Pulmonary Eosinophilic Conundrums

Abstract

Pulmonary eosinophilic syndromes include a heterogeneous group of disorders. They have in common the presence of eosinophils in the airways and/or lung parenchyma. They may manifest peripheral eosinophilia and symptoms vary depending on what additional organs may be involved. The following cases ­highlight pulmonary eosinophilic syndromes as conundrums and emphasize a systematic approach to this heterogeneous group of disorders.

Case 1

A 60-year-old man with a history of well-controlled asthma was transferred to the medical intensive care unit for increasing shortness of breath. The patient was ­initially admitted to the general medicine team with a chief complaint of increasing productive cough, subjective fevers, and increased dyspnea over the past 1 week. Six weeks prior to admission, the patient complained of a non-productive cough and was treated with doxycycline. His symptoms improved temporarily, prompting his return 3 weeks later. Upon admission, the patient also endorsed having nightsweats for the past 3–4 weeks, and a 16-pound weight loss over the past 3 months.

The patient has a history of obstructive sleep apnea for which he uses nightly CPAP, well-controlled asthma, type 2 diabetes, hypothyroidism, gout, and schizoaffective disorder. He lives with his wife and two grandchildren who are 1 and 3 years of age. ­He has a 60 pack-year tobacco smoking history and quit cigarettes 10 years ago, ­occasionally smokes cigars (about 1/week), has no history of illicit drug abuse, and does not drink alcohol. He has two parakeets at home and cleans their cages daily. He worked in a resin plant for 1 year during his military service and thus had exposure to asbestos. He has no family history of any lung diseases or connective tissue disorders.

His list of medications includes citalopram 0.5 mg daily, abilify 20 mg daily, olanzapine 15 mg twice daily, risperidone 3 mg three times daily, diltiazem 360 mg SA daily, hydrochlorothiazide 37.5 mg daily, omeprazole 20 mg daily, indomethacin 75 mg daily, colchicines 0.6 mg daily, mometasone inhaler 220 mcg twice daily, and Combivent^® inhaler four times daily. Review of systems was negative for hemoptysis, diarrhea, sinus congestion, and joint tenderness or erythema.

Physical examination revealed a slightly overweight man in respiratory distress with mild use of accessory muscles but able to answer questions appropriately. He had a temperature of 36.8°C, blood pressure of 121/68 mmHg, heart rate of 74 beats/min, a respiratory rate of 20–26 breaths/min, and an oxygen saturation of 92% on 2 L nasal cannula. No murmurs were appreciated on cardiac examination. Diffuse crackles (louder during the expiratory phase) were heard on lung auscultation, accompanied by an expiratory wheeze. His extremities were without clubbing, cyanosis, or edema and there was no rash on skin examination.

An arterial blood gas revealed a pH of 7.43, PaCO₂ of 57, and a PaO₂ of 64 on supplementation oxygen at 2 L/min by nasal cannula. Laboratory data was notable for an elevated WBC of 18.8 k/mm³ with 2.1% peripheral eosinophils and 88% neutrophils. His serum bicarbonate was 24 mEq/L and his liver panel was unremarkable. His chest x-ray was abnormal with a predominance of diffuse bilateral airspace opacities, increased in both upper lung fields (Fig. 4.1). Over the next 5 days, the patient’s breathing worsened though he maintained oxygen saturations greater than 90% on 6 L nasal cannula. Serial CBC was remarkable for increasing peripheral eosinophilia (maximum of 15%).

Fig. 4.1

(a) AP view of the chest on admission to the medical intensive care unit. Notable for increased opacities bilaterally with a peripheral predominance. (b) Lateral view of the chest on admission to the medical intensive care unit notable for diffuse opacities

With the Presented Data, What Is Your Working Diagnosis?

The patient’s history of asthma and exposure to young children requires consideration of an asthma exacerbation in the setting of a viral or bacterial respiratory infection. Other infectious causes such as active tuberculosis or atypical mycobacterial disease are possible given the patient’s systemic symptoms. In addition, the patient lives with parakeets, which makes hypersensitivity pneumonitis a ­possibility. He is also prescribed an extensive list of medications including most recently an antibiotic, which make drug-induced eosinophilia an important consideration. The patient’s weight loss and presence of nightsweats over the past several months bring hypereosinophilic syndromes and Churg–Strauss syndrome into consideration, and involvement of other organ systems would make these more likely candidates. Furthermore, Churg–Strauss syndrome, also known as “allergic angiitis granulomatosis,” should be investigated in any patient with asthma and peripheral eosinophilia.

