History
Clinical manifestations of nocardiosis depend on the site of infection. [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]
Pulmonary disease is the predominant clinical finding in most patients with nocardiosis. [13, 21, 7] Pulmonary nocardiosis may be acute, subacute, or chronic. Clinical manifestations include inflammatory endobronchial masses or localized or diffuse pneumonia, which may be accompanied by cavitation, abscess formation, pleural effusion, or empyema. Symptoms in patients with nocardiosis are indistinguishable from those in patients with similar pulmonary infections of other microbial etiology. Cough with sputum production and fever are the dominant symptoms. At least 40% of patients with disseminated nocardiosis have a pulmonary infection; therefore, the clinical presentation may be dominated by the pulmonary symptoms.
Primary cutaneous nocardiosis can present as cutaneous infection, lymphocutaneous infection, or subcutaneous infection. Cutaneous nocardiosis generally manifests as either cellulitis or, more likely, single or multiple non-tender erythematous nodule(s) at the site of traumatic inoculation. [24] These nodules occasionally drain purulent material. Lymphocutaneous nocardiosis manifests as similar lesions accompanied by ascending regional lymphadenopathy. The lymphadenopathy may also occasionally drain purulent material. N brasiliensis is the most common cause of progressive cutaneous and lymphocutaneous (sporotrichoid) disease. [25, 26, 27]
Patients with nocardiosis may present with deep abscesses at any site, particularly in the lower extremities or the CNS. In patients with extra-CNS abscesses, fever and local symptoms predominate. Up to 20% of reported nocardiosis cases and 44% of disseminated nocardiosis cases involve the CNS. [3] When occurring in isolation, CNS nocardiosis manifests as a slowly progressive mass lesion, with a host of specific neurologic findings related to the specific location of the abscess. CNS nocardiosis is detected in up to 44% of disseminated nocardial infections. [3, 28] In two-thirds of patients with CNS nocardiosis, clinical findings indicate abscess with or without meningitis, including fever, headache, stiff neck, and/or altered mental status.
Nocardial species can cause mycetoma, a chronic, swollen, purulence-draining, subcutaneous infection of the extremities, typically encountered in tropical areas of the world, but also has been reported from the southern United States, Central, and South Americas, and Australia. It is usually ascribed to N brasiliensis. [20, 16]
Cases of traumatic inoculation or postoperative nocardial keratitis and endophthalmitis have been well described. [29, 30, 31, 32]
Postoperative wound infections due to Nocardia species are rare, but case clusters of nosocomial transmission have been described. [33]
Traumatic inoculation nocardial arthritis has occurred but is rare. This presents as a subacute or chronic monoarthritis, typically involving the knee.
Risk Factors
Pulmonary and disseminated nocardiosis are clearly associated with immunocompromising conditions, with approximately 60% of cases of nocardiosis other than mycetoma occurring in individuals with some compromise of host defense systems. Conditions associated with an increased risk of pulmonary and disseminated nocardiosis include the following:
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Chronic pulmonary disease: Although pulmonary nocardiosis has been described in association with various chronic pulmonary diseases, patients with pulmonary alveolar proteinosis are at particular risk.
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Alcoholism
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Lymphoreticular malignancy
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Solid-organ transplantation [34]
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Bone marrow or stem cell transplantation, particularly allogeneic transplantation with subsequent graft versus host disease
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Long-term corticosteroid use or Cushing syndrome
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Systemic lupus erythematosus
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Systemic vasculitis
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Inflammatory bowel disease on immunomodulating treatments [35]
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Sarcoidosis
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Renal failure
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Treatment with anti–tumor necrosis factor antibody
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HIV infection and AIDS: Nocardiosis in individuals with advanced HIV disease occurs in 0.2-2% of patients and usually presents as a relentlessly progressive infiltrative pulmonary infection. The median CD4 count in patients infected with HIV who develop nocardiosis is approximately 35 cells/µL. [18]
Physical Examination
The physical findings of nocardiosis also vary based on the site of infection.
Patients with primary cutaneous nocardiosis present with cellulitis, cutaneous nodules, nodules with ascending lymphadenopathy, or with a mycetoma can be clinically indistinguishable from similar infections due to other pathogens.
Patients with pulmonary nocardiosis present with findings of pulmonary consolidation with or without evidence of pleural effusions.
The presentation of disseminated nocardiosis depends on the sites of infection. Pulmonary findings frequently predominate. Local findings associated with metastatic abscesses may be present at almost any site but are typically in the lower extremities. The combination of pneumonia and lower-extremity abscess is not specific to but particularly suggestive of nocardiosis. Patients with brain abscess may present with altered mental status, personality changes, or various localizing neurologic findings. Patients with meningitis present with fever, altered consciousness, and meningismus.
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High-power microscopic appearance of Nocardia. Image courtesy of CDC.
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Photomicrograph of tissue biopsy stained with Gomori methenamine silver demonstrating acute inflammatory response and organisms compatible with Nocardia.
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Plain chest radiograph in a patient with nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Chest CT scan in a patient with pleuropulmonary nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Brain CT scan in a patient with nocardial brain abscess. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
