Saudi J Kidney Dis Transplant 2007;18(3):414-418 © 2007 Saudi Center for Organ Transplantation

Saudi Journal of Kidney Diseases and Transplantation

Case Report Tuberculosis After Renal Transplantation: A Case Report Omar Salem Khattab, Omar Abdulwahid Theeb Renal Transplant Center, Medical City Teaching Hospital, Baghdad, Iraq

ABSTRACT. Renal transplant recipients are susceptible to a variety of infections with both common and opportunistic pathogens as a result of immunosuppressive therapy. We report herein a case of a 32-year-old female renal transplant recipient who developed pulmonary tuberculosis with supraglotic mass causing suffocation, 1.7 years after undergoing renal transplantation. She responded well to a combination of tracheostomy and antituberculous therapy. Although tuberculosis is a common infection in transplant recipients, its presentation as a supraglotic mass is unusual. Keywords: Immunosuppression, Renal transplantation, Tuberculosis Introduction Renal transplant recipients are susceptible to a variety of infections with both common and opportunistic pathogens as a result of immunosuppressive therapy.1 These infections cause significant morbidity and mortality. 2 In developing countries, poor socioeconomic conditions contribute to higher rates of infections in such immunosuppressed patients.3 Reprint request and correspondence to: Dr. Omar Salem Khattab Baghdad University, College of Medicine P.O. Box 19503, Baghdad, Iraq e-mail: [email protected]

Little attention has been given to mycobacterial infections compared to other opportunistic infections, such as Pneumocystis carinii and Cytomegalovirus, in renal transplant recipients.4 Although earlier reports mentioned about the rarity of tuberculosis (TB) in renal transplant recipients, 5 more recent ones have documented a high incidence of TB in these patients. 6,7 Apart from the high incidence, TB carries significant morbidity and mortality and may jeopardize the function of renal allograft. 8 We report herein a case of pulmonary TB with supraglotic mass causing suffocation in a renal transplant recipient, 1.7 years after renal transplantation.

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Khattab OA, Theeb, OA

Figure 1. Chest X Ray demonstrated lobar pneumonia

Case Report A 32-year-old female from the south of Iraq was referred to the Renal Transplant Center at the Medical City Teaching Hospital in Baghdad. She was suffering from chronic renal failure secondary to chronic glomerulonephritis and had received a living-related-donor renal transplant in October 2004. She had an uneventful postoperative course and was maintained on azathioprine 50 mg/day, cyclosporine 200 mg/day, prednisolone 10 mg/day, and diltiazem 120 mg/day. She had normal allograft function, with the serum creatinine being 0.8 mg/dl. About 1.7 years after transplantation, she presented with complaints of fever, sore throat, productive cough, fatigue, and weight loss of one month’s duration. She had no previous history of TB or history of contact with a tuberculous patient. The tuberculin skin test and chest X ray of patient and her donor were normal prior to transplant. No chemoprophylaxis for TB was given in the post transplant period. Physical examination

revealed an ill-looking pale patient, with a temperature of 39°C, blood pressure of 120/70 mmHg, pulse rate of 80/min, tender cervical and submental lymph nodes, and expiratory rhonchi. There was no hepatosplenomegaly. Laboratory investigations revealed hemoglobin (Hb) of 12 g/dl, white blood cell count of 7.200/mm 3, platelet count of 200,000/mm3, and ESR of 95 mm/hour. The blood film showed normochromic normocytic anemia; prothrombin time was 14 seconds, partial thromboplastin time was 35 seconds, INR was 1.2, and bleeding time was 1.3 minutes. The serum sodium was 130 mmol/L; potassium, 5.5 mmol/L; calcium, 1.8 mmol/L; phosphate, 1.1 mmol/L; blood urea, 64 mg/dl; serum creatinine, 1.4 mg/dl; and fasting blood sugar was 5.8 mmol/L. Liver function tests and lipid profile were normal. Hepatitis and human immunodeficiency virus screening were negative. The patient was positive for CMV IgG; while she was negative for CMV IgM, EBV IgG and IgM, Widal and Rosebengol

Tuberculosis after renal transplantation

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Figure 2. Chest X Ray demonstrated lobar patch with cavitation

tests, and VDRL. The serum protein electrophoresis, antinuclear factor assay, and C-reactive protein were normal. ENT examination revealed chronic tonsillitis. Abdominal ultrasonography showed normal renal allograft. Urine, throat, and nasal swab cultures were negative. Chest X Ray showed lobar pneumonia (Figure 1). The patient was treated with ampiclox 500 mg four times daily, ciprofloxacin 500 mg twice daily, and metronidazole 500 mg thrice daily. Two weeks later, she developed vomiting, difficulty in swallowing solid food, stridor and became toxic, with significant leukopenia (white blood count 800/mm3); pulse oxymetry revealed oxygen saturation of 50%. Emergency tracheostomy was performed, and laryngoscopic examination revealed a supraglotic mass. Biopsy was taken and the possibility of lymphoma was considered. Tracheal wash and three successive sputum tests were positive for AFB. The supraglotic mass biopsy further confirmed the diagnosis of TB. Repeat chest X Ray revealed lobar patch with cavitation (Figure 2). Antituberculous treatment was started with

rifampicin 600 mg/day, isoniazid 300 mg/day, ethambutol 25 mg/kg/day, and pyrazinamide 20 mg/kg/day. Within two weeks of this treatment, significant improvement occurred, tracheostomy was closed, and she was able to swallow normally. Subsequently, the patient was discharged from hospital with normal renal function and disappearance of the supraglotic mass. She remained healthy at last follow-up. Discussion Tuberculosis is a common opportunistic infection in renal allograft recipients worldwide. Its incidence, as reported in the literature, varies according to ethnic and geographic factors from less than 1% in the West9 to 15% in some developing countries.10 The incidence of TB among transplant recipients is 37- to 50-fold higher than that among the general population.11 This increased incidence is believed to be related to the effect of immunosuppressive drugs used in these patients, especially steroids, azathioprine, and anti-lymphocyte serum.12 The dose of steroids may be

