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Summary Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. Results In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01–0·76] and vitiligo (OR 0·07, 95% CI 0·006–0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02–0·31), lichenoid reactions (OR 0·15, 95% CI 0·03–0·77) and eczematous reactions (OR 0·24, 95% CI 0·07–0·78), all compared with pruritic rash. Conclusions Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy.Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer.The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus.Clinical awareness and specialized dermatological consultation should be advocated.

Background: Pain is not a trivial issue for hidradenitis suppurativa (HS) patients and has been considered a domain in the Core Outcome Set. To date, there is no evidence about pain caused by the ultrasound examinations. Objective: The aim of the study was to assess the presence of pain generated by the ultrasound examinations of HS patients. Methods: A multicentric cross-sectional study for detecting pain during the ultrasound examinations of HS patients using a validated verbal questionnaire immediately after the imaging studies. Statistical analysis included demographic data and possible associations with sex, age, location, clinical (Hurley), and ultrasonographic scoring (SOS-HS). The statistical tests were two proportions Z test, χ2 test, Student’s t test, and ANOVA. A p < 0.05 was considered significant. Results: 317 patients met the criteria. 77.3% of them did not present pain. Of cases with pain, 59.8% were mild, 16.7% moderate, and 23.6% severe. No significant association was found with sex, age, staging, location, or the number of affected regions. Although nonsignificant, severe pain cases were more frequent in the clinical Hurley III and ultrasonographic SOS-HS III stages. Conclusion: Pain generated by the ultrasound examination of HS patients is infrequent.

Objectives Calcium depositions are frequent in multiple inflammatory dermatosis, they can be explored by ultrasound (US) but the patterns of these depositions have not yet been described. The aim of this study is to describe different patterns of calcium deposition in inflammatory dermatoses. Methods The clinical and US data of 58 patients from 7 different centers with inflammatory dermatosis showing ultrasonography-detected calcium depositions was retrospectively reviewed. Results Dystrophic calcinosis represented 86.2%, calciphylaxis 8.6%, and metastatic calcinosis 5.2%. Three different sonographic patterns of calcium deposition were found: 1) thin hyperechoic bands, parallel to the surface of the epidermis, generating a strong and wide posterior acoustic shadow; 2) hyperechoic spots or lumps with a narrow acoustic shadow; and 3) a linear hyperechoic band parallel to the walls of a blood vessel with also a narrow acoustic shadow. The predominant pattern in metastatic calcifications was type 1, in dystrophic calcifications type 2, and in calciphylaxis type 3. In dystrophic calcinosis, cutis deposits were longer and wider than in calciphylaxis (P Conclusion New data on inflammatory dermatoses with calcium deposition may be useful for the diagnosis and monitoring of calcium deposits and could avoid the performance of more invasive tests, such as a skin biopsy.

BACKGROUND Monitoring of disease activity in sclerosing dermatoses (SD) can be challenging and tools to support clinical decision-making are lacking. AIM To analyse the impact of high-frequency ultrasonography (HFUS) on the clinical management of SD and to describe the US characteristics of disease activity. METHODS This was a cohort study of patients with various SD [morphoea, systemic sclerosis (SS) and chronic graft-versus-host disease (cGvHD)] who underwent HFUS between January 2017 and August 2019. HFUS criteria for diagnosing active SD were increased Doppler vascularity and/or meeting all B-mode greyscale US signs of activity. Discordance in SD activity between HFUS and clinical examination was evaluated at the time of the first US assessment. Changes in patient management were instituted after HFUS were recorded. RESULTS In total, 72 patients (31 with morphoea, 19 with SS and 22 with cGvHD), who underwent 163 HFUS sessions in total, were included. All HFUS-active morphoea lesions exhibited increased vascularity, and all HFUS-active SS exhibited dermal thickening and dermal hypoechogenicity. HFUS-active cGvHD displayed increased dermal thickness and loss of definition of the dermal-hypodermal junction, and there were signs of panniculitis in 80% of cases and of increased vascularity in 70%. Discordance in disease activity between clinical and HFUS evaluation was found in 17 (23.6%) patients. Changes in clinical management after HFUS were made for 14 (19.4%) patients: treatment discontinuation for 6 patients (42.9%), treatment initiation for 5 (35.7%), medication change for 2 (14.3%) and skin biopsy taken for 1 (7.1%). CONCLUSION HFUS seems an efficacious support tool in the monitoring of SD activity with a notable impact on clinical management. Further studies are warranted to evaluate the impact of HFUS-supported management changes on SD outcomes.

