Increased risk of suicidality in patients with psoriasis: A Nationwide cohort study in Korea.

BACKGROUND: Psoriasis has a devastating psychological impact on patients' quality of life. However, the relationship between suicidality and psoriasis remains unclear. OBJECTIVE: This study analysed and compared the risk of suicidality (suicidal ideation, suicide attempt and completed suicide) between patients with psoriasis and the general population. METHODS: This nationwide, population-based, retrospective, cohort study analysed the Korean National Health Insurance Service claim data from 2005 to 2018. RESULTS: The study included 348,439 patients with psoriasis aged over 18 years and with age- and sex-matched controls. The risk of suicidality was higher in the psoriasis group than in the control group [adjusted hazard ratio (aHR) 1.21; 95% confidence interval (CI), 1.18-1.24]. The aHR of suicidality was higher in the psoriatic arthritis group (aHR, 1.46; 95% CI, 1.39-1.54) than in the psoriasis-alone group (aHR, 1.17; 95% CI, 1.13-1.20). However, the severity of psoriasis and suicidality showed no correlation (mild psoriasis group: aHR, 1.22; 95% CI, 1.18-1.25; moderate-to-severe psoriasis group: aHR, 1.16; 95% CI, 1.10-1.23). CONCLUSION: Patients with psoriasis have an increased risk of suicidality. In particular, the presence of arthritis in patients had a more significant effect on the risk of suicidality.

Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.

c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer.

BACKGROUND: Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. METHODS: Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. RESULTS: Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Lauren's classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. CONCLUSIONS: Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition.

Endocrine and metabolic comorbidities in primary cicatricial alopecia: A nationwide population-based study.

Primary cicatricial alopecia (PCA) is a rare, scarring, hair loss disorder. Due to its low incidence, little is known about endocrine and metabolic comorbidities in patients with PCA. Thus, we aimed to investigate the association between PCA and endocrine and metabolic disorders. This nationwide, population-based, cross-sectional study included patients diagnosed with PCA or non-cicatricial alopecia (NCA) and normal individuals without history of alopecia registered in the Korean National Health Insurance Service database between January 1, 2011, and December 31, 2020. We calculated the odds ratios of endocrine and metabolic comorbidities of patients with PCA compared to all patients or age- and sex-matched patients with NCA or normal individuals using multivariable logistic regression models. A total of 3 021 483 individuals (mean age [SD], 38.7 [15.0] years, 1 607 380 [53.2%] men), including 11 956 patients with PCA, 601 852 patients with NCA, and 2 407 675 normal participants, were identified. Patients with PCA had an increased risk for dyslipidemia (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.06-1.24), diabetes (aOR 1.38, 95% CI 1.24-1.53), and hypertension (aOR 1.10, 95% CI 1.02-1.19) compared to matched patients with NCA. Regarding PCA subtypes, lichen planopilaris/frontal fibrosing alopecia was positively associated with hypothyroidism (aOR 2.03, 95% CI 1.44-2.86) compared to NCA. Folliculitis decalvans and dissecting cellulitis were positively associated with dyslipidemia (aOR 1.16, 95% CI 1.05-1.28 and aOR 1.16, 95% CI 1.04-1.29, respectively), diabetes (aOR 1.38, 95% CI 1.20-1.58 and aOR 1.52, 95% CI 1.32-1.74, respectively), and hypertension (aOR 1.10, 95% CI 1.00-1.20 and aOR 1.14, 95% CI 1.02-1.27, respectively). Similar trends were observed when each PCA subgroup was compared with the normal control group. This study demonstrates that patients with PCA are more likely to have endocrine and metabolic comorbidities than patients without PCA. Further research on these comorbidities may improve the understanding of PCA.

Hair loss after drug reaction with eosinophilia and systemic symptoms (DRESS): A multicentric retrospective case series.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug adverse reaction characterized by various cutaneous and systemic manifestations. However, reports on the various patterns of alopecia after DRESS are lacking. Thus, we aimed to describe cases of alopecia after DRESS and review the literature. This multicentric retrospective study reviewed the records of 182 patients diagnosed with DRESS from 2009 to 2021; of these, 10 who had alopecia after DRESS were included. Patients were diagnosed with permanent alopecia (n = 4), telogen effluvium (n = 5), and alopecia areata (n = 1), and were treated with topical minoxidil or alfatradiol (6; 60%), topical corticosteroids (3; 30%), dietary supplements (6; 60%), systemic corticosteroids (1; 10%), and intralesional corticosteroid injection (2; 20%). Although patients with permanent alopecia did not show hair regrowth after 6 months, those with telogen effluvium and alopecia areata experienced marked clinical improvement within 6 months. Various types of alopecia can persist over an extended period, even after the resolution of an acute episode of DRESS.

