Tyrosine kinase inhibitors-associated pyoderma gangrenosum, a systematic review of published case reports

Abstract

Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the reported evidence of pyoderma gangrenosum associated with the use of these drugs. A systematic electronic literature search of PubMed and Embase was conducted. In these databases, search terms describing pyoderma gangrenosum were combined with TKIs. Fifteen case reports (eight cases associated with sunitinib, two with imatinib, two with ibrutinib, one with gefitinib, one with pazopanib, and one with dabrafenib and trametinib) were identified over the 14 years. The average Naranjo score of these cases is 6.6, which indicates a probable adverse drug reaction. Pyoderma gangrenosum is a probable and reversible drug reaction associated with some TKIs. Detailed medical history can help to prompt diagnosis of drug-induced pyoderma gangrenosum.Clinicians should be aware of TKI-associated pyoderma gangrenosum when caring for the skin of oncologic patients undergoing therapy with kinase inhibitors. Anti-Cancer Drugs 33: e1-e8

Lenvatinib‐induced pyoderma gangrenosum in a patient with hepatocellular carcinoma: A case report

“…1,2 The onset of PG may differ depending on the TKI owing to the varying strength of their inhibitory activity against these receptors or differences in their chemical structure or physicochemical properties. 2 Although PG is rare, clinicians should be aware of it when caring for the skin of oncological patients receiving a TKI. Further studies are needed to determine the exact mechanism underlying TKIassociated adverse events.…”

“…The mechanism underlying TKI-induced PG is unclear, but the antiangiogenic effect of inhibiting vascular endothelial growth factor receptors and mast/ stem cell growth factor receptor Kit, which promote apoptosis of keratinocytes by inhibiting the negative regulators of apoptosis and increasing the soluble Fas ligand concentration, is suspected. 1,2 The onset of PG may differ depending on the TKI owing to the varying strength of their inhibitory activity against these receptors or differences in their chemical structure or physicochemical properties. 2 Although PG is rare, clinicians should be aware of it when caring for the skin of oncological patients receiving a TKI.…”

“…Although TKIs, such as sunitinib, imatinib, gefitinib, and pazopanib, rarely cause PG as an adverse effect, some cases have been reported. 1,2 Lenvatinib has been linked to two cases of severe skin ulcers, which clinically resembled PG, 3,4 but these cases were not reported by dermatologists, and it remains inconclusive whether they can be definitively diagnosed as PG. To the best of our knowledge, there is only one other report describing lenvatinib-induced PG, which suggested a possible management approach involving dose reduction.…”

Successful treatment of cabozantinib‐induced pyoderma gangrenosum with ixekizumab therapy: A case report

“…kinase inhibitors are a class of medications increasingly associated with PG. 2,3 While the current management includes glucocorticoids and immunosuppressive agents, PG may be managed with targeted inhibition of the interleukin-17 pathway as its pathogenesis involves aberrant neutrophil migration. Here we present a case of cabozantinib-induced pyoderma gangrenosum responsive to ixekizumab therapy.…”

“…Several tyrosine kinase inhibitors have been associated with PG: sunitinib, imatinib, gefitinib, pazopanib, and trametinib. 2,3 Our patient received cabozantinib, a multi-kinase inhibitor with specificity toward vascular endothelial growth factor (VEGF) and mesenchymal-epithelial transition (MET) factor, that is currently approved to treat advanced medullary thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma. Although the mechanism remains unclear, multiple case reports show tyrosine kinase inhibitors (TKIs) with specificity toward VEGF such as sunitinib and bevacizumab are associated with PG development.…”