Differential Diagnosis

• 1. Hypersensitivity pneumonitis

• 2. Churg–Strauss syndrome

• 3. Acute eosinophilic pneumonia

• 4. Chronic eosinophilic pneumonia

• 5. Hypereosinophilic syndromes

• 6. Asthma exacerbation

Workup

Empiric, broad-spectrum antibiotic treatment was initiated given the acuity of this patient’s presentation. A hypersensitivity panel, IgE level as well as ANCA testing was requested, and stool samples were sent to rule out the presence of ova and parasites. A computerized tomography (CT) of the chest was ordered to rule out cavitary lesions or possible abscesses not seen on chest x-rays. Furthermore, a fiberoptic bronchoscopy with a bronchoalveolar lavage (BAL) was performed to assess for possible pulmonary eosinophilia as well as to obtain specimens for culture.

The hypersensitivity panel was negative for bird antigen–antibody reactivity, IgE level was 278 IU/mL (reference range <100 IU/mL), and ANCA testing was negative. Multiple stool samples were negative for the presence of ova and parasites. Blood and sputum cultures were negative for bacterial and fungal infections, and urine Legionella antigen was negative. Sputum was smear negative for ­acid-fast bacilli on three successive samples. A CT of the chest was notable for peribronchial consolidation and opacities in bilateral upper lobes and the right lower lobe, with moderate sparing of the left lower lobe (Fig. 4.2). Small bilateral pleural ­effusions were seen at the bases posteriorly. Small subcentimeter pre-tracheal and subcarinal lymph nodes were identified. A fiberoptic bronchoscopy was performed at the bedside, and BAL fluid consisted of a WBC of 1,300 k/mm³ with 14% neutrophils, 24% lymphocytes, 1% monocytes, and 61% eosinophils. Transbronchial biopsies were negative for granulomas or evidence of vasculitis, but eosinophils were present.

Fig. 4.2

CT chest, lung windows ((a) upper, (b) middle, (c) lower cuts) revealing multilobar opacities with a upper lobe predominance

What Is Your Diagnosis and Why?

Chronic Eosinophilic Pneumonia

The patient had no evidence of a vasculitis or multiorgan involvement, thus excluding Churg–Strauss and hypereosinophilic syndrome. Clinically, the patient had chronic symptoms (weight loss over the past 3 months and nightsweats, cough and dyspnea over the past 3–4 weeks), thus excluding acute eosinophilic pneumonia. He also had alveolar infiltrates on his CXR that initially showed central sparing, and had >40% eosinophils on his BAL, a hallmark of chronic eosinophilic pneumonia.

Discussion

Pulmonary eosinophilic syndromes are characterized by an infiltrative lung disease with a predominance of eosinophils in any or all of the following: peripheral blood (normal <3% or absolute count <500/mm³), sputum, BAL (normal <2%), and lung tissue [1, 2]. Pulmonary eosinophilic syndromes have been stratified in a variety of ways based on clinical, radiographic, and etiologic associations. Table 4.1 groups these pulmonary diseases into those of undetermined cause (idiopathic) such as acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), Churg–Strauss syndrome, and hypereosinophilic syndromes, as well as those of determined cause (secondary) eosinophilic pneumonias due to parasitic infections, drug, toxin or radiation-induced reactions, allergic bronchopulmonary aspergillosis (ABPA) and bronchocentric granulomatosis. A third category encompasses a miscellaneous group of conditions that are associated with eosinophilia, such as asthma, organizing pneumonia, hypersensitivity pneumonitis, neoplasms, as well as systemic diseases such as rheumatoid arthritis and sarcoidosis (Table 4.1) [1, 2].

Table 4.1 Classification of pulmonary eosinophilic syndromes

Thorough history and physical examination is crucial in the workup of ­pulmonary eosinophilic syndromes. The clinical picture is dictated by which organs are infiltrated by eosinophils. This can range from general malaise to fever, shortness of breath, difficult-to-control asthma, or extrapulmonary findings such as a skin rash, rhinosinusitis and heart failure. Information regarding time of onset, duration of symptoms, and precipitating factors such as inhalation of dust are important clues. In addition, a review of new and old medications, occupational and environmental exposures, and travel history are vital in discovering the etiology if not specific kind of eosinophilic pneumonias [2].

