Clinical, histopathologic, immunohistochemical, and electron microscopic findings in cutaneous monkeypox: A multicenter retrospective case series in Spain.

BACKGROUND: The worldwide outbreak of monkeypox has evidenced the usefulness of the dermatologic manifestations for its diagnosis. OBJECTIVE: To describe the histopathologic and immunohistochemical findings of monkeypox cutaneous lesions. METHODS: This is a retrospective histopathologic and immunohistochemical study of 20 patients with positive Monkeypox virus DNA polymerase chain reaction and immunohistochemical positivity for Vaccinia virus in cutaneous lesions. Four cases were also examined by electron microscopy. RESULTS: The most characteristic histopathologic findings consisted of full-thickness epidermal necrosis with hyperplasia and keratinocytic ballooning at the edges. In some cases, the outer root sheath of the hair follicle and the sebaceous gland epithelium were affected. Intraepithelial cytoplasmic inclusion bodies and scattered multinucleated keratinocytes were occasionally found. Immunohistochemically, strong positivity with anti-Vaccinia virus antibody was seen in the cytoplasm of ballooned keratinocytes. Electron microscopy study demonstrated numerous viral particles of monkeypox in affected keratinocytes. LIMITATIONS: Small sample size. Electron microscopic study was only performed in 4 cases. CONCLUSION: Epidermal necrosis and keratinocytic ballooning are the most constant histopathologic findings. Immunohistochemical positivity for Vaccinia virus was mostly detected in the cytoplasm of the ballooned keratinocytes. These findings support the usefulness of histopathologic and immunohistochemical studies of cutaneous lesions for diagnosis of monkeypox.

Ustekinumab to guselkumab transitions: A series of 54 patients emulating the navigate trial in real life.

NAVIGATE clinical trial demonstrated a higher rate of Psoriasis Assesment Severity Index (PASI)90 response in patients treated with guselkumab when compared to ustekinumab and an improved response in those who switched from ustekinumab to guselkumab due to partial response. The objective of the study is to describe ustekinumab to guselkumab switching in clinical practice. Observational, multicentric, descriptive study including 54 psoriasis patients who switched to guselkumab after treatment with ustekinumab from March 2019 to February 2021. Mean basal PASI with ustekinumab (16.7) was higher than with guselkumab (7.2). Up to 49.01% of patients were able to reach PASI90 with ustekinumab and up to 21.56% had a less frequent dosage regime vs. summary of product characteristics. Main reason to start guselkumab was a loss of ustekinumab cutaneous or articular response (82.36%) but up to 17.64% were switched in order to increase dosage regime efficiency. Six months after starting guselkumab, the absolute PASI was lower than 2 in 72% of patients and 38.5% of them were treated with a reduced dosage regime. Guselkumab doses used by our cohort were 19.5% lower than the expected according to the summary of product characteristics. No adverse events reported. There is no real-world evidence regarding patients who switched from ustekinumab to guselkumab. A short paragraph in the article by Fougerousse et al, reported 63 patients with a mean basal PASI of 5.3 and similar efficacy rate at week 16 to NAVIGATE. Our study adds practical information regarding efficacy, safety and efficiency through dose optimization in a real-world cohort.

Discriminative deep learning based benignity/malignancy diagnosis of dermatologic ultrasound skin lesions with pretrained artificial intelligence architecture.

BACKGROUND: Deep-learning algorithms (DLAs) have been used in artificial intelligence aided ultrasonography diagnosis of thyroid and breast lesions. However, its use has not been described in the case of dermatologic ultrasound lesions. Our purpose was to train a DLA to discriminate benign form malignant lesions in dermatologic ultrasound images. MATERIALS AND METHODS: We trained a prebuilt neural network architecture (EfficientNet B4) in a commercial artificial intelligence platform (Peltarion, Stockholm, Sweden) with 235 color Doppler images of both benign and malignant ultrasound images of 235 excised and histologically confirmed skin lesions (84.3% training, 15.7% validation). An additional 35 test images were used for testing the algorithm discrimination for correct benign/malignant diagnosis. One dermatologist with more than 5 years of experience in dermatologic ultrasound blindly evaluated the same 35 test images for malignancy or benignity. RESULTS: EfficientNet B4 trained dermatologic ultrasound algorithm sensitivity; specificity; predictive positive values, and predicted negative values for validation algorithm were 0.8, 0.86, 0.86, and 0.8, respectively for malignancy diagnosis. When tested with 35 previously unevaluated images sets, the algorithm´s accuracy for correct benign/malignant diagnosis was 77.1%, not statistically significantly different from the dermatologist's evaluation (74.1%). CONCLUSION: An adequately trained algorithm, even with a limited number of images, is at least as accurate as a dermatologic-ultrasound experienced dermatologist in the evaluation of benignity/malignancy of ultrasound skin tumor images devoid of clinical data.

