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.

Association between the skin microbiome and lichen striatus hypopigmentation: Cutibacterium acnes as a potential cause.

BACKGROUND: Lichen striatus (LS) is an acquired skin disorder with a linear pattern along Blaschko's lines. It commonly occurs in childhood, and the lesions spontaneously regress within several months. OBJECTIVES: Although up to 50% of LS cases exhibit hypopigmentation that can persist for several months to years, it is unknown why LS is associated with such a high incidence of hypopigmentation compared to other inflammatory skin diseases. Therefore, this study aimed to analyse the differences in the skin microbiome between LS patients with and without hypopigmentation. METHODS: Differences in skin microbiome were analysed using whole genome sequencing of skin biopsies and subsequent bioinformatics analyses. RESULTS: Some microbes commonly found in hypopigmented skin disorders, including Cutibacterium acnes, were more abundant in patients with LS showing hypopigmentation than in those not showing hypopigmentation. CONCLUSIONS: The skin microbiota may be involved in the development of hypopigmentation in LS and may be considered a treatment target to reduce LS duration and hypopigmentation.

Dose-response analysis between alcohol consumption and psoriasis: A systematic review and meta-analysis.

The association between psoriasis and alcohol consumption has been inconsistent across various studies. However, to the best of our knowledge, no dose-response meta-analysis has been performed to date. This study aims to investigate the association between alcohol consumption and psoriasis. The search was performed on July 27, 2021, using Embase and MEDLINE. The restricted cubic spline analysis was used to perform a dose-response analysis. We identified 3,904 studies, of which 48 studies with 1,702,847 individuals across 24 countries were included. Alcohol consumption was positively associated with psoriasis (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.27-1.70). In addition, a significantly increased OR for psoriasis was observed in males (OR, 1.84; 95% CI, 1.13-3.01) but not in females (OR, 1.22; 95% CI, 0.97-1.54). Based on eight studies, including three cohort and five case-control studies, the analysis revealed that with each additional gram of daily alcohol intake, the OR for psoriasis increased by 4%. We found a positive association between alcohol consumption and psoriasis. The association is more prominent in the group drinking more than 45 g of alcohol per day (3.2 alcoholic drink equivalent).

Therapeutic Effect of Dupilumab on Systemic and Vascular Inflammation in Adults with Severe Atopic Dermatitis: Feasibility Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Atopic dermatitis (AD) is an inflammatory skin disease associated with increased systemic and vascular inflammation. Although dupilumab has been proven to be effective against severe AD, imaging studies analysing its inflammation-reducing effect have rarely been reported. The aim of this study was to evaluate the effect of dupilumab on systemic and vascular inflammation in adult patients with severe AD, using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). A total of 33 adult patients with severe AD and 25 healthy controls underwent 18F-FDG PET/CT at baseline. Patients on dupilumab treatment underwent 18F-FDG PET/CT again after achieving a 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75). Patients with AD exhibited increased 18F-FDG uptake values in the liver, spleen, pancreas, and carotid artery compared with healthy controls. However, compared with baseline, there was no statistically significant difference in 18F-FDG uptake in major organs and arteries after achieving EASI-75 with dupilumab treatment. In conclusion, while dupilumab treatment resulted in a significant clinical improvement and reduced serum inflammatory markers in adult patients with severe AD, no changes in systemic and vascular inflammation were observed on 18F-FDG PET/CT imaging.

Change in the Usage of Complementary and Alternative Medicine in the Era of Biologics Among Korean Patients With Psoriasis.

