Chapter 207. Helminthic Infections

Helminths (worms) are variably sized multicellular parasites that can infect a wide range of mammals, including humans. Those causing human disease belong to three groups: (1) nematodes (roundworms), (2) trematodes (flukes), and (3) cestodes (tapeworms) (Table 207-1); trematodes and cestodes are collectively referred to as platyhelminths (flatworms). This chapter focuses only on those helminths that more commonly cause dermatologic disease.

Globally, helminthic infections are among the most common diseases of humans. However, the true prevalence of helminthiases is difficult to determine, particularly since the majority of infected individuals harbor relatively few worms and are asymptomatic. Large worm burdens and symptomatic disease affect a relatively small proportion of those who are infected.

While some helminths such as Enterobius vermicularis and Toxocara canis are found worldwide, others are more geographically restricted (eTable 207-1.1). Most infections occur in developing tropical or subtropical countries, where environmental conditions are conducive to the completion of the life cycle of many helminths, and the requisite animal hosts and vectors for ongoing transmission exist. In addition, the high population density, poverty, and poor sanitation commonly found in these areas further facilitate the transmission of these diseases. Knowledge of the geographic distribution of specific helminths is important for the clinician, and will help to direct appropriate investigations and management.

Helminthic infections are less prevalent in temperate and northern climates, although some diseases are endemic even in these regions (eTable 207-1.1). In developed countries and colder climates, helminthic diseases are more often imported by travelers to or immigrants from endemic areas. Less frequently, helminthic infections in developed nations can be locally acquired (e.g., trichinellosis resulting from improperly prepared food) or transmitted via person-to-person spread (e.g., enterobiasis).

Skin Diseases in Travelers

Dermatologic disorders are the third most common illness in travelers.1 In several observational studies, 5%–17% of travelers to varied destinations developed a dermatologic condition during or after travel.2–6 These figures cannot necessarily be generalized to all travelers; however, as the studies included travelers assessed only in specialty (travel and tropical medicine) clinics, and may also have been subject to geographic biases (due to the specific population of travelers studied and/or the more common travel destinations among these travelers).

Infections, including tropical skin diseases, are common causes of dermatoses among travelers. Insect bites, allergic reactions, and other rashes are among the most prevalent noninfectious dermatologic diagnoses in travelers. Of the helminthic skin infections, cutaneous larva migrans (CLM) is by far the most commonly reported in travelers and accounts for 5%–25% of all skin diseases in this group.6–8 Most other helminthic infections that may be associated with dermatologic findings are relatively rare in travelers.

Skin Diseases in Immigrants and Refugees

The prevalence of dermatologic conditions in immigrants and refugees has not been exhaustively studied. Two studies suggest that skin conditions among these populations occur no more frequently3 or, in one study, much less commonly5 than in travelers; however, these studies are subject to the same biases noted above.

The helminths that cause skin findings in this population, and the clinical presentation, may also differ from those in travelers. For example, filarial infections are more commonly encountered in individuals who have resided in endemic areas for prolonged periods rather than in travelers,8 since they usually require repeated exposures to insect vectors in order for effective transmission to occur. Strongyloidiasis is also more prevalent in immigrants from endemic areas, particularly Southeast Asia, and often presents with eosinophilia or nonspecific abdominal symptoms.9 Acute onchocerciasis may occur in short-term (at least 1 month) visitors to endemic areas and characteristically presents with a hyperimmune response manifest by pruritus and rash (Fig. 207-1),10,11 in spite of low-parasite loads. In contrast, infected immigrants more commonly have chronic onchodermatitis, chronic skin changes including atrophy, hypopigmentation and lichenification, and onchocercal nodules (Fig. 207-2).

Life Cycle and Transmission of Helminths

All helminths have complex life cycles that include maturation from eggs (or other infective forms) to larvae (or other immature forms) to adults. Human disease results from ingestion of eggs or other infective forms or, alternatively, exposure of the skin to infective forms (larvae or cercariae) by direct contact or via the bite of an insect vector. Humans may be the primary hosts for some helminths (e.g., Strongyloides stercoralis), or may be incidental or accidental hosts (e.g., avian schistosomes, animal hookworm, and T. canis). Helminths that are well adapted to humans can mature from the infective stage into adult forms in the human host; infection generally persists for the lifespan of the adult worm, which in some cases can be for many years. In contrast, animal helminths cannot mature into adult forms in humans (who in this setting are therefore “dead-end” hosts), although infection can still cause tissue damage and clinical findings.

In general, helminths do not multiply in the human host. Most helminths (with the notable exception of S. stercoralis) are incapable of completing an entire life cycle in the human host, and depend on the environment (e.g., soil, water), plants, or other animal hosts or insects, for their survival. Consequently, transmission of infection requires the presence of appropriate environmental conditions, specific intermediate hosts (in whom only the asexual reproductive cycle occurs) and/or specific insect vectors, explaining in large part the localized geographic distributions of many helminthic diseases.

Examples of helminthic diseases acquired by ingestion of infective forms (eggs or metacercariae) in contaminated food or water include Ascaris lumbricoides and Fasciola hepatica. In ascariasis (eFig. 207-2.1), swallowed eggs are consumed, larvae are released within the gastrointestinal tract, and migrate through the portal-systemic circulation to the lungs, from where they are swallowed. Skin disease such as urticaria may occur during the larval migration phase. Once in the gastrointestinal tract, larvae mature into adult worms where sexual reproduction may take place; either eggs or adult worms can be shed in stool. Eggs must mature in soil before releasing infective larvae. In fascioliasis, infective metacercariae excyst in the small intestine and migrate through the intestinal wall and peritoneum to their target tissue, the biliary tract, where they become adults. Again, skin findings typically occur as immature forms migrate. Eggs produced by adult flukes are passed in feces and become infective for humans only after maturation in a suitable (intermediate) snail host.

Schistosomiasis results from penetration of intact skin by infective cercariae (eFig. 207-2.2). Dermatologic findings in early disease manifest either at the time of cercarial penetration (swimmer's itch or cercarial dermatitis), or during migration of immature forms (schistosomulae) from the skin and through tissue to the venous systems of their target organs (which may vary depending on the infecting species), where they mature into adults. Migration of schistosomulae in previously unsensitized individuals (usually travelers) can result in acute illness (Katayama fever) consisting of fever, myalgias, cough, and wheezing, and may be accompanied by urticaria. Sexual reproduction leads to the release of eggs into the local circulation. En route to the bladder or bowel, eggs may sometimes become trapped in ectopic tissues, including skin, where they cause a granulomatous reaction. In skin, this may lead to a chronic papular eruption. Eggs excreted in urine or feces hatch in fresh water, releasing cercariae, which must undergo further maturation in one of several intermediate snail hosts in order to infect humans.

Infection can also result from penetration of intact skin by larvae, exemplified by human hookworm infection (eFig. 207-2.3). Larval skin penetration may cause localized papular or vesicular lesions, or creeping eruption. Larvae then migrate to the circulatory system where they are carried to the lungs, penetrate the alveoli, and ascend the bronchial tree, are swallowed, and enter the gastrointestinal tract. Skin findings may also occur during larval migration to the lungs. Maturation into adult worms occurs in the small intestine, where they reproduce and release eggs into stool. Under the appropriate environmental conditions, eggs mature into infective larvae in soil. In contrast, larvae of animal hookworms (e.g., Ancylostoma braziliense) cannot mature beyond the larval stage in humans and tunnel aimlessly in the skin before the infection eventually extinguishes itself.

Larvae can also be introduced through intact skin by insect bites (e.g., in filarial infections). The insect vector and the target tissue both vary according to the infecting species; cutaneous disease may be seen during either migration of larval forms through tissue, or as a result of adult worms in tissue. Microfilariae released from mature adult worms are taken up by an insect during a subsequent blood meal, and then undergo maturation to infective forms within the insect before being introduced into another human host.

A variety of helminths can infect humans and cause cutaneous findings (Table 207-2). Cutaneous manifestations can be seen at every phase of the helminth life cycle in humans: by larvae or cercariae during skin penetration; during larval migration and tissue invasion; and due to the presence of eggs and adult worms in skin and soft tissues. Skin lesions also may occur during either early (acute) or chronic infection.

The pathogenesis of skin lesions in helminthic infections is varied. Direct penetration of skin may lead to a localized immune response, as seen in CLM or cercarial dermatitis. Migration of helminths can cause a generalized immune response (urticaria; maculopapular eruptions), particularly due to migration of larvae or immature forms (e.g., with Ascaris or Toxocara infection); a local inflammatory reaction to adult worms or eggs may also develop, as occurs with cutaneous nodules due to Onchocerca volvulus and in schistosomiasis. Skin changes can also result from disruption of the normal skin structures due to lymphedema, as with filarial infections. Finally, ill-defined systemic immune reactions such as erythema nodosum (EN) or erythema marginatum, rarely reported manifestations of several helminthic infections, may also be present. Skin findings of helminthic infections do not generally result from hematogenous spread of parasites, in contrast to many bacterial and viral infections.

Helminths induce a dramatic expansion of the T helper 2 (Th2) lymphocyte subset, with elevated levels of immunoglobulin E (IgE), peripheral eosinophilia, and an increase in tissue mast cells. It is unclear whether these Th2-derived responses are important in the protective immune response against the parasite, are responsible for immune-mediated pathology, or both.12 Despite high levels of IgE and other features of Th2 cell activation, allergic responses are rarely observed in infected individuals except during the invasive phase of infection, when pruritus and/or urticaria may occur. Infected hosts have evolved elaborate immune evasion strategies that permit long-lived helminthic infections, including the induction of tolerance to parasite antigens.

With the exception of CLM, most travelers and immigrants who present with dermatologic complaints will not have a diagnosis attributable to a helminthic infection. However, clearly these must be considered if the epidemiologic and exposure history and clinical findings are consistent with a helminthic infection, since these are treatable infections that have important clinical implications, such as disseminated strongyloidiasis in an immunocompromised host.

