ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Infectious causes of peripheral eosinophilia

Infectious causes of peripheral eosinophilia
Literature review current through: Jan 2024.
This topic last updated: May 23, 2022.

INTRODUCTION — Peripheral blood eosinophilia (≥500 eosinophils/microL) may be caused by numerous conditions, including allergic, infectious, inflammatory, and neoplastic disorders (table 1) [1,2].

In general, among individuals with eosinophilia, the likelihood of an infectious cause is highest among those with relevant epidemiologic exposures, such as residence in or travel to areas where infectious causes of eosinophilia are endemic [1]. In addition, infectious causes should be considered in patients with ≥1500 eosinophils/microL.

Issues related to infectious causes of eosinophilia are discussed here. Noninfectious causes of eosinophilia and conditions associated with eosinophilic involvement of specific organs are also presented separately. (See "Eosinophil biology and causes of eosinophilia".)

A general approach to evaluation of unexplained peripheral blood eosinophilia is presented separately. (See "Approach to the patient with unexplained eosinophilia".)

DEFINITIONS — The absolute eosinophil count (AEC) refers to the number of eosinophils in peripheral blood, calculated as follows:

White blood cell (WBC) count/microL x percentage of eosinophils = AEC (eosinophils/microL) (calculator 1)

Some laboratories provide the AEC as a component of the complete blood count and differential; others require calculation of the AEC by the clinician.

In most clinical laboratories, eosinophilia is defined by AEC ≥500 eosinophils/microL [3,4]. Eosinophilia is not defined by the percentage of eosinophils (typically <5 percent in healthy individuals), because the percentage varies with the total WBC count and the proportion of other WBC lineages (eg, neutrophils, lymphocytes).

Definitions of peripheral eosinophilia are variable [5-7]. In general, the AEC is typically ≥1500/microL in conditions with marked (or moderate) eosinophilia; the AEC is typically ≥5000/microL in conditions with massive eosinophilia.

INITIAL EVALUATION — The initial evaluation should assess the patient for clinical findings that may be attributable to eosinophilia and seek to determine the underlying cause. A general approach to patients with eosinophilia is presented separately. (See "Approach to the patient with unexplained eosinophilia", section on 'Initial evaluation'.)

History and physical examination — The clinical history should establish a number of details:

Careful documentation of signs and symptoms and their time of onset – Understanding the clinical timeline is important for establishing the likely incubation period, which is useful for narrowing the differential diagnosis.

The nature of any relevant epidemiologic exposure – Relevant epidemiologic exposure includes residence in or travel to areas where infectious causes of eosinophilia are endemic. Some infectious causes of eosinophilia are associated only with specific geographic exposures; others are endemic worldwide and should be considered regardless of where an individual has traveled or resided (table 2).

Relevant activities and exposures (such as consumption of undercooked seafood or meat, swimming in freshwater).

Medical history and medications (including prescribed and non-prescribed medications, as well as supplements).

Physical findings that signal severe illness warranting prompt intervention include hemodynamic instability, respiratory distress, and neurologic findings such as confusion, lethargy, neck stiffness, or focal deficits. The physical examination should also include evaluation for skin lesions, lymphadenopathy, and enlargement of the liver or spleen.

Laboratory tests — An initial approach to laboratory testing for patients with eosinophilia is presented separately. (See "Approach to the patient with unexplained eosinophilia", section on 'Laboratory and diagnostic tests'.)

Stool examination for ova and parasites can be helpful in diagnosing some intestinal and hepatobiliary parasites (table 2); however, the test is relatively insensitive, the timing of symptoms often does not correspond with positive stool examination, and many parasites that cause eosinophilia are not found in the stool. (See "Approach to stool microscopy".)

Diagnostic testing should be targeted to the likeliest possible etiologies based on the epidemiologic exposure and clinical presentation, as discussed below. (See 'Clinical approach' below.)

Overview of causes — A variety of infections may be associated with eosinophilia; these include helminths (worms), fungi, protozoa, bacteria, the retroviruses human immunodeficiency virus (HIV) and human T cell lymphotropic virus type 1 (HTLV-1), in addition to arthropod infestations, such as scabies (a mite infestation). Most acute bacterial infections and viral infections are not associated with eosinophilia.

A clinical approach focusing on infectious causes of eosinophilia based on epidemiologic exposure and clinical manifestations is outlined below. (See 'Clinical approach' below.)

In general, helminths are the most commonly identified infectious causes of eosinophilia [8]. Categories of helminths include flukes (trematodes), tapeworms (cestodes), and roundworms (nematodes). The major helminth infections associated with eosinophilia are discussed below; additional information regarding helminths associated with eosinophilia is summarized in the table (table 2).

Fungal infections classically associated with eosinophilia include allergic bronchopulmonary aspergillosis and coccidioidomycosis. Less commonly, peripheral eosinophilia has been reported in patients with histoplasmosis, paracoccidioidomycosis, cryptococcosis, and basidiobolomycosis.

Protozoal infections associated with eosinophilia include cystoisosporiasis, sarcocystosis, and Dientamoeba fragilis.

Bacterial infections associated with eosinophilia include bartonellosis, syphilis, and resolving scarlet fever.

Mycobacterial infections associated with eosinophilia include tuberculosis and leprosy.

In the setting of HIV infection, eosinophilia may occur as a result of concomitant opportunistic infection or in the context of an associated condition such as eosinophilic folliculitis or adrenal insufficiency [9]. (See "HIV-associated eosinophilic folliculitis" and "Pituitary and adrenal gland dysfunction in patients with HIV".)

HTLV-1 infection has been associated with adult T-cell leukemia/lymphoma (ATL); ATL may be associated with eosinophilia in some circumstances [10]. In addition, HTLV-1 infection is a risk factor for disseminated strongyloidiasis. (See "Human T-lymphotropic virus type I: Disease associations, diagnosis, and treatment".)

CLINICAL APPROACH

Consider the geographic region(s) of exposure — Residence or travel to specific regions may help to include or exclude particular infections on the differential diagnosis for peripheral eosinophilia. Geographic regions for helminth infections associated with eosinophilia are summarized in the table (table 2). Geographic regions for fungal and protozoal infections associated with eosinophilia are described below.

Causes of eosinophilia are discussed further separately:

(See "Approach to illness associated with travel to East Asia".)

(See "Approach to illness associated with travel to Southeast Asia".)

(See "Approach to illness associated with travel to South Asia".)

(See "Approach to illness associated with travel to West Africa".)

(See "Diseases potentially acquired by travel to East Africa".)

(See "Diseases potentially acquired by travel to Central Africa".)

(See "Diseases potentially acquired by travel to North Africa".)

(See "Diseases potentially acquired by travel to Southern Africa".)

(See "Approach to illness associated with travel to Latin America and the Caribbean".)

It is important to avoid diagnostic anchoring biases and maintain a broad differential diagnosis for the clinical scenarios and syndromes below, with special consideration of:

Infections that may be related to travel

Infections that may not be related to travel

Noninfectious etiologies

Consider exposure duration and clinical syndrome

Short-term travelers — Among travelers outside the United States and Europe, important causes of fever and eosinophilia include acute schistosomiasis (due to blood flukes), other fluke infections, roundworm infections, and drug reaction. The epidemiology, clinical manifestations, and diagnosis of these conditions are described below.

In addition to consideration of the conditions outlined below, travelers with fever should be evaluated for malaria and other causes of fever as described separately. (See "Evaluation of fever in the returning traveler".)

Fever and gastrointestinal symptoms

Diagnostic considerations - Travel-related infections associated with peripheral eosinophilia, fever, and gastrointestinal symptoms include:

Fascioliasis – Fascioliasis is a liver fluke infection acquired by ingestion of contaminated aquatic vegetation grown in sheep-raising areas; it occurs globally in temperate climates. Initial clinical manifestations include fever, eosinophilia, right upper quadrant pain, and hepatomegaly; these occur 6 to 12 weeks after ingestion of aquatic plants. These symptoms gradually abate as larvae migrate to the biliary tree, where they may cause biliary obstruction. Computed tomography (CT) of the liver may demonstrate characteristic hypodense nodules or tortuous tracks due to migration of the parasite through the liver. In the acute phase, eosinophilia is marked (3000 to 5000/microL) and eggs are not present in stool; the diagnosis is established via serology (serology may be positive before eggs appear in stool). In the chronic phase, eosinophilia is less prominent (500 to 1000/microL) and eggs may be detected in stool, duodenal aspirates, or bile specimens. (See "Liver flukes: Fascioliasis".)

