A Machine Learning Algorithm Applied to Trichoscopy for Androgenic Alopecia Staging and Severity Assessment.

INTRODUCTION: Androgenic alopecia (AGA) staging is still based on macroscopic scales, yet the introduction of trichoscopy is gradually bringing an important change, even though it remains an eye-based method. However, recently developed artificial intelligence-assisted programs can execute automated count of trichoscopic patterns. Nevertheless, to interpret data elaborated by these programs can be complex. Machine learning algorithms might represent an innovative solution. Among them, support vector machine (SVM) models are among the best methods for classification. OBJECTIVES: Our aim was to develop a SVM algorithm, based on three trichoscopic patterns, able to classify AGA patients and to calculate a severity index. METHODS: We retrospectively analyzed trichoscopic images from 200 AGA patients using Trichoscale Pro® software, calculating the number of vellus hair, empty follicles and single hair follicular units. Then, we elaborated a SVM model, based on these three patterns and on sex, able to classify patients as affected by mild AGA or moderate-severe AGA, and able to calculate the probability of the classification being correct, expressed as percentage (from 50% to 100%). This probability estimate is higher in patients with more AGA trichoscopic patterns and, thus, it might serve as a severity index. RESULTS: For training and test datasets, accuracy was 94.3% and 90.0% respectively, while the Area Under the Curve was 0.99 and 0.95 respectively. CONCLUSIONS: We believe our SVM model could be of great support for dermatologists in the management of AGA, especially in better assessing disease severity and, thus, in prescribing a more appropriate therapy.

Clinical and Trichoscopic Graded Live Visual Scale for Androgenetic Alopecia.

Introduction: Currently, the mostly used classifications of androgenetic alopecia (AGA) only provide a macroscopic and subjective description of this disorder, without evaluating trichoscopic features. Objectives: The aim of this study is to elaborate a graded live visual AGA severity scale including macroscopic and microscopic (trichoscopic) pictures, and to determine the most frequent trichoscopic characteristics associated to each grade. Methods: A retrospective observational study was conducted on 122 patients (50 females and 72 males) affected by AGA. Macroscopic and trichoscopic photographs were taken at standardized scalp points. Results: Each picture was ranked from AGA stage I to VII, according to Hamilton scale for men and Sinclair scale for women, and the most representative images of each severity degree were collected to produce a graded live visual scale. In males, 2 live visual scales, 1 for the anterior and 1 for posterior region of the scalp were created. In females, only 1 scale of the anterior region was realized. For each stage of severity, the corresponding trichoscopic parameters were statistically analyzed. Conclusions: We realized new macroscopic and trichoscopic graded live visual scales for male and female patients affected by AGA, which could help physicians in giving an objective evaluation of the disease and in better managing it.

Adverse skin reactions to personal protective equipment during COVID-19 pandemic in Italian health care workers.

To avoid exposure to SARS-COV-2, healthcare professionals must use personal protective equipment (PPE). Their use has been related to a series of adverse effects; the most frequent adverse events were headache, dyspnoea, and pressure injuries. Skin adverse effects are very common, including contact dermatitis, itching, erythema, and acneiform eruptions. The objective of this study is to evaluate the skin problems caused by personal protection equipment (PPE) in health care workers (HCWs) and to individuate eventual risk factors. From May to June 2020 a retrospective observational multi-centric study conducted by an online survey sent by email, involving 10 hospital centers, was performed. We considered as independent variables gender and age, occupational group and sector, time of utilization, type and material of PPE. We tested 3 types of PPE: gloves, bonnet, and mask for different time of utilization (<1, 1-3, 3-6, >6 h). We performed a multiple logistic regression model to correlate them with skin adverse events occurrence. Among all the 1184 participants, 292 workers reported a dermatological pathology: 45 (15.41%) had psoriasis, 54 (18.49%) eczema, 38 (13.01%) acne, 48 (16.44%) seborrheic dermatitis, and 107 (36.64%) other. In our sample previous inflammatory dermatological conditions, female sex, prolonged use of PPE were significant risk factors for developing skin related adverse events considering all the PPE considered. The use of PPE is still mandatory in the hospital setting and skin adverse reactions still represent a global problem. Although data from Europe are limited, our study highlighted the importance of the problem of PPE skin reactions in a large sample of Italian healthcare professionals.

