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.

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.

Serum Ceruloplasmin as a Potential Clinical Biomarker in Atopic Dermatitis.

BACKGROUND: Although the discovery of new biomarkers in atopic dermatitis (AD) is challenging, it is valuable in diagnosis, assessment of severity, and evaluation of treatment response. OBJECTIVE: This study was designed to identify and validate new candidate protein biomarkers of AD via proteomic analysis. METHODS: Comparison of protein expression in the patients' serum before- and after-treatment and in patients without AD was performed via two-dimensional gel electrophoresis (2-DE), followed by image analysis. Spots showing differential expression in 2-DE image analysis were identified subsequently via nanoscale liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments. Blood tests were conducted to validate the results obtained by measuring the levels of candidate proteins. RESULTS: Based on LC-MS/MS analysis and database search, we identified ceruloplasmin (Cp) as a candidate protein. Serum Cp levels were significantly decreased in in pre-treated AD group than in control group. Additionally, the serum Cp level was higher in the mild group than in the moderate group of AD based on the Eczema Area and Severity Index (EASI) score. CONCLUSION: Low serum Cp levels are associated with AD, suggesting the potential role of Cp as a biomarker for diagnosis and severity assessment of AD.

Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study.

A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in échelle d'évaluation clinique des cicatrices d'acné scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.

The Relation of Autologous Serum Skin Test and Autologous Plasma Skin Test Result with Various Clinical and Laboratory Findings in Patients with Chronic Spontaneous Urticaria.

BACKGROUND: Despite the autologous serum skin test (ASST) and autologous plasma skin test (APST) is widely used test accessing whether a patient with chronic spontaneous urticaria (CSU) has autoreactivity or not, the clinician often encounter difficulty making correlation between the test result and clinical implications. OBJECTIVE: This study was aimed to find any clinical and laboratory findings related to the ASST and APST response. Agreement and correlation between the two tests was also analyzed. METHODS: A retrospective study was conducted on 300 CSU patients who underwent ASST, APST. The subjects were divided into four groups according to the skin test result. Also, the degree of serum and plasma response was recorded. RESULTS: Both ASST and APST positive group had shorter duration of the disease, higher incidence of at least one episode of angioedema than negative group. There were no significant differences in the positivity for autoantibodies including antinuclear, ds-DNA, and thyroid-related between the two groups. The predicted positive rate of ASST and APST according to age showed bimodal peak and decreasing pattern according to disease duration. Predicted positivity of both tests declined with increase in total immunoglobuline E (IgE) level. In the correlation study, the two tests showed high correlation coefficients. CONCLUSION: ASST and APST positivity may be related to disease duration and severity of CSU. The two tests showed a generally consistent result. Autoreactivity may be gradually lost as disease continues. We suggest the autoreactivity in CSU could arise independently from IgE mediated immune process.

Combined treatment of recalcitrant papulopustular rosacea involving pulsed dye laser and fractional microneedling radiofrequency with low-dose isotretinoin.

BACKGROUND: While a considerable number of cases with papulopustular rosacea (PPR) are resistant to conventional medications, therapeutic regimens are not currently established. Pulsed dye laser (PDL) and fractional microneedling radiofrequency (FMR) have previously demonstrated satisfactory results for anti-angiogenesis, anti-inflammation, and dermal remodeling. AIMS: To evaluate the efficacy and safety of novel combination regimen with low-dose oral isotretinoin, PDL, and FMR in the treatment of recalcitrant PPR. PATIENTS AND METHODS: A retrospective study was undertaken for recalcitrant PPR patients to evaluate the clinical course of novel combination regimen. Twenty-five PPR patients who had failed in previous first-line therapies were enrolled. They were treated with three sessions of PDL and FMR consecutively at 4-week intervals, maintaining daily oral administration of 10 mg isotretinoin for 8 weeks. Objective assessments, erythema index measurement, and patients' subjective satisfaction were evaluated at each visit and 16 weeks after the final treatment. RESULTS: At the final follow-up visit, the number of papules and pustules decreased by 71%, and erythema index by 54% compared with baseline (P < 0.05 for both). Physician's global assessment based on rosacea severity score and patients' subjective assessments paralleled with these results. No serious side effect was observed during whole study periods. CONCLUSION: This novel combination regimen demonstrated satisfactory efficacy with reasonable safety profiles for the treatment of recalcitrant PPR.