BACKGROUND: Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. OBJECTIVES: To better define the clinical and histological features, treatment and prognosis of ICI-related severe blistering cutaneous eruptions. METHODS: This retrospective case series was conducted between 2014/05/15 to 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥ 18 years-old, skin eruption with blisters and/or detachment covering ≥ 1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD) or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by 4 experts in EN or LD/UD. Skin biopsies were blindly reviewed. RESULTS: Thirty-two patients were included. Median time to onset was 52 days [3–420]. Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, maximal detachment. Most patients were treated with topical and/or systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. CONCLUSIONS: Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.

Background. The diagnostic imaging techniques in dermatology, such as skin ultrasound, could improve the diagnosis of non-melanocytic benign tumor lesions, especially those of intradermal and subcutaneous nature. Objective. The general objective of this study was to evaluate the validity and diagnostic safety of high-frequency ultrasound as a diagnostic test for non-melanocytic benign skin tumor detection. The specific objectives were to measure the sensitivity and specificity of ultrasound as a measure of the validity relative to the gold-standard test – diagnostic-therapeutic biopsy. Methods. This study was carried out between January 2017 and June 2019. The patients (n = 641) included in this study comprised of 318 women and 323 men who were between 48 and 74 years. All of them underwent an ultrasound examination of the skin tumor in the dermatology clinic, the removal of the non-melanocytic tumor, and a final histopathological examination. Results. The skin ultrasound has a sensitivity and specificity of 93% and 88%, respectively. Furthermore, the positive and negative predictive values of using skin ultrasound are 84% and 94%, respectively. Conclusion. Skin ultrasound is a diagnostic technique with high sensitivity and specificity in the diagnosis of non-melanocytic skin tumors.

Immune-related adverse events (irAEs) are frequent and could be associated with improved response to immune checkpoint inhibitors (ICIs). A prospective cohort of advanced melanoma patients receiving ICI as first-line therapy was retrospectively reviewed (January 2011–February 2019). A total of 116 of 153 patients presented with at least one irAE (75.8%). The most frequent irAEs were dermatological (derm irAEs, 50%), asthenia (38%), and gastrointestinal (29%). Most irAEs appeared within the first 90 days, while 11.2% appeared after discontinuation of the therapy. Mild grade 1–2 derm irAEs tended to appear within the first 2 months of therapy with a median time of 65.5 days (IQR 26-139.25), while grade 3–4 derm irAEs appeared later (median 114 days; IQR 69-218) and could be detected at any time during therapy. Only derm irAE occurrence was related to improved survival (HR 6.46). Patients presenting derm irAEs showed better 5-year overall survival compared to those with no derm irAEs (53.1% versus 24.9%; p < 0.001). However, the difference was not significant when adjusting for the duration of therapy. In conclusion: the timeline of immune-related-AEs differs according to the organ involved. The (apparent) improved survival of patients who present derm AEs during immunotherapy could be partially explained by longer times under treatment.

Summary Background Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. Objective To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. Methods A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. Results From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site (‘COVID arm’, 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. Conclusions Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

The growing incidence of skin cancer, with its associated mortality and morbidity, has in recent years led to the developing of new non-invasive technologies, which allow an earlier and more accurate diagnosis. Some of these, such as digital photography, 2D and 3D total-body photography and dermoscopy are now widely used and others, such as reflectance confocal microscopy and optical coherence tomography, are limited to a few academic and referral skin cancer centers because of their cost or the long training period required. Health care professionals involved in the treatment of patients with skin cancer need to know the implications and benefits of new non-invasive technologies for dermatological oncology. In this article we review the characteristics and usability of the main diagnostic imaging methods available today.