As with all diseases of travelers and immigrants, a thorough history is essential in order to direct the clinician toward the correct diagnosis. The history should focus on aspects related to travel (or residence in endemic areas), general medical conditions, and medications. In addition, specific details of the dermatologic complaints must also be obtained. Finally, the clinician should be knowledgeable about (or know how to find out about) outbreaks of disease that may have been ongoing during an individual's travel or residence in a given area.

Exposure History: Travel and Areas of Residence

The travel history (or history of residence in endemic areas) must be thorough in order to elucidate likely exposures to helminths. Specific details may be more readily obtained in recently returned travelers than immigrants, although immigrants are much more likely to be aware of local and endemic diseases (albeit often by local names). Details to be obtained include the exact dates, durations, and locations of travel or residence; purpose of travel; activities or occupations, inquiring specifically about those that would increase exposure to specific helminths (Table 207-3); dietary intake; a history of similar signs and symptoms in other family members or fellow travelers; and the use of preventive measures.

The exact destinations of travel (urban vs. rural), not only the country or countries visited, are important to obtain. Although some diseases may be endemic throughout a world region or area (eTable 207-1.1), the prevalence of others may vary greatly, sometimes within a given country. For example, onchocerciasis and loiasis are endemic in West Africa, but generally not in other parts of Africa, and both infections are found only in rural areas, unlike Bancroftian filariasis (Wuchereria bancrofti) that is often transmitted in urban centers. The risk of disease may not be present in all areas of a country in which a disease is considered to be endemic; for example, schistosomiasis is found in Brazil, but only in the northeastern region. Duration of travel or residence in an endemic area (and hence duration of exposure) is relevant for some diseases; schistosomiasis can be acquired after a single exposure to infective cercariae in freshwater, whereas filariasis is often acquired only after numerous bites, and therefore is rare among short-term travelers to endemic areas.

The purpose of travel is also correlated with the likelihood of exposure to specific pathogens. Rural and adventure travelers are more likely to be exposed to helminthic infections than are business travelers, travelers whose itineraries are limited to urban areas, and those whose travels are of shorter durations.

Certain activities and occupations will place individuals at greater risks of helminthic infections while abroad (Table 207-3). Examples of common exposures and associated diseases include barefoot walking or walking in open shoes (sandals) (e.g., CLM, strongyloidiasis); freshwater swimming in Africa (e.g., schistosomiasis); and dietary indiscretions such as consumption of salads or undercooked or contaminated meat or fish (e.g., ascariasis, echinococcosis, fascioliasis, gnathostomiasis). Although direct exposure to animals is not a risk factor for helminthic infections, the risk of CLM is greater in areas with a higher prevalence of stray dogs and cats. For those infections that are vector borne, such as filarial infections transmitted by mosquitoes, black flies, and deer flies, the use of preventive measures such as appropriate clothing, insect repellent, and bed nets can reduce the risk of infection.

General Medical History

In addition to the travel history, a general medical history should be obtained. Skin findings may be related to underlying medical conditions, or to any associated treatment for these. The differential diagnosis of skin lesions in a returned traveler or immigrant also includes noninfectious disorders such as contact dermatitis (including to jewelry), drug eruptions, and photosensitivity reactions (that may be precipitated by travel-related medications such as doxycycline). A list of prescription and nonprescription medications or supplements should be obtained, in particular those that may have been started recently and/or prescribed abroad, as well as any recent use of topical medications or products.

Dermatologic History and Physical Findings

The dermatologic history should include details regarding the initial presentation, morphology, and anatomic distribution of skin lesions; the progression and duration of lesions; time of onset relative to potential exposures; and any associated local and systemic signs and symptoms. Although some manifestations of helminthic infections, such as urticaria or maculopapular eruptions, are nonspecific, the differential diagnosis of helminthic dermatoses can often be narrowed based on the description and morphology of the lesion(s) present. For some diseases such as CLM, skin findings are virtually pathognomonic and the diagnosis can be established by history and careful examination of skin lesions, often without the need for additional investigations.

Morphologic Characteristics and Distribution of Skin Lesions Due to Helminthic Diseases

Skin lesions due to helminthic infections can assume a variety of morphologies. The most commonly encountered problem is that of migratory skin lesions. CLM (creeping eruption) is the most common cause of migratory lesions in general. Subcutaneous nodules, papular eruptions, and urticaria and pruritus are also common manifestations of helminthic infections.

Migratory Skin Lesions

Migratory lesions can be caused by multiple helminths. Migratory lesions can be linear (serpiginous) or may be more ill-defined areas of erythema and swelling, and may be painless, painful, or pruritic. Table 207-4 lists the most common helminthic causes of migratory lesions, as well as characteristic features of these lesions.

Serpiginous and linear lesions are most commonly due to CLM (most frequently caused by A. braziliense and Ancylostoma caninum; see also Section “Hookworm-Related Cutaneous Larva Migrans”). Usually one to three (or more) erythematous, serpiginous, and intensely pruritic lesions due to intradermal larval migration are present (Fig. 207-3); bullae and vesicles may also be present (Fig. 207-4). Lesions usually measure 3 mm in width and 15–20 cm in length. Lesions of CLM may rarely be accompanied by severe folliculitis, or may present as papules alone without a linear element (papular larva migrans). Serpiginous skin lesions in S. stercoralis infection, a pathognomonic manifestation of strongyloidiasis known as larva currens, typically present as recurrent, transient, and rapidly moving skin lesions (Fig. 207-5). Larval migration may occur at rates of 5–10 cm/hour, and the lesions usually disappear within hours only to recur over subsequent weeks to years. Lesions typically occur on the buttocks and in the perianal region, as larvae exit the gastrointestinal tract and reinfect the host by penetrating the perianal skin. Linear migratory lesions can also be seen occasionally in human hookworm infection (Ancylostoma duodenale and Necator americanus) at the site of larval penetration, and in gnathostomiasis (usually relatively slow migration at 1 cm/hour). Linear migratory lesions can also be seen in Loa loa infection, and result from movement of the adult worm (not larvae) in tissue, typically under the skin or also across the bulbar conjunctivae (Fig. 207-6).

Migratory subcutaneous swellings and nodules are characteristic of infections due to Fasciola, Gnathostoma, and Paragonimus, and in sparganosis (Spirometra species). Lesions may be painful or pruritic. Migratory swelling due to the movement of adult worms is also seen in dracunculiasis, in which movement within a bullous, vesicular, or edematous lesion on the foot is often noted prior to eruption of the skin lesion and egress of the adult worm (Fig. 207-7). Since the implementation of global eradication and drinking water monitoring programs in endemic countries, cases of dracunculiasis have decreased dramatically and the disease has almost been eliminated.13

Subcutaneous Nodules and Masses

Subcutaneous and soft tissue masses may have variable characteristics, including overlying erythema, pain or tenderness, and pruritus. They may be single or multiple, and fixed or mobile. The more common etiologies of nodular lesions are listed in Table 207-5.

Solitary nodules or masses are found in echinococcosis, filariasis due to Brugia malayi and W. bancrofti (both of which may cause scrotal masses in men, due to lymphatic obstruction), dirofilariasis, and coenurosis. Multiple nodules are typical of cysticercosis (Taenia solium infection), in which small, painless subcutaneous or intramuscular nodules are present, although single nodules can also occur. Subcutaneous cysticercosis, although reported in over 50% of infected individuals in older case series,14 currently occurs in less than 10% of cases. Most other helminths that manifest as subcutaneous nodules or masses may present with single or multiple lesions. Painless nodules are most characteristic of coenurosis, cysticercosis, dirofilariasis, echinococcosis, and onchocerciasis. Painful nodules are seen in paragonimiasis and sparganosis. Transient painful lesions that resolve and subsequently recur in different anatomic areas are characteristic of Gnathostoma infection and loiasis. Fixed lesions are typical of cysticercosis, echinococcosis, and onchocerciasis.

Papular and Macular Lesions

Papules and macules occur in relatively few helminthic infections (Table 207-6). Papular lesions may occur at sites of skin penetration by infective larvae or cercariae in CLM and schistosomiasis. In CLM, papules are typically in the feet or buttocks, similar to the distribution of migratory lesions. In schistosomiasis, exposure to infected freshwater (for avian or human schistosomes) or salt water (avian schistosomes) may cause pruritus, which is followed rapidly by a papular eruption in previously sensitized individuals. Chronic papular lesions (bilharziasis cutanea tarda) may be present in chronic schistosomiasis. Papular lesions may also be manifestations of acute or chronic infection with O. volvulus, and have been reported in disseminated and chronic strongyloidiasis.

Urticaria and Pruritus

Pruritus (Table 207-7) may be present in the absence of skin findings, either as a primary symptom of infection (e.g., filariasis due to Mansonella perstans), or before the onset of skin lesions (e.g., schistosomiasis). Pruritus is a common feature of most helminthic infections, with the noteworthy exceptions of lymphatic filariasis (e.g., due to Brugia species and W. bancrofti) and tapeworm infections. Pruritus ani is characteristic of strongyloidiasis and enterobiasis (pinworm infection).

Urticaria are often present in the acute phase of infection, during which larvae or other immature forms actively invade human tissues. Helminths that infect humans by penetration of skin may cause a local urticarial rash at the sites of penetration. Migration of immature forms in the circulation may cause a generalized hypersensitivity reaction; urticaria is common during this phase of infection by many helminths (Table 207-7).

Localized Edema

Although edema or swelling may be an associated feature of many helminthic skin lesions, localized edema is highly suggestive of the presence of certain infections.

