The safety of systemic Janus kinase inhibitors in atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Janus kinase (JAK) inhibitors have been recently approved by the FDA and are widely used in the treatment of patients with atopic dermatitis. However, a comprehensive safety profile of JAK inhibitors in patients with atopic dermatitis has not been analysed. This study aimed to establish clinical evidence for the safety of systemic JAK inhibitors in patients with atopic dermatitis. Medline, Embase, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and International Clinical Trials Registry Platform (ICTRP) were considered for search databases. Randomized controlled trials reporting the adverse events of systemic therapy in patients with atopic dermatitis were included. The risk of 11 adverse events was compared between the JAK inhibitors and placebo groups. Fourteen randomized controlled trials were analysed published between 2019 and 2022. The JAK inhibitors included in the analysis were abrocitinib (10, 30, 100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (7.5, 15 and 30 mg). The risk of herpes zoster, headache, acne, elevated blood creatinine phosphokinase and nausea was significantly increased, but the risk of serious infection, non-melanoma skin cancer (NMSC), malignancies other than NMSC, major adverse cardiovascular event, venous thromboembolism and nasopharyngitis was not increased. This study provides comprehensive clinical evidence on the risk of various adverse events in patients with atopic dermatitis. However, since the follow-up periods of the studies analysed in this review were mostly limited to 16 weeks or less, it is recommended that comprehensive long-term observational studies be conducted to determine any potential adverse events associated with major cardiovascular events or malignancies, which typically have prolonged courses.

A Case of Cavernous Sinus Syndrome Due to Extranodal Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma accounting for approximately one-third of all cases. DLBCL can present as a lymph node or extranodal tumor. Cavernous sinus (CS) is a small but complex structure in which various arteries, sympathetic plexuses, and cranial nerves are passing through. Cavernous sinus syndrome (CSS) results from any disease process that affects CS including tumor, vascular disease, infection, or inflammation. Herein, we report a case of extranodal DLBCL diagnosed by skin biopsy presenting as CSS. A 58-year-old male presented with a 3-week-old, gradually growing subcutaneous nodule on the left upper lip. He also suffered from ptosis, ophthalmoplegia, diplopia, and headache confined to the right side for 3 months. Histopathologic examination of the left upper lip showed dense dermal infiltration of atypical large tumor cells resembling centroblasts and immunoblasts. Immunohistochemistry studies revealed that the tumor cells were positive for CD20, BCL2, BCL6, MUM1, and MYC. After additional radiologic evaluation with positron emission tomography-computed tomography (PET-CT), brain magnetic resonance imaging, and orbital CT, he was finally diagnosed with extranodal DLBCL involving the right CS, oculomotor muscles, and left upper lip.

High-fluence 1064nm Q-switched Nd:YAG laser treatment for ectopic Mongolian spot.

Q-switched neodymium-yttrium aluminum-garnet (Q-switched Nd:YAG) laser has been reported as an effective treatment for nevus of Ota and acquired bilateral nevus of Ota-like macules (ABNOM). Data on ectopic Mongolian spots have rarely been reported.The present study was performed to investigate the treatment efficacy of a high-fluence 1064 nm Q-switched Nd:YAG laser without tissue whitening in ectopic Mongolian spots.We included 61 patients with ectopic Mongolian spots, and 70 lesions were examined. Thirty-three lesions were treated with a high-fluence 1064 nm Q-switched Nd:YAG laser, and 38 lesions were observed without treatment. The results were assessed using a 5-quantile grading scale and melanin index using a Mexameter®.Mean follow-up duration was 14.1 ± 6.8 months for the treatment group and 17.8 ± 10.0 months for the observation group. Mean 5-quintile grading scale at final follow-up was statistically different (p < 0.001) between the two groups (treatment: 2.85 ± 1.00, observation: 0.49 ± 0.73). There was a significant difference (p < 0.001) in the Δ melanin index (initial melanin index - final melanin index) between the observation (7.1 ± 62.7) and treatment (156.7 ± 78.4) groups.High-fluence Q-switched Nd:YAG laser without tissue whitening showed good results and was well-tolerated in treating ectopic Mongolian spots.

Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression.

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

Giant Cellulitis-like Sweet Syndrome Following Varicose Vein Surgery: A Rare Variant of Sweet Syndrome Mimicking Cellulitis.

Giant cellulitis-like Sweet syndrome (GCS) is the most recently defined variant of Sweet syndrome (SS) which could clinically mimic wide-spreading cellulitis. Although there has been only paucity of reports in the literature, it mostly appears at lower half of the body and histologically shows dense infiltration of neutrophils with occasional histiocytoid mononuclear cells. Although its exact etiology has not been clarified, abnormal conditions (e.g., infection, malignancy and drugs) could be related triggering factors and trauma itself can be one of the causative elements as a 'pathergy phenomenon'. GCS could be confusing manifestation especially when appeared in postoperative condition. A 69-year-old female presented with an erythematous edematous papules and plaques on the right thigh after varicose vein surgery. Skin biopsy revealed diffuse neutrophilic infiltrates that was consistent with SS. To our knowledge, there has been no report of GCS as a postoperative complication after varicose vein surgery. Physicians should be aware of this uncommon reactive neutrophilic dermatoses mimicking infectious cutaneous disease.

Dermoscopic Features of Subcorneal Hematoma on the Palms and Soles: Differences from Acral Melanoma.

BACKGROUND: The diagnosis of subcorneal hematoma (SH) can be challenging because the clinical presentation of SH can resemble melanocytic lesions. Few studies have examined the characteristic dermoscopic features of SH, but a more detailed large-scale study is needed to overcome the diagnostic challenge of differentiating it from acral melanoma. OBJECTIVES: To describe the dermoscopic features of SH. METHODS: We evaluated the clinical and dermoscopic features of 50 SH lesions from 43 patients at the Pusan National University Hospitals (Busan and Yangsan). RESULTS: In the color analysis, 86% of cases showed the bruise color sign; 7 cases had a single color (red to purple: 2; black: 1; brown: 4). Typical dermoscopic features of SH, acral nevi, and acral melanoma-associated patterns were observed in 60%, 0%, and 72% of lesions, respectively. Hematoma-associated patterns were homogenously red-to-black with or without satellite globules (32%) and pebbles on the ridges (28%). Acral melanoma-associated patterns showed a parallel ridge pattern (PRP) (52%), irregular dots and globules (50%), polychromia (34%), asymmetry (24%), irregular blotches (10%), and ulcers (10%). No case showed blue-white veils, regression structures, atypical vascular patterns, or irregular fibrillar patterns. The bruise color sign was positive in most cases, with acral melanoma-associated patterns (88.9%).

Chronic Alcohol Exposure Promotes Cancer Stemness and Glycolysis in Oral/Oropharyngeal Squamous Cell Carcinoma Cell Lines by Activating NFAT Signaling.

Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.

Scar Sarcoidosis: A Retrospective Investigation into Its Peculiar Clinicopathologic Presentation.

BACKGROUND: Scar sarcoidosis (SS), a rare form of cutaneous sarcoidosis, develops from pre-existing scars. Owing to its rarity, the clinicopathologic features and its significance in clinical prognosis have been obscure. OBJECTIVE: This study aimed to investigate clinical, laboratory and histopathologic findings and to clarify characteristics associated with the development of SS and systemic involvement. METHODS: We retrospectively assessed clinical, laboratory and histopathologic findings of SS. Clinical factors including demographics, anatomic area, number of lesion (single, multiple), presence of symptoms, latent period, injury types related to scar and the proportion of systemic involvement were investigated. RESULTS: Of the 21 patients with SS, skin lesions appeared predominantly in females (85.7%) and in the head and neck (57.1%). The mean latent period was 163.5 months and 13 patients (61.9%) had multiple lesions. Injury types were varied, with no specific type identified as associated with SS. Histologically, discrete sarcoidal granulomas surrounded by densely packed collagen bundles with a thickening of numerous fibers were observed. Ten patients (47.6%) had systemic involvement and showed significantly more of the multiple lesions, longer latent period and higher level of mean serum angiotensin-converting enzyme than those without systemic involvement. CONCLUSION: Various causes of scar were related to SS, but no specific injury type was identified as leading to SS. Although the exact pathomechanism remains unclear, the possibility of systemic involvement could be considered when the patients have multiple lesions, longstanding scars, and elevated serum angiotensin-converting enzyme.

