BACKGROUND:Birch pollen food allergy syndrome to apples is prevalent, but no approved or standardized treatment exists so far. OBJECTIVE:To investigate the effect of oral therapy with fresh apples on birch pollen food allergy syndrome to apples using a feasible treatment protocol with different widely available apple cultivars. METHODS:In this uncontrolled phase II/III study, 42 apple cultivars were tested for their allergen content in vivo by skin prick tests and oral provocations. Afterward, 36 patients consumed apples of increasing dose and allergenicity over a period of 12 months. Side effects were documented weekly in a clinical diary. Efficacy was tested before and after therapy by oral provocation and a skin prick test with the Golden Delicious apple. Total IgE, specific IgE, and IgG4 for Mal d 1 and inhibition of basophil activation were analyzed before and after treatment. Other cross-reactive foods were determined by a questionnaire before and after therapy. RESULTS:Oral immunotherapy with apples resulted in a consistent and durable tolerance of apples and a significant augmented tolerance to other Bet v 1 cross-reactive foods. After therapy, specific IgG4 antibodies to Mal d 1 increased significantly; simultaneously specific IgE to Mal d 1 and skin prick test reactivity to apples decreased significantly. Moreover, sera of treated patients displayed blocking activity to Mal d 1. CONCLUSION:Oral allergy-specific immunotherapy with fresh apples is a promising treatment for birch pollen food allergy syndrome to apples and other Bet v 1 cross-reactive foods.

In the original publication [...].

The range of dermatologic diseases of the breast, nipple, and areola (BNA) skin comprises various inflammatory and neoplastic alterations. BNA skin represents a unique functional unit with considerable emotional, sexual, and cosmetic importance. A specialized approach and adequate sensitivity are required for the diagnosis and treatment of dermatologic diseases in this area. This article reviews the normal anatomy of the breast, common inflammatory, infectious, and benign or malignant proliferative diseases or harmatomas that can present in the breast and nipple skin. Skin diseases in the breast area may be specific to this location or not, and can be classified into proliferative diseases, including malformations and neoplasms, and inflammatory diseases, which encompass both infectious and non-infectious inflammations. Benign proliferations include nipple adenoma, fibrous papules, seborrheic keratoses, gynecomastia, benign subcutaneous tumors, melanocytic and epidermal nevi. Malignant neoformations comprise Paget's disease, invasive breast cancer, inflammatory breast cancer, metastases, melanoma, and non-melanoma skin cancers including Merkel cell carcinoma, but also sarcomas. Inflammatory conditions are atopic, irritant, or allergic nipple eczema, radiation dermatitis, mastopathy and Koebner reactions of other skin diseases due to friction in this area. Infections include bacterial, fungal, and viral entities that might be typical for this area such as borrelial lymphocytoma.

Das Spektrum von dermatologischen Erkrankungen der Haut umfasst verschiedene entzündliche und neoplastische Veränderungen. Die Haut von Brust, Areola mammae und Mamille stellt eine einzigartige funktionelle Einheit mit einer erheblichen emotionalen, sexuellen und kosmetischen Bedeutung dar. Für die Diagnose und Behandlung von dermatologischen Erkrankungen in dieser Körperregion sind ein spezieller Ansatz und eine angemessene Sensibilität erforderlich. Dieser Artikel gibt einen Überblick über die normale Anatomie der Brust und über häufige entzündliche, infektiöse, gutartige und bösartige proliferative Erkrankungen sowie Hamartome, die in der Brust‐ und Brustwarzenhaut auftreten können. Hautkrankheiten im Brustbereich können für diese Lokalisation spezifisch oder unspezifisch sein und in proliferative (einschließlich Fehl‐ und Neubildungen) und in entzündliche Erkrankungen (einschließlich Infektionen und nicht‐infektiöse Entzündungen) unterteilt werden. Zu den gutartigen Tumoren gehören Adenome der Mamillen, fibröse Papeln, seborrhoische Keratosen, die Gynäkomastie, gutartige subkutane Tumoren und melanozytäre und epidermale Nävi. Zu den bösartigen Neubildungen gehören der Morbus Paget, der invasive und der entzündliche Brustkrebs, Metastasen, Melanome und nicht‐melanozytäre Hauttumoren, einschließlich des Merkelzellkarzinoms, aber auch Sarkome. Entzündliche Erkrankungen umfassen das atopische, irritative oder allergische Brustwarzenekzem, die Strahlendermatitis, die Mastopathie und Köbner‐Phänomene anderer Hautkrankheiten, die durch Irritationen innerhalb der betroffenen Hautstellen verursacht wurden. Zu den Infektionen zählen vor allem bakterielle, mykotische und virale Infektionen, die in dieser Region auftreten können, wie z. B. das Lymphozytom bei Borreliose.

