Renal Transplantation in a Patient With Chronic Granulomatous Disease: Case Report B. Caliskana,*, H. Yazicib, M. Gulluogluc, Y. Caliskanb, A. Turkmenb, and M.S. Severb a Division of Pediatric Infectious Diseases, Department of Pediatrics, Istanbul University, Istanbul, Turkey; bDivision of Nephrology, Department of Internal Medicine, Istanbul University, Istanbul, Turkey; and cDepartment of Pathology, Istanbul University, Istanbul, Turkey
ABSTRACT Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.
C
HRONIC GRANULOMATOUS DISEASE (CGD) is caused by one of several mutations that structurally alter the enzyme NADPH oxidase [1]. The resulting phenotype is one of immunodeficiency, with affected individuals having serious recurrent bacterial and fungal infections and inflammatory granulomas. In this patient population, the frequency of end-stage renal disease (ESRD) is approximately 3%. The etiology is often multifactorial, attributed to the infections, amyloidosis, and necessary use of nephrotoxic anti-infective agents. Additionally, nephrotic-range proteinuria may occur, and native renal kidney biopsies may demonstrate a variety of histologies, including focal segmental glomerulosclerosis, membranous glomerulopathy (unpublished observations), chronic glomerulonephritis [2], and Henoch-Schonlein nephritis [3]. Regardless of etiology, renal replacement therapy is required in many patients, and the occurrence of chronic life-threatening opportunistic infections suggests that immunosuppression after renal transplantation could be contraindicated. A review of the literature has shown only 4 patients with CGD who underwent renal transplantation, and 2 of them had not undergone bone marrow transplantation [4,5]. In this report, we describe a living related renal transplantation patient with CGD who developed isolated hepatic tuberculosis abscess after kidney transplantation. To our knowledge, this is the first reported case of hepatic tuberculous abscesses without pulmonary involvement in a 0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.07.069
158
renal transplant recipient with CGD. The patient is unique in respect to pretransplantation disease status and underlying comorbidity. This case report also highlights the unexpected benign effects of immunosuppressive therapy in this patient population. CASE REPORT Y.M. was born in 1977, and until 14 years of age, he experienced only minor infections. In 1991, he was admitted to a hospital with a 2-week history of fever, fatigue, and weight loss. The physical examination revealed a body temperature of 39.5 C and no additional abnormalities. Routine laboratory test results showed marked evidence of inflammation. Although the chest radiograph was normal, ultrasound (US) of the abdomen showed 2 cystic masses in the subcapsular inferior posterior region of the right liver lobe. US-guided wedge biopsy and percutaneous drainage were performed, and these cystic masses were diagnosed as focal hepatic tuberculous abscesses by positive culture in Löwenstein-Jensen medium and necrotizing granulomatous inflammation in biopsy specimen. The patient was concomitantly started on systemic antituberculous therapy. At that time, the nitro blue tetrazolium test was performed twice and the score in each test was found as 0%, yielding a diagnosis of CGD. He stayed on isoniazid, rifampin, pyrazinamide, and ethambutol therapy for the first 2 months and continued with isoniazid and rifampin for *Address correspondence to Bahar Caliskan, MD, Division of Pediatric Infectious Diseases, Department of Pediatrics, Istanbul School of Medicine, Capa 34 390, Istanbul, Turkey. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 158e160 (2015)
RENAL TRANSPLANTATION AND CGD another 10 months. For the next 15 years he did not have any remarkable infectious disease under daily trimethoprim/sulfa 400/ 80 mg prophylaxis. At age 29, he presented with edema in the eyelids, hands, and ankles and a 3-month history of nausea and vomiting. Although the physical examination revealed no abnormalities, biochemical tests demonstrated a high serum creatinine level (8 mg/ dL) and marked proteinuria (1.4 g/d). Because the ultrasonography revealed bilateral small-sized kidneys, renal biopsy could not be performed and end-stage renal disease of unknown etiology was diagnosed. After 8 months of hemodialysis treatment, the patient presented for kidney transplantation from his mother. Both the donor and the recipient were counseled regarding the uncertain nature of the proposed transplantation. In June 2007, he underwent a technically uneventful living related renal transplantation from his