Characteristic clinical and radiological features in conjunction with the presence and degree of alveolar or serum eosinophilia are necessary to diagnose pulmonary eosinophilic syndromes. To that end, laboratory data including measurement of peripheral serum eosinophils, cultures, serum IgE levels, spirometry, and radiographic imaging (such as a chest x-ray and computerized tomography) are important adjuncts. A preliminary diagnosis of a pulmonary eosinophilic syndrome should be made if clinical, laboratory and radiographic findings are present.

It is important at this point of the workup to seek out distinguishing clues. For example, the presence of asthma, as in this patient, would narrow down the ­possibilities to the idiopathic “ABC” eosinophilic disorders – AEP, broncho­centric granulomatosis, Churg–Strauss syndrome and CEP. Elevated IgE levels (>1,000 IU/mL) and asthma symptoms should suggest ABPA, hypereosinophilic syndrome, Loeffler’s syndrome and Churg–Strauss syndrome.

Finally, the use of BAL fluid has markedly reduced the need for a lung biopsy. Both video-assisted thoracic surgery (VATS) and transbronchial biopsies are thus reserved for more difficult to diagnose cases, when tissue confirmation is required in confusing cases or to rule out lung cancer and infection before adding cytotoxic drug regimens to systemic corticosteroids [1].

Based on the duration of symptoms and particularly the markedly elevated eosinophils in his BAL, this patient was diagnosed with CEP. CEP consists of respiratory and systemic symptoms that progress over weeks to months [1]. Symptoms can consist of cough, dyspnea, chest pain, weight loss, fatigue, and nightsweats. There is a female predilection with a 2:1 ratio, and the peak incidence occurs in the fifth decade of life, though the age span for this disease ranges from 18 to 80 years [3]. Two-thirds of patients also have asthma, as was the case with our patient. However, neither asthma nor a history of atopy is a prerequisite for CEP.

While the cause of CEP is enigmatic, it is thought that an unknown insult or stimulus leads to an accumulation of eosinophils in the lungs, and these eosinophilic infiltrates predominate on histopathologic examination [4]. The absence of intra­luminal organization of the alveolar filling in the distal airspaces differentiates CEP from cryptogenic organizing pneumonia. Interleukin-5 (IL-5), a cytokine that recruits eosinophils from the bone marrow, plays an important role in the development of CEP [4]. The concentrations of IL-5 as well as other eosinophil-active cytokines such as IL-6 and IL-10 are increased in BAL specimens from patients with CEP. Mepolizumab, an anti-IL-5 antibody, may decrease steroid dosing and improve the care of some patients with hypereosinophilic syndromes, particularly those patients that are negative for the FIP1L1-PDGFRA gene [3].

Imaging for CEP classically reveals peripheral, often bilateral, alveolar ­opacities, and has been described as the “photographic-negative of pulmonary edema” on chest radiographs [1]. The relative central sparing can be appreciated in this patient’s frontal radiograph in Fig. 4.1a. The density of the opacifications can range from ground-glass opacities to dense lung consolidation, and can be migratory [1, 4]. Pulmonary hemorrhage cannot be entirely excluded even in the absence of hemoptysis. Acute pneumonia (viral, bacterial, or fungal) should always remain a concern until infection has been excluded with confidence.

The majority of patients with CEP have peripheral eosinophilia, with mean eosinophil cell counts of >30% of the total blood leukocyte count [2]. C-reactive protein and erythrocyte sedimentation rate are typically elevated, and serum IgE is increased in about half of the cases. The hallmark of CEP, however, is the significant eosinophilia in the BAL fluid, usually >40% [1]. Only hypereosinophilic syndromes or “eosinophilic leukemia” is known to have BAL eosinophilia that can reach higher values, at times >70%.

Pulmonary function tests can be normal in one-third of the patients with CEP, though one-third to one-half of patients can have either obstructive or restrictive defects [1, 4]. Treatment of CEP with corticosteroids typically reverses the abnormalities, though obstructive findings may persist in some.

