Impact of residual skin lesions and previous biologic treatment failure on patient-reported outcomes in patients with psoriasis receiving biologic treatment.

Recent advances in biologic treatments have made clear skin a realistic treatment goal for psoriasis. However, clear skin may not uniformly translate to an absence of impact on patients' quality of life. This retrospective observational study aimed to elucidate the factors influencing patient-reported outcomes in patients with psoriasis who have demonstrated successful clinician-reported outcomes on using biologics. A total of 96 patients who have achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI) scores with ≥6 months of biologic treatment were included. Their median PASI score was 0.4, with 37.5% having achieved PASI 100 (clear skin). Furthermore, 47.9% reported no impact of psoriasis on their quality of life (Dermatology Life Quality Index [DLQI] score 0 or 1), while 52.1% reported a negative impact (DLQI score ≥2). Notably, 28.1% of the participants had a history of biologic treatment failure, defined as the inability to achieve or sustain a 75% PASI improvement with the previously used biologic agent. Multivariable logistic regression analysis revealed a positive association between achieving PASI 100 and reporting no impact of psoriasis on quality of life (adjusted odds ratio [aOR] 3.88, 95% confidence interval [CI] 1.49-10.91, P = 0.007). Conversely, prior biologic treatment failure was negatively associated with reporting no impact of psoriasis on quality of life (aOR 0.13, 95% CI 0.02-0.65, P = 0.023). Furthermore, among patients with clear skin, those with experience of previous biologic treatment failure reported significantly lower quality of life than those without such experience (P = 0.033). In conclusion, minimal residual skin lesions and prior biologic treatment failure were associated with poorer patient-reported outcomes in patients with psoriasis. Opting for a biologic agent with the highest predicted efficacy, rather than pursuing a "step-up" approach with a higher possibility of treatment failure, may be a more suitable strategy in the biologic treatment of psoriasis.

SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-ß Signaling Pathway.

The matricellular secreted protein acidic and rich in cysteine (SPARC; also known as osteonectin), is involved in the regulation of extracellular matrix (ECM) synthesis, cell-ECM interactions, and bone mineralization. We found decreased SPARC expression in aged skin. Incubating foreskin fibroblasts with recombinant human SPARC led to increased type I collagen production and decreased matrix metalloproteinase-1 (MMP-1) secretion at the protein and mRNA levels. In a three-dimensional culture of foreskin fibroblasts mimicking the dermis, SPARC significantly increased the synthesis of type I collagen and decreased its degradation. In addition, SPARC also induced receptor-regulated SMAD (R-SMAD) phosphorylation. An inhibitor of transforming growth factor-beta (TGF-ß) receptor type 1 reversed the SPARC-induced increase in type I collagen and decrease in MMP-1, and decreased SPARC-induced R-SMAD phosphorylation. Transcriptome analysis revealed that SPARC modulated expression of genes involved in ECM synthesis and regulation in fibroblasts. RT-qPCR confirmed that a subset of differentially expressed genes is induced by SPARC. These results indicated that SPARC enhanced ECM integrity by activating the TGF-ß signaling pathway in fibroblasts. We inferred that the decline in SPARC expression in aged skin contributes to process of skin aging by negatively affecting ECM integrity in fibroblasts.

Available Alternative Biologics and Disease Groups Influence Biologic Drug Survival in Patients with Psoriasis and Psoriatic Arthritis.

BACKGROUND: Factors other than efficacy and safety could influence the survival of biologics in patients with psoriasis. Little is known about whether different disease groups affect drug survival of biologics or not. OBJECTIVE: This study aimed to investigate whether the availability of alternative biologics and disease groups could influence drug survival of biologics approved for psoriasis and psoriasis arthritis (PsA). METHODS: A nationwide population-based retrospective cohort study was conducted using the Health Insurance and Review Assessment data in Korea between January 2009 and August 2019. RESULTS: The drug survival analysis included 5,634 biologic episodes. Ustekinumab was the most frequently prescribed drug (n=2,488, 44.2%). Multivariable time-dependent Cox regression analysis showed that higher age, female sex, no comorbidity, concomitant cyclosporine or acitretin use, biologic-experienced and use of tumor necrosis factor (TNF)-α inhibitors were predictors of drug discontinuation. PsA was a predictor of drug persistence, particularly for TNF-α inhibitors. Ustekinumab and adalimumab discontinuation significantly increased after introducing secukinumab and ustekinumab, respectively. CONCLUSION: The availability of alternative biologics and disease groups affect biologic drug survival in patients with psoriasis and PsA.

Association Between Short-Term PASI90 Achievement and Drug Survival of Biologics in Patients with Psoriasis.