human leukocyte antigen full-match mother. This full matching was probably due to consanguineous marriage between parents. The patient did not receive any induction therapy, and was maintained postoperatively on cyclosporine A (CsA) (trough C0 blood levels 200 to 300 ng/mL), mycophenolate mofetil (MMF; 1 g twice daily), and tapering doses of prednisone. In addition, he received viral, bacterial, and fungal prophylaxis with acyclovir 400 mg 4 times daily, trimethoprim/sulfa 800/160 mg daily, and fluconazole 100 mg daily. His postoperative recovery was complicated by a urinary system infection that required 14 days of intravenous meropenem treatment. Eventually, he was maintained on prednisone 5 mg daily, CsA 100 mg daily (leading to 24-hour trough levels of 50 to 150 ng/mL), MMF 1000 mg twice daily, and trimethoprim/sulfa 800/160 mg daily. Isoniazid prophylaxis 300 mg daily also was initiated 3 weeks before transplantation upon positive tuberculin skin test along with the history of previous tuberculous infection. This was done to prevent reactivation of tuberculosis under immunosuppressive therapy in this patient, who was already prone to the infection due to the underlying immunodeficiency. Isoniazid prophylaxis lasted until the first year after transplantation, when the patient quit taking isoniazid inadvertently. Over the ensuing year he gained weight and did not need to be hospitalized at any time for infection. However, he suffered from acne all over his body. At the 22nd month posttransplantation, he was admitted to our service with a history of fever and fatigue for 10 days. On physical examination, body temperature was 39.5 C, blood pressure 135/75 mm Hg, and heart rate 110 beats/min. Abdominal palpation revealed marked tenderness in the right upper abdominal quadrant. Routine laboratory tests showed marked evidence of inflammation: erythrocyte sedimentation rate 95 mm/h, highsensitivity C-reactive protein 105 mg/L (0 to 5 mg/L), and 20,000 leukocytes/mL. An abdominal US revealed 2 abscess-like masses in the subcapsular region of the diaphragmatic surface and anterior region of the right liver lobe. US-guided wedge biopsy and percutaneous drainage were performed, and these masses were diagnosed as focal hepatic abscesses by positive culture for methicillin-sensitive Staphylococcus aureus in medium. The patient was started on ampicillin/ sulbactam 1 g 4 times daily according to the glomerular filtration rate. Ziehl-Neelsen staining for acid-fast bacteria and culture in Löwenstein-Jensen medium were negative for tuberculosis. Control US of the abdomen at the first month of ampicillin/sulbactam treatment showed complete resolution of the abscess. Although the patient was on trimethoprim/sulfa prophylaxis, at the 50th month after transplantation he again was admitted to our service with fever. On physical examination, body temperature was 39.9 C, blood pressure 130/70 mm Hg, and heart rate 116 beats/min. Abdominal palpation revealed marked tenderness in the right upper abdominal quadrant. Routine laboratory tests showed marked evidence of inflammation: erythrocyte sedimentation rate 105 mm/h, high-sensitivity C-reactive protein
159
Fig 1. Foamy macrophages forming groups and scattered individually (arrows) throughout the liver parenchyma (200, hematoxylin and eosin stain). 84 mg/L (0 to 5 mg/L), and 13,400 leukocytes/mL. Serum creatinine was 2.2 mg/dL, and proteinuria was 0.4 g/d. Although the serum aminotransferase levels were normal, serum gamma-glutamyl transpeptidase was 221 U/L, alkaline phosphatase 909 U/L, and total bilirubin 0.68 mg/dL. An abdominal US revealed a normal hepatobiliary system. US-guided Tru-Cut liver biopsy was performed and revealed foamy structures and bright red staining by Ziehl-Neelsen stain within the cytoplasm of histiocytes (Fig 1), but no other evident signs of granulomatous inflammation. Culture performed from the biopsy material in Löwenstein-Jensen medium revealed Mycobacterium tuberculosis. The patient was diagnosed with hepatic tuberculosis reactivation. The patient was started on an antituberculous treatment regimen including isoniazid, rifampicin, pyrazinamide, and ethambutol at doses according to the creatinine clearance. At follow-up, he was asymptomatic. The serum CsA level was monitored more closely after initiation of rifampicin. The antituberculous treatment was ceased at the end of 1 year. The patient was still on clinical follow-up at 75 months posttransplantation, with a serum creatinine level of 1.7 mg/ dL, and was on a triple immunosuppressive regimen (CsA, MMF, prednisolone), isoniazid, and trimethoprim/sulfa prophylaxis.
