Hookworm-related cutaneous larva migrans

INTRODUCTION — Cutaneous larva migrans (CLM) is a clinical syndrome consisting of an erythematous migrating linear or serpiginous cutaneous track; an alternative term is creeping eruption.

It most frequently occurs as a result of human infection with the larvae of the dog or cat hookworms, Ancylostoma braziliense or Ancylostoma caninum; it also may be caused by larvae of other animal parasites that are not natural human parasites [1].

CLM caused by an animal hookworm is commonly referred to as hookworm-related cutaneous larva migrans (HrCLM) [2,3].

Issues related to CLM caused by human infection with larvae of dog or cat hookworms will be reviewed here. Issues related to human hookworm infection (caused by Ancylostoma duodenale or Necator americanus) are discussed separately. (See "Hookworm infection".)

EPIDEMIOLOGY — The hookworms responsible for CLM are distributed worldwide; infection is more frequent in warmer climates, especially in the tropical and subtropical countries of Southeast Asia, Africa, South America, Caribbean, and the southeastern parts of the United States. Larvae are found on sandy beaches, in sand boxes, under dwellings, and in garden plots.

Individuals at greatest risk include travelers, children, swimmers, and laborers whose activities bring their skin in contact with contaminated soil [4-6]. HrCLM is a common cause of dermatologic disease among those returning from travel in tropical regions [7,8].

In one series of British travelers, infections were acquired most commonly in Africa, the Caribbean, Southeast Asia, and, less commonly, Central and South America [9]. In another review of Canadian travelers, infections were acquired most commonly in the Caribbean (most often Jamaica) [10]. In a review of HrCLM developing in 43 travelers returning to France, infections were acquired in the Americas (37 percent), Africa (33 percent), Asia (28 percent), and one case in Portugal [11]. In addition, HrCLM has occurred in residents of several European countries in the absence of travel to tropical regions, likely due to local exposures to animal hookworms [11-14]. (See "Skin lesions in the returning traveler".)

In a study from the Brazilian Amazon, the incidence of HrCLM was 0.52 per person-year; the condition was more common in the rainy months and among boys age 10 to 14 years [6].

Life cycle — The hookworm life cycle in the definitive host is very similar to the hookworm life cycle for human species (figure 1 and figure 2). (See "Hookworm infection".)

Eggs are passed in the stool of the definitive host (adult dog or cat). Under favorable conditions (moisture, warmth, shade), rhabditiform larvae hatch in 1 to 2 days. After 5 to 10 days (and two molts), they become filariform (third-stage) larvae, which are infective and can survive 3 to 4 weeks in favorable environmental conditions.

Upon contact with the nonhuman animal host, the filariform larvae penetrate the skin and are carried through the blood vessels to the lungs, where they penetrate into the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed. The larvae reach the small intestine, where they reside and mature into adults, which attach to the intestinal wall. Some larvae become arrested in the tissues and serve as a source of infection for puppies or kittens via transmammary (and possibly transplacental) routes.

Humans may become infected when filariform larvae in the soil partially penetrate the skin. The larvae of most species cannot mature within the human host since humans are accidental intermediate hosts. The larvae migrate within the epidermis and lack the collagenase necessary to break through the basement membrane [15]. The larvae produce an inflammatory reaction along the cutaneous tract of their migration, which may continue for weeks.

Some larvae may access deeper tissues. Rarely, pulmonary involvement occurs, either via direct invasion or secondary to a systemic immunologic reaction [16].

CUTANEOUS DISEASE — HrCLM occurs most frequently on the lower extremities [9,17]. In a report of 98 travelers, lesions most often involved the lower extremities (73 percent); the buttocks and anogenital region, trunk, and upper extremities were involved in 13, 7, and 7 percent, respectively [18].

Initially, a pruritic erythematous papule can develop at the site of each larval penetration; many patients are unaware of the penetration site. With exposure to heavily contaminated soil, up to several hundred pruritic papules may develop. Within a few days thereafter, intensely pruritic, elevated, serpiginous, reddish-brown tracks appear as the larvae migrate at a rate of several millimeters (up to a few centimeters) per day (picture 1) [19]. The lesions are approximately 3 mm wide and may be up to 15 to 20 mm in length [20], and the larva itself is usually located 1 to 2 cm ahead of the eruption [17]. Usually one to three lesions are present.

Serpiginous lesions usually develop two to six days after exposure but may occur weeks or even many months after exposure [21-24]. In one review, cutaneous lesions appeared after return from travel with a mean time of onset of 5 to 16 days [20]. Vesiculobullous lesions develop in about 10 percent of cases [21,25], and the presence of nodular and bullous lesions may delay the diagnosis [26]. Lesions may become vesiculated, encrusted, or secondarily infected. The pruritus can be so intense that it causes sleep disturbance [10,21,27]. Eventually the lesions resolve spontaneously even in the absence of specific therapy. This usually occurs in two to eight weeks, although longer duration of infection has been reported, and cutaneous symptoms may recur days to months later. In one series, 29 percent of patients had lesions that persisted for one month [18]. Occasionally, larvae persist in follicles and cause disease for as long as two years [28,29].