Eyelid edema in particular may be seen in gnathostomiasis and onchocerciasis (Calabar swelling), and violaceous periorbital edema is characteristic of trichinosis. Limb edema is highly suggestive of lymphatic filariasis (due to Brugia species and W. bancrofti). Rarely, limb edema (“gros bras camerounais”) may occur with acute onchocerciasis, usually in conjunction with pruritus, and typically only after exposures in travelers and expatriates visiting West and Central Africa.15,16

Changes in Skin Texture or Pigmentation

Hypopigmentation of skin can be a feature of chronic infection caused by O. volvulus (“leopard skin”), M. perstans, and Mansonella streptocerca. Hypopigmented macules are the most common cutaneous findings in streptocerciasis.17 In onchocerciasis, depigmentation is characterized by perifollicular pigmentation within macular or minimally depressed areas, with yellow-brown hypopigmentation, and is particularly noticeable in dark-skinned individuals (see Section “Onchocerciasis” in Chapter 75). Hyperpigmentation can also occur with mansonellosis due to M. streptocerca, as well as in chronic schistosomiasis. Lichenification in the context of chronic pruritus is a feature of onchocerciasis (“sowda” in Arabic), and to a lesser extent mansonellosis; hyperpigmented plaques eventually coalesce and become lichenified over time, particularly over the lower extremities and in young adults in Yemen and Sudan. Verrucous lesions may be seen in chronic schistosomiasis (bilharziasis cutanea tarda). Ichthyosis may also be present in chronic onchocerciasis.

Other Cutaneous Manifestations

Petechiae may be present with trichinellosis and are frequently seen in disseminated strongyloidiasis, in which they are particularly prominent on the trunk. Vesicles or bullae may be seen at the site of larval skin penetration in up to 15% of patients with CLM, in human hookworm infection, and occasionally in dracunculiasis, onchocerciasis, and strongyloidiasis. Ulcers are uncommon findings in most helminthiases with the exception of dracunculiasis, in which multiple ulcers are common. Ulcerative genital lesions, particularly in women, may occasionally be present in schistosomiasis and tend to occur more often with acute disease (e.g., in travelers).18

EN is rare in helminthic infections, but has been described as a clinical finding with hookworm infection,19 and in visceral larva migrans,20 sparganosis,21 and lymphatic filariasis. It has also been reported in one patient in conjunction with A. lumbricoides infection,22 although EN in this patient may also have been due to concomitant Chlamydia pneumoniae pneumonia. Erythema multiforme has been reported in CLM.23 Eosinophilic panniculitis has been documented in gnathostomiasis24 and toxocariasis.25,26 Eosinophilic cellulitis (Well's syndrome) may occur in ascariasis,27 onchocerciasis, and toxocariasis.28 Eosinophilic folliculitis due to helminths has rarely been described in CLM and in toxocariasis.29 Exfoliative dermatitis of the affected limb may occur during the resolution phase of W. bancrofti infection.

Interval between Exposure and Onset of Symptoms

The time of onset of skin disease (and other key symptoms) relative to travel and likely exposures can be helpful in establishing a diagnosis (Table 207-8). Some infections such as acute schistosomiasis or CLM become evident within hours to days of exposure, whereas others may not present until months to years after infection.

Progression and Duration of Skin Lesions

Skin lesions due to helminthic infections can persist for variable durations (Table 207-8). For those helminths that cause infection by penetration of skin, local dermatologic findings last only for a short time during infection by human helminths, but may persist longer with animal helminths (e.g., CLM). During the chronic phase of infection, however, the duration of cutaneous manifestations varies depending on the infecting helminth. For infections in which skin findings are the result of inflammatory reactions to larvae or eggs in tissues (e.g., onchocerciasis and schistosomiasis, respectively), clinical manifestations can persist for the lifespan of the adult worms, which in some cases may be years. Even with appropriate therapy for chronic infections, chronic skin changes may not resolve completely.

Complications of Cutaneous Helminthic Infections

Secondary complications including excoriation and secondary superinfection are not uncommon, especially when pruritic lesions are present. Skin changes such as lichenification and pigment changes, as noted above, may be persistent. Other significant complications of cutaneous helminthic diseases are addressed in the discussion of specific helminths.

Associated Symptoms and Related Physical Findings

Apart from the skin, symptoms of helminthic infections tend to most frequently involve the respiratory, gastrointestinal, and neurological systems, and the eye. Disease may also occur in many other tissues due to aberrant migration of larvae and adult worms.

Because the skin lesions of many helminthic infections tend to occur in acute (larval) infection, and nondermatologic symptoms often result from the presence of adult helminths or their products of reproduction, it is important to appreciate that skin findings often precede other manifestations of disease. However, dermatologic and nondermatologic symptoms may coexist in some acute infections, as well as in chronic infections.

Pulmonary Disease

Helminthic diseases in which pulmonary symptoms and skin disease may be present are listed in eTable 207-8.1. Loeffler's syndrome, a hypersensitivity syndrome consisting of dyspnea, wheezing, cough, and fever, typically results from larval migration through lung tissue and may be seen in infection caused by human hookworms, Ascaris, and Strongyloides. Because these symptoms are due to larval migration, they begin shortly after infection and may occur coincidentally with an urticarial rash. Loeffler's syndrome typically lasts for 1–2 weeks.

Other pulmonary symptoms are generally not simultaneous with dermatologic symptoms, occurring after larvae have matured into adult forms. Hemoptysis is uncommon; among helminthic infections it is most frequently a feature of paragonimiasis, but can also be a symptom of echinococcal disease and disseminated strongyloidiasis. Pleural effusions also occur rarely, and in helminthic infections are more likely to be eosinophilic. The most common parasitic etiology is Paragonimus, but effusions can also be caused by a variety of other helminths (eTable 207-8.1).30–32

Gastrointestinal Disease

Helminthic infections causing gastrointestinal symptoms are listed in eTable 207-8.2. Abdominal pain is most commonly seen in ascariasis and human hookworm infection, after dermatologic manifestations have resolved, and in strongyloidiasis. Abdominal pain in strongyloidiasis is typically epigastric in location. Because S. stercoralis can complete its entire life cycle within the human host, larvae and adult worms may coexist simultaneously, and thus abdominal symptoms may be coincident with larva currens and pruritus ani. Right upper quadrant abdominal pain may also be a manifestation of acute fascioliasis, caused by larval penetration of the hepatic capsule; urticaria may also be present during this phase. Diarrhea can be a symptom of strongyloidiasis, and rarely of schistosomiasis.33 Hepatitis may be seen in acute fascioliasis. Liver masses or abdominal masses may be the presenting symptom of echinococcosis. Hepatomegaly is one of the classic findings of visceral larva migrans (toxocariasis), typically occurring in children and usually in conjunction with fever, respiratory symptoms (wheezing), and occasionally urticaria. Hepatomegaly has also been reported as a finding of several other helminthiases. Granulomatous hepatitis may also cause hepatomegaly, and is most commonly encountered in schistosomiasis (due to granuloma formation around eggs in the periportal circulation), but can also be a feature of ascariasis (eggs), strongyloidiasis (larvae), and toxocariasis (larvae). Biliary disease may be due to either occlusion of the biliary tract by adult worms or flukes (e.g., ascariasis, fascioliasis, strongyloidiasis) or due to compression of the biliary tract by a mass lesion (e.g., echinococcosis). Hepatic fibrosis can be a complication of chronic schistosomiasis.

Neurologic Disease

Helminthic infections most commonly affecting the central nervous system include neurocysticercosis and strongyloidiasis. Seizures, typically focal but sometimes generalized, are the most common presentation of neurocysticercosis. Neurocysticercosis should be considered in the presence of subcutaneous cysticercosis. The clinical presentation of neurocysticercosis is determined by the number, size, and location of intracranial lesions, as well as the viability of cysts (dying cysts produce more inflammation and are more likely to be associated with seizures). Globally, neurocysticercosis is among the most common causes of seizure disorders. Seizures may also occur with infection due to Schistosoma species, Paragonimus, and in sparganosis. Meningitis can be seen in strongyloidiasis. S. stercoralis larvae may be visualized in cerebrospinal fluid, but more commonly meningitis is a result of Gram-negative bacteremia, due to Gram-negative enteric organisms that are carried across the bowel mucosa during larval penetration in disseminated disease; abdominal petechiae or purpura are often present. Eosinophilic meningitis or meningoencephalitis may be a feature of cysticercosis, gnathostomiasis, paragonimiasis, schistosomiasis, toxocariasis, and less commonly strongyloidiasis, among others.34 Mass lesions or cysts can be caused by Echinococcus spp., Paragonimus, Taenia spp. causing coenurosis, and Toxocara. In schistosomiasis, intracranial infection is most commonly associated with Schistosoma japonicum infection and may result from the development of granulomas around ectopic eggs. Other central nervous system manifestations of helminthic infections, including brain abscesses, transverse myelitis and myelopathy, and intracranial hemorrhage, may occasionally be seen.

Ocular Disease

While ocular involvement is most frequently associated with infections due to Loa loa and O. volvulus (river blindness), disease involving the conjunctiva, sclera, and all chambers of the eye can be occasional features of most helminthic infections. Onchocerciasis is one of the major causes of blindness worldwide. Ocular symptoms and findings are often related to the presence of larvae or microfilariae migrating through and causing inflammatory reactions in various chambers of the eye and the retina. Onchodermatitis is common in chronic infection, and skin findings and eye disease may be present simultaneously. Ocular disease is also one of the most frequent presentations of sparganosis; in one case series in Thailand,35 ocular disease accounted for half of all cases.

Conjunctivitis is the typical ocular manifestation of gnathostomiasis and sparganosis, but has also been reported in a variety of other infections. Keratitis is most commonly present in onchocerciasis and coenurosis. Uveitis is characteristic of onchocerciasis and schistosomiasis. Retinitis or chorioretinitis may be present in onchocerciasis. Migration of adult worms through the eye may be seen in loiasis and dirofilariasis, and less commonly fascioliasis and gnathostomiasis, and gives rise to a foreign body sensation in the eye. Granulomatous nodules in the eye or conjunctivae may be present in schistosomiasis and M. perstans infection.36 Eyelid swelling (Calabar swelling) may be due to onchocerciasis, and to filariasis caused by M. perstans.

