Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2023;13(2):e2023103 1 Biologics for the Treatment of Severe Acrodermatitis Continua of Hallopeau: Report of Two Cases Successfully Treated with Ixekizumab and Ustekinumab Luigi Gargiulo1,2, Francesco Toso1,2, Luciano Ibba1,2, Mario Valenti1,2, Antonio Costanzo1,2, Alessandra Narcisi1,2 1 Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy 2 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy Key words: psoriasis, acrodermatitis continua of Hallopeau, ixekizumab, ustekinumab, biologics Citation: Gargiulo L, Toso F, Ibba L, Valenti M, Costanzo A, Narcisi A. Biologics for the Treatment of Severe Acrodermatitis Continua of Hallopeau: Report of Two Cases Successfully Treated with Ixekizumab and Ustekinumab. Dermatol Pract Concept. 2023;13(2):e2023103. DOI: https://doi.org/10.5826/dpc.1302a103 Accepted: September 26, 2023; Published: April 2023 Copyright: ©2023 Gargiulo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: Antonio Costanzo has been a consultant and/or speaker for Abb-Vie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Galderma, Boehringer, Novartis, Pfizer, Sandoz, and UCB. Alessandra Narcisi has been a consultant and/or speaker for Abb-Vie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Boehringer, Novartis, Pfizer and UCB. Mario Valenti has been a consultant and/or speaker for, Leo Pharma, Eli Lilly, Boehringer and Sanofi. Luigi Gargiulo, Francesco Toso and Luciano Ibba have nothing to disclose. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Dr. Francesco Toso, MD, Dermatology Unit, Department of Biomedical Sciences IRCCS Humanitas Research Hospital, Humanitas University, Rozzano (MI), Italy. Tel: +39 0282244050 Email: francesco.toso@humanitas.it Introduction Acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis, which involves the distal portion of the digits of hands and feet [1]. The exact pathogenesis of this dis- ease is still not completely understood, and a role of interleukin (IL)-36 and IL-17 related cytokines (IL-17A/F, IL23Receptor) has been proposed [1]. ACH has a chronic-relapsing course, and it can lead to severe nail dystrophies [1]. Given the rarity of this condition, no data are available from clinical trials regard- ing the use of biological drugs in these patients [1,2]. We pres- ent two cases of severe ACH successfully treated with biologics: one patient received ixekizumab, a humanized monoclonal antibody targeting IL-17A, and the second was given usteki- numab, an inhibitor of IL-12/23. Case Presentation A 56-year-old patient presented to our Dermatology de- partment with a history of psoriasis and psoriatic arthritis (PsA), with a Dermatology Life Quality Index (DLQI) score of 28. In the past, she was treated with oral acitretin 10 mg, one capsule daily for 3 months, ineffectively. On clinical examination, we observed intense red erythema on the dis- tal surface of the five fingers of the right foot, along with intense pustulation and severe onychopathy (Figure 1A), 2 Research Letter | Dermatol Pract Concept. 2023;13(2):e2023103 and moderate erythema and onychopathy on the left foot (Figure 1B). A skin biopsy was not performed as the clinical picture was strongly suggestive for ACH. Given the severity of the clinical picture, as screening exams were all in the nor- mal ranges, we prescribed therapy with ixekizumab 80 mg, two injections at baseline followed by one injection every two weeks until week 12, and then every four weeks. At week 36, the patient came back to our department showing complete skin clearance, with the persistence of only slight onychopathy (Figure 2, A and B) and a DLQI of 1. The second patient is a 32-year-old female, who pre- sented to our Institute in 2016 with a history of flares of ACH (with fever and elevated neutrophils count), previously ineffectively treated with oral cyclosporine. On physical examination, several pustules on erythematous skin were observed on the distal surface of the fingers of both hands. Subsequently, after screening exams returned all in the nor- mal ranges, we prescribed ustekinumab 45 mg, 1 injection at weeks 0, 4, and then every 12 weeks. At week 40, the patient showed complete skin clearance. She is still on treatment to date, without any relapse of the disease. Conclusions The treatment of ACH is challenging, due to the lack of randomized clinical trials on biological drugs, given the rar- ity of this condition [2]. There are only a few case reports on the efficacy of ixekizumab in the treatment of pustular variants of psoriasis [3]. In our first case, we prescribed ixekizumab for several reason: the rapid onset of action, the efficacy on PsA and our favorable experience on this drug on difficult-to-treat areas [4,5]. On the other hand, more data are available on ustekinumab in patients affected by ACH [6]. In a multicenter retrospective study, ustekinumab showed improvement in 75.0% of patients [6]. In our case, we decided to prescribe ustekinumab because at the time it was the most recent and most effective biological drug approved for psoriasis. Further studies, with longitudinal design and larger cohorts of patients, are needed to establish the exact role of biologics, including ustekinumab and ixekizumab, in the management of ACH. BA Figure 1. (A) Severe acrodermatitis continua of Hallopeau affecting the digits of the right foot of a 56-year-old patient, with intense pustula- tion on erythematous skin along with severe psoriatic onychopathy. (B) Clinical appearance of the left foot. Research Letter | Dermatol Pract Concept. 2023;13(2):e2023103 3 References 1. Navarini AA, Burden AD, Capon F, et al. European consen- sus statement on phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017;31(11):1792-1799. DOI:10.1111/jdv .14386. PMID: 28585342. 2. Maliyar K, Crowley EL, Rodriguez-Bolanos F, O’Toole A, Gooderham MJ. The Use of Biologic Therapy in the Treatment of Acrodermatitis Continua of Hallopeau: A Review. J Cutan Med Surg. 2019;23(4):428-435. DOI:10.1177/1203475419836435. PMID: 30938189. 3. Miller AC, Holland TE, Cohen DJ. Treatment of acrodermati- tis continua of hallopeau with ixekizumab. J Dermatolog Treat. 2021;32(1):117-119. DOI:10.1080/09546634.2019.1628170. PMID: 31184530. 4. Narcisi A, Valenti M, Cortese A, et al. Anti-IL17 and anti-IL23 biologic drugs for scalp psoriasis: A single-center retrospec- tive comparative study. Dermatol Ther. 2022;35(2):e15228. DOI:10.1111/dth.15228 PMID: 34820969. 5. Husson B, Barbe C, Hegazy S, et al. Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau. J Eur Acad Dermatol Venereol. 2020;34(10):2330-2338. DOI:10.1111/jdv.16265 PMID: 32030802. 6. Gargiulo L, Pavia G, Ibba L, et al. Generalized Pustular Psoriasis and Plaque Psoriasis Successfully Treated With Ixekizumab. Clin Exp Dermatol Ther. 2022;7:183. DOI: 10.29011/2575 -8268.100183. Figure 2. (A,B) Clinical picture at week 36, showing resolution of the cutaneous lesions. Only slight onychopathy is observed.