BACKGROUND: Patients with long-standing psoriasis who are not treated with conventional medicine seek complementary and alternative medicine (CAM). The biological revolution in the field of psoriasis since the late 2000s has progressed, expecting clearance or almost clearance of the disease. The frequency and type of CAM usage may have changed after these advances. We aimed to investigate changes in CAM use in Korean patients with psoriasis before and after the prevalent use of biologics. METHODS: Patients with psoriasis who visited Pusan National University Hospitals (Busan and Yangsan) between March 2020 and June 2022 were made to complete a face-to-face structured questionnaire. These results were compared with our previous study conducted approximately 10 years ago. RESULTS: In total, 207 patients were included. Compared with the previous results, the frequency of CAM use (67.6%) increased (P < 0.001). Oriental medicine (67.1%) has most commonly been used, followed by health supplements and bath therapy. The biggest reason for using CAM was "to try all the potential treatments." Meanwhile, negative concerns about conventional medicine (13.5%) significantly decreased during the 10-year period (P < 0.001). CONCLUSION: Although treatment efficacy has increased with biologics development, CAM usage remains prevalent among Korean patients with psoriasis. Therefore, dermatologists need more efforts to improve patients' understanding of conventional medicine, including biologics.

Effects of the multi-channeled oral irrigation (MCOI) unit in preventing dental plaque formation and gingivitis: A randomized controlled trial.

PURPOSE: To evaluate the efficacy of COMORAL a new multi-channeled oral irrigation (MCOI) unit with pulsating water jet, in plaque score reduction and gingivitis. METHODS: This was a single-blinded clinical randomized controlled trial (NCT05031260). Forty-two healthy subjects between 18 to 35 years old were initially recruited, and the control group (n = 20) and the intervention group (n = 17) were randomly assigned. Both groups were asked to brush their teeth one or two times a day without any supplementary oral hygiene products while the intervention group used COMORAL 3 times a day, 5 days a week. Clinical indices including gingival index (GI), plaque index (PI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were obtained at the baseline (D0), day 14 (D14), and day 28 (D28). Saliva was collected to examine the presence of periodontal pathogens. The repeated measures analysis of variance or generalized estimating equation was used to compare the interaction between groups and time points. The independent t-test or Mann-Whitney test were used for intergroup differences at each time point. RESULTS: At V0, PI, GI, BOP, and PD scores showed no differences between the two groups. At V1 and V2, these scores showed significant difference between two groups (P < 0.05) such that the intervention group showed gradual decreases while the control group showed no change. There were no differences in GR, CAL, and periodontal pathogens between the two groups. COMORAL showed improvement in reducing gingival inflammation and dental plaque formation adjuvant to routine toothbrushing in healthy adults. CLINICAL SIGNIFICANCE: The results of this study can be useful to clinicians when selecting oral hygiene devices that can help improve patients' routine oral hygiene practice and their overall oral health.

Geographic differences in atopic dermatitis risk between urban and rural area: A systematic review and meta-analysis.

Atopic dermatitis is the most common chronic inflammatory skin disease affecting children. Some studies have reported a higher risk of atopic dermatitis in urban areas than in rural areas. We systematically reviewed and carried out a meta-analysis to investigate the differences in the development of atopic dermatitis between urban and rural areas. The search was performed on April 19, 2021, using Embase and MEDLINE databases. Eligible for inclusion were observational studies. Subgroup analyses were performed for age, publication year, and country. We identified 2,115 studies, and 43 studies with 1,728,855 subjects were finally included. Urban residency was associated with an increased risk of atopic dermatitis, with an odds ratio of 1.56 (95% confidence interval, 1.43-1.71). A significantly increased risk was observed only in children, with an odds ratio of 1.55 (95% confidence interval, 1.39-1.73), but not in adults, with an odds ratio of 1.29 (95% confidence interval, 0.99-1.67). The risk has increased in recent decades, with a higher risk in developing countries (odds ratio, 1.95) compared to developed countries (odds ratio, 1.35). Our study provides evidence of an association between atopic dermatitis and urban compared to rural living.

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.

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.

Ultrasonographic findings of pediatric dermoid cyst.