Benzoyl peroxide (BPO) and niacinamide (Niac) are commonly used alone or in combination with other molecules in the treatment of acne. BPO and Niac in the same product could exert complementary and synergistic effects improving efficacy in acne. Furthermore, Niac could reduce some side effects of BPO, such as skin irritation and erythema. A film-forming cream product containing BPO 4% and Niac 4%, vehiculated in a mixture of polyvinyl alcohol (PVA) and perfluoropolyether (PFPE) has been recently developed (B-N cream). A 28-day, assessor-blinded pilot trial was conducted to evaluate the clinical efficacy, skin tolerability, sebum production, skin redness, and skin microbiome modulation of B-N cream in subjects with mild to moderate acne of the face. Twenty-two adult men and women with mild-to-moderate acne of the face participated in this trial, after their written informed consent. B-N cream was applied once daily in the evening. The use of B-N cream was associated with a statistically significant decrease in acne lesions after treatment in comparison with baseline (non-inflammatory lesions: −40%; inflammatory lesions: −43% and total lesions: −41%). The use of the cream was not associated with a skin barrier function alteration. The skin redness score (−11%) and the sebum production (−42%) were significantly reduced after treatment. The use of B-N cream determined a reduction in the relative abundance of the Actinobacteria phylum (Corynebacterium and Propionibacterium, from 56% to 47%) and a significant increase in the abundance of Bacteroidetes phylum (from 3% to 5.2%). In addition, the product was well tolerated. In conclusion, this film-forming, medical device cream was effective in subjects with mild-to-moderate acne, reducing acne lesions and sebum production without altering skin barrier function, offering good skin tolerability. Furthermore, this product exerts positive skin microbiome modulation effects.

BACKGROUND:This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). METHODS:We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT). RESULTS:452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1-8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. CONCLUSIONS:Among patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.

Until now, a systematic approach to the common dermoscopic appearance of cutaneous metastases (CM) from various primary malignancies has been lacking. The article by Danica Tiodovic1 in this issue finally sheds light on this topic and provides important information not only on dermoscopy but also on the localization of metastatic disease in the skin. CM are not uncommon. They occur in approximately 5% of internal malignancies, and as many as 10% of patients with known metastatic cancer develop CM.2 They are a poor prognostic sign with a median survival of less than 1 year after presentation in most studies, with better survival in both melanoma and breast cancer.3 Recognition is important because they are often the first sign of tumour recurrence or may be the first sign of internal malignancy, especially in lung cancer. Verremmen reported that in 18.6% of patients with CM from internal malignancies, they were the first presentation of a previously clinically silent primary malignancy, 80% of which were lung tumours.4 The most common CM from internal malignancies are from breast cancer in women, followed by bronchus and lung, then gastrointestinal cancers, while in men, bronchus and lung are followed by gastrointestinal cancers.4-6 Clinically, they present as single or, more frequently, multiple skin-coloured, blue-brown, black or reddish-purple cutaneous or subcutaneous firm, painless, hard nodules. Ulceration, especially in breast cancer, may occur over time but is usually not the first presenting sign. Clinical appearance may give a clue to the originating cancer, so pigmented metastases are in the vast majority of cases from melanoma in 97.8%,1 while CM from renal cell carcinoma are often red or purple and may mimic hemangiomas or pyogenic granulomas.2, 3 Most clinical variants have been described in metastatic breast cancer, which is not surprising since 23.9% of patients with metastatic breast cancer developed CM in one large study.2 As for the localization of CM, more than 70% are locoregional, for example, melanoma metastases are often located near the primum and along regional lymphatic vessels. In absolute numbers, most CM develop on the trunk (39%), especially for breast cancer. Relative to body surface area, the head and neck were the most common sites of cutaneous metastasis, accounting for 32% of all distant metastases compared to 9% of body surface area.1 Another common site of cutaneous distant metastasis relative to body size is the umbilicus (0.5% of body surface area, rule of palm), with approximately 4% of CM developing there. They are called Sister Mary Joseph nodules and have been associated with gastrointestinal tumours and gynecologic malignancies.2-4 