Skin Lesions Research Articles

The Emergence of Cat-Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Piauí, Brazil.

In Brazil, the emergence of feline sporotrichosis, a neglected subcutaneous mycosis primarily transmitted by cats and caused by the fungus Sporothrix brasiliensis, has been monitored via molecular tools. This approach underscores the geographic expansion of this disease and highlights the critical role of molecular surveillance in understanding its epidemiology and guiding public health interventions. We investigated three domestic cats (Felis catus) with multiple skin lesions in Picos, Piauí, Brazil. The cats were examined, and samples were collected for laboratory diagnosis, including cytological evaluation, fungal culture, and molecular characterisation. The molecular analysis involved a one-tube multiplex probe-based qPCR assay for the diagnosis of Sporothrix species, mating-type determination, and amplified fragment length polymorphism (AFLP, EcoRI-GA/MseI-AG) to assess genetic similarity and potential origin. All three cats were diagnosed with sporotrichosis caused by the hypervirulent S. brasiliensis. A probable case of zoonotic transmission has been reported in a 12-year-old girl who developed Parinaud oculoglandular syndrome after contact with one of the cats with sporotrichosis. The molecular analysis revealed that the cat isolates were MAT 1-2 and formed a single cluster according to the AFLP analysis, suggesting direct transmission (cat-cat) and a potential founder effect. The isolates were also closely related to strains from Pernambuco and Southeast Brazil, indicating a possible introduction from these regions. Identifying S. brasiliensis in Piauí emphasises the need for increased awareness and control measures to prevent further spread. The predominance of the MAT1-2 idiomorphs and the genetic similarity among outbreak isolates suggest clonal expansion, which could have significant implications for public health and veterinary practices. Considering its zoonotic potential and environmental adaptability, a One Health approach is crucial for managing and controlling the spread of cat-transmitted sporotrichosis.

Apremilast in Chronic Graft-Versus-Host Disease: A Paediatric Case Report.

This case report describes the successful use of apremilast in a 10-year-old with chronic graft-versus-host disease and resistant psoriasiform skin lesions. Apremilast led to significant improvement, suggesting its potential as a new treatment option.

A case of Good's syndrome complicated by graft-versus-host disease-like skin lesion

A case of Good's syndrome complicated by graft-versus-host disease-like skin lesion

Haematogenous seeding in mycosis fungoides and Sézary syndrome: Current evidence and clinical implications.

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterised by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. Sézary syndrome (SS) is a unique leukaemia/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis. The pathogenesis of MF/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T-cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T-cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF/SS pathogenesis. Here, we review evidence supporting an alternative model of pathogenesis for MF/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T-cells which colonise the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T-cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression - 'consecutive haematogenous seeding' captures this temporal phenomenon. This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis. This understanding of MF/SS could have several clinical implications, including standardising our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.

Clinico-histopathological characteristics and management outcome of rare chronic infective granulomatous diseases: A case series study

Granulomatous skin diseases are common cutaneous dermatoses commonly encountered by practicing dermatologist. Granulomatous skin lesions are distinctive pattern of chronic inflammatory response of skin due to reaction against various organic and inorganic antigens. Granulomas are characterized by focal collection of epithelioid cells or histiocytes, admixed with variable number of leucocytes (especially mononuclear cells) and multinucleated giant cells. Granulomatous reaction is a type IV hypersensitivity reaction evoked by poorly soluble reactive substances. Incidence and prevalence of different types of granulomatous dermatitis depend on geographic location. Granulomatous skin lesions are common in the eastern parts of India. Many granulomatous skin lesions have identical histomorphology and conversely a single pathology can produce varied histological features. Some rare suppurative chronic granulomatous skin diseases include Botryomycosis, Actinomycosis, Rhinosporoidosis, Nocardiosis, and Cutaneous Tuberculosis. To describe clinical, histopathological features and treatment outcome of rare chronic infective granulomatous diseases. In this observational case series study, we retrospectively analysed six biopsy proven cases of rare chronic infective granulomatous diseases presented to our department (OPD) of Dermatology, Venereology and Leprosy (DVL) over a period of six months between June 2023 to November 2023 at Great Eastern Medical School and Hospital (GEMS), Srikakulam, Andhra Pradesh, India. The patient’s full clinical history, morphology of lesions, histopathological findings and treatment outcome were analysed. Along with histopathology, other necessary laboratory investigations were performed if required. A total of six patients were involved in the study, of whom four were males and two were females. The male to female ratio was 2:1, with a slight male majority. The most common age group was 31-40 years for both males and females. Painful raised lesion for long duration was the predominant complaint among those patients. Out of these six rare chronic granulomatous diseases, bacterial infections were common than fungal infection. All the cases showed clinical improvement after one month of starting treatment.: Most of the patients had a chronic history with improper treatment. So, it is imperative that the clinical diagnosis has to be confirmed with histopathology for the definitive diagnosis and appropriate treatment of these rare chronic infective granulomatous diseases. All these rare cases showed excellent progress after starting the right treatment.

Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, Effective via Oral Administration, for the Prevention of Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced osteoporosis (GIOP) is the leading cause of iatrogenic osteoporosis due to the widespread clinical use of glucocorticoids (GC) as immunosuppressants. Previous research identified the proline-rich tyrosine kinase 2, Pyk2, as a critical mediator of GC-induced bone loss, and that blocking Pyk2 could protect the skeleton from adverse GC actions. However, systemic administration of current Pyk2 inhibitors causes harmful side effects, such as skin lesions. To address this, we developed bone-targeted (BT) Pyk2 inhibitors by conjugating them with bisphosphonates (BP), ensuring adherence to the bone matrix and reducing impact on noncalcified tissues. We synthesized BT-Amide by linking a derivative of TAE-226, a Pyk2 inhibitor, with alendronic acid. Oral administration (gavage) of BT-Amide prevented GC-induced bone loss in mice without causing skin lesions, or elevation of any organ toxicity markers. These findings introduce BT-Amide as the first orally effective bone-targeted Pyk2 inhibitor for preventing GC-induced bone loss while minimizing off-target effects.

Apocrine gland damage and the release of specific keratins in early stage indicate the crucial involvement of apocrine glands in hidradenitis suppurativa.

The apocrine glands (AGs) are not considered to be primarily involved in hidradenitis suppurativa (HS). This study investigated the potential role of AGs in HS pathogenesis using immunohistochemistry and single-cell sequencing of nonlesional skin (NLS) and early lesional skin (LS) from patients with HS (n = 12) and healthy controls (HC, n = 8). AG cell destruction was more frequent and AG size was significantly reduced in the NLS and LS. Barrier-related genes (e.g., claudin 1 and E-cadherin) were downregulated in the AGs of the NLS and LS. Damaged AGs in the LS primarily recruit and activate neutrophils via the CXCL-CXCR and SAA1-FPR2 pathways. Elevated levels of specific keratins (KRT18 and KRT19) released from damaged AGs were observed on the skin surface of patients and were associated with disease severity. KRT19 was also detected in the dermis of the NLS and LS and was surrounded by neutrophils and macrophages. Moreover, serum KRT19 levels in patients (n = 20) were significantly negatively correlated with the age at HS onset. Collectively, our findings provide previously unreported evidence that the AGs are damaged and release specific keratins in early HS lesions, indicating a crucial role of the AGs in HS pathogenesis.

Prospective evaluation of hospital-acquired skin lesions in dogs: A case-control study.

Hospital-related dermatological conditions are well-studied and reported in human medicine. However, studies about these dermatological disorders in veterinary medicine are lacking. To report the incidence, type and distribution of hospital-acquired skin lesions (HASL) in dogs, and to investigate risk factors that may be associated with their development. Hospitalised client-owned dogs with HASL and a control group of hospitalised dogs without skin lesions. Prospective clinical evaluation of all HASL and dermatological tests, when indicated, were performed, over 6 months. A variety of potentially predisposing factors also were recorded. Thirty-one dogs with HASL and a matched control group of 60 hospitalised dogs without skin lesions were included. The incidence of HASL was 11.2% (31 of 278). The most common lesion was erythema in 74.2% of dogs (23 of 31) and the most affected area was the abdomen in 58.1% (18 of 31) of dogs. Faecal and/or urinary incontinence was identified as an important risk factor for the development of skin lesions during hospitalisation (odds ratio 14.445, 95% confidence interval 1.444-144.479, p = 0.023). Immobilisation and changes in body temperature also may play a role in the development of such lesions in dogs. Faecal and/or urinary incontinence was found to be an important factor in the development of HASL. The impact of HASL on patient outcomes and the prevention of these lesions requires further investigation.

