Unexplained deterioration during antituberculous therapy in children and adolescents: clinical presentation and risk factors

Abstract

Background: Patients may unexpectedly deteriorate clinically and/or radiographically during the course of appropriate treatment for tuberculosis. These events have been extensively studied in human immunodeficiency virus-positive patients; however, there are few data about immunocompetent children and adolescents.

Methods: We studied all human immunodeficiency virus-negative patients treated for tuberculosis at our center between January 2002 and July 2009. Demographics, sites of disease at diagnosis and deterioration, and actions at the time of deterioration were reviewed. Cases were compared with patients who remained well during therapy.

Results: Unexplained deteriorations occurred in 15 of 110 patients (14%), all of whom were receiving directly observed therapy. The median time to deterioration was 80 days (range, 10-181 days). Enlarging intrathoracic lymphadenopathy often leading to severe airway compromise was common (7 of 15 patients). Four patients developed symptoms at sites remote from primary disease, including pericardial and pleural effusions and abdominal masses. Corticosteroid therapy was initiated in 9 patients. Deterioration was associated with multiple sites of disease at diagnosis (P = 0.02) and weight-for-age ≤25th percentile (P = 0.03).

Conclusions: Deteriorations during therapy occur frequently among immunocompetent children and may present months into treatment as clinically significant events. Those with lower weight-for-age percentiles and with multiple sites of disease at initial presentation are more likely to deteriorate. Many patients improve with corticosteroids, supporting an immunopathologic basis for many of these episodes. These deteriorations can be difficult to distinguish from drug resistance, treatment failure, or infection with other pathogens.