Why does this woman have pleuritic chest pain? – Pulmonary Pearls

Why does this woman have pleuritic chest pain? – Pulmonary Pearls – pulmonary nocardiosis

John T. Huggins

A 54-year-old woman was referred for evaluation of new onset of pleuritic chest pain and abnormal findings on a chest radiograph. She denied fever, chills, dyspnea, cough, and hemoptysis.

The patient’s medical history included allogeneic bone marrow transplantation that had been performed 2 years prior for refractory acute myelogenous leukemia. She subsequently had chronic graft-versus-host disease of the liver and skin. This complication required intensification of immunosuppression during the past 6 months.

The patient was a lifelong nonsmoker and had no significant travel history. She was active in gardening around her home. Current medications included prednisone (30 mg/d), tacrolimus (1 mg bid), and folic acid.

Physical examination: Temperature, 36.9[degrees]C (98.4[degrees]F); pulse rate, 108 beats per minute; respiration rate, 18 breaths per minute; blood pressure, 141/95 mm Hg; and oxygen saturation as measured by pulse oximetry (while on room air), 89%.

General condition: no ill appearance. Head, eyes, ears, nose, and throat: no lesions. Heart: regular tachycardia. Chest: crackles and bronchovesicular breath sounds auscultated at the right posterior base. Neurologic, abdominal, and integument: no abnormalities were documented.

Laboratory findings: White blood cell count, 17,000/[micro]L; hematocrit, 38%; platelet count, 66,000/[micro]L; sodium, 134 mEq/L; potassium, 3.7 mEq/L; chloride, 99 mEq/L; bicarbonate, 27 mEq/L; creatinine, 0.6 mg/dL; and D dimer, less than 0.43 fibrinogen equivalent units.

The patient’s posteroanterior and lateral chest radiographs (Figures 1A and 1B) and corresponding CT scan (Figure 2) obtained on admission are shown below.


Diagnosis: Pulmonary nocardiosis

Making the diagnosis

The posteroanterior chest radiograph revealed a well-circumscribed, homogeneous mass in the right lower lobe. The lateral chest radiograph showed a parenchymal mass abutting the pleural surface. The chest CT scan confirmed a pleural-based homogeneous mass with surrounding alveolar infiltrates in the right lower lobe.

A CT-guided needle aspiration and biopsy specimen revealed a filamentous, gram-positive organism. On culture, Nocardia nova was identified.


Nocardia is a gram-positive, variable acid-fast, aerobic bacterium that belongs to the order Actinomycetales. Nocardiae are ubiquitous organisms found in soil and decaying organic matter.

The taxonomy of Nocardia is complex and evolving. There is marked heterogeneity in terms of antibiotic susceptibility patterns, biochemistry, and morphology. The 6 major subgroups known to cause infections in humans are Nocardia asteroides, Nocardia farcinica, N nova, Nocardia brasiliensis, Nocardia otitidis-caviarum, and Nocardia transvalensis. (1)

The most accepted mechanisms of infection are inhalation or direct inoculation of a wound. Cases of nosocomial infection have been reported. There is no evidence of respiratory spread from infected animal to human or of human-to-human transmission. (2)

Nocardiosis often presents as an opportunistic infection in an immunocompromised patient; however, it can occur in patients with normal immunity. In an analysis of 455 cases of nocardiosis, 40% of patients had no preexisting illness and were not receiving immunosuppressive therapy. (3)

Hematologic malignancy is an important risk factor for nocardiosis. Structural lung disease leads to colonization, and the use of corticosteroids increases the risk of invasion. Cell-mediated immune dysfunction is a well-recognized risk factor, especially with solid organ transplantation; however, the occurrence of nocardiosis in bone marrow transplantation is rare. Other identified risk factors for nocardiosis include connective tissue disorders, dysgammaglobulinemia, alcoholism, diabetes, and HIV infection. (1)

Nocardia infections in bone marrow transplant recipients have been reported. Only 4 case reports were published in the medical literature before a review reported a rate of nocardial infections of 0.2% (1 of 554) among autologous and 1.7% (5 of 302) among allogeneic bone marrow transplant recipients. (4) The use of prophylactic trimethoprim-sulfamethoxazole did not confer protection against nocardial infection in this subgroup of patients. Four of 6 patients with nocardiosis reported extensive soil exposure before the development of disease. (4)

Pulmonary nocardiosis can present as an acute, subacute, or chronic illness. Men are affected 3 times more often than women. (1) The clinical and radiographic presentation of pulmonary nocardiosis is nonspecific. According to a published review, cough, fever, and purulent sputum production were the most common symptoms; 70% of patients had symptoms for more than 3 weeks before a diagnosis was established. (5) Clinical clues to the presence of nocardial infection are pleural space or chest wall involvement, dissemination to the CNS, and skin disease.

