in a Japanese traveler returning from Central Af-
rica. Trop Med Health 2015; 43(2): 149-53.
[84] Boussinesq M. Loiasis. Ann Trop Med Parasitol 2006; 100(8): 715-
31.
[85] Sanders CJ, Jaspers CA. Onchocerciasis or loiasis? Lancet 2007;
369(9558): 271-2.
[86] Kolá ová L, Horák P, Skírnisson K, Mare ková H, Doenhoff M.
Cercarial dermatitis, a neglected allergic disease. Clin Rev Allergy
Immunol 2013; 45(1): 63-74.
[87] Diaz JH. Gnathostomiasis: An emerging infection of raw fish con-
sumers in gnathostoma nematode-endemic and nonendemic coun-
tries. J Travel Med 2015; 22(5): 318-24.
[88] Malvy D, Ezzedine K, Pistone T, Receveur MC, Longy-Boursier
M. Extensive cutaneous larva migrans with folliculitis mimicking
multimetameric herpes zoster presentation in an adult traveler re-
turning from Thailand. J Travel Med 2006; 13(4): 244-7.
[89] Mukherjee A, Ahmed NH, Samantaray JC, Mirdha BR. A rare case
of cutaneous larva migrans due to Gnathostoma sp. Indian J Med
Microbiol 2012; 30(3): 356-8.
[90] Nath R, Bhuyan S, Dutta H, Saikia L. Human subcutaneous dirofi-
lariasis in Assam. Trop Parasitol 2013; 3(1): 75-8.
[91] Sukumarakurup S, Payyanadan BM, Mariyath R, Nagesh M,
Moorkoth AP, Ellezhuthil D. Subcutaneous human dirofilariasis.
Indian J Dermatol Venereol Leprol 2015; 81(1): 59-61.
[92] Gulanikar A. Dracunculiasis: Two cases with rare presentations. J
Cutan Aesthet Surg 2012; 5(4): 281-3.
[93] Leung AK, Woo T, Robson WL, Trotter MJ. A tourist with tungia-
sis. CMAJ 2007; 177(4): 343-4.
[94] Hakeem MJ, Morris AK, Bhattacharyya DN, Fox C. Tungiasis - a
cause of painful feet in a tropical traveller. Travel Med Infect Dis
2010; 8(1): 29-32.
[95] Creamer A. Widespread skin rash following travel to South-East
Asia. BMJ Case Rep 2014.
[96] Schuster A, Lesshafft H, Talhari S, Guedes de Oliveira S, Ignatius
R, Feldman H. Life quality impairment caused by hookworm-
related cutaneous larva migrans in resource-poor communities in
Manaus, Brazil. PloS Negl Trop Dis 2011; 5(11): e1355.
[97] Dhir L, O'Dempsey T, Watts MT. Cutaneous larva migrans with
optic disc edema: A case report. J Med Case Rep 2010; 4: 209.
[98] Tan SK, Liu TT. Cutaneous larva migrans complicated by Löffler
syndrome. Arch Dermatol 2010; 146(2): 210-2.
[99] Te Booij M, de Jong E, Bovenschen HJ. Löffler syndrome caused
by extensive cutaneous larva migrans: A case report and review of
the literature. Dermatol Online J 2010; 16(10): 2.
[100] Fischer S, Nenoff P. Cutaneous larva migrans: Successful topical
treatment with ivermectin - a case report. J Dtsch Dermatol Ges
2016; 14(6): 622-3.
 177. [101] Veraldi S, Angileri L, Parducci A, Nazzaro G. Treatment of hook-
[72] Leung AK, Rafaat M. Photo quiz. Vesicular rash on the flank and worm-related cutaneous larva migrans with topical invermectin. Int
buttock. Am Fam Physician 2003; 67(5): 1045-6. Dermatol Treat 2017; 28(3): 263.
[73] Leung AK, Robson WL, Leong AG. Herpes zoster in childhood. J [102] Campbell WC. History of avermectin and ivermectin, with notes on
Pediatr Health Care 2006; 20(5): 300-3. the history of other macrocyclic lactone antiparasitic agents. Curr
[74] Leung AK, Barankin B. Tinea corporis. Consultant Pediatr 2014; Pharm Biotechnol 2012; 13: 853-65.
13: 466-9.
Cutaneous Larva Migrans Recent Patents on Inflammation & Allergy Drug
Discovery 2017, Vol. 11, No. 1 11
[103] Campbell WC. Ivermectin: A reflection on simplicity (Nobel lec-
ture). Angew Chem Int Ed Engl 2016; 55(35): 10184-9.
[104] Crump A, Omura S. Ivermectin, 'wonder drug' from Japan: The human use perspective. Proc Jpn Acad Ser Phys Biol Sci
2011; 87(2): 13-28.
[105] Heukelbach J, Winter B, Wilcke T, Muehlen M, Albrecht S, de Oliveira FA, et al. Selective mass treatment with
ivermectin to con-trol intestinal helminthiases and parasitic skin diseases in a severely affected population. Bull World
Health Organ 2004; 82(8): 563-71.
[106] Veraldi S, Bottini S, Rizzitelli G, Persico MC. One-week therapy with oral albendazole in hookworm-related cutaneous
larva mi-grans: A retrospective study on 78 patients. J Dermatol Treat 2012; 23(3): 189-91.
[107] Caumes E, Carriere J, Datry A, Gaxotte P, Danis M, Gentilini M. A randomized trial of ivermectin versus albendazole for
the treatment of cutaneous larva migrans. Am J Trop Med Hyg 1993; 49(5): 641-4.
[108] Soriano LF, Piansay-Soriano ME. Treatment of cutaneous larva migrans with a single session of carbon dioxide laser: A
study of ten cases in the Philippines. J Cosmet Dermatol 2017; 16(1): 91-4.
[109] Geng, J., Elsemore, D.A. Composition, devices, kits and methods for detecting hookworm. US20160145327 (2016).
[110] Eickhoff, J., Zischinsky, G., Koch, U., Rühter, G., Schultz-fademrecht, C., Nussbaumer, P. Pharmaceutically active pyrazolo-
triazine derivatives. US20150111873 (2015).
[111] Spangenberg, T. Azepanyl-derivatives and pharmaceutical compo-sitions comprising the same with antiparasitic activity.
WO2016000827 (2006).
[112] Levine, W.Z., Saffer, A.J., Nussbaum, G. Topical anti-inflammatory combination. US9314491 (2016).
[113] Rane, R.A., Naithani, S., Natikar, R.D., Verma, S., Arulmoli, T. Process for preparation of albendazole. US20130303782
(2013).
[114] Zhang, X., Schnipper, E.F., Perlman, A.J., Larrick, J.W. Use of NK-1 receptor antagonists in pruritus. US20160038462
(2016).
[115] Ji, R.R., Liu, T. Batinic-haberle, I., Warner, D.S. Methods of treat-ing pruritus. US20160324868 (2016).
[116] Kaspar, L., Speaker, T. Methods of treating pain and/or itch with small molecule inhibitors targeting an mTOR pathway.
US20160184279 (2016).
[117] Schwarz, E.M., Hu, Y., Antoshechkin, I., Sternberg, P.W., Aroian, R.V. Composition and methods related to parasites.
US20150329603 (2015).
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