Impact of COVID-19 on patients with atopic dermatitis.

Data on the tolerability and response to biologic therapies for type 2 immune disorders in the context of coronavirus disease 2019 (COVID-19) are currently lacking. Our survey aimed at assessing the adherence of patients to dupilumab therapy and the risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 80 patients with atopic dermatitis treated with dupilumab completed a web-based survey. Of the 80 patients, 7 discontinued dupilumab owing to concerns and difficulties related to COVID-19. Our sample was highly susceptible to viral infection owing to the frequency of risk factors including living in high SARS-CoV-2 burden areas, such as in Northern Italy; having comorbidities, such as asthma, diabetes, and cardiovascular disease; and being of advanced age. Older patients in our sample are particularly exposed to the risk of COVID-19-related cytokine storm, triggered by excessive interleukin-4 production and type 2 immune response. One patient contracted SARS-CoV-2 infection without the progression of COVID-19 despite continuing scheduled dupilumab treatment. Because evidence on the appropriate management of biologic therapy in the setting of COVID-19 is lacking, the collection of clinical data from patients in treatment with dupilumab is a valuable addition to current clinical practice. Our survey provides a contribution to the understanding of the tolerability and response to dupilumab during COVID-19 and suggests a feasible and effective approach to patients being treated with biologics even when social distancing is required.

Recurrence of alopecia areata after covid-19 vaccination: A report of three cases in Italy.

BACKGROUND: Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. MATERIALS AND METHODS: We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. RESULTS: All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. DISCUSSION: Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. CONCLUSION: This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.

Telogen Effluvium after SARS-CoV-2 Infection: A Series of Cases and Possible Pathogenetic Mechanisms.

INTRODUCTION: Physicians have largely studied the cutaneous involvement of coronavirus disease 2019 (COVID-19), but only few reports have focused on telogen effluvium (TE) as a possible sequela of COVID-19. We assessed 14 cases of hair loss occurring after SARS-CoV-2 infection using trichoscopy and trichogram to investigate patterns related to COVID-19. Furthermore, we discussed possible mechanisms involved in COVID-19 TE. CASE PRESENTATION: Fourteen individuals were referred to our post-COVID-19 dermatology office complaining acute hair loss after SARS-CoV-2 infection. Clinical evaluation included pull test, trichoscopy, and trichogram. CO-VID-19 TE occurred after a median of 2 months (range 1-3 months) following SARS-CoV-2 infection. The median duration of hair loss was 5 months (range 1-6 months). Trichoscopy showed variable but typical TE patterns. Trichogram showed different telogen/anagen ratio depending on the interval between onset of hair loss and trichological visit. DISCUSSION/CONCLUSION: Our cases showed TE between 1 and 3 months after the onset of SARS-CoV-2 infection, thus earlier than classic TE. Trichoscopic features and trichogram showed no variations from classic TE. Different pathogenetic mechanisms including pro-inflammatory cytokines and direct viral damage on the hair follicle can be hypothesized; further studies on a larger sample are needed to better understand this condition.

An Open-label Study Comparing Oral Zinc to Lymecycline in the Treatment of Acne Vulgaris.