Lymphadenopathy

Lymphadenopathy is an uncommon finding in helminthic infections, with the exception of filarial infections. Regional lymphadenopathy can be present with lymphatic filariasis (due to infection with Brugia spp. and W. bancrofti), as well in loiasis, mansonellosis due to M. streptocerca, and onchocerciasis. Generalized lymphadenopathy may be present in lymphatic filariasis, and in acute schistosomiasis (Katayama fever).

Other Symptoms

Fever and urticaria can be features of Loeffler's syndrome (eTable 207-8.1), which may be the initial manifestation of infection due to A. lumbricoides, human hookworm, S. stercoralis, and in toxocariasis. Fever in acute trichinellosis usually occurs in conjunction with other symptoms including myalgias. Fever is also a finding in acute schistosomiasis (Katayama fever) and may also be present in other helminthiases, typically during larval migration. Gram-negative sepsis may occur in disseminated strongyloidiasis (see Sections “Neurologic Disease and Strongyloidiasis”).

Laboratory Evaluation

Results of routine blood tests, including eosinophilia, are neither sensitive nor specific for diagnosing helminthic infections. While most hematological and biochemical tests are nonspecific, the presence of eosinophilia can be suggestive of specific diseases when combined with clinical findings and/or the exposure history, and should prompt additional investigations.37,38 Diagnosis of helminthic infections may also be aided by results of ancillary investigations (e.g., chest radiography, abdominal imaging).

Eosinophilia

Eosinophilia, defined as an absolute eosinophil count of greater than 500 eosinophils/mm3, should prompt appropriate investigations for helminthic infections as noted above. Eosinophilia is not typical of infections due to most pathogens other than helminths; helminth antigens are effective stimuli for inducing eosinophilia. Levels of eosinophils in the blood can be affected by host factors including the response to other bacterial, viral or fungal coinfections (which lower eosinophil counts), the use of systemic steroids (which lower eosinophil counts), and an immunosuppressed state. In helminthic infection, eosinophil counts vary according to the stage of infection and the infecting helminth. Eosinophilia is not a feature of infection due to intestinal lumen dwelling helminths, except during the larval migration phase for those helminths in which this occurs; in contrast, helminthic infections in which adults, larvae, or eggs persist in tissues are typically associated with eosinophilia. Eosinophil counts are typically normal during the penetration phase and reach their highest levels (often markedly elevated) during the invasive phase of the cycle. Eosinophilia often accompanies the urticarial rash during the invasive stage of infection; thereafter, the eosinophil count often decreases slowly and may fluctuate more or less above the normal value during the chronic phase of infection. A transient hypereosinophilia may be also observed approximately 10 days after the start of effective antihelminthic treatment, and eosinophilia may persist for 1–2 months after successful helminth eradication.

Helminths typically causing eosinophilia are listed in Table 207-9. Severe or high-grade eosinophilia (an eosinophil count of >3,000/mm3) is suggestive of infection caused by relatively few of these parasites (Table 207-9).

Additional Laboratory Tests

Other laboratory tests may be abnormal but may not aid with establishing a specific diagnosis. Other than leukocytosis, which may reflect only the presence of eosinophilia, hematologic studies obtained when skin lesions are present are unlikely to be helpful. Evidence of disseminated intravascular coagulation may be present in disseminated strongyloidiasis. Iron deficiency anemia due to chronic low-grade intestinal bleeding is a feature of established hookworm infection but occurs well after the resolution of cutaneous disease.

Biochemical testing may reveal abnormal liver function tests and enzymes in acute fascioliasis and toxocariasis, when urticaria may be present. Granulomatous hepatitis may be suggested by an obstructive picture, with a disproportionately elevated alkaline phosphatase. Most biochemical tests are otherwise nonspecific and are of limited use in determining the correct diagnosis.

Radiologic Investigations

Symptomatic patients with Loeffler's syndrome and acute schistosomiasis will typically have diffuse patchy infiltrates on chest radiographs; urticaria may be present at this time. Radiologic findings consistent with acute respiratory distress syndrome may be present in disseminated strongyloidiasis. Chest X-rays may also be abnormal in paragonimiasis (cystic lesions, pleural effusion). Pleural effusions may be present in infection due to other helminths as well (eTable 207-8.1). A solitary pulmonary nodule may be noted in dirofilariasis.

Abdominal imaging [ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI)] should be directed by abdominal symptoms and is suggestive of a diagnosis in relatively few helminthic infections. Septated hepatic cysts are characteristic of echinococcosis, and hepatic masses or nodules (hypodense lesions up to 10 mm in size) may be visualized on ultrasound or CT scan in fascioliasis. Tracts or tunnels representing migration of immature flukes through the liver may also be noted in fascioliasis.39,40

Imaging studies of the central nervous system are diagnostic in neurocysticercosis, in which CT or MRI usually reveals parenchymal cysts and occasionally intraventricular cysts.

Diagnosis of Helminth Infections

The definitive diagnosis of most helminthic infections rests on identification of one or more of the various stages of the helminth (e.g., larvae, eggs, adult worms) in tissue specimens, blood, or excretions (stool or urine). Occasionally adult worms may be observed during medical procedures (e.g., endoscopy, or during surgery). In many helminthic infections causing skin disease, however, cutaneous findings occur during the larval migration phase, and hence precede the presence of adult worms and the production of eggs or larvae. The diagnosis of a helminthic infection is therefore often difficult during the penetration and acute phase of the disease; diagnosis may be suspected because of associated epidemiologic and clinical findings. In chronic infection, the diagnosis can be established based on the identification of parasite eggs or larvae, or occasionally adult worms, but the sensitivity of stool examination can also vary depending on the parasite.

Serologic assays are available for many helminthic infections, but vary greatly in their sensitivity and specificity; their utility is also limited by cross-reactivity of tests among the various helminths. Another significant limitation to serologic testing relates to the delayed appearance of antibodies after acute infection. Although antibody production typically begins during the invasive (acute) phase of disease, when skin lesions are clinically apparent, titers may be negative at this time. Serologic tests may need to be repeated several weeks later, after resolution of cutaneous findings; an increase in titers (seroconversion) retrospectively supports or establishes the clinical diagnosis. Similarly, positive antibody titers may reflect prior infection but do not necessarily imply active or acute disease, although a decrease in antibody titer may be seen following appropriate therapy in some infections, notably strongyloidiasis.

Additional diagnostic tests may include pathologic examination of tissue specimens or blood (for microfilariae), microscopic examination of other specimens (e.g., bronchoscopy specimens in disseminated strongyloidiasis), or molecular testing. Diagnostic tests for helminthic infections are summarized in eTable 207-9.1.

Treatment

Recommended and alternate therapies for treatment for helminthic infections causing cutaneous findings can be found in recent reviews and guidelines,41,42 and in eTable 207-9.2.

Sections that follow below describe key features of the most common and important helminthic infections. CLM syndrome and enterobiasis (pinworm infection) are encountered relatively frequently by clinicians in developed countries. Strongyloidiasis, although not as commonly seen, must be considered in the appropriate clinical context; failure to diagnose and treat the infection may have significant clinical consequences for immunocompromised patients in particular, in whom disseminated strongyloidiasis carries a significant mortality risk. For these reasons, these three infections will be described below. An outline of the other helminthic infections that may present with dermatologic findings is available online.

Cutaneous Larva Migrans Syndrome

The terms CLM and creeping eruption are often used interchangeably when referring to disease caused by animal hookworms. Technically, however, CLM refers to a syndrome in which the larvae of any animal nematode infect humans AND in which the infected human is a dead-end host. These nematodes include animal hookworms, Gnathostoma species, and agents of zoonotic filariases including Spirulina X,43 Pelodera strongyloides, and zoonotic Strongyloides species. By definition, CLM syndrome does NOT include diseases in which creeping eruption is due to: (1) nonlarval forms of parasites (e.g., dracunculiasis, loiasis); (2) larval forms of human nematodes such as S. stercoralis (larva currens); or (3) larval forms of trematodes such as Fasciola gigantica. Creeping eruption refers to the clinical finding (sign) of a migratory serpiginous lesion but does not denote the etiology of the lesion.

Clinically, the hallmark of CLM is a creeping eruption. The different helminthic diseases causing creeping eruption can often be distinguished based on the epidemiologic and exposure history, the characteristics of the cutaneous trail(s) (location, number, width and length, rate of movement) (Table 207-4), and the duration of symptoms (Table 207-8), in addition to other clinical and laboratory findings. The correct diagnosis is required for appropriate treatment.

Hookworm-Related Cutaneous Larva Migrans

Hookworm-related (Hr) CLM (creeping verminous dermatitis, sandworm eruption, plumber's itch, duck hunter's itch) is most commonly caused by animal hookworms, and in particular A. braziliense. Other skin-penetrating hookworm larvae that produce similar disease include A. caninum, Uncinaria stenocephala (hookworm of European dogs), and Bunostomum phlebotomum (hookworm of cattle). A. caninum causes eosinophilic enteritis as well as cutaneous disease. Cats and dogs are hosts for Ancylostoma ceylanicum and A. caninum.

HrCLM is widely distributed but is most commonly found in tropical and subtropical areas, especially the Southeastern United States, Caribbean, Africa, Central and South America, India, and Southeast Asia. Contact with sand or soil contaminated with animal feces is required for infection to occur; infection can be prevented by avoiding skin contact with fecally contaminated soil. Larvae penetrate human skin and migrate up to several centimeters a day, usually between the stratum germinativum and stratum corneum. This induces a localized eosinophilic inflammatory reaction. Most larvae are unable to undergo further development or invade deeper tissues, and die after days to months.

