European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

VACCINE HESITANCY - FROM PARENTAL DISTRUST TO COVID-19 CONSPIRACIES.

Worldwide studies continuously confirm that vaccination is a safe and effective method of combating various infectious diseases and a key component of global public health programs. However, the vaccination status of a population is often lower than needed to achieve collective immunity. A key reason that affects lower vaccination coverage is vaccine hesitancy, identified as one of the ten greatest threats to global public health. So far, vaccine hesitancy has been most investigated in the context of parental refusal of children vaccination. The emergence of the COVID-19 pandemic and the development of its vaccines put vaccine hesitancy further in the focus of investigators as well as healthcare workers and policy makers. We have witnessed its immediate effects on public health and mortality rates as well as even more extreme ways of vaccine refusal than previously documented. The aim of this review article is to summarize relevant scientific understandings of vaccine hesitancy, including its psychological determinants, insights from parental refusal of child vaccination, medical distrust, and conspiracy theories related to the COVID-19 pandemic, as well as recommendations for public health services for combating vaccine hesitancy.

Association of Gut Lachnospiraceae and Chronic Spontaneous Urticaria.

(1) Background: Chronic spontaneous urticaria (CSU) has been linked to the dysbiosis of the gut microbiota. Furthermore, various studies have highlighted the anti-inflammatory properties of short-chain fatty acids (SCFAs), whose production is primarily regulated by the gut microbiota. However, only a few studies have investigated the role of major SCFA producers, such as Lachnospiraceae, in skin inflammatory diseases. (2) Goal: This study aimed to compare the abundance of Lachnospiraceae between CSU patients and healthy controls (HCs). (3) Material and methods: In this case-control study, 16S rRNA sequencing was performed to compare the composition of the gut microbiome between 22 CSU patients and 23 HCs. (4) Results: Beta-diversity revealed significant clustering (p < 0.05) between the CSU patients and HCs. Alpha diversity in the CSU group was significantly decreased according to the Evenness index (p < 0.05). The linear discriminant analysis effect size (LEfSe) identified the significant depletion of the Lachnospiraceae family in CSU patients. (5) Conclusion: Our study revealed the dysbiosis of the gut microbiota in CSU patients, including decreased levels of Lachnospiraceae members, responsible for SCFA production, suggesting that SCFAs may contribute to immune dysfunction in the pathogenesis of CSU. We speculate that the modulation of SCFAs could serve as a prospective additional option in CSU treatment.

Impact of COVID-19 on inpatient care related to skin conditions.

Background: The COVID-19 pandemic significantly affected our society and healthcare system. This study aims to evaluate the effects of COVID-19 on the number of hospitalized patients with dermatological diseases in Croatia, as well as the number of these patients treated surgically and conservatively, before (2017-2019) and during the pandemic (2020-2021). Materials and methods: This is a retrospective, comparative study of the hospital admission rate for patients with skin, subcutaneous tissue, and breast disorders both before and during the pandemic. This study used data from the Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF). Inpatient data for the CHIF data collection were categorized using the Australian Refined Diagnosis Related Groups (AR-DRGs). All hospital admissions for dermatology patients at all non-specialized hospitals in Croatia were tracked during two periods, before (2017-2019) and during the pandemic (2020-2021). Results: The average number of dermatology patients in all hospitals fell by 29% during the pandemic. The overall number of dermatological patients admitted to hospitals fell by 32% in 2020 and by 26% in 2021 when compared to the number of patients admitted each year on average over the preceding 3 years. Additionally, there was an average 22% fall in surgical procedures performed during the pandemic. The only exception for surgical procedures is Major Breast Reconstruction for which is noted an increase, as also for Malignant Breast Disorders, Minor Complexity and Major Skin Disorders, Minor Complexity in a group of non-surgically treated patients. Conclusion: Examining the all consequences of the Croatian dermatological patient care interruption will require more investigation. Reduced access to medical care during the pandemic is anticipated to lead to later illness diagnosis, a later start to treatment, a poorer disease prognosis, as well as higher medical expenditures.

he Influence of Academician Franjo Kogoj on Global Dermatology.