A Novel Combined Light-Based Treatment of Acne Vulgaris With 1,450-nm Diode Laser and 450-nm Blue Light.

BACKGROUND: Nonablative 1,450-nm diode laser (DL) and visible blue light (BL) have been effectively used for acne with superior safety profiles. OBJECTIVE: To evaluate synergistic effects of sequential DL and BL application for acne. METHODS: A 20-week, randomized split-face study was conducted to compare clinical courses between 2 facial sides either receiving sequential application of DL and BL or BL alone in 24 patients with mild to moderate facial acne vulgaris. Patients were scheduled to receive 3 consecutive sessions at 4-week intervals. Objective assessments, including revised Leeds grades, lesion counts, and sebum output measurements, and patients' subjective satisfaction were investigated. RESULTS: Both combination and BL sides demonstrated steady improvement of inflammatory acne lesions with 62.3% and 35.2% decreases at the 12-week follow-up visit compared with baseline respectively. For noninflammatory lesions and seborrhea, only combination regimen demonstrated improvement. Patients' subjective assessments paralleled objective findings. For safety profiles, no severe adverse effect was observed on both sides, and mild symptoms resolved spontaneously within a day. CONCLUSION: The combination regimen demonstrated synergistic efficacies for acne and seborrhea, with satisfactory safety profiles. Therefore, a few sessions of these light-based applications would be a viable option for acne treatments.

Combined treatment for skin laxity of the aging face with monopolar radiofrequency and intense focused ultrasound in Korean subjects.

BACKGROUND: Although various minimal invasive approaches are available for aging skin laxity, they alone may not lead to notably satisfactory results. OBJECTIVE: To evaluate the effectiveness and safety of combination regimen with monopolar radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and tightening. METHODS: Twenty-two Korean participants with aging face received a sequential single session of MRF and IFUS treatment. Objective and subjective assessments for improvement were performed at the 20-week post-treatment. Safety profiles were also recorded, and skin biopsies were taken at baseline and follow-up visit. RESULTS: Based on the objective assessment for the overall facial skin tightening and laxity, 19 patients (90%) demonstrated "moderate" or better improvements (more than 25%) compared with baseline. Specifically, improvements of skin laxity and sagging, and droopy jaw line were more noticeable compared with that of superficial skin texture (P < 0.05). Subjective satisfactions were generally consistent with objective findings, and no serious adverse effect was observed. Histologic evaluation showed increased dermal collagen fibers throughout the dermis after treatments (P < 0.05). CONCLUSION: Combination treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening with satisfactory safety profiles in Asian subjects.

Histologic analyses on the response of the skin to 1,927-nm fractional thulium fiber laser treatment.

BACKGROUND: The histologic responses to varied parameters of 1,927-nm fractional thulium fiber laser treatment have not yet been sufficiently elucidated. OBJECTIVE: This study sought to evaluate histologic changes immediately after 1,927-nm fractional thulium fiber laser session at various parameters. METHODS: The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium fiber laser at varied parameters, with or without skin drying. The immediate histologic changes were evaluated to determine the effects of varying laser parameters on the width and the depth of treated zones. RESULTS: The increase in the level of pulse energy widened the area of epidermal changes in the low power level, but increased the dermal penetration depth in the high power level. As the pulse energy level increased, the increase in the power level under the given pulse energy level more evidently made dermal penetration deeper and the treatment area smaller. Skin drying did not show significant effects on epidermal changes, but evidently increased the depth of dermal denaturation under both high and low levels of pulse energy. CONCLUSION: These results may provide important information to establish treatment parameters of the 1,927-nm fractional thulium fiber laser for various skin conditions.

Combined Fractional Treatment of Acne Scars Involving Non-ablative 1,550-nm Erbium-glass Laser and Micro-needling Radiofrequency: A 16-week Prospective, Randomized Split-face Study.

An optimized therapeutic regimen involving a non-ablative fractionated laser or radiofrequency therapy for acne scars has not yet been established. To evaluate whether the combination of a non-ablative fractional laser (NAF) and fractional micro-needling radiofrequency (FMR) has clinical advantages for the treatment of atrophic acne scars compared with NAF alone, a 16-week prospective, randomized split-face study was performed. Each facial side of a patient was treated with 3 sessions of either NAF with FMR or NAF alone, with a 4-week interval between each session. Although both sides demonstrated significant decreases in the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score, the facial side treated using the combination regimen demonstrated greater improvement in ECCA score regarding degree and onset time than the NAF-treated side. Histopathological and immunohistochemical results confirmed the clinical findings. This study demonstrated that a combination regimen involving NAF and FMR could be a viable option with satisfactory efficacy.