Typical skin lesions appear 1–5 days after exposure. The characteristic lesion of HrCLM is an erythematous, raised, and vesicular, linear, or serpentine cutaneous trail (Fig. 207-3).44 Vesicular or bullous lesions may be seen at the site of larval skin penetration in up to 15% of patients with CLM (Fig. 207-4).7,45 Lesions are approximately 3 mm wide and may reach 15–20 cm in length. They can be single or multiple, are intensely pruritic, and may be painful. The hookworm larvae advance a few millimeters to a few centimeters daily. The most common anatomic sites (usually 3–4 cm from the penetration site) include the feet (Fig. 207-3) and buttocks (Fig. 207-8), although other sites may be affected. Excoriation and impetiginization are uncommon (10% of cases). Skin lesions usually last between 2 and 8 weeks, but have been reported to last for up to 2 years. Systemic signs and symptoms (wheezing, dry cough, urticaria) have been reported in some patients.46

A less frequent but well reported clinical presentation is that of hookworm folliculitis, consisting of 20–100 eosinophilic follicular papules and pustules confined to a particular area of the body, usually the buttocks.47–49 Patients with folliculitis usually also have creeping eruption. Papular lesions without CLM (papular larva migrans) are a less common presentation.50 Other cutaneous signs related to the subcutaneous migration of helminth larvae have been occasionally described, such as urticaria and panniculitis.26

The diagnosis of HrCLM is based on clinical findings. Hookworm folliculitis can also be diagnosed clinically when creeping eruption is also present; if not, skin biopsy may be required. Histopathologic findings include larvae trapped within the follicular canal, the stratum corneum, or the dermis, together with an inflammatory eosinophilic infiltrate.47 Skin scrapings in patients with folliculitis may reveal live and dead larvae when examined by light microscopy with mineral oil.

Both albendazole (400 mg po daily for 3 days) and ivermectin (200 μg/kg daily for 1 or 2 days) are effective therapies for HrCLM.51 Treatment of hookworm folliculitis may require repeated treatments. Topical therapy with thiabendazole or 10% albendazole may also be used. Because larvae have usually migrated beyond the end of the visible skin lesion and their location cannot be reliably determined, surgical excision or cryotherapy are not recommended.

Enterobiasis (Pinworm Infection)

Enterobiasis (threadworm, pinworm or seatworm infection; oxyuriasis) is caused by E. vermicularis. It is among the most widely distributed helminthic infections and is found worldwide. Transmission is by the fecal-oral route; infection results from ingestion of E. vermicularis eggs (e.g., by contact with contaminated fomites or via contaminated fingers) and rarely by inhalation and ingestion of aerosolized eggs in dust. The highest rates of infection are among children. Infection can be prevented by treatment of infected cases and good personal hygiene.

Nocturnal anal and perianal pruritus is the primary clinical feature. The worm may be seen around the anus. The skin may become impetiginized, and cellulitis may occur as a complication. Women may rarely develop vulvovaginitis; a nodular lesion of the vulva has also been described.52 Nondermatologic extraintestinal manifestations are rare but have been reported. Epidemiologically, enterobiasis is often associated with an intestinal protozoan, Dientamoeba fragilis, which may produce gastrointestinal upset. The differential diagnosis includes strongyloidiasis, atopic dermatitis, contact dermatitis, and neurodermatitis.

The diagnosis is established by identification of E. vermicularis eggs in the perianal area, most effectively by the sticky tape method. A piece of tape, sticky side out, can be attached to a wooden tongue depressor and firmly pressed against the perianal skin immediately on waking in the morning, before defecation or bathing. The tape is removed and placed sticky side down on a slide, and examined under a microscope. Sensitivity of this method is 70% with three specimens and increases to almost 100% with seven specimens. Eggs are found in stool in only 10%–15% of infections. Occasionally, the adult worm (white, up to 4 mm in length) is found in the perianal area, vulva, vagina, or underclothes. When ectopic sites are involved, the parasite may be identified in tissue sections.

Enterobiasis is self-limited if reinfection does not occur. Treatment with one dose of albendazole 400 mg, mebendazole 100 mg, or pyrantel pamoate 11 mg/kg, is effective. Treatment of household members is also recommended as household transmission is common. Treatment should be repeated once, 2 weeks after the first course of therapy, since medications are relatively ineffective against developing larvae and newly ingested eggs. Specific personal hygiene measures are also important for eradication of infection.

Strongyloidiasis

Strongyloidiasis is caused by S. stercoralis, which is endemic to Africa, Asia, Southeast Asia, and Central and South America. Disease is also found in the Caribbean, and to a much lesser extent in Europe, Japan, Australia, and parts of the Southern United States. Humans are the only hosts. Infection caused by Strongyloides fuelleborni, found sporadically in Africa and Papua New Guinea, is relatively rare. The prevalence of infection can be high in endemic areas, as well as among institutionalized mentally impaired persons, in former prisoners of war, and in refugees and immigrants from endemic areas. Infection results from penetration of skin or mucous membranes by infective larvae, usually from soil; the risk of infection is high for persons with frequent soil contact (e.g., walking barefoot) in warm, moist areas contaminated by human feces. Appropriate sanitation and avoidance of soil contact by skin in endemic areas reduce the risk of infection. Persons infected with human T-cell lymphotrophic virus type 1 (HTLV-1) and those receiving immunosuppressive therapy may develop hyperinfection (disseminated disease). Persons with a history of prior residence or activities that place them at an increased risk for strongyloidiasis should be evaluated for presence of the infection, and should be treated even if asymptomatic. This is especially important in persons who receive or will receive immunosuppressive therapy.

Most infected persons have low worm burdens and are persistently infected for life, often with minimal or no symptoms. If symptoms are present they are generally intermittent, with long asymptomatic periods between episodes. Cutaneous manifestations may be seen at any phase of infection. Following skin penetration, an urticarial eruption or larva currens may develop. Larva currens, a migratory serpiginous and intensely pruritic lesion caused by intradermal migration of larvae, can be differentiated from CLM by the high rate of movement (up to 5–10 cm/hour). Larva currens typically disappears within a few hours, only to recur over the course of weeks to years. During the invasive phase of the infection, transient pulmonary manifestations (cough, wheezing, infiltrates) are of pulmonary migration and may be associated with urticaria. Chronic strongyloidiasis gives rise to nonspecific gastrointestinal complaints (epigastric pain, nausea, vomiting, diarrhea, constipation, malabsorption, weight loss). Perianal larva currens may be present (Fig. 207-5) and is pathognomonic of chronic infection. Persons chronically infected with Strongyloides may also experience pruritus ani and chronic urticaria, which may be complicated by prurigo nodularis or lichen simplex chronicus.53

Hyperinfection syndrome most often occurs in the presence of impaired cellular immunity, typically because of the use of systemic steroids but also with other immune compromised states including HTLV-1 infection. Interestingly, human immunodeficiency virus infection is not associated with an increased risk of disseminated disease. Insidious gastrointestinal symptoms may be present. Pulmonary disease is the most common extraintestinal manifestation of hyperinfection syndrome and is characterized by diffuse pulmonary infiltrates with dyspnea, cough, wheezing, or hemoptysis. Diarrhea and abdominal pain occur frequently, with inflammation leading to small bowel wall edema; ileus may develop in late stages. In uncontrolled hyperinfection, filariform larvae also penetrate organs not normally involved in the life cycle, including the urinary tract, liver, brain, and skin. The finding of larvae in stool may be an early sign of hyperinfection even in those with minimal symptoms. The dermatologic manifestation of hyperinfection and disseminated strongyloidiasis is a rapidly and progressively diffuse petechial and purpuric eruption, often with a reticular pattern, typically involving the trunk and proximal extremities (Fig. 207-9).54–56 The “thumbprint sign,” a unique pattern of periumbilical purpura resembling multiple thumbprints,57 may also be seen. Gram-negative bacillary infections including bacteremia, peritonitis, meningitis, and sepsis may result from the concurrent migration of bacteria and larvae across the bowel wall. The mortality rate for disseminated disease is approximately 50%.

Peripheral eosinophilia is present in up to 80% of patients with intestinal disease, and may be high-grade during larval migration, but it is rarely a feature of disseminated infection (although pulmonary eosinophilia may be noted in the latter), and may be absent in patient on systemic steroids and who are otherwise severely immunocompromised. In chronic disease, the eosinophil level fluctuates and is often mildly elevated (mild to moderate increase) but may be normal. Hence, the absence of eosinophilia does not rule out strongyloidiasis.

The diagnosis of larva currens is based on its characteristic clinical features. The identification of larvae in the stool, small bowel contents, and, rarely, in other body fluids confirms the diagnosis. Larvae first appear in the stool 2–4 weeks after exposure. Multiple stool examinations are often necessary to make the diagnosis; a single stool specimen may fail to detect larvae in up to 70% of cases, although sensitivity approaches 100% with seven consecutive stool samples. The agar plate method, in which a stool sample is placed on solid bacterial medium, incubated, and subsequently examined for bacterial tracks created by larvae dragging enteric bacteria as they migrate across the plate, is more than 90% sensitive.58 Serologic testing has a sensitivity of approximately 90% but lacks specificity, may cross-react with other helminthic infections (in particular filariasis, ascariasis, and acute schistosomiasis), and cannot reliably distinguish between recent and treated infection since antibodies may persist for years following effective treatment. However, since several recent studies have shown that antibody levels drop significantly over the first year following successful therapy, serology is often used to determine test of cure. Skin biopsy of the larva currens eruption often fails to reveal larvae, whereas they may be visualized in biopsy specimens of purpuric and petechial lesions with hyperinfection.

Treatment of strongyloidiasis in asymptomatic individuals is often successful. Ivermectin 200 μg/kg daily for 2 days is the recommended therapy. Albendazole 400 mg twice daily for 7 days is an alternative, although data are more limited and the drug is not approved by the US Food and Drug Administration for this indication. In contrast, patients with disseminated disease may require prolonged or repeated courses of therapy; some experts also suggest that combination therapy with ivermectin and albendazole be used in this setting. If possible, immunosuppressant therapy should be discontinued in those with hyperinfection.

