Clinical Spectrum of Paradoxical Deterioration During Antituberculosis Therapy in Non-HIV-Infected Patients

Abstract

Paradoxical deterioration during antituberculosis therapy, defined as the clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions in a patient who initially improves, remains a diagnostic dilemma. Although different clinical presentations of paradoxical response have been described, a systematic analysis of the entity in non-HIV-infected patients is lacking. Reported here are two cases of paradoxical deterioration in which sequential changes in lymphocyte counts and tuberculin skin test results are emphasized. In addition, 120 episodes of paradoxical response after antituberculosis treatment were reviewed. Of the total 122 episodes, 101 (82.8%) were associated with extrapulmonary tuberculosis. The median time from commencement of treatment to paradoxical deterioration was 60 days. The median time to onset of central nervous system manifestations (63 days) was longer than the time to onset of manifestations at other sites (56 days) ( P=0.02). Development of new lesions in anatomical sites other than those observed at initial presentation was observed in 31 (25.4%) episodes. A surge in the lymphocyte count, accompanied by an exaggerated tuberculin skin reaction, was observed in our patients during the paradoxical deterioration, analogous to the findings in HIV-positive patients. Treatment of the paradoxical response included surgical intervention (60.7%) and administration of steroids (39.3%). The use of steroids appeared to be safe in this series, as 95% of the Mycobacterium tuberculosis isolates were susceptible to first-line antituberculosis therapy.

Reacción paradojal en meningitis tuberculosa. Presentación de un caso

“…12 L a r e a c c i ó n p a r a d o j a l c o n s i s t e e n e l empeoramiento clínico y/o radiológico, o la aparición de nuevas lesiones no atribuibles al curso habitual de la tuberculosis, en un paciente que inicialmente ha mejorado con el tratamiento antituberculoso y en quien la reacción paradojal ocurra, al menos, luego de dos semanas del inicio de este. 3 Los pacientes VIH positivos pueden presentar reacción paradojal al iniciar el tratamiento antirretroviral y empeoramiento de las lesiones tuberculosis asociado al síndrome de reconstitución inmune. 13 Pero la aparición o el agrandamiento de tuberculomas cerebrales como manifestación paradojal se ha descrito más frecuentemente en pacientes VIH negativos 4 durante el tratamiento de tuberculosis meníngea, como en el caso que presentamos.…”

“…3,4 El aumento de la resistencia del Mycobacterium tuberculosis (M. tuberculosis) a fármacos observado en los últimos años genera mayor preocupación ante la aparición de una reacción paradojal durante el tratamiento. Se presenta el caso de un niño con meningitis tuberculosa que, luego de un mes de tratamiento, presentó una reacción paradojal.…”

Gastrointestinal tract pseudo-obstruction or obstruction due to Mycobacterium tuberculosis breakthrough

“…The worsening should not be expected in the normal course of the disease and it must occur at least two weeks after the initiation of treatment. 6 Urakami suggested that a paradoxical response might be caused by an allergic reaction of the host to the tubercle bacilli. 7 A paradoxical reaction might occur in either pulmonary or extrapulmonary areas.…”

A clinical study on laryngeal manifestations of tuberculosis

“…12 It was seen in one patient with tuberculous pleural effusion who developed hilar and mediastinal adenopathy. In this patient, the nodal size regressed on addition of oral steroids for 1month to ATT.…”