Are You Confident of the Diagnosis?
Cutaneous larva migrans (CLM) is a rather common self-limiting nematode infection (usually from animal hookworms). Infection via human hookworms is known as “ground itch.” Hookworms are intestinal nematodes excreted in fecal matter by infected hosts (usually animals, less commonly humans). The larval form is able to penetrate the epidermis where the infection is usually confined.
What you should be alert for in the history
Exposure and travel history is very important to obtain. Clinical history is significant for exposure to sandy beaches or soil in warm (ie. tropical or subtropical) climates contaminated by fecal matter. Sometimes patients will recall a prickling or burning sensation approximately 30 minutes following larva penetration. The incubation period usually occurs within days but can require several weeks.
CLM occurs worldwide. Infection from the animal hookworm form is common in the southeastern United States, Mexico, Caribbean, Central and South America, Southeast Asia, Africa, and other tropical countries.
Commonly affected areas are the feet and interdigital webspaces of the toes (from walking on the beach) as well as the buttocks and thighs (from sitting on the beach). It can also affect any area of the body that is in contact with the larvae, such as the trunk, hands and knees.
Characteristic findings on physical examination
Clinical examination reveals extreme pruritus. Each larva produces a linear serpiginous erythematous inflammatory 2-3 mm wide tract, which advances by 1-2 cm per day (Figure 1). These tracts may appear as coalescent papules or vesicles and can measure up to 20 cm long. Pruritic follicular papules and pustules (2-5 mm) on the buttocks or thighs in conjunction with serpiginous tracts may be found. Vesicles and bullae are not uncommon in sensitized individuals. Nonspecific localized dermatitis may be present.
Expected results of diagnostic studies
A biopsy is unnecessary for the diagnosis. Histology will demonstrate a tract in the stratum corneum or suprabasalar layer with associated spongiosis and scattered necrotic keratinocytes, and an epidermal and superficial dermal infiltrate with abundant eosinophils. A larva may be present in the biopsy specimen if the sample is taken ahead of the advancing serpiginous tract. Hookworm larvae can also been found in the follicles with the clinical appearance of folliculitis (particularly on the buttocks).
Laboratory investigations are not necessary. A complete blood count with differential may reveal eosinophilia. There are available serologic immunodiagnostic tests for antigens to individual species of nematodes (eg, Ancylostoma caninum antigen by an ELISA method) but these tests are infrequently used. If pulmonary symptoms such as cough and shortness of breath are reported by the patient, a chest x-ray should be performed. Loeffler’s syndrome (peripheral eosinophilia with migratory pulmonary infiltrates) is a rare manifestation of CLM.
The differential diagnosis for CLM includes:
Larva currens (Strongyloidiasis). A nematode infection caused by Strongyloides stercoralis. Percutaneous penetration of larvae or accidental ingestion of larvae can lead to subsequent autoinfection by percutaneous penetration of perianal skin by larvae. Localized or widespread urticarial, pruritic eruption is most prominent in the buttocks, extending to the lower extremities and lower trunk and abdomen. The skin lesions are pruritic when they appear and disappear within hours.
Thumbprint purpura (widespread purpuric macules and patches) is considered a clinical sign for disseminated Strongyloides as filariform larvae from the vasculature cause red blood cell extravasation as they move into dermal connective tissue. Gastrointestinal and pulmonary symptoms and peripheral eosinophilia are common.
Migratory myiasis (associated with Hypoderma bovis or Gasterophilus intestinalis). A self-limited cutaneous eruption caused by larvae from the adult fly of the aforementioned species. Animal hosts include cattle and horses. Humans are unusual hosts but this can occur. Look for larvae that appear as intermittent rapidly moving (approx. 1 cm/hour) painful subcutaneous nodules. These larvae eventually die within tissues or exit via furuncle-like lesions over weeks to months.
Tinea Corporis. Ask about a history of contact with animals or other affected individuals. Look for annular (round) lesions with fine scaling. Potassium hydroxide test can be performed to visualize microscopic fungal elements or fungal cultures may be performed.
Tinea Pedis. Look for fine scaling and/or maceration of the instep and interdigital spaces as well as onychomycosis (fungal nail infection). Potassium hydroxide test can be performed to visualize microscopic fungal elements or fungal cultures. Notably, tinea pedis is uncommon in children.
Scabies (Sarcoptes scabiei parasite). Ask about a history of close contacts with a similar acute onset of pruritus. Look for burrows particularly in the finger and toe webspaces. Pruritic papules are often located within the intertriginous zones and on the scrotum in men.
Contact dermatitis. Ask about a history of potential contact allergens such as new cleansing or cosmetic products, sunscreens, clothing or shoes. Contact dermatitis is usually localized unless the patient develops a hypersensitivity response (Id reaction). It almost never has a serpiginous appearance.
Erythema chronicum migrans (associated with Lyme disease). A pathognomonic sign for infection with Borrelia burgdorferi, which can appear immediately or weeks to months after infection. Look for an asymptomatic enlarging annular (approximately 5 cm) erythematous plaque with central erythema or clearing. Borrelia serology should be obtained and if positive the patient should be treated with appropriate systemic antibiotics.
Impetigo. Ask about a history of abrasion, skin trauma or preexisting chronic skin condition (eg, eczema, psoriasis, etc). Look for honey-colored crusts. Perform bacterial swabs to identify the organism to guide appropriate antimicrobial therapy.
