Cutaneous adverse events induced by azacitidine in myelodysplastic syndrome patients: Case reports and a lesson from published work review

Subcutaneous injection of azacitidine (AZA) is an important treatment option for myelodysplastic syndrome (MDS), which improves overall survival. In hematology, the incidence of AZA-induced cutaneous adverse events (AE) has been known to be relatively high, which has not been well recognized by dermatologists. Discontinuation of AZA can result in the deterioration of MDS disease activity. Therefore, on dermatological consultation, precise evaluation of AE severity and careful consideration is required for post-AE medication management. To enhance our understanding of AZA-induced cutaneous AE, we report four cases with two representative cutaneous AE subtypes and summarize the clinicopathological phenotypes and courses of the cases in the published work. Case 1, a 71-year-old man, developed neutrophilic dermatosis involving the dermis and subcutaneous tissue. The other three cases, a 75-year-old man, a 78-year-old woman and a 68-year-old man, presented injection-site erythema associated with flare-up reaction. Discontinuation of AZA was necessary for case 1 alone. The published work review delineated three major subtypes of AZA-induced cutaneous AE: systemic cutaneous reaction, neutrophilic dermatosis type and erythematous type injection-site reaction. Histologically, the first two subtypes are mostly characterized by neutrophil infiltration, while the third subtype presents lymphocytic cell infiltration. Neither AZA discontinuation nor intensive interventions were required for the erythematous type injection-site reaction, while AZA termination or systemic treatments, represented by corticosteroid administration, were preferentially conducted for the systemic cutaneous reaction or the neutrophilic dermatosis type injection-site reaction subgroup. These observations support the necessity of subtype-dependent treatment strategies for the management of AZA-induced cutaneous AE.