Melanoma, as a cutaneous malignancy, exhibits the most promiscuous metastatic pattern involving virtually all body sites.1 CM have been difficult to recognize due to their variable clinical presentation with wide differential diagnoses that can mimic benign skin lesions including erysipelas, herpes zoster, impetigo, erythema annulare centrifugum, radiation dermatitis, morphea, or pyogenic granuloma or malignant lesions including basal cell carcinoma, Merkel cell carcinoma or primary melanoma.5, 6 Dermoscopy of non-pigmented CM is not statistically different for various metastatic tumours, including melanoma.1 However, a common dermatoscopic pattern was identified that may help differentiate CM from other skin proliferations: structureless white combined with linear serpiginous vessels were found in 76% of cases, rising to 87% of cases when amelanotic melanoma CM were excluded. Not surprisingly, the majority of melanoma CM were pigmented, with structureless blue and brown being the most common patterns with vascular structures. Differentiation from blue nevi may still be difficult, but as the authors note, the presence of vascular structures on dermoscopy, recent onset and history of melanoma helps in differentiation.1 Recognition of CM is important in cancer follow-up in order to initiate treatment in a timely manner and a targeted cutaneous examination especially at the site near the primary tumour, second the head and neck area for all metastatic disease, the thoracic wall especially for breast cancer and the umbilicus for malignant gastrointestinal tumours. None. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

A 61-year-old HIV-negative, man presented with itchy lesions on his genital area, that had developed 3 days before the consultation. Seven days before the eruption, he attended a party where he had unprotected sexual intercourse with men. Physical examination showed 3, 3 to 4 mm, asymptomatic, umbilicated vesicles and multiple pustules on the penis shaft and pubis, accompanied by bilateral lymphadenopathy (Fig 1, A). On follow-up after 10 days, the vesicles and pustules spontaneously resolved, leaving some crusted lesions (Fig 1, B). Dermoscopy of an umbilicated vesicle revealed a trizonal pattern, characterized by a central ulceration-crust, a white peripheral halo with dotted hemorrhagic vessels and a paler pink zone at the periphery (Fig 2). Histopathology showed a cluster of pallor and ballooning degeneration of keratinocytes, with scattered eosinophilic cytoplasmic inclusions (Fig 3).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: What is the most likely diagnosis?A.Molluscum contagiosumB.ChickenpoxC.CryptococcosisD.SmallpoxE.Monkeypox Answers:A.Molluscum contagiosum – Incorrect. Umbilication of lesions raise the possibility of molluscum contagiosum, caused by a poxvirus, but molluscum has a longer incubation period ranging from 2 weeks to 2 to 3 months, skin lesions are characterized by smooth and firm papules without vesiculation and histopathology shows lobular epidermal hyperplasia resulting in a cup-shaped lesion in which keratinocytes are enlarged and filled with eosinophilic inclusion bodies, known as Henderson-Patterson bodies.B.Chickenpox – Incorrect. Chickenpox, caused by the varicella-zoster virus, is more typical of pediatric age and it is characterized by a generalised, cropping vesicular rash with intense pruritus. Histopathologically, keratinocytes are multinucleated, acantholytic with nuclear inclusions with epidermal necrosis similar to herpes simplex. Leucocytoclastic vasculitis may be present.C.Cryptococcosis – Incorrect. Although skin lesions of cryptococcosis present with dome-shaped, firm umbilicated papules, they appear predominantly over the face and histologically reveal layers of clear histiocytes containing spherical fungal structures of 4 to 20 μm.D.Smallpox – Incorrect. Smallpox is caused by the variola virus belonging to genus Orthopoxvirus. The last occurring patient of smallpox was reported in 1977. In 1980, the World Health Organization declared that smallpox had been eradicated and there is no evidence of new cases of smallpox transmission in any part of the world.E.Monkeypox – Correct. Given the current outbreak, a new onset of a vesicular or pustular rash with central umbilication that develop simultaneously with lymphadenopathy in the genital area, in addition to the history of intimate contact with casual sexual partners, is suspicious for monkeypox. In our case, a real-time polymerase chain reaction of a swab was positive for Orthopoxvirus, establishing the diagnosis of monkeypox infection. Moreover, histopathology showing ballooning degeneration of keratinocytes with the presence of eosinophilic intracytoplasmatic inclusion bodies (Guarnieri bodies) is consistent with infection from Orthopoxvirus. Dermoscopy with the trizonal pattern of central necrosis, white peripheral halo, and a paler pink zone has been also described as a reproducible and additional supportive tool to integrate clinico-pathological correlation when dealing with lesions potentially related to monkeypox.1Escudero-Tornero R. Sobral-Costas T.G. Servera-Negre G. Monkeypox infection.JAMA Dermatol. 