Cutaneous larva migrans

Kaliaperumal Karthikeyan, Devinder Mohan Thappa

 Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry - 605 006, India

Correspondence Address:
Devinder Mohan Thappa
Department of Dermatology and STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry - 605 006
India

Introduction

Cutaneous larva migrans (CLM) is a dermatitis caused by the invasion and migration of larva of parasites in the skin.[1] These larvae usually have their origin from nematodes and rarely from insects.[2] This entity is also known by various other names such as creeping eruption, sand worm, plumbers itch, duck hunters itch and epidermatitis linearis migrans.[1] It is commonly known as creeping eruption for its distinctive feature that the lesion creep or migrate and is due to the presence of moving parasite in the skin. The credit for the earliest published report of CLM goes to Lee [2], an English physician of 1874. Crocker [3] coined the term "Cutaneous larva′ migrans" in 1893. Later in 1896, Hammelstjerna proved its parasitic etiology. Since then many cases have been reported and a variety of organisms are incriminated as the causative agents.

Epidemiology

Though cutaneous larva migrans (creeping eruption) has a world wide distribution, it is common in warmer tropical and sub tropical countries.[1] It is endemic in Caribbean islands, Africa, South America, South East Asia and South eastern United States.[5] This disorder frequently occurs during warm and rainy seasons. People who frequent beaches and the children are at a higher risk of acquiring this disease.[1] The endemic nature of this disease depends on two factors namely poor sanitation and appropriate environmental condition. The environmental factors that are essential for development of the larva include temperature between 23 to 30 °C, loose humus soil, shady areas and proper aeration. The factors that influence the occurrence of CLM include the degree of soil contamination and duration of contact with the soil.[6],[7]

Etiopathogenesis

Cutaneous larva migrans can be caused by different parasites. Various organisms causing CLM and their definitive hosts are summarized in [Table - 1]. Mainly, CLM is caused by the larval nematodes, which penetrate into the skin.[1],[8] The normal life cycle of a nematode is described in [Figure - 1]. The embryonated eggs of nematodes are shed in feces by the definitive host and thus reach the soil. Under appropriate temperature and humidity, these eggs hatch and release rhabditiform larvae within 1-2 days. In a week time, these larvae moult, grow and develop into filariform larvae. These infective filariform larvae measure 850 microns in length and have a diameter of 35 microns. They live in the top one half inch of the soil, with their ends projecting upward from the surface, searching for their prey and live within inches of where the eggs are deposited. Under optimal conditions, these larvae may remain infective for several months, though 90% of these larvae die within first 3 weeks. Survival of these larvae is best achieved in the light soil that is protected from flooding and drying.[7] The larvae can migrate vertically through the soil to a potential host in response to contact (thigmotropism), carbon dioxide or warmth. When come in contact with the human skin, the larvae use discontinuities in the epidermis of the host (fissures or hair follicles) to penetrate the skin.[7] The juvenile larvae can penetrate epidermis of any site. The parts most often affected are those which remain in contact with soil such as feet, hands, and buttock.[9] In the skin, the larval migration begins four days after penetration.[10] The movement of the larvae in the epidermis is facilitated by the production of hyaluronidase by them.[11] Within a few days, a typical dermatitis with vesicles, papules and desquamation develops along the track of migration of larva. Since, the larvae are unable to complete their life cycle in human (accidental host), this lead to their death with-in weeks of invasion. These larvae finally degenerate and disease subsides.[12] The sequence of evolution of the lesion in an experimental set up is summarized in the [Table - 2]. All hookworms and Strongyloides that cause CLM in humans are similar morphologically. In contrast, the larvae of Gnathostoma are larger and can be identified by their numerous cuticular spines.[1]

Clinical features

The clinical features of CLM may vary from non-specific dermatitis to typical creeping eruption [Table - 3]. The larva after penetration can lie quiet for weeks or immediately begin creeping activity. The initial lesion is an erythematous, papular itchy lesion. Soon a slightly raised, flesh colored or pink swollen lesion about 2-3 mm thick develops and forms linear, serpentine (serpiginous) or bizarre tracks [Figure - 2], [Figure - 3] & [Figure - 4]. Multiple larvae can be active at the same time with the formation of disorganized loops and tortuous tracks.[13] The larvae migrate about 2-5 cm per day and the visible track moves ahead by 1-2 cm. Multiple vesicles may appear along the lesion. Rarely, folliculitis may be the presenting picture. The eruption is most often located over the feet followed by buttock, anogenital region and upper extremities.[8],[9] Rarely, in severe infections, person may have hundreds of tracks.[9]

The lesions of CLM are intensely itchy, sometimes may produce burning sensation.[13],[14] Itching may be severe enough, to produce insomnia. Since the lesions of CLM are itchy, scratching may lead to secondary changes of dermatitis and bacterial infection.

