(Radiographics. 1999;19:1077-1081.)
© RSNA, 1999
Residents' Teaching Files1
Strongyloides stercoralis Hyperinfection
Nishita N. Kothary, MD ,
Julia M. Muskie, MD and
Sharad C. Mathur, MD
1 From the Department of Diagnostic Radiology, The George Washington University Medical Center, 901 23rd St, NW, Washington, DC 20037. Received February 11, 1999; revision requested March 9 and received April 5; accepted April 29. Address reprint requests to N.N.K.
Index Terms: Gastrointestinal tract, diseases, 70.2081 • Lung, diseases, 60.2081 • Lupus erythematosus, **.6122 • Nervous system, diseases, 10.612 • Parasites, 60.2081, 70.2081
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Introduction
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Disseminated Strongyloides infection is a rare but known complication of immunosuppressive therapy in patients with intestinal parasitism. Although infection with Strongyloides stercoralis (strongyloidiasis) has generally been considered a benign gastrointestinal infection, hyperinfection syndrome has been seen with increasing frequency in patients with impaired immunity. Autoinfection with metamorphosis of rhabditiform into invasive filariform larvae may occur; as a result, larvae may disseminate and involve multiple organs, causing increased morbidity and mortality. Brain and meningeal involvement in the setting of hyperinfection syndrome has been observed at autopsy in several cases; to our knowledge, however, only three cases of central nervous system involvement have been diagnosed before patient death. Strongyloidiasis is a rare disease but is potentially fatal if not treated early. Unfortunately, the relatively nonspecific clinical and imaging features of this disease make diagnosis difficult; therefore, it is important to have a high degree of suspicion and include strongyloidiasis in the differential diagnosis, particularly in patients who have traveled or lived in endemic areas.
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CASE PRESENTATION
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A 33-year-old African woman with systemic lupus erythematosus with skin, kidney, and joint involvement presented to the emergency department with a 1-month history of nausea, vomiting, constant epigastric pain, and shortness of breath. The patient had lost 35 pounds over the past 2 months and had undergone treatment with large doses of prednisone. The patient tested positive for tuberculosis with a normal chest radiograph, positive for hepatitis B, and negative for human immunodeficiency virus. In addition, she had a CD4 count of 182 and suffered from malnourishment.
Physical examination findings at admission included tachycardia, a fever of 39°C, and mild distress due to abdominal pain. However, there was no rash, the lungs were clear at auscultation, and there were no peritoneal or neurologic signs. Significant laboratory findings included anemia, increased white blood cell count with bandemia, eosinophilia, hyponatremia, and hypoalbuminemia. Blood cultures showed no growth of microorganisms.
During her hospitalization, the patient's signs and symptoms of abdominal pain, nausea, vomiting, and shortness of breath worsened and she developed a new, nonproductive cough. Follow-up chest radiography showed a bilateral interstitial-reticulonodular pattern of areas of increased opacity (Fig 1) that later progressed into bilateral alveolar areas of increased opacity and slowly resolved over time. Abdominal computed tomography (CT) showed mildly dilated and thickened loops of duodenum, proximal jejunum, and colon (Fig 2). Unenhanced CT and magnetic resonance (MR) imaging of the brain (Fig 3) showed severe diffuse atrophy, a finding that was inconsistent with the patient's age, and areas of high attenuation or high signal intensity in the white matter, a nonspecific finding that may be seen with small vessel ischemic change. The patient's respiratory status worsened, and she underwent bronchoscopy. Cultures were obtained, and microscopic analysis with special stains revealed hemorrhagic mucosa with clots and Strongyloides larvae. The patient also experienced periods of unconsciousness. Analysis of a cerebrospinal fluid sample showed 59 white cells with 98% lymphocytes, elevated glucose and protein levels, and Strongyloides larvae. Vancomycin-resistant enterococci were also seen. Soon thereafter, the patient developed pulmonary Aspergillus niger, a Pseudomonas line infection, and urinary tract infection (vancomycin-resistant enterococci).
After approximately 4 weeks of treatment with thiabendazole, chloromphenicol, and synercid (a research protocol drug), analyses of the stool, cerebrospinal fluid, and sputum were negative for Strongyloides infection and enterococci and the patient was discharged.
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DISCUSSION
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S stercoralis is ubiquitous in subtropical and tropical climates. In the United States, it is endemic in the southeast and in Appalachia. The estimated prevalence of S stercoralis infection in this country is 0.4%–4%. Many infected hosts remain asymptomatic; however, dissemination of S stercoralis is potentially lethal because of its association with bacterial sepsis.
S stercoralis is a nematode whose primary hosts are humans. Infection begins when infective filariform larvae penetrate the skin, migrate through the lymphatic and venous circulation, enter the capillary bed of the lungs, and penetrate the capillary walls to settle in the alveoli. The larvae subsequently ascend the tracheobronchial tree to the larynx, where they are swallowed and subsequently carried to the duodenum and jejunum. The larvae mature into adult females, which deposit eggs in the intestinal mucosa. The eggs hatch into nonmigratory rhabditiform larvae, which penetrate the intestinal mucosa and are excreted in the feces. In some patients, however, the larvae may remain in the intestine, metamorphose into infective filariform larvae, and penetrate the intestinal mucosa and perianal skin. These larvae then reenter the venous system and repeat the life cycle within the host. This repeated migration can continue indefinitely and establish a cycle of endogenous reinfection (autoinfection) that is unique to S stercoralis. In immunocompromised patients, dissemination occurs when there is massive larval infestation. Mortality increases due to the presence of gram-negative bacterial meningitis and septicemia. These diseases are thought to result from the spillage of gut organisms into the bloodstream concomitant with larval penetration so that "contaminated" larvae lodge in the central nervous system. Risk factors for dissemination include chronic lung disease, old age, lymphoma and leukemia, chronic use of corticosteroids, and surgically created blind loops. It is not known how immunosuppressive therapy alters host reactivity to the parasite. However, suppression of local inflammatory response and lack of containment of invading larvae may play a role. Massive intestinal infestation can cause paralytic ileus, which, working in conjunction with other factors that slow down intestinal motility in hospitalized patients, provides a 24–48-hour time interval for transformation of rhabditiform into invasive filariform larvae.