Determining disease activity from clinical signs in patients with connective tissue panniculitis (CTP) is often challenging but is essential for therapeutic decision making, which largely relies on immunosuppressant treatment. High-frequency ultrasound (HFUS) may be useful in supporting such decisions by accurately determining CTP activity. This study aimed to investigate the accuracy of HFUS in identifying signs of CTP activity or inactivity and assess its usefulness in therapeutic decision making. A prospective cohort study of consecutive patients with biopsy-proven CTP receiving HFUS was conducted in a tertiary university hospital (2016–2020). HFUS was performed at inclusion and at each 3- or 6-month follow-up visit, depending on disease activity. Twenty-three patients with CTP were included, and 134 HFUSs were performed. In 59.7% (80) of the evaluations, the clinical presentation did not show whether CTP was active or not. In these cases, HFUS showed activity in 38.7% (31) and inactivity in 61.3% (49). In 71.25% (57) of the visits, HFUS was the determinant for therapeutic decisions. Further follow-up showed consistent clinical and HFUS responses in all unclear cases after treatment modification. HFUS appears to be a useful adjunct to the clinical examination for CTP to assess activity and make therapeutic decisions.

Patients treated with haematopoietic stem cell transplantation are at increased risk of cutaneous malignant neoplasms. There are no reports on the characteristics of melanocytic lesions in patients with chronic graft versus host disease and the value of recognizing these difficult lesions in high-risk patients. The objective of this study is to describe the clinical and dermoscopic characteristics of melanocytic lesions in patients with chronic graft versus host disease in order to understand their morphology. A prospective cross-sectional study was performed; 10 melanocytic lesions on the trunk and extremities were selected from each patient. A statistically significant association was found between regression and high total dermoscopic score and 7-point checklist score. Lesions were excised or included in short-term digital follow-up. Melanocytic lesions in patients with chronic graft versus host disease developing after allogeneic-haematopoietic stem cell transplantation exhibit marked structural and colour changes similar to melanoma. This is believed to result from the inflammatory process associated with graft versus host disease.

Resumen Introduccion El uso de la ecografia Doppler (ED) se ha afianzado en los ultimos cinco anos en dermatologia. En este trabajo se describen las particularidades del uso de la ED en Cataluna y Aragon. Material y metodos Estudio descriptivo observacional transversal que se realizo en 11 hospitales de Cataluna y Aragon. Durante 5 dias habiles consecutivos en octubre de 2016, se incluyeron pacientes de todas las edades y de ambos sexos, a los que se les realizo una ED. Se excluyeron pacientes con lesiones menores de 0,1mm y/o planas pigmentadas. Resultados Participaron 17 dermatologos, 10 varones y 7 mujeres. La mediana de edad fue de 41 anos (rango: 28-49 anos). La mediana de tiempo de utilizacion de la ED era de 17 meses (rango 2-47 meses). De los 11 hospitales, 7 tenian una consulta monografica de ED. Se realizaron 150 ED a 150 pacientes, lo cual supone una frecuencia de 2,9 ecografias/hospital/dia. Noventa pacientes eran mujeres. La mediana de edad fue de 47 anos (rango 4 meses a 83 anos). Siete (60%) de los centros participantes disponian de atencion pediatrica. Las sospechas diagnosticas al realizar la ED fueron: tumores benignos 35%, enfermedades inflamatorias 21%, hidrosadenitis supurativa 18%, tumores malignos 12%, otras patologias 9% y lesiones vasculares 5%. Conclusiones La ED es una herramienta ampliamente utilizada entre los dermatologos de las comunidades de Cataluna y Aragon. Se aplica para enfermedades inflamatorias y tumorales. Es util para orientar el diagnostico, decidir una terapeutica o documentar una lesion. Introduction Doppler ultrasound (DU) is an imaging technique that has been increasingly used in dermatology during the last five years. This paper describes the characteristics of the use of DU in dermatology departments in Catalonia and Aragon. Material and methods A cross-sectional observational and descriptive study was conducted in 11 hospitals in Catalonia and Aragon. During 5 consecutive working days in October 2016, all patients who underwent cutaneous ultrasound were included. Patients with lesions smaller than 0.1mm and / or pigmented macular lesions were excluded. Results A total of 17 dermatologists, 10 men and 7 women, participated. The median age was 41 years (range: 28-49 years). Their median experience in the use of ultrasound was 17 months (range 2-47 months). There was a specific day and time to perform ultrasound in 7 of the 11 hospitals. A total of 150 DU were performed on 150 patients, with a frequency of 2.9 ultrasounds/hospital/day. Ninety patients were women. The median age of the patients was 47 years (range 4 months to 83 years). Seven (60%) of the participating hospitals had a paediatric unit. The diagnostic suspicions when performing the DU were: benign tumours 35%, inflammatory diseases 21%, hidradenitis suppurativa 18%, malignant tumours 12%, other pathologies 9%, and vascular injuries 5%. Conclusions DU is a widely used tool among dermatologists in the communities of Catalonia and Aragon. It is indicated for inflammatory and neoplastic diseases. In recent years the use of DU in Spain has increased significantly. In our work, we were able to describe the use of dermatological ultrasound in the communities of Catalonia and Aragon and compare these data with other Spanish findings.

