Acute respiratory distress during paradoxical reaction to antituberculous therapy in an 8-month-old child.

Paradoxical reaction during antituberculosis treatment (ATT) is commonly seen as tuberculous lymphadenitis of peripheral lymph node, cerebral tuberculomas, pulmonary infiltrates, and pleural disease. This phenomenon is more commonly associated with extrapulmonary tuberculosis and disseminated tuberculosis. Respiratory distress, as presentation of paradoxical reaction, is rare. We report an 8-month-old child with primary progressive tuberculosis without mediastinal adenopathy, who developed paradoxical reaction with extensive mediastinal adenopathy within 15 days of ATT and presented with severe respiratory distress. The child responded to short course of high-dose steroids.

INTRODUCTION

A paradoxical reaction in tuberculosis (TB) is temporally related to recovery of the immune system, which causes clinical or radiological worsening of pre-existing TB lesions or development of new lesions during antituberculosis treatment (ATT). Sometimes, it can be confused with secondary bacterial infection, resistance to ATT, and/or poor compliance. We report an 8-month-old child with primary progressive pulmonary TB who developed acute respiratory distress (paradoxical reaction) during ATT that responded to high-dose steroids without modification of ATT.

CASE REPORT

An 8-month-old girl presented with complaints of cough and noisy breathing since 1 month. There was no history of contact with known TB. She had been treated with various antibiotics for the same, but there was no response to therapy. On examination, she was febrile and tachypneic (respiratory rate of 60/min) and subcostal retractions were present. She was malnourished (wt-6 kg). Respiratory system examination showed decreased air entry in left upper lobe and right middle lobe with bilateral crepitations. Other systems were normal. On investigation, her hemoglobin was 10.1 gm/dl, white cell count was 13,700/cumm (differential count-polymorphs 61% and lymphocytes 39%), and erythrocyte sedimentation rate (ESR) was 5 mm at end of 1 h. Blood Bactec culture did not grow any organism. Her chest X-ray was suggestive of consolidation in right middle zone, left upper zone, and left lower zone. High resolution CT (HRCT) chest was suggestive of bronchopneumonia without any lymphadenopathy [Figure 1]. Her HIV ELISA was negative and echocardiography showed pericarditis. Sweat chlorides were normal. Bronchoalveolar lavage (BAL) showed acid fast bacillus (AFB) on smear. Hence, patient was started on four drugs ATT (isoniazid 5 mg/kg, rifampicin 10 mg/ kg, ethambutol 20 mg/kg, and pyrazinamide 30 mg/kg) to which she responded and fever spikes decreased, and respiratory distress decreased. Patient was discharged and asked to follow-up in TB OPD after 1 week.

Figure 1

Initial HRCT showing right mid zone and left upper zone and lower zone consolidation

One week later, patient presented with fever, cough, increased respiratory activity, and difficulty in feeding. On examination, patient was febrile with respiratory rate of 72/min. Respiratory system examination showed decreased air entry on left side with rhonchi on right side. Patient was readmitted and investigated. Hemoglobin was 9.3 gm/dl and white cell count was 35,000/cumm (polymorphs 84% and lymphocytes 16%). Chest X-ray was suggestive of opacity in left side and trachea was shifted to right side. HRCT chest showed enlarged necrotic lymph nodes in right paratracheal, aortopulmonary, precarinal, subcarinal, and both hilar regions with splaying of pulmonary artery and carina. Also, there was mass effect on bronchus intermedius and left main bronchus with stretching of left pulmonary artery [Figure 2]. Hence, diagnosis of paradoxical reaction to ATT was made and patient was started on prednisolone (2 mg/kg/day) but she did not respond. The dose of prednisolone was increased to 4 mg/kg/day and ATT was continued to which the child gradually responded. Steroids were gradually tapered to 2 mg/kg/day over next 15 days and repeat X-ray chest after 15 days showed complete resolution. Patient was subsequently discharged and is on regular follow-up.

Figure 2

HRCT after 2 weeks of ATT showing enlarged necrotic lymph nodes in right paratracheal, aortopulmonary, precarinal, subcarinal, and both hilar regions with splaying of pulmonary artery and carina. Also, there was mass effect on bronchus intermedius and left main bronchus with stretching of left pulmonary artery

DISCUSSION

Paradoxical reaction to antituberculous therapy was first described in 1955 by Chloremis.[1] It is defined as the clinical or radiological worsening of pre-existing TB lesions or the development of new lesions during antitubercular treatment and that is temporally related to recovery of the immune system.[2] It is identified in 6–25% of patients receiving antituberculosis therapy.[3-5] Though immune recovery syndromes are commonly seen in HIV-positive patients in form of IRIS, paradoxical reaction can also occur in patients with TB.[6] This phenomenon is more commonly associated with extrapulmonary tuberculosis and disseminated tuberculosis.[3] Paradoxical reactions usually present as peripheral lymphadenopathy, cerebral tuberculomas, or pleural effusion. Abdominal tuberculosis, presenting as paradoxical reaction, has been rarely reported.[3-578]

Time of development of paradoxical reaction ranges from 14 to 270 days after initiation of antituberculosis treatment. In our patient, paradoxical reaction was observed within 15 days of starting ATT. Acute respiratory distress syndrome (ARDS) manifesting as a paradoxical response to initiation of anti-TB medication is very rarely noted in patients with pulmonary tuberculosis.[9] Though our patient did not have ARDS, he presented as severe respiratory distress due to obstruction of bronchus by enlarged mediastinal glands. Pathogenesis of this response is not yet clear. It is mostly attributed to decrease in suppressor mechanisms related to active tuberculosis infection and strengthening of delayed hypersensitivity response of the host. Following bactericidal tuberculosis chemotherapy, there is release of large amounts of tuberculoprotein and other cell wall products which initiate a cascade of cellular and cytokine inflammatory response, causing local tissue damage which can be extensive and severe.[6] The clinical severity of paradoxical reaction is dependent on the appropriateness of immune recovery. Diagnosis is mainly confused with secondary infections, inadequate therapy or drug resistance, poor compliance, and side effect of antituberculosis therapy.[6] In our patient, initial HRCT showed no mediastinal adenopathy whereas a repeat HRCT after 15 days of ATT showed extensive mediastinal adenopathy suggestive of paradoxical reaction. While paradoxical reactions are usually self-limited, respiratory failure and death can occur. Mild paradoxical reaction does not require specific treatment and no alternation in the antituberculosis regimen is needed, but for severe paradoxical reaction such as large intracranial tuberculomas causing obstructive hydrocephalus, massive pleural effusion, and development of deep seated abscesses, a combination of medical and surgical treatment should be considered.[8] Sometimes use of anti-inflammatory therapy is needed, e.g., corticosteroid in short-course by oral route is preferred.[10] In our patient, steroids in higher doses for a short time helped in relieving symptoms as well as led to radiological resolution.

CONCLUSION

Paradoxical reactions should always be considered in patients who have clinical or radiological worsening on antituberculous therapy especially when compliance is proper and patient develops lymphadenopathy, pleural effusion, or cerebral tuberculomas on therapy.