| | Quiz Page August 2009: Respiratory Distress 5 Years After Kidney TransplantationClinical Presentation  A 45-year-old man who had received a kidney transplant 5 years previously presented with cough, shortness of breath, and fever. Focal segmental glomerulosclerosis had been diagnosed that required initiation of hemodialysis therapy in 1995. In 2002, he received a deceased donor kidney transplant that was complicated by Banff 1A rejection 6 months later. This was treated with 3 corticosteroid pulses, but corticosteroid therapy later was withdrawn because of osteoporosis and cataract. In 2003, cyclosporine was replaced with sirolimus because of decreased kidney function (serum creatinine level, 3.6 mg/dL [318.2 μmol/L]) and an estimated glomerular filtration rate of 20 mL/min/1.73 m2 [0.33 mL/s/1.73 m2]). His current medications included sirolimus, mycophenolate mofetil, carvedilol, calcitriol, ezetimibe, and ursodeoxycholic acid. The patient's cough and shortness of breath began 2 weeks previously. His temperature was 36.1°C, blood pressure was 110/70 mm Hg, heart rate was 80 beats/min, and oxygen saturation was 99%. On physical examination, he had pulmonary crackles with reduced breath sounds in the right middle lung field. Laboratory tests showed a stable serum creatinine level of 3 mg/dL (265.2 μmol/L; estimated glomerular filtration rate, 24 mL/min/1.73 m2 [0.40 mL/s/1.73 m2]), white blood cell count of 5 × 103/μL (5 × 109/L) with a normal differential count, and C-reactive protein level of 26.5 mg/L. High-resolution chest computed tomography (CT) showed small airway lesions and centrilobular consolidation in lower lobes. ■ What is the differential diagnosis for this patient's presentation? ■ What are the findings on chest CT? ■ What additional evaluation would be appropriate? ■ How might this patient be managed? Discussion What is the differential diagnosis for this patient's presentation? Considering the patient's history, immunosuppressive therapy, and pulmonary findings, the differential diagnosis must include malignancies, notably lung-infiltrating posttransplantation lymphoproliferative disorder, and infectious processes, including community-acquired pathogens (Haemophilus influentia, Streptococcus pneumoniae, and Legionella species), Pseudomonas aeruginosa, cytomegalovirus, and Nocardia species. Pneumocistis jirovecii must be considered because of the previous discontinuation of prophylactic therapy, as well as Mycobacterium tubercolosis, community respiratory viruses, and Aspergillus species.1 Granulomatous vasculitides and drug toxicity also could account for this presentation. What are the findings on chest CT? High-resolution chest CT showed 2 patterns of lung lesions in different segmental areas: 1.In the anterior-lateral segment of the right lower lobe, bronchiolar cysts and tubular dilatations were associated with micronodules. These sharp contours at the end or on the walls of bronchiolar images are described as a “tree-in-bud” appearance in centrilobular sites (Fig 1A). 2.In the medial segment of the right lower lobe and the posterior-basal and lateral-basal segments of the left lower lobe, there was thickening of the bronchiolar wall with peribronchiolar and centrilobular consolidation located in the peripheral and subpleural lung (Fig 1B). Pattern 1 may be related to small airway granulomas or bronchiolitis obliterans, whereas pattern 2 is indicative of an organizing pneumonia, vasculitides, bronchial alveolar carcinoma, or lymphoma. The association of the 2 patterns is characteristic of bronchiolitis obliterans with organizing pneumonia. What additional evaluation would be appropriate? To exclude pulmonary vasculitides, testing for antinuclear antibodies, extractable nuclear antigen antibodies, antineutrophil cytoplasmic antibodies, and cryoglobulins was performed; results were negative. Next, blood, sputum and urine cultures were evaluated for bacteria, mycobacteria, viruses, fungi, and parasites. Finally, bronchoscopy was performed, which showed nonspecific inflammation with bronchoalveolar lavage fluid rich in inflammatory cells, but negative for microorganisms.2 We concluded the presentation was of a drug-related bronchiolitis obliterans with organizing pneumonia, likely sirolimus-related pneumonia. How might this patient be managed? Sirolimus-related pneumonia is a serious common side effect of sirolimus that presents with dyspnea and cough. Chest CT shows a pattern of bronchiolitis obliterans with organizing pneumonia. It is allergic in nature and resolves with sirolimus therapy withdrawal.3, 4, 5 In this case, withdrawing mTOR (mammalian target of rapamycin) inhibitors would have reexposed the patient to potentially nephrotoxic calcineurin inhibitors and progressive allograft nephropathy.6 As an alternative, we converted sirolimus to everolimus therapy, thus maintaining the immunosuppressive class benefits. One concern in shifting from sirolimus to everolimus therapy is the possibility that lung toxicity is a class effect of mTOR inhibitors, possibly caused by molecular similarities or a common mechanism of action. Several reports of temsirolimus, another mTOR inhibitor, identify similar lung toxicity. After the immunosuppressant therapy conversion, the patient's symptoms resolved. Pulmonary findings returned to normal, and repeated chest CT 12 months later showed strong attenuation of pattern 1 and resolution of pattern 2. Kidney function remained stable with a serum creatinine level of 3 mg/dL (265.2 μmol/L) and estimated glomerular filtration rate of 24 mL/min/1.73 m2 (0.40 mL/s/1.73 m2). The temporal association of symptoms with sirolimus introduction and resolution with drug withdrawal confirmed our diagnosis of sirolimus-related pneumonia. Our results suggest possible differences in side-effect patterns between different mTOR inhibitors. Final Diagnosis Sirolimus-related pneumonia in a kidney transplant recipient. Acknowledgements Support: None. Financial Disclosure: None. References 1. 1Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2004;170:22–48.
CrossRef
2. 2Morelon E, Stern M, Israël-Biet D, et al. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation. 2001;72:787–790. MEDLINE |
CrossRef
3. 3Pham PT, Pham PC, Danovitch GM, et al. Sirolimus-associated pulmonary toxicity. Transplantation. 2004;77:1215–1220. MEDLINE 4. 4Lindenfeld JA, Simon SF, Zamora MR, et al. BOOP is common in cardiac transplant recipients switched from calcineurin inhibitor to sirolimus. Am J Transplant. 2005;5:1392–1396. MEDLINE |
CrossRef
5. 5Champion L, Stern M, Israël-Biet D, et al. Brief communication: Sirolimus-associated pneumonitis: 24 Cases in renal transplant recipients. Ann Intern Med. 2006;144:505–509. 6. 6Yilmaz S, Sar A. Pathogenesis and management of chronic allograft nephropathy. Drugs. 2008;68(suppl 1):S21–S31. Case provided and authored by Giovanni Piotti, MD, 1 Roberto Dore, MD,2 Giulia Bedino, MD,1 Francesca Bosio, MD,1 Pasquale Esposito, MD,1 Marilena Gregorini, MD, PhD,1 Teresa Rampino, MD,1 and Antonio Dal Canton, MD,1 1Unit of Nephrology, Dialysis and Transplantation, and 2Chest and CT Section of Radiology Institute, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Address correspondence to Giovanni Piotti, MD, Unit of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo and University of Pavia; Piazzale Golgi n° 2, 27100 Pavia, Italy. E-mail: gpiotti@yahoo.it PII: S0272-6386(09)00755-0 doi:10.1053/j.ajkd.2009.03.027 © 2009 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | 
 40 of 40
|
| |
|
FULL TEXT00755-0/journalimage?img=PIIS0272638609007550.gr1.lrg.gif&fig=fig1&kwhquery=&issn=0272-6386&ishighres=false&allhighres=false&free=yes','journalimage');)