Normally, the host response to Strongyloides infection includes the appearance of a pruritic reaction at the site of larval skin penetration within 24 hours. In patients with autoinfection, this reaction may be seen in the area of the buttocks and upper thighs. Blood eosinophilia is extremely common and is present in the vast majority of patients, especially those with non-disseminated disease. However, eosinopenia with leukopenia is seen in the late stages of the disease and is a poor prognostic sign.
Signs and symptoms at presentation are predominantly gastrointestinal (as in this case) and include nausea, vomiting, anorexia, diarrhea, weight loss, and, most commonly, midepigastric pain, which may mimic peptic ulcer disease. Colitis and inflammatory bowel disease may cause similar symptoms, and stool analysis can help confirm the diagnosis. Other signs include hematemesis, esophagitis, gastritis, and jejunitis. Protein-losing enteropathy and malabsorption have also been reported.
Review of the radiology literature reveals that the majority of patients with Strongyloides infection have mild to moderate dilation of the first portions of the duodenum and jejunum with diffusely thickened folds. However, another unusual but distinctive manifestation is colitis. At radiography, a thickened colonic wall appears similar to ulcerative colitis. At histologic analysis, Strongyloides infection is characterized by a florid transmural granulomatous inflammatory process with numerous eosinophils and several invasive larvae (1–5).
In this case, abdominal CT revealed both duodenal and jejunal dilatation with diffuse thickening of the colonic wall. The differential diagnosis includes Crohn disease and lymphoma, and biopsy is required. The other manifestation is of narrowed, featureless loops. Abdominal pain, hypomotility, and ileus are prominent clinical features of hyperinfection, and development of these signs and symptoms along with characteristic imaging findings and ova in the stool should cause a high degree of suspicion.
The migration of the larvae through the lungs may be asymptomatic or may cause dyspnea, cough, sputum production, wheezing, and hemoptysis depending on the parasite load. In patients with autoinfection, the migration of the larvae from the capillary bed into the alveoli produces a foreign body reaction within the lungs consisting of inflammatory pneumonitis and pulmonary hemorrhage. Abnormal chest radiographic findings are seen in 95% of patients. Chest radiographs obtained during the migratory phase may show fine miliary nodules or diffuse, reticulonodular interstitial areas of increased opacity. With the development of heavier infestation, bilateral, patchy alveolar areas of increased opacity or segmental or even lobar areas of increased opacity may develop. Serial radiographs may show migration of areas of increased opacity. Because of repeated tissue migration, striking peripheral blood eosinophilia is often associated with these pulmonary areas of increased opacity. Reticulonodular airspace disease associated with eosinophilia is seen in several pulmonary processes. However, the presence of filariform larvae in the sputum, bronchial washings, or lung biopsy specimens is important not only in confirming Strongyloides hyperinfection but also in determining prognosis. The literature shows a statistically significant association between hyperinfection and secondary bacterial bronchopneumonia. Adult respiratory distress syndrome may develop and may ultimately prove fatal (6,7).
Widespread dissemination can occur and involve the heart, lungs, lymph nodes, gastrointestinal tract, liver, skeletal muscles, and central nervous system. In 45% of patients with hyperinfection, serious secondary bacterial or fungal infection can occur, including bacteremia, meningitis, peritonitis, and endocarditis.
Central nervous system involvement includes (a) meningitis due to larvae in the pia arachnoid and (b) global ischemia, atrophy, and microinfarcts, which result from capillary obstruction by the larvae. Radiologic features are nonspecific; thus, use of special stains in microscopic analysis of the cerebrospinal fluid is vital in making the diagnosis (as in this case). Neurologic dysfunction may be present; however, this may be attributable to the bacterial meningitis and metabolic factors frequently associated with hyperinfection. The parasites reach the brain and spinal canal either via arterial blood or by means of migration from the gut toward the brain through the perivascular connective tissue; eventually, they reach the epidural, subdural, and subarachnoid spaces, from which they invade the brain and sometimes lodge in the capillaries. As mentioned earlier, although larvae are seen in the central nervous system at autopsy, very few cases of such involvement are diagnosed before patient death (8–12).
The diagnosis of Strongyloides infection is confirmed by detection of larvae in the stool; however, analysis of a single stool sample may be negative in up to 70% of cases. Therefore, examination of at least three stool samples is necessary. Duodenal aspiration or biopsy may reveal larvae. S stercoralis may also be identified in sputum samples, bronchial washings, bronchial biopsy samples, or cerebrospinal fluid samples in disseminated disease.
Microscopically, the larvae appear as long, tubular esophagi within the body cavity (Fig 4). At histologic analysis, intact larvae can be seen with Gomori methanamine silver stain. Larvae are often not seen with Diff-Quik stain, presumably due to their dislodgment or movement prior to staining (13).
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CONCLUSIONS
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The clinical diagnosis of Strongyloides infection is often delayed because the clinical and radiographic findings are nonspecific. However, the presence of eosinophilia in an immunocompromised patient warrants an aggressive search for this nematode, especially in patients who have lived or traveled in an endemic area.
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Footnotes
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**. indicates multiple body systems. 
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References
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Introduction
CASE PRESENTATION
