Case Report

Isoniazid causing pleural effusion

ABSTRACT
Departments of Tuberculosis
and Respiratory Diseases and Isoniazid (INH) is a first-line antitubercular drug. We report a case of a patient who
1
Medicine, JN Medical College, developed a pleural effusion 2 months after starting antitubercular treatment for spinal
AMU, Aligarh, UP, India tuberculosis. Isoniazid was found to be the culprit and its discontinuation caused
subsidence of the effusion.
Received: 31.03.2008
Revised: 25.04.2008
Accepted: 08.05.2008

Correspondence to:
Dr. Saurabh Kumar Singh
E-mail: doctorsaurabhsingh@
gmail.com
KEY WORDS: Antitubercular drug, isoniazid, paradoxical response, pleural effusion

Introduction mesothelial cells - 6%. LE cells were not found in the pleural
fluid and the ADA level was not elevated (12 IU/l). Antinuclear
Paradoxical response to chemotherapy in tuberculosis is the
antibody (ANA) titer in the fluid was elevated (1:320).
worsening of a preexisting lesion or the appearance of a new
We advised continuation of the antitubercular treatment
lesion during antitubercular treatment. Such lesions usually
and added a corticosteroid to his drug regimen; however, the
disappear on their own but sometimes the administration of
signs and symptoms of the effusion persisted. Considering
steroids or the withdrawal of the offending drug is required.
the possibility of an INH-induced effusion, INH was stopped,
Case History upon which the patient started showing clinical improvement.
A repeat chest x-ray, taken 2 weeks after stopping INH, showed
A 24-year-old male presented to our outpatient department
disappearance of the pleural effusion [Figure 2].
with complaints of fever, chest pain, and shortness of breath
of 1 week’s duration. His clinical examination showed a pulse Discussion
rate of 90/min, respiratory rate of 20/min, and blood pressure
INH is one of the first-line drugs for the treatment of
of 110/80 mmHg. He was anemic. Cyanosis and icterus
tuberculosis. It is a bactericidal drug. After absorption, it is
were absent. He had history of spinal tuberculosis for which
distributed to all body organs. The mechanism of action is
antitubercular drugs (rifampicin, isoniazid [INH], pyrazinamide,
and ethambutol) had been started 2 months earlier. Examination
Figure 1: X-ray chest showing right-sided effusion and pneumonitis
of the respiratory system revealed decrease in chest movements
on the right side. On percussion, there was stony dullness on the
right side, and the breath sounds were absent on auscultation
of the lower lung fields. The left side of the chest was normal.
Laboratory investigation showed hemoglobin of 9 gm%; the
total leucocyte count was 9600/cu mm, with 74% neutrophils,
22% lymphocytes, and 4% eosinophils. Renal and liver function
tests were within normal limits. Test for HIV was negative.
Sputum smear was negative for Mycobacterium tuberculosis.
The chest X-ray (PA view) showed a right-sided pneumonitis
with effusion [Figure 1], although there was no evidence of
pleuroparenchymal tuberculosis in a chest X-ray that had been
taken earlier. MRI of the spine was done and, when compared
with the MRI that had been done earlier, it showed improvement
in the spinal lesion.
On thoracocentesis there was an exudative effusion; cytology
of the fluid revealed lymphocytes - 90%; neutrophils - 4%, and

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Figure 2: X-ray chest showing improvement in effusion after theories have been put forward to explain the phenomenon,
withdrawing of INH such as immunological rebound[3] or an interaction between
mycobacterial products and improving host immunity,[4] none
of these theories have been confirmed.
In our case, the elevated ANA titer was suggestive of INH-
induced lupus; however, the test for LE cells was negative and
there was no improvement in symptoms after the introduction
of a steroid into the treatment. The patient showed improvement
only after discontinuation of INH, ie, dechallenge was positive.
We, however, did not try reintroduction of INH.
There are increasing reports of cases of drug resistance,
but the appearance of new lesions, such as an effusion or a
pneumonitis, in a patient on treatment for tuberculosis may
also be drug-induced; this possibility must always be kept in
mind. Paradoxical worsening of the lesion can also occur in
cerebral tuberculoma and tubercular lymphadenitis.[4] In our
patient, the aspirated pleural fluid was not characteristic of
tuberculosis, which suggested that this was not a case of drug-
resistant tuberculosis.
the inhibition of mycolic acid synthesis. INH is metabolized in References
the liver by acetylation and is excreted in urine. The various
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untoward effects of INH include epigastric discomfort, Chest 1972;62;71-7.
neurological manifestations, hepatitis, etc. These effects are 2. Hiraoka K, Nagata N, Kawajiri T, Suzuki K, Kurokawa S, Kido M, et al. Paradoxical
dose related. The lupus phenomenon, which has also been pleural response to antituberculous chemotherapy and isoniazid-induced lupus:
reported with INH, is an idiosyncratic reaction.[1] There are Review and report of two cases. Respiration 1998;65:152-5.
only a few cases of INH-induced pleural effusion described in 3. Majed SA. Study of paradoxcial response to chemotherapy in tuberculous pleural
effusion. Respir Med 1996;90:211-4.
literature.[2] INH-induced effusion usually begins 3-12 weeks 4. Afghani B, Lieberman JM. Paradoxical enlargement or development of
after starting chemotherapy and regresses after change of intracranial tuberculomas during therapy: Case report and review. Clin Infect Dis
therapy or introduction of steroids or both.[2] Although many 1994;19:1092-9.

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