The sections below briefly describe helminths that can cause dermatologic disease that are not covered in the hard copy textbook. Diagnosis of all infections outlined below is summarized in eTable 207-9.1, and treatment in eTable 207-9.2, and will not otherwise be discussed in detail.

Intestinal Nematodes (Roundworms)

Ascariasis (Ascaris Lumbricoides)

Ascariasis (roundworm infection) is usually caused by A. lumbricoides and rarely Ascaris suum. It is distributed worldwide, with a higher prevalence in tropical and subtropical climates. Infection occurs via the fecal–oral route; humans become infected by ingesting infective eggs in contaminated food and water, and on contaminated hands. Disease can be prevented by proper sanitation and avoidance of ingestion of fecally contaminated soil.

Urticaria occurs only during the invasive phase of the disease and may be associated with the pulmonary manifestations of Loeffler's syndrome (cough, wheezing, and dyspnea), which occurs 10–14 days after ingestion of eggs. Urticaria resolve spontaneously at the end of this phase. Gastrointestinal symptoms occur much later and in the absence skin findings. Eosinophilia may accompany the invasive stage. The mainstay of diagnosis is the identification of eggs in feces, which does not occur until after dermatologic manifestations have resolved, approximately 6–8 weeks after onset of infection.

Differential Diagnosis

The differential diagnosis includes other causes of urticaria.

Hookworm Infection (Ancylostoma Duodenale, Necator Americanus)

Humans are the main reservoir for A. duodenale and N. americanus, and become infected when infective larvae penetrate intact skin (e.g., when walking barefoot on contaminated soil). The disease is most common in rural tropical and subtropical areas but can also occur in temperate areas when sanitation is poor. Infection can be prevented by proper sanitation, and avoidance of barefoot walking.

Cutaneous manifestations may be seen at two stages of infection. Within 1–2 days after contact, the area of skin penetrated by the larvae may have localized erythema, edema, and papular or papulovesicular lesions (ground itch).59 This eruption is most commonly located on the feet and lasts 1–2 weeks. The pulmonary migration phase, seen in a minority of patients, begins 1–3 weeks after infection and presents with cough, wheezing, and shortness of breath; urticaria may be present and disappear spontaneously at the end of this phase. Peripheral eosinophilia begins as early as 2–3 weeks after initial infection, and may be high-grade during the invasive phase. The diagnosis is made by identification of eggs in stool, but eggs are not passed until after skin findings have resolved, approximately 6–8 weeks after onset of infection. In chronic infection, abnormal laboratory values include iron deficiency anemia, hypoalbuminemia, and gross or occult blood in feces.

Differential Diagnosis

Ground itch may be confused with cellulitis, a cellulitis-like reaction after an arthropod bite or sting, and folliculitis. For the differential diagnosis of acute urticaria, see Chapter 38.

Tissue Nematodes (Roundworms)

Dirofilariasis (Dirofilaria Immitis)

Dirofilariasis (dog heartworm infection) is most prevalent in North and South America, Australia, Europe, Japan, India, and China. Sporadic infections with other Dirofilaria spp.—Dirofilaria tenuis (raccoon), Dirofilaria repens (dog), and Dirofilaria ursi (bear)—have been reported from all continents.60

The characteristic cutaneous finding in dirofilariasis is a solitary, erythematous to flesh-colored, well-defined, firm subcutaneous nodule or mass.61 The lesion is usually 1–5 cm in diameter and may be tender; rarely, the lesion is migratory.62 Nodules most commonly occur in the head, neck, breast, extremities, and scrotum. Dirofilaria immitis also causes pulmonary disease (most often asymptomatic but may cause cough, chest pain, low-grade fever, and occasionally hemoptysis). In pulmonary dirofilariasis, chest X-rays demonstrate a solitary coin lesion that may be calcified.

Differential Diagnosis

Other helminthic causes of nodular lesions (Table 207-5), as well as epidermal inclusion cysts, lipomas, other benign tumors, and malignant tumors make up the differential diagnosis of subcutaneous dirofilariasis.

Dracunculiasis (Dracunculus Medinensis)

Dracunculiasis (Guinea worm disease, Medina worm infection) is transmitted by ingestion of infective copepods in water. The disease was endemic in Sub-Saharan Africa but as a result of a widespread water filtration and monitoring program,13,63 the disease has been almost completely eliminated. In 2009, only 3,190 cases were reported worldwide, compared with 25,000 in 2006.13

Symptoms associated with the migration of the worm may precede the emergence of the worm. The characteristic clinical findings include a bullous lesion, typically on the foot, that ruptures and ulcerates after contact with water (Fig. 207-7). Cellulitis and abscess formation can occur. Most infected individuals harbor multiple worms, but usually fewer than six. The adult worm may be palpated or can be seen emerging from the ulcer, and typically dies after reaching the skin and releasing larvae.

Differential Diagnosis

The differential diagnosis includes causes of localized cutaneous bullae, ulcers, and carbuncles.

Filarial Infections

Filarial infections have been broadly grouped into three categories of disease based on their location of disease: (1) lymphatic, (2) cutaneous, and (3) body cavity.64 Morbidity is almost entirely attributable to those species that cause lymphatic disease, and to a lesser extent cutaneous disease. Body cavity infection, due to Mansonella ozzardi, is usually asymptomatic and will not be discussed below. Filarial infections are summarized in eTable 207-9.3.

Lymphatic Filariasis (Brugia Malayi and Brugia Timori; Wuchereria Bancrofti)

Lymphatic filariasis is caused mainly by W. bancrofti (Bancroftian filariasis), which causes 90% of disease, and B. malayi (Malayan filariasis), which accounts for only 10% of all cases.65 Infection caused by B. timori is rare. Lymphatic filariasis is widely distributed in both urban and rural areas of tropical and subtropical areas, with the largest number of infections occurring in India, South Asia, East Asia, the Pacific Islands (eFig. 207-9.1), and Sub-Saharan Africa. W. bancrofti is also endemic in northern parts of South America (Guyana, Surinam, and some coastal regions of Brazil). In developed countries, infections are seen primarily in immigrants and persons with prolonged visits to endemic areas.

Infection is transmitted to humans by mosquitoes, and can be prevented by avoidance of mosquito bites. The incubation period is usually 5–18 months, during which time microfilariae migrate to the lymphatic system, mature into adults, mate, and release microfilariae (larvae); occasionally symptoms develop within 3 months of exposure. Lymphatic filariasis is first acquired in childhood, often with as many as one-third of children in endemic areas infected before the age of 5.66 However, the characteristic symptoms typically occur years after infection and the prevalence of clinical disease increases after age 20 in endemic areas. Adult worms live an average of 10–15 years, and microfilariae probably 6–12 months. Symptoms and sequelae can persist after the death of all parasites.

Clinical manifestations may be acute, chronic, or recurrent.67 Initial infection may be subclinical but may also cause recurrent lymphangitis with characteristic retrograde progression, lymphadenitis, orchitis, epididymitis, or occasionally fever. Lymphangitis typically recurs 6–10 times per year, with each episode lasting 3–7 days. The affected body part clinically appears normal between early episodes, although during the resolution of the acute phase of W. bancrofti filariasis, there may be extensive exfoliation of the skin of the affected limb. Intermittent fevers and adenolymphangitis can recur during the lifetime of the adult worm. Travelers (>1 month) to endemic areas less frequently acquire infection but may present with more intense inflammatory reactions to filarial parasites. The findings may include lymphangitis, lymphadenitis, groin pain from the associated lymphatic inflammation, urticaria, and peripheral eosinophilia.

Chronic disease with sequelae of lymphatic obstruction (lymphedema, elephantiasis, hydrocele, and chyluria), becomes evident 10–15 years after infection. The skin over the involved area can become hypertrophic, verrucous, and fibrotic with redundant skin folds (Fig. 207-10). Fissures, ulceration, secondary bacterial infection, and gangrene may occur. The lower extremity, scrotum, and penis are most commonly affected, and less frequently the upper extremity, breast, and vulva are involved. Treatment does not reverse the late findings of scarring and lymphatic obstruction.

Eosinophilia, sometimes high-grade, and elevated IgE levels are common. Infiltrates may be present on chest radiography in individuals with tropical pulmonary eosinophilia. The diagnosis is made by demonstrating microfilariae at night in blood, urine, and other body fluids, and tissue. However, persons with active filarial infection may not be microfilaremic. Inguinal lymph node ultrasound may show active microfilariae (“filarial dance sign”), more commonly seen in men than in women. Lymph node biopsy is contraindicated.

Differential Diagnosis

Acute infection may resemble bacterial lymphangitis and other causes of nodular lymphangitis (e.g., sporotrichosis, leishmaniasis). Other causes of lymphedema and elephantiasis must be considered during evaluation of chronic disease.

Cutaneous Filariasis: Loiasis (Loa Loa)

Loiasis is endemic in rural areas of Central and West Africa, affecting an estimated 3–13 million residents. Loa loa is transmitted by the day-biting Chrysops fly; infection can be prevented by avoiding bites from Chrysops in endemic areas, diethylcarbamazine chemoprophylaxis, and treatment of infected humans to reduce source of parasites. Symptoms usually begin an average of 24 months after exposure, but can begin as early as 4 months or as late as a decade or more after infection. Microfilariae first appear in the bloodstream 5–6 months after the person becomes infected. The adult worm can live longer than 20 years in the human host.

The characteristic finding of loiasis is the Calabar swelling (Fig. 207-11),68 a localized area of angioedema due to migration of adult worms through subcutaneous tissues. Calabar swellings usually begin years after infection, typically around joints of the upper extremities, generally last 2–4 days, and may be associated with pruritus or pain. They range in size from 5–20 cm in diameter and may be recurrent. Fatigue, myalgias, arthralgias, and fever are rare. A rapidly moving creeping eruption that usually lasts only a few hours may occur when the adult worm migrates under the skin; adult worms may also be seen moving across the bulbar conjunctiva of the eye (Fig. 207-6). Pruritus may also occur. Peripheral eosinophilia (high-grade), leukocytosis, and elevated IgE are often present.