Radiation Therapy for Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report and Review of the Literature

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from plasmacytoid dendritic cells. It commonly presents as cutaneous lesions. To date, no standard treatment protocol for BPDCN exists. Traditionally treated similarly to acute leukemia or lymphoma, its prognosis remains poor. Radiation therapy is employed for isolated skin lesions, for patients that are ineligible for chemotherapy due to age or comorbidities and for post-chemotherapy recurrence. However, very limited reports are available on radiotherapy for BPDCN. We present a case involving a 94-year-old BPDCN patient treated with radiation therapy, highlighting an atypical situation of two separate radiotherapy sessions with different dosages for isolated skin lesions. Initially, 45 Gy was administered in 15 fractions (45 Gy/15 Fr), followed by a second session of 30 Gy in 10 fractions (30 Gy/10 Fr) after disease recurrence. This case is unique in detailing radiation therapy for the exceedingly rare BPDCN, particularly dose fractionation. The findings indicate that 45 Gy/15 Fr can provide adequate local control, while even a lower dose of 30 Gy/10 Fr may be effective. This case report contributes to the limited literature by proposing potential therapeutic approaches and dosage guidelines to refine future BPDCN treatment protocols.

Enhanced Multi-Class Skin Lesion Classification of Dermoscopic Images Using an Ensemble of Deep Learning Models

This study presents an advanced approach to multi-class skin lesion classification by leveraging an ensemble model comprising the Inception-V3, ResNet-50, and VGG16 architectures. The classification task focuses on categorizing skin lesions into distinct classes, including Melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), using the ISIC dataset, a comprehensive collection of dermoscopic images. In order to properly balance the dataset, the oversampling strategy is utilized, as some lesion types are underrepresented due to inherent imbalances in the dataset. By ensuring that the model is trained on a more representative dataset, this balancing improves the algorithm's capacity to categorize all lesion types properly and impartially. By combining the complementary features of ResNet-50, Inception-V3, and VGG16, the ensemble technique improves the overall classification performance. ResNet-50 is chosen for its deep feature extraction capabilities, which help capture fine details in lesion patterns. Inception-V3 is selected for its multi-scale processing, allowing it to effectively analyze lesions at varying resolutions and sizes. VGG16 is included due to its simple yet highly effective architecture for image classification tasks. The ensemble model with data augmentation significantly outperforms individual models in skin lesion classification for both the original and balanced ISIC datasets regarding accuracy, precision, recall, and F1-score. This method offers a robust solution for skin lesion classification, contributing to more accurate and reliable diagnostic tools in dermatology.

Clinical Characteristics and Genomic Profile of Malignant Proliferating Trichilemmal Tumor: A Systematic Review of the Literature.

Malignant proliferating trichilemmal tumors (MPTT) are rare skin lesions arising from the outer sheath of the hair follicle root. Because of their rarity and difficulty in pathologic identification, these skin lesions are often initially misdiagnosed. After a literature review, we found initial clinical or histopathological misdiagnosis has an associated 10.4-fold increase in recurrence and 2.18-fold increase in deaths.

