Paradoxical reaction to the treatment of tuberculosis uncovering previously silent meningeal disease

Abstract

The development of paradoxical clinical worsening following initiation of tuberculosis treatment may complicate the clinical course of both HIV-infected and uninfected patients. We report a severe manifestation of the so called paradoxical reaction to the treatment of tuberculosis that unmasked previously silent meningeal disease in a 34-year-old HIV-infected male patient. Key-words: AIDS. Antiretroviral therapy. Paradoxical reaction. Tuberculosis. Tuberculous meningitis.Resumo O desenvolvimento de piora clínica paradoxal como resposta ao início do tratamento da tuberculose pode complicar a evolução de pacientes com e sem infecção pelo HIV. Apresentamos uma grave manifestação da chamada reação paradoxal ao tratamento da tuberculose, que revelou doença meníngea previamente silenciosa em um paciente HIV-positivo de 34 anos. Palavras-chaves: AIDS. Meningite tuberculosa. Reação paradoxal. Terapia anti-retroviral. Tuberculose. Concomitantly treating active tuberculosis (TB) and HIV infection is a challenging task. There is a great potential for adverse effects and clinically significant pharmacological interactions. The development of paradoxical clinical worsening on TB treatment may further complicate patient management. We report a life-threatening manifestation of paradoxical worsening following TB treatment initiation in an antiretroviral (AR)-experienced patient. CASE REPORTA 34-year-old HIV-infected male patient with previous experience to the HIV reverse transcriptase inhibitors zidovudine and didanosine, to the HIV protease inhibitor saquinavir and on Pneumocystis carinii prophylaxis developed an enlarging cervical mass associated with a 2-month history of fever, weigh loss and malaise. At that point laboratory evaluation showed mild anemia (hemoglobin 11,3mg/dL), 60 CD4 cells/mm 3 and a plasma HIV viral load of 25,000 copies/mL (all viral load measurements were performed using the nucleic acid sequence-based amplification assay). Chest X-ray was normal. He had never had an opportunistic disorder but was treated for pleural TB during early adulthood. Histopathology disclosed TB lymphadenitis and Mycobacterium tuberculosis grew from the node aspirate. Rifabutin (as an alternative rifamycin to be combined with a protease inhibitor) at a dose of 150mg/day, isoniazid, pyridoxine and pyrazinamide were started and the AR regimen was changed to stavudine, lamivudine and indinavir. He significantly improved and remained well until ten weeks later when recrudescence of fever and severe headache developed. Signs of meningeal irritation were absent, as were cognitive, behavioral or focal neurologic abnormalities. Computed tomography of the brain was normal. Cerebrospinal fluid (CSF) studies revealed marked pleocytosis (220 cells/mm 3 , 71% polymorphonuclear, 29% mononuclear cells), glucose 52mg/dL and elevated protein (156mg/dL) and were negative for acid-fast bacilli, mycobacterial cultures, other infectious agents and neoplastic cells. Ophthalmologic examination disclosed TB choroidal nodules (previous evalu...

Choroidal tuberculoma showing paradoxical worsening in a patient with miliary TB

“…4 The worsening of TB symptomatology and lesions in response to ATT has previously been reported and called ''paradoxical reaction'' by some investigators. 5,6,7 Since the first report of paradoxical reaction in 1890 by Robert Koch, the paradoxical worsening of tuberculosis after initiation of ATT has been well documented in systemic TB, including intracranial tuberculomas, 8 meningeal disease, 9 tuberculous meningeal radiculitis 10 and pleural effusion. 11 However, ocular paradoxical worsening associated with TB has been reported only rarely.…”

Risk Factors for Development of Paradoxical Response During Antituberculosis Therapy in HIV-Negative Patients

“…. Paradoxical worsening of pre-existing pulmonary and extrapulmonary tuberculosis has been increasingly reported in HIV-positive patients, which produces a diagnostic challenge to caring infectious disease and respiratory physicians [5,6,7,8,9,10,11,12,13,14,15,16]. In recent studies, this condition was found in 11-36% of patients receiving highly active antiretroviral therapy (HAART) [7,8,15].…”

A case of isoniazid-resistant miliary tuberculosis in which tuberculous meningitis paradoxically developed despite systemic improvement

“…Generally, paradoxical worsening does not require a change of therapeutic regimen, but our case required a change. Most cases of paradoxical worsening in patients with intracranial tuberculosis are caused by tuberculomas in the brain parenchyma [8], and there are few reports of paradoxical worsening in tuberculous meningitis [13].…”