Potentially Fatal Lingual Angioedema in Everolimus Treated Metastatic Renal Cell Carcinoma

Everolimus is commonly used as a second line therapeutic option in the treatment of metastatic renal cell carcinoma (mRCC). Angioedema is a well described adverse event of everolimus treatment in the transplant area, where it is used as an immunosuppressant. However this is an extremely rare adverse event when everolimus is used in the treatment of mRCC.
We describe a case of an acute onset of severe everolimus-induced lingual angioedema in a 70 year-old man, who received everolimus 10 mg in the treatment of mRCC. Complete resolution occurred when everolimus was withdrawn. After re-administration of a reduced dose no recurrence was observed during a follow-up period of 11 months. During and after the onset of lingual angioedema, we opted not to terminate the administration of an angiotensin-converting enzyme (ACE) inhibitor, showing that everolimus was synergistic for the occurrence of this event.
We concluded that the occurrence of lingual angioedema in this particular case was an adverse event associated with everolimus treatment. In the literature, as in our case, a strong association between the co-administration of an ACE inhibitor and an inhibitor of the mammalian target of rapamycin (mTOR) is described.