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Infectious Diseases in Clinical Practice:
Special Articles

Clinical Pathological Conference

Gebo, Kelly M.D., M.P.H.

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Department of Medicine

Johns Hopkins University

School of Medicine

This feature discloses the opinion of the discussant and the opinion of the audience by vote from the options that are listed in the differential diagnosis from the discussant. Comments are welcome (reprinted from The Johns Hokins University ID Website, http://www.hopkins-id.edu, with permission).

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A 60-Year-Old Woman with Brain Lesions

History of present illness

A 60-year-old woman was diagnosed with pauciimmune glomerulonephritis by renal biopsy in July 2000. She was started on prednisone 30 mg daily in July, and mycophenolate (CellCept®) was started in August. In November of 2000, she presented to her primary care physician with a right foot drop and right leg weakness. Her symptoms progressed to numbness of the right foot as well as the right arm and neck. She developed right-sided twitching without loss of consciousness, and a computed tomographic scan of the brain showed multiple ring-enhancing lesions. She was transferred for further evaluation.

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Past medical history

* Recurrent urinary tract infections

* Hypertension

* Osteoporosis

* Hypercholesterolemia

* Fibrocystic breast changes

* Appendectomy

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Medications

* Decadron

* Pyrimethamine

* Sulfasalazine

* Dilantin

* Prednisone

* Mycophenolate

* Atorvastatin

* Enalapril

* Folate

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Social history

The patient lives in Delaware with her husband and works in a mentoring program in an elementary school. She does not drink alcohol, smoke, or use illicit drugs. There is no history of recent travel outside of Delaware and Maryland.

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Physical examination

Temperature, 36.7°C; pulse, 88 beats per minute; respiratory rate, 16/min; blood pressure, 142/72; oxygen saturation, 97% on room air.

Head, neck, skin, chest, cardiovascular, and abdominal examinations were unremarkable. Neurologic examination: the patient was alert and oriented to name, place, and time. Cranial nerves II–XII were intact. Sensation to light touch was decreased in the lower extremities bilaterally (right > left). Strength was 3+ in the right lower extremity and 4− in right upper extremity. Deep tendon reflexes were 3+ in the upper extremities (right > left) without clonus. The Babinski reflex was absent.

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Laboratory and radiologic data

TABLE

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Differential diagnosis

1. Polymicrobial brain abscess

2. Staphylococcus aureus

3. Actinomycosis

4. Nocardiosis

5. Mycobacterium tuberculosis

6. Nontuberculous mycobacteria

7. Toxoplasmosis

8. Candida spp.

9. Aspergillus spp.

10. Zygomycosis

11. Fusarium spp.

12. Wegener’s granulomatosis

13. Lymphoma

14. Other malignancy (primary or metastatic)

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Discussion

In summary, this is a 60-year-old woman being treated for pauciimmune glomerulonephritis with immunosuppressive agents, who presents with neurologic signs and symptoms and multiple ring-enhancing lesions on magnetic resonance imaging (MRI) (Figs. 1 and 2).

Figures 1
Figures 1
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Brain abscesses are most often polymicrobial, with mixed flora of anaerobes and streptococci, sometimes with coliforms as well. Streptococci (aerobic, anaerobic, and microaerophilic) are cultured in up to 70% of brain abscesses. S. aureus accounts for 10% to 15% of isolates; however, this usually occurs in patients with cranial trauma or endocarditis. Recent attention to proper culture techniques has increased the isolation of anaerobic organisms, particularly Bacteroides and Prevotella species. Enteric gram-negative bacilli, such as Proteus spp., Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa have been isolated, particularly in patients who are immunocompromised or those with otitis. M. tuberculosis and nontuberculous mycobacteria may cause focal central nervous system lesions, particularly in the setting of human immunodeficiency virus (HIV).

Brain abscess attributed to Actinomyces spp. is usually secondary to hematogenous spread from a primary infection in the lung, abdomen, or pelvis, although contiguous spread from the sinus or ear may occur. Brain abscesses attributed to Nocardia spp. are usually seen in patients with defects in cell-mediated immunity, including patients receiving corticosteroid therapy, organ transplant recipients, patients infected with HIV, or patients receiving chemotherapy for neoplastic disease.