Introduction Les inhibiteurs de checkpoint (ICI) induisent toxicites dermatologiques, surtout des exanthemes et dermatoses lichenoides (DL). Les eruptions les plus severes (bulles, decollements, atteinte muqueuse), imposent l’arret definitif de l’ICI. La nosologie de ces eruptions graves, necrolyses epidermiques (NE, syndromes de Stevens-Johnson et de Lyell) ou DL graves, est imprecise. Nous avons conduit une etude retrospective multicentrique pour caracteriser les toxidermies bulleuses induites par ICI. Materiel et methodes Un appel a cas a ete lance a 4 reseaux nationaux ou internationaux de dermatologues. Les criteres d’inclusion etaient: adultes, toxidermie bulleuse avec decollement ≥ 1% et ≥ 1 atteinte muqueuse, entre 01/2015 et 04/2021, avec ICI suspecte. Les pemphigoides bulleuses etaient exclues. Le clinicien a donne sa conclusion diagnostique: NE, DL ou dermatose inclassable (DI). Les photos ont ete revues par 4 specialistes des NE et toxidermies aux ICI, en aveugle de la conclusion du clinicien. La relecture des histologies est prevue. La base mondiale de pharmacovigilance (PV) a ete interrogee. Resultats Nous avons inclus 29 patients (18 H, âge median 61 ans). Les cancers les plus frequents etaient le poumon (n = 13) et le melanome (n = 7). L’ICI etait une 1re ligne dans 11 cas. Le suspect etait le pembrolizumab (n = 13), le nivolumab (n = 8), une association anti-CTLA4 + anti-PD1 (n = 6) ou un anti-PDL1 (n = 2). Une NE etait diagnostiquee dans 20 cas, une DL dans 6 et une DI dans 3. Le delai median de survenue etait de 52 jours (3–420). Le patient etait traite par corticotherapie (CT) locale (n = 12), et/ou generale (n = 13), pour une duree mediane de 30 jours (3–120). Neuf patients (tous classes NE) recevait aussi un immunomodulateur, 2 n’avaient que des soins de support. A 6 semaines, 6 (20%) etaient decedes. L’ICI suspect n’etait pas repris chez 21/23 patients vivants. Deux patients DL, avec anti-CTLA4 + nivo ou nivo seul suspects, ont repris le nivo et ont recidive. Deux avec anti-PD1 suspect ont recu l’autre anti-PD1 avec bonne tolerance. Trois ont eu des tests allergologiques, negatifs. Apres revue des photos de 23 patients, parmi 14 NE, 6 etaient reclassees en DL ou DI sur les criteres suivants: etat general preserve, pas/peu d’atteinte oculaire, lesions buccales lichenoides, eruption seche/desquamative, atteinte palmoplantaire, decollement superficiel. La base mondiale de PV rapporte 390 cas de NE et 200 cas d’«eruption bulleuse» sous ICI. Discussion Les ICI peuvent induire des NE, DL ou DI graves. Comme suggere dans la litterature, certaines NE pourraient etre plutot des DL. Le delai d’induction est variable. La CT est admise, avec des modalites a ce jour variables. La securite du switch pour un autre anti-PD1 ne peut etre ici precisee. Un registre prospectif permettra de preciser la nosologie et la prise en charge de ces eruptions graves sous ICI.

