Infliximab-induced amicrobial pustulosis of the folds in a patient with Crohn disease.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Genetic analysis of different subtypes of aseptic pustulosis in the Chinese population.

Aseptic pustulosis involves inflammatory skin conditions with nonbacterial pustules on erythema, accompanied by neutrophil and eosinophil infiltration in the epidermis. Dysregulation of the interleukin (IL)-36 pathway leads to neutrophil aggregation and pustule formation. Variants in IL36RN, CARD14, AP1S3, MPO, SERPINA3 and BTN3A3 have been identified in generalized pustular psoriasis (GPP) in the past. Some patients with acrodermatitis continua of Hallopeau (ACH), palmoplantar pustulosis and acute generalized exanthematous pustulosis (AGEP) also exhibit mutations in IL36RN, CARD14 and AP1S3, albeit with regional and population-specific variations. This study aims to explore a shared genetic foundation among those with aseptic pustulosis. We performed Sanger sequencing on six genes in 126 patients with aseptic pustulosis. Genetic analysis identified IL36RN variants strongly associated with ACH, AGEP and subcorneal pustular dermatosis (SPD). Immunohistochemistry revealed elevated inflammatory cytokines in all subtypes. This study establishes a significant association between IL36RN variants and ACH, AGEP and SPD, emphasizing the IL-1/IL-36-chemokine-neutrophil axis as a common pathogenic mechanism. Targeting this axis holds promise for therapeutic interventions for aseptic pustulosis.

[Autoimmune bullous diseases in children]. / Dermatoses bulleuses auto-immunes chez les enfants.

Auto-immune bullous diseases (AIBD) are rare in children. Although their pathogenesis is similar to their adult counterpart, there are differences in the clinical presentation. Moreover certain AIBD prevail at certain ages. There are no guidelines for the treatment of AIBD specific for children. In this review the recent literature is summarised with attention to recent data including diagnostic criteria. We also propose a treatment algorithm.

Les maladies bulleuses auto-immunes (MBAI) sont rares chez les enfants. Bien que la pathogenèse soit similaire à celle de l'adulte, il existe des différences concernant la présentation clinique et la prévalence des MBAI selon l'âge. À ce jour, il n'y a pas de recommandations spécifiques pour leur prise en charge chez l'enfant. Dans cet article, nous présentons une revue des données actuelles, des critères diagnostiques et proposons un algorithme de prise en charge.

A deep learning approach to direct immunofluorescence pattern recognition in autoimmune bullous diseases.

BACKGROUND: Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning (DL) 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 (AIBDs) remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of DL to classify DIF patterns automatically, including the intercellular (ICP) and linear pattern (LP), holds promise for improving the diagnosis of AIBDs. OBJECTIVES: To develop AI algorithms for automated classification of AIBD DIF patterns, such as ICP and LP, in order to enhance diagnostic accuracy, streamline disease management and improve patient outcomes through DL-driven immunofluorescence interpretation. METHODS: We collected immunofluorescence images from skin biopsies of patients suspected of having an AIBD between January 2022 and January 2024. Skin tissue was obtained via a 5-mm punch biopsy, prepared for DIF. Experienced dermatologists classified the images as ICP, LP or negative. To evaluate our DL approach, we divided the images into training (n = 436) and test sets (n = 93). We employed transfer learning with pretrained deep neural networks and conducted fivefold 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 224 × 224 pixels for both convolutional neural networks (CNNs) and the Swin Transformer. RESULTS: Our study compared six CNNs and the Swin Transformer for AIBD image classification, with the Swin Transformer achieving the highest average validation accuracy (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 AIBD classes. Visualization with Grad-CAM (class activation mapping) highlighted the model's reliance on characteristic patterns for accurate classification. CONCLUSIONS: The study highlighted the accuracy of CNNs in identifying DIF features. This approach aids automated analysis and reporting, offering reproducibility, speed, data handling and cost-efficiency. Integrating DL into skin immunofluorescence promises precise diagnostics and streamlined reporting in this branch of dermatology.