Opisthorchiasis and clonorchiasis – Opisthorchiasis and clonorchiasis are liver fluke infections transmitted via ingestion of raw fish; the incubation period is two to three weeks. The diagnosis can be established by identifying eggs in stool, duodenal aspirates, or bile specimens. (See "Liver flukes: Clonorchis, Opisthorchis, and Metorchis".)

Opisthorchiasis is endemic to Southeast Asia and the former Soviet Union. Clinical manifestations of opisthorchiasis include fever, abdominal pain, headache, diarrhea, nausea, vomiting, and occasional jaundice. Laboratory findings include cholestatic liver enzyme abnormalities with peripheral eosinophilia; the severity of cholestasis correlates with degree of eosinophilia (may be >10,000/microL). CT may demonstrate hypodense lesions in the liver.

Clonorchiasis is endemic to East and Southeast Asia. It is often asymptomatic or with subtle, nonspecific complaints. However, among travelers in particular, an acute syndrome with right upper quadrant pain, nausea, and occasional fever or cough may develop. Eosinophilia can be >1500/microL.

Gnathostomiasis (rare) – Gnathostomiasis is a roundworm infection transmitted via ingestion of raw fish, shellfish, eel, or frog; it is endemic in most Asian countries as well as Latin America. Clinical manifestations include abdominal pain with nausea, vomiting, and diarrhea along with generalized malaise, urticaria, headache, and fever (incubation period 24 to 48 hours; diagnosis at this stage is rare). Three to four weeks later, larvae may migrate through subcutaneous, visceral, or neural tissues. The diagnosis is usually presumptive; in the setting of subcutaneous nodules, a definitive diagnosis can be established via detection of larvae on skin biopsy. (See 'Allergic or dermatologic symptoms' below and "Skin lesions in the returning traveler", section on 'Gnathostomiasis' and "Eosinophilic meningitis", section on 'Gnathostomiasis'.)

Capillariasis (rare) – Hepatic capillariasis is a rare roundworm infection. It has been observed worldwide and is acquired via ingestion of contaminated soil and has an autoinfection cycle. The incubation period is not well understood; clinical manifestations include fever, eosinophilia, and hepatomegaly. The diagnosis may be established by detection of eggs and/or adult worms on liver biopsy; eggs are not passed in the stool. (See "Miscellaneous nematodes", section on 'Hepatic capillariasis'.)

Clinical approach – For short-term travelers presenting with peripheral eosinophilia, fever, and gastrointestinal symptoms, our approach to the initial diagnostic evaluation includes:

Evaluation for malaria (which could present concomitantly with another condition). (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)

Stool ova and parasite examination; if negative (since ova may be absent in stool at the time of clinical presentation), we pursue repeat examination two months later. (See "Approach to stool microscopy".)

Stool multiplex polymerase chain reaction (PCR) testing.

Liver function tests.

For patients with abnormal liver function tests and/or right upper quadrant pain: abdominal imaging (such as liver ultrasonography or computed tomography).

For patients with relevant epidemiologic exposure for fascioliasis and at least two weeks of symptoms: serology for fascioliasis.

Fever and respiratory symptoms

Diagnostic considerations − Travel-related infections associated with eosinophilia, fever, and respiratory symptoms include:

Acute schistosomiasis syndrome – Acute schistosomiasis syndrome (Katayama syndrome) is a blood fluke infection characterized by fever, urticaria and angioedema, chills, myalgia, arthralgia, dry cough, diarrhea, abdominal pain, and headache. It is acquired by swimming in fresh water contaminated with cercariae (the infectious form of the parasite). It mostly occurs in Africa but is also found in South America, East Asia, and the Middle East. The incubation period is three to eight weeks. The diagnosis is often made on clinical suspicion and confirmed when serology becomes positive or eggs are visualized in the urine or stool. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis".)

StrongyloidiasisStrongyloides stercoralis is a roundworm transmitted via skin contact with contaminated soil; it is endemic in rural areas of tropical and subtropical regions worldwide. Uncommonly, transpulmonary migration of Strongyloides larvae is associated with dry cough, throat irritation, dyspnea, wheezing, and hemoptysis (Loeffler syndrome). A years-long latency period may occur between the initial exposure and development of symptoms. In the setting of chronic infection, eosinophilia may be observed in approximately two-thirds of cases; in the setting of the hyperinfection syndrome, peripheral eosinophilia is usually absent. Diagnostic testing primarily consists of serology and/or stool analysis; however, the sensitivity is limited. (See "Strongyloidiasis" and 'Gastrointestinal symptoms without fever' below.)

Paragonimiasis – Paragonimiasis is a fluke infection transmitted via consumption of raw or undercooked crab or crayfish; it occurs in the Far East, West Africa, and the Americas. During larval migration in the peritoneum (initial two months of infection), manifestations may include fever, malaise, diarrhea, epigastric pain, and urticaria. As larvae penetrate the diaphragm and migrate within the pleural cavity, pleuritic chest pain may develop; additional symptoms may include dyspnea, cough, and malaise. Pneumothoraces can occur. This early phase may resemble Loeffler syndrome; during this phase (prior to egg production), a diagnosis can be made only presumptively based on clinical presentation and exposure history. During late infection, the diagnosis can be established via identification of Paragonimus eggs in sputum, bronchoalveolar lavage, or stool and with serology. (See 'Allergic or dermatologic symptoms' below and "Paragonimiasis".)

Loeffler syndrome (rare) – Loeffler syndrome is a condition associated with transpulmonary passage of roundworm larvae; it is most commonly associated with Ascaris but is also associated with hookworms (Ancylostoma duodenale, Necator americanus) and S. stercoralis. It is characterized by respiratory symptoms (dry cough, dyspnea, fever, wheezing), characteristic radiographic findings (migratory bilateral round infiltrates), and peripheral eosinophilia. The incubation period is days to weeks. The diagnosis may be definitively established via visualization of Ascaris, hookworm, or Strongyloides larvae in respiratory secretions or gastric aspirates; stool examination is not useful for diagnosis of pulmonary infection. (See 'Allergic or dermatologic symptoms' below and 'Gastrointestinal symptoms' below and "Ascariasis" and "Hookworm infection".)

Tropical pulmonary eosinophilia (rare) – Tropical pulmonary eosinophilia is a clinical manifestation of lymphatic filariasis, a roundworm infection. The disease is characterized by gradual onset of nonproductive cough (frequently paroxysmal and nocturnal) and peripheral eosinophilia (usually above 3000/microL). The disease is transmitted by a number of mosquito vectors throughout the Caribbean, South America, Africa, Asia, and the Pacific islands; the incubation period is approximately one month. The diagnosis is usually established via serology. (See "Tropical pulmonary eosinophilia".)

Fungal infections – Travel-related fungal infections associated with eosinophilia, fever, and respiratory symptoms include:

-Coccidioidomycosis – Coccidioidomycosis should be suspected patients with exposure in endemic areas (southwestern United States, Mexico, Central America, and parts of South America) and a respiratory illness of more than a week's duration. The incubation period is 7 to 21 days. The diagnosis is established via serology or culture. (See "Primary pulmonary coccidioidal infection".)

-Paracoccidioidomycosis – Paracoccidioidomycosis should be suspected in patients with endemic exposure (Mexico, Central America, and South America), pulmonary infiltrates, and chronic mucosal ulcers in the upper airways. The incubation period is not well defined. The diagnosis is established via microscopic visualization of fungal elements suggestive of Paracoccidioides spp, culture, and/or serologic testing. (See "Clinical manifestations and diagnosis of chronic paracoccidioidomycosis".)

