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.

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.

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.

The risk of alopecia areata and other related autoimmune diseases in patients with sleep disorders: a Korean population-based retrospective cohort study.

Study Objectives: The aim of our study was to investigate the risk of alopecia areata occurrence in patients with sleep disorders. Methods: This study was a retrospective cohort study based on the National Health Insurance Service-National Sample Cohort database of patients with a sleep disorder, along with age- and sex-matched control subjects from 2003 to 2013. The hazard ratio (HR) of alopecia areata was compared between the patients with sleep disorders and control subjects adjusting comorbid diseases which could affect the incidence of alopecia areata. We also compared the prevalence of comorbid diseases in the patients with sleep disorders and control subjects. Results: Among the 25,800 patients with sleep disorders and the 129,000 control subjects, patients with sleep disorders were at a significantly increased risk for alopecia areata when compared with control subjects (adjusted HR 1.651 [95% CI 1.382-1.974]), especially in younger age groups (0-24 and 25-44 years). In a multivariate logistic analysis, sleep disorders were not only associated with alopecia areata (OR 1.913 [95% CI 1.717-2.171]), but also with other comorbid diseases, including solid-organ cancers (OR 1.099 [95% CI 1.049-1.151]), Graves' disease (OR 1.717 [95% CI 1.562-1.886]), Hashimoto thyroiditis (OR 1.641 [95% CI 1.413-1.905]), vitiligo (OR 1.539 [95% CI 1.236-1.917]), and rheumatoid arthritis (OR 1.886 [95% CI 1.780-1.998]). Conclusions: This study demonstrated that sleep disorder is an independent risk factor for alopecia areata, especially in individuals under the age of 45 years old.

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.

Serum Zinc Status and Its Association with Allergic Sensitization: The Fifth Korea National Health and Nutrition Examination Survey.

Zinc (Zn) is an essential trace element that plays important roles in the immune system. There is little known about the role of trace elements in allergic diseases, and previous reports have shown conflicting results. The aim of this study was to investigate the relationship between serum Zn levels and total or allergen-specific immunoglobulin E (IgE) levels. The initial candidates for this study were those who participated in the 5th Korean National Health and Nutrition Examination Survey 2010 (n = 8,958), and 1,867 adults who had serum total and allergen specific-IgE levels measured were included. Upon adjusting for covariates, mean total IgE, Dermatophagoides farinae and dog-specific IgE levels increased significantly as the Zn levels decrease from the highest to the lowest quartile (p = 0.009, 0.004, and < 0.001, respectively). The multiple logistic regression analyses showed significant negative linear correlations between serum Zn levels and total, D. farinae-, cockroach-, and dog-specific IgE levels (p-value for linear trend = 0.004, 0.006, 0.027, and < 0.001, respectively). This study demonstrated that total/allergen specific IgE and Zn levels are significantly inversely related.

Antiviral prophylaxis for preventing herpes zoster in hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

The optimal duration of prophylaxis for the varicella-zoster virus following hematopoietic stem cell transplantation (HSCT) remains unclear. The purpose of this study was to systematically review the available literature to determine the optimal duration of antiviral prophylaxis for preventing herpes zoster (HZ) in allogeneic and autologous HSCT recipients. The MEDLINE and EMBASE databases were searched to identify relevant studies. The relative risk (RR) of HZ was calculated using fixed effects or random effects models depending on heterogeneity across the included studies. We analyzed six observational studies comprising a total of 3420 patients. In all HSCT recipients, the overall incidence of HZ in the prophylaxis group and the control group was 7.8% and 25.6%, respectively, with a pooled RR of 0.31 (95% CI, 0.26-0.37). The incidence of HZ in the subgroup wherein prophylaxis was given for at least 1 year and in the subgroup wherein prophylaxis was given for less than 1 year was 2.1% and 15.4%, respectively, with a pooled RR of 0.23 (95% CI, 0.04-1.39). Taken together, our results demonstrate that antiviral prophylaxis can significantly reduce HZ in HSCT recipients, and suggests that long-term prophylaxis given for at least 1 year may be recommended for better preventive effects.