Artificial intelligence (AI) is transforming healthcare through machine and deep learning (computer systems that can learn and adapt, and make complex decisions, without receiving explicit instructions), improving disease management in dermatology, particularly in detecting skin cancer. However, AI's potential in automating immunofluorescence imaging in autoimmune bullous (blistering) skin diseases (AIBDs) remains largely untapped. Manual interpretation of direct immunofluorescence (DIF ­ a type of microscopy) can reduce efficiency. However, using deep learning to automatically classify DIF patterns (for example, the 'intercellular pattern' (ICP) and the 'linear pattern' (LP)) holds promise in helping with the diagnosis of AIBDs. This study aimed to develop AI algorithms for the automated classification of AIBD DIF patterns, such as ICP and LP, to improve diagnostic accuracy and streamline disease management. Immunofluorescence images were collected from skin biopsies of patients with a suspected AIBD between January 2022 and January 2024. Dermatologists classified the images into three categories: ICP, LP and negative. The dataset was divided into training (436 images) and test sets (93 images). A transfer learning framework (where what has been learned previously in one setting is used to improve performance in another) was used to make up for the limited amount of training data, to explore different models for the AIBD classification task. Our results revealed that a model called the 'Swin Transformer' achieved an average accuracy of 99% in diagnosing different AIBDs. The best model attained 95% accuracy on the test set and was reliable in identifying and ruling out different AIBDs. Visualization with Grad-CAM (a technique used in deep learning) highlighted the model's use of characteristic patterns to classify the diseases accurately. Overall, integrating deep learning in skin immunofluorescence promises to improve diagnostics and streamline reporting in dermatology, which could improve consistency, speed and cost-efficiency.

Two cases of infancy associated eosinophilic pustular folliculitis (I-EPF) comparing the profile of infiltrating cells with classic EPF by immunohistochemical study.

Infancy associated eosinophilic pustular folliculitis (I-EPF) is a clinical variant of EPF that develops in childhood. Previous studies have suggested that I-EPF exhibits clinical and histological differences distinct from other variants, including classic EPF. Herein, we report two patients with I-EPF treated with topical indomethacin. These two cases exhibited less perifollicular and more perivascular eosinophilic infiltration, which is different in distribution from that of classic EPF. Immunohistochemical study demonstrated that the infiltrating mononuclear cells were CD4-dominant T cells in classic EPF and I-EPF, whereas the number of CD68-positive cells was significantly higher in classic EPF than in I-EPF. Immunohistochemical staining was also performed for eosinophilic pustular folliculitis (HPGDS), which has been reported to induce eosinophils and is a therapeutic target of indomethacin in classic EPF. HPGDS-positive cells were also observed in I-EPF, which may explain the effectiveness of topical indomethacin. Although clinical and histopathological features of I-EPF are different from other variants, the arachidonic acid pathway could be involved in eosinophil infiltration, not only in classic EPF but also in I-EPF.

[The main autoimmune bullous diseases]. / Les principales maladies bulleuses auto-immunes.

Autoimmune bullous diseases are disorders in which the immune system mistakenly attacks certain molecules that act as "glue" in the various layers of the skin, leading to the formation of bullae or vesicles. A bulla is a liquid-containing lesion over five millimeters in size on the skin or mucous membranes. It forms due to a loss of cohesion between the epidermis and dermis, or between keratinocytes within the epidermis. Diagnosis is based on biopsies, which show the presence of autoantibodies and the depth of skin detachment. A blood test can be used to identify circulating autoantibodies.

Immune cells in pemphigus vulgaris and bullous Pemphigoid: From pathogenic roles to targeting therapies.

Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are two major subtypes of autoimmune bullous diseases (AIBD), characterized by blisters and erosions of skin and/or mucous membranes with dysregulated immune activity. Current literature established that T and B cells are the main executors of PV and BP. Emerging evidence revealed that macrophages and related cytokines also contribute to these diseases. While the role of lymphocytes on PV and BP is well established, the definitive functions of macrophages in disease progression are not fully understood. Furthermore, current status of clinical trials targeting immune cells is poorly recapitulated in PV and BP. In this review, we summarized current knowledge in this rapidly advancing field, with emphasis on the individual functions of immune cells and their interactions, as well as ongoing clinical trials targeting immune cells, to provide novel insights in mechanistic understanding and clinical management of PV and BP.