Dermoscopy for cutaneous fungal infections: A brief review.

BACKGROUND: Fungal dermatological diseases are significant public health issues. Dermoscopy is a useful bedside assessment tool that helps clinicians diagnose various skin neoplasms and general dermatological diseases. AIM: This brief review aims to update clinicians on the dermoscopic features of cutaneous fungal infections such as tinea capitis, tinea corporis, tinea incognito, onychomycosis, and pityrosporum folliculitis. METHODS: The PubMed database was searched using the terms "dermoscopy" or its synonyms, "tinea capitis", "tinea corporis", "tinea incognito", "onychomycosis" and "pityrosporum folliculitis". RESULTS: The diagnostic value of dermoscopy is well-recognised in the evaluation of tinea capitis and onychomycosis. There are fewer studies investigating the dermoscopic features of tinea corporis, tinea incognito and pityrosporum folliculitis, but the current data suggest that dermoscopy can aid clinical evaluation of these diseases. Understanding dermoscopic features of cutaneous fungal infection has the potential to increase diagnostic accuracy. CONCLUSION: Dermoscopy in the evaluation of fungal dermatological diseases has the potential to optimize diagnostic accuracy, reduce unnecessary testing, and, consequently, improve clinical practice.

Dermoscopy-guided Mohs micrographic surgery in post-laser basal cell carcinomas: is dermoscopy helpful for demarcation of the surgical margin?

BACKGROUND: Mohs micrographic surgery (MMS) in cases where the tumor margin is poorly defined to the naked eye can lead to the need to take an increased number of Mohs stages. OBJECTIVE: To evaluate the usefulness of dermoscopy in determining MMS surgical margins of BCCs with a history of ablative laser treatment. METHODS: Patients were randomly allocated to naked eye (n = 69) or dermoscopy (n = 64) groups by the surgical margin detection method. Surgical outcomes of 133 post-laser BCC patients treated with MMS were analyzed. RESULTS: The lateral margin involvement rate at the first MMS stage was significantly lower in the dermoscopy group than in the naked eye group (4.7% vs. 29.0%; p < .001). However, the deep margin involvement rate at the first and mean MMS stages were not significantly different between the groups. The ablative laser treatment duration correlated to the number of MMS stages (p = .026). CONCLUSION: The results demonstrated that lateral margin was mostly controlled within the first MMS stage with dermoscopy. Dermatosurgeons could focus on the deep margin after the first MMS stage; thus, the performance of MMS could be improved with dermoscopic assistance in post-laser BCC patients.

Crosstalk between fibroblasts and T cells in immune networks.

Fibroblasts are primarily considered as cells that support organ structures and are currently receiving attention for their roles in regulating immune responses in health and disease. Fibroblasts are assigned distinct phenotypes and functions in different organs owing to their diverse origins and functions. Their roles in the immune system are multifaceted, ranging from supporting homeostasis to inducing or suppressing inflammatory responses of immune cells. As a major component of immune cells, T cells are responsible for adaptive immune responses and are involved in the exacerbation or alleviation of various inflammatory diseases. In this review, we discuss the mechanisms by which fibroblasts regulate immune responses by interacting with T cells in host health and diseases, as well as their potential as advanced therapeutic targets.

Infantile Hemangiomas with Minimal and Arrested Growth: Clinical Features and Treatment Outcomes with 0.5% Topical Timolol Maleate.

