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.

Dutasteride in the treatment of frontal fibrosing alopecia: Systematic review and meta-analysis.

Frontal fibrosing alopecia (FFA) is a scarring alopecia with fronto-temporo-parietal hairline recession. Although no proven treatment for FFA exists, dutasteride has been suggested as a potential treatment option. We aimed to evaluate the therapeutic response of oral dutasteride in FFA patients. The identification and selection of studies were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 criteria. To assess the risk of bias for each study, we used the Cochrane's risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. A random effects model meta-analysis was performed. Estimated proportion of stabilization for eligible studies was calculated to evaluate the effectiveness of dutasteride for treating FFA. Among patients who achieved stabilization, subgroup analysis was conducted on those showing improvement. Seven studies including 366 patients who received oral dutasteride were identified. The estimated proportion of patients who experienced stabilization of FFA with oral dutasteride was 0.628 (95% CI: 0.398-0.859). In subgroup analyses of patients who experienced improvement, the estimated proportion of improvement was 0.356 (95% CI: 0.163-0.549). In this systematic review and meta-analysis, oral dutasteride revealed to be a good treatment option for disease stabilization or improvement in patients with FFA.

Exposure to air pollution and incidence of atopic dermatitis in the general population: A national population-based retrospective cohort study.

BACKGROUND: To date, little evidence is available to determine whether atopic dermatitis (AD) can be caused by exposure to air pollutants, including gases and particulate matter. OBJECTIVE: We aimed to evaluate the relationship between air pollutants and incidence of AD using the National Health Insurance Service-National Sample Cohort database. METHODS: We included 209,168 subjects from the general population previously not diagnosed with AD between 2008 and 2013. Long-term average concentration of air pollutants before diagnosis was calculated for each subject. RESULTS: For 1,030,324 person-years, incident cases of AD were observed in 3203 subjects. There was a significant positive association between incidence of AD and long-term average concentration of particulate matter smaller than 2.5 µm in diameter (hazard ratio [HR], 1.420; 95% CI, 1.392-1.448; for 1 µg/m3), particulate matter smaller than 10 µm in diameter (HR, 1.333, 95% CI, 1.325-1.341; for 1 µg/m3), sulfur dioxide (HR, 1.626; 95% CI, 1.559-1.695; for 1 parts per billion), nitrogen dioxide (HR, 1.200; 95% CI, 1.187-1.212; for 1 parts per billion), and carbon monoxide (HR, 1.005; 95% CI, 1.004-1.005; for 1 parts per billion) after adjusting for age, sex, income, comorbid diseases, and meteorologic variables. LIMITATIONS: The National Health Insurance Service database lacks detailed information on individual subjects. CONCLUSIONS: This study demonstrated that long-term exposure to air pollutants, including gases and particulate matter, is an independent risk factor for developing AD.

Late Onset Nephrogenic Systemic Fibrosis in a Patient with Stage 3 Chronic Kidney Disease: a Case Report.

Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. It can lead to severe complications and even death. NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). In this report, however, we describe the case of a patient with NSF that occurred during early CKD. A 65-year-old man with stage 3a CKD was transferred to our hospital because of lower extremity edema. The medical history revealed that he was exposed to gadolinium 185 days earlier, and the result of his tibial skin biopsy was consistent with NSF. The patient underwent a combined therapy with ultraviolet-A1 phototherapy and methotrexate and steroid therapy for 6 months. The combined therapy stopped the systemic progression of NSF.

Epidemiology and Medication Trends in Patients with Psoriasis: A Nationwide Population-based Cohort Study from Korea.

This study investigated the prevalence of psoriasis and trends in prescription of medications for patients with psoriasis using the Korean National Health Insurance Claims Database from 2006 to 2015. The prevalence of psoriasis and psoriatic arthritis per 10,000 people increased from 47.4 to 61.5 and from 0.04 to 0.23 respectively. The prescription of topical agents was a mean of 73.3%. For systemic agents, prescription of acitretin decreased from 74.8 to 44.5%, methotrexate showed a fluctuation, with a mean of 14.9% and cyclosporine increased from 9.0 to 41.2%. The prescription of biological agents increased sharply from 18 to 1,127 patients. Use of ustekinumab increased from 4.1 to 82.4%; use of infliximab decreased from 20.7 to 6.7% and etanercept decreased from 100 to 6.1%. This study showed an increasing trend in the prevalence of psoriasis. We also reported a rapid increase in the use of biologics in recent years.

