A 5½-year-old girl was admitted with low grade fever of 1 week duration, drowsiness of two days, signs of meningeal irritation and papilledema. CSF study showed pleocytosis; 150 cells/cumm3, 70% lymphocytes, with protein 88 mg/dL and sugar 32 mg/dL. Bacterial and AFB cultures of CSF were negative. CSF was also negative for TB PCR, HSV PCR and Cryptococcus. Her HIV ELISA was negative. Chest X-Ray showed right sided pneumonia, Mantoux test and gastric aspirate for AFB were negative. Initial completed tomography (CT) of brain revealed no abnormality. She was initially started on ceftriaxone and acyclovir. She had a history of contact with tuberculosis in grandfather. She had been started on INH chemoprophylaxis 1 year ago, but stopped after 1 month. Repeat CT brain after 1 week showed hydrocephalus. After 1 week, in view of poor improvement and history of contact with tuberculosis, X-ray chest findings and compatible neuroimaging findings, a diagnosis of CNS tuberculosis was made and ATT (SHRZ) was started along with oral steroids. She improved slowly and was discharged after 1 month of daily ATT; streptomycin was changed to ethambutol at discharge.

Fig. 1 CT Scan showing hydrocephalus, brain edema, tuberculoma in right temporal region and exudates around circle of Willis.

Six weeks after initial presentation (one week after discharge), she was re-admitted with worsening of the condition. She had fever, vomiting, frontal headache of three days duration, papilledema and anisocoria. Repeat CT scan with contrast revealed, moderate hydrocephalus, diffuse cerebral edema, abnormal nodular enhancement in right temporal region suggestive of tuberculoma, and diffuse exudates around the Circle of Willis (Fig. 1). In addition to tuberculoma, there was also gyral enhancement (Fig. 2). Repeat CSF study showed 570 cells: 60% polymorphs, protein 102 mg/dL, sugar 45 mg/dL and sterile cultures. Repeat Mantoux test was strongly positive (25 mm).

Fig. 2 CT Scan showing gyral enhancement.

In view of the clinical worsening and restoration of Mantoux positivity, the possibility of IRIS was considered. She was restarted on decongestive measures along with parenteral dexamethasone; ATT was continued. She stabilized over the next week and was discharged on ATT and oral prednisolone after 10 days of hospitalization. Prednisolone was tapered after 12 weeks and 0.5 mg/day was continued for total of 6 months, till the papilledema disappeared. She is now stable after follow-up of 6 months.

Diagnosis of CNS tuberculosis in this child was in accordance with the Modified Ahuja Criteria [4]. IRIS was diagnosed on the basis of clinical and CT findings, and restoration of Mantoux test positivity [5].

IRIS is common in HIV patients with or without tuberculosis, but rare in immuno-competent HIV-negative patients. Among the two types – paradoxical and unmasking – the diagnosis of paradoxical IRIS (worsening of symptoms/new manifestations of a known condition) was considered in this child. Unmasking IRIS (appearance of diseases not previously suspected that become apparent shortly after initiation of treatment) was unlikely in this case [6-8]. Apart from tuberculosis, IRIS can occur in herpes infections, hepatitis, fungal infections, human papilloma virus infections, malignancies and sarcoidosis.

IRIS is the result of a disordered immune recovery leading to dysregulated immune response to an antigen and resultant exaggerated inflammatory features within a milieu of pro-inflammatory cytokines [3]. In the diagnosis of IRIS, it should be ensured that deterioration is not due to non-adherence to treatment, insufficient therapy and development of resistance to specific therapy. If symptoms are not severe, watchful approach is recommended with anti-inflammatory agents and specific therapy [9]. In unmasking IRIS, specific antimicrobial therapy for the unmasked disease is also warranted with or without additional anti-inflammatory agents.