RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.

Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications of Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk of leukemia development. Here, we propose that RUNX1 isoform disequilibrium with RUNX1A bias is key to DS-associated myeloid leukemia (ML-DS). Starting with Hsa21-focused CRISPR-CRISPR-associated protein 9 screens, we uncovered a strong and specific RUNX1 dependency in ML-DS cells. Expression of the RUNX1A isoform is elevated in patients with ML-DS, and mechanistic studies using murine ML-DS models and patient-derived xenografts revealed that excess RUNX1A synergizes with the pathognomonic Gata1s mutation during leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium in patient-derived xenografts in vitro and in vivo. Moreover, pharmacological interference with MYC:MAX dimerization using MYCi361 exerted strong antileukemic effects. Thus, our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidy, and paves the way for the development of specific and targeted therapies for ML-DS, as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.

Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms.

Peripheral T-cell lymphomas (PTCLs), especially angioimmunoblastic and follicular TCLs, have a dismal prognosis because of the lack of efficient therapies, and patients' symptoms are often dominated by an inflammatory phenotype, including fever, night sweats, weight loss, and skin rash. In this study, we investigated the role of inflammatory granulocytes and activated cytokine signaling on T-cell follicular helper-type PTCL (TFH-PTCL) disease progression and symptoms. We showed that ITK-SYK-driven murine PTCLs and primary human TFH-PTCL xenografts both induced inflammation in mice, including murine neutrophil expansion and massive cytokine release. Granulocyte/lymphoma interactions were mediated by positive autoregulatory cytokine loops involving interferon gamma (CD4+ malignant T cells) and interleukin 6 (IL-6; activated granulocytes), ultimately inducing broad JAK activation (JAK1/2/3 and TYK2) in both cell types. Inflammatory granulocyte depletion via antibodies (Ly6G), genetic granulocyte depletion (LyzM-Cre/MCL1flox/flox), or IL-6 deletion within microenvironmental cells blocked inflammatory symptoms, reduced lymphoma infiltration, and enhanced mouse survival. Furthermore, unselective JAK inhibitors (ruxolitinib) inhibited both TCL progression and granulocyte activation in various PTCL mouse models. Our results support the important role of granulocyte-driven inflammation, cytokine-induced granulocyte/CD4+ TCL interactions, and an intact JAK/STAT signaling pathway for TFH-PTCL development and also support broad JAK inhibition as an effective treatment strategy in early disease stages.

Sensitization against medical hyaluronidase in patients with confirmed hypersensitivity against hymenoptera species and its clinical implications.

BACKGROUND: Hyaluronidase is an ubiquitious enzyme, present, amongst others, in hymenoptera venom and in medical formulations. The latter include use as an emergency treatment or to correct undesired outcomes of medical and aesthetic procedures using hyaluronic acid fillers. By performing detailed allergy work-ups including prick-testing we investigated here if patients with a history of allergic reaction to hymenoptera venom are also sensitized to medical grade hyaluronidase. METHODS: Ninety patients with a history of type-1 reaction to hymenoptera venom with and without a history of previous specific venom immunotherapy were included in the study. All underwent skin prick tests for medical hyaluronidase. All patients also underwent serological analysis for Api m2, the only commercially available IgE-test for a hymenoptera hyaluronidase. RESULTS: Of the 90 patients with previous type-1 reactions to hymenoptera venom hyaluronidase included in the study, 60 had undergone previous venom immunotherapy, 30 did not. A majority (73/90) were allergic to wasps, followed by honeybees (14/90) and 3 were allergic to both. Neither patients having undergone previous immunotherapy nor those allergic to bees showed positive skin prick tests to medical hyaluronidase. Of those with a wasp allergy and naïve to immunotherapy, over 20% (5/23) showed positive skin prick tests to medical hyaluronidase. Healthy controls (0/30) without previous allergic reactions to hymenoptera did not show positive skin prick tests to medical hyaluronidase. CONCLUSION: Sensitization to hyaluronidase is most common in wasp-allergic patients who have not had previous specific immunotherapy. As allergic reactions to medical hyaluronidase are reported to be scarce, this group is probably at the highest risk to develop anaphlaxis to medical hyaluronidase. While all patients with untreated anaphylaxis to hymenoptera venom should consult an allergy specialist, particularly those with untreated wasp allergies need to seek a specialist's advice before treatment with medical hyaluronidase is initiated.