Academician Franjo Kogoj graduated medicine in 1920 in Prague, where he then pursued training in dermatovenerology. During later years, he also visited other dermatology clinics in Europe, where he collaborated with renowned dermatologists of the time, such as in Breslau (present day Wroclaw in Poland) with Josef Jadassohn and in Strasbourg with Lucien-Marie Pautrier. He was also active in the famous Saint-Louis hospital in Paris. Academician Kogoj's scientific interests were especially focused on allergies, exanthemas, skin tuberculosis, and keratodermas. Kogoj was very active in defining a precise and useful terminology for various dermatological conditions, where the terminology was in many ways confusing and often overlapping, such as in cases of eczema and dermatitis. Kogoj performed experimental studies of allergic reactions in eczema and atopic dermatitis and introduced the term pruridermatitis (Pruridermatitis allergica chronica) into dermatological terminology instead of the name neurodermitis and other synonyms essentially describing atopic dermatitis (endogenous eczema, prurigo-asthma, prurigo Besnier). Academician Kogoj managed to define Mal de Meleda as a separate form of hereditary keratoderma and was engaged in the clinical symptomatology, serology, and therapy of syphilis, whereby he emphasized the so-called "critical moment" in the treatment of syphilis. Academician Kogoj's most famous scientific achievement was his histological definition of the spongiform pustule in the pathomorphology of psoriasis, which became a groundbreaking histological novelty in the classification of psoriasis, thus bearing Kogoj's name in the medical literature to this date. Academician Kogoj published many scientific and professional articles, books, monographs and contributions to manuals and textbooks. He was honored nationally as well as internationally as a leading expert in the field of medicine and dermatology, receiving many eminent awards and recognitions throughout his scientific career.

Parental Attitudes Towards Vaccination and Adolescent Sexual Health - A Cross-sectional Study.

Positive parental role modeling is a protective factor for adolescent sexual and reproductive health (SRH). Our aim was to investigate parental opinion on adolescents' SRH and vaccination as well as sociodemographic determinants of child-parent communication regarding SRH. This nationally representative cross-sectional telephone survey with a random stratified sample included 500 parents from Croatia (74% mothers), with at least one child under 18 years of age. Stratification was performed by (a) region, and (b) size of settlement. Differences were found between parental beliefs regarding quality, safety, and efficacy of vaccines and potential hazardous effects. Although 95% confirmed their child was vaccinated according to the national program, only 12% vaccinated with optional, self-paid vaccines (excluding human papillomavirus). Almost every third parent was not acquainted with SRH, more commonly fathers. The preferred sources of information for parents regarding SRH were friends, followed by the media and professional healthcare sources, while communication with adolescents was reported by 84% respondents. More than 10% parents claimed that their child did not have accurate knowledge regarding SRH. Our study confirms predominantly positive parental attitudes vaccination and communication with adolescents regarding SRH. We emphasize the importance of effective parental engagement and indicate the need for educational interventions to strengthen knowledge on immunization and SRH.

From Morphea to Dermatofibrosarcoma Protuberans.

