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.

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.

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.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

A Phase 3, Randomized, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Neu-BoNT/A in Treatment of Primary Axillary Hyperhidrosis.

BACKGROUND: Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis. METHODS: The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored. RESULTS: Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests. CONCLUSION: Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Echinochrome A Treatment Alleviates Fibrosis and Inflammation in Bleomycin-Induced Scleroderma.

Scleroderma is an autoimmune disease caused by the abnormal regulation of extracellular matrix synthesis and is activated by non-regulated inflammatory cells and cytokines. Echinochrome A (EchA), a natural pigment isolated from sea urchins, has been demonstrated to have antioxidant activities and beneficial effects in various disease models. The present study demonstrates for the first time that EchA treatment alleviates bleomycin-induced scleroderma by normalizing dermal thickness and suppressing collagen deposition in vivo. EchA treatment reduces the number of activated myofibroblasts expressing α-SMA, vimentin, and phosphorylated Smad3 in bleomycin-induced scleroderma. In addition, it decreased the number of macrophages, including M1 and M2 types in the affected skin, suggesting the induction of an anti-inflammatory effect. Furthermore, EchA treatment markedly attenuated serum levels of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, in a murine scleroderma model. Taken together, these results suggest that EchA is highly useful for the treatment of scleroderma, exerting anti-fibrosis and anti-inflammatory effects.

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.

Aplasia cutis congenita in Korea: Single center experience and literature review.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital malformation characterized by a localized absence of skin. which most commonly affects the scalp. We performed the present study to elucidate the basic clinical data regarding ACC in Korea, including demographics, clinical features, radiological and therapeutic results. METHODS: Fifty-nine patients (70 lesions) with ACC (35 from our department and 24 from a Koreamed database search) were enrolled. We assessed demographics, family and obstetrical histories, clinical features (multiplicity, subtype, size, shape, hair collar sign, location, and Frieden's classification), and radiologic and therapeutic results. RESULTS: The mean age of patients was 2.62 years, with a male-to-female ratio of 1.03. A minority of patients had a family history (three patients), birth trauma (one patient), maternal drug use (two patients), or human immunodeficiency virus infection (one patient) during pregnancy, and fetus papyraceus of placental infarcts (two patients). Six patients (6/59, 10.17%) had multiple lesions. Scarring was the most common manifestation (39/70, 55.71%). The scalp was the most commonly affected site (50 cases, 71.43%). Thirty-nine patients (66.10%) met Frieden's type I classification (scalp ACC without multiple anomalies). Radiological investigations were performed in 30 patients (30/59, 50.85%) with abnormal findings in eight patients. Twenty-five patients (42.37%) were managed conservatively, and 17 patients (28.81%) were treated with local wound care. CONCLUSIONS: This is the first and largest study assessing the basic clinical data of ACC in Korea. The results of the present study could be useful for pediatricians and dermatologists who routinely manage ACC.

Clinical and Laboratory Differences Between Early-Onset and Late-Onset Adult Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) in adults is not uncommon, and its prevalence has been increasing in the recent decades. However, there is a paucity of data about the differences between early-onset and late-onset adult AD. OBJECTIVE: The objective of this study is to investigate the clinical and laboratory characteristics of adult AD, focusing on the differences between early-onset and late-onset adult AD. METHODS: We retrospectively reviewed the medical records and clinical photos of 214 adult AD patients (≥18 years of age) over a 3-year period. We classified the patients into 2 groups: early-onset (first onset of AD before 12 years of age) and late-onset (first onset of AD at 12 years of age or later). RESULTS: Among 214 patients, 151 patients (70.6%) belonged to the early-onset group (mean age 24.5 years), while 63 patients belonged to the late-onset group (mean age 29.5 years). An association with allergic asthma or rhinitis, a family history of atopic disease, elevated total serum IgE, and sensitivity to food allergens were more commonly seen in the early-onset group. The late-onset group had a significant likelihood of nonflexural involvement (38.1% vs 13.2%). There was no significant difference in the mean eczema area severity index score, eosinophil count, and sensitivity to aeroallergens between 2 groups. CONCLUSION: Adult AD shows different clinical and laboratory characteristics depending on the age of onset. This study could help to create awareness about the heterogeneity of AD in adulthood and encourage further studies on clinical outcomes and different therapeutic methods depending on the age of onset.

Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose PET/CT.

BACKGROUND: Evidence suggests that psoriasis might be associated with metabolic syndrome and an increased risk for cardiovascular disease. OBJECTIVE: To determine whether ustekinumab reduces systemic and vascular inflammation associated with metabolic syndrome and cardiovascular disease, measured using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). METHODS: Patients with psoriasis and healthy controls underwent baseline 18F-FDG PET/CT imaging. Patients with moderate-to-severe psoriasis were treated with ustekinumab and underwent 18F-FDG PET/CT again after a Psoriasis Area and Severity Index of 75 was achieved. RESULTS: After a Psoriasis Area and Severity Index of 75 was achieved with ustekinumab treatment, standardized uptake values were reduced in the liver, spleen, and 5 parts of the aorta (P < .05). LIMITATIONS: Our study does not provide outcome data concerning cardiovascular events or metabolic syndrome; it only shows surrogate markers in a limited (Korean) population. CONCLUSION: Ustekinumab treatment was significantly associated with decreased systemic and vascular inflammation related to metabolic syndrome and cardiovascular disease among patients with psoriasis.

Atrial natriuretic peptide accelerates human endothelial progenitor cell-stimulated cutaneous wound healing and angiogenesis.

Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs. Furthermore, small interfering RNA-mediated silencing of natriuretic peptide receptor-1, which is a receptor for ANP, abrogated ANP-induced migration, tube formation, and proliferation of EPCs. In a murine cutaneous wound model, administration of either ANP or EPCs had no significant effect on cutaneous wound healing or angiogenesis in vivo, whereas the coadministration of ANP and EPCs synergistically potentiated wound healing and angiogenesis. In addition, ANP promoted the survival and incorporation of transplanted EPCs into newly formed blood vessels in wounds. These results suggest ANP accelerates EPC-mediated cutaneous wound healing by promoting the angiogenic properties and survival of transplanted EPCs.

Association between Breslow thickness and dermoscopic findings in acral melanoma.

BACKGROUND: Dermoscopy is a useful tool for the diagnosis of acral melanomas (AMs). However, little is known about the influence of tumor thickness on the dermoscopic findings of AM. OBJECTIVE: To investigate the affect Breslow thickness (BT) has on the dermoscopic patterns of AM. METHODS: Data on cases of AM on the glabrous skin were collected from 4 university hospitals. We investigated the frequency of each dermoscopic feature of AM according to the BT. Statistical analysis was performed to investigate the association between the specific dermoscopic patterns and BT. RESULTS: Multivariable analysis revealed that the colors red (odds ratio [OR] 16.482, 95% confidence interval [CI] 3.605-99.016); blue (OR 7.092; 95% CI 1.707-37.435); and white (OR 5.048, 95% CI 1.152-22.897) were more common in AM with BT >2 mm than those with BT ≤2 mm. Regarding patterns, atypical vascular (OR 34.589, 95% CI 6.458-305.852); blue-white veils (OR 9.605, 95% CI 1.971-72.062); and ulcers (OR 5.084, 95% CI 1.145-24.152) were more frequently detected in cases with BT >2 mm than those with BT ≤2 mm. LIMITATIONS: A retrospective study design and small sample size. CONCLUSION: This study showed an association between dermoscopic patterns and tumor thickness among patients with AM. Dermoscopy can be a useful adjuvant tool for predicting BT in AM.