DISCUSSION
CGD is a rare immune disorder that occurs in approximately 1 in 200,000 live births in the United States [1,6]. The primary genetic defect is caused by mutation on 1 of 4 genes, the most common being the x-linked gene gp91phox, which is also the most severe form. The 3 other known mutations, p22phox, p47phox, and p67phox, are autosomal recessive and tend to lead to clinically less severe disease. The mutation causes a failure of the NADPH oxidase enzyme complex in phagocytic cells to produce adequate reactive oxygen intermediates to promote intracellular killing [7]. In addition to the decreased immune response to engulfed organisms, these patients have dysregulation of the inflammatory response that is demonstrated clinically by their tendency to form noncaseating granulomas, manifested in the skin and subcutaneous soft
160
tissues, as well as in the lungs and other viscera. The underlying mechanism of this aberrance is not well elucidated [8]. Patients generally present early in life with recurrent infections of the lungs, skin, soft tissues, and abdominal viscera. The majority of these infections are caused by a few catalase-positive organisms, including Staphylococcus aureus, Burkholderia cepacia, and Serratia marcescens; Nocardia species; and Aspergillus species [9]. Many of these infections can be refractory to treatment and lifethreatening despite surgical debridement and protracted courses of aggressive antibiotic therapy. Drug-related toxicity from these repeated and often prolonged courses of antibiotics can result in liver failure, pulmonary fibrosis, and renal failure [10]. From the perspective of patient safety, there was ongoing concern that the need for T-cell suppression would result in an unacceptable level of overall immunosuppression in a patient with a pre-existing immunodeficiency. In CGD, patients have little to no effective phagocytic cell population. Additionally, renal transplant recipients are considered to be at special risk of reactivating old tuberculous lesions due to their clinically induced chronic immunosuppression. Of interest, in the present case, after renal transplantation, hepatic tuberculosis without granuloma formation was diagnosed and a marked improvement in the cutaneous manifestations of the disease was observed. That was probably due to therapeutic levels of immunosuppression, which might have resulted in a considerable decrease in granuloma formation. However, it should also be kept in mind that immunosuppression can obscure the diagnostic tests, such as causing a false-negative tuberculin skin test result. Because the symptoms often are masked by the immunosuppressive therapy, diagnosis of tuberculous infection may be delayed and the mortality might be as high as 30% [11]. Quadruple therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) is recommended as the antituberculosis protocol because of the increasing incidence of drugresistant tuberculosis. At least 1 year of medical therapy is generally required, as in many other extrapulmonary manifestations of tuberculosis [12]. Our patient also received a therapy course of 1 year, quadruple therapy for the initial 2 months and continuing with isoniazid and rifampin for the next 10 months. Extrapulmonary tuberculosis has a high incidence and high mortality in the posttransplantation
CALISKAN, YAZICI, GULLUOGLU ET AL
population [13]. Therefore, high attention should be given to its differential diagnosis in clinical practice. With early diagnosis and prompt effective treatment, the prognosis of hepatic tuberculosis is usually good. However, if there are indications for surgery or difficulties in diagnosis, surgical procedures along with antituberculous therapy could be adopted. The previous literature has reported only a few cases involving organ transplantation in CGD patients [4,5]. Nevertheless, the current report confirms and expands upon the prior conclusions that renal transplantation is possible and perhaps a preferred therapy in CGD patients with ESRD.