BACKGROUND: The precise diagnosis of dermoid cysts, which are usually located deeper than other common cysts, is important because dermoid cysts occasionally recur after incomplete excision. Ultrasonography (US) could give useful preoperative information of dermoid cysts but only a few studies have been conducted on US findings related to dermoid cysts. This study aimed to investigate clinical and US findings on pediatric dermoid cysts. METHODS: We retrospectively reviewed the medical records, clinical photographs, and US findings of 31 pediatric patients (≤18 years of age) with histopathologically diagnosed dermoid cysts who visited the Pusan National University Hospital between 2007 and 2016. RESULTS: Of the 31 patients, 25 underwent ultrasonography. The mean long diameter, short diameter, and depth of the cysts were 12.7, 9.0, and 3.8 mm, respectively. Sixteen cysts (64%) were ovoid, 23 (92%) showed hypoechogenicity, 20 (80%) showed heterogeneity, 19 (76%) showed well-demarcated outer margins, and all cysts showed positive posterior acoustic enhancement. All cysts extended to the subcutaneous tissue, and 15 (60%) showed a connection with the underlying muscle. CONCLUSIONS: Ultrasonography may be a useful diagnostic method to visualize the extent and location of the dermoid cyst and make an accurate diagnosis prior to surgical intervention.

Characteristic Clinical and Dermoscopic Features of Nonvolar Poroma.

BACKGROUND: A poroma typically presents as a solitary, pink-to-red papule or nodule in acral volar areas. However, in nonvolar areas, this typical clinical feature (TCF) can be difficult to identify. OBJECTIVE: We aimed to compare clinical and dermoscopic characteristics between nonvolar poroma (NVP) and volar (ie, typical) poroma (VP). METHODS: We assessed the clinical and dermoscopic characteristics of 40 patients with poromas who were divided into the NVP and VP groups. RESULTS: Of the 40 patients, 20 (50.0%) were allocated to the NVP group and 20 (50.0%) to the VP group. Pigmented variants were more common in the NVP group than in the VP group (60.0% vs 5.0%). The TCF of poroma was observed less frequently in the NVP than the VP group (45.0% vs 85.0%). Approximately one-third (30.0%) of patients with NVP received an initial clinical diagnosis of skin cancer. Dermoscopic patterns associated with melanoma or basal cell carcinoma were more common in the NVP group than in the VP group (65% vs 30%). CONCLUSIONS: Skin cancer-associated clinicodermoscopic features were more frequently observed in patients with NVP, who simultaneously lost dermoscopic patterns associated to poromas and acquired those associated with skin cancer, than those with VP.

Comparison of Dermoscopic Features Between Melanoacanthomas and Melanoacanthoma-Like Malignant Melanomas in Korean Patients.

BACKGROUND: A melanoacanthoma (MA) is a pigmented variant of seborrheic keratosis. Owing to the pigmentation, MAs may mimic the clinical appearance of malignant melanomas (MMs). However, the dermoscopic patterns of MAs and MA-like MMs have rarely been compared. OBJECTIVE: To elucidate the clinical and dermoscopic differences between MAs and MA-like MMs. METHODS: This study included 77 MA and 33 MA-like MM patients. We retrospectively reviewed the medical records, clinical findings, and dermoscopic findings of the two groups. RESULTS: Crypts and comedo-like openings (71.4%) in MAs and the blue-white veil (60.6%) in MMs were the most common dermoscopic findings. Crypts, comedo-like opening, milia-like cysts, fissures, and hairpin vessels appeared more frequently in MAs (P < .05). However, atypical pigment networks, blue-white veils, pseudopods and streaks, and atypical vessels were more common in MMs (P < .05). MAs often showed melanoma-specific dermoscopic findings, especially blue-white veils (22.1%). Furthermore, fissures (42.4%), crypts (21.2%), and comedo-like openings (15.2%) were observed in MMs, although they are typically benign patterns. CONCLUSION: Differences in dermoscopic patterns might provide important clues for the differential diagnosis of MA-like lesions. However, MAs such as MMs and true-benign MAs may overlap clinically in appearance and on dermoscopy. Several benign patterns were frequently observed in MMs (fissures, globular pattern, crypts, comedo-like openings, cerebriform appearance, and milia-like cysts), and several malignant patterns were observed in MAs (blue-white veil, pseudopod, and atypical pigment network). Importantly, if any of the melanoma-associated features or atypical vessels are present, the lesion should be biopsied to establish a diagnosis.