The standard therapy for CEP is systemic corticosteroids. A rapid response to treatment both symptomatically (within 48 h in 80% of patients) as well as radiographically (within 1 week in 70% of patients) is characteristic of CEP [1]. The recommended initial dose is 0.5 mg/kg/day of oral prednisone for 2 weeks with a gradual taper. There is no proven protocol and every taper must be individualized over months to 1 year or longer. Though typically described as having a good ­prognosis once treated, the rate of relapse is high and may require re-dosing of ­corticosteroids and, in some patients, prolonged maintenance doses for disease ­control. In addition to managing symptoms of the eosinophilic disorder as well as the side-effects of corticosteroids, spirometry should be performed during follow-up since airway obstruction may occur in the absence of other findings [4].

Given the severity of his symptoms, this patient was treated with methylprednisone 1 g/day for 3 days, then 1 mg/kg of prednisone with a gradual taper. His symptoms and radiographic abnormalities improved within the first 3–5 days of treatment initiation and follow-up: (Figs. 4.3 and 4.4). However, his disease has proven to be very steroid dependent, and he has required treatment doses of 15–30 mg daily of prednisone during the first year after diagnosis. The patient also removed the parakeets from his home shortly after diagnosis to eliminate any possible additional aeroallergens. Unfortunately, our patient increased not only his number of cigars to daily but also restarted smoking cigarettes on a daily basis. Thus, controlling both his asthma and CEP has proven to be difficult, albeit on an outpatient basis.

Fig. 4.3

AP views of the chest during hospitalization (a) Hospital day 6: progression of opacities with alveolar filling diffusely, pre-treatment with corticosteroids. (b) Hospital day 10: 3 days after initiation of corticosteroid therapy. Note a decrease in the multilobar opacities. (c) Hospital day 11: 4 days after initiation of corticosteroid therapy, with continued radiographic improvement

It is important to note several key differences between CEP and AEP. AEP ­presents in a much more acute fashion, typically with radiographic findings of ­diffuse bilateral pulmonary infiltrates often mistaken for acute lung injury or acute respiratory distress syndrome, and the patient typically requires mechanical ventilation [2]. In further contrast to CEP, AEP has a male predominance and patients do not typically have a history of asthma. Symptoms include cough, dyspnea, malaise, myalgias, nightsweats of less than 1 month’s duration, and physical findings include fevers, rales, rhonchi and hypoxemia. A BAL with >25% eosinophils is one of the diagnostic findings of AEP in the absence of known drugs or infections that can cause the same. AEP is also notable for the absence of peripheral eosinophilia initially (though this can be seen within the next 3–4 weeks of disease onset). Patients with AEP respond quickly to corticosteroid therapy and have complete clinical and radiographic resolution without recurrence or residual of their illness within several weeks of therapy [2]. Table 4.2 outlines the diagnostic criteria for AEP and CEP and Table 4.3 compares the primary pulmonary eosinophilic syndromes.

Table 4.2 Diagnostic criteria for AEP and CEP

Table 4.3 Comparison of primary pulmonary eosinophilic syndromes

Case 2

A 74-year-old Mien-speaking woman was referred for consultation of difficult-to-control asthma. For the last 10 years, she suffered from recurrent episodes of ­shortness of breath, dyspnea on exertion, and at least three nocturnal awakenings per week ­secondary to a non-productive cough and occasional audible wheeze. Her activities of daily living were limited by dyspnea on exertion. She endorsed no known triggers, and denied a seasonal variation to her symptoms. In the past 1 year, she had two emergency room visits for presumed asthma exacerbations but was never hospitalized.

Her past medical history was significant for type-2 diabetes mellitus, gastroesophageal reflux, osteoporosis, and depression. Prior surgeries consisted of one cesarean-section. She had no family members with known asthma. She emigrated over 10 years prior from Laos and resided with her daughter and husband. She never smoked, though she endorsed second hand exposure to tobacco from her husband’s smoking. She neither drank nor used illicit drugs. She had no pets. Review of systems was ­negative for gastrointestinal, cardiac, renal or hepatic diseases, but positive for a persistent pruritic skin rash on her upper and lower extremities. Her medications consisted of Duo-Neb^® (ipratropium/albuterol nebulizer) treatment as needed, levalbuterol as needed (about four times daily), montelukast daily, loratadine, pulmicort respules twice daily, paroxetine 20 mg daily, novolog insulin 6 units pre-meal, lantus 10 units nightly, fosamax 70 mg weekly, calcium and vitamin D supplements.