-Histoplasmosis – Histoplasmosis is transmitted by inhalation of aerosolized particles and occurs worldwide; it proliferates in soil contaminated with bird or bat droppings. Histoplasmosis infection may be associated with a broad array of pulmonary symptoms. The incubation period is 3 to 17 days. The diagnosis may be established via histopathology, culture, antigen detection, and/or serology [11]. (See "Pathogenesis and clinical features of pulmonary histoplasmosis" and "Diagnosis and treatment of pulmonary histoplasmosis".)

-Cryptococcosis – Cryptococcosis is an invasive fungal infection that affects both immunocompetent and immunocompromised hosts; it causes pneumonia and central nervous system disease. Transmission is via environmental exposure. Eosinophilia may be a feature of cryptococcal infection in immunocompetent patients; in one study, the prevalence was 42 percent [12-14]. Diagnostic tools include staining, antigen testing, and culture. (See "Cryptococcus neoformans infection outside the central nervous system".)

Clinical approach – For short-term travelers presenting with peripheral eosinophilia, fever, and respiratory symptoms, our approach to the initial diagnostic evaluation includes:

Evaluation for malaria (which could present concomitantly with another condition). (See "Malaria: Clinical manifestations and diagnosis in nonpregnant adults and children".)

Chest imaging (initially with a chest radiograph) to evaluate for consolidation, adenopathy, cavitation, nodules, and/or pleural disease.

For patients with potential epidemiologic exposure to helminth (worm) infections, we pursue stool ova and parasite examination (for paragonimiasis or schistosomiasis) two months after potential exposure.

For patients with potential epidemiologic exposure to fungal infections, we pursue serologic testing and a urine histoplasma antigen test two weeks after potential exposure.

Conditions diagnosed clinically include acute schistosomiasis (Katayama syndrome), tropical pulmonary eosinophilia, and Loeffler syndrome; if any of these is suspected based on epidemiologic exposure, we pursue serologic testing (two weeks after potential exposure) and stool ova and parasite examination (two months after potential exposure).

For patients with severe illness of uncertain etiology, bronchoscopy with bronchioalveolar lavage warrant consideration.  

Fever and myositis

Diagnostic considerations – Travel-related infections associated with eosinophilia, fever, and myositis include:

Trichinellosis – Trichinellosis (trichinosis) is a roundworm infection transmitted via ingestion of raw or undercooked meat (including pork, wild boar, bear, and walrus); it is endemic worldwide. The incubation period is one to four weeks, and eosinophil levels are often very high. Clinical manifestations include fever and myalgia (occasionally preceded by diarrhea); in addition, edema (including periorbital or facial edema) is common. The diagnosis may be confirmed by serology; however, antibody levels are not detectable until after three or more weeks of infection so are not helpful for early diagnosis. A definitive diagnosis may be established by identifying larvae on muscle biopsy; this is not generally required but may be useful in the setting of diagnostic uncertainty. (See "Trichinellosis".)

Sarcocystosis – Sarcocystosis is a protozoan infection that causes a gastrointestinal or myositis syndrome, depending on the ingested species. Muscular sarcocystosis is transmitted via consumption of food or water contaminated with oocysts from snakes (leading to muscular sarcocystosis); the incubation period is 9 to 13 days [15]. Eosinophilia is associated with muscular involvement in up to two-thirds of cases [16,17]. Most reported cases have occurred from Malaysia. A presumptive diagnosis can be made in the setting of compatible epidemiology, clinical, and laboratory findings; definitive diagnosis is established via identification of sarcocysts in muscle tissue. (See "Sarcocystosis".)

Clinical approach – For short-term travelers presenting with peripheral eosinophilia, fever, and myositis, in the setting of potential exposure including high-risk food consumption, our approach to the initial diagnostic evaluation includes:

Creatine kinase.

Serology for trichinellosis at the two-week time point after exposure.

Radiographic imaging – Ultrasonography of the affected region may aid in diagnosis; if nondiagnostic, magnetic resonance imaging of the affected region may be helpful.

Muscle biopsy may help confirm a diagnosis, but it is not required for most cases.

Fever and neurologic symptoms — Infectious causes of eosinophilia, fever, and neurologic symptoms are discussed separately. (See "Eosinophilic meningitis".)

Gastrointestinal symptoms without fever — Travel-related infections associated with gastrointestinal symptoms in the absence of fever include:

Clinical approach

Stool ova and parasite test – Stool testing may be negative for two months following helminth infection; however, stool for protozoal infections (such as Cystoisospora) may be positive as early as seven days after exposure. If an initial stool ova and parasite test is negative but symptoms persist, we pursue repeat testing.

Stool multiplex PCR testing, if relevant pathogens are included.

Strongyloides serology at least two weeks after potential exposure.

Diagnostic considerations

Hookworm – Hookworm infection is caused by A. duodenale (found in Mediterranean countries, Iran, India, Pakistan, and Asia) or N. americanus (found in North America, South America, Central Africa, Indonesia, the South Pacific, and parts of India) with some geographic overlap of these species [18]. These worms infect humans by larval penetration through intact skin. The incubation period is 8 to 21 days. Clinical manifestations include rash, transpulmonary passage (this is usually asymptomatic but may be associated with cough), gastrointestinal symptoms, anemia, and chronic nutritional impairment. The diagnosis is established via stool examination. (See "Hookworm infection" and "Overview of pulmonary eosinophilia", section on 'Transpulmonary passage of helminth larvae (Löffler syndrome)'.)

StrongyloidiasisS. stercoralis is a roundworm transmitted via direct skin contact with contaminated soil; it is endemic in rural areas of tropical and subtropical regions worldwide. Infection may be asymptomatic or manifest as waxing and waning gastrointestinal, cutaneous, or pulmonary symptoms. Eosinophilia may be the only indication of subclinical infection. A years-long latency period may occur between the initial exposure and development of symptoms. Diagnostic testing consists of serology and/or stool analysis; however, the sensitivity is limited. (See 'Fever and respiratory symptoms' above and "Strongyloidiasis".)

Cystoisospora (formerly Isospora) belli C. belli is a protozoan infection that causes gastrointestinal and systemic symptoms such as diarrhea and weight loss. Cystoisosporiasis has a worldwide distribution and is primarily an opportunistic infection in individuals with HIV infection; less commonly, it may infect immunocompetent hosts as well. Transmission is fecal-oral. Among immunocompetent patients, eosinophilia may be seen in up to 50 percent of cases; among immunocompromised patients, eosinophilia is typically absent [19]. The diagnosis is usually made by detection of stool oocysts. (See "Epidemiology, clinical manifestations, and diagnosis of Cystoisospora (Isospora) infections".)

Echinostomiasis (rare) – Echinostomiasis is an intestinal fluke infection endemic in East Asia; it is acquired through ingesting uncooked freshwater or brackish water fish, shellfish, and amphibians. The incubation period is a few weeks; clinical manifestations include a diarrheal illness with abdominal pain and accompanying eosinophilia although many are asymptomatic. The diagnosis is established by finding characteristic eggs in the stool. (See "Intestinal flukes", section on 'Echinostomiasis'.)

Allergic or dermatologic symptoms — Travel-related infections associated with allergic or dermatologic symptoms include:

Anisakiasis – Anisakiasis is a roundworm infection transmitted to humans by ingestion of undercooked, raw, or pickled infected fish. It is most common in Japan and Europe. The clinical presentation may include gastrointestinal symptoms, allergic symptoms (ie, urticaria, angioedema, or anaphylaxis), or both. Gastric involvement usually develops one to eight hours after ingestion of raw fish; intestinal involvement usually develops five to seven days following ingestion of raw fish. Eosinophilia typically develops several days after onset of clinical symptoms. The diagnosis may be established by visualization of the worm recovered from emesis or by endoscopy. (See "Miscellaneous nematodes", section on 'Anisakiasis'.)

