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.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Systematic review and meta-analysis: Effect of Helicobacter pylori eradication on chronic spontaneous urticaria.

BACKGROUND: Helicobacter pylori (HP) infection is considered to play a role in the pathogenesis of chronic spontaneous urticaria (CSU). However, the efficacy of HP eradication therapy on CSU symptom improvement has not been well established. This meta-analysis was conducted to estimate the association between HP infection and CSU and to evaluate whether HP eradication therapy benefits patients with CSU. MATERIAL AND METHODS: In October 2018, we searched databases for studies investigating the efficacy of HP eradication therapy for patients with CSU. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using random effects models. RESULTS: The meta-analysis included 22 studies with a total of 1385 patients with CSU. When comparing the spontaneous remission of urticarial symptom in patients with HP-positive to HP-negative patients, HP-negative patients showed significantly higher spontaneous remission of urticarial symptoms. (risk ratio 0.39; 95% confidence interval: 0.19-0.81). Among HP-positive CSU patients, remission of CSU was more likely shown in HP eradication therapy group compared to untreated group, aside from achieving HP elimination (risk ratio 2.10; 95% confidence interval: 1.20-3.68). However, there was no significant difference in the remission of CSU whether antibiotic therapy was successful in eradication of HP or not (risk ratio 1.00; 95% confidence interval: 0.65-1.54). CONCLUSIONS: The results of this meta-analysis show that HP might be associated with the occurrence and persistence of CSU. The effectiveness of HP eradication therapy in suppressing CSU symptoms was significant. Interestingly, we found that resolution of CSU was not associated with successful eradication of HP infection. CSU Patients who were undergone antibiotic therapy for HP eradication showed significant higher CSU remission with or without HP eradication. Further studies are recommended to evaluate the mechanisms associated with relation of HP with CSU.

Clinicopathologic Features and Prognostic Factors of Primary Cutaneous Melanoma: a Multicenter Study in Korea.

BACKGROUND: Malignant melanoma is a cutaneous malignancy with a high mortality rate and high potential for metastases. Detailed information on the clinicopathologic characteristics and prognostic factors of cutaneous melanoma is currently limited in Korea. This study aimed to identify the epidemiological and clinicopathologic characteristics of primary cutaneous melanoma in Korean patients, and to assess which prognostic variables could influence both the development of metastases in primary cutaneous melanoma and overall survival (OS). METHODS: A total of 261 patients diagnosed with primary cutaneous melanoma in seven medical centers between 1997 and 2017 were retrospectively investigated with regard to clinical presentation, localization of the tumor, histopathologic subtype, and survival time. RESULTS: The nodular histologic subtype, ulceration, and Breslow thickness were significantly associated with the development of metastasis; and overweight and obesity (body mass index > 23) were significantly associated with increased Breslow thickness. The location of the metastases appeared to influence OS: brain metastases were associated with the highest risk of death, followed by gastrointestinal, lung, and extra-regional lymph node metastases. CONCLUSION: In this study, tumor thickness, nodular histologic subtype, and ulceration predicted metastatic spread of primary cutaneous melanoma. In addition, OS was associated with the location of metastases. Obesity was related to the prognosis of primary cutaneous melanoma. Clinicians should bear these findings in mind when forming a diagnosis because of the risk of a poor prognosis.

Psychological Health Status and Health-related Quality of Life in Adults with Atopic Dermatitis: A Nationwide Cross-sectional Study in South Korea.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Patients with AD often experience psychological distress and poor health-related quality of life (HRQoL). The aim of this study was to investigate the association of several psychological health statuses and poor HRQoL in an adult population with AD in South Korea. A total of 37,578 adults who participated in the Korean National Health and Nutrition Examination Survey, a nationwide, population-based, cross-sectional health survey between 2008 and 2013 were included. HRQoL was assessed by EuroQoL (EQ) 5-dimension questionnaire and EQ-visual analogue scale scores. Multiple logistic regression analysis was performed to identify the association of stress, sleep duration, depressive mood, depression, suicidal ideation, and HRQoL with AD relative to matched controls. After adjusting in patients with AD confounding factors, stress, depressive mood, depression, suicidal ideation and poor HRQoL were significantly associated with AD. Dermatologists should be concerned with improving HRQoL and managing the psychological health status of adult patients with AD.

Factors Associated With Achieving Complete Skin Clearance Compared to Almost Complete Skin Clearance in Patients With Moderate to Severe Psoriasis Treated With Biologics: A Retrospective Chart Review.