Immunophenotypic Differences in Tumor-Infiltrating Lymphocytes and Neovascularization Between Primary Cutaneous Melanoma With and Without Metastasis: An Immunohistochemical Study of 80 Cases.

ABSTRACT: The prognostic implications of the immunophenotype of the tumor-infiltrating lymphocytes (TILs) in primary cutaneous melanoma are well known. In recent years, the study of this immunophenotype has also resulted in immunotherapeutic consequences. The aims of this study were to characterize the subpopulations of TILs in primary cutaneous melanoma, in cases with and without metastasis, as well as the neovascularization associated with the primary neoplasm, and its influence on the development of metastasis. To this end, the immunophenotype of TILs and the neovascularization of 80 patients with primary cutaneous melanoma (40 each with metastatic and non-metastatic melanoma) were analyzed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, CD31, and D2-40 antibodies. We found that higher frequencies of TILs with brisk pattern, and CD4+, CD8+, and CD20+ cells in TILs, and a lower frequency of CD31+ vessels were histopathological features associated with better prognosis in primary cutaneous melanoma. Our results support the notion that the immunohistochemical study of TILs and neovascularization in primary cutaneous melanoma may be helpful tools for identifying patients at increased risk of metastasis development.

Dermatologic Ultrasound in Primary Care: A New Modality of Teledermatology: A Prospective Multicenter Validation Study.

OBJECTIVES: This study aimed to validate dermatologic ultrasound as a complementary teledermatologic imaging modality in primary and tertiary care centers. METHODS: Six primary care centers and 1 tertiary care dermatology department collaborated in the program. Images were sent through the institutional teledermatologic platform to the tertiary care dermatology department. At the reference hospital, ultrasound images and clinical data were received and registered by a physician trained in dermatologic ultrasound. An in-person consultation was scheduled to confirm the teleultrasound diagnosis. The time of response by the tertiary center, quality and size of the teledermatologic image, and concordance with the in-person diagnosis were assessed for each dermatologic lesion. RESULTS: A total of 147 teleultrasound consultations with 143 patients (93 women and 50 men; mean age ± SD, 47 ± 23 years) were evaluated between June 2018 and January 2019. Nine teleultrasound consultations (6.1%) were not valid. Discordance between teleultrasound and the in-person diagnosis was evident in 6 of 138 cases (4.3%). Most cases corresponded to benign skin tumors (66.7%), followed by inflammatory skin lesions (15.9%), nonmelanoma skin lesions (13%), and other skin lesions (4.3%). All malignant tumors were detected (sensitivity, 100%), although 2 cases of benign lesions were telediagnosed as malignant (specificity, 97.8%). The positive and negative predictive values of a teleultrasound diagnosis of cutaneous malignancy were 90% and 100%, respectively. CONCLUSIONS: Asynchronous primary care teleultrasound combined with dermatologic ultrasound training at tertiary centers is an effective teledermatologic modality.

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Position Statement on Dermatologic Ultrasound.

Dermatologic ultrasound is a recent application of ultrasound for the evaluation of healthy skin and appendages and their diseases. Although the scientific literature regarding this application is still not sufficient for evidence-based guidelines, general recommendations issued by scientific societies are necessary. The EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) steering committee for dermatologic ultrasound has developed a series of consensus position statements regarding the main fields of dermatologic ultrasound (technical requirement, normal skin and appendages, inflammatory skin diseases, tumoral skin diseases, aesthetic dermatology and practice-training requirements). This document is the foundation for future evidence-based recommendations and guidelines for dermatologic ultrasound practice.

Dermatologic ultrasound in the management of childhood linear morphea.

