Saudi Journal of Kidney Diseases and Transplantation

: 2008  |  Volume : 19  |  Issue : 5  |  Page : 819--820

Sirolimus-induced Aphthous Ulcers which Disappeared with Conversion to Everolimus

Rapur Ram, Gudithi Swarnalatha, Prasad Neela, Kaligotla Venkata Dakshinamurty 
 Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta Hyderabad-500082, India

Correspondence Address:
Rapur Ram
Department of Nephrology, Nizam«SQ»s Institute of Medical Sciences, Punjagutta Hyderabad-500082

How to cite this article:
Ram R, Swarnalatha G, Neela P, Dakshinamurty KV. Sirolimus-induced Aphthous Ulcers which Disappeared with Conversion to Everolimus.Saudi J Kidney Dis Transpl 2008;19:819-820

How to cite this URL:
Ram R, Swarnalatha G, Neela P, Dakshinamurty KV. Sirolimus-induced Aphthous Ulcers which Disappeared with Conversion to Everolimus. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2021 Nov 29 ];19:819-820
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Full Text

To the Editor,

A 45-year-old gentleman with IgA nephro­pathy as primary kidney disease had under­gone cadaver donor renal transplantation in the year 2003. He received basilaximab as induc­tion immunosuppression along with predniso­lone, mycophenolate mofetil and cyclosporine. In August 2006, his serum creatinine started rising gradually from 1.4 mg/dl to 2.3 mg/dl along with an increase in 24-hour urine protein excretion to 586 mg. A renal allograft biopsy revealed features of chronic allograft nephro­pathy. He was initiated on sirolimus (6 mg on the first day followed by 2 mg/day as mainte­nance dose) in place of cyclosporine. Within a month after this, the patient presented with a painful confluent aphthous ulcers, on the tongue and lower lip [Figure 1]. He also complained of burning sensation in the retrosternal area and difficulty in swallowing. On examination, he had signs of dehydration like sunken eyes and loss of skin turgor. The serum creatinine had risen further to 4.9 mg/dl, urea to 256 mg/dL, sodium to 152 meq/L while the serum potassium remained low at 3.2 meq/L. Anti­bodies to herpes simplex virus 1 and 2 were negative. The Tzanck smears from the ulcers did not reveal any inclusion bodies or multi­nucleate giant cells. Everolimus was introduced in place of sirolimus at a dose of 0.75 mg twice a day. Two weeks following this, the aph­thous ulcers disappeared [Figure 2]. The serum creatinine levels declined once the dehydration was corrected with intravenous fluids.

Initial studies suggested that infection with the herpes simplex virus, cytomegalovirus, and epstein-barr virus, as well as pneumocystis carinii occurred at a greater frequency among sirolimus-treated renal transplant recipients. Multicenter phase III trials revealed aphthous mucosal ulcers to occur more frequently, par­ticularly among patients receiving sirolimus in a dose of 5 mg/day than those receiving 2 mg/day or placebo, in the Global (p= 0.002) but not the U.S. trial. [1] Aphthous stomatitis associated with sirolimus was reported in 9% of 150 psoriatic patients who received siro­limus. [2] Hyperlipidemia and microcytic anemia were observed to be the common adverse effects of everolimus, but not pneumonitis or aphthous ulcers. [3] The occurrence of aphthous ulcers of this severity, to the extent of worsening renal function, caused by sirolimus, has not been described in the past.


1Kahan BD. Two-year results of multicenter phase III trials of the effect of the addition of sirolimus to cyclosporine-based immunosup­pressive regimens in renal transplantation. Transplant Proc 2003;35(3):37S-52S.
2Reitamo S, Spuls P, Sassolas B, Lahfa M, Claudy A, Griffiths CE. Sirolimus European Psoriasis Study Group. Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treat­ment of severe psoriasis: a randomized con­trolled trial. Br J Dermatol 2001;145(3):438-45.
3Pascual J. Everolimus in clinical practice-renal transplantation. Nephrol Dial Transplant 2006; 21(l3):iii18-23.