On presentation, the patient’s temperature was 99°F, and her blood pressure was 131/70 mmHg, heart rate was 99 beats/min, and her respiratory rate was 18 breaths/min. Her oxygen saturation was 90% on ambient air. She had no oral thrush and no sinus tenderness on palpation. There was no palpable lymphadenopathy in the cervical, supraclavicular or axillary chains. She had a diffuse wheeze bilaterally on lung auscultation. Her heart had a regular rate and rhythm and was without murmurs. No peripheral edema, clubbing or cyanosis was seen on her extremities. She had a skin rash on the upper and lower extremities bilaterally which consisted of pink circumscribed lesions that were non-blanching, and some excoriations were noted (Fig. 4.5). She had no focal neurological abnormalities.

Fig. 4.5

Left arm: notable for a maculopapular skin rash

Her CBC was notable for a microcytic anemia (hemoglobin 9.1 g/mm³, MCV 60%) and peripheral eosinophils of 4.7% (0.4 k/mm³). Her chemistry panel was unremarkable. An IgE level drawn 1 year prior was 4,010 IU/mL. Her liver panel was unremarkable. Office spirometry was notable for a reduced FEV1 (0.72 L, 48% of predicted), FVC (0.84, 44% predicted), and an FEV1/FVC ratio of 86%. Chest x-ray was remarkable for the presence of a left lingular alveolar density without pleural effusions (Fig. 4.6). A CT chest performed 2 years prior revealed mediastinal lymphadenopathy and bilateral atelectasis.

Fig. 4.4

CT chest, lung windows ((a) upper, (b) middle cuts): 2 month follow-up: notable for near-complete resolution of multilobar opacities

Fig. 4.6

PA view of the chest: remarkable for lingular opacity

With the Presented Data, What Is Your Working Diagnosis?

This patient has severe persistent asthma that is poorly controlled, requiring ­corticosteroids and frequent medical attention for acute exacerbations. However, she also has several other signs and symptoms that warrant further investigation of the etiology of her worsening condition. The syndrome of asthma, pruritic rash, infiltrates on imaging, and an elevated IgE prompt workup of Churg–Strauss ­syndrome, ABPA, and parasitic infections.

Differential Diagnosis

• 1. Churg–Strauss syndrome

• 2. Allergic bronchopulmonary aspergillosis

• 3. Loeffler’s syndrome

• 4. Severe persistent asthma

Workup

As part of an assessment for allergies as well as ABPA, a radioallergosorbent test (RAST) against aeroallergens should be performed, and the presence for IgG and IgE precipitin for Aspergillus species should be assessed. Also, testing the stool for ova and parasite should be included in the workup for all patients with peripheral eosinophilia. One may also consider performing a skin biopsy to further evaluate her rash and the possibility that this may be part of a vasculitis.

The patient’s RAST panel was negative for aeroallergens and serum precipitins were negative against Aspergillus fumigatus. A repeat IGE level was again elevated at 2,137 IU/mL. Her stool ova and parasite test was remarkable on multiple specimens for larvae resembling Strongyloides stercoralis.

What Is Your Diagnosis and Why?

Strongyloides stercoralis with Loeffler’s Syndrome

While the patient’s asthma was poorly controlled, her adherence to the use of ­bronchodilators, inhaled corticosteroids, oral corticosteroids and repeat acute exacerbations indicate that an alternative diagnosis should be pursued. Although an IgE level >1,000 IU/mL warrants consideration of ABPA, her serum precipitins were negative for Aspergillus fumigatus. Furthermore, the patient’s skin rash prompts evaluation for a vasculitis with consideration of Churg–Strauss syndrome. However, this patient’s stool ova and parasite testing was diagnostic for Strongyloides stercoralis.

Discussion

Parasitic eosinophilic pneumonias are the most common cause of eosinophilic pneumonias worldwide [1]. Clinical findings are typically non-specific, and ­clinicians must maintain a high index of suspicion in order to make this diagnosis in a timely fashion. The more common parasitic infections are caused by Wuchereria bancrofti and Brugia malayi, Ascaris lumbricoides, Toxocara canis, and Strongyloides stercoralis.

