Sirolimus-induced pneumonitis, sinusitis and macular oedema

Sir,

Sirolimus is being used increasingly in calcineurin inhibitor-free regimens in solid organ transplant immunosuppression [1,2]. However, it has potential pulmonary toxicity due to a capillary leak syndrome [3,4]. We report for the first time one such case with involvement of the paranasal sinuses and retina in addition to sirolimus-induced pneumonitis, all probably related to the same underlying pathophysiology.

A 54-year-old male with presumed chronic tubulointerstitial nephritis and end-stage renal disease (ESRD) on intermittent haemodialysis treatment underwent cadaver renal transplantation in August 2003. He was given daclizumab induction, followed by mycophenolate mofetil (MMF) 1000 mg per day and sirolimus (6 mg loading followed by 2 mg once daily) and low dose prednisolone as immunosuppression. Cyclosporin was avoided due to delayed graft function. MMF was withdrawn and cyclosporin (3 mg/kg) was introduced after 2 weeks once adequate graft function was established. His baseline serum creatinine at this time was 1.8 mg/dl. One month post-transplant, he was found to have diabetes mellitus for which he was put on insulin therapy. Two months post-transplant, he presented with complaints of increasing breathlessness and headache. He was afebrile, normotensive and had no systemic oedema. Chest examination revealed bilateral crepitations. Fundoscopy showed bilateral macular oedema. Blood chemistry showed a haemoglobin of 11.2 g/dl, TLC 11 300/mm3, serum urea 83 mg/dl and creatinine 1.8 mg/dl. Chest X-ray showed bilateral non-homogeneous opacities in the middle and lower zones, and X-ray of the paranasal sinuses revealed bilateral opaque maxillary sinuses and hazy frontal sinuses. Computed tomography (CT) scan showed mucosal oedema and thickening of all the sinuses (frontal, ethmoid, sphenoid and maxillary). Sputum cultures were sterile. Fluorescein fundus angiography showed pooling of contrast suggestive of central serous retinopathy.

Sirolimus was stopped and he was managed conservatively without antibiotics as there was no evidence of infection. A sirolimus trough level was not done as we did not have the facility at our centre. Bronchial alveolar lavage was not done due to rapid resolution of symptoms. His breathlessness and headache subsided during the next 48 h. At repeat X-rays of chest and paranasal sinuses, the initial findings were almost cleared up and at fundus examination a decreased macular oedema was found.

There have been several case reports of pneumopathy with the usage of sirolimus [3–5]. None of them have reported involvement of paranasal sinuses and the retina, probably because this was not looked for in view of the dominant pulmonary symptomatology. Case reports mention high drug levels, graft dysfunction and hypervolaemia to be possible risk factors [2,3].

This case reminds us of the importance of identification of potential toxicities of the immunosuppressive regimens, e.g. sirolimus. The acute toxic effects as a rule are reversible, and cessation of the drug usually leads to resolution of the side effects.

Conflict of interest statement. None declared.

Shivanand Karopadi Nayak, Tarun K. Jeloka and Subhramanyam V. Sreepada

Global Hospital Nephrology Department Hyderabad, AP India Email: nayak{at}pol.net.in

References

  1. Groth CG, Backman L, Morales JM et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporin. Transplantation 1999; 67: 1036–1042[ISI][Medline]
  2. Morelon E, Mamzer-Bruneel MF, Peraldi MN et al. Sirolimus: a new promising immunosuppressive drug. Towards a rationale for its use in renal transplantation. Nephrol Dial Transplant 2001; 16: 18–20[Free Full Text]
  3. Morelon E, Stern H, Kreis H. Interstitial pneumonitis associated with sirolimus therapy in renal transplant recipients. N Engl J Med 2000; 343: 225–226[Free Full Text]
  4. Singer SJ, Tiernan R, Sullivan EJ et al. Interstitial pneumonitis associated with sirolimus therapy in renal transplant recipients. N Engl J Med 2000; 343: 1815–1816[Free Full Text]
  5. Mahalati K, Murphy DM, West ML. Bronchiolitis obliterans and organizing pneumonia in renal transplant recipients. Transplantation 2000; 69: 1531–1532[ISI]
  6. Kaplan MJ, Ellis CN, Csorgo ZB et al. Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis. Arch Dermatol 1999; 135: 553–557[Abstract/Free Full Text]
  7. Haydar Ali A, Denton M, West A, Rees J, Goldsmith DJA. Sirolimus-induced pneumonitis: three cases and a review of the literature. Am J Transplant 2004; 4: 137–139[CrossRef][ISI][Medline]




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