2022; 158: 1203https://doi.org/10.1001/jamadermatol.2022.3975Crossref PubMed Scopus (5) Google Scholar Question 2: Which of the following best describes the mode of transmission of monkeypox to humans?A.The monkeypox virus is transmitted from human to human only through contact with infected skin and body fluidsB.The monkeypox virus is transmitted from human to human only through respiratory dropletsC.The monkeypox virus cannot be transmitted from human to human but only be transmitted from animal to human through scratch, and direct contactD.The monkeypox virus is transmitted from human to human only by sexual contactsE.The monkeypox virus is transmitted from human to human by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding, towels, clothes, objects, electronics and surfaces Answers:A.The monkeypox virus is transmitted from human to human only through contact with infected skin and body fluids – Incorrect. Monkeypox virus is transmitted from human to human through direct and indirect contact with infected skin and body fluids and respiratory droplets.B.The monkeypox virus is transmitted from human to human only through respiratory droplets – Incorrect. Monkeypox virus is transmitted from human to human through respiratory droplets and direct and indirect contact with infected skin and body fluids.C.The monkeypox virus cannot be transmitted from human to human but only be transmitted from animal to human through scratch, and direct contact – Incorrect. Monkeypox virus is transmitted from both animal to human and human to human.D.The monkeypox virus is transmitted from human to human only by sexual contacts – Incorrect. A fomite transmission by clothing, bedding, towels, objects, electronics, and surfaces is admitted as well as through respiratory droplets.E.The monkeypox virus is transmitted from human to human by close contact with lesions, body fluids, respiratory droplets, and contaminated materials such as bedding, towels, clothes, objects, electronics, and surfaces – Correct.2Ramos-Rodríguez D. Mercader-Salvans J. Algarra-Sahuquillo J. Aleman-Valls M.R. Pestana-Eliche M.M. Hernandez-Leon N. Dermoscopy of monkeypox: histopathology and clinical correlation.J Eur Acad Dermatol Venereol. 2022; (Epub ahead of print)https://doi.org/10.1111/jdv.18596Crossref PubMed Scopus (3) Google Scholar Monkeypox virus is transmitted from human to human through respiratory droplets and direct and indirect contact with infected skin and body fluids. Question 3: Which is the best treatment for monkeypox in the dermatological setting?A.Topical steroidsB.Specific antiviral therapy with a new agent such as ecovirimat should be given to all patients with monkeypoxC.Acyclovir 800 mg 5 times a day for 7 days should be given at the first symptomsD.Specific antiviral therapy with cidofovirE.There is no specific clinically-proven therapy for monkeypox disease and only supportive symptom management is considered. Skin lesions show spontaneous resolution. However, the use of topical antibiotics may be useful in case of a secondary infection Answers:A. Topical steroids – Incorrect. Like in most viral skin diseases, such as herpes virus infections,topical steroids are not recommended and patients should avoid applying steroids on active lesions of monke-ypox for the risk of spreading.B.Specific antiviral therapy with a new agent such as ecovirimat should be given to all patients with monkeypox – Incorrect. Tecovirimat, that is a new antiviral drug still under evaluation by clinical trials for monkeypox is only indicated in high-risk patients such as immunocompromised people, or those with severe disease.C.Acyclovir 800 mg 5 times a day for 7 days should be given at the first symptoms – Incorrect. This is the treatment indicated for chickenpox and herpes zoster infections.D.Specific antiviral therapy with cidofovir – Incorrect. Cidofovir is an antiviral medication that is approved for the treatment of cytomegalovirus retinitis in patients with AIDS. Data are not still available on the effectiveness of cidofovir in the treatment of monkeypox virus infection. Moreover cidofovir is nephrotoxic.E.There is no specific clinically-proven therapy for monkeypox disease and only supportive symptom management is considered. Skin lesions show spontaneous resolution. However, the use of topical antibiotics may be useful in case of a secondary infection – Correct.3Kumar N. Acharya A. Gendelman H.E. Byrareddy S.N. The 2022 outbreak and the pathobiology of the monkeypox virus.J Autoimmun. 2022; 131102855https://doi.org/10.1016/j.jaut.2022.102855Crossref PubMed Scopus (159) Google Scholar Skin lesions show a spontaneous resolution, therefore in most cases no treatment or supportive symptoms management are required. None disclosed.