BACKGROUND: Biologics have demonstrated high efficacy in achieving 'almost complete' skin clearance in patients with moderate to severe psoriasis. Nonetheless, achieving 'complete' skin clearance remains a treatment goal for some highly biologics-resistant patients, as residual lesions impact their quality of life. OBJECTIVE: The risk factors for failure to achieve a Psoriasis Area and Severity Index (PASI) 100 response in patients with good response to biologics remain unknown. METHODS: This retrospective study evaluated the risk factors by comparing patients who achieved complete skin clearance (PASI100) with those who achieved almost complete skin clearance (PASI90). A database of 131 psoriasis patients treated with biologics, who achieved a PASI90 or PASI100 response, was reviewed from a tertiary referral hospital in South Korea. The patients were classified into PASI90 and PASI100 groups according to their PASI response. RESULTS: The PASI100 group had a lower prevalence of smoking history (adjusted odds ratio [OR], 0.34; 95% confidence interval [CI], 0.14-0.85; p=0.021) and psoriasis on the anterior lower legs at baseline (adjusted OR, 0.18; 95% CI, 0.03-0.99; p=0.049) than patients in the PASI90 group. CONCLUSION: This study suggested that smoking history and psoriatic skin lesions on the anterior lower legs are considered as the risk factors for the failure to achieve a PASI100 response in psoriasis patients treated with biologics.

Gelsolin as a Potential Clinical Biomarker in Psoriasis Vulgaris.

Although discovering novel biomarkers for psoriasis is challenging, it may play an essential role in diagnosis, severity assessment, and prediction of treatment outcome and prognosis. The study was aimed to determine potential serum biomarkers of psoriasis via proteomic data analysis and clinical validity assessment. Thirty-one subjects manifested psoriasis and 19 subjects were healthy volunteers who were enrolled in the study. Protein expression was performed via two-dimensional gel electrophoresis (2-DE) using psoriasis patients' sera before and after treatment and sera of patients without psoriasis. Image analysis was then performed. Nano-scale liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments subsequently identified points showing differential expression in 2-DE image analysis. To measure levels of candidate proteins to validate results obtained from 2-DE, enzyme linked immunosorbent assay (ELISA) was then conducted. Gelsolin was identified as a potential protein through LC-MS/MS analysis and database search. Serum gelsolin levels were lower in the groups of psoriasis patients before treatment than in the control group and the group of psoriasis patients after treatment. Additionally, in subgroup analysis, serum gelsolin level was correlated with various clinical severity scores. In conclusion, low serum gelsolin levels are associated with the severity of psoriasis, proposing the potential role of gelsolin as a biomarker for severity assessment and evaluation of treatment response of psoriasis.

A Case of Generalized Xerotic Eczema in a Patient with Congenital Insensitivity to Pain with Anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disease characterized by insensitivity to pain, anhidrosis, and intellectual disability. CIPA is caused by a genetic mutation in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene on chromosome 1. The anhidrosis leads to cutaneous changes such as skin dryness, lichenification, and impetiginization. Moreover, patients with CIPA may experience repeated trauma and recalcitrant eczema due to excessive scratching of wounds on their skin, because they do not feel any pain. Severe whole-body eczema in a patient with CIPA may be overlooked, leading these patients to be frequently diagnosed with atopic dermatitis and common eczema. Indeed, in patients with treatment-resistant or atypically distributed eczema and underlying anhidrosis, CIPA should be considered as a potential causative disease. Increased awareness of CIPA among dermatologists is necessary to ensure that patients receive an appropriate diagnosis. Herein, we report a rare case of generalized xerotic eczema in a patient with CIPA.

Erratum: Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

This corrects the article on p. 419 in vol. 34, PMID: 36478424.

Painful eccrine spiradenoma containing nerve fibers: a case report.

An eccrine spiradenoma is a rare benign tumor most often seen in the head, neck and upper trunk of young adults. Although spontaneous pain or tenderness is a typical symptom of eccrine spiradenomas, the underlying mechanism has not been fully elucidated. Here, we report the case of a 47- year-old woman who had a spiradenoma in the subcutaneous tissue of her posterior neck accompanied by agonizing pain which was triggered by pressure. Multiple nodular lesions were excised and the typical histopathological findings of spiradenoma were seen. The histopathological architecture of a disorganized nerve fiber encasing the tumor nodules appeared to correlate with the unique clinical symptom of pain.

Prevalence and risk factors for atopic dermatitis: a cross-sectional study of 6,453 Korean preschool children.