Cutaneous larva migrans can be grouped into several types depending upon the species responsible for the lesions and their clinical appearance.[15]

Type 1 Animal hookworms

CLM produced by Ancylostoma duodenale and Ancylostoma caninum is characterized by well-defined tracks that extend several centimeters from their point of origin. These juveniles (larvae) migrate at the rate of 3.5 to 5 cm per day. The infection can be chronic, lasting for months.[15]

Type 2 Human hookworms

Ancylostoma duodenale and Necator americanus produce marked blister formation, short tracks and intense itching. This type of larva migrans is also known as "ground itch". They eventually migrate to the lungs and intestine where the parasites mature into adults.[7],[15]

Type 3 Strongyloides, stercoralis

Human strongyloides produce a type of CLM known as "larva currens".[13] The lesion begins in the perineal area and then advances to the extremities and other sites. The track is wide, poorly defined and long. It is called as larva currens as the larvae migrate at a rate of up to 5 cm per hour.[13],[16],[17]

Type 4 Animal strongyloides

CLM produced by strongyloides of animal origin is variable. Some lesions are similar to those seen in Strongyloides stercoralis infection.[18] Infections with Strongyloides myopotomi and Strongyloides procyonis produce lesions resembling erythema multiforme.[19] The typical burrows are seen on examination with indirect light.

Type 5 Gnathostoma

CLM produced by gnathostoma is usually confined to Japan, Thailand and less often in other countries of Southeast Asia.[20] Parasitic infection can occur in two ways. It can occur due to the migration of ingested larva from the intestine to the skin or by direct penetration of the parasite through the skin while handling animal flesh.[21] The lesions are wide tracks that disappear and reappear at a distant location. The rate of migration is variable, in the epidermis the larvae travel at the rate of 4.5 cm per day while in dermis, it is about 3 cm per hour. Gnathostoma larvae can be easily visualized by naked eye because of their size. They can be recovered easily if a small incision is made over the lesion.[11],[20],[22]

Type 6 Insect larvae

Some species of gastrophilus and hypoderma can migrate through the skin producing linear lesions sometimes called as "myiasis linearis". The characteristic lesion consists of single continuous track without blister formation, moving at a rate of 3 to7.5 cm per day.[15] The larvae can be easily visualized by blanching the skin with slight pressure from a magnifying glass or by rubbing the skin with mineral oil.[23] The larva can be extracted intact by excoriating the superficial epidermis.[23]

Other features associated with CLM

Usually, there are few, if any systemic symptoms. CLM produced by Strongyloides can be associated with Loeffler′s syndrome as a result of migrating larvae reaching the lungs.[15],[34] In these patients with prominent pulmonary symptoms and signs, the larvae can be recovered from the sputum. Migration of the larvae in the cornea may produce inflammation leading to corneal opacity.[16] CLM produced by Ancylostoma caninum can be associated with myositis as result of the larva invading deep into the muscles.[27]

Pathology

The histopathology of the lesion shows an empty tunnel with polymorphonuclear cell infiltrate consisting mainly of eosinophils and necrotic keratinocytes in the epidermis. The larva is seldom seen in the tissue sections because the clinical lesion develops long after the larva has passed through.[28] If the larva is found, it is located in a burrow or in a hair follicle without inflammation.[15] The site of migration of the larva may vary. All hookworm larva appear to migrate through epidermis in the stratum malpighi while strongyloides larva is found in the upper dermis.[29] The larvae of Gnathostoma, Gastrophilus and Hypoderma are present in both epidermis and dermis.[15] It is impossible to identify various hookworm larvae in the cross section but Gastrophilus, Gnathostoma and Hypoderma are larger and have distinct morphological features.[15]

Diagnosis

Since larvae in the skin are rarely recovered, and they are not readily or easily identified when found, the species involved in individual cases is usually unknown. Laboratory investigations may not be helpful in the diagnosis of CLM.[30],[31],[32] Rarely, patient may have associated eosinophilia or an increase in the immunoglobulin E (IgE) rate. Stool examination is worthless expect for Strongyloides where the larvae may be seen in the stools. Skin biopsy is not recommended as a diagnostic modality.[1] Recently epiluminescent microscopy has been found to be an effective and non-invasive method for detecting a larva to confirm the diagnosis of CLM.[30] Some authors have suggested search for specific IgG with enzyme-linked immunosorbent assay (ELISA) methods.[32] Thus, the diagnosis of CLM is based mainly on clinical features and typical history.