Unilateral facial erythematous patch as the presenting sign of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can have many cutaneous manifestations including malar rash, discoid rash or oral ulcer. Isolated unilateral involvement of face is uncommon in SLE. It lacks typical clinical features of LE, and may impose a diagnostic challenge for clinicians. Herein we report a case of 62-year-old woman presenting with a 2-year history of erythematous patches on left cheek and eyelid. Initially, she was diagnosed as having recurrent blepharitis or cellulitis that did not respond to conventional treatment with ophthalmic medicaments. As time went by, the patches spread to her left cheek, and she was referred to our dermatologic department. Histopathologic examination was consistent with LE. Further physical and laboratory tests have found that she had oral ulcers, proteinuria, thrombocytopenia and abnormal titer of anti-nuclear antibody satisfying the diagnosis of SLE. From this case, we think unilateral erythematous patches on face could be a rare manifestation of SLE and more intention should be paid to this type of patients, because unilateral facial symptom may mimic other dermatoses.

Removal of Pre-Existing Periodontal Inflammatory Condition before Tooth Extraction Ameliorates Medication-Related Osteonecrosis of the Jaw-Like Lesion in Mice.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but detrimental intraoral lesion that predominantly occurs in patients with long-term use of antiresorptive agents, such as bisphosphonate and denosumab, a human anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Ab). Surgical intervention, such as tooth extraction, is a known risk factor for MRONJ, which is often performed to eliminate preexiting pathologic inflammatory conditions, such as periodontal diseases. Nonetheless, it remains unknown whether pre-existing periodontal disease condition exacerbates, or removal of such condition ameliorates, MRONJ development after tooth extraction. In this study, we combined the ligature-induced periodontitis and the tooth extraction mouse models under the administration of zoledronic acid (ZOL) or anti-RANKL Ab, and provide experimental evidence that a pre-existing pathologic inflammatory condition exacerbates MRONJ development after tooth extraction in mice. Under ZOL administration, tooth extraction alone induced ONJ lesions; however, extraction of a ligature-placed tooth further exacerbated ONJ development. When the ligature was removed and the inflammatory condition was deescalated, ONJ development was ameliorated. Anti-RANKL Ab administration resulted in similar outcomes. Interestingly, unlike ZOL-administered mice, anti-RANKL Ab-administered mice exhibited complete absence of osteoclasts, suggesting that physical presence of osteoclasts is not directly involved in ONJ development. Collectively, our study demonstrated that periodontal disease is a functionally linked risk factor that predisposes ONJ development after tooth extraction in the presence of bisphosphonate and denosumab.

Elevated expression of JMJD6 is associated with oral carcinogenesis and maintains cancer stemness properties.

Cancer stem cells (CSCs) are defined as a small subpopulation of cancer cells within a tumor and responsible for initiation and maintenance of tumor growth. Thus, understanding of molecular regulators of CSCs is of paramount importance for the development of effective cancer therapies. Here, we identified jumonji domain-containing protein 6 (JMJD6) as a novel molecular regulator of oral CSCs. JMJD6 is highly expressed in CSC-enriched populations of human oral squamous cell carcinoma (OSCC) cell lines. Moreover, immunohistochemical staining revealed significantly high level of JMJD6 in OSCC tissues compared to normal human oral epithelia, suggesting that expression of JMJD6 positively correlates with oral carcinogenesis. Subsequent functional analysis showed that knockdown of endogenous JMJD6 in OSCC strongly suppressed self-renewal capacity, a key characteristic of CSCs, and anchorage-independent growth. Conversely, ectopic expression of JMJD6 enhanced CSC characteristics including self-renewal, ALDH1 activity, migration/invasion and drug resistance. Expression of CSC-related genes was also markedly affected by modulating JMJD6 expression. Mechanistically, JMJD6 induces interleukin 4 (IL4) transcription by binding to its promoter region. IL4 rescues self-renewal capacity in JMJD6- knocked down OSCC cells, suggesting the importance of JMJD6-IL4 axis in oral CSCs. Our studies identify JMJD6 as a molecular determinant of CSC phenotype, suggesting that inhibition of JMJD6 may offer an effective therapeutic modality against oral cancer.