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Background: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. Objectives: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. Methods: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. Results: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. Conclusion: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

This work was supported by a Biomolecular Analyses for Tailored Medicine in AcneiNversa (BATMAN) project, funded by ERA PerMed, by a grant from the Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo/Italian Ministry of Health’ (RC16/2018), by a grant from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan (Protocol No. 487_2020) and by Starting Grant (SG-2019- 12369421) founded by the Italian Ministry of Health.

Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed.

A paradigmatic example of the critical role of cutaneous immunology is evident in prurigo nodularis. Since marked and lasting responses may not always be achievable from available treatments, this condition can represent a complex clinical scenario. An upregulation of IL-4 and signal transducer and activator of transcription 6 expression has been found in skin lesions of patients with prurigo nodularis (4), leading to the consideration of dupilumab as a potential therapeutic option in this condition (5).Cao et al.reported intriguing findings that highlight the effectiveness of dupilumab in prurigo nodularis, even in patients who had previously undergone multiple therapies. In recent years, this has led to a debate aimed at understanding which patient group benefits more from immunotherapy (12).Jaeger et al.attempted to address this question through a meta-analysis, revealing that NRAS-mutant cutaneous melanoma demonstrated an increased likelihood of a partial or complete tumor response compared to NRAS-wildtype cutaneous melanoma. [...]genomic screening for NRAS mutations in patients with metastatic melanoma could enhance predictive ability when initiating immunotherapy.

Primary cutaneous gamma-delta T cell lymphomas (PCGDTCLs) are rare and aggressive cutaneous malignancies that have been diagnostically challenging for dermopathologists and clinicians since their first published descriptions in 1991. Since then, the availability of immunostaining for T cell receptors γ and δ in formalin-fixed paraffin-embedded samples has greatly increased our knowledge of the gamma-delta phenotype by showing that it may also be present in the context of indolent entities, such as mycosis fungoides (MFs) and lymphomatoid papulosis, and this has raised questions concerning its diagnostic and prognostic implications. We here describe the histological and clinical differences between the dermo-epidermal and subcutaneous sub-groups of PCGDTCL observed in a cohort of 20 patients attending a single experienced centre, with particular focus on cases with an MF-like presentation, which are still less well defined than those of classic MF.

Cutaneous vasculitides encompass a heterogeneous group of clinicopathological entities, which may occur as single-organ vasculitis of the skin or present as skin-limited variant of systemic vasculitis (i.e., skin-limited ANCA-associated vasculitis), and are triggered by various factors, including infections, drugs and vaccines. The COVID-19 pandemic has challenged us with a variety of both disease- and vaccine-associated skin manifestations, including vasculitis. Among the latter, cutaneous small-vessel vasculitis, previously known as leukocytoclastic vasculitis, seems to be the most reported in either scenario, i.e., natural infection and vaccination. Vasculopathy without true vasculitic changes on histology develops in but a minority of cases, mostly severe/critical COVID-19 patients, and appears to be the result of endothelial injury due to pauci-immune thromboembolic mechanisms. Herein, we provide an overview of the available literature on COVID-19-associated and anti-SARS-CoV-2-vaccine-associated cutaneous vasculitis. Although evidence is mostly limited to isolated reports, with a proportion of cases lacking histopathological confirmation, ample overlap with pre-pandemic forms is shown.

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by circulating autoantibodies toward the hemidesmosomal antigens BP180 and BP230. Cases of BP have been described following vaccinations against tetanus, poliomyelitis, diphtheria, influenza, pneumococcus, meningococcus, hepatitis B and rabies. The putative mechanism by which COVID-19-vaccines may induce BP has not been clarified. An Italian multicentre study was conducted to collect clinical, histopathological and immunopathological data of patients with BP associated with COVID-19-vaccines. Twenty-one cases were collected, including 9 females and 12 males (M/F = 1.3) with a median age at diagnosis of 82 years. Seventeen patients received the COMIRNATY Pfizer-BioNTech vaccine, two the Moderna mRNA-1273 vaccine, one the ChAdOx1/nCoV-19-AstraZeneca/ Vaxzevria vaccine and one received the first dose with the ChAdOx1/nCoV-19-AstraZeneca/Vaxzevria vaccine and the second dose with the COMIRNATY Pfizer-BioNTech vaccine. Median latency time between the first dose of anti-SARS-CoV-2 vaccine and the onset of cutaneous manifestations was 27 days. Median BPDAI at onset was 42. Eleven out of seventeen patients (65%) had positive titres for anti-BP180 antibodies with a median value of 106.3 U/mL on ELISA; in contrast, only five out of seventeen (29%) were positive for anti-BP230 antibodies, with a median of 35.3 U/mL. In conclusion, in terms of mean age, disease severity at diagnosis and clinical phenotype vaccine-associated BP patients seem to be similar to idiopathic BP with an overall benign course with appropriate treatment. On the other hand, the slight male predominance and the reduced humoral response to BP230 represent peculiar features of this subset of patients.

Cutaneous manifestations of hematologic malignancy represent both a clinical challenge for the treating physician and a pathophysiological model for advancing the knowledge on individual neoplasms. Indeed, a growing body of evidence supports the concept of recurrent molecular defects associating with specific clinical features, as best exemplified by VEXAS. Herein neutrophilic and eosinophilic dermatoses of potential interest for both hematologists and dermatologists will be reviewed, including subcorneal pustular dermatosis-type IgA pemphigus, neutrophilic eccrine hidradenitis, Sweet’s syndrome as well as myelodysplasia cutis and VEXAS, pyoderma gangrenosum, eosinophilic annular erythema, eosinophilic dermatosis of hematological malignancy, Wells syndrome and cutaneous involvement in hypereosinophilic syndromes. Possible management approaches are discussed for each, emphasizing scenarios that require treatment of the underlying condition to achieve remission at the skin level.

Only some cases of pityriasis rosea (PR)/pityriasis rosea-like eruption (PRLE) after anti-SARS-CoV-2 vaccination have been reported. In the period May 2021 - February 2022 we observed five cases of clinically typical PR that appeared 2 to 3 weeks after anti-SARS-CoV-2 vaccination with BNT162b2 (3 patients) or mRNA-1273 (2 patients). In four patients PR appeared after the first vaccination; in one patient after the second one. In three patients a biopsy for histopathological examinations was carried out. Results were typical for PR. In all patients laboratory examinations were within normal ranges. All patients were treated with cetirizine. Complete remission was observed within 14-30 days. Four patients were subjected to the second vaccination, but no skin lesions appeared. All patients are currently in good general health. It is possible that a relationship anti-Sars-CoV-2 vaccination−PR/PRLE exists; however, it is very rare, in consideration of millions of vaccinated subjects and the low number of reported cases of PR/PRLE. The pathogenesis of this relationship is unknown. However, some hypotheses may be advanced: PR/PRLE following anti-Sars-CoV-2 vaccination may be just a coincidence; anti-Sars-CoV-2 vaccines cause a reactivation of HHV-6 and/or HHV-7; vaccines can induce a delayed hypersensitivity response clinically similar to drug-induced PRLE.