Illuminating characteristic patterns of inflammatory dermatoses: A comprehensive dual-imaging approach using Optical coherence tomography and Line-field confocal optical coherence tomography.

BACKGROUND: Inflammatory skin diseases, such as psoriasis, atopic eczema, and contact dermatitis pose diagnostic challenges due to their diverse clinical presentations and the need for rapid and precise diagnostic assessment. OBJECTIVE: While recent studies described non-invasive imaging devices such as Optical coherence tomography and Line-field confocal OCT (LC-OCT) as possible techniques to enable real-time visualization of pathological features, a standardized analysis and validation has not yet been performed. METHODS: One hundred forty lesions from patients diagnosed with atopic eczema (57), psoriasis (50), and contact dermatitis (33) were imaged using OCT and LC-OCT. Statistical analysis was employed to assess the significance of their characteristic morphologic features. Additionally, a decision tree algorithm based on Gini's coefficient calculations was developed to identify key attributes and criteria for accurately classifying the disease groups. RESULTS: Descriptive statistics revealed distinct morphologic features in eczema, psoriasis, and contact dermatitis lesions. Multivariate logistic regression demonstrated the significance of these features, providing a robust differentiation between the three inflammatory conditions. The decision tree algorithm further enhanced classification accuracy by identifying optimal attributes for disease discrimination, highlighting specific morphologic criteria as crucial for rapid diagnosis in the clinical setting. CONCLUSION: The combined approach of descriptive statistics, multivariate logistic regression, and a decision tree algorithm provides a thorough understanding of the unique aspects associated with each inflammatory skin disease. This research offers a practical framework for lesion classification, enhancing the interpretability of imaging results for clinicians.

Subjective Discomfort during Botulinumtoxin Injections Dependent on Injection Site and Needle Size: A Comparison Between 30G, 33G and 34G Needles.

BACKGROUND: Botulinumtoxin application in the face is amongst the most common aesthetic procedures in the head and neck region. It also has numerous medical uses. One of the main reasons for patients to refrain from it is the subjective discomfort that is experienced during injections. OBJECTIVES: The study at hand aimed to determine whether needles with 33G and 34G offer an advantage in terms of individual pain perception during botulinumtoxin injections. METHODS: We conducted a prospective study where patients were asked to grade subjective discomfort on a visual analogue scale for each region (forehead, glabella, temple) that was treated directly after treatment and 15 minutes after. Patients were treated with 30G, 33G or 34G needles, respectively. RESULTS: Ninety-nine patients that underwent treatment of 189 regions were included in the study. Patients were evenly distributed amongst the different needle sizes and regions. Subjective discomfort was greatest in all regions for 30G needles (3.9 ± 1.6 forehead, 4.3 ± 1.7 glabella and 4.0 ± 1.6 temple) followed by 33G (2.7 ± 1.5 forehead, 2.7 ± 1.9 glabella and 2.2 ± 1.2 temple) and 34G (1.7 ± 1.2 forehead, 1.6 ± 1.4 glabella and 1.6 ± 1.4 temple). All differences between needle size were statistically significant (p < 0.05) CONCLUSION: 33G and 34G needles seem to offer smaller discomfort during BTX treatments of the head and neck, with 34G being superior to 33G. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Line-field confocal optical coherence tomography, a novel non-invasive tool for the diagnosis of onychomycosis.