Cutaneous larva migrans – Cutaneous larva migrans develops when infective larvae of animal hookworms (usually Ancylostoma braziliense) penetrate the skin and migrate in superficial tissues, producing a characteristic serpiginous eruption. Infection occurs worldwide; humans become infected after direct skin contact with soil, sand, or other material contaminated with feces from hookworm-infected animals, usually dogs or cats. Lesions appear within several days of exposure. Mild peripheral eosinophilia is seen in fewer than 10 percent of cases. The diagnosis is based on clinical history and physical findings. (See "Hookworm-related cutaneous larva migrans".)

Ascariasis – Ascariasis is a roundworm infection; it is endemic worldwide and is acquired via fecal-oral transmission. In the setting of heavy inoculum, generalized urticaria can occur during the first five days of infection; however, most patients with ascariasis are asymptomatic. Additional manifestations may include respiratory symptoms and gastrointestinal symptoms. The diagnosis is established via stool microscopy for ova or via examination of adult worms (which may be passed per rectum, coughed up, or passed in urine). (See 'Fever and respiratory symptoms' above and "Ascariasis".)

Gnathostomiasis – Gnathostomiasis is a roundworm infection that causes subcutaneous nodules or swellings that migrate to various areas of the body and can last for years. The soft tissue findings may begin following an acute febrile gastrointestinal illness; however, the gastrointestinal stage may be subclinical or occur many weeks prior to onset of soft tissue symptoms. The swellings frequently last one to two weeks and may be associated with pruritus, erythema, and pain. (See 'Fever and gastrointestinal symptoms' above and "Skin lesions in the returning traveler", section on 'Gnathostomiasis' and "Eosinophilic meningitis", section on 'Gnathostomiasis'.)

Paragonimiasis – Paragonimiasis is a fluke infection that can cause nontender, migratory subcutaneous nodules, which rarely appear at the time of pulmonary involvement; more commonly they precede pulmonary symptoms or can occur in the absence of other symptoms. Lesions are typically on the abdominal wall and have rarely been reported in travelers. (See "Paragonimiasis", section on 'Subcutaneous infection' and 'Fever and respiratory symptoms' above.)

Onchocerciasis (rare) – Onchocerciasis is a filarial nematode infection transmitted via black fly in sub-Saharan Africa. In travelers, the median interval to development of symptoms is 18 months from the time of exposure (range: three months to three years). The most common manifestations are pruritus, rash (commonly a papular dermatitis), and subcutaneous nodules. Ocular signs are relatively rare in travelers. Marked eosinophilia is seen (1000 to 2000/microL) but microfilariae are difficult to find in skin snips because of the relatively low burden of infection that results from a short exposure; in such cases the diagnosis is based on serology and clinical and epidemiologic clues. (See "Onchocerciasis".)

Lymphatic filariasis (rare) – Lymphatic filariasis is a nematode infection transmitted via mosquitoes. Wuchereria bancrofti occurs in sub-Saharan Africa, Southeast Asia, the Indian subcontinent, many of the Pacific islands, and focal areas of Latin America. Brugia malayi occurs mainly in China, India, Malaysia, the Philippines, Indonesia, and various Pacific islands. Brugia timori occurs on the Timor Island of Indonesia. Clinical manifestations usually develop one to two months following infection and include extremity edema and/or scrotal swelling; these may be associated with painful lymphadenopathy and mild to marked eosinophilia. The diagnosis is based on clinical and epidemiologic clues together with laboratory evaluation (including blood smears and/or antigen testing). (See "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis".)

Loiasis (rare) – Loiasis is a filarial nematode transmitted by biting deerflies in west and central Africa. The minimum incubation period is four to six months, but infection may occur years after exposure. Nonimmune individuals who travel to endemic regions are generally more prone to hypersensitivity reactions than local residents. The most common symptoms among travelers are Calabar swellings (migratory angioedema) on the limbs and/or face; these are nonpainful and nonpruritic and typically resolve in one to three days. Other symptoms include pruritus and urticaria. Eosinophilia is typically 3000 to 4000/microL. However, microfilaremia is often not detected in these patients; in such cases the diagnosis is based on clinical and epidemiologic clues. (See "Loiasis (Loa loa infection)".)

Bartonellosis (rare) – Bartonellosis refers to several related clinical syndromes from infection with organisms in the Bartonella genus. Organisms like Bartonella henselae (causing cat scratch disease) or Bartonella quintana (causing trench fever) are acquired from percutaneous injuries from cats and the feces of the human body louse inoculated into wounds or mucous membranes. Eosinophilia is reported in cases of invasive bartonellosis, such as B. henselae and B. quintana infection [20-22]. (See "Bartonella quintana infections: Clinical features, diagnosis, and treatment" and "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease".)

Asymptomatic patients — In many short-term travelers with eosinophilia, no cause is identified. For asymptomatic patients with negative diagnostic evaluation, periodic monitoring of the eosinophil count is reasonable; eosinophilia is self-resolving (over three to four months) in many cases [1]. For patients with eosinophilia lasting longer than this time period and with no obvious source, administration of empiric treatment for strongyloidiasis, soil-transmitted helminths, and flukes may be reasonable. (See 'Management and follow-up' below.)

Individuals with prolonged exposure — Individuals with prolonged exposure include long-term residents of endemic areas as well as immigrants/refugees from these areas. The causes of eosinophilia associated with short-term travel described above can also occur among individuals with prolonged exposure. However, individuals with prolonged exposure to parasitic infections typically have more subtle symptoms, and the degree of eosinophilia tends to be lower. Therefore, some infections mentioned above are discussed again in the following section, to highlight the differences in clinical presentation among individuals with prolonged exposure.

Gastrointestinal symptoms

Diagnostic considerations – Among individuals with prolonged exposure, infections associated with eosinophilia and gastrointestinal symptoms include:

Echinococcosis – Cystic echinococcosis is a tapeworm infection caused by Echinococcus granulosus; it is endemic in South America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, South Asia, and the former Soviet Union. Cysts typically occur in the liver; less commonly they can occur in the lung or other organs. Infection is often asymptomatic; when present, clinical manifestations include right upper quadrant discomfort, malaise, and weight loss. The incubation period may be years or decades. Echinococcus is not typically associated with eosinophilia; however, intermittent eosinophilia can occur in the days and weeks following leakage of antigenic material from the cyst(s). The diagnosis is typically established by ultrasound imaging and serologic testing. (See "Echinococcosis: Clinical manifestations and diagnosis" and 'Respiratory symptoms' below and 'Allergic or dermatologic symptoms' below.)

Ascariasis – Ascariasis is a roundworm infection; it is endemic worldwide and is acquired via fecal-oral transmission. Individuals from endemic areas may have heavy worm burdens; these may be associated with abdominal complaints, particularly in children. Complications include intestinal obstruction, appendicitis, or cholangitis. Eosinophilia is uncommon in chronic infection and mild when present. The diagnosis is established via stool microscopy for ova or via examination of adult worms. (See 'Fever and respiratory symptoms' above and 'Allergic or dermatologic symptoms' above and "Ascariasis".)

Trichuriasis – Trichuriasis is a fecal-oral transmitted roundworm infection that occurs most commonly in tropical climates. Most patients are asymptomatic; in the setting of large worm burden, dysentery occurs in association with eosinophilia, iron deficiency anemia, and rectal prolapse. The incubation period is two to three months. The diagnosis is made by stool examination for eggs. (See "Enterobiasis (pinworm) and trichuriasis (whipworm)", section on 'Trichuriasis (whipworm)'.)

Strongyloidiasis – Strongyloidiasis can persist for many decades after initial exposure, due to autoinfection. Chronic strongyloidiasis is typically asymptomatic; when present, clinical manifestations may include diarrhea, constipation, intermittent vomiting, and borborygmi. In one study including more than 800 immigrants with imported strongyloidiasis, eosinophilia was present in 82 percent of cases [23]. (See 'Gastrointestinal symptoms without fever' above and "Strongyloidiasis".)