BACKGROUND: Acne is a chronic multifactorial skin disease with a high prevalence among adolescents. The therapeutic approach for mild to moderate papulopustular acne includes the use of systemic tetracycline. Increased risk of antibiotic resistance necessitates research into alternative therapeutic approaches, such as zinc sulphate. Efficacy of zinc sulphate in acne treatment is widely reported in the literature, but drug comparison studies are lacking. OBJECTIVE: We sought to compare the efficacy and safety of zinc sulphate to lymecycline for the treatment of mild to moderate papulopustular acne. METHODS: One hundred patients were equally randomized to receive either zinc sulphate or lymecycline. Acne severity was evaluated using the subjective Global Acne Grading System (GAGS) and the Acne-specific Quality of Life (AQoL) questionnaire at baseline and after four and 12 weeks. RESULTS: Both zinc sulphate and lymecycline induced a statistically significant reduction in GAGS scores at four and 12 weeks of treatment. The improvements in AQoL scores in patients treated with zinc sulphate were significantly higher than those in the lymecycline group. CONCLUSIONS: Our study suggests that zinc sulphate is a valid alternative therapeutic approach in the treatment of mild to moderate papulopustular acne relative to lymecycline in terms of clinical efficacy, tolerability, and the occurrence of side effects.

New systemic therapies for cutaneous melanoma: why, who and what.

Incidence of melanoma has been increasing in both sexes in the last decades. Advanced melanoma has always been one of the deadliest cancers worldwide due to his high metastatic capacity. In the last ten years, progresses in the knowledge of the molecular mechanisms involved in the melanoma development and progression, and in immune-response against melanoma, empowered the development of two new classes of systemic therapeutic agents: target-therapies and immunotherapies. Both classes consist of monoclonal antibodies inhibiting specific molecules. Target-therapies are selectively directed against cells harboring the BRAFV600-mutation, while immunotherapies target the two molecules involved in immune-checkpoint regulation, enhancing the immune response against the tumor: cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 receptor (PD-1). Target- and immunotherapy demonstrated to improve both progression-free and overall survival in melanoma patients either in metastatic or in adjuvant settings. Several drugs have been approved in recent years as monotherapy or in combination, and many other drugs are currently under investigation in clinical trials. In the current review on new systemic therapies for cutaneous melanoma, we revised the molecular basis and the mechanisms of actions of both target- and immunotherapy (why). We discussed who are the best candidate to receive such therapies in both the adjuvant and metastatic setting (who) and which were the most important efficacy and safety data on these drugs (what).

Ingenol mebutate therapy in erythroplasia of Queyrat: a new approach.

BACKGROUND: Erythroplasia of Queyrat (EQ) is a rare squamous cell carcinoma in situ, usually occurring on the glans penis, the prepuce, or the urethral meatus. Therapy is mandatory because it can progress to invasive carcinoma in up to 30% of cases. Treatment options include 5-fluorouracil, curettage, cryotherapy, radiotherapy, laser, partial or total penectomy, and microsurgery, as also with imiquimod and photodynamic therapies. METHODS: Between 2015 to 2018 we treated five patients, with histologically confirmed EQ, with ingenol mebutate (IM) 0.015% gel applied for 3 days consecutively. RESULTS: Three patients showed complete response at one year follow up. Two patients showed partial response after two months, so they received a second course of therapy with IM. At one-year follow-up, one of them showed complete response, the other partial response. CONCLUSIONS: Our experience demonstrated that IM may be considered as an effective and safe treatment option in EQ. IM offers various advantages such as easy and fast application, rapid complete remission, better compliance, few side effects and excellent cosmetical results. The authors call for further exploitation in bigger trials.

Do Diet and Lifestyles Play a Role in the Pathogenesis of NMSCs?