BACKGROUND AND OBJECTIVES: Onychomycosis is common and important to distinguish from other nail diseases. Rapid and accurate diagnosis is necessary for optimal patient treatment and outcome. Non-invasive diagnostic tools have increasing potential for nail diseases including onychomycosis. This study evaluated line-field confocal optical coherence tomography (LC-OCT) as a rapid non-invasive tool for diagnosing onychomycosis as compared to confocal laser scanning microscopy (CLSM), optical coherence tomography (OCT), and conventional methods. PATIENTS AND METHODS: In this prospective study 86 patients with clinically suspected onychomycosis and 14 controls were examined using LC-OCT, OCT, and CLSM. KOH-preparation, fungal culture, PCR, and histopathology were used as comparative conventional methods. RESULTS: LC-OCT had the highest sensitivity and negative predictive value of all methods used, closely followed by PCR and OCT. Specificity and positive predictive value of LC-OCT were as high as with CLSM, while OCT scored much lower. The gold standard technique, fungal culture, showed the lowest sensitivity and negative predictive value. Only PCR and culture allowed species differentiation. CONCLUSIONS: LC-OCT enables quick and non-invasive detection of onychomycosis, with advantages over CLSM and OCT, and similar diagnostic accuracy to PCR but lacking species differentiation. For accurate nail examination, LC-OCT requires well-trained and experienced operators.

Divergent in situ expression of IL-31 and IL-31RA between bullous pemphigoid and pemphigus vulgaris.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.

Antibiotic Prophylaxis of Surgical Site Infections in Cutaneous Surgery: A Prospective Observational Study.

The use of perioperative antibiotic prophylaxis in cutaneous surgery is controversial due to unclear efficacy and, thus, potentially unnecessary side-effects. This prospective observational study analysed the efficacy of oral perioperative antibiotic prophylaxis in preventing surgical site infections. Adult patients undergoing cutaneous surgery between August 2020 and May 2021 at Ludwig-Maximilian University Hospital Munich, Germany, without prior signs of infection were eligible. Propensity score weighting was used for covariate adjustment to account for non-randomized treatment assignment. Of 758 included patients, 23 received perioperative antibiotic prophylaxis (3.0%). In this group, a surgical site infection occurred in 1 of 45 lesions (2.2%) compared with 76 of 1,189 lesions (6.5%) in the group without perioperative antibiotic prophylaxis (735 patients, 97.0%). With covariate adjustment, the odds ratio for the occurrence of a surgical site infection in patients receiving perioperative antibiotic prophylaxis was 0.114 (95% confidence interval 0.073-0.182; p <0.001) on a per lesion level. The number of lesions needed to treat to prevent 1 surgical site infection was 17.6 (95% confidence interval 16.8-19.2). This prospective observational study shows a reduction in the incidence of surgical site infection in cutaneous surgery performed with perioperative antibiotic prophylaxis. The large size difference between the 2 study groups limits the study.

Cognitive Variables in Social Anxiety Disorder in Children and Adolescents: A Network Analysis.

Clark and Wells' prominent model of social anxiety disorder (SAD) assumes that cognitive variables such as negative expectations or dysfunctional cognitions play a central role in the symptomatology of SAD. In contrast to adults, it is less clear how well the cognitive model can be applied to children and adolescents. A network analysis with seven nodes was conducted to explore the importance of cognitive variables and their interaction with symptoms of SAD based on N = 205 children and adolescents (8-18 years, M = 11.54 years). Cognitive variables had a high but differential impact within the positively connected network of SAD. Dysfunctional cognitions were most strongly connected within the network. Dysfunctional cognitions, as predicted by Clark and Wells' model, seem to act as a hub affecting several symptoms. The association between negative expectations and avoidance indicates that negative expectations may particularly contribute to the maintenance of SAD.

Perioperative antibiotic prophylaxis in skin surgery - Position paper of the Antibiotic Stewardship working group of the German Society for Dermatologic Surgery (DGDC), Part 1: Procedure- and patient-related risk factors.