Hookworm folliculitis is an uncommon form of HrCLM, occurring in less than 5 percent of cases; it consists of numerous follicular, erythematous, and pruritic papules and pustules [2,30,31]. Serpiginous tracks may be absent or relatively short [17,32,33].

Diagnosis — The diagnosis of HrCLM is based on clinical history and physical findings. Infected patients typically have a history of exposure to contaminated soil or sand (walking barefoot or lying on sand) and the characteristic serpiginous lesion on the skin (picture 1). Eosinophilia is rare.

There are emerging reports of dermoscopy being used to facilitate diagnosis of CLM; features include translucent, brown, structureless areas corresponding to the larval bodies, and red-dotted vessels corresponding to an empty burrow [34-36]. Fluorescence-advanced videodermatoscopy has also been used to localize larvae in HrCLM [37].

Ultrasonography may demonstrate subepidermal and intrafollicular structures that are small, linear, hyperechoic, and hyper-refringent (suggestive of larvae fragments) [38,39]. Additional findings may include dermal and hypodermal hypoechoic tunnels with inflammation, reflecting lymphatic duct dilatation.

Treatment — Anthelminthic therapy for HrCLM is helpful for relieving symptoms and reducing the likelihood of bacterial superinfection.

Options for treatment include ivermectin or albendazole. The preferred treatment is ivermectin (200 mcg/kg orally once daily for one or two days) [40-42]. A single dose of ivermectin results in cure rates of 94 to 100 percent [20]. Patients with hookworm folliculitis should be treated with two doses of ivermectin [43,44]. Albendazole (400 mg orally with fatty meal for three days) is an acceptable alternative treatment. For patients with extensive or multiple lesions, a seven-day course of albendazole may be administered [45]. Symptoms generally disappear within one week after treatment; frequently, the pruritus settles before the dermatitis [17].

Treatment of hookworm folliculitis may be difficult, and repeated courses of oral anthelmintic agents may be required [17].

Topical agents are an alternative treatment option, though they can be difficult to obtain. Topical thiabendazole (15 percent in a hygroscopic base for five days) is effective in alleviating pruritus and halting progression of lesions, usually within two days [18,40]. A topical 10% albendazole ointment, prepared by crushing three 400 mg tablets of albendazole in 12 g of petroleum jelly, has also been reported to be effective when administered three times daily for 10 days [46].

In addition to antiparasitic agents, antihistamines are helpful for management of pruritus. In patients with severe allergic reactions, symptomatic treatment with topical corticosteroids may be administered. (See "Topical corticosteroids: Use and adverse effects".)

PULMONARY DISEASE — Hematogenous dissemination of larvae to the lungs is a rare complication of infection [16,47-51]. The most frequent manifestation is dry cough that starts about one week after cutaneous penetration. The cough usually lasts for one to two weeks but may rarely persist for up to nine months.

Diagnosis — A presumptive diagnosis of pulmonary involvement in cutaneous larva migrans is made when respiratory symptoms develop in the presence of the typical cutaneous lesions. Further diagnostic evaluation is not usually necessary.

Chest radiography may demonstrate transient migratory infiltrates (image 1) [52,53]. Blood eosinophilia is common, and bronchoalveolar lavage may also demonstrate eosinophils. Definitive diagnosis consists of recovery of larvae from respiratory secretions or bronchoalveolar lavage fluid, although such procedures are rarely needed.

Stool examination and serologic tests are not helpful.

Treatment — Beyond treatment of HrCLM, additional anthelminthic therapy for the pulmonary involvement is generally not required since the illness is usually mild and self-limited.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of HrCLM includes:

●Strongyloidiasis – The main differential diagnosis of a creeping eruption is the larva currens ("running" larva) of strongyloidiasis [54,55]. Larva currens has a prominent urticarial component and is notable for its rapidity. The larval track of larva currens can progress approximately 1 cm in five minutes and 5 to 15 cm per hour; the larval track of HrCLM can progress up to 1 to 2 cm per day. The diagnosis of strongyloidiasis is established by larva detection and/or serology. (See "Strongyloidiasis".)

●Gnathostomiasis – Migrating Gnathostoma larvae cause localized swellings that typically last one to two weeks and are associated with edema, pain, itching, and erythema [56]. The diagnosis is established by larva detection and/or serology. (See "Skin lesions in the returning traveler", section on 'Gnathostomiasis'.)

●Loiasis – Loiasis is associated with transient localized subcutaneous swellings (known as Calabar swellings); typically, they are nonerythematous and measure 5 to 20 cm in diameter. The diagnosis is established by visualization of organisms or via serology. (See "Loiasis (Loa loa infection)", section on 'Calabar swellings'.)

●Dracunculiasis – Dracunculiasis is associated with migration of worms in the subcutaneous tissues, followed by development of a painful papule and emergence of one or more worms accompanied by a burning sensation. The diagnosis is based on clinical manifestations. (See "Miscellaneous nematodes", section on 'Dracunculiasis'.)

