Radiation recall dermatitis induced by eribulin mesylate

Dear Editors, Recall dermatitis is characterized by delayed local inflammation arising in the area previously exposed to a specific drug, radiation, or infections.1-3 In particular, drug-induced inflammation that develops in previously irradiated areas is defined as radiation recall dermatitis (RRD).3 Several drugs, such as taxane, alkylating agents, and antibiotics, may evoke RRD.3 Herein, we report a case of eribulin mesylate (ERB)-induced RRD. A 39-year-old woman with a history of right breast cancer presented with erythema on her trunk. She had been administered epirubicin/endoxan with docetaxel and had undergone resection. Eleven months before presentation, postmastectomy radiation therapy (PMRT) was initiated at a dose of 50 Gy to the right chest wall and 60 Gy to the parasternal and supraclavicular area. Lung and brain metastases developed; therefore, a 30 Gy dose of radiation to the brain was initiated 8 months after PMRT, followed by ERB 1 month later. A rash developed one day after receiving ERB. The patient was referred to our hospital four days after the rash developed. Physical examination revealed erythema and red papules on the right chest and axilla (Figure 1a), back, and groin. Because the rash developed in the previously irradiated area, she was diagnosed with RRD. Topical steroid and oral fexofenadine hydrochloride treatment improved the lesions after 2 weeks (Figure 1b). Readministration of ERB was suspended to prevent relapse of dermatitis. Clinical manifestation of RRD typically appears as erythema in 80% of the cases.4 Less frequently, edema, desquamation, and vesicles develop.4 RRD is commonly confined to previously irradiated areas. However, cutaneous involvement may spread to other regions.3 Sears reported a patient with RRD who developed pigmentation on the chest 16 days after hydroxyurea treatment, which subsequently spread over the irradiated chest area.5 Moreover, in a phase 1 study of trimetrexate, a patient with lung cancer who was previously irradiated on the chest developed RRD in the chest after trimetrexate treatment, resulting in a generalized maculopapular rash.6 Because our patient presented with erythema and papules in the irradiated area as well as the non-irradiated area, the differential diagnosis included maculopapular drug eruption. Maculopapular drug eruption usually develops several days after the first exposure to causative reagents with multiple administrations, whereas sensitized cases can develop rash in a few hours.7 In contrast, RRD usually develops within a few days after administering causative drugs; however, the timing of RRD development can vary from a few hours to several months.3 Discrepancies in the timing of RRD and drug eruptions after exposure to causative agents may be explained by the etiology of RRD. Although the precise mechanism remains elusive, hypersensitivity reactions may contribute to the development of RRD. Radiation can induce damage in various cell types, including keratinocytes, fibroblasts, and endothelial cells, leading to the expression of inflammatory cytokines.8, 9 These cytokines are believed to lower the threshold for an inflammatory response, indicating that the cellular damage caused by introducing chemotherapy agents after radiation can activate inflammation, resulting in RRD.8, 9 Furthermore, RRD is reported to frequently develop after the administration of the first dose of the causative drug,8, 9 highlighting its distinct pathogenesis from drug eruptions. Given that our patient had no previous history of ERB treatment and that the rash developed 1 day after ERB treatment, we favored a diagnosis of ERB-induced RRD, although the rash was distributed in a non-irradiated area. Several cases of RRD have been reported in association with microtubule inhibitors; however, there is only one report of RRD following ERB exposure. Tran et al. reported RRD with purpuric erythema and edema over the irradiated site after two courses of ERB.10 In contrast, our patient developed RRD 1 day after ERB treatment, indicating that ERB-induced RRD can appear as quickly as other treatments. Rechallenge of causative treatment may be reasonable for patients with RRD based on therapeutic benefit against the risk of recurrence of RRD. Indeed, approximately half of the patients do not experience a recurrence of RRD after rechallenge.4 Among the patients who had RRD recurrence, 45.7% had milder reactions than the initial RRD, 28.6% had the same extent of reactions, and 25.7% experienced exacerbated RRD at the recurrence.4 Given that one reported patient experienced a fulminant rash after rechallenge with ERB,10 caution may be necessary when rechallenging ERB after RRD. Our case report highlights the involvement of ERB in RRD development. However, further studies are needed to reveal the characteristics of ERB-induced RRD and the safety of ERB readministration. None.