MANEJO DE FERIDAS EM COELHO ATRAVÉS DO USO DA PELE DE TILÁPIA LIOFILIZADA

The study addresses the importance of treating skin lesions in veterinary medicine, with an emphasis on wound healing in rabbits with pododermatitis, including the use of Nile tilapia skin as a therapeutic alternative for grafting after debridement of necrotic ulcers. Skin lesions can be caused by trauma, bites or other causes, compromising vital skin functions, such as protection and defense against infections. Tilapia skin is rich in type I collagen and has been highlighted as an accessible and effective biomaterial in the treatment of wounds, stimulating cell regeneration and healing. The work reports the case of a rabbit, named Paçoca, diagnosed with ulcerative pododermatitis in the left pelvic limb, a chronic condition that can lead to serious complications. The clinical signs of the pathology are pain, abdominal and limb alopecia, edema, ulcerative lesions, loss of joint mobility with the presence of osteolytic reactions. Pododermatitis in rabbits is often related to factors such as cage floor quality, excess weight, and sedentary lifestyle. The rabbit’s treatment included debridement of necrotic tissue and the application of tilapia skin as a graft. The tilapia skin was prepared through a rigorous sterilization and preservation process, involving immersion in specific solutions and the application of antibiotics. The use of this skin as an occlusive dressing helped stimulate growth factors essential for skin regeneration, such as fibroblasts and keratinocytes. The use of this biomaterial proved effective in the treatment of wounds with significant tissue loss, avoiding the need for sutures and promoting healing through the formation of new tissue. Postoperative follow-up included the use of antibiotics and anti-inflammatories, and treatment with tilapia skin contributed to the successful recovery. The study highlights the effectiveness of the biomaterial in the management of skin wounds in rabbits, especially in the recovery of lesions caused by ulcerative pododermatitis. Therefore, after treatment, the rabbit presented good healing, the wound evolved positively, with formation of granulation tissue and epithelialization.

Effect of Epstein-Barr virus on macrophage M2/M1 migration and EphA2 expression in adverse drug reactions.

This study aims to investigate the effect of Epstein-Barr virus (EBV) reactivation or EBV reactivation with dexamethasone (DXM) in patients with adverse drug reactions (ADRs) through evaluating the levels of monocyte, macrophage M2/M1, and cytokines, and investigating whether expression of EBV receptor EphA2 could specifically influence EBV activation in ADRs. We performed a prospective longitudinal study to analyze the monocytes, macrophages, M2/M1 ratio, and cytokines, including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IFN-β, C-X-C motif chemokine ligand (CXCL)9, and CXCL10, in patients with maculopapular exanthema (MPE) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and control groups after disease onset. Skin biopsy samples from these patients were subjected to hematoxylin and eosin (H&E) staining to examine tissue architecture and inflammatory cell infiltration, as well as Epstein-Barr virus-encoded RNA (EBER) staining to detect the presence of EBV within the skin lesions. Peripheral blood mononuclear cells collected from these patients were co-cultured with EBV or EBV combined with DXM to assess the impact on monocytes, macrophages, the M2/M1 ratio, and the associated cytokine profile. Furthermore, we sought to identify which cytokines might be crucial in mediating the interaction between the M2/M1 ratio and EBV. EPhA2 expression was evaluated to determine its role in the reactivation of EBV and its correlation with increased viral load in MPE and SJS/TEN patients. Selective depletion of macrophages occurred during the acute stage of SJS/TEN, while a shift towards M2 macrophages was observed in MPE. Both IFN-β and CXCL9 levels were elevated in MPE and SJS/TEN. Additionally, our study demonstrated the presence of EBV in the skin lesions of SJS/TEN and MPE patients through H&E and EBER staining, confirming EBV's involvement in these conditions. Activation of EBV and EBV combined with DXM led to a shift from M1 to M2 macrophages, accompanied by increased levels of IL-4, IFN-γ, and CXCL9 in MPE and SJS/TEN, compared to healthy individuals. Specifically, EBV combined with DXM primarily drove IFN-γ and IL-4 expansions in MPE, while CXCL9 was predominantly elevated in SJS/TEN. The increased IL-4 levels were associated with the relative rise in EBV viral loads after EBV combined with DXM stimulation. Furthermore, EphA2 expression in monocytes was significantly higher in SJS/TEN and MPE patients compared to controls, with further increases on EBV stimulation. This elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients. The gradual shift from M1 to M2 cell development observed during the clinical course of MPE and SJS/TEN is mediated by the predominance of EBV and EBV with DXM at the acute stage, leading to elevated IL-4, IFN-γ, and CXCL9 levels, which may exacerbate allergic reactions. The elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients, suggesting that adverse drug reactions may induce EPhA2 expression, facilitating EBV replication and activation. EphA2 could thus serve as an indicator of EBV activation and a marker for assessing the risk of EBV in patients with adverse drug reactions.