Linear morphea is the most common subtype of localized scleroderma in the pediatric population. This condition can be quite disabling, with complications such as growth defects and painful flexion contractures. Assessment of disease progression and early intervention are key to minimize morbidity. We report linear morphea in a previously healthy 12-year-old girl. The patient presented with a one-year history of a linear plaque crossing her left antecubital fossa, measuring 7x3cm. The diagnosis was confirmed by biopsy, in which deep tissue involvement was noted. Subsequent management and evaluation of the disease activity was done by ultrasound, which allowed precise guidance of pharmacotherapy. The patient improved both clinically and sonographically with a methotrexate course. Sonographic changes accurately described the disease activity on follow up assessments. Features suggestive of an active phase include a thickened and hypoechoic dermis contrasting hyperechoic subcutaneous tissue. The atrophic stage is characterized by a thinned-out dermis and subcutaneous area. Typical vascular traits of each disease phase can also contribute to the assessment. Ultrasound is a grossly underused tool in the field of dermatology. It can provide accurate and sensitive information about disease activity in linear morphea, allowing for more timely intervention and optimal patient management.

Increased Marginal Stiffness Differentiates Infiltrative From Noninfiltrative Cutaneous Basal Cell Carcinomas in the Facial Area: A Prospective Study.

OBJECTIVES: Basal cell carcinoma (BCC) is the most common dermatologic malignant skin cancer. Infiltrative histologic variants are more aggressive and require wider surgical margins or Mohs surgery, in contrast with noninfiltrative variants, which are commonly treated with standard surgical excision. Elastography has not been used to date to differentiate between the histologic variants of BCC. The purpose of this study was to differentiate infiltrative from noninfiltrative BCCs on elastography. METHODS: A total of 31 facial BCCs were studied. Preoperatively, color Doppler ultrasound and strain elastographic examinations of the lesions were performed. The size, intralesional vascularization, and presence of hyperechoic dots were considered relevant B-mode and color Doppler variables. Strain ratios of the tumors were obtained with respect to adjacent healthy tissue. Increased marginal stiffness, which was considered hardness in greater than 50% of the tumor margin, was also blindly evaluated. Histologic confirmation and subtyping (infiltrative or noninfiltrative) were performed in all cases. RESULTS: Infiltrative BCCs did not differ in the size, presence or absence of hyperechoic dots, or vascularization from noninfiltrative BCCs. Strain ratios were similar in both infiltrative and noninfiltrative BCCs (mean ± SD, 1.82 ± 0.879 versus 2.2 ± 1.11). However, infiltrative BCCs had statistically increased marginal stiffness in comparison with noninfiltrative BCCs (88.0% versus 18.8%). Increased marginal stiffness had sensitivity and specificity of 0.89 and 0.82 respectively, with a positive predictive value of 0.67 for infiltrative BCCs and a negative predictive value of 0.95 for noninfiltrative BCCs. CONCLUSIONS: Histologic variants of BCC have different elastographic patterns. These differences may be of help in preoperative assessments of the BCC subtype and specific surgical planning, avoiding unnecessary skin biopsies.

Ex Vivo High-Frequency Ultrasound for Assessment of Basal Cell Carcinoma.

The use of Mohs micrographic surgery for poorly defined cutaneous tumors is present in a few departments in Spain. Reintervention is occasionally necessary when the margins of the surgical specimen are invaded by the tumor. We propose the use of ultrasound to assess these margins by imaging the surgical specimen once excised.

Primary Subcutaneous Synovial Sarcoma: First Reported Subcutaneous Case Showing TLE1 Immunoreactivity.

Synovial sarcoma (SS) accounts for 5%-10% of all soft tissue sarcomas. It is a well-defined soft tissue neoplasm with biphasic and monophasic histologic subtypes and unknown histogenesis. It usually occurs in the extremities, especially the thigh-knee region of young adults. Recurrences are frequent and distant metastasis developed in approximately half of the patients. SSs are characterized by a recurrent nonrandom chromosomal translocation, t(X; 18) (p11; q11), which is considered the primary genetic event in more than 90% of cases. Only 4 cases of cutaneous and subcutaneous SSs have been published in the literature so far. We report a case of primary subcutaneous SS in the forearm of a young woman and discuss the histopathologic differential diagnosis with other similar neoplasms. This is the first reported case of primary cutaneous SS showing immunoreactivity for TLE1 in the nuclei of neoplastic cells, supporting the use of this marker for diagnosis of this rare cutaneous neoplasm.

Ultrasound Evaluation as a Complementary Test in Hidradenitis Suppurativa: Proposal of a Standarized Report.

