- Email: [email protected]
Drug fever caused by mycophenolate mofetil in a renal transplant recipient—a case report
Drug Fever Caused by Mycophenolate Mofetil in a Renal Transplant Recipient—A Case Report S-C. Chueh, J-C. Hong, C-Y. Huang, and M-K. Lai
M
YCOPHENOLATE MOFETIL (MMF, CellCept) has been shown to reduce the incidence of biopsyproven acute rejection episodes in renal allograft recipients.1,2 Its use has been associated with leukopenia, infection, nausea, vomiting, and diarrhea.1–3 Herein, we report a case of drug fever induced by MMF in a renal transplant patient. PATIENT AND METHODS A 41-year-old man with end stage renal disease due to cryptic etiology received his second renal allograft from his sister in mid-December 1998. His first renal transplant (cadaveric) was engrafted 3 years ago. That allograft failed in a few weeks because of severe acute rejection. After this second transplant, he had an episode of moderate acute cellular rejection (Banff type IB) on postoperative day 8, which was successfully rescued by 7 days of rabbit antithymocyte immunoglobulin therapy, and mycophenolate mofetil (MMF, 1 to 2 g/d) has been administered since then. In addition, he received cyclosporine microemulsion (CsA) and steroids from the beginning of this transplant. About 1 month after this transplant, he began to suffer from intermittent fever (spiking pattern, once or twice a day, maximum 39.5°C). He was admitted then. The infectious work-up included
serologic studies and pan cultures of blood, urine, cerebrospinal fluid, peritoneal fluid, stool, and bone marrow in search of tuberculosis, cytomegalovirus, hepatitis B, hepatitis C, Epstein Barr virus, herpes simplex virus, toxoplasmosis, cryptorcoccus, fungus, and bacteria. And many image studies (ultrasonography and magnetic resonance imaging of abdomen and pelvis, chest x-ray, high resolution computed tomography of chest) were also performed. All these studies yielded negative results. His C-reactive protein was within normal limit, and 67Gallium inflammation scan did not reveal any sign of focal inflammation. Yet, the patient continued to suffer from aggravating intermittent spiking fever in spite of treatment with broad-spectrum antibiotics. Drug fever was considered because no definite infections could
From the Department of Urology (S-C.C., M-K.L.) and Internal Medicine (J-C.H.), College of Medicine, National Taiwan University, Taipei, Taiwan, and (M-L.L.) LoTung Po-Hai Hospital, I-Lan, Taiwan. Supported by a grant from the National Science Council, Taiwan, Republic of China (NSC-88-2314-B-002-190). Address reprint requests to Dr Ming-Kuen Lai, Superintendent, Lo-Tung Po-Hai Hospital, 81 Nan-Chang Street, Lo-Tung, I-Lan, 265 Taiwan.
Fig 1. The temporal relationship of body temperature changes and medications used. See text for detailed description.
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/00/$–see front matter PII S0041-1345(00)01495-0
Transplantation Proceedings, 32, 1925–1926 (2000)
1925
1926 be found. MMF was most suspected since this was a new drug he had never had before. To discontinue MMF and in view of his highly sensitized immune system causing rejections under CsA coverage, CsA was first changed to FK-506 (See Fig 1).