Sarcoidosis is a multiorgan disease characterized by the formation of noncaseating granulomas and possible skin involvement. Cutaneous sarcoidosis (CS) can be explored by ultrasonography when deep dermal or subcutaneous nodules are the clinical presentation. We reviewed the ultrasound characteristics of 14 patients (86% female; mean age, 55 years) with CS. Ultrasonography revealed dermal or subcutaneous hypoechoic areas with increased echogenicity and hypervascularity of the neighboring subcutaneous tissue. In 42.9% of cases a cobblestone pattern of the subcutaneous tissue suggestive of septal involvement was detected. These US features can support the detection of dermal and subcutaneous abnormalities in CS and its early diagnosis.

Background and aim There is increasing interest regarding SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory diseases (AI/IMID) with some discrepancies in different cohorts about their risk and outcomes. The aim was to describe a multidisciplinary cohort of patients with AI/IMID and symptomatic SARS-CoV-2 infection in a single tertiary center and analyze sociodemographic, clinical, and therapeutic factors associated with poor outcomes. Methods A retrospective observational study was conducted from the 1st of March until May 29th, 2020 in a University tertiary hospital in Barcelona, Spain. Patients with an underlying AI/IMID and symptomatic SARS-CoV-2 infection were identified in our local SARS-CoV-2 infection database. Controls (2:1) were selected from the same database and matched by age and gender. The primary outcome was severe SARS-CoV-2 infection, which was a composite endpoint including admission to the intensive care unit (ICU), need for mechanical ventilation (MV), and/or death. Several covariates including age, sex, and comorbidities among others were combined into a multivariate model having severe SARS-CoV-2 as the dependent variable. Also, a sensitivity analysis was performed evaluating AID and IMID separately. Results The prevalence of symptomatic SARS-CoV-2 infection in a cohort of AI/IMID patients was 1.3%. Eighty-five patients with AI/IMID and symptomatic SARS-CoV-2 were identified, requiring hospitalization in 58 (68%) cases. A total of 175 patients admitted for SARS-CoV-2 (58 with AI/IMID and 117 matched-controls) were analyzed. In logistic regression analysis, a significant inverse association between AI/IMID group and severe SARS-CoV-2 (OR 0.28; 95% CI 0.12–0.61; p = 0.001), need of MV (OR 0.20; IC 95% 0.05–0.71; p = 0.014), and ICU admission (OR 0.25; IC 95% 0.10–0.62; p = 0.003) was found. Conclusions Patients with AI/IMID who require admission for SARS-CoV-2 infection have a lower risk of developing severe disease, including the need to stay in the ICU and MV., Highlights • Patients with AI/IMID fwho required admission for SARS CoV2 infection have a lower risk of developing severe disease. • Among patients with AID and IMID, there were no differences in terms of severity. • According to the 7-category ordinal scale, maximum oxygen requirement was lower among AI/IMID group.

Since December 2019, coronavirus disease 2019 (COVID‐19) has spread worldwide to become a pandemic. Multiple skin manifestations related to the infection have been described progressively. Recalcati1 asserted that 20.4% of infected patients developed cutaneous manifestations and Galvan‐Casas et al2 have recently proposed 5 clinical patterns (pseudo‐chilblain, vesicular, urticarial, maculopapular and livedo/necrosis). We report a case of COVID‐19 with retiform purpura and its histopathological correlation.

Jellyfish stings often cause immediate local skin reactions, and, less frequently, the affected individuals may develop delayed allergic reactions days or months after the sting. Here, we present 4 such cases. In all cases, color Doppler ultrasonography was performed at the time of diagnosis, and in 3 of the cases, clinical follow-ups with ultrasonographic evaluations were performed. Ultrasonography initially showed dermal thickening with decreased echogenicity that progressively normalized during follow-up. Ultrasonography was useful in quantifying inflammation by measuring the thickness of the dermis and was more precise than standard clinical follow-up of cutaneous lesions in these cases.

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