ORF virus causes tumor-promoting inflammation in sheep and goats.

ORF virus (ORFV) causes contagious ecthyma ("ORF"), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling.

Rapid Efficacy of riSankizumab in pretibial psoriasis invOLVEment: RESOLVE.

Background: Despite extraordinary improvements in the management of psoriasis in recent times, some areas of the body, such as the pretibial area, still show an unsatisfactory response and a more significant impact on patient quality of life. This multicentre study focuses on psoriasis affecting sensitive areas (particularly the pretibial area), its impact on quality of life and the therapeutic response to risankizumab. Methods: This multicentre prospective observational study recruited patients with moderate-to-severe psoriasis with pretibial area involvement. All patients underwent treatment with risankizumab (150 mg every 3 weeks), and efficacy was assessed after 24 weeks. Results: The study included 128 patients with a mean age of 51 years, suffering from moderate-to-severe psoriasis with involvement of the pretibial area with median total Psoriasis Area Severity Index score of 17.05 and Dermatology Life Quality Index of 16.27. The group was further divided into two sub-groups: the 'mother patch' group, in whom the very first psoriatic plaque appeared in the pretibial region (45 patients), and the 'non-mother patch' group, in whom the psoriatic lesion in the pretibial region was present but not as the first manifestation (83 patients). In order to better assess the involvement of psoriasis in the pretibial area, the pretibial plaque lesion severity index was also calculated at baseline in all patients: extent 2.75, erythema 2.64, infiltration 2.45 and desquamation 2.38. All participants in this study showed a good therapeutic response, with a reduction in all scores. Conclusions: The pretibial area is becoming an object of therapeutic interest due to some resistance to clearance and the consequent impairment of patient quality of life. This study showed that risankizumab can give favourable therapeutic results not only in patients with moderate-to-severe psoriasis with involvement of the difficult-to-treat areas but particularly in patients with recalcitrant plaques in the pretibial area.

Dupilumab: Direct Cost and Clinical Evaluation in Patients with Atopic Dermatitis.

Health care spending in Italy is high and continues to increase; assessing the long-term health and economic outcomes of new therapies is essential. Atopic dermatitis (AD) is a chronic, pruritic, immune-mediated inflammatory dermatosis, a clinical condition that significantly affects patients' quality of life at a high cost and requires continuous care. This retrospective study aimed to assess the direct cost and adverse drug reactions (ADRs) of Dupilumab and patients' clinical outcomes. All AD patients treated with Dupilumab at the Sassari University Hospital, Italy, between January 2019 and December 2021 were included. Eczema Area Severity Index, Dermatology Life Quality Index, and Itch Numeric Rating Scale scores were measured. ADRs and drug expenses were analyzed. A statistically significant posttreatment improvement was observed for all the indices measured: EASI (P < 0.0001), DLQI (P < 0.0001), NRS (P < 0.0001). The total expenditure for Dupilumab, in the observed period, amounted to € 589.748,66 for 1358 doses, and a positive correlation was shown between annual expenditure and delta percentage of variation pre- and posttreatment for the clinical parameters evaluated.

Molecular Insights into the Genetic Variability of ORF Virus in a Mediterranean Region (Sardinia, Italy).

Orf virus (ORFV) represents the causative agent of contagious ecthyma, clinically characterized by mild papular and pustular to severe proliferative lesions, mainly occurring in sheep and goats. In order to provide hints on the evolutionary history of this virus, we carried out a study aimed to assess the genetic variation of ORFV in Sardinia that hosts a large affected small ruminant population. We also found a high worldwide mutational viral evolutionary rate, which resulted, in turn, higher than the rate we detected for the strains isolated in Sardinia. In addition, a well-supported genetic divergence was found between the viral strains isolated from sheep and those from goats, but no relevant connection was evidenced between the severity of lesions produced by ORFV and specific polymorphic patterns in the two species of hosts. Such a finding suggests that ORFV infection-related lesions are not necessarily linked to the expression of one of the three genes here analyzed and could rather be the effect of the expression of other genes or rather represents a multifactorial character.

Elastosis perforans serpiginosa: causes and associated disorders.

BACKGROUND: Elastosis perforans serpiginosa (EPS) is an uncommon cutaneous disorder classified under perforating diseases (PD); a group of dermatoses with transepidermal extrusion of collagen or elastic tissue. Three EPS subtypes have been reported that differ according to aetiology, associated diseases, and histopathological features. Herein, we report a systematic review of the literature, as well as a case of a 41-year-old woman with Wilson disease treated with penicillamine (PCM), who developed EPS after 11 years of drug intake. OBJECTIVES: To analyse and characterise EPS subtypes based on an evaluation of potential different histological patterns. MATERIALS & METHODS: A systematic literature search in Pubmed was performed to identify articles describing EPS. RESULTS: A peculiar histological pattern was identified in EPS PCM-related patients, either in affected or unaffected skin samples. Using specific elastic fibre stains (Verhoeff-van Gieson, Weigert, and Orcein), fibres appeared with an irregular surface with thorn-like protrusion, probably due to weaker fibre cross-links, making them unable to re-expand after contraction along their long axis. Interestingly, similar histological patterns have also been reported in elastic tissues of vessel walls of the lungs and upper respiratory tract, joints, visceral adventitia, and kidney. CONCLUSIONS: A distinctive histological pattern of PCM-related EPS is observed in affected and normal-appearing skin, as well as extracutaneous elastic tissue, suggesting serious potential widespread drug-induced systemic elastolytic damage.