A deep learning approach for Direct Immunofluorescence pattern recognition of Autoimmune Bullous Diseases.

BACKGROUND: Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning to enhance disease management. Dermatology has seen improved diagnostics, particularly in skin cancer detection, through the integration of AI. However, the potential of AI in automating immunofluorescence imaging for autoimmune bullous skin diseases remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of deep learning to automatically classify DIF patterns, including the Intercellular Pattern (ICP) and the Linear Pattern (LP), holds promise for improving the diagnosis of autoimmune bullous skin diseases. OBJECTIVES: The objectives of this study are to develop AI algorithms for automated classification of autoimmune bullous skin disease DIF patterns, such as ICP and LP. This aims to enhance diagnostic accuracy, streamline disease management, and improve patient outcomes through deep learning-driven immunofluorescence interpretation. METHODS: We collected immunofluorescence images from skin biopsies of patients suspected of AIBD between January 2022 and January 2024. Skin tissue was obtained via 5-mm punch biopsy, prepared for direct immunofluorescence. Experienced dermatologists classified the images into three classes: ICP, LP, and negative. To evaluate our deep learning approach, we divided the images into training (436) and test sets (93). We employed transfer learning with pre-trained deep neural networks and conducted 5-fold cross-validation to assess model performance. Our dataset's class imbalance was addressed using weighted loss and data augmentation strategies. The models were trained for 50 epochs using Pytorch, achieving an image size of 224x224 for both CNNs and the Swin Transformer. RESULTS: Our study compared six CNNs and the Swin transformer for AIBDs image classification, with the Swin transformer achieving the highest average validation accuracy of 98.5%. On a separate test set, the best model attained an accuracy of 94.6%, demonstrating 95.3% sensitivity and 97.5% specificity across AIBDs classes. Visualization with Grad-CAM highlighted the model's reliance on characteristic patterns for accurate classification. CONCLUSIONS: The study highlighted CNN's accuracy in identifying DIF features. This approach aids automated analysis and reporting, offering reproducibility, speed, data handling, and cost-efficiency. Integrating deep learning in skin immunofluorescence promises precise diagnostics and streamlined reporting in this branch of dermatology.

Follicular scales, scalp and ocular involvement in patients with papulopustular rosacea: prevalence and association with Demodex mite proliferation.

Facial follicular scales, dandruff, scalp itching and ocular alterations are lesser-known signs of rosacea and demodicosis. The aim of this prospective original study was to investigate the presence of these signs and symptoms in patients with almost-clear, mild and moderate papulopustular rosacea (PPR) and to study the differences between Demodex-positive (D+) and Demodex-negative (D-) rosacea. Twenty-seven out of 60 patients (45%) presented follicular scales, 24 (40%) ocular involvement and 22 (36.67%) scalp involvement. Follicular scales were more frequently observed in mild and moderate than in almost-clear rosacea (P<0.001). Itching of the scalp was more frequently reported in patients with moderate rosacea than in those with mild disease (P=0.05). Follicular scales (P=0.002) and scalp itching (P=0.05) were more frequently reported in D+ than in D- patients. Among D+ patients, scalp itching was more frequently reported in mild than in almost clear rosacea (P=0.01) and ocular symptoms associated to scalp itching were more frequently reported in moderate than in almost-clear rosacea (P=0.05). We suggest looking for these signs and symptoms in all patients with PPR, because they can be a sign of a more severe form of rosacea or of demod-icosis.