BACKGROUND: A minority of infantile hemangiomas showing minimal or arrested growth (IH-MAGs) have been recognized in the literature. Nevertheless, the clinical features and treatment outcomes of IH-MAGs have not been well investigated. OBJECTIVE: This study aimed to understand the clinical characteristics of IH-MAGs better and their response to treatment with topical timolol maleate. METHODS: We retrospectively reviewed medical records and clinical images of patients with IH-MAGs. Treatment response with topical timolol was assessed in both IH-MAGs and classic infantile hemangiomas (IHs) groups. RESULTS: Of the 1,038 patients with IHs, only 31 (3.0%) were diagnosed with IH-MAGs. Lesions with non-proliferative components were more frequently distributed in the lower half of the body (61.5%) than those with proliferative components (16.7%). In 14 patients treated with topical timolol, the global assessment scale showed more significant and rapid improvement than in those with classic IHs. CONCLUSION: Although the prevalence of IH-MAGs may be relatively low, understanding their clinical features will help in differential diagnosis. Furthermore, these type of lesions might be more responsive to topical timolol than classic IHs.

DYRK1A is required for maintenance of cancer stemness, contributing to tumorigenic potential in oral/oropharyngeal squamous cell carcinoma.

DYRK1A, one of the dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs), plays an important role in various biological processes by regulating downstream targets via kinase-dependent and independent mechanisms. Here, we report a novel role of DYRK1A in maintaining tumor growth and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC) cells. Deletion of DYRK1A from OSCC cells abrogated their in vivo tumorigenicity and self-renewal capacity, the key features of cancer stem-like cells (CSCs; also referred to as tumor-initiating cells). The DYRK1A deletion also induced the suppression of CSC populations and properties, such as migration ability and chemoresistance. Conversely, ectopic expression of DYRK1A in OSCC cells augmented their CSC phenotype. Among five DYRK members (DYRK1A, 1B, 2, 3, and 4), DYRK1A is the most dominantly expressed kinase, and its expression is upregulated in OSCC compared to normal oral epithelial cells. More importantly, DYRK1A was highly enriched in various CSC-enriched OSCC populations compared to their corresponding non-CSC populations, indicating its pivotal role in cancer progression and stemness. Further, our study revealed that fibroblast growth factor 2 (FGF2) is a key regulator in the DYRK1A-mediated CSC regulation. Functional studies demonstrated that the loss of DYRK1A inhibits CSC phenotype via reduction of FGF2. Overexpression of DYRK1A promotes CSC phenotype via upregulation of FGF2. Our study delineates a novel mechanism of cancer stemness regulation by DYRK1A-FGF2 axis in OSCC. Thus, inhibition of DYRK1A would lead to a potential novel therapeutic option for targeting CSCs in OSCC.

Cryosurgery as a Minimally Invasive Alternative Treatment for a Patient with Erosive Adenomatosis of the Nipple.

Erosive adenomatosis of the nipple (EAN), also known as nipple adenoma, florid papillomatosis, or papillary adenoma of the nipple, is a benign neoplasm originating from a lactiferous duct of the breast. Although the potential for malignant change is invariably negligible, the nature of the disease is quite intractable despite several treatment methods. Surgical excision is known as the treatment of choice, but this invasive approach is generally not acceptable to the vast majority of patients due to the cosmetic outcomes. Cryosurgery could be an alternative choice to preserve the structure of the nipple-areola complex, though its application has not been studied due to the paucity of cases. A 22-year-old female presented with a unilateral, crater-like erosion of the left nipple with serosanguineous discharge. The skin biopsy revealed proliferation of tubular structures, which corresponded to EAN. She was treated with 4 sessions of cryosurgery (open cryospray with liquid nitrogen) over 6 months, and the skin lesion resolved completely without any recurrence for 12 months. Although further study is required to determine the optimal treatment regimen for EAN, cryosurgery should be considered as an effective option to surgical excision.