Nocardiosis

Pulmonary nocardiosis is a well-described infection in immunocompromised patients; however, it is less well documented in patients with AIDS. The pulmonary manifestation in 21 HIV-positive patients who developed pulmonary infection with Nocardia asteroides is described. The radiographic picture included lobar or multilobar consolidation (52 percent [11/21]), solitary masses (24 percent [5/21]), reticulonodular infiltrates (33 percent [7/21]), and pleural effusion (33 percent [7/21]). Cavitation was common (62 percent [13/21]), and upper lobes were more commonly involved (71 percent [15/21]). Although the radiographic picture is variable, nocardiosis should be suspected in an HIV-positive patient who has subacute pulmonary disease with an unexplained lung mass or cavitary lesions.

Since the first description by Nocard[1] more than 100 years ago, nocardiosis has been extensively reported in the medical literature. The incidence of nocardiosis is estimated to be between 500 and 1,000 cases every year in the United States,[2] and Nocardia asteroides is by far the most common pathogen of that genus. The common organs infected in humans are the lung, skin, and, less commonly, the brain.[3,4]

Studies in laboratory animals have shown that cell-mediated immunity plays a major role in the host's defense against nocardial infections. Therefore, it is not surprising that a significant number of cases with nocardiosis occur in immunocompromised hosts such as post-transplant patients.[6,7] Since the beginning of the AIDS epidemic, only a few reports have mentioned the association of nocardiosis and AIDS.[8-10] Over a period of six years, 21 cases of pulmonary nocardiosis associated with HIV infection were diagnosed at the University of Miami. The clinical manifestation is described, with a focus, in this report, on the radiographic appearance of this opportunistic infection.

MATERIALS AND METHODS

Between 1983 and 1989, some 21 HIV-positive patients with pulmonary nocardiosis were diagnosed at the University of Miami. Patients with extrapulmonary nocardial infection but with no evidence of pulmonary disease were excluded. The medical records, bacteriologic reports, and chest roentgenograms were reviewed. There were 17 men and four women. Ages ranged from 21 to 56 years (median, 32 years). Ten were homosexuals, six were intravenous drug abusers, and in five cases, no apparent risk factor was known.

All tested positive to HIV (ELISA only before 1988; ELISA and Western blot thereafter), and their total T-helper cell counts ranged between 15/cu mm and 266/cu mm (mean, 80/cu mm). Diagnosis was made by sputum cultures in seven patients and by bronchoscopy in 13 patients, of whom bronchoalveolar lavage culture was positive in 11, and transbronchial biopsies were positive in ten of these patients. Gram or acid-fast stains of sputum were positive in only four cases. In one cases, diagnosis was obtained by mediastinoscopy and mediastinal lymph node biopsy. One patient had concomitant cutaneous involvement, and Nocardia was isolated from the skin, as well as from bronchoalveolar lavage fluid. In six cases the diagnosis was confirmed by autopsy. All cultures yielded N asteroides. Other concomitant disorders in these patients were oral thrush (18/21) and concomitant Pneumocystis carinii (2/21). Kaposi's sarcoma, cytomegaloviral retinitis, and cerebral toxoplasmosis were present in one patient each. The diagnosis of AIDS had been made prior to the current hospitalization in seven patients (three had PCP, two had candidal esophagitis, one had cryptococcosis, and one had disseminated tuberculosis).

RESULTS

The radiologic picture of pulmonary nocardiosis varies significantly in patients with AIDS (Table 1). The most common radiographic pattern is consolidation, which was seen in 11 (52 percent) of the 21 patients (Fig 1-3). Consolidation usually involves large areas and includes several lobes. A diffuse interstitial pattern was observed in seven patients (33 percent), and a solitary well-defined mass was seen in five patients (24 percent) (Fig 4,5). Cavitary lesions within the consolidated areas or within the solitary masses were common and were observed in 13 (62 percent) of the 21 patients (Fig 3, 4, 6). Pleural effusion occurred in a third of the patients, mostly on the ipsilateral side of the pulmonary parenchymal infiltrate (five cases) and, less commonly, bilaterally (two cases). In three cases, mediastinal adenopathy was present; in one patient, it was only chest abnormality. In one patient, no abnormality was seen in the chest x-ray film. The upper lobes were involved in 15 (71 percent) of the cases; ten of them (47 percent of all cases) involved the right upper lobe and four (20 percent) the left upper lobe. Unilateral disease was noted in 14 cases (67 percent) and bilateral disease in seven cases (33 percent). The clinical presentations in our patients were nonspecific and included respiratory symptoms (dyspnea; cough; sputum production) and fever. Pleuritic chest pain was present in a third of the patients. Two cases were complicated by cerebral abscesses, and in one of them, cutaneous involvement was reported. Although most of these patients (17/21) died after follow-up of between one day and 18 months after the diagnosis was made, in 11 cases an impressive clinical as well as radiologic improvement was noted. Most of the patients were treated with sulfasoxazol, a trimethoprim-sulfamethoxazole combination, or minocycline; however, in ten patients, disease progression was seen, despite proper treatment, probably because of advanced disease.