BACKGROUND: Staging and monitoring of patients with hidradenitis suppurativa (HS) have been traditionally based on clinical findings. However, the physical examination may show important limitations because of its poor sensitivity for differentiating between different lesion subtypes, and its low sensitivity to define the disease's activity. OBJECTIVE: To develop a consensus ultrasound (US) report that could summarize the relevant anatomical characteristics and staging of patients considering the experience of radiologists and dermatologists working on imaging of HS. METHODS: A questionnaire on different aspects related to US examination in HS was performed. A working group, called DERMUS, composed of doctors from 9 countries who have been working in dermatologic US applied in patients with HS on a regular basis were included to evaluate the different items provided. RESULTS: A consensus US report to evaluate HS patients was established. CONCLUSION: The authors present the first attempt to define a HS standardized sonographic report. This model would be the first effort to include this imaging technique as the first elective medical test for staging and monitoring patients, which can support therapeutic decisions by providing earlier, objective, deeper, anatomical, and comparative evaluations in this difficult to treat disease.

Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic findings.

Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease characterized by skin lesions separated from the lesions of the gastrointestinal tract. The diagnosis of MCD is essentially histological,showing noncaseating granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD with vulvar involvement and clinical, histopathological, and ultrasonographic findings of this disease.

High-Frequency Color Doppler Sonography of Bullous Pemphigoid: Correlation With Histologic Findings.

Bullous pemphigoid is the most frequent autoimmune-mediated blistering skin disease, belonging to the group of subepidermal bullae. We performed high-frequency color Doppler sonography in 3 cases of bullous pemphigoid, in bullous and adjacent non-bullous skin, which showed homogeneous sonographic findings. Subepidermal cystic structures with dermal hypoechogenicity were observed in bullous skin. In nonbullous skin, the dermis showed hypoechogenicity compared to normal skin. Color Doppler signals were increased in both areas. These findings correlate histologically with subepidermal bullae and dermal inflammatory infiltrates.

Guidelines for Performing Dermatologic Ultrasound Examinations by the DERMUS Group.

OBJECTIVES: To support standardization for performing dermatologic ultrasound examinations. METHODS: An international working group, called DERMUS (Dermatologic Ultrasound), was formed, composed of physicians who have been working on a regular basis and publishing in peer-reviewed articles on dermatologic ultrasound. A questionnaire on 5 critical issues about performance of the examinations was prepared and distributed by e-mail. The areas of discussion included technical aspects, main areas of application, minimum number of examinations per year required for assessing competence, qualifications of the personnel in charge of the examination, and organization of courses. Final recommendations were approved on the basis of the agreement of more than 50% of the members. RESULTS: The minimum frequency recommended for performing dermatologic examinations was 15 MHz. Routine use of color Doppler ultrasound and the performance of spectral curve analysis for assessing the main vascularity of lesions were suggested. Three-dimensional reconstructions were considered optional. The main dermatologic applications were benign tumors, skin cancer, vascular anomalies, cosmetic field, nail disorders, and inflammatory diseases. The minimum number of examinations per year suggested by the group for assessing competence was 300. A physician and not a sonographer was recommended to be the person in charge of performing the examination. On course organization, a minimum of 2 levels of complexity (basic and advanced) was suggested. CONCLUSIONS: There is a need to standardize the performance and quality of dermatologic ultrasound examinations. The present guidelines written by an international group of specialists in the field may support this objective.

Use of high frequency ultrasonography in dermatology departments in Spain.

BACKGROUND: High Frequency Ultrasonography (HFUS) is a rapid, reliable, and effective diagnostic technique that has become progressively employed within the past years among dermatologists. OBJECTIVE: To describe the use of HFUS among dermatology departments in Spain. METHODS: An observational, cross-sectional descriptive study was conducted in 23 dermatology departments at Spanish public hospitals. Study data was collected during 10 working days. RESULTS: Fifty dermatologists from 11 Spanish regions participated in the study; 659 HFUS procedures were undertaken in 633 patients. HFUS indications were benign tumors (41%), malignant tumors (28%), inflammatory diseases (18%), skin appendage conditions (10%), and cosmetic conditions (1%). HFUS was performed for assessing the clinical differential diagnosis (58% of cases), surgical planning (17%), follow-up (17%), and other reasons (7%). Among the diagnostic group, the scan confirmed clinical diagnosis in 82% of cases and helped to change the clinical diagnosis in 17% cases (10% of total scans). HFUS procedure duration was less than 5 minutes (45%), between 5 and 10 minutes (32%), and more than 10 minutes (21%). Mean patient satisfaction score (range 0 to 5) was 4.8. CONCLUSIONS: The use of HFUS in usual practice is increasing, especially among younger dermatologists. This procedure is effective both for confirming and changing diagnosis, as well as for therapy decision making and follow-up. It is also worth remarking that a very high degree of patient satisfaction was recorded. The descriptive results reported in this study support the use of ultrasonography techniques and further reinforce their use in Dermatology.

Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity.

HSV-1 establishes life-long latency that can result in clinical relapses or in asymptomatic virus shedding. Although virtually all adults have been exposed to HSV-1, the clinical course varies remarkably. Genetic host variability could be related to this clinical diversity. In this study, we analyzed the contribution of gene families in chromosomes 1, 6, 12, and 19, which encode key regulators of the innate and adaptive immunity, in a cohort of 302 individuals. Class I and class II alleles of the HLA system, the copy-number variation of NK cell receptor genes (KIR and NKG2C), the combinations of killer cell Ig-like receptor and their HLA ligands, and CD16A and CD32A allotypes of variable affinity for IgG subclasses were all studied. Although no major susceptibility locus for HSV-1 was identified, our results show that the risk of suffering clinical HSV-1 infection is modified by MHC class I allotypes (B*18, C*15, and the group of alleles encoding A19), the high-affinity receptor/ligand pair KIR2DL2/HLA-C1, and the CD16A-158V/F dimorphism. Conversely, HLA class II and CD32A polymorphisms and NKG2C deletion did not seem to influence the clinical course of herpetic infection. Collectively, these findings support an important role in host defense against herpetic infection for several polymorphic genes implicated in adaptive immunity and in surveillance of its subversion. They confirm the crucial role of cytotoxic cells (CTL and NK) and the contribution of genetic diversity to the clinical course of HSV-1 infection.

Development of a Patient Journey Map for Improving Patient Experience and Quality of Atopic Dermatitis Care.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects both children and adults. AD increases the risk of developing comorbidities like asthma, allergic rhinitis and food allergies. AD patients face difficulties, including itching, lack of effective treatments, lack of funding and discomfort in seeking a diagnosis or treatment. This study aims to identify the main barriers and opportunities to improve the experience of patients with AD and provide high-quality care. METHODS: Patients, caregivers and healthcare professionals were recruited from the Dermatology Department at Puerta de Hierro Majadahonda University Hospital (Madrid, Spain). Interviews with patients, caregivers and professionals were performed. Participants used storyboards to depict their preferred scenarios for improving healthcare interactions and create a Patient Journey Map. RESULTS: A total of 15 participants were included in the study. Early symptoms of AD were commonly described as undefined stages. As symptoms worsened, patients and caregivers expressed uncertainty and frustration. Patients became concerned about AD after their first serious flare and started experiencing intense itching, eczema, wounds, shedding or asthma. Topical corticosteroids were used to manage flares, but their effectiveness diminished over time, causing further frustration. Because of the ineffectiveness of their initial treatments, dermatologists observed that patients tended to downplay symptoms and how they affected their quality of life. The specialized treatment of severe AD significantly changed patients' emotional states. Despite AD's chronic nature, patients strived to enjoy remission periods and cope with flares. Psychological and emotional support was crucial for patients and caregivers, a need addressed by the Patients' School initiative at HUPHM hospital. CONCLUSION: The severity of AD has a profound impact on patients' lives. Patient and caregiver emotional and social needs can be met by adequate communication, access to effective treatments and comprehensive psychological support.

Sonography of a case series of talar callosities.

Talar callosity is an uncommon condition characterized by asymptomatic hyperkeratotic plaques located on the dorsum of one or both feet. We have detected an increased number of children presenting with this condition after the COVID-19 lockdown. High-frequency ultrasound was performed in all patients who consulted because of talar callosity. All four cases shared similar ultrasound findings: thickening of the epidermis with effacement of the subepidermal low-echogenic band and diffuse thickening of the dermis and subcutaneous cellular tissue, with a diffuse decrease in echogenicity. The bone cortex was respected in all cases. No increase in vascularization was detected. Although it is a benign condition, it is important to recognize talar callosity to exclude worse conditions and to prevent unnecessary biopsies. To our knowledge, we are the first to describe ultrasonographic findings of talar callosity.