The aim of perioperative antibiotic prophylaxis (PAP) is to prevent the occurrence of surgical site infections (SSIs) or other infectious complications (especially bacterial endocarditis or septic arthritis). PAP is effective in surgeries where overall infection rates are high even without considering patient-related risk factors (such as orthopedic surgery or fracture repair). Surgery on airways, gastrointestinal, genital, or urinary tract is also considered to be associated with a risk of infection and may require PAP. Overall, SSIs in skin surgery are relatively rare and vary between 1% and 11% depending on the localization, complexity of the wound closure and patient cohort. Therefore, the general surgical recommendations regarding PAP only partially reflect the needs of dermatologic surgery. In contrast to the USA, where recommendations on the use of PAP in skin surgery already exist, there are currently no guidelines for the use of PAP specifically designed for dermatologic surgery in Germany. In the absence of an evidence-based recommendation, the use of PAP is guided by the experience of the surgeons and leads to a heterogeneous use of antimicrobial substances. In this work, we summarize the current scientific literature on the use of PAP and make a recommendation depending on procedure- and patient-related risk factors.

Perioperative antibiotic prophylaxis in skin surgery - Position paper of the Antibiotic Stewardship working group of the German Society for Dermatologic Surgery (DGDC), Part 2: Special indications and situations.

In addition to prevention of surgical site infections after skin surgery, perioperative antibiotic prophylaxis (PAP) aims to prevent the occurrence of other postoperative infectious complications, especially bacterial endocarditis and hematogenous joint prosthesis infections. This article discusses specific indications for the use of PAP. For example, patients who have undergone any type of heart valve replacement, including transcatheter valve replacement or use of prosthetic material to correct the heart valve, or patients who have experienced bacterial endocarditis, require PAP during skin surgery on mucosal membranes or ulcerated tumors. The use of PAP in special situations such as secondary wound healing, septic dermatosurgery or ulcer surgery is also presented and discussed in detail in this paper based on the current scientific literature. This paper represents the second part of the position paper of the Antibiotic Stewardship Working Group of the German Society for Dermatologic Surgery (DGDC) and summarizes evidence-based recommendations for the administration of PAP during skin surgery for special indications and situations. This is particularly important because, as detailed in Part 1 of this position paper, PAP can and usually should be avoided in skin surgery.

Surgical site infection in skin surgery-An observational study.

BACKGROUND: Surgical site infection (SSI) has a significant impact on patients' morbidity and aesthetic results. OBJECTIVE: To identify risk factors for SSI in dermatologic surgery. PATIENTS AND METHODS: This prospective, single-centre, observational study was performed between August 2020 and May 2021. Patients that presented for dermatologic surgery were included and monitored for the occurrence of SSI. For statistical analysis, we used a mixed effects logistic regression model. RESULTS: Overall, 767 patients with 1272 surgical wounds were included in the analysis. The incidence of SSI was 6.1%. Significant risk factors for wound infection were defect size over 10cm2 (OR 3.64, 95% confidence interval [CI] 1.80-7.35), surgery of cutaneous malignancy (OR 2.96, CI 1.41-6.24), postoperative bleeding (OR 4.63, CI 1.58-13.53), delayed defect closure by local skin flap (OR 2.67, CI 1.13-6.34) and localisation of surgery to the ear (OR 7.75, CI 2.07-28.99). Wound localisation in the lower extremities showed a trend towards significance (OR 3.16, CI 0.90-11.09). Patient-related factors, such as gender, age, diabetes, or immunosuppression, did not show a statistically significant association with postoperative infection. CONCLUSION: Large defects, surgery of cutaneous malignancy, postoperative bleeding, and delayed flap closure increase the risk for SSI. High-risk locations are the ears and lower extremities.

In vivo examination of healthy human skin after short-time treatment with moisturizers using confocal Raman spectroscopy and optical coherence tomography: Preliminary observations.