Often, the chest radiograph shows confluent bronchopneumonia, lobar and multilobar consolidation, and pleural involvement. Empyema is reported in 25% of cases, and up to 50% of patients have pleural involvement at the time of presentation, manifested as either pleural thickening or effusion. Large, irregular nodular densities, which may cavitate, are a frequent radiographic presentation for pulmonary nocardiosis. Less common radiographic manifestations include a solitary pulmonary mass, a reticular pattern, and small irregular nodules. Rarely, Nocardia infection can cause a fungus ball in a preexisting cavity (Table). (6)

Dissemination to the CNS occurs in 33% of cases. The signs and symptoms of nocardial brain infection are highly variable.

Needle aspiration of a cerebral mass in the setting of documented pulmonary nocardiosis is not always necessary. However, in patients who have HIV infection, the potential for CNS lymphoma or concomitant infection mandates a tissue diagnosis even if pulmonary nocardiosis is established. (2)

Before the introduction of sulfonamide therapy, mortality rates approached 90% in patients with disseminated disease. Current mortality rates are approximately 20% in patients with isolated pulmonary disease. However, only 10% to 30% of CNS abscesses are cured with chemotherapy.

Current treatment recommendations for Nocardia infection are based on anecdotal evidence, outcomes in animal studies, and in vitro susceptibility studies. Sulfonamides are the first-line agents. Other drugs used are minocycline, amikacin, imipenem, amoxicillin/ clavulanate, and linezolid. (2)

The optimal duration of therapy is uncertain, but long-term therapy is the rule because of the propensity of Nocardia infections to relapse. Nonimmunosuppressed patients with pulmonary or systemic nocardial infection, excluding CNS involvement, should be treated for at least 6 to 12 months. (2) Those with CNS infections and all immunosuppressed patients require 12 months of therapy.

Parenteral therapy should be initiated in all patients who are extremely ill at presentation. Once the clinical status improves and antimicrobial susceptibilities are known, patients’ parenteral regimens can be switched safely to oral therapy, typically in 3 to 6 weeks. (2)

In summary, Nocardia infections in bone marrow transplant recipients are infrequent but are important infectious complications. Cell-mediated immune dysfunction, long-term corticosteroid use, and HIV infection are well-recognized risk factors for the development of disease. A history of substantial soil exposure should increase the clinical suspicion of Nocardia infection. Although there are many radiographic patterns of pulmonary nocardiosis, a solitary lung mass is an infrequent finding.

Outcome in this case

The patient was treated with minocycline, because of an allergy to sulfa, after CNS dissemination was excluded. After 2 months of therapy, a follow-up chest radiograph revealed complete resolution of the infiltrate.

The patient received an additional 10 months of therapy and remained well 2 months later, without recurrence of nocardiosis.


manifestations of

pulmonary nocardiosis


Lobar/multilobar consolidation

Large, irregular nodular densities

Mediastinal/hilar lymphadenopathy


Pleural effusions


Less common

Solitary pulmonary mass

Reticular pattern

Small, Irregular nodules


Miliary pattern

Nocardial fungus ball in preexisting


Diffuse pulmonary infiltrates

Bronchopleural fistula


(1.) McNeil MM, Brown JM. The medically important aerobic actinomycetes: epidemiology and microbiology. Clin Microbiol Rev. 1994;7:357-417.

(2.) Lerner PI. Nocardiosis. Clin Infect Dis 1996:22:891-905.

(3.) Curry WA. Human nocardiosis. A clinical review with selected case reports. Arch Intern Med. 1980;140: 818-826.

(4.) Choucino C, Goodman SA, Greer JP, et al. Nocardial infections in bone marrow transplant recipients, Clin Infect Dis. 1996;23:1012-1019.

(5.) Menendez R, Cordero PJ. Santos M. et al. Pulmonary infection with Nocardia species: a report of 10 cases and review. Eur Respir J. 1997;10:1542-1546.

(6.) Feigin DS. Nocardiosis of the lung: chest radiographic findings in 21 cases. Radiology 1986;159: 9-14.

Clinical Pearls

1. Nocardiosis is rare among bone marrow transplant recipients compared with solid organ transplant recipients.

2. Nocardia may cause disease in approximately 40% of patients who have normal immunity.

3. Dissemination to the CNS can occur in a third of cases of pulmonary nocardiosis.

4. Patients with isolated pulmonary infections are treated for at least 6 months; 12 months of therapy is mandated for patients with CNS involvement and compromised immunity.

5. Sulfonamides are the first-line therapy for nocardiosis.

The authors are affiliated with the division of pulmonary and critical care medicine, allergy and clinical immunology at the Medical University of South Carolina in Charleston. Dr Huggins is senior fellow, and Dr Flume is associate professor of medicine. Dr Sahn’s credentials are listed below.

Dr Heffner is professor of medicine and associate dean at the Medical University of South Carolina in Charleston. Dr Sahn is professor of medicine and director of pulmonary and critical care medicine, allergy and clinical immunology at the Medical University of South Carolina in Charleston. In addition, he is codirector of the asthma-allergy center at the Medical University Hospital.

COPYRIGHT 2003 Cliggott Publishing Co.

COPYRIGHT 2003 Gale Group