REFERENCES [1] Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, bio-chemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 2000;79:170e200. [2] Frifelt JJ, Schonheyder H, Valerius NH, Strate M, Starklint H. Chronic granulomatous disease associated with chronic glomerulonephritis. Acta Paediatr Scand 1985;74:152e7. [3] Kimpen J, Van Damme-Lombaerts R, Van den Berghe G, Proesmans W. Autosomal recessive chronic granulomatous disease associated with 18q-syndrome and end-stage renal failure due to Henoch-Schonlein nephritis. Eur J Pediatr 1991;150:325e6. [4] Bolanowski A, Mannon RB, Holland SM, et al. Successful renal transplantation in patients with chronic granulomatous disease. Am J Transplant 2006;6:636e9. [5] Peces R, Ablanedo P, Seco M. Amyloidosis associated with chronic granulomatous disease in a patient with a renal transplant and recurrent urinary tract infections. Nefrologia 2002;22:486e91. [6] Winkelstein JA, Marino MC, Johnston RB, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine 2000;79:155e69. [7] Rosenzweig SD, Holland SM. Phagocyte immunodeficiencies and their infections. J Allergy Clin Immunol 2004;113:620e6. [8] Jackson SH, Gallen JI, Holland SM. The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med 1995;182:751e8. [9] Segal BH, Holland SM. Primary phagocytic disorders in childhood. Pediatr Clin North Am 2000;47:1311e38. [10] Harbath S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH. The epidemiology of nephrotoxity associated with conventional amphotericin B therapy. Am J Med 2001;111:528e34. [11] Eastwood JB, Corbishley CM, Grange JM. Tuberculosis and the kidney. J Am Soc Nephrol 2001;12:1307e14. [12] Mert A, Ozaras R, Tabak F, Ozturk R, Bilir M. Localized hepatic tuberculosis. Eur J Intern Med 2003;14:511e2. [13] Aguado JM, Herrero JA, Gavaldá J, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Transplantation 1997;63:1278e86.
ABSTRACT Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.
C
HRONIC GRANULOMATOUS DISEASE (CGD) is caused by one of several mutations that structurally alter the enzyme NADPH oxidase [1]. The resulting phenotype is one of immunodeficiency, with affected individuals having serious recurrent bacterial and fungal infections and inflammatory granulomas. In this patient population, the frequency of end-stage renal disease (ESRD) is approximately 3%. The etiology is often multifactorial, attributed to the infections, amyloidosis, and necessary use of nephrotoxic anti-infective agents. Additionally, nephrotic-range proteinuria may occur, and native renal kidney biopsies may demonstrate a variety of histologies, including focal segmental glomerulosclerosis, membranous glomerulopathy (unpublished observations), chronic glomerulonephritis [2], and Henoch-Schonlein nephritis [3]. Regardless of etiology, renal replacement therapy is required in many patients, and the occurrence of chronic life-threatening opportunistic infections suggests that immunosuppression after renal transplantation could be contraindicated. A review of the literature has shown only 4 patients with CGD who underwent renal transplantation, and 2 of them had not undergone bone marrow transplantation [4,5]. In this report, we describe a living related renal transplantation patient with CGD who developed isolated hepatic tuberculosis abscess after kidney transplantation. To our knowledge, this is the first reported case of hepatic tuberculous abscesses without pulmonary involvement in a 0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.07.069
158
renal transplant recipient with CGD. The patient is unique in respect to pretransplantation disease status and underlying comorbidity. This case report also highlights the unexpected benign effects of immunosuppressive therapy in this patient population. CASE REPORT Y.M. was born in 1977, and until 14 years of age, he experienced only minor infections. In 1991, he was admitted to a hospital with a 2-week history of fever, fatigue, and weight loss. The physical examination revealed a body temperature of 39.5 C and no additional abnormalities. Routine laboratory test results showed marked evidence of inflammation. Although the chest