Tropical pulmonary eosinophilia is due to the filarial parasites Wuchereria bancrofti and Brugia malayi. Larvae are deposited by mosquitoes on human skin, which then enter into the bloodstream and develop into mature worms that reside in ­lymphatic vessels [1]. Symptoms consist mostly of cough, which may be accompanied by fever, weight loss and anorexia. Chest radiograph shows multiple bilateral ­opacities, and there is marked alveolar eosinophilia on BAL. The diagnosis is made by a strongly positive serology in patients residing in an endemic area who have ­persistent blood eosinophilia and elevated IgE levels. Clinical improvement is seen within weeks of initiating therapy with diethylcarbamazine.

Ascaris lumbricoides is the most common helminth that infects humans. It is more commonly seen in tropical and subtropical regions [1]. It is transmitted through food that is contaminated by human feces containing parasitic eggs. Loffler’s syndrome can be evident during the migration of the larvae through the lung. Symptoms include cough, wheezing, transient fever, and pruritic lesions, and blood eosinophilia is also present.

Visceral larva migrans syndrome is caused by Toxocara canis, and can occur worldwide. Children are at highest risk of infestation by ingesting the eggs released by female worms in the feces of infected dogs, typically through oral ingestion of soil from public playgrounds [1]. Most hosts remain asymptomatic, while others can suffer from fevers, seizures, cough, dyspnea and wheeze, and pulmonary infiltrates on chest radiographs. Eosinophils are elevated both in the blood as well as on BAL.

Strongyloides stercoralis, present in this patient, is an intestinal nematode found in temperate regions of the United States (southern Appalachian region including eastern Tennessee, Kentucky and West Virginia), tropics and subtropics, and in Africa, the West Indies, Southeast Asia, South America, Bangladesh and Pakistan [5]. Approximately 55–100 million people are infected worldwide. Infected immigrants to the United States are often misdiagnosed for an average of 5 years, particularly when they reside in non-endemic areas [5].

The life cycle of Strongyloides is more complex than that of other parasites, and consists of a free-living cycle and a parasitic cycle. As part of the parasitic cycle, the filariform larvae in the soil penetrate intact skin and infect the human host. The larvae then enter the bloodstream and are transported to the lungs, where they penetrate the alveolar space [6]. The larvae then ascend the airways and trigger the host to cough, at which point they are swallowed and arrive into the gut. Once embedded into the intestinal mucosa, they reproduce asexually and lay eggs that hatch into rhabditiform larvae. The larvae then migrate into the intestinal lumen, and either leave the host through feces or mature into filariform larvae that infect the intestinal mucosa or skin of the perianal region and restart the parasitic cycle. This form of autoinfection can result in the persistence of infection for decades. If the rhabditoform larvae leave the host via feces, it can either mature into infectious filariform larvae or enter the free-living cycle.

Given the various stages in the parasite’s life cycle, clinical manifestations of the infection are multiform, and include Loeffler’s syndrome (presence of pulmonary infiltrates), chronic intestinal infection, asymptomatic autoinfection, and dissemination in the form of hyperinfection syndrome [6]. In the immunocompetent host, chronic and symptomatic infections may include abdominal discomfort, bloating, nausea, vomiting, diarrhea and anorexia, as well as respiratory complaints such as cough, dyspnea, and wheeze. Some individuals may develop a maculopapular or urticarial serpiginous rash called larva currens, pathognomonic for Strongyloides infection [5]. Fluctuating eosinophilia is present in about 75% of infected individual patients.

Autoinfection can result in the most life-threatening forms of the disease, hyperinfection syndrome (an increase in the worm burden) and dissemination (spread of the parasite to other organs) [5]. Clinical findings associated with hyperinfection vary from fever, chills, paralytic ileus, ulcerative enteritis, acute respiratory distress syndrome that may require mechanical ventilation, as well as alveolar hemorrhage. In the immunosuppressed patient, peripheral eosinophilia may be absent, which portends to a poorer prognosis. With dissemination, the patient may develop bacteremia, meningitis, and gram-negative sepsis.

Risk factors for hyperinfection syndrome and dissemination of the parasite include any form of immunosuppression such as immunosuppressive therapies including corticosteroids, human T-lymphotropic virus-1 (HTLV-1) infection, solid organ transplantation, hematologic malignancies, hypogammaglobulinemia, chronic alcohol consumption, uremia, severe malnutrition, and diabetes mellitus [5].