The impact of occlusive vs non-occlusive application of methyl aminolevulinate on the efficacy and tolerability of daylight photodynamic therapy for actinic keratosis.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is an effective treatment for actinic keratoses (AKs) and nonmelanoma skin cancer which exploits the photosensitizing properties of methyl aminolaevulinate (MAL). Daylight photodynamic therapy (DL-PDT) is an alternative to c-PDT which does not require the application of MAL in occlusion and that is better tolerated by patients. The impact of occlusion on the efficacy of DL-PD has not been investigated by previous studies. OBJECTIVE: To compare the efficacy and tolerability of occlusive and non-occlusive DL-PDT. METHODS: We conducted a prospective intraindividual left/right comparison study. AKs of the face or scalp were marked in two symmetrical treatment areas. The two target areas were randomly assigned to DL-PDT with occlusive and non-occlusive application of MAL. The efficacy and cosmetic outcome were determined by a "blinded" investigator. RESULTS: Lesions in occluded areas showed a better response in the clearance rate of the lesions (65.5% vs 35.0 %, p < 0.001 %), and cosmetic outcome (P < 0.001). There was no difference in phototoxicity or pain between occluded and non-occluded areas. CONCLUSION: The occlusive application of MAL improves the efficacy of DL-PDT in clearing AKs and does not increase the incidence of side effects.

Atypical Manifestations of Syphilis: A 10-Year Retrospective Study.

Background: The incidence of syphilis has increased in high-income countries in the past few decades, especially among men who have sex with men. In the present study, we aimed to analyze the correlations between atypical syphilis manifestations and the demographic, clinical, and laboratory features of patients and to review unusual presentations of syphilis reported in the literature. Methods: We conducted a retrospective analysis of 307 patients with syphilis diagnosed between 1 January 2013 and 31 October 2023 at the sexually transmitted infection (STI) centers of the University of Genoa and University of Foggia with both typical and atypical manifestations of disease. Results: In our series, atypical manifestations were detected in 25.8% of the patients, especially in the secondary stage of the disease. Lesions with annular morphology and lesions presenting as itchy erythematous scaly plaques with a psoriasiform appearance were the most common atypical presentations of secondary syphilis. A statistical analysis revealed that homosexual orientation, syphilis reinfection, and venereal disease research laboratory (VDRL) titers > 1:32 were correlated with atypical manifestations. Conclusions: Our study demonstrates that the spectrum of syphilis manifestations, in all the stages of the disease, is wide; atypical manifestations often pose diagnostic challenges, may delay the provision of appropriate treatment, and facilitate the spread of the infection.

Histopathologic and transmission electron microscopic findings in monkeypox cutaneous lesions.

Background: a few pathologic and ultrastructural findings of monkeypox skin lesions are available in the literature. To integrate such evidence, we aimed to describe the pathologic features of monkeypox skin lesions and to show monkeypox virions by transmission electron microscopy (TEM). Methods: we studied the cutaneous biopsies of three patients affected by monkeypox during the 2022 monkeypox outbreak. Skin biopsies have been collected only from body sites with a recent laboratory-confirmed mpox virus infection, defined by a polymerase chain reaction (PCR) positive result in specimens taken through skin swabs. Results: in all the samples the epidermis showed keratinocytes ballooning degeneration; perivascular/periadnexal infiltrates composed of neutrophils and lymphocytes were observed in the deep dermis. Immunohistochemistry showed that the infiltrate was mostly composed of CD3+ T-cells. TEM revealed monkeypox virus-like particles in various stages of morphogenesis in the dermis and epidermis; virions were interspersed among keratinocytes and within their cytoplasm. At the intracellular level, virions showed a biconcaveshaped central core, surrounded by lateral bodies and an external membrane; they also appeared as rectangular, brick-shaped, or oval particles with eccentric nucleoids. The histologic features of our skin samples confirmed the few other studies on this topic, except for the eosinophilic inclusions of the cytoplasm of keratinocytes (Guarnieri's bodies). Conclusion: the role of molecular biology is crucial for monkeypox diagnosis but when it is not disposable and/or in doubtful cases, skin biopsy and TEM may be helpful to establish the diagnosis.

Immunotherapy in cutaneous melanoma and biologics in psoriatic disease: similarities and differences from a clinical multidisciplinary perspective.