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critical. Doses of 10 mg or less of prednisolone are rarely associated with TB; however, higher doses, especially when used with azathioprine, are associated with increased risk of developing TB.13 In addition, the presence of uremia before transplantation may contribute to this increased susceptibility by altering phagocytosis, bactericidal activity, and lymphocyte transformation.14 TB in these patients is predominantly the result of reactivation of an old dormant tuberculous focus. Rarely, it is caused by nosocomial acquisition or donor transmission.8 Pulmonary TB continues to be the most common form of TB in renal transplant recipients.8 Chest radiograph is abnormal in the majority of such patients with TB, showing focal infiltrates, nodules, military pattern, pleural effusion, and/or diffuse interstitial infiltrates.8 The clinical features of TB can be unusual and may be masked because of the blunted response to infection. 4,6,7 In addition, extrapulmonary lesions are more frequent in patients following transplantation compared to patients without immunosuppression.8 Disseminated TB is common in renal transplant patients, accounting for 40% of cases, in contrast to the 0.6–1.4% incidence in the general population.8 Disseminated TB in these patients commonly presents as fever of unknown origin.8 The overall mortality among renal allograft recipients with TB is 29%.8 Treatment of TB in renal transplant patients is not different from that in the normal host. However, the use of rifampicin must be undertaken with caution because of its frequent drug interaction, and blood levels of immunosuppressive drugs should be monitored.7,8 Although the issue of chemoprophylaxis against TB has remained controversial, isoniazid prophylaxis for highrisk patients is desirable.8,10

Khattab OA, Theeb, OA

In conclusion, TB is a common and serious condition in renal transplant recipients. Because the infection carries significant morbidity and mortality and may jeopardize the function of renal allograft, especially when there is delay in diagnosis and treatment, physicians who treat renal transplant recipients should be familiar with the manifestations of mycobacterial disease in this group of patients. A thorough search for TB is mandatory during pre- and posttransplant follow-up. Chemoprophylaxis against TB with isoniazid for high-risk patients seems advisable. References 1. Batata AM. Pulmonary tuberculosis in a renal transplant recipient. JAMA 1977;237: 1465-7. 2. Whinnearls CG, Lane DJ, Kurtz J. Infectious complications after renal transplantation. In: Morris PJ, ed. Kidney Transplantation: Principles and Practice, 2nd edition. New York: Grune and Stratton, 1984:427-67. 3. Hussain Z, Naqvi R, Hashmi A, Hafiz S, Naqvi R, Rizvi A. Tuberculosis in renal transplant recipients. Transplant Proc 1993;24:1912-5. 4. Millar JW, Horne NW. Tuberculosis in immunosuppressed patients. Lancet 1979;1:1176-9. 5. Lloveras J, Peterson PK, Simmon RL, Najarian JS. Mycobacterial infections in renal transplant recipients: seven cases and review of the literature. Arch Intern Med 1982;62:359-62. 6. McWhinney N, Khan O, Williams G. Tuberculosis in patients undergoing maintenance hemodialysis and renal transplantation. Br J Surg 1981;68:408-11. 7. Klote MM, Agodoa LY, Abbott K. Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000. Am J Transplant 2004:4(9):1523-8.

Tuberculosis after renal transplantation

8. Hussam A, Faraj SA, Haider A. Renal allograft tuberculosis. Ann Saudi Med 2002:22:346-8. 9. Neff TA, Hudgel DW. Miliary tuberculosis in a renal transplant recipient. Am Rev Resp Dis 1973;108:677-8. 10. Navqi SA, Hussain M, Askari H, et al. Is there a place for prophylaxis against tuberculosis following renal transplantation? Transplant Proc 1992;24:1912-4. 11. Ho KJ. Galloping caseous pneumonia with miliary dissemination in a renal transplant recipient: emphasis on pretransplant detection and prophylaxis. Nephron 1992;62:363-4. 12. Mullerova M, Pekarek J, Nouza K, Svejcar J, Trnka L, Matousek V. Immunosuppression and experimental tuberculosis. II. The effects of immunosuppressive agents and antilymphocyte serum on the organ dissemination of mycobacteria and the development of specific delayed hypersensitivity. Bio-medicine 1974:20:390-7.

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13. Walker JF, Cronin CJ, O’Nell S, McNulty J, Hanson JS. Tuberculosis affecting a cadaveric renal allograft. Clin Nephrol 1982;17:262-5. 14. Montgomerie JZ, Kalmanson GM, Guze LB. Leukocyte phagocytosis and serum bactericidal activity in chronic renal failure. Am J Med Sci 1972;264:385-93. 15. Dooley DP, Carpenter JL, Rademacher S. Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin Infect Dis 1997;25;872-87.

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Figure 1. Chest X Ray demonstrated lobar pneumonia. Case Report. A 32-year-old female from the south of ... skin test and chest X ray of patient and her donor were normal prior to transplant. No chemoprophylaxis for TB ... The blood film showed normochromic normocytic anemia; prothrombin time was. 14 seconds, partial ...

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