DELAYEDDIAGNOSISOF HIVRELATEDTUBERCULOSIS To the Editor:
The recent report of Kramer et al [l] holds practical importance to clinicians caring for patients with acquired immunodeficiency syndrome (AIDS) and provides an updated reminder of a problem that long preceded the human immunodeficiency virus (HIV) epidemic: failure to pursue assiduously the diagnosis of tuberculosis in patients with unexplained fever or clinical abnormalities consistent with that disease [2]. The authors retrospectively attributed most (60%) missed opportunities for early diagnosis to insufficient study of sputum. Sputum examination may be inadequate for several reasons, including the patient’s inability to produce specimens, lack of supervised collection, or the physician’s (mistaken) perception that the yield would be low (e.g., in pleural, lymphatic, or miliary disease). In many cases, however, the fundamental problem lies in diagnostic thinking rather than in acquisition of diagnostic specimens. In our experience at an institution in which HIV-related tuberculosis is diagnosed weekly, failure to give leading consideration to tuberculosis remains an important cause of delayed diagnosis. Given the array of infectious diseases common in AIDS, physicians may focus initial attention on other possibilities (bacterial or Pneumocystis pneumonia, infectious endocarditis, cerebral toxoplasmosis, and so forth) to the neglect of tuberculosis. Moreover, the clinical and radiographic findings are nonspecific in most AIDS-related infections, leading to legitimate diagnostic confusion in some instances. In others, tuberculosis is “cryptic” at presentation or is not recognized initially because of a concomitant disease. Hesitancy to begin antituberculous therapy empirically is yet another factor.
Recently, we have seen one or more HIV-infected patients each year whose tuberculosis was identified only at autopsy. To better understand the implications of their study, it would be helpful to know the initial diagnostic impressions and management plans of the physicians treating the patients reported by Kramer et al [l]. Unlike these authors, we believe that “atypical,” nonspecific, and occult presentations of tuberculosis in AIDS patients contribute substantially to delayed diagnosis [3]. Indeed, the much lower rate of late diagnosis in their non-HIV-infected patients suggests that the same is true at their institution. Given the varied presentations of tuberculosis, it is unlikely that the problem of delayed or missed diagnosis can be eliminated entirely, although improved methods for rapid diagnosis will help. A.Ross HILL,M.D.,C.M. State University of New York Health Science Center Brooklyn, New York 1. Kramer F, Modilevsky T, Waliany AR, Leedom JM. Barnes PF. Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection. Am J Med 1990; 89: 451-6. 2. Campbell IG. Miliary tuberculosis In British Columbia. Can Med Assoc J 1973; 108: 1517-26. 3. Hill AR, Premkumar S. Brustein S, eta/. Disseminated tuberculosis in the AIDS era. Am Rev Respir Dis. In press. Submitted
January
15. 1991, and accepted
March 13, 1991
The Reply:
Dr. Hill points out some common pitfalls that result in failure to make the diagnosis of tuberculosis in HIV-infected patients. We agree that the fundamental problem lies in failure to consider the possibility of tuberculosis and have emphasized this factor in prior publications [l-3]. In the report cited by Hill, we focused on physician failure to obtain an adequate number of sputum specimens because it is a quantifiable variable that reflects the physician’s diagnostic considerations. Tuberculosis was not included in the differential diagnoSeptember
1991 The American
sis for 12 of the 15 patients in whom fewer than three sputum samples were obtained for mycobacterial culture. Pneumocystis carinii pneumonia was the presumptive diagnosis in most cases. Bacterial pneumonia, bacterial endocarditis, and sepsis were leading diagnoses in a minority of patients. The frequency with which tuberculosis in HIV-infected patients is diagnosed postmortem varies widely in published series. Investigators in New York noted that 26% to 28% of their HIV-infected patients with tuberculosis were undiagnosed till death [4,5], compared with 9% (11 of 119) of HIV-infected patients in Los Angeles [2], and 5% (seven of 132) of those in San Fransisco [6]. Tuberculosis diagnosed after death is the most extreme example of delayed diagnosis, and less obvious delays in diagnosis are undoubtedly more common. Unlike Dr. Hill, we have not found atypical or occult presentations of tuberculosis to be a common cause of delayed diagnosis of tuberculosis in HIV-infected patients [l-3]. Further study is essential to establish the underlying reasons for these delays in a variety of inpatient and outpatient settings, so that appropriate corrective measures can be taken. Recent reports of tuberculosis outbreaks from HIV-infected source cases [7,8] emphasize the importance of timely diagnosis of tuberculosis, which remains the most effective means to prevent transmission of the disease. FRANCOISEKRAMER,M.D. PETERF.BARNES?M.D. Los Angeles County- Universrty of Southern California Medical Center Los Angeles, California 1. Modilevsky T, Sattler FR. Barnes PF. Mycobacterial disease In patients with human immunodeficiency virus infection. Arch Intern Med 1989; 149: 2201-5. 2. Kramer F, Modilevsky T. Waliany AR, Leedom JM, Barnes PF. Delayed dragnosis of tuberculosis in patients with human rmmunodeficrency virus infection. Am J Med 1990; 89: 451-6.