INTRODUCTION: Immunomodulating therapies harness the power of the immune system to combat disease. In advanced melanoma, immune checkpoint inhibitors have significantly improved survival outcomes by activating the immune system to recognize and eliminate cancer cells. In psoriasis, interleukin inhibitors effectively suppress inflammation and improve disease symptoms. AREAS COVERED: We provide a meta-opinion-based consensus paper on the analogies and differences in treatment mechanisms, duration, frequency between immunotherapy for advanced melanoma and biologics for psoriasis. Combining the current scientific evidence with expert insights, we provide valuable guidance for future research and decision-making processes. EXPERT OPINION: The development of immunological treatments in melanoma and psoriasis has revolutionized dermatology, but the quest for tailored therapies that maximize efficacy continues. Managing cutaneous exacerbations during melanoma immunotherapy in psoriatic patients remains challenging. Similarly, treating oncologic psoriasis patients resistant to traditional therapies requires individualized approaches. Research is needed to identify response predictors in both conditions and address the sustainability of healthcare systems due to the high cost of biologics. Drug delay studies for psoriasis and longer follow-up evaluations after immunotherapy discontinuation in melanoma are essential for optimizing treatment outcomes and resource allocation.

Bimekizumab for the Treatment of Plaque Psoriasis With Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

Diffuse Melanosis Cutis as the First Sign of Recurrence of Low-Risk Melanoma: Case Report and Systematic Review.

INTRODUCTION: Diffuse Melanosis Cutis (DMC) is a rare and late complication of metastatic malignant melanoma (MM) characterized by progressive pigmentation of skin and sometimes mucous membranes. The distinctive feature is the widespread and progressive deposition of melanin precursors in the dermis. OBJECTIVES: The purpose of this review is to define the clinical and demographic features of DMC and to promote a deeper insight into the clinical manifestation, histological findings, and pathophysiology behind DMC. METHODS: We have conducted a systematic review of the literature on published DMC in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We also reported a case of DMC secondary to low-risk melanoma. RESULTS: Overall, including our case report, we reported 53 articles described 62 DMC patients. Breslow level of primary melanoma was reported having a mean value of 3.3 mm. The mean survival rate from onset of DMC resulted being 4.36 months. CONCLUSIONS: Among the most widely accepted etiopathogenetic hypotheses are deposition of melanic precursors in the dermis following tumor lysis, melanocyte proliferation induced by neoplastic growth factors, and the presence of diffuse dermal micro-metastases of MM. However, unanimous consensus on the proposed etiopathogenetic models of DMC is still lacking.

Sexual functioning in patients with psoriasis: the role of body dissatisfaction and cognitive biases toward sexuality.

Psoriasis is a chronic disease, involving skin and joints, characterized by inflamed lesions. Psoriasis negatively impacts the patients' quality of life due to the physical, emotional, and social burden that accompanies this condition. Also, psoriasis is associated with a number of psychiatric comorbidities, including sexual dysfunctions. The present study investigates the variables associated with sexual functioning in psoriasis patients. One-hundred-three psoriasis patients and 101 matched control subjects took part in the present study. Each participant completed five self-report measures investigating the presence of depression, anxiety and stress symptoms, body image, quality of life, and sexual experience. Our results show that differences in sexual activity, but not in sexual functioning, emerged between groups. In men with psoriasis, more sexual difficulties were associated with more negative automatic thoughts about sexuality. In women, more sexual difficulties were associated with more negative automatic thoughts; anxiety, depression, and stress; severity of symptoms; comorbid disease; age; quality of life. Our findings expand the current knowledge about sexual functioning in psoriasis and shed light on specific cognitive, psychological, and demographic variables associated with sexual impairment in men and women with psoriasis.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Prurigo-like atopic dermatitis in a child with CARD11-associated severe combined immunodeficiency successfully treated with dupilumab.

A 12-year-old boy affected by severe combined immunodeficiency due to a heterozygous variant in the CARD domain of CARD11, c.169G>A; p.Glu57Lys, developed severe atopic dermatitis and alopecia areata. After failure of conventional systemic therapy, dupilumab was administered at a dose of 400 mg subcutaneously, followed by 200 mg every 14 days. The patient had an excellent clinical response after 1 month and complete remission after a year, with the absence of side effects, demonstrating good efficacy and safety profile.