Background: With accumulating evidence that achieving a 90% improvement in the Psoriasis Area and Severity Index score (PASI90) has better correlation with improved health-related quality of life as compared to PASI75 achievement, there has been demand for establishing new treatment goals for psoriasis. We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement. Objective: We investigated whether the short-term PASI90 achievement would predict longer drug survival as compared to PASI75 achievement. Methods: This single-center retrospective cohort study reviewed 180 treatment series in 128 patients with plaque psoriasis, who were treated with tumor necrosis factor-alpha inhibitors (n=12), ustekinumab (n=88), secukinumab (n=23), guselkumab (n=45), and ixekizumab (n=12). The first effectiveness assessment, usually performed within 12 to 20 weeks, was considered a short-term treatment response to biologics. Results: After adjustment for covariates, time-dependent Cox proportional hazards regression analysis showed that moderate responders (short-term achievement of ≥PASI75 but

Differences in Clinical Responses to Ustekinumab Treatment among Body Regions: Results from a Real-World Prospective, Observational, and Multi-Center Study in Korea.

BACKGROUND: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions. OBJECTIVE: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans. METHODS: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis. RESULTS: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits. CONCLUSION: We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.

Association of Rosacea With Cardiovascular Disease: A Retrospective Cohort Study.

Background There is emerging evidence that rosacea, a chronic cutaneous inflammatory disease, is associated with various systemic diseases. However, its association with cardiovascular disease (CVD) remains controversial. We aimed to investigate whether patients with rosacea are at increased risk of developing CVD. Methods and Results This retrospective cohort study from the Korean National Health Insurance Service-Health Screening Cohort included patients with newly diagnosed rosacea (n=2681) and age-, sex-, and index year-matched reference populations without rosacea (n=26 810) between 2003 and 2014. The primary outcome was subsequent CVD including coronary heart disease and stroke. Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios for subsequent CVD adjusted for major risk factors of CVD. Compared with the reference population (13 410 women; mean [SD] age, 57.7 [9.2] years), patients with rosacea (1341 women; mean [SD] age, 57.7 [9.2] years) displayed an increased risk for CVD (adjusted hazard ratios, 1.20; 95% CI, 1.03-1.40) and coronary heart disease (adjusted hazard ratios, 1.29; 95% CI, 1.05-1.60). The risk for stroke was not significantly elevated (adjusted hazard ratios, 1.12; 95% CI, 0.91-1.37). Conclusions This study suggests that patients with rosacea are more likely to develop subsequent CVD. Proper education for patients with rosacea to manage other modifiable risk factors of CVD along with rosacea is needed.

Complete and transparent reporting of primary end points of randomized trials in the dermatology literature: A comparison of registered and published primary end points.

BACKGROUND: Appropriate primary end points in randomized controlled trials (RCTs) improve the quality of the measurement and enable comparison of the findings with those of other trials. OBJECTIVE: To assess the quality of reporting primary end points in RCTs recently published in dermatology journals. METHODS: We identified 134 primary reports of RCTs among original articles in 4 dermatology journals published from January 2016 to December 2018. Details were extracted from articles, supplements, and trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with adequate primary end point reporting. RESULTS: Adequate primary end point reporting was conducted in 76 of 134 RCTs (56.7%). Nine missed the definition of primary end points, and 13 did not define the timing of primary end points in the publications. Among 113 RCTs reporting primary end points explicitly in the articles, 16 showed discrepancies between registration and publication, and 21 were not able to valuate prespecification of primary end points. Multicenter studies and sponsor-initiated trials were significantly associated with adequate reporting quality after adjusting for covariates. LIMITATIONS: Prespecification was evaluated based on a comparison of the article and registry. CONCLUSIONS: The quality of primary end point reporting, particularly in prespecification, has remained unsatisfactory in the recent dermatology literature.

Effects of reflection and immediate feedback to improve clinical reasoning of medical students in the assessment of dermatologic conditions: a randomised controlled trial.

BACKGROUND: There are few studies that directly compared different interventions to improve medical students' clinical reasoning for dermatologic conditions. OBJECTIVE: To investigate the effectiveness of adding practice with reflection and immediate feedback on traditional dermatology electives in improving medical students' ability in evaluating skin lesions. METHODS: The participants were fourth-year medical students of Seoul National University College of Medicine, Korea, who were enrolled to take a 2-week dermatology elective course (n = 87). Students were assigned to one of the three educational interventions: 2-h training involving 10 written clinical cases (experimental); 1-h lecture and 1-h outpatient clinic (lecture); and 2-h outpatient clinic (no intervention). Before and at the end of rotation, diagnostic accuracy was estimated using 20 written clinical cases with photographs (10 novel cases presented in diagnostic training [training set], 10 cases with diagnoses not included in training [control set]). RESULTS: There was a significant interaction effect of intervention×set×time. A post hoc analysis indicated that the students in the experimental group outperformed students in the other two groups only in the training set of the final tests; after completing the 2-week rotation, for the training set, the mean score was higher in the experimental group (7.5 ± 1.3) than in the lecture (5.7 ± 1.6) and no intervention (5.6 ± 1.3) groups, producing an effect size of 1.2 standard deviation (SD) and 1.5 SD, respectively. CONCLUSION: Practicing written clinical cases with reflection and feedback is superior to a lecture-based approach and yields additional benefits to a dermatology elective, thereby enhancing medical students' ability to accurately diagnose skin lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03472001. Registered 21 March 2018.