RESULTS
His fever subsided one day after discontinuing mycophenolate mofetil. No more fever episode was experienced since then (Fig 1). His graft function was stable under FK-506 and steroid coverage. CONCLUSION AND DISCUSSIONS
There has been no report of MMF-induced drug fever in the literature thus far. A strong temporal relationship between the cessation of MMF and subsidence of fever is
CHUEH, HONG, HUANG ET AL
shown in the figure. Immunosuppressants, including cyclosporine and azathioprine, but not MMF, had been associated with drug fever.4,5 This patient was given CsA at his first transplant without causing fever, which excluded CsA as the cause of his fever. Rechallenge with MMF was suggested for confirmation of the diagnosis, but the patient strongly objected. REFERENCES 1. Sollinger HW, et al: Transplantation 60:225, 1995 2. Keown P, et al: Transplantation 61:1029, 1995 3. Rothwell WS, Gloor JM, Morgenstern BZ, Milliner DS: Transplantation 68:158, 1999 4. Sabeel A, AlMeshari K, Abutaleb N, et al: Nephrol Dial Transplant 13:1004, 1998 5. Thomas MD, Cook LJ: BMJ 317:1291, 1998
M
YCOPHENOLATE MOFETIL (MMF, CellCept) has been shown to reduce the incidence of biopsyproven acute rejection episodes in renal allograft recipients.1,2 Its use has been associated with leukopenia, infection, nausea, vomiting, and diarrhea.1–3 Herein, we report a case of drug fever induced by MMF in a renal transplant patient. PATIENT AND METHODS A 41-year-old man with end stage renal disease due to cryptic etiology received his second renal allograft from his sister in mid-December 1998. His first renal transplant (cadaveric) was engrafted 3 years ago. That allograft failed in a few weeks because of severe acute rejection. After this second transplant, he had an episode of moderate acute cellular rejection (Banff type IB) on postoperative day 8, which was successfully rescued by 7 days of rabbit antithymocyte immunoglobulin therapy, and mycophenolate mofetil (MMF, 1 to 2 g/d) has been administered since then. In addition, he received cyclosporine microemulsion (CsA) and steroids from the beginning of this transplant. About 1 month after this transplant, he began to suffer from intermittent fever (spiking pattern, once or twice a day, maximum 39.5°C). He was admitted then. The infectious work-up included
serologic studies and pan cultures of blood, urine, cerebrospinal fluid, peritoneal fluid, stool, and bone marrow in search of tuberculosis, cytomegalovirus, hepatitis B, hepatitis C, Epstein Barr virus, herpes simplex virus, toxoplasmosis, cryptorcoccus, fungus, and bacteria. And many image studies (ultrasonography and magnetic resonance imaging of abdomen and pelvis, chest x-ray, high resolution computed tomography of chest) were also performed. All these studies yielded negative results. His C-reactive protein was within normal limit, and 67Gallium inflammation scan did not reveal any sign of focal inflammation. Yet, the patient continued to suffer from aggravating intermittent spiking fever in spite of treatment with broad-spectrum antibiotics. Drug fever was considered because no definite infections could
From the Department of Urology (S-C.C., M-K.L.) and Internal Medicine (J-C.H.), College of Medicine, National Taiwan University, Taipei, Taiwan, and (M-L.L.) LoTung Po-Hai Hospital, I-Lan, Taiwan. Supported by a grant from the National Science Council, Taiwan, Republic of China (NSC-88-2314-B-002-190). Address reprint requests to Dr Ming-Kuen Lai, Superintendent, Lo-Tung Po-Hai Hospital, 81 Nan-Chang Street, Lo-Tung, I-Lan, 265 Taiwan.
Fig 1. The temporal relationship of body temperature changes and medications used. See text for detailed description.
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/00/$–see front matter PII S0041-1345(00)01495-0
Transplantation Proceedings, 32, 1925–1926 (2000)
1925
1926 be found. MMF was most suspected since this was a new drug he had never had before. To discontinue MMF and in view of his highly sensitized immune system causing rejections under CsA coverage, CsA was first changed to FK-506 (See Fig 1).
RESULTS
His fever subsided one day after discontinuing mycophenolate mofetil. No more fever episode was experienced since then (Fig 1). His graft function was stable under FK-506 and steroid coverage. CONCLUSION AND DISCUSSIONS
There has been no report of MMF-induced drug fever in the literature thus far. A strong temporal relationship between the cessation of MMF and subsidence of fever is
CHUEH, HONG, HUANG ET AL
shown in the figure. Immunosuppressants, including cyclosporine and azathioprine, but not MMF, had been associated with drug fever.4,5 This patient was given CsA at his first transplant without causing fever, which excluded CsA as the cause of his fever. Rechallenge with MMF was suggested for confirmation of the diagnosis, but the patient strongly objected. REFERENCES 1. Sollinger HW, et al: Transplantation 60:225, 1995 2. Keown P, et al: Transplantation 61:1029, 1995 3. Rothwell WS, Gloor JM, Morgenstern BZ, Milliner DS: Transplantation 68:158, 1999 4. Sabeel A, AlMeshari K, Abutaleb N, et al: Nephrol Dial Transplant 13:1004, 1998 5. Thomas MD, Cook LJ: BMJ 317:1291, 1998