BACKGROUND AND AIMS: Literature highlights the role of risk factors like age, body mass index (BMI), tobacco smoking, alcohol intake and diet in the pathogenesis of several cancer types but little is known for non-melanoma skin cancers (NMSC). The aim of this epidemiological study was to evaluate the correlation between modifiable risk factors (BMI, metabolic panel, diet, lifestyle, medical history) and not modifiable risk factors (gender, age) and NMSC development. METHODS: From February 2018 to September 2019, 162 patients affected by NMSC were compared to a group of 167 controls. A univariate and multivariate analysis was conducted to elaborate the data collected through face-to-face interviews. RESULTS: While our evidence did not always reach statistical significance, NMSC study group patients exhibited high rates of analyzed risk factors (male gender aging over 55 years, high BMI, reduced physical activity) compared to the control group. CONCLUSIONS: Our study indicates that practicing more than 30 min of physical activity daily could be a protective factor against the NMSC onset. Other risk factors were not correlated with NMSC, but more evidence is needed to establish a possible link.

Efficacy and safety of systemic isotretinoin treatment for moderate to severe acne (insights from the real-life clinical setting).

Acne is a chronic inflammatory relapsing disease that affect predominantly adolescents, with scarring as a frequent sequele. Early and appropriate therapy allows better management of the disease, longer remission, scars risk reduction, and improvement of quality of life. According to therapeutic algorithm, systemic isotretinoin can be used in severe acne and also in moderate forms resistant to other systemic treatments. The aims of this real-life observational study were to determine and compare the effectiveness of isotretinoin evaluated by Global Acne Grading System and Acne Quality of Life in moderate and in severe acne, correlation between efficacy and cumulative dose of isotretinoin, tolerability, and recurrence rate. Moreover, the differences in efficacy and tolerability between male and female patients were compared. The treatment with systemic isotretinoin led to an improvement in acne severity and quality of life in all observed subjects.

Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review.

This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We searched MEDLINE for articles on BRAF inhibitor resistance in patients with melanoma published since January 2010 in the following areas: (1) genetic basis of resistance; (2) epigenetic and transcriptomic mechanisms; (3) influence of the immune system on resistance development; and (4) combination therapy to overcome resistance. Common resistance mutations in melanoma are BRAF splice variants, BRAF amplification, neuroblastoma RAS viral oncogene homolog (NRAS) mutations and mitogen-activated protein kinase kinase 1/2 (MEK1/2) mutations. Genetic and epigenetic changes reactivate previously blocked mitogen-activated protein kinase (MAPK) pathways, activate alternative signaling pathways, and cause epithelial-to-mesenchymal transition. Once BRAF inhibitor resistance develops, the tumor microenvironment reverts to a low immunogenic state secondary to the induction of programmed cell death ligand-1. Combining a BRAF inhibitor with a MEK inhibitor delays resistance development and increases duration of response. Multiple other combinations based on known mechanisms of resistance are being investigated. BRAF inhibitor-resistant cells develop a range of 'escape routes', so multiple different treatment targets will probably be required to overcome resistance. In the future, it may be possible to personalize combination therapy towards the specific resistance pathway in individual patients.

BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions.

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells. In addition to their molecularly targeted activity, BRAF inhibitors have immunomodulatory effects. The MAPK pathway is involved in T-cell receptor signalling, and interference in the pathway by BRAF inhibitors has beneficial effects on the tumour microenvironment and anti-tumour immune response in BRAF-mutant melanoma, including increased immune-stimulatory cytokine levels, decreased immunosuppressive cytokine levels, enhanced melanoma differentiation antigen expression and presentation of tumour antigens by HLA 1, and increased intra-tumoral T-cell infiltration and activity. These effects promote recognition of the tumour by the immune system and enhance anti-tumour T-cell responses. Combining BRAF inhibitors with MEK inhibitors provides more complete blockade of the MAPK pathway. The immunomodulatory effects of BRAF inhibition alone or in combination with MEK inhibition provide a rationale for combining these targeted therapies with immune checkpoint inhibitors. Available data support the synergy between these treatment approaches, indicating such combinations provide an additional beneficial effect on the tumour microenvironment and immune response in BRAF-mutant melanoma.

Evaluation of Cardiovascular Risk in Hidradenitis Suppurativa Patients Using Heart Rate Variability (HRV) Analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.