Comment on 'A prospective real world study evaluating serum levels of arginine and cysteine in females with chronic telogen effluvium: do we really need blanket prescription with amino acid supplementation?'

Dear Editor, We read with great interest the recent article in Clinical and Experimental Dermatology by Megna et al., focusing on the clinical and histological features and skin cytokine milieu in patients with eczematous drug eruption (EDE) induced by anti-interleukin (IL)-17A monoclonal antibodies. The authors showed that the rate of EDEs (2.8%) during treatment with an anti-IL-17A drug are in line with the lowest percentages reported in the previous literature. In particular, the authors reported that IL-22 could be a potential trigger of the spongiotic phenotype diseases induced by anti-IL-17A. Biologics have become increasingly used in dermatology, with the result that related eczematous paradoxical reactions (E-PRs) have been observed with all categories of biologics, including tumour necrosis factor (TNF)-a inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, IL-23 inhibitors and IL-4/13 inhibitors. Reports of E-PRs in the biological treatment of psoriasis (PSO) have been increasing. The recent article by Megna et al. therefore provides a good guiding significance for clinical practice. However, we would like to highlight some key points. First and foremost, the authors showed that other biologics had been used previously by 179 patients (61.9%), mainly adalimumab (45%), etanercept (40.8%) and ustekinumab (33.2%), but did not state if paradoxical reactions had been observed with these biologics. Moreover, subgroup analysis of patients using previous different medicines (conventional systemic drugs, adalimumab, etanercept and ustekinumab) was not reported and is required for a deeper understanding. Previous studies reported that TNF-a inhibitors accounted for the most cases of eczematous reaction; a subgroup analysis might verify whether these previous treatments have an impact on the proportion of eczematous drug eruption when IL-17 inhibitors are used later. The mechanisms of eczematous eruption or E-PRs remain unclear. Some patients treated with monoclonal antibodies develop so-called PRs, that is, development of a de novo immune-mediated disorder or worsening of a preexisting immune-mediated disorder after starting the drug. Several hypotheses have been proposed, which mainly include three aspects: (i) aggravated imbalance of the cytokine milieu, (ii) paradoxical inflammation driven by T-cell polarization skewing and (iii) genetic susceptibility. However, more studies are needed to confirm the mechanisms of biologics related to E-PRs.