Dear Editor, Morphea profunda (MP) is a chronic autoimmune disease, a subtype of localized scleroderma that presents clinically as local discomfort due to the impairment of skin motility (1). Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue neoplasm that not only infiltrates the dermis and subcutaneous tissue, but can also affect the muscles and bones with finger-like extensions, usually present on the trunk and the proximal extremities (2). DFSP is known for its indolent clinical course, locally aggressive behavior, and high local recurrence rates, but relatively low risk of metastatic spread (2). DFSP frequently arises in middle-aged adults, affecting both sexes equally with an incidence of 4 per 1,000,000 people (3). We report the case of a 39-year-old female patient who first presented to our clinic at the age of 20 years due to a brownish atrophic coin-sized lesion appearing on the left side of the abdomen. Medical reports indicated that biopsies had been performed previously on 3 occasions, and histopathologic findings confirmed the diagnosis of MP. The aforementioned lesion on the abdomen had been growing slowly over the years, and the patient finally visited our clinic 15 years later after noticing two palpable nodules developing within the affected skin (Figure 1, A, B). Clinical examination revealed an indurated ill-defined plaque measuring 10 cm with partially atrophic surface and 2 centrally located palpable nodules measuring between 3 and 5 mm. A deep biopsy of the lesion was performed, and histopathology and immunohistochemical analysis of CD34 expression confirmed the diagnosis of dermatofibrosarcoma protuberans (Figure 1, C, D). Computed tomography scans of the thorax, abdomen, and pelvic region were subsequently performed, revealing no further disease progression. Complete excision of the tumor was performed and followed by wide scar re-excision due to narrow surgical margins of only 1 mm. No further disease progression or recurrences have been noted during the follow-up, and the patient has been disease-free for one year postoperatively. Although the etiology of DFSP is unknown, trauma has been hypothesized as a predisposing factor. It usually presents on the trunk and the proximal extremities (4). Patients usually report disease progression over a long period of time, ranging from several months to years. The tumor is associated with variable color changes, even proximal skin discoloration, and often presents with a slowly growing indurated dermal plaque or firm nodule attached to the skin (4). Clinically, it can be difficult to distinguish DFSP from a wide number of diagnoses, including morphea, idiopathic atrophoderma, atrophic scar, anetoderma, lipoatrophy, cellular dermatofibroma, fibrosarcoma, malignant fibrous histiocytoma, atypical fibroxanthoma, desmoplastic melanoma, Kaposi sarcoma, and solitary fibrous tumors (5). Immunohistochemistry staining for CD34 cells can be helpful in differentiation, since spindle cells stain positively in DFSP (6). Due to alteration of dermal collagen, histopathological differential diagnoses of DFSP includes lichen sclerosus, atrophic scars and keloids, as well as morphea (7), atrophic dermatofibroma, and undifferentiated pleomorphic sarcoma (6). The mainstay of DFSP treatment is tumor excision performed either by wide local excision or Mohs surgery and having surgical margins between 1 and 5 cm. Several studies have confirmed that patients treated with the Mohs technique have significantly lower recurrence rates (8). Due to the high number of unsatisfactory primary excisions, wide free surgical margins are important for disease control (3). Radiotherapy might be considered as a therapeutic option for inoperable tumors or relapses, as well as an adjuvant therapy after primary excision or re-excision with positive margins (8). Furthermore, recent findings indicate positive therapeutic efficacy after administration of imatinib mesilat - a tyrosine kinase inhibitor due to over expression of PDGFß (9). Clinical follow-up of patients with DFSP after tumor excision should be performed every six months for the first five years, followed by yearly intervals thereafter for up to 10 years (3). Previous case reports have claimed that the diagnosis of DSFP is commonly delayed as a result of slow tumor growth and nonspecific initial clinical findings (10). To the best of our knowledge, our case is the first description in the literature of DFSP developed within a MP plaque. We speculate that trauma from repeated punch biopsies taken from the sclerotic morpheaform plaque may represent the trigger for the development of the DFSP. Another notable clinical challenge was the surgical excision itself, since the majority of cases presented in literature mentioned unsatisfactory resection margins and a high risk of local disease recurrence. Although complete excision of the neoplasm was performed, re-excision was performed in order to provide wider resection margins. Surgical resection remains the main treatment for dermatofibrosarcoma protuberans, with the main challenge being the achievement of clean excision margins. Proper management of the disease and continuous follow-up are important in order to prevent local recurrence of dermatofibrosarcoma protuberans or its potential metastases.

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. AIMS: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. PATIENTS/METHODS: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days. RESULTS: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). CONCLUSIONS: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.

A Case of Segmental Darier Disease.

