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.

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.

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.

"De Novo" Psoriasis and Relapse of Psoriasis Induced by Dupilumab: Three New Cases and Review of the Literature.

Atopic dermatitis and psoriasis are traditionally considered diseases that cannot coexist, since they are described as the result of the activation of opposing inflammatory pathways. However, this belief has been debunked, and numerous cases of psoriasis induced by dupilumab, a biologic treatment for atopic dermatitis, have been reported. We report three cases of dupilumab-induced psoriasis and we present a literature review including cases of "de novo" psoriasis and of the relapse of psoriasis that occurred during treatment with dupilumab. In total, 39 publications met the inclusion criteria, including 112 AD patients, 101 of whom developed "de novo" psoriasis, and 11 with a flare of pre-existent psoriasis. In the first group, patients more frequently developed plaque psoriasis on the scalp and extremities, after an average latency period from the initiation of dupilumab of 5 months. In the second group, the incidence of dupilumab-induced relapses of psoriasis was 43%, after an average of 4 months since the first administration. The most common psoriasis type was plaque psoriasis, with the involvement of the scalp and upper extremities. Dupilumab was interrupted in 38% of patients with "de novo" psoriasis and in 50% of relapsed patients, leading, in most cases, to an improvement of psoriasis. In conclusion, atopic dermatitis and psoriasis can definitely co-exist, and biologic drugs used to treat the former can promote the latter. It is thus crucial to perform a careful personal and familiar anamnesis before prescribing any biologic treatment. Moreover, a study of cytokine expression and blood proteomic markers could be considered in these patients.

Environmental factors in autoimmune bullous diseases with a focus on seasonality: new insights.

Autoimmune bullous diseases are a heterogeneous group of rare conditions clinically characterized by the presence of blisters and/or erosions on the skin and the mucous membranes. Practically, they can be divided into two large groups: the pemphigoid group and the pemphigus group, depending on the depth of the autoimmune process on the skin. A family history of autoimmune diseases can often be found, demonstrating that genetic predisposition is crucial for their development. Moreover, numerous environmental risk factors, such as solar radiation, drugs, and infections, are known. This study aimed to evaluate how seasonality can affect the trend of bullous pemphigoid and pemphigus vulgaris, especially considering the number of hospitalizations recorded over the course of individual months. The total number of hospitalizations in the twelve months of the year was evaluated. Moreover, blood chemistry assay and, for some patients, enzyme-linked immunosorbent assay were executed to evaluate antibodies. Regarding the severity of the disease, the bullous pemphigoid area index and the pemphigus disease area index score systems were used. Results showed a complex interplay between environmental factors such as seasons and autoimmune conditions.

Improvement in quality of life and sexual function in patients affected by vulvar lichen sclerosus treated with combined autologous platelet-rich plasma and fat grafting.

BACKGROUND: Vulvar lichen sclerosus (LS) severely impairs patients' quality of life. OBJECTIVES: To evaluate the impact of a combined application of autologous platelet-rich plasma (PRP) and fat grafting as treatment for vulvar LS on patient quality of life. MATERIALS & METHODS: We reviewed the clinical charts of 72 patients affected by LS, who underwent regenerative surgery. The patients' quality of life was assessed using: the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the patient-administered - Clinical Scoring System (CSS). RESULTS: After reconstructive surgery, all scores improved: Skindex-29 (-31.8 [IQR: 42.1, -21.8] points; p<0.001), FSFI (7.6 [IQR: 2.7, 14.7)] points; p<0.001), Patient-administered CSS (-24 [IQR: -30, -15] points; p<0.001), DLQI (-9 [IQR: -17, -7] points; p<0.001), Physician-administered CSS (-5 [IQR: -7, -5] points; p<0.001), and IGA (median ΔIGA: -4, IQR: -4, -3; p<0.001). CONCLUSION: Combined treatment with PRP and fat grafting proved to be effective in improving the quality of life of patients with vulvar LS.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

Immunosuppressive treatment for autoimmune blistering diseases does not impair production of neutralizing antibodies after "booster" dose of COVID-19 vaccine.