Opisthorchiasis and clonorchiasis – Chronic opisthorchiasis and clonorchiasis are typically asymptomatic or accompanied by nonspecific abdominal symptoms (pain, flatulence, dyspepsia). In the absence of complications (such as cholangitis, cholelithiasis, cholangiocarcinoma), liver function tests are usually unremarkable. Most patients have a mild eosinophilia (<1000/microL). Ultrasonography demonstrates increased periductal echogenicity indicating periductal fibrosis. Establishing the diagnosis is important given the increased risk of cholangiocarcinoma associated with chronic infection. (See 'Fever and gastrointestinal symptoms' above and "Liver flukes: Clonorchis, Opisthorchis, and Metorchis".)

Hymenolepis nana – Hymenolepis nana is a tapeworm infection found in tropical and subtropical countries worldwide. It occurs most commonly in children, with fecal-oral transmission and an autoinfection life cycle; production of new eggs begins approximately 20 to 30 days after initial infection. Most patients are asymptomatic; symptoms develop as the parasite burden increases. Eosinophilia may or may not be present. (See "Tapeworm infections", section on 'Hymenolepiasis'.)

Schistosomiasis – Hepatosplenic schistosomiasis is caused by infection due to major species Schistosoma mansoni (Africa and South America) and Schistosoma japonicum (East Asia) and minor species Schistosoma mekongi (Laos, Cambodia) and Schistosoma intercalatum (West and Central Africa). It is caused by occlusion of portal venules by schistosome eggs, leading to periportal fibrosis and portal hypertension. Transmission to humans is via skin contact with fresh water where snails (intermediate host) reside. Among individuals with lifelong exposure, hepatomegaly, and/or splenomegaly develops in the second to third decade. In addition, intestinal symptoms include bloody stools and colicky abdominal pain. Varices can develop but cirrhosis is not seen. Mild eosinophilia (<1000/microL) is seen in approximately half of patients [24,25]. The incubation period is three to eight weeks. The diagnosis is established by serology or visualization of eggs in stool. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis" and 'Respiratory symptoms' below and 'Genitourinary symptoms' below.)

Clinical approach – For individuals with eosinophilia and gastrointestinal symptoms in the setting of prolonged exposure, our approach includes:

Stool ova and parasite exam

Stool multiplex PCR testing (if available)

Serologic testing for schistosomiasis and strongyloidiasis

Respiratory symptoms

Diagnostic considerations - Among individuals with prolonged exposure, infections associated with eosinophilia and respiratory symptoms include:

Paragonimiasis Paragonimiasis is a fluke infection endemic in East Asia, the Americas, and Central/West Africa. It is transmitted via consumption of raw or undercooked crab or crayfish; the incubation period is 2 to 20 days following ingestion. Patients present with a subacute to chronic cough that is mildly productive of blood-streaked sputum. Radiographic evidence of consolidation or cavitary lesions may occur and may be mistaken for tuberculosis; moderate to marked eosinophilia helps distinguish paragonimiasis from tuberculosis. During late infection, the diagnosis may be established by identifying Paragonimus eggs in the sputum, bronchoalveolar lavage, or stool. (See "Paragonimiasis".)

Echinococcal lung cyst (rare) Cystic echinococcosis is a tapeworm infection caused by E. granulosus; it is endemic in South America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, South Asia, and the former Soviet Union. Cysts typically occur in the liver; less commonly they can occur in the lung or other organs. Lung cysts cause a rise in eosinophils several days after rupture; symptoms include chest pain and/or cough. The incubation period may be years or decades. The diagnosis is typically established by ultrasound imaging and serologic testing. (See "Echinococcosis: Clinical manifestations and diagnosis" and 'Gastrointestinal symptoms' above and 'Allergic or dermatologic symptoms' below.)

Tropical pulmonary eosinophilia (rare) – Tropical pulmonary eosinophilia is a clinical manifestation of lymphatic filariasis, a roundworm infection. The disease is transmitted by a number of mosquito vectors throughout the Caribbean, South America, Africa, Asia, and the Pacific islands. Patients present with nocturnal cough, wheezing, dyspnea, and eosinophilia nearly always >3000/microL, often 10,000 to 20,000/microL. The incubation period is approximately one month. The diagnosis is usually established via serology. (See 'Fever and respiratory symptoms' above and "Tropical pulmonary eosinophilia".)

Chronic schistosomiasis (rare) – Schistosomiasis is acquired by swimming in fresh water contaminated with cercariae (the infectious form of the parasite); it occurs in Africa, South America, East Asia, and the Middle East. The incubation period is three to eight weeks. In the setting of chronic infection, eggs may travel anywhere in the body; pulmonary angiopathy and cor pulmonale have been described in the context of egg migration to the lungs. The diagnosis may be made via serology; the burden of infection may be determined via microscopy (of stool or urine, for egg detection) or antigen detection (in urine). (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis" and 'Gastrointestinal symptoms' above and 'Genitourinary symptoms' below.)

Tuberculosis − Tuberculosis is one of the most common infections worldwide; the highest rates are in sub-Saharan Africa, India, and the islands of Southeast Asia and Micronesia. Mycobacterium tuberculosis most commonly affects the lungs, but can involve every organ system. The infection may remain latent for decades, and active disease is more common with older age and immunocompromise such as with HIV infection. Rarely, modest eosinophilia associated with tuberculosis has been described [26,27].

Clinical approach − For individuals with eosinophilia and respiratory symptoms in the setting of prolonged exposure, our approach includes:

Chest imaging.

Sputum examination for acid fast bacilli.

Sputum ova and parasite test examination (for Paragonimus).

Stool ova and parasite exam (for schistosomiasis, Paragonimus infection).

Schistosomiasis serology.

If chest imaging is compatible with echinococcal infection − we pursue serology and ultrasonography to evaluate for hepatic cysts.

Genitourinary symptoms — Among individuals with prolonged exposure in the setting of eosinophilia and genitourinary symptoms, schistosomiasis is the likeliest infectious cause. It is a fluke infection acquired by swimming in fresh water contaminated with cercariae (the infectious form of the parasite); it occurs in Africa, South America, East Asia, and the Middle East. The incubation period is three to eight weeks. Chronic schistosomiasis due to S. haematobium should be suspected in patients from endemic areas with intermittent hematuria and/dysuria, chronic suprapubic pain, or obstructive uropathy; in addition, women may present with infertility. The diagnosis may be made via serology; the burden of infection may be determined by urine microscopy (for egg detection) and/or urine antigen detection. (See "Schistosomiasis: Epidemiology and clinical manifestations" and "Schistosomiasis: Diagnosis" and 'Gastrointestinal symptoms' above and 'Respiratory symptoms' above.)

Neurologic symptoms — Infectious causes of eosinophilia and neurologic symptoms are discussed separately. (See "Eosinophilic meningitis".)

Allergic or dermatologic symptoms — Among individuals with prolonged exposure, infections associated with eosinophilia and allergic or dermatologic symptoms include:

StrongyloidiasisStrongyloides stercoralis is a roundworm transmitted via skin contact with contaminated soil; it is endemic in rural areas of tropical and subtropical regions worldwide. Patients with strongyloidiasis may develop dermatologic manifestations such as larva currens ("running" larva, a pathognomonic finding) (picture 1) or a nonspecific urticarial rash. Larva currens is typically observed years after initial infection. Diagnostic testing consists of serology; however, the sensitivity is limited. Therefore, if serology is negative and clinical suspicion for strongyloidiasis persists, empiric treatment may be warranted in some circumstances. (See "Strongyloidiasis".)

Echinococcal cyst – Cystic echinococcosis is a tapeworm infection caused by E. granulosus; it is endemic in South America, the Middle East and eastern Mediterranean, some sub-Saharan African countries, western China, South Asia, and the former Soviet Union. Echinococcal cysts can cause anaphylaxis after rupture into the peritoneal or pleural cavity. The incubation period may be years or decades. Echinococcus is not typically associated with eosinophilia; however, intermittent eosinophilia can occur in the days and weeks following leakage of antigenic material from the cyst(s). The diagnosis is typically established by ultrasound imaging and serologic testing. (See "Echinococcosis: Clinical manifestations and diagnosis" and 'Gastrointestinal symptoms' above and 'Respiratory symptoms' above.)