Multiple Spitz nevi after allogeneic hematopoietic stem cell transplantation.

Spitz nevus commonly appears as a solitary lesion. A 12-year-old male patient presented with a 6-month history of several pigmented lesions on his trunk and lower extremities. He had undergone chemoradiotherapy and unrelated umbilical cord blood transplantation against recurring acute lymphoblastic leukemia for 6 years. After that, several pigmented lesions abruptly developed on his trunk and lower extremities, and the number of those increased significantly. Pathologically, the diagnosis of multiple Spitz nevi was made. In a clinical correlation, we diagnosed multiple Spitz nevi resulting from such an immunocompromised condition. This is the first description of clinical, dermoscopic, and histopathologic features of multiple Spitz nevi in the hematopoietic cell transplantation (HSCT) recipient child.

Increased Risk of Atrial Fibrillation in the Early Period after Herpes Zoster Infection: a Nationwide Population-based Case-control Study.

BACKGROUND: Herpes zoster (HZ) is a chronic inflammatory disease that could result in autonomic dysfunction, often leading to atrial fibrillation (AF). METHODS: From the Korean National Health Insurance Service database of 738,559 subjects, patients newly diagnosed with HZ (n = 30,685) between 2004 and 2011, with no history of HZ or AF were identified. For the non-HZ control group, 122,740 age- and sex-matched subjects were selected. AF development in the first two-years following HZ diagnosis, and during the overall follow-up period were compared among severe (requiring hospitalization, n = 2,213), mild (n = 28,472), and non-HZ (n = 122,740) groups. RESULTS: There were 2,204 (1.4%) patients diagnosed with AF during follow-up, and 825 (0.5%) were diagnosed within the first two years after HZ. The severe HZ group showed higher rates of AF development (6.4 per 1,000 patient-years [PTPY]) compared to mild-HZ group (2.9 PTPY) and non-HZ group (2.7 PTPY). The risk of developing AF was higher in the first two-years after HZ diagnosis in the severe HZ group (10.6 PTPY vs. 2.7 PTPY in mild-HZ group and 2.6 PTPY in non-HZ group). CONCLUSION: Severe HZ that requires hospitalization shows an increased risk of incident AF, and the risk is higher in the first two-years following HZ diagnosis.

Median canaliform nail dystrophy treated with a 1064-nm quasi-long pulsed Nd:YAG laser.

Median canaliform nail dystrophy (MCND) is an uncommon and idiopathic dystrophic change, which typically appears as central, longitudinal groove or split involving one or both thumbnails. Various treatments including a potent topical steroid, an intralesional injection of triamcinolone 2.5-3 mg/dL, medications for systemic treatment, and topical psoralen plus ultraviolet A (PUVA) have been tried to treat the disease. However, each treatment has limitations including severe pain, inconsistent treatment results, long treatment periods, and dissatisfaction with effects of treatment. In recent years, 1064-nm Nd:YAG laser is used for skin rejuvenation by the effect of collagen synthesis and remodeling via induction of growth factor expression. Therefore, we tried 1064-nm Nd:YAG laser to treat this nail dystrophy. A 53-year-old man presented with median nail dystrophy on both thumbs for 3 years. The nail dystrophy was treated only with 1064-nm quasi-long pulsed Nd:YAG laser. He was offered 10 sessions of treatment, and the right thumbnail showed good response and the left thumbnail showed fair response. He experienced severe pain during the treatment (Numerical rating scale (NRS) 8) and was satisfied moderately with the results (NRS 6.5). We report a case of treatment of MCND with 1064-nm quasi-long pulsed Nd:YAG laser with excellent clinical improvement.

Comparison of effect between high intense focused ultrasound devices for facial tightening: Evaluator-blinded, split-face study.