Skin Cancer Diagnosis by Lesion, Physician, and Examination Type: A Systematic Review and Meta-Analysis.

Skin cancer is the most common cancer in the US; accurate detection can minimize morbidity and mortality. To assess the accuracy of skin cancer diagnosis by lesion type, physician specialty and experience, and physical examination method. PubMed, Embase, and Web of Science. Cross-sectional and case-control studies, randomized clinical trials, and nonrandomized controlled trials that used dermatologists or primary care physicians (PCPs) to examine keratinocytic and/or melanocytic skin lesions were included. Search terms, study objectives, and protocol methods were defined before study initiation. Data extraction was performed by a reviewer, with verification by a second reviewer. A mixed-effects model was used in the data analysis. Data analyses were performed from May 2022 to December 2023. Meta-analysis of diagnostic accuracy comprised sensitivity and specificity by physician type (primary care physician or dermatologist; experienced or inexperienced) and examination method (in-person clinical examination and/or clinical images vs dermoscopy and/or dermoscopic images). In all, 100 studies were included in the analysis. With experienced dermatologists using clinical examination and clinical images, the sensitivity and specificity for diagnosing keratinocytic carcinomas were 79.0% and 89.1%, respectively; using dermoscopy and dermoscopic images, sensitivity and specificity were 83.7% and 87.4%, and for PCPs, 81.4% and 80.1%. Experienced dermatologists had 2.5-fold higher odds of accurate diagnosis of keratinocytic carcinomas using in-person dermoscopy and dermoscopic images compared with in-person clinical examination and images. When examining for melanoma using clinical examination and images, sensitivity and specificity were 76.9% and 89.1% for experienced dermatologists, 78.3% and 66.2% for inexperienced dermatologists, and 37.5% and 84.6% for PCPs, respectively; whereas when using dermoscopy and dermoscopic images, sensitivity and specificity were 85.7% and 81.3%, 78.0% and 69.5%, and 49.5% and 91.3%, respectively. Experienced dermatologists had 5.7-fold higher odds of accurate diagnosis of melanoma using dermoscopy compared with clinical examination. Compared with PCPs, experienced dermatologists had 13.3-fold higher odds of accurate diagnosis of melanoma using dermoscopic images. The findings of this systematic review and meta-analysis indicate that there are significant differences in diagnostic accuracy for skin cancer when comparing physician specialty and experience, and examination methods. These summary metrics of clinician diagnostic accuracy could be useful benchmarks for clinical trials, practitioner training, and the performance of emerging technologies.

MalenoCare - Skin Cancer Detection and Prescription using CNN and ML

Machine learning (ML) and convolutional neural networks (CNNs) have driven significant advancements in healthcare, particularly in dermatology, by enabling the automation of diagnostic processes for skin cancer. Skin cancer, being one of the most common types of cancer, requires early detection and accurate classification to improve patient outcomes and reduce mortality rates. This review paper explores various studies and CNN-based tools that enhance skin cancer detection and support preventive care through image analysis. The paper also discusses the effectiveness of different CNN architectures, including VGG16, ResNet, and Inception, in achieving high accuracy rates in skin lesion classification. A combination of recent research findings, model evaluation metrics, and graphical data highlights the accuracy, interpretability, and real-world applications of ML models, offering insights into their potential for integration into clinical practice.