Darier disease (DD), also known as Darier-White disease, follicular keratosis, or dyskeratosis follicularis, is an uncommon autosomal dominant genodermatosis with complete penetrance and variable expressivity. This disorder is caused by mutations in the ATP2A2 gene and affects the skin, nails, and mucous membranes (1,2). A 40-year-old woman, without comorbidities, presented with pruritic, unilateral skin lesions on the trunk since she was 37 years old. Lesions had remained stable since onset, with physical examination revealing tiny scattered erythematous to light brown keratotic papules beginning at the patient's abdominal midline, extending over her left flank and onto her back (Figure 1, a, b). No other lesions were observed, and family history was negative. Skin punch biopsy revealed parakeratotic and acanthotic epidermis with foci of suprabasilar acantholysis and corps ronds in the stratum spinosum (Figure 2, a, b, c). Based on these findings, the patient was diagnosed with segmental DD - localized form type 1. DD usually develops between the ages of 6 and 20 and is characterized by keratotic, red to brown, sometimes yellowish, crusted, pruritic papules in a seborrheic distribution (3,4). Nail abnormalities, alternating red and/or white longitudinal bands, fragility, and subungual keratosis can be present. Mucosal whitish papules and palmoplantar keratotic papules are also frequently observed. Insufficient function of the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA2) leads to calcium dyshomeostasis, loss of cellular adhesion, and characteristic histological findings of acantholysis and dyskeratosis. The main pathological finding is the presence of two types of dyskeratotic cells, "corps ronds", present in the Malpighian layer, and "grains", mostly located in the stratum corneum (1). Approximately 10% of cases present as the localized form of disease, with two phenotypes of segmental DD having been observed. The more common, type 1, is characterized by a unilateral distribution along Blaschko's lines with normal surrounding skin, whereas the type 2 variant presents with generalized disease and localized areas of increased severity. Although generalized DD is associated with nail and mucosal involvement, as well as positive family history, these findings are rarely seen in localized forms (1). Family members with identical ATP2A2 mutations may have notable differences in clinical manifestations of the disease (5). DD is usually a chronic disease with reccurent exacerbations. Exacerbating factors include sun exposure, heat, sweat, and occlusion (2). Infection is a common complication (1). Associated conditions include neuropsychiatric abnormalities and squamous cell carcinoma (6,7). Increased risk of heart failure has also been observed (8). Type 1 segmental DD may be clinically and histologically hard to distinguish from acantholytic dyskeratotic epidermal nevus (ADEN). Age of onset plays an important role in differentiation, as ADEN is often congenital (3). However, some studies suggest ADEN is a localized form of DD (1). Other differential diagnoses include herpes zoster, lichen striatus, lichen planus (4), severe seborrheic dermatitis, and Grover disease. Our patient was treated with a topical retinoid, for the first two weeks in combination with a topical corticosteroid. She was advised on the use of proper daily skincare with antimicrobial cleansers and emollients, as well as behavioral measures such as avoiding triggering factors and wearing light clothing, resulting in substantial clinical improvement (Figure 1, c, d) and amelioration of pruritus. Other treatment options include salicylic and lactic acid as well as topical 5-fluorouracil, while oral retinoids are reserved for more severe disease (1-3). Doxycycline and pulsed dye laser have also been reported to be effective (2,9). One in vitro study showed that COX-2 inhibitors may reinstitute the dysregulated ATP2A2 gene (4). In summary, DD is a rare keratinization disorder that can present in a generalized or localized pattern. Although uncommon, segmental DD should be included in the differential diagnosis of dermatoses that follow Blaschko's lines. Treatment options include various topical and oral treatments, depending on disease severity.

Painful and Itchy Dermatoses Carry the Highest Psychological Burden for Dermatovenereological Patients.

BACKGROUND: Most dermatovenereological diseases are not life-threatening but nevertheless are highly prevalent disorders. Psychosocial aspects of skin diseases and physical symptoms strongly influence patient's quality of life (QoL) which results in the development of different coping mechanisms in patient's behaviour. Development of psychiatric comorbidity in patients with skin diseases is well known. On the other hand, little is known about psychological comorbidity associated with dermatovenereological diseases. Aims of this study were to investigate QoL and psychological burden among dermatovenereological patients. SUBJECTS AND METHODS: Two hundred and ninety patients suffering from different dermatological and venereological diseases participated in the study, divided into three study groups: itchy/painful dermatoses, non-itchy/non-painful dermatoses and venereological diseases. Participants completed standardized psychological questionnaires: Dermatology Specific Quality of Life (DSQL), Beck Depression Inventory (BDI) and State and Trait Anxiety Inventory (STAI). Intensity of the disease and localisation of the lesions were also assessed. RESULTS: Physical aspect of QoL was mostly influenced by itchy/painful dermatoses but psychological aspect and everyday activities and choices were mostly affected by patients with non-itchy/non-painful dermatoses and venereological diseases. 4.1% of participants had serious depressive symptoms, 11.5% had high and very high anxiety symptoms as state and 15.6% as trait. However, participants with severe skin conditions were more depressed, while participants with always and sometimes exposed lesions were more anxious. CONCLUSION: It is essential to recognise subgroups of dermatovenereological patients whose treatment approach should be interdisciplinary. Further studies are needed to detect psychosocial needs of patients with venereological diseases.