Assessment of Effects of Low-Level Light Therapy on Scalp Condition and Hair Growth.

Background: The appearance of the scalp and hair is very important aesthetically regardless of age or sex. Although there are many drugs and treatment methods for scalp problems and hair loss, the treatment response is still insufficient. Aims and Objectives: To evaluate the efficacy of low-level light therapy in a helmet-like device. Materials and Methods: This study was designed as a 24-week trial with 50 participants. All participants used a helmet-shaped device emitting 630-690, 820-880, and 910-970 nm light wavelengths, for 20 minutes, daily for 24 weeks. A phototrichogram for hair density and thickness, Global Aesthetic Improvement Scale score, erythema index, and sebum secretions of the scalp were evaluated at baseline and at 12 and 24 weeks. Results: After 24 weeks of treatment, hair density and hair thickness were found to have significantly increased (P <.01 and P =0.013, respectively) and sebum secretion of vertex area had decreased significantly (P <.01). Of 49 participants, 73.47% of the participants showed improvement in the overall appearance of the scalp (n = 36). Conclusion: A helmet-like low-level light therapy device can improve the appearance of the hair, with thickening and increase in the density of the hair, and can improve scalp condition by decreasing sebum secretion.

The Relationship Between Rosacea and Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

INTRODUCTION: Rosacea and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the skin and the gut, which are interfaces between the environment and the human body. Although growing evidence has implicated a possible link between rosacea and IBD, it remains unclear whether IBD increases the risk of rosacea and vice versa. Therefore, we investigated the association between rosacea and IBD in this study. METHODS: We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. RESULTS: Eight eligible studies were included in this meta-analysis. Overall, the prevalence of rosacea was higher in the IBD group than in the control group, with a pooled odds ratio (OR) of 1.86 (95% confidence interval [CI](1), 1.52-2.26). Both the Crohn's disease and the ulcerative colitis groups had higher prevalences of rosacea than the control group, with ORs of 1.74 (95% CI 1.34-2.28) and 2.00 (95% CI 1.63-2.45), respectively. Compared with those in the control group, the risks of IBD, Crohn's disease, and ulcerative colitis were significantly higher in the rosacea group, with incidence rate ratios of 1.37 (95% CI 1.22-1.53), 1.60 (95% CI 1.33-1.92), and 1.26 (95% CI 1.09-1.45), respectively. CONCLUSION: Our meta-analysis suggests that IBD is bidirectionally associated with rosacea. Future interdisciplinary studies are needed to better understand the mechanism of interaction between rosacea and IBD .

Serious infections and tuberculosis in psoriasis patients receiving systemic therapy in Korea: a nationwide population-based cohort study.

BACKGROUND: Psoriasis itself, as well as its immunomodulatory drugs, may alter the immune system, increasing the risk of infections. Recent research has indicated that patients with psoriasis are at an increased risk of developing severe infections including tuberculosis. OBJECTIVES: To evaluate and compare the incidence of serious infectious diseases in Korea between patients with psoriasis and participants without psoriasis regarding each treatment modality. MATERIALS & METHODS: This nationwide cohort study utilized claims data based on the National Health Insurance Service between January 2005 and December 2018. RESULTS: In total, 293,073 patients with psoriasis enrolled for the analysis of serious infection and 272,400 patients enrolled for the analysis of tuberculosis. Participants without psoriasis matched by age and sex (1:1 ratio) were also enrolled. For serious infection overall, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.21 (1.20-1.23), 1.23 (1.17-1.28), and 1.33 (1.09-1.63) for the non-systemic, non-biologic systemic, and biologic groups, respectively. For tuberculosis overall, the aHRs were 1.15 (1.10-1.20), 1.32 (1.10-1.57), and 6.72 (4.28-10.56) for the non-systemic, non-biologic systemic, and biologic groups, respectively. CONCLUSION: This study reveals that the risk of serious infection and tuberculosis in patients with psoriasis was significantly higher than in participants without psoriasis. Moreover, patients with psoriasis who received systemic therapy other than phototherapy had a higher risk of these infections compared to those without psoriasis. Also, biologics appeared to increase the risk of tuberculosis in patients with psoriasis. Dermatologists should consider these potential risks when selecting treatment modalities for psoriasis.

Early onset female pattern hair loss: A case-control study for analyzing clinical features and genetic variants.