The aims of this study were to evaluate the prevalence, severity and risk factors for atopic dermatitis in Korean pre-school children as determined by dermatological examination vs questionnaire survey. A total of 6,453 pre-school children from 59 kindergartens and 14 day-care centres were evaluated. Parents responded to an International Study of Asthma and Allergies in Childhood (ISAAC)-based questionnaire containing questions concerning 23 risk factors, as well as the prevalence, and severity of atopic dermatitis. Fourteen dermatologists then examined the participants according to the Korean diagnostic criteria for atopic dermatitis, and the Eczema Area and Severity Index (EASI) score. Atopic dermatitis prevalence determined by dermatological examination was lower than the questionnaire-based prevalence (9.2% vs 19.1%). Most patients (96.2%) had mild atopic dermatitis according to the EASI score (mean ± SD 3.91 ± 4.73; median 1.5; range 0.2-38.0). However, 17.4% had sleep disturbance, and 56.7% had not obtained complete remission of their rash over the previous 12 months. Among the 12 risk factors, "changing the patient's house to a newly built house during the first year of life" had significant odds ratio. In conclusion, the prevalence of atopic dermatitis in Korea in the ISAAC-based survey conducted by paediatricians was similar to that in several European countries, and lower than the 2006 Korean figure (28.9%). In addition, the prevalence of atopic dermatitis was lower when assessed by dermatological examination than by questionnaire.

Quality of life and disease severity are correlated in patients with atopic dermatitis.

Quantification of quality of life (QOL) related to disease severity is important in patients with atopic dermatitis (AD), because the assessment provides additional information to the traditional objective clinical scoring systems. To document the impact of AD on QOL for both children and adults as well as to quantify the relationship with disease severity, QOL assessments were performed over a 6-month period on 415 patients with AD. A questionnaire derived from the Infants' Dermatitis Quality of Life Index (IDQOL), the Children's Dermatology Life Quality Index (CDLQI) and the Dermatology Life Quality Index (DLQI) was used to determine the QOL for 71 infants, 197 children and 147 adults, respectively. To measure AD severity, both the Rajka & Langeland scoring system and the Scoring of Atopic Dermatitis (SCORAD) index were used. The mean scores were as follows: 7.7 ± 5.5 for IDQOL, 6.6 ± 6.3 for CDLQI, and 10.7 ± 7.9 for DLQI. In conclusion, these QOL scores are correlated with AD severity scores as estimated by the Rajka & Langeland severity score and the SCORAD. The outcome of the QOL instruments in this study demonstrates that atopic dermatitis of both children and adults affects their QOL.

Clinical Implication of Serum Adiponectin Levels in Adult Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is characterized by chronic, relapsing, pruritic inflammatory skin disease. Adiponectin has been reported to have anti-inflammatory effects not only on metabolic disorders but also on various inflammatory disorders. The study aimed to validate adiponectin as a potential biomarker for AD disease severity and treatment response. Seventy-five patients with AD and 28 healthy volunteers were enrolled in the study. Patient information, including Eczema Area and Severity Index (EASI) scores and pruritus numeric rating scales (NRSs), were collected. An enzyme linked immunosorbent assay (ELISA) was conducted to measure levels of serum adiponectin. Additionally, sera of patients treated with dupilumab were collected and measured at 16 and 52 weeks from baseline. Serum adiponectin levels were significantly lower in moderate and severe AD patients than in the control and mild AD patients. Serum adiponectin level was negatively correlated with the EASI score and pruritus NRS. However, no significant changes were observed according to biologic treatment for AD. Low serum adiponectin levels are associated with moderate to severe AD, suggesting a potential role for adiponectin as a biomarker for severity assessment of AD.

Relationships of Serum Homocysteine, Vitamin B12, and Folic Acid Levels with Papulopustular Rosacea Severity: A Case-Control Study.

Background: Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin B12 in patients with rosacea. Objective: To investigate serum Hcy, vitamin B12, and folic acid levels in patients with papulopustular rosacea (PPR), we characterized the association of these levels with PPR severity. Methods: This case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin B12, and folic acid were measured. A correlation was assessed between disease severity and serum levels of Hcy, vitamin B12, and folic acid. Results: Serum vitamin B12 and folic acid levels were significantly lower in PPR patients than in the healthy controls (p = 0.011 and p = 0.0173, respectively). Although serum Hcy levels did not significantly differ between PPR patients and healthy controls, PPR severity was positively correlated with serum Hcy levels (p < 0.001). Conclusions: Our results suggest a possible association between hyperhomocysteinemia and vitamin B12 deficiency in patients with PPR.

Assessment of Disease Severity and Quality of Life in Patients with Atopic Dermatitis from South Korea.