Three cases of subcorneal pustular dermatosis with immunohistochemical examinations.

Subcorneal pustular dermatosis, a rare, benign skin disease, is a type of neutrophilic dermatosis. The authors reported three cases of subcorneal pustular dermatosis. In case 1, a 9-year-old girl developed a skin rash with blisters following a mycoplasma infection and had a flare-up due to a common cold. She was successfully treated with a topical corticosteroid. In case 2, a 70-year-old woman who had been treated for rheumatoid arthritis with adalimumab, salazosulfapyridine, and leflunomide developed 3- to 5-mm pustules on her trunk and thighs 4 days after flu vaccination. The rash disappeared with drug withdrawal and treatment with diaminodiphenyl sulfone. In case 3, an 81-year-old man, who was diagnosed with pyoderma gangrenosum at 61 years old, developed multiple small flaccid pustules on his trunk and extremities due to an infection in the arteriovenous shunt area on the forearm. The pustule disappeared with intravenous antibiotic therapy; however, the pustules subsequently flared up along with ulcers typical of pyoderma gangrenosum. He was given oral prednisolone therapy, which was effective for the small pustules and some ulcers. Immunohistochemical examination of the three cases revealed neutrophilic infiltration in the subcorneal layer of the epidermis. The pustules contained neutrophils as well as some CD68+ and a few CD1a+ cells. The epidermis and dermis were more predominantly infiltrated by CD4+ cells than by CD8+ cells. Positive stainings for interleukin 8, interleukin 36γ, and phospho-extracellular signal-regulated kinases 1 and 2 were observed in the upper layers of the epidermis below the pustules. Although the pathogenesis of subcorneal pustular dermatosis has not been clarified, the current results suggest that a variety of inflammatory cells, including those responsible for both innate and acquired immunity, are involved in the accumulation of neutrophils in subcorneal pustular dermatosis.

Genetics of Generalized Pustular Psoriasis: Current Understanding and Implications for Future Therapeutics.

Psoriasis is a chronic inflammatory skin disease characterized by the appearance of clearly demarcated erythematous and scaly plaques. It can be divided into various types, including plaque, nail, guttate, inverse, and pustular psoriasis. Plaque psoriasis is the most commonly occurring type, though there is another rare but severe pustular autoinflammatory skin disease called generalized pustular psoriasis (GPP), which manifests with acute episodes of pustulation and systemic symptoms. Though the etiopathogenesis of psoriasis is not yet fully understood, a growing body of literature has demonstrated that both genetic and environmental factors play a role. The discovery of genetic mutations associated with GPP has shed light on our comprehension of the mechanisms of the disease, promoting the development of targeted therapies. This review will summarize genetic determinants as known and provide an update on the current and potential treatments for GPP. The pathogenesis and clinical presentation of the disease are also included for a comprehensive discussion.

[Mucosal anomalies in autoimmune bullous diseases]. / Mucosale afwijkingen bij blaarvormende auto-immuunziekten.

Mucosal anomalies are frequently seen in autoimmune bullous diseases, particularly in pemphigus vulgaris and mucous membrane pemphigoid. The blistering, erosions, ulceration or erythema may present anywhere on the oral mucosa, but also on other mucosal sites. A differential diagnosis is needed of (erosive) oral lichen planus, systemic autoimmune disease, inflammatory bowel diseases, chronic graft-versus-host disease, infectious causes, Behçet's syndrome and recurrent aphthous stomatitis. A quick diagnosis and initiation of adequate treatment are important because of the potential severity of the disease and to prevent complications due to cicatrization. Besides a biopsy for histopathological analysis, a perilesional biopsy for direct immunofluorescence microscopy and immunoserological tests are needed for diagnosis of pemphigus or pemphigoid. In addition to a mucosal biopsy, a biopsy for direct immunofluorescence of the skin can contribute to a diagnosis of a bullous disease. Besides topical corticosteroids, immunosuppressive treatment is often required for treating autoimmune bullous diseases, such as treatment with rituximab in patients with pemphigus.