A 62-year-old male of Pakistani origin, who had undergone orthotopic liver transplantation (OLT) for hepatitis C cirrhosis 4 years previously, presented with increasing confusion, lethargy, and vomiting of 4 days' duration. There were no specific localizing neurological signs. There was no history of fever, weight loss, or respiratory problems. He did not give any history of having contracted tuberculosis (TB), although his sister had been treated for pulmonary TB 5 years previously. The patient had been resident in the United Kingdom for more than 30 years and traveled to Pakistan every 2 to 3 years but had not made any trips after his transplant. A pretransplant chest X-ray had not revealed any evidence of TB, and a Mantoux test had been negative. He had received 300 mg of isoniazid (INH) daily for 6 months post-OLT for latent TB infection according to the unit protocol for high-risk patients. His posttransplant course had been largely uneventful with no episodes of acute rejection, and cyclosporine and azathioprine immunosuppression was maintained. CT, computed tomography; INH, isoniazid; OLT, orthotopic liver transplantation; TB, tuberculosis. A contrast-enhanced computed tomography (CT) scan of the brain showed discrete ring-enhancing lesions in the right occipital lobe and the cerebellum with surrounding vasogenic edema and a mass effect (Fig. 1). There were additional pulmonary lesions on a chest CT scan. A stereotactic brain biopsy revealed a liquefied purulent material, from which Mycobacterium tuberculosis grew in a culture. The patient was started on triple-drug antitubercular therapy with INH, rifampicin, and pyrazinamide with pyridoxine for 9 months, following which his neurological status improved. His graft function remained stable throughout his treatment course, but he required multiple readmissions for social reasons. A repeat CT scan 3 years after his craniotomy showed complete resolution of the lesion (Fig. 2). He made a complete recovery and remains well 40 months after the completion of treatment. Ring-enhancing lesion in the occipital lobe with surrounding edema. Three-year follow-up CT scan showing complete resolution of the lesion. The incidence of TB after organ transplantation varies from 0.8% to up to 15% in developing countries.1, 2 The diagnosis of posttransplant TB infection can be challenging, and patients may not present with classical clinical features. Disseminated and extrapulmonary disease is common among solid-organ transplant recipients, although intracranial TB infection is uncommon.3, 4 Risk factors for the development of posttransplant TB include diabetes, chronic liver disease, and a history of TB.5 INH prophylaxis is used for high-risk populations in most transplant units, with debatable benefit and the risks of hepatotoxicity and development of drug-resistant strains.3, 6, 7 A recent randomized control trial for INH prophylaxis in renal transplant recipients revealed a nonsignificant trend toward protection from active disease post-prophylaxis.8 Immigrants from areas of high TB incidence, such as the Indian subcontinent, may benefit from a treatment for latent TB infection, which may range from 6 to 9 months. This patient had received a 6-month course of INH prophylaxis after OLT, which is standard in this unit. Although it is possible that this patient acquired a new infection after the INH treatment because of re-exposure, antitubercular therapy may delay the emergence of active infection.9 In rare cases, TB infection can also be acquired from the donor.10 An intracerebral malignancy such as lymphoma or intracerebral metastases as well as abscesses can present with ring-enhancing lesions on a contrast-enhanced CT scan and should be considered in the differential diagnosis. The final diagnosis is based on a histological examination of tissue or the growth of M. tuberculosis in a culture. Antitubercular therapy in solid-organ transplant recipients poses special problems because of drug interactions with immunosuppressive regimens, which can precipitate rejection.11 INH, rifampicin, and pyrazinamide can cause significant derangement of liver function, and close liver monitoring is necessary during treatment. Alternative treatment regimens using rifabutin have been described with acceptable results and good graft survival.12 In summary, intracranial tubercular infection following OLT is extremely rare but should be considered in the differential diagnosis of a ring lesion on a head CT scan, especially in ethnic groups with a high background incidence of TB. To our knowledge, this is only the second such case after OLT reported in the literature.4 In contrast to the previously reported patient, this patient made a complete recovery following 9 months of antitubercular therapy.
Read full abstract