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* From the Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO.
Correspondence to: Darren M. Boé, MD, PhD, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E Ninth Ave, C272, Denver, CO 80262; e-mail: Darren.boe{at}uchsc.edu
Key Words: eosinophilia • hemoptysis • paragonimiasis • paragonimus • Paragonimus westermani • parasitic lung diseases • pulmonary eosinophilia
Case Presentation
A 31-year-old man presents for further evaluation of chronic cough and hemoptysis. His cough has been present for the past 5 years. Although the cough was nonproductive initially, hemoptysis has developed over the past year and a half. Since that time, he produces blood-tinged sputum daily. He reports occasional chest tightness and mild shortness of breath, which is worse with exercise or changes in temperature. On occasion, his cough becomes so severe that it is associated with nausea. He denies fever, chills, weight loss, night sweats, abdominal pain, or vomiting.
Over the past 5 years, he has been treated with a number of antibiotics, as well as voriconazole, without improvement. In 2005, he underwent a CT-guided biopsy of a "lung mass" that was nondiagnostic. A bronchoscopy at that time reportedly showed narrowing of one of the airways. The review of systems was positive for mild fatigue, occasional postnasal drip, and occasional nausea.
His medical history is significant for a pneumothorax requiring chest tube placement in September 2005 following the CT-guided lung biopsy, pneumonia on one occasion, and recurrent bronchitis as a teenager. He currently takes no medications and has no known drug allergies.
He reports a history of smoking (three to five cigarettes per day from age 18 to 27 years) and a history of regular marijuana use from age 20 to 28 years. He reports regular cocaine use over the last 3 years (snorting and smoking); however, he reports continued hemoptysis even during times when he is not actively using cocaine. He drinks four alcoholic beverages per day. He denies significant exposures to second-hand smoke, humidifiers, swamp coolers, hot tubs, mold, or mildew. He has two dogs but no other pets. He works as a carpenter/contractor with some exposure to wood dust; however, he denies exposures to other fumes, chemicals, or asbestos. His family history is negative for respiratory problems, allergies, coronary artery disease, diabetes, collagen vascular disease, or malignancy. He denies exposure to tuberculosis or foreign travel.
On physical examination, he appears comfortable and is in no apparent distress. His vital signs are as follows: temperature, 35.8°C; pulse rate, 66 beats/min; BP, 120/72 mm Hg; and respiratory rate, 20 breaths/min. His oxygen saturation is 98% on room air by pulse oximetry. In general, he is a well-developed, well-nourished man in no acute distress. His pupils are equal and reactive, and examination of his fundi, tympanic membranes, and oropharynx are unremarkable. His neck is supple, without lymphadenopathy, thyromegaly, jugular venous distention, or bruits. His heart is regular, with a normal S1 and S2 and no murmurs. His chest is clear to auscultation bilaterally, with no wheezes, rubs, or rhonchi. His abdomen is soft, nontender, with good bowel sounds and no hepatosplenomegaly. He has no peripheral edema and has normal distal pulses bilaterally.
Laboratory Evaluation
CBC count reveals a WBC count of 7.7 x 103/µL, with a differential of 57% neutrophils, 22% lymphocytes, 8% monocytes, and 13% eosinophils. His hemoglobin is 16.1, hematocrit is 47.6, and platelets are 288 x 103/µL. Other pertinent laboratory values include the following: erythrocyte sedimentation rate, 10 mm/h; C-reactive protein, 0.08 mg/L; antinuclear antibody, 1:40; rheumatoid factor < 20; IgE, 1,767 ng/mL (normal reference value, 0–100); IgG, 1,710 ng/mL (normal reference value, 700–1,620); and IgM, 66 ng/mL (normal reference value, 44–266). His HIV serum test result is negative, and his angiotensin-converting enzyme level, coccidioides antibodies, cryptococcal antigen, aspergillus, blastomyces, and histoplasma antibodies, chlamydia polymerase chain reaction, mycoplasma polymerase chain reaction, and allergic bronchopulmonary aspergillosis skin testing are unrevealing. His tuberculin skin test result is negative. A chest radiograph (Fig 1
) and a representative section from chest CT (Fig 2
) are shown.