Differential Diagnosis

The differential diagnosis includes all of the causes of migratory and nodular skin lesions (Tables 207-4 and 207-5).

Cutaneous Filariasis: Mansonelliasis (Mansonella Perstans, Mansonella Streptocerca)

Infection due to both M. perstans and M. streptocerca is often asymptomatic, but symptoms when present are primarily cutaneous. M. perstans is endemic in Sub-Saharan Africa, as well as parts of Central and South America. It is transmitted by biting Culicoides midges. Like lymphatic filariasis, infection during childhood is common, and reinfection may occur.69 In highly endemic areas, the prevalence of infection may be as high as 80%.70 Cutaneous manifestations include Calabar-like swellings, typically in the forearms, hands and face, and pruritus with or without a papular rash.71 The exact interval between infection and onset of symptoms is unclear.

M. streptocerca is endemic in forested areas of West and Central Africa. Transmission is also by infected midges. Cutaneous manifestations of M. streptocerca infection include pruritus, papular lesions, and hypopigmented, hyperpigmented, or lichenified macules, typically found on the upper chest.

Eosinophilia is often present in Mansonella infections, but may also be due to the high prevalence of coinfection with other filarial or helminthic infections.

Cutaneous Filariasis: Onchocerciasis (Onchocerca Volvulus)

Onchocerciasis (river blindness; erysipelas de la costa in Mexico and Guatemala; sowda in Arabic speaking areas; craw-craw in West Africa) is concentrated in rural areas of Equatorial Africa and the Arabian peninsula (eFig. 207-11.1), and in Latin America (eFig. 207-11.2). Onchocerciasis is transmitted by black flies of the genus Simulium. In the human, infective larvae mature to adult worms that are encapsulated in fibrous tissue and reside in nodules in the subcutaneous tissue and deep fascia. The incubation period is usually 1–2 years with a range of months to several years, although microfilariae may first appear 3–15 months after exposure; symptoms may precede microfilaremia but often develop only after months or years of infection. Microfilariae can survive in humans for up to 2–3 years, and adult worms for 10–15 years. The primary means of preventing onchocerciasis is through vector control and mass treatment with ivermectin of the population in endemic areas.

Infected individuals may be asymptomatic. Clinical manifestations most commonly involve the skin and eye. Six different patterns of skin changes have been described in onchocerciasis: (1) acute papular onchodermatitis and (2) chronic papular onchodermatitis (Fig. 207-1), (3) lichenified onchodermatitis, (4) atrophy, (5) depigmentation (see Section “Onchocerciasis” in Chapter 75), and (6) onchocercal nodules (Fig. 207-2). More than one pattern of skin involvement may be present simultaneously, or one pattern of skin involvement may evolve into another pattern.

Pruritus is often the first symptom of infection. Acute papular onchodermatitis most often involves the face, extremities, and trunk, and includes widespread small pruritic papules, vesicles and pustules, sometimes with associated erythema and edema. Short-term visitors to endemic regions typically present with acute pruritus and rash (Fig. 207-1),11 and demonstrate immune hyperresponsiveness despite low levels of parasites10; skin nodules and eye involvement are usually absent. After exposures in forested areas of West and Central Africa, travelers and expatriates may have an acute form of onchocerciasis characterized by acute pruritic and erythematous swelling of a limb known as gros bras camerounais15 or onchocerciasis-associated limb swelling.16

The skin lesions of chronic papular onchodermatitis are macules and lichenoid papules varying in size from 3–9 mm in diameter. Pruritus is common, and postinflammatory hyperpigmentation may be present. The most commonly affected anatomic areas are the buttocks, shoulders, and waist (Fig. 207-1). Palpable asymptomatic onchocercal nodules containing the adult worm involve the deep dermis and subcutaneous tissue (Fig. 207-2), and occur over bony prominences such as the skull, iliac crest, knee, rib, sacrum, scapula, and trochanter.

Peripheral eosinophilia and elevated IgE levels are common findings.

Differential Diagnosis

Acute onchodermatitis may resemble miliaria, insect bites, scabies, or eczema. Chronic onchodermatitis may resemble a chronic or lichenoid eczema or atopic dermatitis. Skin changes resembling lichenified onchodermatitis can be due to conditions causing significant pruritus or rubbing. Atrophic changes resemble those associated with aging. Onchocercal depigmentation may be confused with postinflammatory hypopigmentation or depigmentation. The differential diagnosis for onchocercal nodules includes other parasitic causes of nodules (Table 207-5) and epidermal inclusion cysts.

Gnathostomiasis (Gnathostoma Spinigerum)

Gnathostomiasis is caused by Gnathostoma spinigerum and less commonly other Gnathostoma species.72 It is endemic in Southeast Asia, especially Thailand and Japan. Since the 1970s, the prevalence of gnathostomiasis has increased in Peru, Ecuador, and Mexico. Sporadic cases have been reported in the Americas, Africa, Europe, and Australia. In the last two decades, an increase has been noted in the cases in travelers returning from endemic countries.73–75 Infection is acquired by ingestion of larvae in undercooked or raw flesh of infected animals (typically fish, amphibians, and reptiles) or contaminated water. Imported fish and other animal flesh can be a source of infection outside of endemic areas.

The penetration phase occurs within 1–2 days of larval ingestion and includes acute urticaria and fever, malaise, anorexia, nausea, vomiting, diarrhea, and epigastric pain, which resolve spontaneously within 2 days.76 Migration of the larvae in the skin and subcutaneous tissue causes migratory swellings (eosinophilic panniculitis), creeping dermatitis (1 cm/hour), papules, and nodules.77 Solitary or multiple migratory swellings usually occur 3–4 weeks after infection, are intermittent, and associated with erythema, pruritus, and pain (Fig. 207-12). The swellings develop rapidly, persist for 1–4 weeks, then resolve, only to reappear in a different anatomic location after an asymptomatic interval of weeks to months. Over time, episodes become less frequent, less intense, and shorter in duration, but may continue for months to years. Rarely, infection may present as a papular lesion or limb swelling. The most common anatomic locations include the trunk, upper body, and thighs. Peripheral eosinophilia may be high-grade during larval migration.

Differential Diagnosis

The differential diagnosis includes causes of migratory lesions (Table 207-4), panniculitis, limb swelling (e.g., loiasis, onchocerciasis, eosinophilic cellulitis, other), and skin nodules (Table 207-5).

Toxocariasis (Toxocara Canis, Toxocara Cati)

Toxocariasis (visceral larva migrans) is most commonly caused by the dog roundworm T. canis. It is most prevalent in tropical and temperate climates where humans and dogs coexist, but is found worldwide. Transmission is via the fecal–oral route, with the highest rates of infection in children and individuals with pica.

Most infections are asymptomatic or mild. Severe illness can occur, with disease involving the liver, heart, brain, spinal cord, eyes, and muscle. The most common cutaneous symptoms include urticaria during larval migration, and chronic pruritus or prurigo.78,79 In acute infection, urticaria is often accompanied by other symptoms including fever, abdominal pain, wheezing, and myalgias. Since larvae can survive and wander through tissues for 10 years or more, urticaria may also persist after resolution of acute symptoms. Other less common cutaneous manifestations include eosinophilic panniculitis,25,26 eosinophilic cellulitis (Well's syndrome),28 and eosinophilic folliculitis.29 Henoch–Schonlein purpura80 and subcutaneous granulomas81 have also been reported. Peripheral eosinophilia, often high-grade, may be persistent, and liver enzymes may be elevated during acute infection.

Differential Diagnosis

The differential diagnosis mainly includes other causes of urticaria.

Trichinosis (Trichinella Spiralis)

Trichinosis (trichinellosis) is present in most countries, but there is marked variation in the incidence. Humans are accidental dead-end hosts and become infected by eating raw or undercooked flesh of animals infected with Trichinella, most commonly bears or boars. Human infection can be sporadic or epidemic. Sporadic infections can occur worldwide by shipment of contaminated meat.

Infection may be asymptomatic. Symptomatic disease occurs during larval migration and varies in severity. Death is uncommon (1%–2% of recognized infections) and is usually related to neurologic or cardiac involvement.

Abdominal pain, diarrhea, and vomiting occur during the first week of infection. Ten days after the ingestion of larvae, fever (in 90% of the cases), cutaneous manifestations (75% of cases),82 fatigue, and severe myalgia develop. The most frequent skin findings are periorbital and facial edema (75%–95% of cases), conjunctivitis, and less commonly a macular or papular (sometimes urticarial) rash. Hand swelling and volar surface erythema followed by desquamation have been reported.83 Subconjunctival and subungual hemorrhages can occasionally be seen (eFig. 207-12.1). Peripheral eosinophilia may be marked and may persist for months. Muscle enzymes (creatine phosphokinase, CPK) are increased.

The diagnosis is usually based on the epidemiological history (e.g., an ongoing epidemic, or suspected dietary exposure), the clinical triad (fever, facial edema, myalgias), and laboratory findings (eosinophilia, increased CPK). A definitive diagnosis is possible after the 17th day and relies on the identification of the parasite in muscle.

Differential Diagnosis

The differential diagnosis includes allergic reactions, dermatomyositis, vasculitis, causes of urticaria, and eosinophilia–myalgia syndrome.

Trematodes (Flukes)

Fascioliasis (Fasciola Hepatica, Fasciola Gigantica)

Fascioliasis caused by F. hepatica is found worldwide in sheep- and cattle-raising areas84,85 and has been reported from all continents. Disease due to F. gigantica is rare. Infection, which may be asymptomatic, results from ingestion of encysted cercariae on water plants (e.g., watercress).

Symptomatic acute infection presents with fever, abdominal pain, nausea, and diarrhea, which occur during the migration of immature flukes. Urticaria and wheezing may be present during the invasive phase. Less commonly, ectopic subcutaneous nodules may develop; lesions are typically erythematous, pruritic and painful, occurring on the abdomen, back, and extremities. Rarely, eosinophilic panniculitis may be present. Chronic infection does not typically involve the skin. Eosinophilia is typically present during the invasive phase. The identification of eggs in stool only occurs well after symptoms of invasive disease have subsided. Serology may be helpful.