A Reminder of Skin Cancer During the COVID-19 Pandemic.

The year 2020 has been marked by the coronavirus disease 2019 (COVID-19) pandemic, caused by an RNA virus called SARS-COV2 (severe acute respiratory syndrome coronavirus). The fight against this epidemic has become the center of our daily clinical practice as well as of our private lives, in which avoiding infection has become one of our most important goals. Even though COVID-19 is a potentially lethal disease, especially for the elderly and people with chronic diseases, it did not cause all the other life-threatening diseases to vanish. On the contrary, many scheduled medical activities and procedures, especially preventive and non-urgent internal and surgical activities, had to be postponed due to COVID-19 crisis. This interruption in the health care system can negatively affect the diagnosis and management of our patients with other health issues, namely malignant skin tumors, of which melanoma is the most aggressive. In this letter, we as dermatovenereologists from the Croatian Referral Centre of The Ministry of Health for Melanoma needed to express our concern regarding the increasing number of patients with delayed diagnosis of skin cancer, with special emphasis on melanoma detection and treatment. In the last few months, a large number of our newly-diagnosed patients with melanoma, as well as those with non-melanoma skin cancers, reported that they had noticed a suspicious skin lesion a few months ago but decided not to seek help from dermatologist due to the worrisome epidemiologic situation. In the current environment, clinical skin examination may be viewed as less important and thus postponed, but neglecting melanoma throughout the virus outbreak may lead to increased rates of morbidity, mortality, and consequently a greater financial burden for the health system (1). There are several reasons for such a relaxed attitude towards skin health in our patients. Unlike cardiac, pulmonary, or digestive difficulties, which patients consider life-threatening and for which they seek emergency care despite the coronavirus pandemic, skin tumors do not cause great subjective or significantly noticeable objective symptoms. Moreover, all of the skin tumors and especially melanoma , mostly present as small changes of just a few millimeters in diameter in the early stage at which they are prognostically most favorable. For the average person with no medical education, such small lesions usually do not cause any concern as they have no awareness of the fact that small and inconspicuous skin lesions may be dangerous and potentially even lethal. According to the recommendations concerning patient management during COVID-19 pandemic, oncological examinations should still be performed regularly (2). In spite of that, the cancelation of appointments, especially by patients who are being monitored for high-risk lesions, is inevitable when COVID-19 is disrupting everyone's lives. With the pandemic evolving and no clear solutions in sight, now is the time to emphasize the importance of self-examination and teledermatology in early melanoma diagnosis. Even though diagnosing and managing pigmented skin lesions usually requires face-to-face examinations and dermoscopy as a crucial tool in early melanoma detection, in these times, and especially for people with a higher risk of SARS-COV2 infection, remote communication could prevent delays resulting in worse prognosis and could also eliminate the risk of infecting healthcare workers. Moreover, teledermatology can also be initiated by doctors asking patients to monitor lesions between clinical visits (3). However, we should not rely solely on this technology but should instead assess every patient individually and insist on a face-to-face examination for those at greater risk, with the aim that, if necessary, surgery be performed in timely manner. The collaboration between general practitioners and dermatologists represents an important aspect of achieving the most rational and effective health care in terms of performing triage of patients who can be assessed by teledermatology as well as referring to hospital centers those who need face-to-face examination and further treatment. During the first breakout of the epidemic in March 2020, the multidisciplinary team for melanoma from the Croatian National Referral Melanoma Centre provided recommendations for the management of patients with melanoma during COVID epidemic, designed according to the guidelines of the National Comprehensive Cancer Network (NCCN) (4) and considering the specifics of health care and clinical practice in the Republic of Croatia. Due to epidemic circumstances, preventive actions such as Euromelanoma and many other campaigns that included massive preventive skin examinations of the population and which were conducted for years by Croatian dermatologists throughout the country, could not be organized this year. This is particularly worrisome because on average about 800 patients are diagnosed with melanoma annually in Croatia, of which 60 during public health preventive actions. Despite these circumstances, we were able to maintain public awareness of the importance of early skin cancer recognition by sending the message through different media such as newspapers, television, and social media (Facebook and Instagram). We find that now more than ever it is essential to remind and teach the population about the importance of regular monthly skin self-examinations and recognition of atypical lesions. Clearly, a thorough dermatological examination includes full skin examination from head to toe. Herein we would also like to remind our readers that most skin cancers develop in the head and neck area, which is the most UV-exposed part of the body. Therefore, despite the epidemic conditions, the removal of patients' masks and thorough inspection of the face is mandatory. We find it most practical and efficient to perform the body and scalp examination first, followed by the face examination after the patient gets dressed. Prior to removal of the mask, we ask the patient not to talk during close examination. Even though this could make dermoscopic examination harder to perform, we strongly suggest wearing a protective shield and mask during close examination whenever possible. Between patients, the examining room should be disinfected and ventilated. As doctors, we live in uncertain times when we are heavily burdened by the currently unstoppable COVID epidemic, always awaiting new instructions from the state administration every day and wondering whether perhaps tomorrow we dermatologists will be assigned solely to the service of patients with COVID-19. In the end, we would like to once again remind you that despite the ravaging COVID pandemic and all the epidemiological measures that come with it, other diseases still exist. It is expected of us to draw attention to the still growing incidence of skin cancers and the serious consequences that can occur as a result of a delayed diagnosis.

