Phase 1/2 trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

A clinical investigation of early-onset alopecia areata in children: Onset earlier than 4 years of age might have a better short-term prognosis.

Alopecia areata (AA) is a non-scarring autoimmune hair loss of the scalp or body. While an early onset is considered a primary factor for poor prognosis, children with early-onset AA show varied responses to treatment. This study aimed to describe the clinical characteristics and assess the prognostic factors of early-onset AA in children. We performed a retrospective study of AA patients aged <10 years who visited our dermatologic clinic between January 2013 and December 2020, with a follow-up period >12 months. A clinical review of medical records, photographs, and telephonic interviews was performed. Treatment efficacy was assessed based on the degree of hair regrowth at a 12-month follow-up. Of 162 patients treated with topical corticosteroids, alone or in combination with other modalities, 57.4% showed >50% hair regrowth. On comparing the good and poor treatment response groups, no significant differences were observed in the presence of known prognostic factors, except for personal atopic history. In addition, patients aged <4 years at onset responded significantly better than older patients (p = 0.0127). There is a possibility that the patients with early-onset AA, especially those aged <4 years, demonstrate good treatment response. Further studies on long-term prognosis are required.

Impact of the COVID-19 pandemic on telogen effluvium: a nationwide multicentre interrupted time series study.

BACKGROUND: There is ongoing debate regarding the association between telogen effluvium (TE) and COVID-19, as well as COVID-19 vaccines. OBJECTIVES: To investigate the impact of the COVID-19 pandemic and vaccination on the development of TE among patients visiting dermatology clinics in South Korea. METHODS: Between 2017 and 2022, data regarding patients with TE and other types of hair loss were collected from 22 hospitals in South Korea. An interrupted time series analysis was conducted, dividing the time into periods before and after the COVID-19 pandemic, as well as before and after the COVID-19 vaccination. RESULTS: There was a significant slope change in the percentage of cases of TE during the postpandemic period (slope change 0.011, 95% confidence interval 0.005-0.017, P < 0.001), but no significant changes were observed after vaccination. The percentage of patients with other types of hair loss was not associated with COVID-19 or vaccination. The retrospective nature of the study may have limited the ability to establish causation. CONCLUSIONS: This multicentre study provides insights into the epidemiology of TE, showing a significant increase in cases of TE following the COVID-19 pandemic. However, there was no association between the occurrence of TE and COVID-19 vaccines.

Do the Clinical Characteristics of Lipomas Influence the Incision Length During Minimal Incision Extraction?

BACKGROUND: Minimal incision extraction technique is widely accepted for the surgical removal of lipomas, but no consensus for the incision length has been made yet. OBJECTIVE: To investigate the clinical characteristics of lipomas which affect the minimal incision length during the minimal incision extraction. METHODS: We retrospectively analyzed 50 patients who underwent minimal incision extraction for 55 medium-sized (3-5 cm) or large lipomas (> 5 cm) between March 2020 and May 2022. If the mass is not fully dissected, or adequate visual field for hemostasis was not provided through the initial one-third incision, the incision was extended to the minimal extent. RESULTS: There were 33 males and 17 females with a mean age of 53.5 ± 12.7 years. There was no statistical difference in the minimal % incision length, defined as [(incision length) / (tumor diameter)] x 100, between the medium-sized (n = 31) and large lipomas (n = 24). Lipomas of the long incision group (minimal % incision length ≥66.7%, n = 21) had a higher frequency of head and neck location than lipomas of the short incision group (minimal % incision length <66.7%, n = 34) (odds ratio = 14.5, P < .05). However, no association was found between the tumor diameter or depth and the minimal % incision length. The occurrence of postoperative complications was not associated also (P = .296). CONCLUSION: The minimal % incision length for lipoma removal does not show statistical difference between medium-sized and large lipomas, and is affected by its anatomical location, but not by tumor diameter or depth.

Clinical Implication of the Regional Thickness of the Lower Facial Skin, Superficial Fat, and Superficial Musculoaponeurotic System on High-Intensity Focused Ultrasound Treatment.

