Maculopapular Drug Eruption Caused by Apalutamide: Case Report and Review of the Literature

Abstract

Apalutamide, an oral androgen receptor signaling inhibitor, is approved for the treatment of nonmetastatic castration-resistant prostate cancer and metastatic prostate cancer. In the international randomized placebo-controlled clinical trials, apalutamide was associated with a higher rate of rash than placebo. However, given that reports from a dermatological perspective are limited, the skin manifestations and histopathology of the skin lesions caused by apalutamide are largely unknown. Here, we report a case of apalutamide-induced drug eruption. A 66-year-old man developed itchy maculopapular erythema on the trunk and extremities 10 weeks after starting apalutamide for progressive prostate cancer. A biopsy specimen showed interface dermatitis with perivascular lymphocytic infiltration in the upper dermis. The lymphocyte transformation test was positive for apalutamide. The skin manifestations improved after discontinuation of apalutamide and treatment with topical corticosteroids and systemic prednisolone. A review of the dermatology literature on apalutamide-induced drug eruption yielded only six cases, including our case. Dermatologically, there were four cases of maculopapular rash and two of toxic epidermal necrolysis and histopathologically, there were three cases of interface dermatitis, two of epidermal necrosis, and one of spongiotic dermatitis. Four patients had peripheral eosinophilia.A lymphocyte transformation test was performed in three cases and was positive for apalutamide in all cases. Except for the two cases of toxic epidermal necrolysis, which were fatal, the skin eruptions appeared 10 weeks after starting apalutamide. Considering the increasing number of patients with prostate cancer being treated with apalutamide, cases of apalutamide-induced drug eruption need to be accumulated and analyzed.

Cutaneous adverse reactions associated to apalumide: two case reports of DRESS syndrome and maculopapular exanthema

“…In our case, the rash developed 3 months after drug initiation. CAE during apalutamide display rather long delay [3,5,10]. Katsuta found that patients with severe CAE had a shorter mean onset time than patients with moderate CAE, 5.2 weeks and 9.6 weeks, respectively [10].…”

“…Postmarketing follow-up usually allows a better classification of those CAE. Apalutamide is mainly responsible for benign maculo-papular exanthema (MPE), xerosis, lichenoid reactions [3][4][5]. But potentially life threating condition such as acute generalized exanthematous pustulosis [6], DRESS [7,8] or toxic epidermal necrolysis [3] have been described in the literature.…”

“…Apalutamide is mainly responsible for benign maculo-papular exanthema (MPE), xerosis, lichenoid reactions [3][4][5]. But potentially life threating condition such as acute generalized exanthematous pustulosis [6], DRESS [7,8] or toxic epidermal necrolysis [3] have been described in the literature. We report two cases from our clinic illustrating the clinical spectrum of the CAE.…”

Case report: Apalutamide-induced severe lethal cutaneous adverse effects in China

“…On the basis of previous literature, dermatologic adverse events (dAEs) remain the most reported side effects of apalutamide. Up to now, 15 case reports and 3 retrospective analyses of apalutamiderelated drug eruptions have been published, with a divergent geographic distribution indicating the Japanese most vulnerable to dAEs of apalutamide (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, most of the dAEs remain mild and moderate with a fair prognosis (16,17).…”

Characteristics of mild and severe apalutamide‐related cutaneous adverse events in patients with prostate cancer: A review of the literature

“…Various clinical manifestations of ARCAEs have been reported. Mild ARCAEs include maculopapular, 1–3 lichenoid, 1,4 and exanthematous eruptions, 5,6 while severe ARCAEs include toxic epidermal necrolysis (TEN), 7–11 acute generalized exanthematous pustulosis, 12 and drug reaction with eosinophilia and systemic symptoms 13 . However, the clinical differences among severe and mild types of cutaneous adverse events remain unclear.…”