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited. OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea. METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. RESULTS: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt. CONCLUSION: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

Association between Skin Cancer and Systemic and Ocular Comorbidities in South Korea.

BACKGROUND: In this study, we investigated the associations between various systemic and ocular comorbidities and skin cancer, in a nationwide cohort of South Koreans. METHOD: We reviewed the data of 1,103,302 individuals in the South Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2015. Of these, 1202 individuals diagnosed with skin cancer from 2004 were included in the study group. The control group was matched in a 1:5 ratio based on propensity scores. RESULTS: The prevalence rates of melanoma and non-melanoma skin cancer increased from 2004 to 2015. Multivariate logistic regression analysis revealed that, among the various systemic conditions, hypertension was significantly associated with skin cancer, while among ocular comorbidities, macular degeneration showed a significant association with skin cancer. CONCLUSIONS: This is the first study to demonstrate associations between skin cancer and various systemic and ocular comorbidities. The results suggest that hypertension and macular degeneration may increase the risk of skin cancer development, or vice versa. Further studies are needed to evaluate the causal relationships between these conditions.

Consensus Update for Systemic Treatment of Atopic Dermatitis.

BACKGROUND: In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). OBJECTIVE: We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. METHODS: We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. RESULTS: We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. CONCLUSION: We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Clinical outcomes in adult patients with plaque psoriasis treated with ustekinumab under real-world practice in Korea: A prospective, observational, multi-center, postmarketing surveillance study.

Postmarketing surveillance is conducted to establish drug safety and effectiveness under real-world practice. We aimed to validate the effectiveness and safety of ustekinumab in the treatment of adult Korean patients with plaque psoriasis under real-world practice. This was a prospective, observational, and multi-center study. Subjects aged 18 years or older who were treated with ustekinumab for plaque psoriasis were enrolled. We enrolled 977 patients; 654 (66.9%) were men, with mean body surface area (BSA, ± standard deviation) of 27.0 ± 18.3% and mean psoriasis area severity index (PASI) score of 18.1 ± 9.7. The effectiveness analysis was performed in 581 patients who had at least one follow-up assessment and met treatment criteria per local label and reimbursement guidelines. Of these patients, 287 had effectiveness data for visit 6 at 53.7 ± 2.1 weeks. At visit 6, 91.6% (263/287), 51.2% (147/287), and 9.4% (27/287) patients achieved PASI 75, 90, and 100 responses, respectively. Adverse events (AEs) occurred in 112 of the 977 (11.5%) patients with an incidence rate of 21.5 per 100 patient-years (PYs). Serious AEs occurred in eight (0.8%) patients with an incidence rate of 1.2 per 100 PYs. The estimated 1-year drug survival rate was 87.7%. The multiple logistic regression analysis showed that higher baseline PASI score and no prior biologic exposure were significant predictors for PASI 90 response at visit 6. Ustekinumab was effective and safe, and displayed a high survival rate in the treatment of adult Korean patients with plaque psoriasis in real-world practice.

Perceptions and Behavior Regarding Skin Health and Skin Care Products: Analysis of the Questionnaires for the Visitors of Skin Health Expo 2018.

BACKGROUND: Social standards for skin health have changed and have led to a rise in the general population's interest to achieve flawless skin. OBJECTIVE: To survey the Korean public's perception of skin health and dermatologists and skin-health-related behaviors. METHODS: A total of 355 participants of the Skin Health Expo 2018, held by the Dermatological Research Foundation of the Korean Dermatological Association from September 14 to 16, 2018, completed a questionnaire that assessed demographics, status, and behaviors regarding skin health. The questionnaire also included lifestyle characteristics, satisfaction, behavioral factors, and perceptions regarding skin-care products. RESULTS: Participants were using various skin-care products including toners, lotions, hydrating or nutrition creams, sunscreens, essences, serums, facial masks and packs, body, hand, and foot moisturizers, eye creams, and hair products. The participants believed that the most reliable source of information on skin-care product recommendations was the dermatologist (41.55%). However, purchases were also being made at skin-care product stores (27.64%) based on the recommendation of a friend or acquaintance (40.11%). The results also revealed that 23.8% of participants experienced side effects from using skin-care and cosmetic products, and about 40% of participants could not yet distinguish hospitals run by dermatologists. CONCLUSION: Demand for skin-care products has been increasing, and dermatologists should provide proper information about skin health to prevent adverse effects from skin-care products. Educational and informative activities, such as the expo planned by dermatologists, are necessary to improve skin health in the general population.