Eczematous eruption during anti‐interleukin 17 treatment of psoriasis: an emerging condition

Dear Editor, Major advances in psoriasis pathogenesis have resulted in the development of effective new drugs for its treatment. In particular, biologics have revolutionized disease management.1 Tumour necrosis factor (TNF)‐α inhibitors were the first in 2000.1 Thus, adverse cutaneous reactions to their use have been extensively investigated.2 However, the anti‐interleukin (IL)‐17 agents secukinumab, ixekizumab and brodalumab have been introduced more recently for moderate‐to‐severe psoriasis.1 As a consequence, possible skin adverse events as a result of their use are not so fully elucidated. Eczematous eruption (EE) has been previously reported in 5–20% of patients with various inflammatory diseases treated with anti‐TNF‐α.3 Conversely, only anecdotal cases of EE induced by anti‐IL‐12/23 or anti‐IL‐17 in patients with psoriasis have been described.4,5 We performed a 2‐year retrospective study to evaluate the frequency of EE in a cohort of patients with moderate‐to‐severe psoriasis treated with anti‐IL‐17 agents. Data were collected analysing the computer‐based databases of the psoriasis care centres of two Italian university hospitals (Napoli and Catanzaro), from June 2016 to June 2018, collecting demographic, disease and treatment data. A total of 185 patients [109 men (58·9%); mean age 50·8 years] were enrolled. In total, 115 patients (62·2%) had been treated with secukinumab with a mean therapy duration of 17·2 months and 70 patients (37·8%) with ixekizumab (mean duration: 9·2 months). Previous conventional systemic drugs had been used in 82·7% (n = 153) of the patients whereas biologics had been used in 57·8% (n = 107), with adalimumab and etanercept playing a major role (45% and 41%, respectively). A total of four patients (4/185, 2·2%) with EE, probably induced by anti‐IL‐17 therapy, were observed (Table 1). Mean treatment duration at EE onset was 13·5 weeks. Three patients were on secukinumab therapy (mean treatment duration 14·6 weeks) and one on ixekizumab (mean therapy duration 10 weeks). Anti‐IL‐17‐induced EE diagnosis was established after clinical and histological examination as well as the execution of a patch test with the Italian Society of Allergologic, Professional and Environmental Dermatology baseline series. Anti‐IL‐17 treatment discontinuation was required in three patients, as topical and/or systemic corticosteroids were not able to achieve stable and sustained improvement of the EEs. Clinical features of patients with eczematous eruption (EE) IL, interleukin; ACD, allergic contact dermatitis; NB‐UVB, narrowband ultraviolet B. Clinical features of patients with eczematous eruption (EE) IL, interleukin; ACD, allergic contact dermatitis; NB‐UVB, narrowband ultraviolet B. In this study we reported for the first time the frequency of EE in patients with psoriasis treated with anti‐IL‐17. This adverse reaction is unreported and little investigated. In 2012, Pernet et al. reported the first case of EE occurring after the administration of ustekinumab4 and recently Burlando et al. observed a case of atopic‐like dermatitis occurring after every secukinumab injection for 6 months.5 EE resulting from anti‐TNF‐α treatment has been previously described.4,6 (An additional table outlining case reports or case series describing EEs during biological therapy in patients with psoriasis is available from the authors on request.) These reactions usually occur 1–14 days after drug administration, are usually moderate and short term and do not require anti‐TNF‐α discontinuation.3 Conversely, in our study EE occurred several months after starting biologics (mean 13·5 weeks) and was of moderate‐to‐severe intensity. Furthermore, in 75% of the patients anti‐IL‐17 discontinuation was necessary to definitively resolve the EE. Interestingly, all our patients had a positive personal history of atopy, which appeared as a risk factor in line with Esmailzadeh et al.'s case of anti‐TNF‐α‐induced EE.7 The pathogenesis of EE with biologic use is not clear. Psoriasis and eczema are diseases caused by an imbalance in the T helper (Th)1/Th2 immune response, with Th1 being more prominent in psoriasis and Th2 in eczema.1,5 It is thought that the Th1 and Th2 pathways are closely related in that when the Th1 response is blocked or decreased, the Th2 balance will in turn increase, and vice versa.5 Anti‐IL‐17 drugs block the Th1 pathway, thus explaining the probable reason why eczema appeared in our patients. Moreover, Stoffel et al. reported that EE induced by anti‐TNF‐α showed high levels of IL‐22, not only when compared with psoriasiform lesions that occurred with anti‐TNF‐α treatment, but also compared with conventional psoriasis and eczema lesions.8 Indeed, IL‐22 has been demonstrated to promote epidermal hyperplasia and to inhibit epidermal differentiation in spongiotic lesions.8 However, Mangan et al. showed that in an imiquimod‐induced skin inflammation model the use of anti‐IL‐17 antibody did not reduce IL‐22 serum concentration.9 Therefore, we could speculate that IL‐22 may be a key mediator in the pathogenesis of EE induced by anti‐IL‐17 agents. In conclusion, our 2‐year retrospective study shows that EE appears to be an emerging condition in patients with psoriasis on anti‐IL‐17 treatment. EE developed in 2·2% of patients treated with anti‐IL‐17 agents, requiring treatment discontinuation in 75%. A personal history of atopy seems to be a risk factor. Further studies are needed to evaluate the frequency of these eruptions and their management. Funding sources: none. Conflicts of interest: none to declare.