Sunitinib: A Cause of Bullous Palmoplantar Erythrodysesthesia, Periungual Erythema, and Mucositis

Evolving Strategies for the Management of Hand–Foot Skin Reaction Associated with the Multitargeted Kinase Inhibitors Sorafenib and Sunitinib

“…Extensive and linear layers of keratinocyte necrosis are observed, which correlate with the time of initial exposure to the MKI [36]. Histologic examination reveals necrotic subepidermal, intraepidermal, or subcorneal blister formation that is followed by acanthosis with hyperkeratosis or parakeratosis [12,39]. Few cases show mild cystic degenerative changes of the eccrine coil; in rare cases, some squamous metaplasia of these glands has also been observed [34,40].…”

“…In addition, eccrine glands express c-KIT and PDGFR, which are both targets of sorafenib and sunitinib [19,43]. Because an overlap in targets for sorafenib and sunitinib lies in VEGFR and PDGFR inhibition, HFSR may be an indirect effect of the inhibition of these proangiogenic pathways [14,34,39]. Inhibition of VEGFR and PDGFR could potentially prevent vascular repair mechanisms from functioning properly, thereby causing HFSR in high-pressure areas, such as the palms and soles, which may be repeatedly exposed to subclinical trauma [14].…”

Error in “Methods” Section in: Delayed Immune-Mediated Adverse Effects of Polyalkylimide Dermal Fillers: Clinical Findings and Long-term Follow-up

“…Histologic analysis of the amputated limb revealed extensive suppurative granulomatous inflammation in all skin layers with infiltration of the bone. Eccrine syringosquamous metaplasia and neutrophilic eccrine hidradenitis, as described elsewhere, 3,4 in initial PPE or histopathologic findings resembling those in an acute graftvs-host disease (AGVHD) could not be detected.…”

“…3 As for many other chemotherapy drugs, such as bleomycin sulfate, capecitabine, cyclophospha- mide, and doxorubicin, PPE has been described in patients treated with sunitinib. 3,5 However, mild sunitinibassociated acral erythema (hand-foot-skin reaction) might occur as a dosage-limiting adverse effect after 2 to 4 weeks of treatment. 6,7 On the one hand, the pathologic process of PPE has been hypothesized to result from direct toxic effects of medications in the eccrine glands.…”

Small Molecule Multikinase Inhibitors

“…Stomatitis and cheilitis have been reported in 19-35% of sunitinib treated patients, and 19-26% with sorafenib [62,69,78,87]. Lesions usually occur during the first weeks of treatment, can be painful and impair alimentation.…”