Prospective Comparison of Dual Wavelength Long-Pulsed 755-nm Alexandrite/1,064-nm Neodymium:Yttrium-Aluminum-Garnet Laser versus 585-nm Pulsed Dye Laser Treatment for Rosacea.

BACKGROUND: Rosacea treatments including oral/topical medications and laser therapy are numerous but unsatisfactory. OBJECTIVE: To compare the effectiveness of the dual wavelength long-pulsed 755-nm alexandrite/1,064-nm neodymium: yttrium-aluminum-garnet laser (LPAN) with that of 585-nm pulsed dye laser (PDL) for rosacea. METHODS: This was a randomized, single-blinded, comparative study. Full face received four consecutive monthly treatments with LPAN or PDL, followed-up for 6 months after the last treatment. Erythema index was measured by spectrophotometer, and digital photographs were evaluated by consultant dermatologists for physician's global assessment. Subjective satisfaction surveys and adverse effects were recorded. RESULTS: Forty-nine subjects with rosacea enrolled and 12 dropped out. There were no significant differences between LPAN and PDL in the mean reduction of the erythema index (p=0.812; 3.6% vs. 2.8%), improvement of physician's global assessment (p=1.000; 88.9% vs. 89.5%), and subject-rated treatment satisfaction (p=0.842; 77.8% vs. 84.2%). PDL showed more adverse effects including vesicles than LPAN (p=0.046; 26.3% vs. 0.0%). No other serious or permanent adverse events were observed in both treatments. CONCLUSION: Both LPAN and PDL may be effective and safe treatments for rosacea.

Case of Pleomorphic Dermal Sarcoma of the Eyelid Treated with Micrographic Surgery and Secondary Intention Healing.

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal neoplasm sharing histopathological features with atypical fibroxanthoma (AFX), but has additional features of deep invasion of the superficial subcutis, tumor necrosis and vascular/perineural invasion. It is not well documented in the literature because of its rarity, and its clinical course has been debated due to the lack of homogenous criteria. We describe here the case of a 91-year-old female with a 6-month history of a solitary, asymptomatic, well-defined, 3.4-cm-sized, reddish, hard, protruding mass on the lateral aspect of the right upper eyelid. On the basis of initial punch biopsy results, storiform cellular infiltrate of pleomorphic spindle and polygonal cells with frequent atypical mitoses, the lesion was identified as AFX. Following the initial biopsy, micrographic surgery was performed and a tumor-free margin was confirmed. Considering the conservation of the periocular function and the advanced age of the patient, we planned secondary intention healing rather than primary suturing. After surgery, skeletal muscle infiltration was found and the diagnosis was revised to PDS by a pathologist based on the currently accepted criteria for PDS. There has been no evidence of recurrence or periocular functional defects during a 2-year follow-up without adjuvant therapy. Although the PDS is highly malignant, complete excision under micrographic surgery can prevent recurrence without adjuvant therapy. Also, the secondary intention healing is an effective method for closure of large defects on the face.

Effects of repetitive photodynamic therapy using indocyanine green for acne vulgaris.

BACKGROUND: Indocyanine green (ICG) is a photosensitizer recently introduced for the treatment of acne. OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) using ICG in subjects with acne vulgaris and to evaluate whether there was a difference in the efficacy of ICG-PDT between different numbers of treatment. MATERIALS AND METHODS: Subjects with acne on the face were included. ICG lotion (0.1%) was applied for 30 minutes, and a long pulse diode laser was used. Three or five treatments per subject were performed over 2 weeks. Acne lesion counts and Leeds revised acne grades were evaluated at baseline and 2 weeks after the last treatment. RESULTS: In total, 47 subjects completed the study. After both three and five ICG-PDT sessions, a significant reduction in acne lesions and significant improvement in Leeds revised acne grades were found in all treated subjects compared to baseline. In the subjects receiving five ICG-PDT sessions, the reduction of papules/pustules was greater than in the subjects receiving three ICG-PDT sessions (P < 0.01, respectively). However, there was no significant change in the count of nodules/cysts, although it is a negative trend (P = 0.066). Adverse effects were minimal. CONCLUSION: ICG-PDT using long-pulsed diode laser can be a safe and effective tool for acne vulgaris. Moreover, repetitive treatments of five can cause further improvement of inflammatory acne lesions.

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.

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.