Journal of the European Academy of Dermatology and VenereologyVolume 37, Issue 3 p. e418-e420 LETTER TO THE EDITOR A rare case of agminated juvenile Xanthogranuloma: Clinical and dermatoscopic evolution Maria Pichler, Maria Pichler orcid.org/0000-0002-0449-5958 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, ItalySearch for more papers by this authorTobias Thuile, Tobias Thuile Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, ItalySearch for more papers by this authorKlaus Eisendle, Corresponding Author Klaus Eisendle [email protected] orcid.org/0000-0002-8234-9964 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, Italy Claudiana Research, University Pool of Health-Care Professions Claudiana, Bolzano, Bozen, Italy Correspondence Klaus Eisendle, Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, 39100 Bolzano/Bozen, Italy. Email: [email protected]Search for more papers by this author Maria Pichler, Maria Pichler orcid.org/0000-0002-0449-5958 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, ItalySearch for more papers by this authorTobias Thuile, Tobias Thuile Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, ItalySearch for more papers by this authorKlaus Eisendle, Corresponding Author Klaus Eisendle [email protected] orcid.org/0000-0002-8234-9964 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano, Italy Claudiana Research, University Pool of Health-Care Professions Claudiana, Bolzano, Bozen, Italy Correspondence Klaus Eisendle, Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Teaching Hospital Bolzano/Bozen, 39100 Bolzano/Bozen, Italy. Email: [email protected]Search for more papers by this author First published: 30 September 2022 https://doi.org/10.1111/jdv.18618Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Dehner LP. Juvenile xanthogranuloma in the first decades of life. A clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestation. Am J Surg Pathol. 2003; 27(5): 579– 93. 2Song M, Kim S-H, Jung D-S, Ko H-C, Kwon K-S, Kim M-B. Structural correlations between dermoscopic and histopathological features of juvenile xanthogranuloma. J Eur Acad Dermatol Venereol. 2011; 25(3): 259– 63. 3Zelger BW, Sideroff A, Orchard G, Cerio R. Non-Langerhans cell histiocytosis. A new unifying concept. Am J Dermatopathol. 1996; 18(5): 490– 504. 4Freyer DR, Kennedy R, Bostrom BC, Kohut G, Dehner LP. Juvenile xanthogranuloma: forms of systemic disease and their clinical implications. J Pediatr. 1996; 129(2): 227– 37. 5Calderon C, Ramsingh A, Pattron R, Umakanthon S, Ramnarine D. Multiple intracranial juvenile xantogranouloma not a straightforward diagnosis (a case report). Int J Surg Case Rep. 2021; 85:106265. https://doi.org/10.1016/j.ijscr2021.106265 6Vargas-Mora P, Orlandi D, Aranibar L, Carreno L. A large congenital cutaneous tumor. J Dtsch Dermatol Ges. 2021; 19(5): 779– 81. 7Hernandez Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol. 1997; 36(3pt1): 355– 67. 8Moon SH, Cho SH, Lee JD, Kim HS. A case of segmental (zosteriform) juvenile Xanthogranuloma. Ann Dermatol. 2017; 29(6): 806– 8. 9Ng SY. Segmental juvenile xanthogranuloma. Pediatr Dermatol. 2014; 31(5): 615– 7. 10Kaur MR, Brundler MA, Stevenson MC. Disseminated clustered juvenile xanthogranuloma: an unusual morphological variant of a common condition. Clin Exp Dermatol. 2008; 33(5): 575– 7. Volume37, Issue3March 2023Pages e418-e420 ReferencesRelatedInformation

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Prolonged treatment response of a giant basal cell carcinoma to vismodegib after treatment cessation Cinzia Carriere, Cinzia Carriere Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorElena Polestra, Elena Polestra Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorFrancesca Ingannamorte, Francesca Ingannamorte Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorMaria Pichler, Maria Pichler orcid.org/0000-0002-0449-5958 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorKlaus Eisendle, Corresponding Author Klaus Eisendle [email protected] orcid.org/0000-0002-8234-9964 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, Italy Claudiana Research, Claudiana College of Health-Care Professions, Bolzano/Bozen, Italy Italian Society of Dermatologic Surgery and Oncology SIDCO, Siena, Italy 'Dermatologic Surgery Workgroup' of the Italian Society of Dermatology Medical, Surgical, Esthetical and of Sexually Transmitted Diseases SIDEMAST, Rome, Italy Department of Dermatology and Venereology, Rīga Stradiņš University, Riga, Latvia Correspondence Klaus Eisendle, Department of Dermatology, Venereology and Allergology, Academic Teaching Department (Medical University Innsbruck), Central Hospital Bolzano/Bozen, Böhlerstr. 