Skin is our barrier against environmental damage. Moisturizers are widely used to increase hydration and barrier integrity of the skin; however, there are contrasting observations on their in vivo effects in real-life settings. In cosmetic studies, corneometers and tewameters are traditionally used to assess skin hydration. In this study, two novel noninvasive diagnostic techniques, optical coherence tomography (OCT) and confocal Raman spectroscopy, were used to analyze stratum corneum and epidermal thickness (ET), water content, blood flow in function of depth, skin roughness, attenuation coefficient, natural moisturizing factor, ceramides and free fatty acids, cholesterol, urea, and lactates in 20 female subjects aged between 30 and 45 before and after 2 weeks application of a commercially available moisturizing lotion on one forearm. The untreated forearm served as control. A third measurement was conducted 1 week after cessation of moisturizing to verify whether the changes in the analyzed parameters persisted. We noticed a reduction in skin roughness, an increase in ceramides and free fatty acids and a not statistically significant increase in ET. As a conclusion, short time moisturizing appears insufficient to provide significant changes in skin morphology and composition, as assessed by OCT and RS. Novel noninvasive imaging methods are suitable for the evaluation of skin response to topical moisturizers. Further studies on larger sample size and longer treatment schedules are needed to analyze changes under treatment with moisturizers and to standardize the use of novel noninvasive diagnostic techniques.

Are Specific Body Sites Prone for Wound Infection After Skin Surgery? A Systematic Review and Meta-Analysis.

INTRODUCTION: Identifying risk factors for wound infection may guide clinical practice for optimal use of perioperative antibiotic prophylaxis in dermatologic surgery. OBJECTIVE: To summarize the current evidence whether specific body sites have higher risks for surgical site infections (SSI). METHODS: The systematic literature search included MEDLINE, Embase, CENTRAL, and trial registers. Only observational studies qualified for inclusion and meta-analysis. We assessed the risk of bias according to the Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 33,086 surgical wounds were eligible. Eight studies were of good, 4 of fair, and 6 of poor quality. The mean infection rate was 4.08%. Meta-analysis showed that the lips had significantly higher infection rates. The lower extremity and ears had or tended toward a higher risk for infection, but studies were clinically heterogeneous. A large prospective trial found that surgical wounds on the hands were at higher risk for infection. The trunk showed the lowest infection rate. The risk for SSI in other body locations was not different or remained uncertain because of substantial heterogeneity among studies. CONCLUSION: Lips, lower extremities, and probably ears and hands may have a higher risk for wound infection after skin surgery. The trunk showed the lowest infection rate.

Procedure-Related Risk Factors for Surgical Site Infection in Dermatologic Surgery.

BACKGROUND: Identifying risk factors is essential for preventing surgical site infections (SSIs) in dermatologic surgery. OBJECTIVE: To analyze whether specific procedure-related factors are associated with SSI. METHODS: This systematic review of the literature included MEDLINE, EMBASE, CENTRAL, and trial registers. The Newcastle-Ottawa Scale was used for risk bias assessment. If suitable, the authors calculated risk factors and performed meta-analysis using random effects models. Otherwise, data were summarized narratively. RESULTS: Fifteen observational studies assessing 25,928 surgical procedures were included. Seven showed good, 2 fair, and 6 poor study quality. Local flaps (risk ratio [RR] 3.26, 95% confidence intervall [CI] 1.92-5.53) and skin grafting (RR 2.95, 95% CI 1.37-6.34) were associated with higher SSI rates. Simple wound closure had a significantly lower infection risk (RR 0.34, 95% CI 0.25-0.46). Second intention healing showed no association with SSI (RR 1.82, 95% CI 0.40-8.35). Delayed wound closure may not affect the SSI rate. The risk for infection may increase with the degree of preoperative contamination. There is limited evidence whether excisions >20 mm or surgical drains are linked to SSI. CONCLUSION: Local flaps, skin grafting, and severely contaminated surgical sites have a higher risk for SSI. Second intention healing and probably delayed wound closure are not associated with postoperative wound infection.