radiograph was normal, ultrasound (US) of the abdomen showed 2 cystic masses in the subcapsular inferior posterior region of the right liver lobe. US-guided wedge biopsy and percutaneous drainage were performed, and these cystic masses were diagnosed as focal hepatic tuberculous abscesses by positive culture in Löwenstein-Jensen medium and necrotizing granulomatous inflammation in biopsy specimen. The patient was concomitantly started on systemic antituberculous therapy. At that time, the nitro blue tetrazolium test was performed twice and the score in each test was found as 0%, yielding a diagnosis of CGD. He stayed on isoniazid, rifampin, pyrazinamide, and ethambutol therapy for the first 2 months and continued with isoniazid and rifampin for *Address correspondence to Bahar Caliskan, MD, Division of Pediatric Infectious Diseases, Department of Pediatrics, Istanbul School of Medicine, Capa 34 390, Istanbul, Turkey. E-mail: [email protected] ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 158e160 (2015)
RENAL TRANSPLANTATION AND CGD another 10 months. For the next 15 years he did not have any remarkable infectious disease under daily trimethoprim/sulfa 400/ 80 mg prophylaxis. At age 29, he presented with edema in the eyelids, hands, and ankles and a 3-month history of nausea and vomiting. Although the physical examination revealed no abnormalities, biochemical tests demonstrated a high serum creatinine level (8 mg/ dL) and marked proteinuria (1.4 g/d). Because the ultrasonography revealed bilateral small-sized kidneys, renal biopsy could not be performed and end-stage renal disease of unknown etiology was diagnosed. After 8 months of hemodialysis treatment, the patient presented for kidney transplantation from his mother. Both the donor and the recipient were counseled regarding the uncertain nature of the proposed transplantation. In June 2007, he underwent a technically uneventful living related renal transplantation from his human leukocyte antigen full-match mother. This full matching was probably due to consanguineous marriage between parents. The patient did not receive any induction therapy, and was maintained postoperatively on cyclosporine A (CsA) (trough C0 blood levels 200 to 300 ng/mL), mycophenolate mofetil (MMF; 1 g twice daily), and tapering doses of prednisone. In addition, he received viral, bacterial, and fungal prophylaxis with acyclovir 400 mg 4 times daily, trimethoprim/sulfa 800/160 mg daily, and fluconazole 100 mg daily. His postoperative recovery was complicated by a urinary system infection that required 14 days of intravenous meropenem treatment. Eventually, he was maintained on prednisone 5 mg daily, CsA 100 mg daily (leading to 24-hour trough levels of 50 to 150 ng/mL), MMF 1000 mg twice daily, and trimethoprim/sulfa 800/160 mg daily. Isoniazid prophylaxis 300 mg daily also was initiated 3 weeks before transplantation upon positive tuberculin skin test along with the history of previous tuberculous infection. This was done to prevent reactivation of tuberculosis under immunosuppressive therapy in this patient, who was already prone to the infection due to the underlying immunodeficiency. Isoniazid prophylaxis lasted until the first year after transplantation, when the patient quit taking isoniazid inadvertently. Over the ensuing year he gained weight and did not need to be hospitalized at any time for infection. However, he suffered from acne all over his body. At the 22nd month posttransplantation, he was admitted to our service with a history of fever and fatigue for 10 days. On physical examination, body temperature was 39.5 C, blood pressure 135/75 mm Hg, and heart rate 110 beats/min. Abdominal palpation revealed marked tenderness in the right upper abdominal quadrant. Routine laboratory tests showed marked evidence of inflammation: erythrocyte sedimentation rate 95 mm/h, highsensitivity C-reactive protein 105 mg/L (0 to 5 mg/L), and 20,000 leukocytes/mL. An abdominal US revealed 2 abscess-like masses in the subcapsular region of the diaphragmatic surface and anterior region of the right liver lobe. US-guided wedge biopsy and percutaneous drainage were performed, and these masses