5, Bolzano/Bozen 39100, Italy. Email: [email protected]Search for more papers by this author Cinzia Carriere, Cinzia Carriere Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorElena Polestra, Elena Polestra Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorFrancesca Ingannamorte, Francesca Ingannamorte Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorMaria Pichler, Maria Pichler orcid.org/0000-0002-0449-5958 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, ItalySearch for more papers by this authorKlaus Eisendle, Corresponding Author Klaus Eisendle [email protected] orcid.org/0000-0002-8234-9964 Department of Dermatology, Venereology and Allergology, Academic Teaching Department of Medical University Innsbruck, Central Hospital Bolzano/Bozen, Bolzano/Bozen, Italy Claudiana Research, Claudiana College of Health-Care Professions, Bolzano/Bozen, Italy Italian Society of Dermatologic Surgery and Oncology SIDCO, Siena, Italy 'Dermatologic Surgery Workgroup' of the Italian Society of Dermatology Medical, Surgical, Esthetical and of Sexually Transmitted Diseases SIDEMAST, Rome, Italy Department of Dermatology and Venereology, Rīga Stradiņš University, Riga, Latvia Correspondence Klaus Eisendle, Department of Dermatology, Venereology and Allergology, Academic Teaching Department (Medical University Innsbruck), Central Hospital Bolzano/Bozen, Böhlerstr. 5, Bolzano/Bozen 39100, Italy. Email: [email protected]Search for more papers by this author First published: 13 March 2023 https://doi.org/10.1111/jdv.19032Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1Zoccali G, Pajand R, Papa P, Orsini G, Lomartire N, Giuliani M. Giant basal cell carcinoma of the skin: literature review and personal experience. J Eur Acad Dermatol Venereol. 2012; 26: 942– 52. 2Pierer G, Pülzl P, Deluca J, Müller H, Zelger B, Putzer D, et al. Extraordinary giant basal cell carcinoma with full-thickness infiltration of the abdominal wall: single-staged resection and simultaneous reconstruction. J Cutan Med Surg. 2014; 18: 127– 31. 3Jacobsen AA, Aldahan AS, Hughes OB, Shan VV, Strasswimmer J. Hedgehog pathway inhibitor therapy for locally advanced and metastatic basal cell carcinoma: a systematic review and pooled analysis of interventional studies. JAMA Dermatol. 2016; 152: 816– 24. 4Dolton MJ, Chiang PC, Ma F, Jin JY, Chen A. Physiologically based pharmacokinetic model of vismodegib: deconvoluting the impact of saturable plasma protein binding, pH-dependent solubility and nonsink permeation. AAPS J. 2020; 22: 117. 5Gonnissen A, Isebaert S, Haustermans K. Hedgehog signaling in prostate cancer and its therapeutic implication. Int J Mol Sci. 2013; 14: 13979– 4007. 6LoRusso PM, Rudin CM, Reddy JC, Tibes R, Weiss GJ, Borad MJ, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011; 17: 2502– 11. 7Maughan BL, Suzman DL, Luber B, Wang H, Glavaris S, Hughes R. Pharmacodynamic study of the oral hedgehog pathway inhibitor, vismodegib, in patients with metastatic castration-resistant prostate cancer. Cancer Chemoter Pharmacol. 2016; 78: 1297– 304. 8Giammona A, Crivaro E, Stecca B. Emerging roles of hedgehog signaling in cancer immunity. Int J Mol Sci. 2023; 24: 1321. 9Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Bastholt L, et al. Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines. Eur J Cancer. 2019; 118: 10– 34. 10Ascierto PA, Schadendorf D. Update in the treatment of non-melanoma skin cancers: the use of PD-1 inhibitors in basal cell carcinoma and cutaneous squamous-cell carcinoma. J Immunother Cancer. 2022; 10:e005082. 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BACKGROUND:Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS:An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS:The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION:An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