Impact of the COVID-19 pandemic on patients with hidradenitis suppurativa.

The COVID-19 pandemic caused collateral damage to patients with acute and chronic conditions. In this mono-centre cross-sectional study, we sought to evaluate the impact of the COVID-19 pandemic on patients with hidradenitis suppurativa (HS). In June 2020, we sent an anonymous survey to 109 patients, who were diagnosed with HS in our outpatient clinic from May 2018 to April 2020. Fifty patients (45.9%) completed and returned the survey. Forty-five participants (90.0%) denied any cancellation of hospitalisation due to the COVID-19 pandemic. Hospitalisation was postponed in 8% of cases and cancelled in 2%. Compared to prior to the pandemic, fewer patients consulted their primary physician for changing wound dressings and more changed the dressings themselves or were assisted by their family members. 13% of patients avoided doctor visits due to fear of COVID-19 and 26.1% minimised doctor visits. The Dermatology Life Quality Index showed a moderate to very severe impact on patients' Quality of Life (mean score = 10.06). Only one patient used telemedicine. Due to limited access to primary care and fear of COVID-19, the pandemic had a detectable impact on the hospital management of patients with HS in our facility. Telemedicine still plays a negligible role in primary wound care.

Patient-dependent risk factors for wound infection after skin surgery: A systematic review and meta-analysis.

Postoperative wound infection in dermatologic surgery causes impaired wound healing, poor cosmetic outcome and increased morbidity. Patients with a high-risk profile may benefit from perioperative antibiotic prophylaxis. The objective of this systematic review was to identify risk factors for surgical site infection after dermatologic surgery. In this article, we report findings on patient-dependent risk factors. The literature search included MEDLINE, EMBASE, CENTRAL and trial registers. We performed meta-analysis, if studies reported sufficient data to calculate risk ratios with 95% confidence intervals. Study quality was assessed according to the Newcastle-Ottawa-Scale. Seventeen observational studies that analysed 31213 surgical wounds were eligible for inclusion. Fourteen studies qualified for meta-analysis. Nine studies showed good, three fair and five poor methodological quality. The reported incidence of surgical site infection ranged from 0.96% to 8.70%. Meta-analysis yielded that male gender and immunosuppression were significantly associated with higher infection rates. There was a tendency towards a higher infection risk for patients with diabetes, without statistical significance. Meta-analysis did not show different infection rates after excision of squamous cell carcinoma or basal cell carcinoma, but studies were substantially heterogenous. There was no significant association between risk for wound infection and smoking, age over 60 years, oral anti-aggregation or anti-coagulation or excision of malignant melanoma. In conclusion, the risk for surgical site infection in dermatologic surgery is low. Infection rates were increased significantly in male as well as immunosuppressed patients and non-significantly in diabetics.

New-generation diagnostics in inflammatory skin diseases: Immunofluorescence and histopathological assessment using ex vivo confocal laser scanning microscopy in cutaneous lupus erythematosus.