Differential diagnosis

The features of CLM are typical and rarely missed. This dermatosis requires differential diagnosis from other parasitoses e.g., subcutaneous nodules or granulomas due to other species, and different pictures of myiasis, but also from simpler and more common pathologies such as allergic contact dermatitis, urticaria factitia, other types of dermatitis, and pyodermas.[32] The various other differential diagnosis of this condition includes scabies, urticaria, photodermatitis, erythema chronicum migrans and stings of Portuguese man- of-war or jellyfish.[5],[8] In some cases, the diagnosis may be further complicated by superadded bacterial infection and eczematization.[1],[2],[3],[4],[5],[6],[7],[8]

Treatment

Although, CLM normally disappears by itself within anything from 1 to 6 months or rarely, longer, the intense itching, the unpleasant sensation felt by the patient of the larva slowly creeping below the skin, and the possible complications suggest that treatment should be given that can reduce the length of the disease, even if different therapeutic options turn out to be somewhat ineffective or difficult to put into practice.[32] It can be treated by physical modalities (surgery e.g., in creeping eruption due to Gnathostoma sphinigerum), cryotherapy, topical drugs and systemic therapy.[31],[32] Cryotherapy which can be used for limited number of lesions, is obsolete, as it is a painful and imprecise way to kill the migrating larvae which is usually 1-2 cm ahead of the visible track.[5],[8],[33] Further more, the larva can withstand temperature as low as -21 °C for more than 5 minutes, resulting in failure of therapy.[34] Surgery often ineffective as the larva is easily missed, being ahead of the visible track. Surgery and cryotherapy may be appropriate in pregnancy.[8] Various topical agents such as 15% thiabendazole, 2% gamrriexane cream, 25% piperazine citrate and metriphonate have also been tried in the treatment of CLM.[10],[11],[12],[13],[14] Among these topical agents, thiabendazole has been found to effective in killing the larvae and. alleviating symptoms.[5],[35] Though topical thiabendazole is effective, it requires repeated application, can result in an irritant reaction and is often followed by recurrences.[36] Oral thiabendazole has been reported to have a very high efficacy and is usually given in the dose of 25-50 mg per kg body weight, once or twice daily for 2-5 days.[5],[32],[37] It is not widely used because of the high incidence of side effects such as nausea, anorexia, headache and gastrointestinal disturbances.[37] Further, it is not available in many countries.[5]

Albendazole, yet another drug was first used to treat CLM in 1982 and subsequently many, reports have substantiated its effectiveness and is now considered to be the drug of choice for this disorder.[38],[39],[40] It is used in the dosage of 400 800mg/day for a period that may vary from 1-7 days.[31],[41] This anti-helminthic is effective against eggs, larvae and adult stage of numerous helminthes. The mechanism of action is not very clear. It may act by reducing or blocking the uptake of glucose, thus depleting glycogen reserves leading to decrease or cessation in production of adenosine triphosphate (ATP). It may also induce degeneration of cytoplasmic microtubules with death of the parasite by autolysis. Some authors believe that it acts by inhibiting microtubule polymerization.[31] Albendazole as such is well tolerated if administered for a short length of time. Its long term use may, lead to elevated liver enzymes, alopecia, allergic reactions, leukopenia and thrombocytopenia.[31],[32] The major advantage with albendazole is thatiit relieves pruritus in 3-5 days and results in resolution of the cutaneous lesions by 5-7 days after treatment.[32] It is teratogenic and embryotoxic in the rot and rabbit, but does not seem to be either mutagenic or, carcinogenic.[31]

Another possible drug for use in, CLM is a single 150-200ig/kg dose of ivermectin, a drug capable of eradicating the parasite with minimum or no side effects, but which still needs more thorough research.[32] In a study, single dose of 12 mg of ivermectin was found to be more effective than single dose of 400mg of albendazole.[41],[42],[43],[44] Flubendazole,(200 mg/day for 5 days), is another anti -helminthic drug, currently under experimental stage, would appear to offer good prospect for the future.[32]

Prevention

Eradication of larvae causing CLM is impractical. The most appropriate preventive measure is to avoid contact of exposed skin with contaminated soil. Wearing shoes and using a beach towel when lying on sand can avoid exposure to the larvae. Periodic deworming of domestic cats and dogs reduces soil contamination. Sand boxes and other similar facilities where children frequently play should be protected from dogs and cats.[1] Thus, CLM can be prevented by adequate precautionary methods, failing which, it can spoil a dream vacation.[45]

Significance in the context of India

Significance in the context of India is its occurrence in the coastal areas of the country where suitable conditions for this entity exist.[42] Children may be advised not to sit, lie, or walk barefoot on wet soil or sand of beaches. The ground should be covered with impenetrable material when sitting or lying on the ground.

To conclude, CLM is a clinical condition with a characteristic presentation that is easily recognizable. Despite the ubiquitous distribution of A. braziliense and A. caninum, CLM seems to restricted mainly to tropical and subtropical countries. The typical patient is a person who has visited a beach or a returning traveler from a tropical or subtropical climate who gives a history of beach exposure. The characteristic skin lesion is a pruritic, erythematous serpiginous or linear raised track. Effective treatment modalities now exist for this entity.

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