Association of TG2 from mast cells and chronic spontaneous urticaria pathogenesis.

BACKGROUND: Mast cells and their mediators play important roles in chronic spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed in activated mast cells and contributes to airway inflammation in allergic asthma. OBJECTIVE: To investigate the role of TG2 in CSU. METHODS: Patients with CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived human mast cells and peripheral blood-derived human mast cells were activated with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene C4, and cytokines, were measured in serum or supernatant from cultured mast cells by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was determined in skin tissues by immunofluorescence. RESULTS: TG2 activity was significantly higher in serum samples from patients with CSU than in serum samples from healthy controls (P < .001). Colocalization of mast cell surface marker c-kit and TG2 was significantly increased in the lesional skin of patients with CSU compared with that in healthy controls. The levels of histamine, leukotriene C4, tumor necrosis factor α, transforming growth factor ß, and interleukins 4, 5, and 6 were significantly higher in patients with CSU than in healthy controls (P < .001). Serum TG2 levels had positive correlations with each inflammatory mediator (P < .001). TG2 activity was increased in cord blood-derived human mast cells (CBMCs) and peripheral blood-derived human mast cells activated with IgE compared with those without activation (P < .05). CONCLUSION: Our findings suggest that TG2 expressed in and released from mast cells plays an important role in CSU pathogenesis.

Periostin and Interleukin-13 Are Independently Related to Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.

Avoidance Behavior against Positive Allergens Detected with a Multiple Allergen Simultaneous Test Immunoblot Assay in Patients with Urticaria: Factors Associated with Avoidance Success/Failure.

BACKGROUND: Avoidance behavior against positive allergens detected by using multiple allergen simultaneous test (MAST)-immunoblot assay in patients with urticaria has been rarely reported. OBJECTIVE: We aimed to assess the avoidance behavior of patients with urticaria against positive allergens detected with a MAST. METHODS: One hundred and one urticaria patients who showed positivity to at least one allergen on a MAST completed a questionnaire regarding their test results. The avoidance behavior of the patients was evaluated, and relevant determining factors of avoidance success/failure were statistically assessed. RESULTS: We detected 144 different data (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) from 101 patients with urticaria. The avoidance failure rates were 33.3% for food allergens, 70.6% for pollen allergens, and 30.3% for aeroallergens. The pollen group showed a significantly higher avoidance failure rate than the food and aeroallergen groups (p<0.05). The patients with higher educational levels or more severe urticaria tended to successfully avoid allergens (p<0.05). The monthly household income level and patients' reliability to the test showed borderline correlations (p=0.057 and p=0.075, respectively). CONCLUSION: We believe that the results of this study could be helpful in predicting avoidance success or failure against allergens in patients with urticaria when clinicians conduct allergen-specific immunoglobulin E tests.

Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal.

This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker). However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K(+) channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

Green nail syndrome treated with the application of tobramycin eye drop.

Green nail syndrome (chromonychia) is a nail disorder characterized by onycholysis and green-black discoloration of the nail bed. This condition is often associated with chronic paronychia. Pseudomonas aeruginosa is the most commonly identified organism in cultures from the affected area. Despite the various treatment options available, removal of the nail is still necessary in many cases. A 35-year-old man presented with dark-greenish discoloration of the nail plate and onycholysis on the left thumbnail. He had been treated with oral antifungal and antibiotic agents for several months; however, the lesion showed no improvement. The diagnosis of green nail syndrome was established after a positive bacterial culture, and on the basis of the antibiotic sensitivity test result, tobramycin eye drop (Tobrex®) was then prescribed. Three weeks later, the nail discoloration almost vanished but the onycholysis remained. Herein, we recommend the application of tobramycin eye drop as an easy and safe treatment option for green nail syndrome.

Beta-lactam antibiotic sensitization and its relationship to allergic diseases in tertiary hospital nurses.

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi(2)=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi(2)=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi(2)=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.