BACKGROUND: Knowledge of the topographic thickness of the skin and soft tissues is necessary when performing a high-intensity focused ultrasound (HIFU) procedure. Thermal tissue injury to the superficial musculoaponeurotic system (SMAS) or deeper can injure the facial nerve and its branches. OBJECTIVE: To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS. MATERIALS AND METHODS: The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed. RESULTS: The mean age was 41.1 ± 13.7 years (range, 19-76 years). The jowl had thinner skin, thicker superficial fat, and deeper superficial and deep margins of the SMAS than the preauricle or lower cheek. The thickness of the superficial fat decreased with age, especially on the preauricle, lower cheek, and jowl. Women had thicker superficial fat than men on the preauricle and lower cheek. The superficial and deep margins of the SMAS were located more superficially in old and male patients with a slim facial figure than in young and female patients with a chubby facial figure. CONCLUSION: The present findings provide anatomical information regarding the superficial fat and SMAS, which is useful in determining the focal penetration depth of HIFU treatment for lower face rejuvenation.

Serial Hydrolysis for the Simultaneous Analysis of Catecholamines and Steroids in the Urine of Patients with Alopecia Areata.

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.

Sex-related differences in urinary immune-related metabolic profiling of alopecia areata patients.

INTRODUCTION: Alopecia areata is a well-known autoimmune disease affecting humans. Polyamines are closely associated with proliferation and inflammation, and steroid hormones are involved in immune responses. Additionally, bile acids play roles in immune homeostasis by activating various signaling pathways; however, the roles of these substances and their metabolites in alopecia areata remain unclear. OBJECTIVES: In this study, we aimed to identify differences in metabolite levels in urine samples from patients with alopecia areata and healthy controls. METHODS: To assess polyamine, androgen, and bile acid concentrations, we performed high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Our results showed that spermine and dehydroepiandrosterone levels differed significantly between male patients and controls, whereas ursodeoxycholic acid levels were significantly higher in female patients with alopecia areata than in controls. CONCLUSION: Our findings suggested different urinary polyamine, androgen, and bile acid concentrations between alopecia areata patients and normal controls. Additionally, levels of endogenous substances varied according to sex, and this should be considered when developing appropriate treatments and diagnostic techniques. Our findings improve our understanding of polyamine, androgen, and bile acid profiles in patients with alopecia areata and highlight the need to consider sex-related differences.

Distribution of polyamines may be altered in different scalp regions of patients with hair loss.

Hair loss, from the vertex or front of the head, generally occurs due to increased androgenic steroid levels. Androgenic steroids, particularly testosterone and dihydrotestosterone, are distributed differently across the vertex and occipital regions and are involved in inducing ornithine decarboxylase expression. Therefore, we hypothesized that the distribution of polyamines may be altered in different scalp regions. For the overall metabolic profiling of polyamines in patients with hair loss, a liquid chromatography-mass spectrometry was used. We investigated the differential polyamine levels in different regions of the hair of patients with male pattern baldness and those with female pattern hair loss. The levels of most polyamines were higher in the vertex region than in the occipital region, and N-acetyl polyamine levels differed significantly. We proposed to test our hypothesis by profiling polyamines in human hair fibre to evaluate the distribution of metabolites in various regions of the scalp.

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss.

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid-frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α-reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset.

A Case of Phacomatosis Pigmentokeratotica Associated With Multiple Basal Cell Carcinomas.

Phacomatosis pigmentokeratotica is a recently identified disease characterized by the coexistence of an epidermal nevus with sebaceous differentiation arranged along Blaschko lines and a speckled lentiginous nevus showing a checkerboard pattern, mostly in association with various extracutaneous defects. A 52-year-old man presented with asymptomatic ulcerative plaque on his left side of perioral area. A 2 × 2-cm-sized fleshy colored ulceration on his left perioral area was consistent with basal cell carcinoma with nevus sebaceous. Next to the ulceration, there was a light pinkish to fleshy colored papule on his left cheek that showed syringocystadenoma papilliferum. On his chin area, there was a 2 × 0.3-cm-sized skin colored papule that was consistent with trichilemmoma. Moreover, various sized light brownish macules and dark brownish papules were also located on his left side of the chest wall, back, and arm. Biopsy specimens from macules on the left side of the trunk confirmed the clinical diagnosis of speckled lentiginous nevus and multiple black papules beside that a speckled lentiginous nevus also revealed basal cell carcinomas. Herein, we present a rare case of a patient with phacomatosis pigmentokeratotica who had no extracutaneous abnormalities and who developed basal cell carcinoma, syringocystadenoma papilliferum, and trichilemmoma in nevus sebaceous on the face and speckled lentiginous nevus on the trunk. This syndrome needs adequate follow-up due to the possibility of malignant transformation.

