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Pulmonary Tuberculosis and

Steroids
Tuberculosis is

an

ancient

scourge

revisited. The

recent increase in tuberculosis is disturbing and


not entirely related to the increase in AIDS. Although

corticosteroid therapy has been one of the great


therapeutic advances in the history of medicine, for
decades it has been appreciated that steroid therapy
given to patients with untreated or unrecognized tuberculosis results in overwhelming disease and death.
Eleanor Roosevelt died of undiagnosed miliary tuberculosis while being treated with steroids for what
was thought to be sarcoidosis. Therefore, it is easy to
understand the reluctance to use steroids as adjunctive therapy for tuberculosis when steroids have such
a profound effect on untreated tuberculosis.
However, in Latin America, Asia, and Africa, steroids have long been used in the treatment of various
forms of tuberculosis to reduce the toxicity associated
with acute, severe, or fulminant disease. The experience with steroids and tuberculosis over decades in
these areas of the world has been favorable, when
used in conjunction with effective antituberculous
regimens. Traditionally, steroid therapy has been
beneficial in tuberculous meningitis, tuberculous
pericarditis, and in miliary tuberculosis. Many clinicians have noted that steroids given to patients
receiving antituberculous medications suffer no ill
effects, and many of these patients benefit clinically
from the addition of steroids to their treatment regimen. Since steroids given in concert with antituberculous drugs do not result in the progression of
tuberculosis or make the disease worse, and because
no harmful effects can be ascribed to steroid therapy
in this setting, some investigators over the years have
tried to demonstrate the benefits of steroids in the
various forms of pulmonary tuberculosis.
The study and review by Dr. Muthuswamy and his
colleagues from the Cook County Hospital in Chicago, published in this issue of CHEST (see page
1621), is a small but well-done study which, importantly, shows the benefits of steroids in a group of
young, predominantly African-American men. The
authors selected patients with pulmonary tuberculosis who had persistent fever and weight loss while
verifying bacteriologic response in sputum smears to
effective antituberculous therapy.
The authors were careful to exclude other causes
of persistent fever in their patients, eg, drug fever.
Drug fever secondary to antituberculous therapy is a
common complication of antituberculous therapy
and is usually due to isoniazid or rifampin. Drug fever is usually manifested by an elevated temperature
accompanied by a rise in serum transaminase levels/
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relative bradycardia. Unlike drug fevers due to nontuberculous medications, eosinophilia secondary to
isoniazid or rifampin therapy is uncommon. An elevation of the erythrocyte sedimention rate (ESR) is a
common abnormality in drug fever. Serial ESRs may
be used to follow disease activity and should decrease
as the patient responds to therapy. An initial decrease
in serial ESRs followed by a subsequent rise in the
ESR may be the first manifestation of impending
drug fever.
Most patients promptly responded to 40 mg of
prednisone per day within 24 h of being started on a
regimen of steroid therapy. In addition to rapidly
decreasing temperature, patients experienced a decrease in the toxemia associated with tuberculosis,
increased appetite and weight, and their serum
albumin levels also increased while receiving prednisone. Importantly, there were no untoward effects
due to prednisone therapy in these patients during
the 4 to 8 weeks when steroids were administered,
even though the study group was small. The authors
are careful to note that adjunctive steroid therapy
should be used only in patients responding to effective antituberculous drugs, eg, no resistance to firstline antituberculous medications. Three patients in
their study did not respond to once-daily prednisone
administration but required twice-daily doses. This
apparently was due to the well-known effect of
rifampin in decreasing the serum half-life of prednisone by the induction of liver enzymes. The study
of Muthuswamy et al agrees with other published
reports in the literature, that there were no untoward
effects or negative consequences ascribed to adjunctive short-term steroid therapy in patients with pulmonary tuberculosis.
The authors have also provided a valuable service
in carefully reviewing the literature on tuberculosis
and steroids and presenting it in tabular form in their
article. This study is noteworthy, not for its numbers
but for its detailed observations.
Review of the literature reveals that the effects of
steroids on tuberculosis in patients being treated with
effective antituberculous medications are beneficial,
but the benefits are variable.''10 There is little doubt
that adjunctive steroid therapy may be lifesaving in
patients with miliary tuberculosis. Steroid therapy
seems to be beneficial in patients with acute, extensive cavitary pulmonary tuberculosis. Steroids may
be beneficial in (1) patients with endobronchial
tuberculosis, (2) patients with extensive primary tuberculosis with a large pleural effusion, or (3) patients
with severe hypoxemia secondary to advanced disease. Steroids should not be used in "short course"
antituberculous regimens, mild to moderate cavitary
disease without toxemia, old fibrocavitary disease, or
in patients showing resistance to one or more antituEditorials

