Phase I/II 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: To investigate 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 I open-label trial followed by a phase II randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase I, intravenous (IV) administration of hcMSCs at two doses (1×106 and 5×105 cells/kg) was safe and well-tolerated in 20 subjects. Since there was no difference between the two dosage groups (P=0.9), it was decided to administer low-dose hcMSCs only for phase II. In phase II, subjects receiving three weekly IV infusions of hcMSCs at 5x105 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=0.038). The differences between groups in the dermatology life quality index and pruritus numerical-rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: Our findings demonstrate that hcMSCs treatment resulted in a significantly higher rate of achieving EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSCs 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 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.

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.

Primary Cutaneous Solitary Fibrous Tumor on the Back.

Solitary fibrous tumors (SFT) are uncommon mesenchymal tumors. SFT have several synonyms including localized fibrous tumor, benign mesothelioma, localized fibrous mesothelioma, and submesothelial fibroma. SFT usually occur in the pleura or other serosal surfaces, but SFT can also develop in extrapleural areas including the nasal cavity, orbit, retroperitoneum, and pelvis. Cutaneous SFT is extremely rare, and more likely to occur in the head and neck region. Histologically, this tumor can mimic a variety of benign and malignant tumors such as dermatofibroma, dermatofibrosarcoma protuberans, spindle cell lipoma or other mesenchymal tumors. Most cases of SFT show non-aggressive clinical courses, with low recurrence rates. Herein, we describe a case of primary cutaneous SFT which presented with huge mass on the back.

Treatment of Recalcitrant Viral Warts with Combination Therapy of Systemic Acitretin and Diphenylcyclopropenone Immunotherapy.

Viral warts are benign proliferations of the epithelium caused by human papilloma virus (HPV) infection. Diverse therapeutic options are available for viral warts, depending on extension and severity of the disease. We report a case of a 19-year-old man who presented with multiple viral warts on hands and feet for 5 years. He was treated at other clinics before visiting our hospital, but there was no improvement. We treated the lesions with a combination therapy of systemic acitretin and diphenylcyclopropenone (DPCP) immunotherapy for 6 months. A significant improvement was observed during the 12th week of therapy. Herein, we report a case of recalcitrant viral warts showing complete regression when a combination therapy of oral acitretin and immunotherapy was administered.

A Case of Livedoid Vasculopathy Successfully Treated with Sulodexide.

We report a 29-year-old female with a one-month history of non-healing multiple erythematous to violaceous plaques with crusts over both legs and feet. Tender, scarring ulcers with surrounding erythema were present. The clinical manifestation, together with histopathologic findings of fibrinoid plugs within vascular lumens and walls, as well as red blood cell extravasation, led to diagnosis of livedoid vasculopathy. The patient experienced recurrent painful violaceous plaques with ulcerations during the two years of treatment with oral pentoxifylline 400 mg three times daily. The cutaneous lesions and symptoms dramatically improved after the treatment regimen changed to oral sulodexide (250 lipasemic units) three times daily. Sulodexide, a highly purified mixture of glycosaminoglycans including dermatan sulfate and low-molecular weight heparin, could be an effective therapy for recalcitrant livedoid vasculopathy. Herein, we report a case of livedoid vasculopathy treated with sulodexide, which has not previously been reported.