DISCUSSION

Nocardiosis is not currently considered a disease that fulfills the CDC criteria for the diagnosis of AIDS, even in the presence of a positive HIV serology; however, several reports have pointed out the association between the disease and AIDS.[8-10] Nocardia is quite a common pathogen in other immuno-deficient states,[2,3] in particular after organ transplantation.[6,7,11,12] Other underlying conditions that predispose to infection with Nocardia are hematologic malignancies, long-term steriod administration (commonly associated with chronic obstructive pulmonary diseases), collagen vascular disease, and, rarely, primary pulmonary proteinosis.[13] Nocardia may also colonize the airways without producing parenchymal disease;[3] however, in the setting of continuous immunosuppression, colonization might progress to tissue invasion and dissemination. [TABULAR DATA OMITTED]

The radiographic picture is variable in AIDS-associated nocardiosis; however, it seems not to be significantly different from that in patients without AIDS. In Feigins'[14] report of a similar sized group of patients without AIDS, a similar variety of findings was noted. Consolidation, large masses with cavitation, an interstitial pattern, and pleural effusion were the main patterns, which are similar to this report. This is not surprising, since most patients of that group were a variety of immunocompromised hosts as well, although none of them had AIDS. In contrast, in patients receiving allogeneic organ transplants, a more uniform pattern was observed, and the common finding was of a solitary lung nodule or abscess, which was present in 89 percent of the heart transplants at Stanford.[7] Similarly, nodular lesions were the common presentation and occurred in 52 percent of inpatients receiving renal transplants.[6] Cavitary changes were reported in only 19 percent, and pleural effusion occurred in 23 percent of the cases in that group.

Several clinical clues may suggest the diagnosis. First, the finding of a solitary, well-defined oval or rounded mass (Fig 5), with or without cavitation, is very suggestive of Nocardia in an immunocompromised host. Moreover, a "classic" radiographic picture of tuberculosis (upper lobe cavitary infiltrate) (Fig 2, 6) that is unresponsive to appropriate antituberculosis medication should raise the suspicion of nocardial infection. This is particularly true in patients with AIDS, in whom the radiographic picture of tuberculosis commonly does not include cavitation or upper lobe lesions.[15] Finally, concomitant extrapulmonary sites of nocardial infection in soft tissues (usually the skin) or cerebral involvement should be highly suggestive of nocardiosis.

Nevertheless, the final diagnosis should always be based upon a positive sputum culture or bronchoscopic findings. Fortunately, many of the patients with positive HIV serology and respiratory symptoms are commonly treated with a sulfonamide combination for presumed PCP. Treatment at this dosage will usually cover Nocardia as well; however, a definite diagnosis should be made, since the treatment for nocardial infection is much longer than for pneumocystosis and may require a period of 6 to 12 months. It should also be remembered that multiple pulmonary pathologic findings are common in AIDS, and P carinii or mycobacterial disease may coexist with nocardiosis, and therefore Nocardia can be easily overlooked.

The diagnosis of AIDS could be established in only 13 out of the 21 cases. Six of these had previously fulfilled the criteria for AIDS, and an additional seven cases had had other concomitant AIDS-related disorders. In view of the poor outcome in our patients and if similar results are seen elsewhere, it may be justified to consider the diagnosis of nocardiosis in an HIV-positive patient as a sufficient criterion for AIDS.

In conclusion, the radiographic picture of pulmonary nocardiosis in patients with AIDS is variable; however, the possibility of Nocardia should be kept in mind in HIV-positive patients with subacute infection and an atypical radiographic lesion.

REFERENCES

[1] Nocard E. Note sur la maladie de boeufs de la Guadeloupe: connue sous le nom de farcin. Ann Inst Pasteur 1888; 2:293

[2] Beaman BL, Burnside J, Edwards B, Causey W. Nocardial infections in the United States, 1972-1974. Rev Infect Dis 1976; 134:286-89

[3] Curry WA. Human nocardiasis: a clinical review with selected case reports. Arch Intern Med 1980; 140:818-26

[4] Chazen G. Nocardia. Infection Control 1987; 8:260-63

[5] Deem RL, Doughty FA, Beaman BL. Immunologically specific directed lymphocytic-mediated killing of Nocardia asteroides. J Immunol 1981; 2401-06

[6] Wilson JP, Turner HR, Kirchner KA, Chapman SW. Nocardial infections in renal transplant recipients. Medicine 1989; 68:38-57

[7] Simpson GL, Stinson EB, Eggar MJ, Remington JS. Nocardial infections in the immunocompromised host: a detailed study in a defined population. Rev Infect Dis 1981; 3:492-507

[8] Rodrigez JL, Barrio JI, Pitchenik AE. Pulmonary nocardiasis in the AIDS: diagnosis with bronchoalveolar lavage and treatment with non-sulphor containing drugs. Chest 1986; 90:912-14

[9] Yaeger BA, Hoxie J, Weisman RA, Greenberg MS, Bilaniuk LT. Actinomycosis in the AIDS-related complex. Arch Otololaryngol Head Neck Surg 1986; 112:1293-95

[10] Holtz HA, Larvey DP, Kapila R. Actinomycosis infection in the AIDS. Ann Intern Med 1985; 102:203-05

[11] Krick JA, Stinson EB, Remington JS. Nocardia infection in heart transplant patients. Ann Intern Med 1975; 82:18-26

[12] Patel NP, Corry RJ. Pulmonary infections in renal transplant recipients. Dialysis Transplantation 1979; 8:337-41

[13] Burbank B, Morrion TG, Cutler TS. Pulmonary alveolar proteinosis and nocardiosis. Am J Med 1960; 28:1002-07

[14] Feigin DS. Nocardiosis of the lung: chest radiographic finding in 21 cases. Radiology 1986; 159:9-14

[15] Pitchenik AE, Fertel D, Bloch AB. Mycobacterial disease: epidemiology, diagnosis, treatment and prevention. Clin Chest Med 1988; 9:425-38

COPYRIGHT 1990 American College of Chest Physicians
COPYRIGHT 2004 Gale Group