It Looked Like COVID-19, But It Was Not: The Importance of an Early Diagnosis of Disseminated Tuberculosis

To the Editors:

The improved hand hygiene, the universal masking, and the closure of schools reduced the spread of respiratory infections among children during the COVID-19 pandemic, and a decrease in admission to the Emergency Department was observed.¹ This pandemic aggravated an already suboptimal global tuberculosis (TB) response, and there was an increase in advanced forms of disease and intensive care requirement.²

An immunocompetent 4-year-old boy was admitted to the Pediatric Emergency Department with a 6-day history of fever and acute respiratory distress. Past medical history revealed a chronic failure to thrive. His family history highlighted a Romanian origin, parent’s consanguinity and a maternal pulmonary TB 6 years before.

On admission: respiratory rate 70 breaths/min, heart rate 180 beats/min and oxygen saturation 82% on room air. Physical examination revealed ill-appearing, skin pallor, severe respiratory distress, normal pulmonary auscultation and hepatomegaly. Laboratory studies were remarkable for elevated transaminases, and mild elevation of inflammatory markers (C-reactive protein 2.3 mg/dL). The chest radiograph showed a diffuse micronodular pattern (Fig. 1A). Rapid SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) at admission was negative. QuantiFERON test resulted positive on 2nd day, and a 4-drug anti-TB treatment was started. He developed an acute respiratory distress syndrome (ARDS) that required intubation for 10 days with lung-protective mechanical ventilation, prone ventilation and nitric oxide treatment and corticotherapy was added to the treatment on the 6th day. During the second week, the transaminases increased and a computed tomography was done (Fig. 1B,C). He remained afebrile from 5th day, with progressive improvement. Ocular fundus was normal, and brain magnetic resonance (MRI) revealed meningeal enhancement without tuberculoma (Fig. 1D); high doses of anti-TB drugs and corticoids were then applied.

FIGURE 1.

A: Chest radiograph: diffuse micronodular pattern compatible with miliary tuberculosis. B: Chest and abdominal CT: left para-aortic adenopathic block (arrow). Hepatomegaly without focal lesions. C: Chest CT: infiltrates adjacent to adenopathic block in left upper lobe with a bubble compatible with a lung cavitation (arrow); diffuse bilateral ground glass infiltrates. D: Cerebral MRI. Axial T1 +Gd. Leptomeningeal and cortical enhancement (arrow) with white matter dot lesions (arrow).

Mycobacterium tuberculosis complex DNA was detected in a tracheal aspirate sample by real-time PCR Xpert MTB/RIF Ultra on the 5th day. There were no mutations in the rpoB, katG and inhA genes; ethambutol was then discontinued on the 20th day. M. tuberculosis was isolated from liquid culture media (Bactec MGIT 960 and VersaTREK) from 3 tracheal aspirate samples. He received treatment for 1 year with favorable outcome.

The intrafamilial contact study revealed no reactivation of TB disease in his mother. A regional TB database (Spoligotyping and IS6110-RFLP) could determine the patient’s M. tuberculosis strain corresponded to the most prevalent pattern in our region (SIT42), that was different to the mother’s one studied 6 years before but coinciding with the pattern of a neighbor diagnosed with pulmonary TB at that time.

Disseminated tuberculosis remains rare in pediatric patients, especially in immunocompetent children, usually preceded by long-lasting unspecific symptoms.³

Communication with microbiologist and the availability of rapid TB microbiological diagnostic tests, were crucial to achieve an early diagnosis, to provide information about antimicrobial resistances and local patterns for epidemiological purposes.⁴ The early initiation of treatment, the respiratory care provided in the Pediatric Intensive Care Unit and the use of steroids, can explain the noteworthy favorable outcome, despite the clinical severity and the presence of several risk factors, such as young age, malnutrition, central nervous system involvement, ARDS and disseminated disease.³