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Chest imaging shows focal consolidation in the medial segment of the right lower lobe with cavitation and areas of necrosis and nodule formation. The focal and cavitary nature of these radiographic findings is most consistent with malignancy, focal infection, or tuberculosis. Although pulmonary vasculitis can present with cavitary lesions, the focal nature of his disease is inconsistent with this diagnosis. Likewise, there is no evidence for arteriovenous malformation or bronchiectasis on the chest radiographs. Malignancy is also less likely, given his young age and lack of significant progression of disease over the previous 2 years.
The presence of eosinophilia and an elevated IgE level raises further possibilities. One potential cause of eosinophilic lung disease and hemoptysis is parasitic infection. In the United States, the most common parasitic causes of eosinophilic lung disease are Strongyloides, Ascaris, Toxocara, and Ancylostoma, although case reports of Paragonimus infection have also been described.1 However, given his lack of a significant travel history or other pertinent exposures, a diagnosis of parasitic infection is less likely. The presence of eosinophilia may also be seen in patients with fungal infection, particularly coccidioidomycosis and aspergillus; however, it is usually absent in histoplasmosis, blastomycosis, candidiasis, and cryptococcosis. Churg-Strauss syndrome is another important consideration in a patient with hemoptysis, eosinophilia, and elevated IgE levels; however, peripheral blood eosinophilia is usually more substantial and chest radiographic findings are generally nonfocal. Similarly, allergic bronchopulmonary aspergillosis is commonly associated with eosinophilia and elevated IgE levels; however, it is rarely associated with hemoptysis or unilateral, focal abnormalities on chest radiography. Other more common causes of eosinophilia, such as simple pulmonary eosinophilia, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, and idiopathic hypereosinophilic syndrome, are not common causes of hemoptysis and do not fit with the clinical presentation of our patient.
Clinical Course
Following presentation, he underwent another bronchoscopy with BAL. This revealed a WBC count of 3.8 x 106/µL, with 62% macrophages, 20% neutrophils, 5% lymphocytes, and 13% eosinophils. BAL cytology, cultures (bacterial, acid-fast bacilli, fungal, mycoplasma), and silver stain results were negative. Transbronchial biopsy showed nonnecrotizing granulomas within the bronchial wall, moderate chronic inflammation with abundant eosinophils, and a markedly thickened subbasal lamina. However, these biopsies were nondiagnostic.
Ultimately, given his persistent hemoptysis without a clear diagnosis as well as his focal abnormalities on chest imaging, he underwent right lower lobe basilar segmentectomy. The pathology provided a definitive diagnosis, and is shown in Figure 3 .
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Discussion
Histology shows necrotizing granulomatous inflammation with parasitic ova consistent with Paragonimus species. Prominent eosinophilic reaction was also noted, and Gram and acid-fast stains showed no pyogenic organisms or mycobacteria. Following the diagnosis, a paragonimus immunoblot assay was performed and was found to be positive for the presence of Paragonimus westermani antibodies.
Paragonimiasis, also known as lung fluke disease, is caused by infection by one of several species of the lung fluke Paragonimus. P westermani is endemic to southeast Asia (90% of cases; approximately 20 million with infection), parts of Latin America (primarily Peru), and Africa (primarily Nigeria), while other less-defined species cause infection in West Africa, Central America, and South America.2345 Widespread screening and prevention campaigns in endemic areas have resulted in a drastic decrease in the number of cases of paragonimiasis; however, it has re-emerged as an important pathogen in many of these regions.6 Although it is rarely a cause of infection in the North America, Paragonimus kellicotti has been shown to cause infection within the United States.78910 Of note, infection with P westermani has only rarely been described in the United States and almost always occurs following emigration from a region of endemicity.
Human infection is acquired through ingestion of raw, salted, or wine-soaked fresh water crabs or crawfish that contain the parasite4511 (Fig 4 ). Within crabs and crawfish, the parasite lives in the metacercarial stage. Once ingested, the metacercariae penetrate the duodenal wall and enter the peritoneal cavity. On entry into the peritoneal cavity, they migrate to the diaphragm, penetrate it, and enter the pleural space and lung parenchyma in 2 to 8 weeks. Within the lung, which is the main habitat of the adult fluke, the parasites form areas of inflammation surrounded by eosinophils, neutrophils, and later mononuclear leukocytes. Local necrosis occurs, with the formation of a thin layer of fibrous tissue. Within this fibrous capsule, the flukes mature and begin egg production (typically by the seventh or eighth weeks of infection). Egg production results in the formation of nodules, which can grow and ultimately rupture within the airways, releasing eggs into the sputum. These eggs may be either expectorated or swallowed and excreted in stool. If the excreted eggs reach water, the life cycle begins again.