Who is at Risk for Developing this Disease?
CLM affects both genders and all races and ages, particularly children. It is one of the most common skin infestations seen in tropical disease clinics.
At-risk populations include:
Beachgoers or sunbathers walking in barefeet or sitting on infested sand in humid (tropical or subtropical) climates
Persons engaging in hobbies (e.g. surfer) or occupations (e.g. lifeguard, plumber, carpenter, farmers) that involve spending extensive time in contact with sand or soil either on the beach or in humid climates
Children playing in the sand either on the beach or in sandboxes
What is the Cause of the Disease?
Common nematodes causing CLM are:
Ancylostoma canium and braziliense (hookworm of wild and domestic dogs and cats)
Ancylostoma duodenale and Necator americanus (human hookworms)
Ancylostoma caninum (dog hookworm) in Australia
Uncinaria stenocephala (dog hookworm) in Europe
The lifecycle of these nematodes can occur as follows:
Host infection via percutaneous penetration (animal hookworm). Hookworms live in animal intestines and ova are contained in fecal matter. Moist humid environments facilitate hatching of ova and larva survival on the ground, and following two molting stages (rhabditiform, then strongyloid) the infective filariform larvae are able to invade human skin. The filariform larvae contain proteases that can penetrate small fissures or wounds, hair follicles or even intact skin. These larvae do not contain collagenase which is required to invade the human dermis and therefore remain as a superficial infestation in the epidermis.
Host infection via inadvertent ingestion (human hookworm). More so with the human species of hookworms, migration of larvae into the lymphatic and/or venous circulation occurs following inadvertent ingestion. The larvae travel towards the lungs where they penetrate the alveoli and invade the trachea, where they are swallowed and progress to sexual maturity within the intestine. Reproduction with the intestines produces additional ova, which are again excreted in fecal matter continuing the parasitic infestation cycle. Autoinfection can occur when larvae near the perineum penetrate the skin.
Systemic Implications and Complications
Systemic complications are uncommon, but can occasionally occur. Loeffler’s syndrome, considered a rare hypersensitivity response to soluble hookworm antigen, manifests as eosinophilic migratory pulmonary infiltrates. Notably, peripheral eosinophilia with elevated immunoglobulin E (IgE) can also occur with any parasitic infection.
Oral albendazole is considered the treatment of choice. Dosage: 400-800mg daily (adults), 10-15 mg/kg/day (children, maximum 800 mg/day) in divided doses for 3 days
Ivermectin (single dose): 12 mg or 150-200 μg/kg (adults), 150 μ/kg (children)
Oral thiabendazole: 25 mg/kg twice daily for 3 days. Note that thiabendazole is no longer commercially available in Canada, United States and several other countries worldwide
Topical 10 to 15% albendazole (or thiabendazole) solution or ointment (under occlusion) for localized lesions
Oral antibiotics for secondary cellulitis
Cryotherapy (for solitary lesions): 1-2 cm ahead of the erythematous tract
Optimal Therapeutic Approach for this Disease
The primary role of active treatment for CLM is to provide rapid symptomatic improvement (ie. severe pruritus and discomfort) and secondary complications (ie. cellulitis, autoinfection, etc.). Pruritus usually settles within 24-72 hours of treatment. The cutaneous lesions tend to resolve within 1-2 weeks. Even without any treatment, CLM will resolve within weeks to months in almost all infected individuals but can persist for up to 2 years. The larvae eventually die in human hosts since they cannot complete their lifecycle (ie. dead-end hosts).
The treatment of choice is oral albendazole (a third-generation anthelminth agent). Other anthelmintics such as thiabendazole and mebendazole are also effective. Albendazole is relatively well tolerated, whereas thiabendazole has been associated with a higher incidence of gastrointestinal symptoms (ie. nausea, diarrhea). If compliance is an issue, a single dose of ivermectin can be used with high cure rates.
Topical albendazole (or thiabendazole) is much less efficacious than systemic therapy. Topical albendazole or thiabendazole must be applied under occlusion 3 to 4 times per day for at least 2 weeks. This may be an option for patients with localized disease only and who are absolutely unable to tolerate oral therapy, but the efficacy of topical treatment is low. Cases of irritant contact dermatitis have been reported.
The efficacy of cryotherapy is variable and not usually recommended. Larvae are able to survive in –20° C for more than 5 minutes. Aggressive cryotherapy is painful and can result in large bullae and ulcer formation.
It is also important to examine and treat the patient for a secondary soft tissue infection or cellulitis. Treatment with oral antibiotics would be appropriate.
Prevention is the most important factor. Persons traveling to high-risk tropical or subtropical beaches should be encouraged to wear appropriate protective footwear or sit on towels. Pet owners should also be educated and ensure that their pets receive the appropriate treatment if infected. In the future, hookworm vaccines may be available. A topical analgesic such as pramoxine could be of benefit.
Patients should be reassured that CLM is a self-limiting condition in most people. A follow-up appointment 4 to 6 weeks after treatment would be appropriate to document clinical improvement or resolution.
Chronic autoinfection can occur, especially with human hookworms, and follow-up should be arranged until the infection is completely cleared.
Unusual Clinical Scenarios to Consider in Patient Management
Loeffler’s syndrome (peripheral eosinophilia with migratory pulmonary infiltrates) is a rare manifestation of CLM.
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