Dermatofibroma: sonographic findings and pathologic correlation.

Background Ultrasound has been increasingly used for the evaluation of superficial soft tissue lesions. Dermatofibroma is one of the most common dermal lesions. Experiences in ultrasound examinations of dermatofibromas have been accumulated. Purpose To evaluate sonographic findings of dermatofibroma and to correlate them with pathologic findings. Material and Methods A total of 18 dermatofibromas in 15 patients were included. Sonographic findings were assessed for location, depth, size, shape, margin, spiculation, echogenicity, internal hyperechoic dots, change in echogenicity of adjacent soft tissue, and vascularity, by two musculoskeletal radiologists in consensus. Pathologic findings were evaluated by one pathologist. Ultrasonographic characteristics were correlated with the pathologic findings by discussion between one radiologist and one pathologist. Results On ultrasound, all lesions were found to be located in the dermis, and 14 lesions (78%) extended into the subcutaneous layer. Mean size was 7 mm (range = 3 to 10 mm). Characteristic findings were ill-defined margins (n = 15, 83%), spiculated margins (n = 12, 67%), change in echogenicity of adjacent soft tissue (n = 14, 78%), and no Doppler flow (n = 14, 78%). Histologically, depth, margin, and spiculation were correlated with sonographic findings. Reactive fibrosis and chronic inflammation were seen in adjacent dermis and subcutaneous fat layer of echogenicity change. Conclusion On ultrasound, dermatofibromas are usually visible as avascular dermal lesions with extension into the subcutaneous layer, and are characterized by ill-defined margins, marginal spiculation, and change in echogenicity of surrounding soft tissues.

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean population.

The heat shock 70 kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5'-untranslated region (5'UTR) SNP rs6457452 and a promoter SNP rs2763979 (-1140C > T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p < 0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p ≤ 0.04) and that rs2763979 was only weakly related to the type of AA lesion (p = 0.041). In conclusion, we suggest that the 5'UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.

Real-world experience of baricitinib in atopic dermatitis: including add-on therapy for patients using dupilumab.

BACKGROUND: Little real-world experience regarding the use of baricitinib, an oral selective JAK1/JAK2 inhibitor, for treating moderate to severe atopic dermatitis (AD) has been reported. METHODS: This study aimed to assess the overall outcomes in Korean patients with AD treated with baricitinib. All patients with moderate to severe AD treated with baricitinib between June 2021 and June 2022 were included, and their cases were retrospectively analyzed using medical records. Patients with moderate to severe AD, aged ≥18 years who had failed previous therapies, including those who demonstrated unsatisfactory improvement with dupilumab, were prescribed baricitinib. Patients whose follow-up period was <8 weeks were excluded. The dermatologist evaluated the AD status, including eczema area and severity index (EASI), itch Numeric Rating Scale, and improvement of remaining lesions despite dupilumab therapy. RESULTS: We analyzed 34 AD patients who received baricitinib. Twelve patients treated with dupilumab were additionally prescribed baricitinib due to unsatisfactory treatment effects and demonstrated improvement in the remaining lesions despite dupilumab treatment. Their itching improved after 1.4 weeks. Among them, eight patients (66.7%) had head and neck dermatitis, and seven of them demonstrated improvement after the coadministration of baricitinib. Among the other 22 patients who were prescribed baricitinib only, 10 patients (45.5%) achieved EASI 75 at 8 weeks, with five (22.7%) revealing EASI 90. CONCLUSIONS: Overall, baricitinib was well tolerated and resulted in clinical improvement in AD patients in a real-world clinical setting. Additionally, baricitinib may be beneficial in treating lesions refractory to dupilumab therapy.