The mammalian target of rapamcyin (mTOR) is a protein kinase that plays a critical role in cell growth and proliferation. Inhibitors of mTOR have both anticancer and immunosuppressive activity and are utilized to treat certain malignancies (eg, renal cell carcinoma, pancreatic neuroendocrine tumors, advanced breast cancer) and to prevent solid organ transplant rejection.

Patients treated with mTOR inhibitors may experience a variety of cutaneous and mucosal adverse effects including stomatitis, acneiform eruptions, exanthems, edema and angioedema, and nail dystrophy.

MTOR inhibitor-associated stomatitis (mIAS) is a dose-dependent toxicity that typically occurs within the first 8 weeks of therapy. It is characterized by well-circumscribed aphthous ulcerations on the nonkeratinized mucosa and is estimated to occur in 30%-60% of patients taking mTOR inhibitors.

Rashes that can occur in the setting of mTOR inhibitor therapy include morbilliform (maculopapular / exanthematous) eruptions, eczematous eruptions, and acneiform eruptions. Acneiform eruptions secondary to mTOR inhibitors are characterized by inflamed papules and pustules, usually affecting the trunk, face, and scalp. Overall, these eruptions appear similar to those induced by epidermal growth factor receptor (EGFR) inhibitors but are usually milder. Onset is typically within the first couple weeks of treatment.

Peripheral edema, periorbital edema, and angioedema have been reported to occur in the setting of mTOR inhibition. Edema can occur anywhere from a few days to 3 years after treatment initiation and is more common with sirolimus compared to everolimus. It is believed that mTOR inhibitors, particularly sirolimus, impede effective lymphatic drainage by interfering with the expression of vascular endothelial growth factor receptor-3 (VEGFR-3).

Nail changes associated with mTOR inhibitor therapy include longitudinal ridging, onycholysis, and nail plate erythema. Periungual pyogenic granulomas and paronychia, reported in patients using EGFR inhibitors, have also been reported in patients undergoing mTOR inhibition.