Sparganosis – Sparganosis is a tapeworm infection acquired in East Asia from ingesting uncooked amphibian or reptile meat or drinking unpurified water; the incubation period may be up to several years. Most commonly, sparganosis causes a firm subcutaneous mass; this presentation is not associated with eosinophilia. Eosinophilia may occur in the setting of infection due to Spargunum proliferum, which may be associated with systemic illness, disseminated cutaneous lesions, and/or central nervous system disease. The diagnosis is often based on compatible clinical and radiographic appearance, supported by pertinent epidemiology and serology; definitive diagnosis is based on identification of a worm in surgically resected material. (See "Tapeworm infections", section on 'Sparganosis'.)

Onchocerciasis – Onchocerciasis is a filarial nematode infection transmitted via black fly in sub-Saharan Africa. It usually presents with chronic papular dermatitis, mimicking atopic dermatitis; other findings include depigmentation, scaling, and enlarged inguinal lymph nodes. Mild eosinophilia is observed in 70 to 80 percent of cases. In patients with lichenified onchodermatitis ("sowda"), which presents with hyperpigmented pruritic papules and plaques limited to one limb, eosinophilia is typically marked. The incubation period is 10 to 12 months. The diagnosis is based on a history of compatible epidemiologic exposure, clinical manifestations, and supportive laboratory evidence of infection. (See "Onchocerciasis" and 'Allergic or dermatologic symptoms' above.)

Loiasis – Loiasis is a filarial nematode transmitted by biting deerflies in west and central Africa. The minimum incubation period is four to six months, but infection may occur years after exposure. Among individuals from endemic areas, loiasis is often asymptomatic; clinical manifestations include ocular symptoms and Calabar swellings (migratory angioedema) on the limbs and/or face; these are nonpainful and nonpruritic and typically resolve in one to three days. Mild eosinophilia (<1000/microL) is observed in approximately half of patients. The diagnosis may be established by identifying a migrating adult worm in the subcutaneous tissue or conjunctiva or by detecting microfilariae in a blood smear. (See "Loiasis (Loa loa infection)".)

Lymphatic filariasis – Lymphatic filariasis is a filarial nematode infection transmitted via mosquitoes. W. bancrofti occurs in sub-Saharan Africa, Southeast Asia, the Indian subcontinent, many of the Pacific islands, and focal areas of Latin America. B. malayi occurs mainly in China, India, Malaysia, the Philippines, Indonesia, and various Pacific islands. B. timori occurs on the Timor Island of Indonesia. Clinical manifestations usually develop one to two months following infection and include extremity edema and/or scrotal swelling; these may be associated with painful lymphadenopathy. Eosinophilia is observed in approximately 20 percent of patients with chronic infection. The diagnosis is based on clinical and epidemiologic clues together with laboratory evaluation (including blood smears and/or antigen testing). (See "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis" and 'Allergic or dermatologic symptoms' above.)

Leprosy – Leprosy (also known as Hansen disease) is a chronic infectious disease of the skin and peripheral nerves due to Mycobacterium leprae complex. The disease is transmitted via the respiratory route. Regions with high incidence include India, Brazil, Indonesia, Bangladesh, and Nigeria. Chronic infection may result in dermatologic changes and peripheral neuropathy. The diagnosis is confirmed via skin biopsy. Eosinophilia is a rare feature; however, it may be observed when dapsone is used in the treatment of the infection [28,29]. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Individuals with no travel outside the United States or Europe

Respiratory symptoms — Among individuals with no travel outside the United States or Europe, infections associated with eosinophilia and respiratory symptoms include:

Allergic bronchopulmonary aspergillosis – Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction of the airways that occurs when bronchi become colonized by Aspergillus species. Patients at increased risk for ABPA include those with chronic lung disease and bronchiectasis, particularly cystic fibrosis. The diagnosis should suspected in patients with eosinophilia >500/microL, together with other manifestations including recurrent asthma exacerbations responsive to corticosteroids and supporting chest radiograph findings; the diagnosis is established by fulfillment of diagnostic criteria summarized separately. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

Coccidioidomycosis – Coccidioidomycosis is an endemic mycosis prevalent in the southwestern United States and parts of Latin America, with an expanding geographic distribution [30-34]. This fungus is inhaled and may cause pneumonia and disseminated disease. The incubation period is 7 to 21 days. In localized pulmonary infection, mild eosinophilia may be seen in 40 percent of cases. In disseminated disease (particularly with liver and skin involvement), marked eosinophilia may be seen. Diagnosis is based on serologic testing; culture is useful in some cases. (See "Primary pulmonary coccidioidal infection".)

Paragonimiasis – Paragonimiasis is a fluke infection; in the United States, it is caused by infection due to Paragonimus kellicotti; most cases have been acquired in Missouri as a result of eating raw infected crayfish. The average incubation period is 4 weeks (range 2 to 12 weeks). Clinical manifestations include cough, pleural effusion, fever, and weight loss, with mean eosinophil count 1600/microL. Early infection may resemble Loeffler syndrome; during this phase (prior to egg production), a presumptive diagnosis can be made based on clinical presentation and exposure history. During late infection, the diagnosis can be established via identification of Paragonimus eggs in sputum, bronchoalveolar lavage, or stool. (See "Paragonimiasis" and 'Fever and respiratory symptoms' above.)

DirofilariasisDirofilaria immitis, the dog heartworm, is a zoonosis transmitted from dogs to humans via mosquitos. Dirofilariasis is particularly common in the Mediterranean region; it has also been described in the United States, Eastern Europe, and Central Asia. Most human infections are asymptomatic; however, symptoms may develop after four to eight months. Pulmonary infection may be identified incidentally on chest imaging. Some patients develop chest pain, cough, hemoptysis, fever, and malaise. Eosinophilia is observed in approximately 10 percent of patients. Definitive diagnosis of dirofilariasis requires biopsy of the involved tissue for histopathologic identification. (See "Miscellaneous nematodes", section on 'Dirofilariasis'.)

Abdominal symptoms

Diagnostic considerations – Among individuals with no travel outside the United States or Europe, infections associated with eosinophilia and abdominal symptoms include:

StrongyloidiasisS. stercoralis is a roundworm transmitted via skin contact with contaminated soil; it is endemic in rural areas of tropical and subtropical regions worldwide, including the United States (Appalachian regions of Kentucky, Tennessee, North Carolina, and Virginia, and possibly other areas). Infection may be asymptomatic or manifest as waxing and waning gastrointestinal, cutaneous, or pulmonary symptoms. Eosinophilia (typically <1000/microL) may be the only indication of subclinical infection; it occurs in fewer than half of cases. A years-long latency period may occur between the initial exposure and development of symptoms. Diagnostic testing consists of serology, but the sensitivity is limited. Therefore, if serology is negative and clinical suspicion for strongyloidiasis persists, empiric treatment may be warranted in some circumstances. (See "Strongyloidiasis".)

Toxocariasis – Toxocariasis (also called visceral larva migrans or ocular larva migrans) is caused by nematodes Toxocara canis or Toxocara cati; these organisms preferentially infect dogs and cats, respectively, with humans as accidental hosts. Toxocara spp are endemic worldwide and are transmitted via the ingestion of soil or food contaminated by animal feces (most frequently among children). After an incubation period of two to four days, clinical manifestations range from asymptomatic infection to severe organ injury. Presentations include visceral larva migrans (typically hepatitis and pneumonitis as the larvae migrate through the liver and lungs, respectively) and ocular larva migrans (unilateral visual impairment and subsequent strabismus). Eosinophil counts may be as high as 15,000 to 100,000/microL. The diagnosis may be established clinically and via serology. (See "Toxocariasis: Visceral and ocular larva migrans".)