Fungal brain abscess is often unexpected and may be first diagnosed at autopsy. The incidence of fungal brain abscess seems to be increasing, however, because of greater use of immunosuppressive agents and broad-spectrum antimicrobial therapy. Risk factors for invasive infection by Candida spp. include the use of corticosteroids, broad-spectrum antimicrobial therapy, hyperalimentation, and central venous catheterization. Other pathogenic fungi that should be considered in the differential diagnosis of fungal brain abscess, particularly in the immunosuppressed patient, include Aspergillus spp. and zygomycosis. Conditions predisposing to zygomycosis include diabetes mellitus (70% of cases—usually in association with diabetic ketoacidosis), hematologic neoplasms, renal transplantation, injection drug use, and the use of deferoxamine.

Toxoplasma gondii characteristically causes intracerebral mass lesions or encephalitis in immunocompromised hosts. The number of cases of central nervous system toxoplasmosis has increased dramatically since 1981, specifically in patients with HIV infection.

Noninfectious possibilities included Wegener’s granulomatosis and lymphoma; however, it was thought that the patient’s immune suppression had been of relatively short duration to develop cerebral lymphoma.

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Discussant’s vote

Nocardiosis

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Audience’s vote

Nocardiosis

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Diagnostic procedure

The patient underwent brain biopsy on the seventh hospital day. Cultures from these biopsies revealed Nocardia nova (Figs. 3 and 4).

Figure 3
Figure 3
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Figure 4
Figure 4
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Clinical course

The patient was started on imipenem-cilastin after her diagnosis, with slow resolution of her symptoms. After 3 weeks of imipenem-cilastin, she developed a druginduced hepatitis. She was switched to intravenous trimethoprim-sulfamethoxazole for a total of 6 weeks. She is currently on oral therapy, and a repeat MRI scan at 12 weeks showed reduction in the brain lesions.

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Comment

Nocardia spp. were first described by Edmond Nocard in 1888 from cattle. It is a genus of aerobic actinomycetes that can cause localized or disseminated infections. Nocardia spp. appear on microscopy as branching, filamentous organisms.

Approximately 80% of Nocardia infections are attributed to N. asteroides complex. N. brasiliensis typically causes cutaneous and lymphocutaneous disease, but it may also cause systemic and, occasionally, central nervous system infection. Immunocompromise is a well-established risk factor for nocardiosis.

In one study, central nervous system involvement was recognized in nearly 50% of cases of systemic nocardiosis [1]. The diagnosis is often missed or delayed because of the lack of clinical and laboratory signs of bacterial infection, and silent invasion and persistence make diagnosis and management difficult. Therefore, cerebral biopsy should be undertaken promptly in an immunocompromised patient because of the potential implications for treatment [1].

The choice and dose of antimicrobial drugs and the duration of therapy depends on the extent of infection, underlying host factors, the species of Nocardia, and the clinical response to initial management. Sulfonamides are the treatment of choice for nocardiosis. The use of additional drugs in severely ill patients (e.g., amikacin, imipenem, or ceftriaxone) may improve the prognosis, especially in an immunocompromised host. As primary therapy, parenteral combinations containing imipenem, amikacin, and a third-generation cephalosporin should be considered experimental until further data are available.

One author has suggested that surgery should be performed in patients with cerebral abscesses caused by Nocardia spp. When the lesions are accessible and relatively rare, the patient’s condition deteriorates, lesions progress within 2 weeks of therapy, or no reduction in abscess size is seen within a month [2]. Although decompression of lesions may be accomplished by stereotactic aspiration, in some cases, cure is effected only after craniotomy and total excision [3]. Small abscesses can be cured by prolonged antimicrobial therapy. Because abscesses may progress in the face of appropriate therapy, all patients should be monitored frequently with cranial computed tomography or other imaging modalities [4].

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References

1. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev 1994; 7:213–64.

2. Mamelak AN, Obana WG, Flaherty JF, et al. Nocardial brain abscess: treatment and factors influencing outcome. Neurosurgery 1994; 35:622–31.

3. Byrne E, Brophy BP, Perrett LV. Nocardia cerebral abscess: new concepts in diagnosis, management, and prognosis. J Neurol Neurosurg Psychiatry 1979; 42:1038–45.

4. Filice GA, Simpson GL. Management of nocardia infections. Curr Clin Top Infect Dis 1984; 5:49–64.

© 2001 Lippincott Williams & Wilkins, Inc.