BACKGROUND: Various high intense focused ultrasound (HIFU) devices have been introduced in recent years for improving skin laxity, with satisfactory results. However, there is no comparative study on the efficacy and safety of available HIFU devices. OBJECTIVE: To compare the efficacy and safety of two HIFU devices for facial skin tightening and subsequently, to validate the quantitative assessment. METHODS AND MATERIALS: We performed a split-face comparative study in 20 Korean patients. Two different HIFU devices were used on each side of the face. Patients received one treatment session on the same number of coagulative zones. Patient assessments were recorded. Three blinded clinicians evaluated paired pretreatment and post-treatment photographs. Quantitative assessment using a fixed point as well as a variable point was additionally performed for objective evaluation. RESULTS: Qualitative assessments of both HIFU devices conducted by both clinicians and patients generally showed mild to moderate improvement, similar to previous studies. The two devices had similar efficacy in blinded clinician and quantitative assessment, although there were some differences in patient satisfaction and degree of pain. There was a correlation between clinician qualitative scores and quantitative values, which suggests successful skin tightening. CONCLUSION: To the author's knowledge, both HIFU devices tested can be used safely and effectively for facial tightening.

Carbon dioxide laser combined with botulinum toxin A for patients with periorbital syringomas.

BACKGROUND: Although various destructive methods have been described for treating syringomas, they are often associated with significant scarring and recurrence. In 2007, multiple-drilling method using carbon dioxide (CO2) laser was introduced as an alternative modality to gain good cosmetic results. OBJECTIVE: To retrospectively evaluate the effectiveness of CO2 laser combined with botulinum toxin A (BTXA) as treatment for syringomas. MATERIAL AND METHODS: Forty-eight patients with periorbital syringomas were treated with topical application of BTXA immediately after CO2 laser treatment. Forty-four patients were treated with CO2 laser only. RESULTS: Patients who were treated with CO2 laser combined with BTXA required significantly (p = 0.038) fewer treatment sessions compared with those treated with CO2 laser only. When the clinical improvements of the two treatment sessions were compared, the combined therapy (CO2 laser and BTXA) had significantly (p = 0.044) higher rate of results showing good (disappearance of 60-80% of lesion) or excellent (80-100%) than the CO2 laser only therapy (87.5% vs. 70.5%). CONCLUSIONS: CO2 laser combined with BTXA showed better effect than CO2 laser only.

Beneficial effects of early treatment of nevus of Ota with low-fluence 1,064-nm Q-switched Nd:YAG laser.

BACKGROUND: Childhood nevus of Ota is likely to be more superficial than the adult nevus, therefore early laser treatment of nevus of Ota might have some beneficial effects in children. OBJECTIVE: To evaluate the beneficial effects of early treatment of nevus of Ota with a low-fluence 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser. MATERIALS AND METHODS: The authors performed a retrospective study of 31 Korean patients (Fitzpatrick skin Type IV) with nevus of Ota. The patients received a series of 6 to 32 treatment sessions at 2- to 3-week intervals with a Q-switched Nd:YAG laser at settings of 7- or 8-mm spot, 1.9 to 5.0 J/cm2 mean fluence. RESULTS: The mean fluence was less in patients younger than 10 years (2.2 ± 0.3 J/cm2) than in those older than 10 years (2.8 ± 0.8 J/cm2) (p = .006). Patients who started their first treatment earlier required fewer treatment sessions to reach moderate, marked, and near total improvement (p < .05). By starting treatment early, low mean fluence was required to reach the end point in each session (p < .001). Post-treatment hyperpigmentation was observed in 1 patient. CONCLUSION: This treatment was clinically effective and safe for early nevus of Ota using a low-fluence Q-switched Nd:YAG laser.

The Photoprotective Effect of S-Methylmethionine Sulfonium in Skin.