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Chest radiography findings may be normal in 12.8 to 20% of patients with confirmed paragonimiasis.12 During early infection and migration into the pleural cavity, pneumothorax or pleural effusions may develop (which at times are massive). Migration into the pulmonary parenchyma results in the formation of transient, migratory, soft pulmonary infiltrates. Once chronic infection ensues, one or more lesions are visible on chest radiography in 80% of cases, and may include ring shadow lesions caused by relative lucency of the contents of cystic cavities, linear streaks (often adjacent to the ring shadows, which represent burrowing tracts of the flukes), parenchymal nodules and mass lesions, pleural thickening, and occasionally air fluid levels. Common chest CT findings include subpleural or subfissural nodules, often containing a necrotic, low-attenuation area. Clinical and radiographic findings may resemble those of lung cancer (often positive on positron emission tomography), tuberculosis, mesothelioma, or metastatic disease.1213 Although our patient’s radiographic findings were nonspecific, the presence of focal areas of cavitation, necrosis, and nodule formation was consistent with chronic Paragonimus infection.
The diagnosis may be challenging, as most symptoms, radiographic abnormalities, and laboratory findings are nonspecific.14 Pleural effusions, which typically occur early during infection as the flukes migrate into the pleural cavity, are exudative and laden with eosinophils. Prominent leukocytosis with eosinophilia occurs during early pulmonary parenchymal involvement but later resolves or is minimal. Chest CT findings, although often subtle, may support the diagnosis if focal fibrotic pleural thickening is seen adjacent to a pulmonary nodule. Paragonimus eggs may be found in sputum, BAL, or stool samples, thus confirming the diagnosis, and 24-h sputum collection enhances the sensitivity of egg detection. Transbronchial biopsies may also confirm the diagnosis. Enzyme-linked immunosorbent assay and immunoblot serologic tests are also available and can point to the diagnosis.15 These tests are available at no cost from the Centers for Disease Control and Prevention, and have a high sensitivity (96%) and specificity (99%) for infection with P westermani. However, cross-reactivity with other Paragonimus species is variable; thus, negative serology does not completely rule out Paragonimus infection. Likewise, a positive serology does not definitively diagnose infection with the P westermani species; rather, it confirms infection with one of many Paragonimus species. Paragonimus kellicotti is a more common cause of Paragonimus infection within the United States,78910 and infection with P westermani is less likely in our patient given that he had no history of foreign travel to a region of endemicity.
Regardless of the species responsible for Paragonimus infection, treatment remains the same. Standard treatment is with praziquantel (25 mg/kg tid for 2 days) and results in a high cure rate.613 Triclabendazole has been shown to have better clinical tolerance, a more rapid parasitologic response, and comparable resolution of clinical symptoms when compared to praziquantel.16
In retrospect, the diagnosis of Paragonimiasis could have potentially been made by serology. However, there was very little in his history to suggest such an infection. He did have eosinophilia, as well as an elevated IgE level; however, he denied any travel outside of the United States and reported no significant exposures to raw seafood. On further questioning following his diagnosis, he did report eating sushi on one occasion, 2 years prior to presentation to our clinic; however, this could hardly be considered a significant exposure risk for parasitic infection. In our patient, his symptoms, radiographic abnormalities, and laboratory findings were nonspecific, and transbronchial biopsies were nondiagnostic. He was treated with praziquantel (25 mg/kg tid for 2 days) and was seen in clinic 1 month later, at which time he reported only occasional cough and intermittent shortness of breath. He denied recurrent hemoptysis or fever.
In summary, Paragonimiasis should be suspected in patients with hemoptysis, particularly when more common causes have been excluded. A history of ingestion of fresh water crabs or crawfish or travel to an endemic area may also be important clues to the diagnosis. Although laboratory findings are often nonspecific, the presence eosinophilia should further raise the possibility of parasitic infection. Likewise, the presence of ring shadow lesions with adjacent linear streaks on chest imaging may be suggestive of the diagnosis. Overall, this case demonstrates the importance of maintaining a broad differential diagnosis in cases of hemoptysis, especially when the workup is negative for more common causes of this condition.
Footnotes
The authors have no conflicts of interest to disclose.
Received for publication March 22, 2007. Accepted for publication April 18, 2007.
References
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