Paragonimiasis (Paragonimus Westermani)

Paragonimus westermani is widely distributed in East and Southeast Asia and Africa. Other species of Paragonimus can infect humans and are found in Asia, Africa, and the Americas.86–88 Worldwide, an estimated 10 million persons are infected with paragonimiasis. Infection is prevalent in Asia, where raw, undercooked, salted, pickled, or marinated crustaceans are frequently eaten.

Infection is often asymptomatic. Urticaria may occur early. Migratory subcutaneous nodules containing immature flukes may appear as early as 2 weeks, and are present in 10% of those with P. westermani infection and 20%–60% of patients with Paragonimus skrjabini and Paragonimus szechuanensis infection. Lesions may be up to 6 cm in diameter, are migratory, firm, slightly mobile, and tender to palpation. The lesions are most commonly located on the lower abdomen and inguinal region. Pulmonary involvement is common in chronic infection, but often asymptomatic. Peripheral eosinophilia may be present.

Schistosomal Infections

Cercarial Dermatitis

Cercarial dermatitis (swimmer's itch) occurs worldwide and may be acquired by contact with infective cercariae of many species of non-human schistosomal parasites, in both freshwater and salt water. Attack rates during outbreaks usually range from 55%–100% of those exposed, with highest attack rates in those with a history of previous cercarial dermatitis.89

Clinical findings are confined to the skin and are usually distributed on skin surfaces exposed directly to water. Pruritus may begin while swimming, followed rapidly by the appearance of an erythematous macular rash that persists for several hours. Ten to fifteen hours after exposure, papules, vesicles, and urticaria develop. Marked pruritus is characteristic. Symptoms peak 48–72 hours after exposure, and gradually resolve spontaneously over the next several weeks.

Schistosomiasis (Schistosoma Hematobium, Schistosoma Intercalatum, Schistosoma Japonicum, Schistosoma Mansoni, Schistosoma Mekongi)

An estimated 200 million people worldwide are infected with schistosomiasis (bilharziasis) and over half-a-billion live in endemic areas (eFigs. 207-12.2 and 207-12.3). Humans are the only important reservoir for S. haematobium. Infection can be acquired after a brief exposure in an endemic area; many outbreaks have been reported in travelers,90,91 typically after swimming, wading, rafting, or bathing in slow-moving freshwater in endemic areas. Attack rates in nonimmune exposed persons (e.g., travelers) can be as high as 100%. Cutaneous manifestations can be seen at every phase of the infection.

Cercariae penetrate intact skin within 30 seconds to 10 minutes and may elicit a local inflammatory response (penetration phase). The first exposure to cercariae typically results in erythema and pruritus that resolve within hours. In those previously sensitized, a pruritic, erythematous, papular, and urticarial rash develops, usually lasting 1 week. Migration of the larvae (schistosomulae) in the body usually occurs 2–6 weeks after exposure and leads to an acute parasitic toxemia with a hypersensitivity reaction and circulating immune complexes. This invasive phase (Katayama fever) has historically been described with S. japonicum (Katayama fever, sensu stricto), S. mansoni, and, to a lesser extent, with S. haematobium. Symptoms of Katayama fever are most prominent in primary infection in nonimmune persons and include fever, fatigue, myalgia, and headache that may persist for several weeks. Abdominal symptoms and diarrhea may also be present. Urticaria, purpura, subungual hemorrhages, and edema of the face, the extremities, genitals, and trunk may be seen during the invasive phase.

Chronic schistosomiasis (bilharziasis cutanea tarda) may begin after years of infection and result from a granulomatous inflammatory reaction to the deposition of eggs in the dermis (Fig. 207-13), which may continue for the lifespan of the adult worm (up to 10 years). It is seen primarily in persons who have lived in endemic regions. Lesions are skin-colored or slightly pigmented, 2- to 4-mm firm, pruritic, oval papules that appear in crops and clusters, typically on the trunk and especially the periumbilical region, and remain unchanged without treatment. Lesions also appear in the genital area buttocks, especially on the vulva in women and the scrotum and penis in men. Chronic lesions may also include painless, skin-colored, pink or brown eroded papules and warty, vegetative, polypoid lesions that may be ulcerated and necrotic, with fistulous tracts. Chronic disease can be complicated by lymphedema and elephantiasis, secondary bacterial infection, and squamous cell carcinoma.

Prominent eosinophilia may be present in early infection, especially during the invasive phase, and subsequently fluctuates more or less above the normal value during the chronic phase. Onset of eosinophilia may lag behind appearance of clinical symptoms. Acute disease can be suspected based on the history of exposure and cercarial dermatitis. Identification of eggs in the stool occurs only after the acute phase of infection.

Differential Diagnosis

The differential diagnosis during acute disease includes other causes of urticaria. Bilharziasis cutanea tarda of the genitals and buttocks must be differentiated from syphilis, condyloma latum, condyloma acuminatum, other granulomatous diseases, malignancy, and hemorrhoids.

Cestodes (Tapeworms)

Coenurosis (Multiceps Multiceps, Multiceps Serialis)

Reported human cases of coenurosis, caused most commonly by Multiceps multiceps and less often by Multiceps serialis, are rare and sporadic, with the majority from Africa.92 Infections have occurred in Asia, Europe, and North America,93 particularly in areas where sheep are common. Intramuscular and subcutaneous cysts are the most common presentation, especially in cases from Africa,92 but disease may also involve the eye and the central nervous system.93

Cysticercosis (Taenia Solium)

T. solium (pork tapeworm) is a common parasite in Central and South America, Africa, parts of Asia, and Eastern Europe, although domestic acquisition of infection has also been well documented in the United States. Cysticercosis is the most common helminthic infection of the central nervous system. Humans acquire cysticercosis by ingesting eggs in food, water, or on fingers contaminated with human feces, but may also acquire intestinal disease from eating undercooked or raw pork containing cysts with infective larvae.

Humans can have either form of disease, or both; intestinal taeniasis is found in up to 50% of patients with cysticercosis.

Less than 10% of patients with cysticercosis present with subcutaneous nodules, although earlier studies reported a detection rate of 50%.14 Nodules are mobile, well-defined and characteristically nontender, measuring 2 cm in size on average, and commonly found on the extremities and the trunk. The time from infection to the appearance of subcutaneous nodules is highly variable and may be from months to years. Neurocysticercosis is frequently asymptomatic; symptomatic disease presents with seizures in more than two-third of cases.94 Ectopic disease in other sites is less common.

Differential Diagnosis

The differential diagnosis of subcutaneous nodules includes benign cysts, soft-tissue tumors, and other parasitic causes of nodules (Table 207-5).

Echinococcosis (Echinococcus Granulosus, Echinococcus Multilocularis)

Echinococcus granulosus (cystic hydatid disease) is prevalent in southern South America, the Mediterranean region, parts of the former Soviet Republic, the Middle East, Asia, and Northern and Eastern Africa. Infections are sporadic in other world regions, except Antarctica. Echinococcus multilocularis (alveolar hydatid disease) is more limited in distribution, and has been documented in North America, Europe, Asia, India, and Iran. Infection caused by other species (Echinococcus vogeli, Echinococcus oligarthrus, and others) is rare. Humans are incidental intermediate hosts who become infected by ingesting infective eggs (shed in feces of dogs or, for E. multilocularis, foxes) in contaminated food or water.

Most echinococcal infections are asymptomatic; symptoms develop years after infection and are related to the location and size of cysts. Cysts are usually single, but in 25% of cases multiple cysts are present. Most cysts are hepatic (50%–75%) and pulmonary (20%–30%), with other sites infrequently involved. Typically, the signs and symptoms include an enlarging firm but fluctuant, nontender abdominal mass (Fig. 207-14), epigastric and right upper quadrant pain, jaundice, hepatomegaly, nausea, and vomiting. True skin and soft-tissue manifestations are rare except when cyst leakage occurs. Significant leaks may produce an “anaphylactoid reaction” with eosinophilia, urticaria, and wheezing. Urticaria alone may occur alone in mild cases. Echinococcal cysts implant in soft tissues in less than 2% of infected patients.95 Infection with E. multilocularis has been reported to cause supraumbilical cutaneous and subcutaneous nodules with ulceration, surrounding inflammation, and painless cutaneous fistulae resulting from extension of an underlying visceral lesion.96 Eosinophilia is usually absent, except in the case of cyst leakage.

Differential Diagnosis

The differential diagnosis includes other cutaneous nodules (Table 207-5) and other cystic lesions of soft tissues.

Sparganosis (Spirometra Mansoni, Spirometra Erinacei, Spirometra Mansonoides)

Spirometra species are found in animals on all continents, but most reported human cases are from China, Japan, and Southeast Asia. Cases have also been reported from Africa, Australia, the Caribbean, Southern Europe, and the Americas. Infection is acquired by ingestion of infective tapeworm larvae in contaminated water or animal (fish, amphibian, reptile) flesh, or by use of infected flesh in topical poultices.

The severity of infection depends on the route of infection, the number of parasites, and the anatomic locations involved.97 Ingestion of larvae leads to a slow-growing subcutaneous or intramuscular nodule (Fig. 207-15), which is occasionally migratory, 3 weeks to 14 months after ingestion. The lesion may be pruritic and tender or nontender and may persist for years. Sparganosis due to the application of poultices made with infected flesh is characterized by localized pruritus, erythema, edema, and subcutaneous nodules that are painful to palpation.

Helminthic infections can cause a spectrum of cutaneous disease. Migratory lesions of CLM are most likely to be encountered by clinicians in the developed world. Recognition of specific dermatologic findings, in conjunction with a thorough epidemiologic and exposure history, can establish the diagnosis and/or direct further investigations, and lead to appropriate therapy.