●Paragonimiasis – Paragonimiasis can be associated with painless, migratory subcutaneous swellings of various sizes or tender, firm mobile nodules containing immature flukes. The diagnosis is established via serology. (See "Paragonimiasis", section on 'Subcutaneous infection'.)

●Fascioliasis – Ectopic fascioliasis results in eosinophilic and mononuclear infiltration with secondary tissue damage. The most common ectopic site is the subcutaneous tissue of the abdominal wall. Tender, migrating, erythematous, itchy nodules (1 to 6 cm in diameter) can develop. (See "Liver flukes: Fascioliasis", section on 'Ectopic fascioliasis'.)

Other causes of non-migratory skin lesions include:

●Tinea pedis – Acute tinea pedis consists of intensely pruritic, sometimes painful, erythematous vesicles or bullae between the toes or on the soles, frequently extending up the instep. The diagnosis can be confirmed by potassium hydroxide examination of scrapings from the lesions. (See "Dermatophyte (tinea) infections", section on 'Tinea pedis'.)

●Contact dermatitis – Contact dermatitis is a localized inflammatory skin response to a range of chemical or physical agents. Clinical features include erythema, edema, vesicles, and bullae; lesions are typically pruritic. The diagnosis is established by history and physical examination. (See "Irritant contact dermatitis in adults".)

●Impetigo – Impetigo is a superficial bacterial infection of the skin. Lesions progress from papules to vesicles surrounded by erythema; subsequently, they become pustules that rapidly break down to form crusts with a characteristic golden appearance. Lesions are typically painful. The diagnosis is established by history and physical examination. (See "Impetigo".)

●Myiasis – Myiasis due to the botfly or tumbu fly consists of skin lesions containing fly larvae; the lesions enlarge over time but are not migratory and the organism can be visualized moving within the lesion. The diagnosis is established by history and physical examination. (See "Skin lesions in the returning traveler", section on 'Myiasis'.)

●Scabies – Scabies is an infestation of the skin by the mite Sarcoptes scabiei. Scabies usually manifests as small, erythematous, nondescript papules or as thin, linear burrows and most commonly involves the sides and webs of the fingers (interdigital spaces); it can be intensely pruritic. The diagnosis is usually established by history and physical examination. (See "Scabies: Epidemiology, clinical features, and diagnosis".)

●Folliculitis – Causes of folliculitis that warrant consideration in patients with potential HrCLM exposures include "sea lice" (also called seabather's eruption, caused by jellyfish larvae) and swimmers itch (caused by skin penetration by cercariae of nonhuman schistosomes). (See "Skin lesions in the returning traveler", section on 'Swimmer's itch' and "Skin lesions in the returning traveler", section on 'Seabather's eruption'.)

SUMMARY AND RECOMMENDATIONS

●Cutaneous larva migrans (CLM) occurs most commonly as a result of human infection with the larvae of the dog or cat hookworm; it may also be caused by other animal hookworms (hookworm-related cutaneous larva migrans [HrCLM]). The terms CLM and "creeping eruption" refer to subcutaneous intradermal migration of nonhuman filariform zoonotic larvae that may manifest as a cutaneous track. (See 'Introduction' above.)

●Infection occurs most frequently in the tropical and subtropical countries of Southeast Asia, Africa, South America, Caribbean, and the southeastern parts of the United States. Larvae may be found where infected dogs and cats defecate on soils including sandy beaches, in sand boxes, and under dwellings. Individuals at greatest risk include travelers, children, swimmers, and laborers whose activities bring their skin in contact with contaminated soil. (See 'Epidemiology' above.)

●The hookworm life cycle in the definitive host is very similar to the hookworm life cycle for human species (figure 1 and figure 2). Humans may become infected when filariform larvae in the soil penetrate the skin. The larvae of most species cannot mature within the human host; they migrate within the epidermis and produce an inflammatory reaction. (See 'Life cycle' above.)

●HrCLM occurs at sites of skin exposure to contaminated soil, most frequently on the lower extremities. Initially, a pruritic erythematous papule develops at the site of each larval penetration. Days, weeks, or months later, intensely pruritic, elevated, serpiginous, reddish-brown lesions appear as the larvae migrate at a rate of several millimeters per day (picture 1). (See 'Cutaneous disease' above.)

●We suggest treatment of HrCLM with anthelminthic therapy (Grade 2C); treatment is helpful for relieving symptoms and reducing the likelihood of bacterial superinfection. We suggest systemic treatment with either ivermectin (200 mcg/kg orally once daily for one or two days) or albendazole (400 mg orally with fatty meal for three days) (Grade 2C). Topical agents are an alternative treatment option though they can be difficult to obtain and use. (See 'Treatment' above.)

●Hematogenous dissemination of larvae to the lungs is rare. The most frequent manifestation is dry cough that starts about one week after cutaneous penetration. Specific anthelminthic therapy for the pulmonary involvement is generally not required since the illness is usually mild and self-limited. (See 'Pulmonary disease' above.)