were diagnosed as focal hepatic abscesses by positive culture for methicillin-sensitive Staphylococcus aureus in medium. The patient was started on ampicillin/ sulbactam 1 g 4 times daily according to the glomerular filtration rate. Ziehl-Neelsen staining for acid-fast bacteria and culture in Löwenstein-Jensen medium were negative for tuberculosis. Control US of the abdomen at the first month of ampicillin/sulbactam treatment showed complete resolution of the abscess. Although the patient was on trimethoprim/sulfa prophylaxis, at the 50th month after transplantation he again was admitted to our service with fever. On physical examination, body temperature was 39.9 C, blood pressure 130/70 mm Hg, and heart rate 116 beats/min. Abdominal palpation revealed marked tenderness in the right upper abdominal quadrant. Routine laboratory tests showed marked evidence of inflammation: erythrocyte sedimentation rate 105 mm/h, high-sensitivity C-reactive protein
159
Fig 1. Foamy macrophages forming groups and scattered individually (arrows) throughout the liver parenchyma (200, hematoxylin and eosin stain). 84 mg/L (0 to 5 mg/L), and 13,400 leukocytes/mL. Serum creatinine was 2.2 mg/dL, and proteinuria was 0.4 g/d. Although the serum aminotransferase levels were normal, serum gamma-glutamyl transpeptidase was 221 U/L, alkaline phosphatase 909 U/L, and total bilirubin 0.68 mg/dL. An abdominal US revealed a normal hepatobiliary system. US-guided Tru-Cut liver biopsy was performed and revealed foamy structures and bright red staining by Ziehl-Neelsen stain within the cytoplasm of histiocytes (Fig 1), but no other evident signs of granulomatous inflammation. Culture performed from the biopsy material in Löwenstein-Jensen medium revealed Mycobacterium tuberculosis. The patient was diagnosed with hepatic tuberculosis reactivation. The patient was started on an antituberculous treatment regimen including isoniazid, rifampicin, pyrazinamide, and ethambutol at doses according to the creatinine clearance. At follow-up, he was asymptomatic. The serum CsA level was monitored more closely after initiation of rifampicin. The antituberculous treatment was ceased at the end of 1 year. The patient was still on clinical follow-up at 75 months posttransplantation, with a serum creatinine level of 1.7 mg/ dL, and was on a triple immunosuppressive regimen (CsA, MMF, prednisolone), isoniazid, and trimethoprim/sulfa prophylaxis.
DISCUSSION
CGD is a rare immune disorder that occurs in approximately 1 in 200,000 live births in the United States [1,6]. The primary genetic defect is caused by mutation on 1 of 4 genes, the most common being the x-linked gene gp91phox, which is also the most severe form. The 3 other known mutations, p22phox, p47phox, and p67phox, are autosomal recessive and tend to lead to clinically less severe disease. The mutation causes a failure of the NADPH oxidase enzyme complex in phagocytic cells to produce adequate reactive oxygen intermediates to promote intracellular killing [7]. In addition to the decreased immune response to engulfed organisms, these patients have dysregulation of the inflammatory response that is demonstrated clinically by their tendency to form noncaseating granulomas, manifested in the skin and subcutaneous soft
160
tissues, as well as in the lungs and other viscera. The underlying mechanism of this aberrance is not well elucidated [8]. Patients generally present early in life with recurrent infections of the lungs, skin, soft tissues, and abdominal viscera. The majority of these infections are caused by a few catalase-positive organisms, including Staphylococcus aureus, Burkholderia cepacia, and Serratia marcescens; Nocardia species; and Aspergillus species [9]. Many of these infections can be refractory to treatment and lifethreatening despite surgical debridement and protracted courses of aggressive antibiotic therapy. Drug-related toxicity from these repeated and often prolonged courses of antibiotics can result in liver failure, pulmonary fibrosis, and renal failure [10]. From the perspective of patient safety, there was ongoing concern that the need for T-cell suppression would result in an unacceptable