Since vaccines against COVID-19 are available, it has been debated if immunosuppressed patients with autoimmune blistering diseases (AIBDs) should be advised to interrupt the immunosuppressive therapy before receiving the vaccine, with consequent risk to experience a flare of disease. In the present study, we measured the neutralizing antibodies production after anti-SARS-CoV-2 vaccination in patients with AIBDs on immunosuppressive treatment, compared to healthy controls. Our results give strength to the hypothesis that these patients do not need to discontinue their therapy to produce effective levels of neutralizing antibodies, in other words to achieve successful protection.

Usefulness of Dermoscopy in Eruptive Syringomas in an Elderly Woman.

Introduction: Eruptive syringomas (ES) are a rare variant of syringomas, benign adnexal tumors of eccrine sweat glands' ducts. They mostly affect young-to middle-aged women, but rarely they may also occur in the elderly, requiring generally no specific treatment. Case Presentation: We present the case of a 76-year-old woman with sudden onset of ES. Clinical examination evidenced brown-to-orange papules and plaques on the anterior neck, corresponding dermatoscopically to orange-brownish structureless areas, with barely hinted peripheral incomplete network, superimposed on areas of light pink. Histology showed dermal proliferation of epithelial cells forming cords and ductules, confirming the clinical-dermoscopic suspect of ES. The lesions remained stable at 12-month follow-up without treatment. Discussion: This case highlights the role of dermoscopy to help differentiate ES from other clinically similar but more serious entities, such as histiocytosis, mastocytosis, and lichen planus, and to schedule the required confirmatory biopsy in due time without haste.

A novel moisture for xerosis in psoriatic patients: a single center study.

BACKGROUND: Xerosis is an extremely common condition, especially in the elderly population. It is the most common cause of pruritus in the older adult. Since xerosis is generally caused by a lack of epidermal lipids, the use of leave-on skin care products is the mainstay treatment. The aim of this open prospective analytical observational study was to investigate the clinical and self-reported hydrating efficacy of a moisturizer formulation containing a synergy between amino-inositol and urea (INOSIT-U 20) in patients with psoriasis and xerosis. METHODS: Twenty-two patients with psoriasis successfully treated with biologic therapy, and who presented xerosis, were recruited. Each patient was instructed to apply the topical with a frequency of two applications per die on the identified skin area. Corneometry values and a VAS itch questionnaire were measured at baseline (T0) and after 28 days (T4). To evaluate the cosmetic efficacy, the volunteers also completed a self-assessment questionnaire. RESULTS: Comparing Corneometry values at T0 and T4, a statistically significant increase value was observed in the area subjected to topical treatment (P<0.0001). A significant decrease in itch (P=0.001) was also observed. Moreover, the patients' ratings of the cosmetic properties of the moisturizer showed significant confirmation rates. CONCLUSIONS: This study provides preliminary evidence that INOSIT-U20 provides a good hydrating effect on xerosis, further reducing self-reported itch.

Pilot study investigating BP-180 in extracellular vesicles derived from blister fluid of bullous pemphigoid patients.

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the haemidesmosomal proteins, mainly BP180. Extracellular vesicles (EVs) have been demonstrated to carry tissue-specific autoantigens in the setting of autoimmune diseases and transplant organ rejection; this phenomenon was demonstrated to have pathogenic implications in autoimmune diseases and to correlate with transplant rejection severity. The purpose of this study was to identify the presence of BP targeted autoantigens in blister fluid derived EVs. We isolated, by size exclusion chromatography, EVs derived from blisters of BP-patients and from suction blisters of healthy donors. EV characterization was performed by flow cytometry and nanoparticle tracking analysis. Western blot analysis was used to investigate the presence of autoantigens. A suspension enriched in EVs was efficiently obtained from blister fluid from patients and healthy donors. EV-enriched fractions were enriched in particles with a size distribution characterizing small-EVs (main peak was present at 94.5 nm). BP180 was found, by western blot analysis, in EVs derived from blister fluid of 3 out 6 BP patients and in none of EVs isolated from suction blister fluid of healthy donors. BP230 and Dsg1 were not detectable in EVs of any of the samples. No specific clinical characteristics seemed to correlate to the presence of BP180 in EVs. The discovery of BP180 in EVs derived from blister fluid might help understanding BP pathogenesis.