Burden of Disease in the Real-Life Setting of Patients with Atopic Dermatitis: Italian Data From the MEASURE-AD Study.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease that negatively impacts the quality of life and work productivity of patients. OBJECTIVES: We sought to evaluate the real-world burden of AD patients in Italy. METHODS: This sub-analysis of the MEASURE-AD multicountry study conducted between December 2019-2020 included patients diagnosed with moderate-to-severe AD eligible for or receiving systemic therapy in the previous 6 months. During a single visit, physician and patient-reported questionnaires were used. RESULTS: A total of 118 adult patients were enrolled and 57.6% (N = 68) of patients had moderate-to-severe AD at the time of enrolment according to the Eczema Area and Severity Index. Sleep disorders interfered with daily function in the previous week in 58.5% (N = 69) of patients, pruritus was severe in 50% (N = 59) and 42.4% (N = 50) reported a flare lasting >7 days in the previous 6 months. According to the Dermatology Quality of Life Index, 37.3% (N = 44) of patients reported a severe impact of AD and approximately 10% had clinical depression/anxiety. Current drug therapy was considered inadequate in controlling AD in 26.3% (N=31) of patients. Work activity impairment was 38.6±31.7% and monthly AD-related expenses were 148.6±134.6 Euros per patient. CONCLUSIONS: This real-life study documents a high burden of disease in patients with moderate-severe AD in Italy.

Efficacy of Human Papillomavirus Vaccines for Recalcitrant Anogenital and Oral Warts.

Human papillomavirus (HPV) vaccines are preventive measures to decrease HPV infection rates. Knowledge of their efficacy as treatment options for anogenital warts (AGWs) and oral warts (OWs) is limited. To evaluate the efficacy of HPV vaccinations in recalcitrant AGWs and OWs (lesions persisting more than 6 months despite conventional treatments), we compared a group of patients treated with standard therapies plus an HPV vaccine with a group of patients treated with standard therapies only. The response to treatment (in terms of the number of lesions) in the two groups was compared. Data were analyzed with the χ2 test and p values < 0.05 were considered to be statistically significant. The study included 14 patients (group A = cases) who received 3 doses of an intramuscular HPV vaccine (Gardasil 4 or Gardasil 9) in addition to the standard treatments for AGWs and OWs, and 15 age- and sex-matched patients (group B = controls) with an analogous number of lesions to group A who received only standard therapies. After 12 months, 85% of patients of group A versus 33% of group B had positive clinical outcomes (0.004). Our findings suggest a possible therapeutic role of HPV vaccines in addition to standard treatments for AGWs/OWs. Preventive vaccines, blocking the viral entry through the induction of L1-specific antibodies, can prevent autologous reinfections (through auto-inoculation) and favor the elimination of the virus.

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Has the Use of the Mask Exacerbated Rosacea During the Pandemic?

INTRODUCTION: During the COVID-19 pandemic, personal protective equipment, particularly face masks, became an essential requirement to engage in various activities. Several articles reported an increase of recurrences of dermatologic facial diseases (ie, acne, rosacea) related to mask use. OBJECTIVES: To evaluate the number of recurrences of rosacea related to face mask use. METHODS: This prospective study was conducted on adult patients with a pre-pandemic diagnosis of mild and moderate papulopustular rosacea. All patients had previously achieved either partial or complete remission after a 4-month treatment with topical ivermectin in 2019. We collected data in two different phases characterized by different intensity of mask use during the pandemic and post-pandemic period. We collected data through clinical assessment of the disease, questionnaires on personal habits and standardized skin surface biopsy to study the Demodex mites count. RESULTS: We enrolled a total of 30 patients. In the pandemic period, 5/30 patients had a relapse of mild papulopustular rosacea; the Demodex sample resulted positive in 4/5 relapsed patients. In the post-pandemic period, 4/30 patients reported a relapse of mild rosacea (3 patients) and moderate papulopustular rosacea (1 patient). At the Demodex exam, 1/4 relapsed patients resulted positive. CONCLUSIONS: We did not find a significant increase in relapses of papulopustular rosacea during the pandemic. An appropriate anti-parasitic treatment may reduce the number of recurrences due to mask use.