Ultrasound Assessment of Regional Lymph Nodes in Melanoma Staging.

BACKGROUND: Melanoma can early metastasize to regional lymph nodes. The sentinel lymph node (SLN) is the first lymph node draining directly from the site of primary melanoma, and the pathohistological status of the SLN is the most significant prognostic factor for overall survival prevalence and prognosis in patients with melanoma. Ultrasound is a very useful for the imaging of regional lymph node metastases, combined with Doppler and cytopuncture. OBJECTIVE: The aim of this study was to investigate the role of ultrasound assessment of regional lymph nodes in melanoma staging. PATIENTS AND METHODS: The study included all patients with primary melanoma detected in the period between 2003 and 2012, in whom diagnostic processing has not proven distant metastases or physical examination did not find enlarged lymph nodes. In total, 202 surgically treated patients were included in the study, of which 101 patients underwent ultrasound examination of regional lymph nodes using a linear probe of at least 12 MHz, while ultrasound of regional lymph nodes was not performed for 101 patients. RESULTS: The results of this study emphasize the importance of ultrasound in the diagnostics and treatment of patients with melanoma. Based on the observation of the occasional positive ultrasound and fine needle aspiration cytology (FNAC) in regional lymph nodes, our results indicate that a proportion of patients can avoid sentinel lymph node biopsy (SLNB). In case of a positive ultrasound findings (complemented with FNAC of suspicious nodes), direct dissection of regional lymph nodes is recommended. However, negative ultrasound findings do not exclude the presence of micrometastases due to poor sensitivity of this method and is not a contraindication for SLNB. CONCLUSION: Therefore, there is a need for further studies on metastatic melanoma, especially those in the sentinel lymph nodes and in its early stage.

Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

Dermoscopic Features as Predictors of BRAF Mutational Status and Sentinel Lymph Node Positivity in Primary Cutaneous Melanoma.

Dermoscopy is a diagnostic tool widely used in clinical practice for the detection of skin tumors, especially early stages of melanoma. Recent studies have shown that different dermoscopic features are associated with important prognostic parameters of melanoma, such as BRAF mutational status and sentinel lymph node status. More than half of all melanomas harbor a mutation in the BRAF oncogene. The current management of advanced-stage melanomas is greatly determined by the presence or absence of a mutation in this gene, as targeted therapy with BRAF kinase inhibitors is one of the first therapeutic choices for these patients. Sentinel lymph node status is one of the most significant predictors of a melanoma patient's survival. Recent studies have shown that different dermoscopic patterns are also associated with sentinel lymph node status. This short article reviews studies that investigated correlations between dermoscopic features, BRAF mutation status and sentinel lymph node status.