Double-Condensing Attention Condenser: Leveraging Attention in Deep Learning to Detect Skin Cancer from Skin Lesion Images

Skin cancer is the most common type of cancer in the United States and is estimated to affect one in five Americans. Recent advances have demonstrated strong performance on skin cancer detection, as exemplified by state of the art performance in the SIIM-ISIC Melanoma Classification Challenge; however, these solutions leverage ensembles of complex deep neural architectures requiring immense storage and computation costs, and therefore may not be tractable. A recent movement for TinyML applications is integrating Double-Condensing Attention Condensers (DC-AC) into a self-attention neural network backbone architecture to allow for faster and more efficient computation. This paper explores leveraging an efficient self-attention structure to detect skin cancer in skin lesion images and introduces a deep neural network design with DC-AC customized for skin cancer detection from skin lesion images. We demonstrate that our approach with only 1.6 million parameters and 0.32 GFLOPs achieves better performance compared to traditional architecture designs as it obtains an area under the ROC curve of 0.90 on the public ISIC 2020 test set and 0.89 on the private ISIC test set, over 0.13 above the best Cancer-Net SCa network architecture design. The final model is publicly available as a part of a global open-source initiative dedicated to accelerating advancement in machine learning to aid clinicians in the fight against cancer. Future work of this research includes iterating on the design of the selected network architecture and refining the approach to generalize to other forms of cancer.

Photodynamic inactivation strategies for maximizing antifungal effect against Sporothrix spp. and Candida albicans in an in vitro investigation.

Sporotrichosis is a zoonotic disease caused by the dimorphic fungus Sporothrix spp., leading to skin lesions that can, in some cases, progress and result in the death of infected individuals. Candida albicans is another fungus involved in several skin, oral, and vaginal mucosal infections. Fungal diseases are concerning due to increasing incidence and the limited variety of antifungal classes available for treatment. Furthermore, antifungal medications can cause various side effects, exacerbated by their prolonged use during infection treatment. There is a need to explore alternatives to conventional drugs that are effective, fast, and safe in combating sporotrichosis. This study aimed to achieve in vitro elimination of the fungi Sporothrix brasiliensis and Sporothrix schenckii through Photodynamic Inactivation (PDI), using curcumin as a photosensitizer and in combination with antifungal agents used in the treatment of sporotrichosis. Yeasts of Candida albicans, Sporothrix brasiliensis, and Sporothrix schenckii were subjected to Photodynamic Inactivation (PDI) using light at a wavelength of 450 ± 10 nm, irradiance of 35 mW/cm2, delivering a fluence of 31.5 J/cm2, with curcumin as the photosensitizer at doses ranging from 0.75 to 150 μg/mL. After determining the Minimum Inhibitory Concentration (MIC) values of the antifungal drugs itraconazole, ketoconazole, and potassium iodide, sub-MIC doses of these antifungals were combined with sub-MIC doses of curcumin in a new PDI session. Photodynamic inactivation is a promising technique in the treatment of sporotrichosis, as well as its combination with antifungals. The combination of curcumin in concentrations ranging from 0.75 g/mL a 7.5 g/mL with sub-MIC concentrations of itraconazole, ketoconazole, and potassium iodide was able to completely inactivate the fungi C. albicans, S. brasiliensis and S. schenckii, indicating that PDI may increase the effectiveness of antifungals. However, further studies are needed to establish protocols for future clinical applications.

Abstract 4124430: Calcinosis Cutis and Heart Failure---A Rare Manifestation Which Should Never Be Ignored!

Introduction: Heart failure can be a manifestation of underlying immune mediated myopathies like dermatomyositis/polymyositis which can present in broad range of clinical manifestations and sometimes dermatologic lesions can be the only manifestation of these underlying pathologies without typically involving the muscle weakness. Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue. There are five subtypes of calcinosis cutis, dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Case summary: 70-year-old female was evaluated for bilateral lower extremity swelling. Past medical history was significant for Graves’ disease, atrial fibrillation, mechanical aortic valve on warfarin, hypertension, hyperlipidemia, ascending aortic aneurysm. Work up showed BNP of 4700 pg/ml with normal cardiac enzymes. Transthoracic echocardiogram revealed newly reduced ejection fraction of 25—30% with severely dilated left ventricle. Patient refused cardiac catheterization. Nuclear stress test showed no evidence of ischemia. Patient was started on guideline directed medical therapy and biventricular Implantable cardioverter defibrillator device was placed as per cardiology recommendation. Six months later patient developed multiple calcinosis cutis lesions on abdominal wall requiring surgical excisions. Endocrine work up including PTH, serum Ca level was normal, however creatin kinase level was high normal (150 U/L). Serum aldolase was ordered which was found to be elevated(25U/L). Muscle biopsy was performed as per recommendations of rheumatology which was diagnostic of dermatomyositis. Patient was started on high dose steroids and methotrexate and eventually IV immunoglobulins as per rheumatology recommendation. Follow up echocardiogram revealed improved ejection fraction to 40--45% with resolution of any further lesion of calcinosis cutis afterwards. Conclusion: Cardiac involvement such as congestive heart failure can be a part of presentation of underlying untreated myopathies. Calcinosis cutis can be the only clinical manifestation of dermatomyositis affecting heart. Etiology of calcinosis cutis in patients with heart failure should be worked up properly. Dystrophic calcinosis cutis is the subtype associated with underlying autoimmune connective tissue diseases.

MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect.

The recent outbreak of monkeypox virus (MPXV) has caused global concern. How the virus evades the interferon (IFN) response is still poorly understood. We analyzed type I/II IFN (IFN-I/II) expression in clinical samples from MPXV-infected patients and measured IFN-I kinetics in MPXV-infected cells. We also evaluated the anti-MPXV activity of IFN-I/II in A549, HeLa and Vero-E6 cell lines. IFN-I/II mRNA expression was detected in skin lesions, anal swabs, nasopharyngeal samples and peripheral blood mononuclear cells (PBMC), with the highest levels in skin lesions (p < 0.05). High MPXV DNA levels in clinical samples were associated with increased IFN-I levels. In vitro, MPXV infection induced a peak of IFN-I between 48 and 72h post-infection (p < 0.01). Pre-treatment of the A549, HeLa and Vero-E6 cells with high concentrations (≥ 100,000 International Unit, IU/ml) of IFN-α and IFN-ω did not inhibit or had little effect on MPXV replication, while IFN-β moderately reduced MPXV replication by 2.7-1.5 log10 at 100,000 IU/ml. In clinical samples there was a trend for elevated levels of IFN-γ in association with lower MPXV load and in vitro IFN-γ (3,600 IU/ml) strongly reduced viral titers by 3.4-1.6 log10. There were no significant differences in expression of select IFN-stimulated genes (ISGs) in MPXV infection in vitro. This study shows that MPXV delays IFN-I induction and inhibits expression of selected ISGs in vitro and is associated with an IFN-I resistance phenotype in vivo. However, MPXV is less resistant to IFN-γ in vivo and is sensitive to IFN-γ treatment in vitro, suggesting a potential therapeutic role for IFN-γ.

ScSEETV‐Net: Spatial and Channel Squeeze‐Excitation and Edge Attention Guidance V‐Shaped Network for Skin Lesion Segmentation

Early detection of skin cancer ensures the survival of many cases. There are still challenges in segmenting dermoscopic skin lesion images. Artifacts in the lesion images, such as various dirt, hairs, low contrast, and unclear boundaries, are challenges that affect segmentation accuracy. Convolutional neural networks have brought success in skin lesion segmentation. U‐shaped and V‐shaped deep learning‐based segmentation architectures learn boundary information in the first layers. However, this information becomes weaker in the following layers. Herein, the Edge‐aTtention module is added to the V‐Net architecture to move edge information to the last layer, and the spatial and channel squeeze‐excitation module is added to emphasize high‐level features by recalibrating the channel information to learn lesion boundaries better. The scSEETV‐Net is supported by fusing the binary cross‐entropy, which calculates the loss on a pixel‐based, and the focal Twersky loss function, which has significant success in class imbalances. The proposed architecture achieves 0.9212 Jaccard and 0.9552 Dice in the ISIC2016 dataset, 0.8273 Jaccard and 0.8949 Dice in the ISIC2017 dataset, and 0.8070 Jaccard and 0.8831 Dice in the ISIC2018 dataset. Comparative analyses show that the proposed methodology outperforms the state‐of‐the‐art techniques in the literature.