Pediatr Nephrol (2015) 30:2109–2110 DOI 10.1007/s00467-014-2974-5
CLINICAL QUIZ
Fever of Unknown Origin (FUO) in a pediatric kidney transplant recipient: Questions Shahid Nadeem & Lakshmi Sukumaran & David A. Siegel & Stephanie M. Jernigan & Larry A. Greenbaum
Received: 19 September 2014 / Revised: 20 September 2014 / Accepted: 22 September 2014 / Published online: 15 October 2014 # IPNA 2014
Keywords Children . Kidney transplantation . Fever of unknown origin . Pancytopenia . Interstitial lung disease
A 13-year-old Caucasian male with juvenile nephronophthisis developed fever of unknown origin 15 months after living-related kidney transplantation and bilateral native nephrectomies. His initial post-transplant immunosuppression was basiliximab induction and tacrolimus, mycophenolate mofetil, and prednisone. Per protocol, following a 6-month surveillance biopsy without evidence of rejection, his tacrolimus was discontinued and he was started on sirolimus.
The answers to these questions can be found at http://dx.doi.org/10.1007/ s00467-014-2973-6 S. Nadeem (*) Division of Pediatric Nephrology, LSU Health Science Center in Shreveport, 1501 Kings Hwy, Shreveport, LA 71130-3932, USA e-mail: [email protected] L. Sukumaran Division of Infectious Diseases, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA D. A. Siegel Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA S. M. Jernigan : L. A. Greenbaum Division of Nephrology, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA
His course was uneventful until a 12-month surveillance biopsy showed Banff grade IIA acute cellular rejection and >50 % C4d staining; he also tested positive for donor-specific antibody. These test results supported a diagnosis of antibodymediated rejection. His creatinine had been stable and his sirolimus levels were within the target range (10–15 ng/mL). At this time he received 10 mg/kg of methylprednisolone daily for 3 consecutive days, a 5-day course of Thymoglobulin, and 1 g/kg of intravenous immunoglobulin. He was also restarted on tacrolimus and sirolimus was stopped. There were no concerns for non-adherence. Two days after the Thymoglobulin course he developed fever. A blood culture was negative, and no Epstein–Barr virus (EBV) or cytomegalovirus (CMV) was detected by whole blood polymerase chain reaction (PCR). The patient was given a provisional diagnosis of serum sickness secondary to Thymoglobulin and was treated with prednisone 60 mg daily, after which he defervesced. One and one-half months later the mycophenolate mofetil treatment was converted to leflunomide due to new-onset BK viremia, although the patient showed no evidence of BK nephropathy on the 12-month protocol biopsy and subsequent follow-up biopsies. There was significant improvement in rejection (borderline cellular and weakly positive C4d stain) on the follow-up biopsies. The patient was hospitalized several times for fever, with an unremarkable work-up each time. These fevers responded to prednisone, but they recurred when the prednisone dose was reduced. During his fourth hospitalization for fever recurrence, he also had intermittent abdominal pain, headache, and myalgia. His physical examination was unremarkable except for an enlarged spleen 4–5 cm below his left costal margin and right lower quadrant abdominal tenderness without rebound, guarding, or rigidity. The findings of an
2110
abdominal magnetic resonance imaging with contrast were unremarkable except for presence of significant interstitial opacities in the lower lungs, which were confirmed on a chest x-ray. He had no respiratory symptoms apart from mild shortness of breath with walking. During this hospitalization, the patient developed pancytopenia (white blood cell count 1,970 /uL, hemoglobin 10.3 g/dL, platelets 63,000/uL, absolute neutrophil count 1,580/uL). Renal allograft function, based on serum creatinine, remained stable during this entire period.
Pediatr Nephrol (2015) 30:2109–2110
Questions 1. What are the possible causes of interstitial lung disease in a transplant patient? 2. What are the causes of pancytopenia in a kidney transplant recipient? 3. Which diagnoses unify the findings of persistent fever, interstitial lung disease, and pancytopenia in a kidney transplant recipient?