Basidiobolomycosis (very rare) – Basidiobolomycosis is an emerging fungal pathogen [35,36]. It usually causes subcutaneous infection, transmitted via traumatic inoculation. Gastrointestinal basidiobolomycosis is rare; it is associated with mass or inflammatory lesions in the gastrointestinal tract. Cases have occurred worldwide, particularly in the Middle East and the southwestern part of the United States. Such patients present with abdominal pain and gastrointestinal symptoms; eosinophilia is typically 1000 to 2000/microL. The diagnosis is established via histopathology and culture. (See "Eosinophilic gastrointestinal diseases".)

Clinical approach – Most causes of eosinophilia in this context are not infectious. (See "Approach to the patient with unexplained eosinophilia".).

Investigations for infectious causes are best guided by the clinical history. For example, there is autochthonous transmission of strongyloides in parts of the southern United States; in such cases, serologic testing is helpful. Similarly, toxocariasis is present worldwide; the diagnosis may be confirmed with serology.

Neurologic symptoms — Among individuals with no travel outside the United States or Europe in the setting of eosinophilia and neurologic symptoms, baylisascariasis (a disease caused by a raccoon parasite in the United States) is the likeliest infectious cause. Transmission occurs via ingestion of infective Baylisascaris procyonis eggs from the environment; typically, this occurs among young children playing in the dirt. Clinical manifestations include involvement of the brain, spinal cord, and eyes. The incubation period is two to four weeks. Blood and cerebrospinal fluid eosinophilia are commonly observed. Definitive diagnosis requires morphologic identification of larvae on tissue biopsy; serologic testing is also available. (See "Eosinophilic meningitis", section on 'Baylisascariasis'.)

Dermatologic symptoms

Diagnostic considerations - Among individuals with no travel outside the United States or Europe, infections associated with eosinophilia and dermatologic symptoms include:

Eosinophilic folliculitis – Eosinophilic folliculitis occurs in the setting of HIV infection; it is a chronic pruritic skin eruption associated with low CD4 counts. Clinical manifestations include intensely pruritic follicular lesions generally on the upper trunk, face, neck, or scalp. The diagnosis is established via skin biopsy. (See "HIV-associated eosinophilic folliculitis".)

Scabies – Scabies is a skin infestation caused by the mite Sarcoptes scabiei. Transmission usually occurs via skin-to-skin contact but may occur via fomites. Crusted scabies is associated with a much higher mite burden and is more likely to be associated with eosinophilia; it usually occurs in older adults or immunocompromised individuals [37,38]. A diagnosis of scabies may be suspected based upon the patient history and physical examination; it is confirmed via detection of scabies mites, eggs, or feces on microscopic examination. (See "Scabies: Epidemiology, clinical features, and diagnosis".)

Resolving scarlet fever – Scarlet fever is a cutaneous hypersensitivity reaction to Streptococcus pyogenes toxins; it typically coincides with a syndrome of pharyngitis. The rash has an erythematous "sandpaper"-like quality; the diagnosis is established clinically. Eosinophilia may occur during the acute illness or, more commonly, during the recovery phase [39]. (See "Complications of streptococcal tonsillopharyngitis".)

Bartonellosis (rare) – Bartonellosis refers to several related clinical syndromes from infection with organisms in the Bartonella genus. Organisms like B. henselae (causing cat scratch disease) or B. quintana (causing trench fever) are acquired from percutaneous injuries from cats and the feces of the human body louse inoculated into wounds or mucous membranes. Eosinophilia is reported in cases of invasive bartonellosis, such as B. henselae and B. quintana infection [20-22]. (See "Bartonella quintana infections: Clinical features, diagnosis, and treatment" and "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease".)

Clinical approach – Diagnostic evaluation should be guided by the clinical history; as an example, in patients with intense pruritus and a compatible syndrome, we perform skin scrapings to evaluate for scabies.

MANAGEMENT AND FOLLOW-UP — A definitive diagnosis is established in about one-third of patients with eosinophilia [40]. Patients with eosinophilia due to an infectious cause should be treated accordingly; the approach to treatment of specific conditions is discussed in separate topics.

Eosinophilia resolves spontaneously in some circumstances. For patients with no definitive diagnosis who are clinically stable, a complete blood count may be repeated in one to three months to assess for resolution. (See "Approach to the patient with unexplained eosinophilia".)

For individuals with persistent, unexplained eosinophilia and risk factors for strongyloidiasis (eg, skin contact with contaminated soil in tropical and subtropical regions), administration of empiric treatment (ivermectin 200 mcg/kg orally, single dose) is reasonable, given limited sensitivity of diagnostic tools for strongyloidiasis [40]. However, empiric ivermectin should not be administered to individuals who reside or have resided in West and Central African regions endemic for Loa loa, given risk for encephalopathy following ivermectin therapy due to high L. loa microfilarial burden. (See "Strongyloidiasis" and "Loiasis (Loa loa infection)".)

For individuals with persistent, unexplained eosinophilia who have traveled to or resided in regions where helminths are endemic, administration of empiric treatment for soil-transmitted helminths (albendazole 400 mg orally, single dose) and fluke infections (praziquantel 40 mg/kg orally divided in two doses) is reasonable [1].

The optimal approach to empiric management of eosinophilia in the absence of definitive diagnosis is uncertain, and there are no clinical trial data to guide the approach. For patients with unexplained eosinophilia and relevant epidemiologic exposure for strongyloidiasis (eg, skin contact with contaminated soil in tropical and subtropical regions), we favor administration of empiric treatment for strongyloidiasis with ivermectin. For patients with persistent eosinophilia four to six months later as well as relevant epidemiologic exposure for soil-transmitted helminths, we favor empiric treatment with albendazole.

During treatment of helminth infection, eosinophilia may increase transiently. Following treatment of helminth infection, eosinophilia may persist for weeks or months; this may be because killed helminths in tissues may act as an ongoing source of antigens. The magnitude of post-treatment eosinophilia depends on the parasite burden and host immune response [24,41]. Routine follow-up testing for eosinophilia after empiric treatment is not necessary.

SUMMARY AND RECOMMENDATIONS

Peripheral blood eosinophilia (≥500 eosinophils/microL) may be caused by numerous conditions, including allergic, infectious, inflammatory, and neoplastic disorders (table 1). A general approach to patients with eosinophilia is presented separately. (See "Approach to the patient with unexplained eosinophilia", section on 'Initial evaluation'.)

Among individuals with eosinophilia, the likelihood of an infectious cause is highest among those with relevant epidemiologic exposure (residence in or travel to areas where infectious causes of eosinophilia are endemic). In addition, infectious causes should be considered in patients with ≥1500 eosinophils/microL. (See 'Introduction' above.)

The clinical history should establish a number of details, including the signs and symptoms, the time of onset, the nature of any relevant epidemiologic exposures, medical history, and medications (table 1). (See 'History and physical examination' above.)

An initial approach to laboratory testing for patients with eosinophilia is presented separately (see "Approach to the patient with unexplained eosinophilia", section on 'Laboratory and diagnostic tests'). Stool examination for ova and parasites can be helpful in diagnosing some intestinal and hepatobiliary parasites; however, the test is relatively insensitive, the timing of symptoms often does not correspond with positive stool examination, and many parasites that cause eosinophilia are not found in the stool. (See 'Laboratory tests' above.)

A variety of infections may be associated with eosinophilia; these include helminths (worms), fungi, protozoa, some bacteria, the retroviruses HIV and human T cell lymphotropic virus type 1, and scabies (a mite infestation). Helminths are the most commonly identified infectious causes of eosinophilia; categories include flukes (trematodes), tapeworms (cestodes), and roundworms (nematodes) (table 2). (See 'Overview of causes' above.)

Components of the clinical approach include consideration of the geographic region(s) of exposure, the duration of exposure (short-term versus prolonged exposure), the presenting signs and symptoms, and the incubation period. The diagnostic evaluation should be targeted to the likeliest possible etiologies based on these factors. (See 'Clinical approach' above.)