CAN SKIN BE A MARKER FOR INTERNAL MALIGNANCY? EVIDENCE FROM CLINICAL CASES.

Although there are many single case reports on paraneoplastic dermatoses in the literature, there are very rare articles containing multiple cases. A retrospective study was performed to examine paraneoplastic dermatoses and accompanying malignancies based on skin manifestations and appropriate diagnostic evaluations. We recorded outcomes, current conditions, and surgical/oncologic treatments. Analysis revealed paraneoplastic dermatoses in 17 patients with various skin lesions, i.e. eczematous dermatitis, vasculitis, subacute cutaneous lupus erythematosus, pruritus, chronic urticaria/angioedema, alopecia areata, flushing, bullous pemphigoid, dermatomyositis, and localized scleroderma (morphea). They were associated with different solid and hematologic malignancies (3 gastric, 2 prostate, 2 bladder, 2 thyroid, and 2 lymphoma), along with 1 case each of the following: lung, hepatocellular, esophageal, endometrial, kidney, and multiple myeloma. The majority of skin lesions gradually regressed after malignancy treatment. To our knowledge, our three cases of paraneoplastic eczematous dermatitis are the first to be associated with gastric, prostate and endometrial cancer. Additionally, we report a case of a patient with alopecia areata of the beard associated with thyroid cancer. Early malignancy detection based on skin markers makes early introduction of surgical/oncologic therapy possible and usually leads to skin lesion regression while reducing revolving door visits to specialists and the (financial) burden on the healthcare system.

Novel yeast extract is superior to colloidal oatmeal in providing rapid itch relief.

BACKGROUND: Approximately, 13.5% of the population suffers from chronic itch. Many cosmetic and pharmaceutical treatments for itch are available; however, cosmetic treatments are not reliably effective and most pharmaceutical formulations carry the risk of adverse events with chronic use. AIMS: Previously, we have reported a novel extraction process of Saccharomyces cerevisiae, that is, Baker's yeast. The extract obtained from the novel process demonstrates superior anti-itch properties compared to other yeast extracts. In our previous study, we demonstrated that, after 30 minutes, the extract significantly reduced itch when compared to a placebo lotion (P = .002). METHODS: In the present study we conducted a head-to-head comparison with the leading cosmetic itch product: lotion containing colloidal oatmeal (CO). A randomized double-blinded study of 60 patients was conducted. RESULTS: In our study, the novel yeast extract was vastly superior to the CO containing lotion (Aveeno™ Eczema Therapy Moisturizing Cream). We saw statistically significant difference in the reduction of itch (P = .0001) using the novel yeast extract vs the CO lotion. Additionally, the yeast extract was shown to relieve itch in as little as one minute after application. CONCLUSION: The novel yeast extract rapidly relieves itch and is superior to the cosmetic market leader, CO lotion.

Recent information on photoaging mechanisms and the preventive role of topical sunscreen products.

The main environmental element causing photoaging is ultraviolet (UV) light, and this involves an extrinsic mechanism of skin aging superimposed on an intrinsic process. Clinical (evident) characteristics of photoaging include the presence of deep wrinkles, deterioration of skin laxity, and hyperpigmentation. In the UV light spectrum, UVA and UVB radiation cause the most damage in photoaging. UVB light has shorter wavelengths and is mostly absorbed by the stratum corneum, causing erythema and changes in the epidermis, whereas UV rays with longer wavelengths (i.e., UVA) penetrate to the deepest layer of the skin (i.e., the dermis) and interact with DNA. As a result of UV radiation, chemical reactions in the skin produce reactive oxygen species (ROS), which cause protein denaturation, impairment of RNA and DNA synthesis, and damage to the skin structure. Using local sunscreen agents can not only prevent sunburn, but also help prevent photocarcinogenesis and photoaging. Therefore, many epidemiological studies have been conducted with results showing credible and positive evidence for the safety and efficacy of sunscreen to prevent photoaging and photocarcinogenesis.