berculous drugs, especially if there is rifampin resistance. There are inadequate data on the effects of
steroids on tuberculosis treatment in patients with
AIDS to make specific recommendations, but there is
no reason to expect that they would respond any
differently than normal individuals and might benefit in the face of severe disease.
Certainly, disagreements about the benefits of adjunctive steroid therapy in patients being treated for
tuberculosis will continue.24'910 Few will disagree
that steroids should be used to treat central nervous
system, cardiac, or disseminated forms of tuberculosis. Most will agree that steroids have no place in
treating mild to moderate disease, far advanced
chronic disease, or tuberculosis resistant to rifampin
or other antituberculous drugs." 3'6-8 Hopefully, the
study by Dr. Muthuswamy and colleagues will help
to further define the role for steroids in selected patients with pulmonary tuberculosis, ie, patients with
bacteriologic but not clinical improvement, where
the benefits from adjunctive steroids is impressive
and predictable. In the proper clinical setting, steroids can be expected to accelerate clinical and
radiologic improvement with a rapid decrease in
toxemia and temperature in the types of patients with
pulmonary tuberculosis that Dr. Muthuswamy et al
described. Aside from curing patients, which is our
role as physicians, it is important to consider the patient's rate of recovery in selecting therapeutic
options, and in doing so, possibly decrease the length
of hospitalization or frequency of clinic visits. In an
era of cost containment and a search for cost-effective therapies, it would seem that steroid therapy for
some forms of pulmonary tuberculosis is an idea

come, again.

Burke A. Cunha, MD
Mineola, New York

Infectious Disease Division, Winthrop-University Hospital, Mineola.


Reprint requests: Dr. Cunha, Infectious Disease Division, Dept
of Medicine, Winthrop-University Hospital, Mineola, NY 11501

REFERENCES
1 Weinstein HJ, Koler JJ. Adrenocorticosteroid in the treatment
of tuberculosis. N Engl J Med 1959; 260:412-17
2 Lee CH, et al. Corticosteroids in the treatment of tuberculous
pleurisy: a double-blind, placebo-controlled, randomized study.
Chest 1988; 94:1256-59
3 Horne NW. Prednisolone in treatment of pulmonary tuberculosis: a controlled trial. BMJ 1960; 5215:1751-56
4 Marcus H, Voo HY, Akyol T, et al. A randomized study of the
effects of corticosteroid therapy on healing of pulmonary
tuberculosis as judged by clinical, roentographic and physiologic measurements. Am Rev Respir Dis 1963; 88:55-64
5 Malik SK, Martine CS. Tuberculosis, corticosteroid therapy, and
pulmonary function. Am Rev Respir Dis 1969; 100:13-8
6 Angel JH, Chu LS, Lyons HA. Corticotropin in the treatment
of tuberculosis. Arch Intern Med 1961; 108:75-91
7 Tuberculosis Research Centre. Study of chemotherapy regimens of 5 and 7 months' duration and the role of corticosteroids in the treatment of sputum-positive patients with pulmonarv tuberculosis in South India. Tubercle 1983; 64:73-91
8 Johnson JR, Taylor BC, Morrissey JF, et al. Corticosteroids in
pulmonary tuberculosis. Am Rev Respir Dis 1965; 92:376-91
9 Busey JF, Fender EPK, Hepper NG, et al. Adrenal corticosteroids and tuberculosis: American Thoracic Society. Am Rev
Respir Dis 1968; 97:484-85
10 Alzeer AH, FitzGerald JM. Corticosteroids and tuberculosis:
risks and use as adjunct therapy. Tubercle Lung Dis 1993;
74:6-11

CHEST / 107 / 6 / JUNE, 1995


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