level of overall immunosuppression in a patient with a pre-existing immunodeficiency. In CGD, patients have little to no effective phagocytic cell population. Additionally, renal transplant recipients are considered to be at special risk of reactivating old tuberculous lesions due to their clinically induced chronic immunosuppression. Of interest, in the present case, after renal transplantation, hepatic tuberculosis without granuloma formation was diagnosed and a marked improvement in the cutaneous manifestations of the disease was observed. That was probably due to therapeutic levels of immunosuppression, which might have resulted in a considerable decrease in granuloma formation. However, it should also be kept in mind that immunosuppression can obscure the diagnostic tests, such as causing a false-negative tuberculin skin test result. Because the symptoms often are masked by the immunosuppressive therapy, diagnosis of tuberculous infection may be delayed and the mortality might be as high as 30% [11]. Quadruple therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) is recommended as the antituberculosis protocol because of the increasing incidence of drugresistant tuberculosis. At least 1 year of medical therapy is generally required, as in many other extrapulmonary manifestations of tuberculosis [12]. Our patient also received a therapy course of 1 year, quadruple therapy for the initial 2 months and continuing with isoniazid and rifampin for the next 10 months. Extrapulmonary tuberculosis has a high incidence and high mortality in the posttransplantation
CALISKAN, YAZICI, GULLUOGLU ET AL
population [13]. Therefore, high attention should be given to its differential diagnosis in clinical practice. With early diagnosis and prompt effective treatment, the prognosis of hepatic tuberculosis is usually good. However, if there are indications for surgery or difficulties in diagnosis, surgical procedures along with antituberculous therapy could be adopted. The previous literature has reported only a few cases involving organ transplantation in CGD patients [4,5]. Nevertheless, the current report confirms and expands upon the prior conclusions that renal transplantation is possible and perhaps a preferred therapy in CGD patients with ESRD.
REFERENCES [1] Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, bio-chemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 2000;79:170e200. [2] Frifelt JJ, Schonheyder H, Valerius NH, Strate M, Starklint H. Chronic granulomatous disease associated with chronic glomerulonephritis. Acta Paediatr Scand 1985;74:152e7. [3] Kimpen J, Van Damme-Lombaerts R, Van den Berghe G, Proesmans W. Autosomal recessive chronic granulomatous disease associated with 18q-syndrome and end-stage renal failure due to Henoch-Schonlein nephritis. Eur J Pediatr 1991;150:325e6. [4] Bolanowski A, Mannon RB, Holland SM, et al. Successful renal transplantation in patients with chronic granulomatous disease. Am J Transplant 2006;6:636e9. [5] Peces R, Ablanedo P, Seco M. Amyloidosis associated with chronic granulomatous disease in a patient with a renal transplant and recurrent urinary tract infections. Nefrologia 2002;22:486e91. [6] Winkelstein JA, Marino MC, Johnston RB, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine 2000;79:155e69. [7] Rosenzweig SD, Holland SM. Phagocyte immunodeficiencies and their infections. J Allergy Clin Immunol 2004;113:620e6. [8] Jackson SH, Gallen JI, Holland SM. The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med 1995;182:751e8. [9] Segal BH, Holland SM. Primary phagocytic disorders in childhood. Pediatr Clin North Am 2000;47:1311e38. [10] Harbath S, Pestotnik SL, Lloyd JF, Burke JP, Samore MH. The epidemiology of nephrotoxity associated with conventional amphotericin B therapy. Am J Med 2001;111:528e34. [11] Eastwood JB, Corbishley CM, Grange JM. Tuberculosis and the kidney. J Am Soc Nephrol 2001;12:1307e14. [12] Mert A, Ozaras R, Tabak F, Ozturk R, Bilir M. Localized hepatic tuberculosis. Eur J Intern Med 2003;14:511e2. [13] Aguado JM, Herrero JA, Gavaldá J, et al. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Transplantation 1997;63:1278e86.
