Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Analysis of the Russian Database of Spontaneous Reports.

(1) Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design-a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%-TEN. In total, 30% were pediatric SRs, 21.2%-SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Anatomy of the Lateral Antebrachial Cutaneous Nerve: Landmarks for Procedures in the Cubital Fossa.

PURPOSE: The research outlines anatomical landmarks that may help surgeons in identifying the lateral antebrachial cutaneous nerve (LABCN) to minimize nerve damage during procedures in the cubital fossa. METHODS: Twenty-eight fresh cadaveric upper extremities were dissected. The course of the LABCN was followed from the emerging point at the biceps brachii tendon (BT) to the mid-forearm. The nerve's relationships with the BT, lateral epicondyle (LE), antebrachial vein, and brachioradialis (BR) muscle were measured and documented. RESULTS: The LABCN emerged lateral to the BT in all specimens and crossed medially at the top of the BT in 50% of the cadavers. It was deep to the forearm superficial fascia in all cadavers. At the level of the LE, the nerve was located at a mean of 6.3 ± 3.1 mm medial to the BR. The LABCN aligns with the medial border of the BR at a mean of 68 mm distal to the interepicondylar line. The mean distance from the LE to the LABCN at the interepicondylar line was 24.5 ± 7.2 mm. The LABCN and antebrachial vein are in the same deep fascia plane, on average 47.6 ± 5 mm (37-55) from the LE. At the elbow joint level, 82.1% of the specimens have two branches for the LABCN, whereas 17.9% demonstrated only a single branch. CONCLUSIONS: Lateral antebrachial cutaneous nerve was situated approximately 6.8 cm distal to the interepicondyle line, positioned at the ulnar edge of the BR, and runs parallel with the antebrachial vein deep to the forearm fascia plane. The nerve crossed over the biceps tendon in 50% of the specimens. These findings suggest that the nerve should be identified 6-7 cm distal to the LE, followed by a proximal dissection. CLINICAL RELEVANCE: This study may help surgeons in identifying LABCN, and reducing the potential risk of LABCN injury.

Grading differentiation in cutaneous squamous cell carcinoma: a review of the literature.

Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as "very high risk". Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists' system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.

First report of Leishmania tropica in domestic and wild animal hosts in hyperendemic areas of human cutaneous leishmaniasis in western Yemen: a neglected tropical disease needing One Health approach.

Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent. This study aims to investigate the occurrence and distribution of Leishmania parasites in domestic and wild animals in CL endemic areas in the western highlands of Yemen. A cross-sectional study was conducted in the Utmah District of western Yemen. Blood and skin scraping specimens were collected from 122 domestic and wild animals and tested for the Leishmania DNA using internal transcribed spacer 1 (ITS1) nested polymerase chain reaction. Phylogenetic analyses were performed on 20 L. tropica sequences obtained from animals in this study and 34 sequences from human isolates (collected concurrently from the same study area) retrieved from the GenBank. Overall, L. tropica was detected in 16.4% (20/122) of the examined animals, including 11 goats, two dogs, two bulls, one cow, one donkey, one rabbit, one rat and one bat. None of the examined cats and sheep was positive. The animal sequences were segregated into four different L. tropica haplotypes, with the majority of the animal (15/20) and human (32/34) sequences composed of one dominant haplotype/genotype. These findings represent the first confirmed evidence of natural L. tropica infections in different kinds of domestic and wild animals in western Yemen, suggesting these animals potentially have a role in the transmission of CL in Yemen. Therefore, a One Health approach is required for the effective prevention and control of this devastating disease among endemic populations.

Cutaneous Metastasis Following a Six-Year History of Bladder Urothelial Carcinoma in Situ: A Case Report.

Bladder cancer with cutaneous metastasis is a rare manifestation of the advanced stage of the disease. It can result from direct invasion, lymphatic or hematogenous spread, or iatrogenic implantation. We present a case of a 67-year-old patient initially diagnosed with urothelial carcinoma (UC) in situ of the bladder, who underwent transurethral resection of bladder tumor, along with induction and maintenance Bacillus Calmette-Guerin immunotherapy. Six years post-diagnosis, the patient developed multiple ulcerating fungating lesions in the right lower extremity, confirmed as metastases from UC. The patient additionally developed right foot gangrene with subsequent infection, which progressed into sepsis and caused the patient's demise.

