Effectiveness of brodalumab in acrodermatitis continua of Hallopeau: A case report

Abstract

Dear Editor, Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic pustolosis involving one or more fingers or toes; the sterile pustules arise on erythematous skin of the distal phalange and are often associated with paronychia (Di Costanzo, Napolitano, Patruno, Cantelli, & Balato, 2014). If left untreated the disease leads to skin atrophy, onychodistrophy, and osteolysis; therefore, ACH has a high negative impact on quality of life of patients (Smith et al., 2019). Although some authors consider ACH as a distinct entity, it is generally considered as a variant of pustular psoriasis. Indeed, it may be associated with mutations in IL36RN, and especially in CARD14 and AP1S3 genes, as reported for pustular psoriasis (Smith et al., 2019). Due to the chronic-relapsing course of the disease and to the lack of treatment guidelines, the therapeutic choice for ACH is a challenge for the clinician. Only case reports describing the use of several therapies with equivocal results are reported in the literature. Efficacy of some biological drugs has been outlined in recent years (Smith et al., 2019). A 37-year-old female patient was referred to us for a 23-year history of a pustular eruption of the distal phalange of all the fingers of both the hands. Physical examination showed erythema, pustules, erosions, and crusting involving the fingertips and the perionychium (Figure 1a). The patient reported that skin lesions were painful and significantly affected the patient s hairdressing activity. Histology showed intraepidermal spongiform pustules with aggregation of neutrophils; moreover, lymphoistiocytic infiltrate, focal edema, and elongated and tortuous vessels were found in the dermis. Previous treatments with topical and systemic corticosteroids, cyclosporine, and methotrexate improved the disease only slightly and temporarily. Based on recent reports of successful treatment of ACH with anti-interleukin (IL) 17 biologic agents (Galluzzo, D Adamio, Teoli, Bianchi, & Talamonti, 2019; Miller, Holland, & Cohen, 2019), therapy with brodalumab was considered. Brodalumab is a human anti-IL17 receptor A monoclonal antibody. The drug was administered subcutaneously at the dose of 210 mg at weeks 0–2, followed by 210 mg every 2 weeks. After the second administration of brodalumab, all the lesions showed a complete remission (Figure 1b). The patients also reported that the pain disappeared, thus returning to be fully able to practice her work. Currently, the patient has been in treatment for 6 months and during this period there have been no recurrences or side effects. Treatment of ACH is a challenge for the dermatologist. Indeed, resistance to therapies and an absence of therapeutic recommendations make it difficult to manage. Topical treatment with potent corticosteroids, 5-fluorouracile, calcineurin inhibitors, and analogous of vitamin D, or systemic treatment with retinoids, methotrexate, cyclosporine, apremilast, and phototherapy gave conflicting results (Smith et al., 2019). Therapies with biologic drugs appear to be increasingly promising. Indeed, anti-TNFα, anti-IL12/23, and anti-IL1 agents were proven to be effective in some cases of ACH (Smith et al., 2019). More recently, encouraging results were reported for anti-IL17 agents since both secukinumab (Galluzzo et al., 2019) and ixekizumab (Miller et al., 2019) were reported to be efficacious in severe and recalcitrant cases of ACH. Very recently, a case of ACH recalcitrant to the treatment with anti-IL17 agents secukinumab and ixekizumab and successfully treated with brodalumab was reported (Milani-Nejad & Kaffenberger, 2019). The pathophysiology of ACH is not yet known, but shares many aspects with pustular psoriasis (Smith et al., 2019). Mutations in IL36RN, CARD14, and AP1S3 genes in patients with pustular psoriasis have been associated with loss of function of IL-36R antagonist and consequent promotion of the synthesis of IL17 (Arakawa et al., 2018). These genes also appear to be involved in the pathogenesis also of ACH (Smith et al., 2019). Navarini et al. reported that the expression of both IL17A and IL17F isoform in palmoplantar pustular psoriasis was consistently high (Navarini, 2017). Brodalumab blocks the IL17RA receptor and is therefore able to inhibit the binding of both IL17A and IL17F (Navarini et al., 2017). In a long-term Phase III study, 12/13 patients with generalized pustular psoriasis achieved complete remission after 52 weeks of treatment with brodalumab (Yamasaki, Nakagawa, Kubo, & Ootaki, 2017). These observations could explain the dramatic response to brodalumab in our patient and, as reported in the literature (Milani-Nejad & Kaffenberger, 2019), also in patients with ACH resistant to the treatment with secukinumab and ixekizumab, since these two drugs only target IL17A. Although limited to a single patient, our experience suggests that brodalumab might be considered as a possible valid choice for the management of recalcitrant ACH.