Journal
of Medicine
Volume
91
319
The recent report of Kramer et al [l] holds practical importance to clinicians caring for patients with acquired immunodeficiency syndrome (AIDS) and provides an updated reminder of a problem that long preceded the human immunodeficiency virus (HIV) epidemic: failure to pursue assiduously the diagnosis of tuberculosis in patients with unexplained fever or clinical abnormalities consistent with that disease [2]. The authors retrospectively attributed most (60%) missed opportunities for early diagnosis to insufficient study of sputum. Sputum examination may be inadequate for several reasons, including the patient’s inability to produce specimens, lack of supervised collection, or the physician’s (mistaken) perception that the yield would be low (e.g., in pleural, lymphatic, or miliary disease). In many cases, however, the fundamental problem lies in diagnostic thinking rather than in acquisition of diagnostic specimens. In our experience at an institution in which HIV-related tuberculosis is diagnosed weekly, failure to give leading consideration to tuberculosis remains an important cause of delayed diagnosis. Given the array of infectious diseases common in AIDS, physicians may focus initial attention on other possibilities (bacterial or Pneumocystis pneumonia, infectious endocarditis, cerebral toxoplasmosis, and so forth) to the neglect of tuberculosis. Moreover, the clinical and radiographic findings are nonspecific in most AIDS-related infections, leading to legitimate diagnostic confusion in some instances. In others, tuberculosis is “cryptic” at presentation or is not recognized initially because of a concomitant disease. Hesitancy to begin antituberculous therapy empirically is yet another factor.
Recently, we have seen one or more HIV-infected patients each year whose tuberculosis was identified only at autopsy. To better understand the implications of their study, it would be helpful to know the initial diagnostic impressions and management plans of the physicians treating the patients reported by Kramer et al [l]. Unlike these authors, we believe that “atypical,” nonspecific, and occult presentations of tuberculosis in AIDS patients contribute substantially to delayed diagnosis [3]. Indeed, the much lower rate of late diagnosis in their non-HIV-infected patients suggests that the same is true at their institution. Given the varied presentations of tuberculosis, it is unlikely that the problem of delayed or missed diagnosis can be eliminated entirely, although improved methods for rapid diagnosis will help. A.Ross HILL,M.D.,C.M. State University of New York Health Science Center Brooklyn, New York 1. Kramer F, Modilevsky T, Waliany AR, Leedom JM. Barnes PF. Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection. Am J Med 1990; 89: 451-6. 2. Campbell IG. Miliary tuberculosis In British Columbia. Can Med Assoc J 1973; 108: 1517-26. 3. Hill AR, Premkumar S. Brustein S, eta/. Disseminated tuberculosis in the AIDS era. Am Rev Respir Dis. In press. Submitted
January
15. 1991, and accepted
March 13, 1991
The Reply:
Dr. Hill points out some common pitfalls that result in failure to make the diagnosis of tuberculosis in HIV-infected patients. We agree that the fundamental problem lies in failure to consider the possibility of tuberculosis and have emphasized this factor in prior publications [l-3]. In the report cited by Hill, we focused on physician failure to obtain an adequate number of sputum specimens because it is a quantifiable variable that reflects the physician’s diagnostic considerations. Tuberculosis was not included in the differential diagnoSeptember
1991 The American
sis for 12 of the 15 patients in whom fewer than three sputum samples were obtained for mycobacterial culture. Pneumocystis carinii pneumonia was the presumptive diagnosis in most cases. Bacterial pneumonia, bacterial endocarditis, and sepsis were leading diagnoses in a minority of patients. The frequency with which tuberculosis in HIV-infected patients is diagnosed postmortem varies widely in published series. Investigators in New York noted that 26% to 28% of their HIV-infected patients with tuberculosis were undiagnosed till death [4,5], compared with 9% (11 of 119) of HIV-infected patients in Los Angeles [2], and 5% (seven of 132) of those in San Fransisco [6]. Tuberculosis diagnosed after death is the most extreme example of delayed diagnosis, and less obvious delays in diagnosis are undoubtedly more common. Unlike Dr. Hill, we have not found atypical or occult presentations of tuberculosis to be a common cause of delayed diagnosis of tuberculosis in HIV-infected patients [l-3]. Further study is essential to establish the underlying reasons for these delays in a variety of inpatient and outpatient settings, so that appropriate corrective measures can be taken. Recent reports of tuberculosis outbreaks from HIV-infected source cases [7,8] emphasize the importance of timely diagnosis of tuberculosis, which remains the most effective means to prevent transmission of the disease. FRANCOISEKRAMER,M.D. PETERF.BARNES?M.D. Los Angeles County- Universrty of Southern California Medical Center Los Angeles, California 1. Modilevsky T, Sattler FR. Barnes PF. Mycobacterial disease In patients with human immunodeficiency virus infection. Arch Intern Med 1989; 149: 2201-5. 2. Kramer F, Modilevsky T. Waliany AR, Leedom JM, Barnes PF. Delayed dragnosis of tuberculosis in patients with human rmmunodeficrency virus infection. Am J Med 1990; 89: 451-6.
Journal
of Medicine
Volume
91
319