The key to success in blocking lateral cutaneous branches with re-modified thoracoabdominal nerves block through perichondrial approach: a newly discovered space between the endothoracic fascia, diaphragm, and costodiaphragmatic recess.

PURPOSE: This study aimed to determine whether the administration of a modified thoracoabdominal nerves block through perichondrial approach (M-TAPA) could result in the blockade of the lateral cutaneous branches. This study focused on a newly discovered anatomical space/plane adjacent to the M-TAPA plane, which we termed "space between the endothoracic fascia, diaphragm, and costodiaphragmatic recess: SEDIC." METHODS: Thirteen sides of nine formalin-embalmed cadavers were macroscopically dissected to investigate the anatomical spaces related to the effects of M-TAPA. Furthermore, ten adult volunteers were administered 20 mL of 0.2% ropivacaine into the abdominal plane (corresponding to the M-TAPA plane) and the SEDIC, and a pinprick test was performed 1 h after the injection. RESULTS: Cadaver macrodissection revealed the presence of the SEDIC adjacent to the M-TAPA plane. The SEDIC was completely spatially isolated from the M-TAPA plane by the presence of costal cartilage and/or tendinous structures. In the volunteer study, the administration of local anesthetics into the SEDIC effectively blocked the lateral cutaneous branches of T8-T12, in addition to the anterior branches. CONCLUSION: Our study revealed the presence of the SEDIC adjacent to the M-TAPA plane. Administration of local anesthetics into the SEDIC, named re-modified TAPA, may have the potential to enhance the analgesic effect in the abdominal region.

Dyskeratosis congenita associated with a novel missense variant in TERT: Approach for the dermatologists.

Dyskeratosis congenita (DC) is a telomeropathy presenting diagnostic and therapeutic challenges across multiple specialties; yet, subtle dermatological signs enable early detection, altering patient prognosis. A specific DC genetic sequencing was performed according to the clinical criteria of our patient in study. Subsequently, cross-checked information in the main genetic databases was carried out. Additionally, an extensive review of the literature was made to organize the main dermatological aspects in DC. We report a novel variant of DC. Additionally, we share 10 useful and practical messages for dermatologists and any specialist caring for this group of patients.

Acceptability of compounded preparations - A Romanian pediatric hospital perspective.

Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children's acceptability of compounded preparations and to provide information regarding compounding practices' characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children's first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as "easy/very easy" to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.

Targeting the Hippo Pathway in Cutaneous Melanoma.

Melanoma is the most aggressive form of skin cancer. In the advanced stage of development, it is resistant to currently available therapeutic modalities. Increased invasiveness and metastatic potential depend on several proteins involved in various signal transduction pathways. Hippo signaling plays a vital role in malignant transformation. Dysfunctions of the Hippo pathway initiate the expression of tumor growth factors and are associated with tumor growth and metastasis formation. This review summarizes the recent achievements in studying the role of the Hippo pathway in melanoma pathogenesis and points to the potential specific targets for anti-melanoma therapy.

Identification of novel disulfidptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of skin cutaneous melanoma patients.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive form of malignant melanoma with poor prognosis and high mortality rates. Disulfidptosis is a newly discovered cell death regulatory mechanism caused by the abnormal accumulation of disulfides. This unique pathway is guiding significant new research to understand cancer progression for targeted treatment. However, the correlation between disulfidptosis with long non-coding RNAs (lncRNAs) in SKCM remains unknown at present. METHODS: The Cancer Genome Atlas database furnished lncRNA expression data and clinical information for SKCM patients. Pearson correlation and Cox regression analyses identified disulfidptosis-related lncRNAs associated with SKCM prognosis. ROC curves and a nomogram validated the model. TME, immune infiltration, GSEA analysis, immune checkpoint gene expression profiling, and drug sensitivity were assessed in high and low-risk groups. Consistent clustering categorized SKCM patients for personalized clinical treatment guidance. RESULTS: A total of twelve disulfidptosis-related lncRNAs were identified for the development of prognosis prediction models. The area under the curve (AUC) values of the ROC curve and the nomogram provided reliable discrimination to evaluate the prognostic potential for SKCM patients. The TME played a crucial role in tumorigenesis, progression and prognosis, and the risk scores were closely related to immune cell infiltration. Meanwhile, the combination of chemotherapy, targeted therapy, and immunotherapy was recommended for low-risk patients based on drug sensitivity and immune efficacy analyses. CONCLUSION: We identified a risk model of twelve disulfidptosis-related lncRNAs that could be used to predict the prognosis of SKCM patients and help guide immunotherapy and chemotherapy for personalized treatment plans.

Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is an aggressive form of skin cancer with limited treatment options for advanced stages. Prognostic markers that accurately predict patients' outcomes and guide therapeutic strategies are crucial for improving melanoma management. SETD2 (SET Domain-Containing Protein 2), a histone methyltransferase involved in chromatin remodeling and gene regulation, has recently emerged as a tumor suppressor. Its dysfunction is involved in oncogenesis in some cancers, but little is known about its functions in progression and therapeutic response of melanoma. METHODS: RNA-seq and clinical data from public database were used to evaluate the survival analysis, gene set enrichment, IC50 of therapeutics and immunotherapy response. SETD2 knock-out A375 cell line (A375SETD2ko) was developed by Crispr/cas9 and CCK-8 analysis and nude mice used to evaluate the proliferation and invasion of melanoma cells in vitro and in vivo, while Western blotting tested the MMR-related protein. RESULTS: SETD2 was commonly down-regulated in melanoma samples which demonstrated an unfavorable survival. Cells without SETD2 expression tend to have a more progressive and invasive behavior, with resistance to chemotherapy. However, they are more sensitive to tyrosine kinase inhibitors (TKIs). They also exhibit inflamed features with lower TIDE (Tumor Immune Dysfunction and Exclusion) score and higher tumor mutation burden (TMB), showing that these patients may benefit from immunotherapy. CONCLUSIONS: This study revealed that SETD2 dysfunction in melanoma implied a poor prognosis and chemotherapy resistance, but highly sensitive to TKIs and immunotherapy, highlighting the prognostic and therapeutic value of SETD2 in cutaneous melanoma.

Diagnostic accuracy of high-frequency ultrasound for cutaneous neoplasms: a narrative review of the literature.

High-frequency ultrasound has been used to visualize depth and vascularization of cutaneous neoplasms, but little has been synthesized as a review for a robust level of evidence about the diagnostic accuracy of high-frequency ultrasound in dermatology. A narrative review of the PubMed database was performed to establish the correlation between ultrasound findings and histopathologic/dermoscopic findings for cutaneous neoplasms. Articles were divided into the following four categories: melanocytic, keratinocytic/epidermal, appendageal, and soft tissue/neural neoplasms. Review of the literature revealed that ultrasound findings and histopathology findings were strongly correlated regarding the depth of a cutaneous neoplasm. Morphological characteristics were correlated primarily in soft tissue/neural neoplasms. Overall, there is a paucity of literature on the correlation between high-frequency ultrasound and histopathology of cutaneous neoplasms. Further studies are needed to investigate this correlation in various dermatologic conditions.

Mogamulizumab-associated rash - Case series and review of the literature.

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas.

The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies.

CONTEXT: Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities. OBJECTIVE: To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors. EVIDENCE ACQUISITION: A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs). EVIDENCE SYNTHESIS: Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender. CONCLUSIONS: Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.

Infectious Endocarditis Accompanied by Leukocytoclastic Vasculitis.

Bacterial endocarditis is a rare infection that can present with variable clinical manifestations. Rarely, it can present as cutaneous vasculitis characterized by a purpuric rash mimicking immune-mediated vasculitis. There have been a few case reports of leukocytoclastic vasculitis (LCV) due to infectious endocarditis. It is important to recognize endocarditis as a potential cause of vasculitis because treatment with immunosuppressive agents can have devastating consequences. We report a case of a 53-year-old male with endocarditis who developed a palpable purpura of the bilateral lower extremities. A skin biopsy was performed, and histopathologic and immunofluorescence studies demonstrated LCV.