CLINICAL QUIZ
Fever of Unknown Origin (FUO) in a pediatric kidney transplant recipient: Questions Shahid Nadeem & Lakshmi Sukumaran & David A. Siegel & Stephanie M. Jernigan & Larry A. Greenbaum
Received: 19 September 2014 / Revised: 20 September 2014 / Accepted: 22 September 2014 / Published online: 15 October 2014 # IPNA 2014
Keywords Children . Kidney transplantation . Fever of unknown origin . Pancytopenia . Interstitial lung disease
A 13-year-old Caucasian male with juvenile nephronophthisis developed fever of unknown origin 15 months after living-related kidney transplantation and bilateral native nephrectomies. His initial post-transplant immunosuppression was basiliximab induction and tacrolimus, mycophenolate mofetil, and prednisone. Per protocol, following a 6-month surveillance biopsy without evidence of rejection, his tacrolimus was discontinued and he was started on sirolimus.
The answers to these questions can be found at http://dx.doi.org/10.1007/ s00467-014-2973-6 S. Nadeem (*) Division of Pediatric Nephrology, LSU Health Science Center in Shreveport, 1501 Kings Hwy, Shreveport, LA 71130-3932, USA e-mail: [email protected] L. Sukumaran Division of Infectious Diseases, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA D. A. Siegel Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA S. M. Jernigan : L. A. Greenbaum Division of Nephrology, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA
His course was uneventful until a 12-month surveillance biopsy showed Banff grade IIA acute cellular rejection and >50 % C4d staining; he also tested positive for donor-specific antibody. These test results supported a diagnosis of antibodymediated rejection. His creatinine had been stable and his sirolimus levels were within the target range (10–15 ng/mL). At this time he received 10 mg/kg of methylprednisolone daily for 3 consecutive days, a 5-day course of Thymoglobulin, and 1 g/kg of intravenous immunoglobulin. He was also restarted on tacrolimus and sirolimus was stopped. There were no concerns for non-adherence. Two days after the Thymoglobulin course he developed fever. A blood culture was negative, and no Epstein–Barr virus (EBV) or cytomegalovirus (CMV) was detected by whole blood polymerase chain reaction (PCR). The patient was given a provisional diagnosis of serum sickness secondary to Thymoglobulin and was treated with prednisone 60 mg daily, after which he defervesced. One and one-half months later the mycophenolate mofetil treatment was converted to leflunomide due to new-onset BK viremia, although the patient showed no evidence of BK nephropathy on the 12-month protocol biopsy and subsequent follow-up biopsies. There was significant improvement in rejection (borderline cellular and weakly positive C4d stain) on the follow-up biopsies. The patient was hospitalized several times for fever, with an unremarkable work-up each time. These fevers responded to prednisone, but they recurred when the prednisone dose was reduced. During his fourth hospitalization for fever recurrence, he also had intermittent abdominal pain, headache, and myalgia. His physical examination was unremarkable except for an enlarged spleen 4–5 cm below his left costal margin and right lower quadrant abdominal tenderness without rebound, guarding, or rigidity. The findings of an
2110
abdominal magnetic resonance imaging with contrast were unremarkable except for presence of significant interstitial opacities in the lower lungs, which were confirmed on a chest x-ray. He had no respiratory symptoms apart from mild shortness of breath with walking. During this hospitalization, the patient developed pancytopenia (white blood cell count 1,970 /uL, hemoglobin 10.3 g/dL, platelets 63,000/uL, absolute neutrophil count 1,580/uL). Renal allograft function, based on serum creatinine, remained stable during this entire period.
Pediatr Nephrol (2015) 30:2109–2110
Questions 1. What are the possible causes of interstitial lung disease in a transplant patient? 2. What are the causes of pancytopenia in a kidney transplant recipient? 3. Which diagnoses unify the findings of persistent fever, interstitial lung disease, and pancytopenia in a kidney transplant recipient?