The digital transformation has made its way into many areas of society, including medicine. While AI-based systems are widespread in medical disciplines, their use in psychiatry is progressing more slowly. However, they promise to revolutionize psychiatric practice in terms of prevention options, diagnostics, or even therapy. Psychiatry is in the midst of this digital transformation, so the question is no longer "whether" to use technology, but "how" we can use it to achieve goals of progress or improvement. The aim of this article is to argue that this revolution brings not only new opportunities but also new ethical challenges for psychiatry, especially with regard to safety, responsibility, autonomy, or transparency. As an example, the relationship between doctor and patient in psychiatry will be addressed, in which digitization is also leading to ethically relevant changes. Ethical reflection on the use of AI systems offers the opportunity to accompany these changes carefully in order to take advantage of the benefits that this change brings. The focus should therefore always be on balancing what is technically possible with what is ethically necessary.

Background: Changes in public attitudes toward “authorities” in general, as well as shifts in medical practice toward participative models of diagnosis and treatment, imply fundamental transformations in the patient–doctor relationship. However, consistency in reciprocal role expectations cannot be assumed, and this study reveals significant discrepancies in attitudes and behaviors in primary health consultations. Methods: We conducted a study in the tri-lingual northeastern Italian region of South Tyrol to determine whether perceptions of the patient’s role were congruent or differed. In a mixed method approach, the quantitative research part consisted of a survey with 34 identical questions for general practitioners (n = 109) and adult primary care patients (n = 506) on verbal communication, self-initiative and health literacy, interpersonal and social qualities of the patient–physician relationship, and formal aspects of the consultation. Patients were interviewed via telephone, and general practitioners responded online. In the qualitative part, 26 semi-structured in-depth interviews were conducted with the patients and analyzed. Results: General practitioners considered patients’ communicative efforts (p < 0.001), self-initiative (p < 0.001), compliance (p = 0.0026), and openness regarding psychosocial issues (p < 0.001) to be significantly more important, whereas patients showed a tendency to give increased importance to formal aspects such as politeness and hygiene (p < 0.001). Perception of the patient’s role differed significantly between the Italian and German linguistic groups. Conclusions: Patients and general practitioners differ in their understanding of patients’ roles. These data suggest that a considerable proportion of the population lacks a clear and tangible idea of the active role they could play in consultations. Targeted information on the identified aspects of patient–provider communication may facilitate participatory behavior and positively impact the longitudinal quality of the patient–general practitioner relationship.

Skin often represents a target organ for adverse drug reactions and this also applies to the mRNA vaccines against Sars-CoV-2. Here we present a case of extensive livedoid reaction after 2nd dose of BNT162b-2 vaccine with massive blood skin extravasation and no systemic symptoms apart from anemization. The 30-year-old woman developed progressively enlarging livedoid lesions on limbs and abdomen. Histology showed a near-normal epidermis and a very mild interstitial mixed inflammatory infiltrate with extensive blood extravasation in mid- and deep dermis. Diagnosis was adverse reaction to vaccine with skin capillary hyperpermeability and anaemization with lower than diagnostic features of cutaneous small vessel vasculitis. To date, no cases of a livedoid skin reaction associated to Covid-19 vaccine have been reported, and this case illustrates that massive livedoid reaction can be another kind of skin reaction to mRNA Covid-19 vaccine.