S-Methylmethionine sulfonium (SMMS) was reported to have wound-healing effects; we therefore have investigated the photoprotective effect of SMMS in the present study. SMMS increased the viability of keratinocyte progenitor cells (KPCs) and human dermal fibroblasts (hDFs) following ultraviolet B (UVB) irradiation, and reduced the UVB-induced apoptosis in these cells. SMMS increased the phosphorylation of extracellular signal-regulated kinases (ERK), and the inhibitor of the mitogen-activated protein kinase pathway significantly decreased the SMMS-induced viability of KPCs and hDFs. In addition, SMMS attenuated the UVB-induced reactive oxygen species (ROS) generation in KPCs and hDFs. SMMS induced the collagen synthesis and reduced the matrix metalloproteinase-1 expression in UVB-irradiated hDFs. In animal studies, application of 5% and 10% SMMS before and after UVB-irradiation significantly decreased the UVB-induced erythema index and depletion of Langerhans cells. In summary, SMMS protects KPCs and hDFs from UVB irradiation, and reduces UVB-induced skin erythema and immune suppression. Therefore, SMMS can be used as a cosmetic raw material, and protect skin from UVB.

Exposure to Long-Term Air Pollution and Incidence of Peripheral Arterial Disease in the General Population: A Korean National Population-Based Retrospective Cohort Study.

This study aimed to evaluate the causal relationship between long-term outdoor air pollutants and incidence of peripheral arterial disease (PAD) using the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. We included 292,091 subjects from the general population who had previously not been diagnosed with PAD by the NHIS-NSC between 2008 and 2014. Hourly air pollutant data (particulate and gaseous) and climate data were collected. Correlation analysis of the collected data confirmed the relationship between air pollution and PAD incidence. For 1,836,965.4 person-years, incident cases of PAD were observed in 5243 subjects (285.4/100,000 person-years). In the Cox proportional hazard analysis, exposure to long-term average concentration of sulfur dioxide (SO2) [hazard ratio (HR), 1.686; (95% confidence interval (CI), 1.108-2.565) for .01ppm] and nitrogen dioxide (NO2) [HR, 1.200; (95% CI, 1.077-1.336) for .01 ppm] significantly increased the risk of PAD occurrence after the adjustment for several variables. This study demonstrated that SO2 and NO2 exposure are independent predictors of PAD.

Metastatic Histiocytic Sarcoma with Secondary Involvement of the Skin: A Case Report.

Histiocytic sarcoma (HS) is a rare malignant neoplasm of presumed hematopoietic origin, showing morphologic and immunophenotypic evidence of histiocytic differentiation. A 61-year-old woman presented with an abdominal mass. She had a history of HS in both adrenal glands. The tumour cells of the left adrenal gland were very large epithelioid cells with abundant eosinophilic cytoplasm and large, round-to-oval nuclei. Similarly, the cutaneous lesion of the skin was composed of polygonal cells with well-defined cell borders and high nuclear/cytoplasm (N/C) ratios. Immunohistochemically, both tumours were positive for histiocyte-associated antigens but negative for epithelial, melanocyte, lymphoid, dendritic, and Langerhansl nuclei. Similarly, the cutaneous lesion of the skin was composenose correctly. It is important to recognise the morphological features and immunohistochemical characteristics of metastatic cells in order to achieve accurate diagnoses.

Long-Term Exposure to Air Pollution and Incidence of Venous Thromboembolism in the General Population: A Population-Based Retrospective Cohort Study.

To date, the relationship between air pollutants and venous thromboembolism (VTE) has not been well established. Our aim is to investigate the association between ambient air pollutants and the incidence of VTE using the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database. From 2003 to 2015, 338,616 subjects from the general population not previously diagnosed with VTE were included. The long-term average concentration of air pollutants before diagnosis for each subject was calculated. During the study period, there were 3196 incident cases of VTE. After adjusting for age, gender, economic status, body mass index, physical activity, smoking, alcohol consumption, comorbid diseases, and meteorological variables, the risk of VTE was observed to increase significantly with the long-term average concentration of particulate matter < 10 µm in diameter: PM10 (hazard ratio (HR) = 1.064 (95% confidence interval [CI] 1.053−1.074) for 1 µg/m3), SO2 (HR = 1.118 (95% CI 1.079−1.158) 1 ppb), and O3 (HR = 1.039 (95% CI 1.026−1.053) for 1 ppb), respectively. A difference between the date of the health screening and the date of diagnosis of the disease was observed. Long-term exposure to air pollutants including PM10, SO2, and O3 may be an independent risk factor for the development of VTE.