BACKGROUND: Female pattern hair loss (FPHL), the most common cause of alopecia in adult women, is classified into two subtypes: early onset and late onset (or postmenopausal). Little is known about the clinical features and genetic characteristics of early onset female pattern hair loss (eFPHL). OBJECTIVES: To investigate the clinical features and genetic characteristics of eFPHL. METHODS: Patients with eFPHL and controls without eFPHL were prospectively recruited. The demographic and clinical features were collected. Single nucleotide polymorphisms (SNPs) located around the selected 30 candidate genes potentially associated with eFPHL were evaluated. RESULTS: eFPHL patients (n = 63) manifested a decreased hair shaft density and cross-sectional area of the hair shaft compared to the control group (n = 341). eFPHL is associated with androgen-related features, including scalp greasiness, folliculitis, hirsutism, and polycystic ovary syndrome. Scalp pain and itching have been reported more frequently in patients with eFPHL. Forty-nine SNPs located around PPARGC1A, ABCC4, CYP11B2, FSHB, and CYP19A1 were found to be significant for eFPHL, including two PPARGC1A-associated SNPs: rs186530605 and rs192713767 (p = 3.94 × 10-11). CONCLUSIONS: This study provided clinical features and genetic variants for eFPHL, which could provide insight into the underlying pathologic etiology. Considering the limited number of patients, a large-scale study is required in the future.

Good Clinical Responders to Topical Timolol in Patients with Infantile Hemangiomas: A 7-Year Retrospective Study of 328 Korean Patients.

BACKGROUND: Topical timolol is widely used for treatment of superficial infantile hemangioma (IH). However, little is known about factors that affect the response to topical timolol treatment. OBJECTIVE: This study aimed to investigate the efficacy, safety, and predictive value for good response to topical timolol for IH. METHODS: A retrospective review of medical records and clinical photos of 328 patients with IH treated with topical timolol 0.5% solution was conducted. Serial clinical photographs were compared with those at the initial visit using a 100-mm visual analogue scale (VAS). Treatment response was defined as an improvement of at least 75% from baseline in IH lesions within 12 months of treatment. RESULTS: Overall, IH patients treated with topical timolol showed significant improvement from baseline, showing that the final VAS score within 12 months of treatment was 69.7±20.4. The multivariable logistic regression analysis showed age at initiation of treatment (p=0.007), length of gestation and fetal growth (p=0.03), depth (p=0.01), and flexural area (p=0.007) were significantly associated with treatment response. Only four patients (1.1%) reported local irritation. CONCLUSION: This study demonstrated that topical timolol treatment was an effective and well-tolerated treatment for IHs. Physicians are encouraged to consider several patient- or lesional factors that might affect treatment response to achieve better clinical outcomes.

Analysis of the Microbiome of the Ear Canal in Normal Individuals and Patients with Chronic Otitis Externa.

BACKGROUND: Recently, microbiome research has been actively conducted for various skin areas. However, no study has yet compared the microbiome of bacteria and fungi in the ear canal of healthy individuals and patients with chronic otitis externa in Korea. OBJECTIVE: This study aimed to investigate the difference in the distribution of fungal and bacterial microbial communities in ear canal samples of healthy individuals and patients with chronic otitis externa. METHODS: In 24 patients with bilateral chronic otitis externa and 24 healthy controls, cotton swabs were used to obtain samples from the bilateral ear canal. To characterize the fungal and bacterial communities, we sequenced and analyzed the 16S rRNA V4-V5 and ITS1 regions using Quantitative Insights into Microbial Ecology 2, respectively. RESULTS: The alpha diversity analysis for bacteria and fungi confirmed that both richness and evenness decreased in the patient group. The beta diversity analysis for bacteria confirmed that these parameters differed between the control and patient groups. The beta diversity analysis for fungi showed no difference between the groups. CONCLUSION: We observed different skin microbiomes in the patients with chronic otitis externa compared with those in the healthy individuals.

Risk of malignancy in patients with psoriasis according to treatment modalities in Korea: a nationwide cohort study.

Intrinsic immunologic disparity of psoriasis itself, along with chronic inflammation and immunomodulatory anti-psoriatic treatments could be associated with increased risk of malignancy. We aimed to estimate the risk of malignancy in patients with psoriasis by treatment modality compared with that in individuals without psoriasis in Korea. We conducted a nationwide cohort study using the claims database of the National Health Insurance Service from January 2005 to December 2018. A total of 255,471 patients with psoriasis, and age- and sex-matched non-psoriasis participants (1:1 ratio) were enrolled. The adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] for malignancy without nonmelanoma skin cancer (NMSC) were 1.10 [1.08-1.12] in patients with psoriasis, 1.13 [1.00-1.27], 1.05 [0.97-1.13], and 1.24 [0.84-1.83] in phototherapy, non-biologic systemics, and biologics cohort, respectively. Among the non-biologic systemics cohort, patients treated with cyclosporin showed higher risk of malignancy without NMSC (aHR [95% CI], 1.20 [1.04-1.39]). The risk of malignancy without NMSC in patients with psoriasis was higher than that in individuals without psoriasis. Phototherapy and biologics were not associated with significant increase of risk; however, cyclosporin appeared to increase its risk. Dermatologists should be vigilant about this potential risk while managing patients with psoriasis.

Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Tofacitinib and ruxolitinib have been used off-label to treat alopecia areata. Although a number of case reports and small studies have been published, there are no comprehensive reviews examining the outcomes of using tofacitinib and ruxolitinib for the treatment of alopecia areata. AIMS: The aim of the study was to examine the outcome of patients with alopecia areata treated with oral tofacitinib or ruxolitinib in previously published studies. METHODS: A search of MEDLINE, Embase and Cochrane library was conducted. A systematic review and meta-analysis were performed focusing on the Severity of Alopecia Tool 50 achievement rate, the frequency of adverse events and recurrence after discontinuation of treatment. RESULTS: A total of 1244 studies were identified of which only 12 studies met the inclusion criteria. Of the 346 patients in these 12 studies, 288 had received oral tofacitinib and 58 had received oral ruxolitinib. The overall Severity of Alopecia Tool50 achievement rate was 66% (95% confidence interval, 54%-76%). Subgroup analysis revealed that drug choice, mean age, sex ratio and alopecia areata subtype ratio did not significantly affect the treatment response. Infections and laboratory abnormalities were the most common adverse events (98 and 65 cases of 319 patients, respectively). Patients treated for more than six months had a greater frequency of laboratory abnormalities as compared to those treated for shorter durations (24% vs. 7%; P = 0.04). Recurrence of alopecia areata was observed within three months after discontinuation of treatment in the majority (74%) of patients. LIMITATIONS: This analysis was limited by the small number of observational studies available for review, the heterogeneity of patient characteristics and the lack of long-term data. CONCLUSION: Both oral tofacitinib and ruxolitinib are effective and well tolerated in the treatment of alopecia areata. Clinicians should be aware of the expected efficacy, adverse events and high recurrence rate of oral JAK inhibitors for alopecia areata to effectively counsel these patients before starting therapy.

Janus kinase inhibitors: An innovative treatment for alopecia areata.

Alopecia areata (AA) is a relatively common disease, but no satisfactory treatment has yet been developed. Recently, research progress has been made in the pathogenesis of AA, revealing that autoreactive cytotoxic T cells are important and that the Janus kinase (JAK) pathway is involved. Therefore, the potential of JAK inhibitors as therapeutic agents for AA is attracting attention. Several single-arm clinical trials and retrospective studies demonstrated that oral JAK inhibitors are effective and tolerable treatments for moderate to severe AA. Although JAK inhibitors are emerging as an innovative treatment for AA, further placebo-controlled clinical trials are required to confirm their efficacy and long-term safety.

Hypomelanosis of Ito with Multiple Congenital Anomalies.

Hypomelanosis of Ito (HI) is a neurocutaneous disorder, also known as incontinentia pigmenti achromians. HI has been associated with chromosomal abnormalities, especially mosaicism. Herein, we report a case of HI with multiple congenital anomalies. A 2-month-old girl presented with multiple linear and whorling hypopigmentation on the face, trunk, and both extremities and patch alopecia on the scalp. Moreover, she had conical teeth, aniridia of the both eyes, and multiple musculoskeletal problems, including syndactyly and coccyx deviation. Cytogenetic analysis on peripheral blood was normal 46, XX, and no mutation was found in IKBKG gene test.

Real-World Experience with Etanercept Therapy and the Switching Pattern among Korean Patients with Psoriasis after Withdrawal of Etanercept.

BACKGROUND: The efficacy and safety of etanercept in the treatment of psoriasis has been proven, and the drug was approved for the treatment of moderate to severe psoriasis. However, there have been few studies that have presented real-world data focused on concomitant treatment during etanercept treatment, and the switching pattern after discontinuation of etanercept. OBJECTIVE: To reveal the real-world treatment pattern of etanercept-based psoriasis treatment and to investigate the switching pattern after withdrawal of etanercept. METHODS: We enrolled 66 patients with psoriasis who were treated with etanercept. We collected data regarding the demographic characteristics of the patients, etanercept treatment schedules, and other treatments administered during the etanercept treatment period. We also investigated the treatment pattern after the discontinuation of etanercept with emphasis on the drug-free interval and the administered treatment modalities. RESULTS: The mean treatment duration was 22.7±26.1 months and the mean number of etanercept injections was 21.5±27.9. Thirty-six patients were administered concomitant systemic medication or phototherapy. After discontinuation of etanercept, 54 patients were followed up and 34 of these patients were administered other systemic medication or phototherapy; phototherapy and cyclosporine was the most commonly administered treatment modality and 27.4% of treatments used biologics. CONCLUSION: The treatment schedule for etanercept was modified according to the severity of psoriasis and concomitant treatment was administered to improve the effectiveness of treatment in the patients enrolled in the study. We also found that most patients required other treatment modalities to control psoriasis during the period of etanercept treatment.