Eccrine Syringofibroadenoma Associated with Bowen's Disease: A Case Report and Review of the Literature.

Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal neoplasm which usually manifests as a solitary nodule on the extremities of elderly patients. Few case reports have described an association between ESFA and carcinomas including squamous cell carcinoma, porocarcinoma, and basal cell carcinoma. A 66-year-old male presented with a pruritic, erythematous brownish solitary plaque with crusted and verrucous surface on the extensor side of the right thigh. The lesion developed 6 to 7 years ago, and had been growing slowly. Biopsy revealed anastomosing epithelial strands which were composed of 2 areas: the upper area consisting of dysplastic cells with prominent nucleoli and abundant mitoses, and the lower area consisting of oval and round cells, and occasionally small luminal ducts. Dysplastic cells comprised almost the entire epidermis but did not invade into the dermis. Benign syringofibroadenomatous lesion surrounded the dysplastic cells in the lowermost portion of the epidermis. Although it is still unclear whether ESFA undergoes malignant transformation or it is a reactive change to carcinoma, complete excision should be performed to prevent malignant transformation with unknown risk.

Pervasive Misclassification and Misconception of Study Designs in Asian Dermatology Journals Listed in Science Citation Index-Expanded.

BACKGROUND: Misclassification of study designs of journals can hinder the readers from assessing the strengths and weaknesses of the study and evaluating the applicability of the study in the real-world setting. However, it seems that it is common for authors to neglect to classify the study design. OBJECTIVE: We aimed to evaluate the accuracy of the classification of study designs and examine the common errors. METHODS: This descriptive study analyzed four Asian dermatology journals listed in the science citation index expanded from January 2018 to December 2018. We investigated discrepancies between author-reported and actual study designs. Design Algorithm for Medical Literature on Intervention (DAMI) was used to determine the actual study design. RESULTS: Of the 177 papers analyzed, only 72 articles (40.7%) revealed their study design and among them, 23 articles (32.0%) showed discrepancies between the author-reported and the actual study designs. Case-control studies were the most commonly misclassified study designs by authors. CONCLUSION: There were considerable differences between the author-reported study design and the actual study design in Asian dermatology journals. Proper classification of study designs by the authors is essential to strengthen evidencebased medicine.

Efficacy and Safety of Oral Alitretinoin in Hand Eczema and Palmoplantar Pustulosis in Korean Patients.

BACKGROUND: Previous studies have demonstrated efficacy and safety of oral alitretinoin in hand eczema (HE) whereas in palmoplantar pustulosis (PPP), which can be difficult to distinguish from HE, efficacy of alitretinoin is still controversial. OBJECTIVE: This study aimed to investigate the efficacy and safety of oral alitretinoin in HE and PPP and factors that affect the response of these disorders to alitretinoin. METHODS: We retrospectively analyzed Korean adult patients with moderate-to-severe HE and PPP treated with oral alitretinoin, 46 patients for efficacy assessment and 55 patients for safety assessment. RESULTS: Among 46 patients who were treated with alitretinoin for at least 1 month, 29 patients (61.1% in HE and 40.0% in PPP) showed response to alitretinoin in the median 14 weeks after treatment. Hyperkeratotic HE showed higher response rate than either vesicular HE or PPP (p=0.026 and p=0.026, respectively). However, PPP with hyperkeratotic features showed as much response as hyperkeratotic HE (p=0.554). When responders and non-responders in total patients were compared, morphology, not diagnosis or initial severity, was the only significantly different factor between the two groups. After alitretinoin discontinuation in responders, relapse rate was 63.6% (7/11) and median time to relapse was 150 days (range, 76~730 days). Adverse events occurred in 47.3% (26/55); however, there were no serious adverse events. CONCLUSION: In HE or PPP, lesions with hyperkeratotic morphology can be predicted to respond well to alitretinoin regardless of diagnosis.

Hair Follicle Nevus Located on the Neck: Comparison with Accessory Tragus, Cervical Chondrocutaneous Branchial Remnants and Trichofolliculoma.

Hair follicle nevus (HFN) is a rare, benign, follicular hamartoma that most frequently presents as a congenital nodule on the face. We experienced a rare case of HFN on the neck of a 14-year-old boy and performed a pilot immunohistochemical study with cytokeratin 19 (CK19) to compare the staining pattern of hair follicles in HFN and its differential diagnoses, accessory tragus, cervical chondrocutaneous branchial remnants (CCBR) and trichofolliculoma. With hematoxylin and eosin stain, HFN showed numerous tiny hair follicles in the dermis with several sebaceous and eccrine glands, and perifollicular fibrous thickening. With CK19 stain, some hair follicles in HFN and CCBR showed positive expression, a few hair follicles in accessory tragus showed weak expression, and no hair follicles in trichofolliculoma showed expression. The present report supports the view that HFN, accessory tragus and CCBR are within the same spectrum of hamartomas.