Ex vivo confocal laser scanning microscopy (CLSM) offers real-time examination of excised tissue in reflectance, fluorescence and digital haematoxylin-eosin (H&E)-like staining modes enabling application of fluorescent-labelled antibodies. We aimed to assess the diagnostic performance of ex vivo CLSM in identifying histopathological features and lupus band test in cutaneous lupus erythematosus (CLE) with comparison to conventional histopathology and direct immunofluorescence (DIF). A total of 72 sections of 18 CLE patients were stained with acridine orange (AO), anti-IgG, anti-IgM and anti-IgA; 21 control samples were stained with AO. Subsequently, ex vivo CLSM examination of all samples was performed in reflectance, fluorescence and digital H&E-like staining modes. Superficial and deep perivascular inflammatory infiltration (94.4%), interface dermatitis (88.9%), spongiosis (83.3%) and vacuolar degeneration (77.7%) were the most common features detected with ex vivo CLSM. Kappa test revealed a level of agreement ranging within "perfect" to "good" between ex vivo CLSM and conventional histopathology. ROC analysis showed that the combination of perivascular infiltration, interface dermatitis and spongiosis detected by ex vivo CLSM has the potential to distinguish between CLE and controls. Basement membrane immunoreactivity with IgG, IgM and IgA was identified in 88.8% (n = 15), 55.5% (n = 10) and 55.5% (n = 10) of the CLE samples using ex vivo CLSM, respectively, whereas DIF showed IgG, IgM and IgA positivity in 94.4% (n = 17), 100% (n = 18) and 88.9% (n = 16) of patients, respectively. In conclusion, ex vivo CLSM enables simultaneous histopathological and immunofluorescence examination in CLE showing a high agreement with conventional histopathology, albeit with a lower performance than conventional DIF.

Optical coherence tomography for patch test grading: A prospective study on its use for noninvasive diagnosis of allergic contact dermatitis.

BACKGROUND: The diagnosis of allergic contact dermatitis should be confirmed by skin patch tests. Distinguishing between irritant and allergic reactions is sometimes difficult. OBJECTIVES: To analyse the in vivo morphological changes in patch test reactions compared to healthy skin, and to detect subclinical changes in doubtful reactions using optical coherence tomography (OCT). To develop an OCT-based algorithm to support patch-test grading. METHODS: One hundred twenty-nine skin patch-test areas were scanned with OCT to evaluate the following features: architectural and vascular morphology, epidermal thickness, optical attenuation coefficient (AC), and blood flow at 0.1, 0.2, and 0.35 mm depth. RESULTS: Most common OCT features of acute contact allergic reactions in patch tests were spongiosis with microvesicles (94.8%), macrovesicles (60.3%), and coalescing vesicles (46.6%), the latter useful in differentiating acute allergic from irritant dermatitis (P-value < .05). Objective quantitative parameters correlated well with the severity grade: epidermal thickness due to spongiosis, AC (P-value < .05) and blood flow at 0.2 and 0.35 mm (P-value < .01). CONCLUSIONS: OCT as a noninvasive diagnostic tool, established for skin cancer diagnosis, is useful for evaluating contact allergic patch-test reactions. Not only morphological but also objective features such as blood flow and AC correlate with the reaction severity. Further studies are needed to explore the differences in irritant and allergic contact dermatitis.

[Artificial intelligence in ex vivo confocal laser scanning microscopy]. / Künstliche Intelligenz in der ex­vivo konfokalen Laserscanmikroskopie.

BACKGROUND: Visual data, such as clinical photographs or pictures from imaging examination methods, such as ex vivo confocal laser scanning microscopy (CLSM), are particularly suitable for machine learning techniques. OBJECTIVES: The aim was to find out whether data have already been published on this innovative application in ex vivo CLSM and what potential challenges and limitations could arise. MATERIAL AND METHODS: Review of the literature and summary of current knowledge and personal experience on the use of artificial intelligence (AI) in ex vivo CLSM. RESULTS: Successful integration of digital hematoxylin-eosin-like staining has made ex vivo CLSM significantly more accessible for digital assessments. Several machine learning techniques have been developed to date in such a way that they have been able to identify malignant skin lesions on clinical photographs and pathological microscopic images with similar accuracy compared to experts, or even find visual patterns that have been overlooked by experts and that correlate with certain dermatological diseases. One study on the use of AI in ex vivo CLSM for automated tumor detection has been published to date. Several challenges and limitations can arise when using AI in ex vivo CLSM. CONCLUSIONS: The already digitized ex vivo CLSM, which was established for rapid section examination purposes, is a predestined method for the development and use of new applications with machine learning in the healthcare sector. The results of further studies on this topic are anticipated with great hope.