A definitive diagnosis is established in about one-third of patients with eosinophilia. For patients with no definitive diagnosis who are clinically stable, a complete blood count may be repeated in one to three months to assess for resolution. (See 'Management and follow-up' above.)

The optimal approach to empiric management of eosinophilia in the absence of definitive diagnosis is uncertain, and there are no clinical trial data to guide the approach (see 'Management and follow-up' above):

For patients with unexplained eosinophilia and relevant epidemiologic exposure for strongyloidiasis (eg, skin contact with contaminated soil in tropical and subtropical regions), we suggest administration of empiric treatment for strongyloidiasis with ivermectin (Grade 2C). However, empiric ivermectin should not be administered to individuals who reside or have resided in West and Central African regions endemic for Loa loa, given risk for encephalopathy due to high L. loa microfilarial burden following ivermectin therapy. (See 'Management and follow-up' above.)

For patients with persistent eosinophilia four to six months later as well as relevant epidemiologic exposure for soil-transmitted helminths, we suggest administration of empiric treatment with albendazole (Grade 2C).

  1. O'Connell EM, Nutman TB. Eosinophilia in Infectious Diseases. Immunol Allergy Clin North Am 2015; 35:493.
  2. Butt NM, Lambert J, Ali S, et al. Guideline for the investigation and management of eosinophilia. Br J Haematol 2017; 176:553.
  3. Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc 2005; 80:75.
  4. Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol 2010; 126:39.
  5. Akuthota P, Weller PF. Eosinophils and disease pathogenesis. Semin Hematol 2012; 49:113.
  6. Boyer DF. Blood and Bone Marrow Evaluation for Eosinophilia. Arch Pathol Lab Med 2016; 140:1060.
  7. Valent P, Klion AD, Horny HP, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 2012; 130:607.
  8. Wilson ME, Weller PF. Eosinophilia. In: Tropical Infectious Diseases: Principles, Pathogens and Practice, 3rd ed, Guerrant RL, Walker DH, Weller PF (Eds), Saunders Elsevier, Philadelphia 2011. p.939.
  9. Chou A, Serpa JA. Eosinophilia in patients infected with human immunodeficiency virus. Curr HIV/AIDS Rep 2015; 12:313.
  10. Vukelja SJ, Weiss RB, Perry DJ, Longo DL. Eosinophilia associated with adult T-cell leukemia/lymphoma. Cancer 1988; 62:1527.
  11. Bullock WE, Artz RP, Bhathena D, Tung KS. Histoplasmosis. Association with circulating immune complexes, eosinophilia, and mesangiopathic glomerulonephritis. Arch Intern Med 1979; 139:700.
  12. Gao LW, Jiao AX, Wu XR, et al. Clinical characteristics of disseminated cryptococcosis in previously healthy children in China. BMC Infect Dis 2017; 17:359.
  13. Luo FL, Tao YH, Wang YM, Li H. Clinical study of 23 pediatric patients with cryptococcosis. Eur Rev Med Pharmacol Sci 2015; 19:3801.
  14. Marwaha RK, Trehan A, Jayashree K, Vasishta RK. Hypereosinophilia in disseminated cryptococcal disease. Pediatr Infect Dis J 1995; 14:1102.
  15. Fayer R, Esposito DH, Dubey JP. Human infections with Sarcocystis species. Clin Microbiol Rev 2015; 28:295.
  16. Esposito DH, Stich A, Epelboin L, et al. Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012. Clin Infect Dis 2014; 59:1401.
  17. Italiano CM, Wong KT, AbuBakar S, et al. Sarcocystis nesbitti causes acute, relapsing febrile myositis with a high attack rate: description of a large outbreak of muscular sarcocystosis in Pangkor Island, Malaysia, 2012. PLoS Negl Trop Dis 2014; 8:e2876.
  18. Hoagland KE, Schad GA. Necator americanus and Ancylostoma duodenale: life history parameters and epidemiological implications of two sympatric hookworms of humans. Exp Parasitol 1978; 44:36.
  19. Apt WB. Eosinophilia in Isospora infections. Parasitol Today 1986; 2:22.
  20. Baylor P, Garoufi A, Karpathios T, et al. Transverse myelitis in 2 patients with Bartonella henselae infection (cat scratch disease). Clin Infect Dis 2007; 45:e42.
  21. Arvand M, Schäd SG. Isolation of Bartonella henselae DNA from the peripheral blood of a patient with cat scratch disease up to 4 months after the cat scratch injury. J Clin Microbiol 2006; 44:2288.
  22. Foucault C, Brouqui P, Raoult D. Bartonella quintana characteristics and clinical management. Emerg Infect Dis 2006; 12:217.
  23. Salvador F, Treviño B, Chamorro-Tojeiro S, et al. Imported strongyloidiasis: Data from 1245 cases registered in the +REDIVI Spanish Collaborative Network (2009-2017). PLoS Negl Trop Dis 2019; 13:e0007399.
  24. Reimert CM, Fitzsimmons CM, Joseph S, et al. Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel. Clin Vaccine Immunol 2006; 13:584.
  25. Bierman WF, Wetsteyn JC, van Gool T. Presentation and diagnosis of imported schistosomiasis: relevance of eosinophilia, microscopy for ova, and serology. J Travel Med 2005; 12:9.
  26. Gill AM. Eosinophilia in Tuberculosis. Br Med J 1940; 2:220.
  27. Flores M, Merino-Angulo J, Tanago JG, Aquirre C. Late generalized tuberculosis and eosinophilia. Arch Intern Med 1983; 143:182.
  28. Mehrotra S, Dhiman RK, Sircar AR. Hyper-eosinophilic syndrome with lepromatous leprosy. J Assoc Physicians India 1988; 36:287.
  29. Vinod KV, Arun K, Dutta TK. Dapsone hypersensitivity syndrome: A rare life threatening complication of dapsone therapy. J Pharmacol Pharmacother 2013; 4:158.
  30. Simons CM, Stratton CW, Kim AS. Peripheral blood eosinophilia as a clue to the diagnosis of an occult Coccidioides infection. Hum Pathol 2011; 42:449.
  31. Harley WB, Blaser MJ. Disseminated coccidioidomycosis associated with extreme eosinophilia. Clin Infect Dis 1994; 18:627.
  32. Drake KW, Adam RD. Coccidioidal meningitis and brain abscesses: analysis of 71 cases at a referral center. Neurology 2009; 73:1780.
  33. Ragland AS, Arsura E, Ismail Y, Johnson R. Eosinophilic pleocytosis in coccidioidal meningitis: frequency and significance. Am J Med 1993; 95:254.
  34. McCotter OZ, Benedict K, Engelthaler DM, et al. Update on the Epidemiology of coccidioidomycosis in the United States. Med Mycol 2019; 57:S30.
  35. Pezzani MD, Di Cristo V, Parravicini C, et al. Gastrointestinal basidiobolomycosis: An emerging mycosis difficult to diagnose but curable. Case report and review of the literature. Travel Med Infect Dis 2019; 31:101378.
  36. Vikram HR, Smilack JD, Leighton JA, et al. Emergence of gastrointestinal basidiobolomycosis in the United States, with a review of worldwide cases. Clin Infect Dis 2012; 54:1685.
  37. Sluzevich JC, Sheth AP, Lucky AW. Persistent eosinophilia as a presenting sign of scabies in patients with disorders of keratinization. Arch Dermatol 2007; 143:670.
  38. Roberts LJ, Huffam SE, Walton SF, Currie BJ. Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. J Infect 2005; 50:375.
  39. Friedman S. Eosinophilia in scarlet fever. Am J Dis Child 1935; 49:933.
  40. van Doorn HR, Koelewijn R, Hofwegen H, et al. Use of enzyme-linked immunosorbent assay and dipstick assay for detection of Strongyloides stercoralis infection in humans. J Clin Microbiol 2007; 45:438.
  41. Ottesen EA, Weller PF. Eosinophilia following treatment of patients with schistosomiasis mansoni and Bancroft's filariasis. J Infect Dis 1979; 139:343.
Topic 120281 Version 8.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