The diagnosis of Strongyloides includes stool testing for the larvae. Detection of the larvae from a single stool sample is only 25%, and multiple specimens (three are recommended) must be obtained for this reason. A complete blood cell count should be obtained to check for peripheral eosinophilia (again, this may be absent in the immunosuppressed patient). Those with respiratory symptoms should have their sputum samples evaluated for the parasite.

Strongyloides infection is treated with ivermectin, thiabendazole, or albendazole. Ivermectin is better tolerated and is the standard of care at 200 mcg/kg once daily for 2 days [5]. The cure rate is 94–100% [6]. Follow-up stool tests should be ­performed over a 3-month period to determine that the infection was successfully treated. Serology titers and peripheral eosinophilia should also decrease. For hyperinfection and disseminated disease, ivermectin is administered until symptoms resolve and stool tests become negative for 2 consecutive weeks.

Diagnostic workup for our patient was notable for two out of three stool ­specimens being positive for the presence of Strongyloides larvae. Serology was also notable for significantly elevated IgG antibody against the threadworm. She was treated with albendazole and on follow-up, her rash had improved, but her asthma was still poorly controlled. Three consecutive stool samples obtained 6 months later were negative for the larvae. Serum IgG antibody against the parasite was also decreased on follow-up. However, given that her rash had not resolved completely and her asthma was still poorly controlled, she was prescribed a second round of treatment with albendazole, after which her rash resolved, and her asthma management improved significantly.

Questions

• 1. What is the gender predominance with CEP?

  • (a) Male

  • (b) Female

• 2. What are the lowest accepted cutoffs for alveolar eosinophilia (obtained on BAL) for CEP?

  • (a) >10%

  • (b) >25%

  • (c) >40%

  • (d) >75%

• 3. Which form of eosinophilic pneumonia typically has radiographic evidence of infiltrates with peripheral predominance?

  • (a) AEP

  • (b) ABPA

  • (c) CEP

  • (d) Parasitic eosinophilic pneumonia

• 4. How does AEP differ from CEP with regard to response to treatment and follow-up?

  • (a) Unlike CEP, AEP has a slow response to treatment but rarely recurs

  • (b) Unlike CEP, AEP has a slow response to treatment and frequently recurs

  • (c) Unlike CEP, AEP has a rapid response to treatment and rarely recurs

  • (d) Unlike CEP, AEP has a rapid response to treatment but frequently recurs

• 5. What role do transbronchial biopsies play in the diagnosis of eosinophilic pneumonias?

  • (a) They are essential in the diagnosis of eosinophilic pneumonias

  • (b) They have replaced the need for a VATS-guided lung biopsy

  • (c) They can be used interchangeably with BAL fluid

  • (d) They are deemed necessary only in difficult to diagnose cases

• 6. What is the most common cause of eosinophilic pneumonias worldwide?

  • (a) Parasitic eosinophilic pneumonias

  • (b) ABPA

  • (c) Drug-induced eosinophilic pneumonias

  • (d) Asthma-associated eosinophilic pneumonias

• 7. Describe the mechanism for autoinfection with Strongyloides stercoralis?

  • (a) Filariform larvae in the soil penetrate intact skin and infect the human host

  • (b) Once embedded into the intestinal mucosa, they reproduce asexually and lay eggs that hatch into rhabditiform larvae

  • (c) The larvae ascend the airways and trigger the host to cough, at which point they are swallowed and arrive into the gut

  • (d) The larvae migrate into the intestinal lumen and mature into filariform larvae that infect the intestinal mucosa or skin of the perianal region and restart the parasitic cycle

• 8. What percentage of persons with chronic Strongyloides are asymptomatic?

  • (a) <15%

  • (b) <25%

  • (c) >50%

  • (d) >75%

• 9. While there is no gold standard for diagnosis, how is the diagnosis of Strongyloides typically made?

  • (a) Testing a minimum of three stool samples for larvae

  • (b) It is a diagnosis of exclusion and proper history and physical examination are imperative

  • (c) Peripheral eosinophilia and at least two stool samples tested for larvae

  • (d) Peripheral eosinophilia and the presence of respiratory symptoms

• 10. What are the risk factors for developing hyperinfection?

  • (a) Host immunosuppression

  • (b) Residence in an endemic region

  • (c) Ingesting contaminated foods

  • (d) Being younger than 18 years of age

Answer key: 1. (b), 2. (c), 3. (c), 4. (c), 5. (d), 6. (a), 7. (d), 8. (c), 9. (a), 10. (a)