CCR8/CCL1 and CXCR3/CXCL10 axis mediated memory T cell activations in recalcitrant drug-induced hypersensitivity patients.

BACKGROUND: As a drug-induced hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) is potentially fatal. Most patients with DRESS recover within a few weeks; however, some patients may suffer from a prolonged disease course and develop autoimmune sequelae. OBJECTIVE: We investigated the immune mechanism and therapeutic targets of patients with recalcitrant DRESS with a prolonged disease course. METHODS: A total of 32 patients with recalcitrant DRESS with a prolonged treatment course ≥8 weeks, 28 patients with short-duration DRESS with a treatment course <2 weeks, and 26 healthy individuals were enrolled in the study for analysis. RESULTS: Bulk transcriptome results demonstrated that mRNA expression levels of CCR8 and CXCR3 were significantly increased in the blood samples from patients in the acute stage of prolonged DRESS (adjusted p-values: CCR8=1.50×10-9 and CXCR3=2.60×10-4, respectively, for comparison of patients with prolonged DRESS to the healthy donor group). Serum and skin lesional concentrations of CCL1 and CXCL10, as the ligands of CCR8 and CXCR3, respectively, were significantly elevated in patients with prolonged DRESS as compared to those patients with short-duration DRESS. The results from high-parameter flow cytometry and autoantibody screening also identified significant escalations of CD8+ GNLY+CXCR3+effector memory T cells, CD8+central memory T cells, CD4+CCR8+Th2 cells, and IgG-anti-HES6 autoantibodies in patients with prolonged DRESS. Furthermore, in vitro blocking assays revealed that JAK inhibitors (mainly tofacitinib and upadacitinib) significantly decreased the release of CCL1 and CXCL10, and some patients with prolonged DRESS were successfully treated with JAK inhibitors. CONCLUSIONS: JAK inhibitors (tofacitinib and upadacitinib) were associated with decreased concentrations of CCL1 and CXCL10, suggesting that they may attenuate CCR8/CCL1- and CXCR3/CXCL10-axis-mediated memory T cell activation, which contribute to disease pathogenesis for patients with recalcitrant DRESS and a long-term treatment course.

Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations.

BACKGROUND: The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized. OBJECTIVE: We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA). STUDY DESIGN: 27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis. RESULTS: The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-5-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04). CONCLUSIONS: Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review.

The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic predisposition is known to contribute to the pathogenesis of psoriasis. Hence, pharmacogenomics gives the hint of predictive treatment response individually. This review highlights the current pharmacogenetic and pharmacogenomic studies of medical therapy in psoriasis. HLA-Cw*06 status remains the most promising predictive treatment response in certain drugs. Numerous genetic variants (such as ABC transporter, DNMT3b, MTHFR, ANKLE1, IL-12B, IL-23R, MALT1, CDKAL1, IL17RA, IL1B, LY96, TLR2, etc.) are also found to be associated with treatment response for methotrexate, cyclosporin, acitretin, anti-TNF, anti-IL-12/23, anti-IL-17, anti-PDE4 agents, and topical therapy. Due to the high throughput sequencing technologies and the dramatic increase in sequencing cost, pharmacogenomic tests prior to treatment by whole exome sequencing or whole genome sequencing may be applied in clinical in the future. Further investigations are necessary to manifest potential genetic markers for psoriasis treatments.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Chromoblastomycosis in Taiwan: A report of 30 cases and a review of the literature.

Chromoblastomycosis (CBM) is an implantation mycosis characterized by the presence of pigmented muriform cells in tissue. CBM is endemic in Taiwan, but only three formal cases have been reported to date because of underreporting. To describe and update its epidemiologic features, we report a series of 30 cases between 2003 and 2016 at a single medical center. Patients were predominately male (2.75:1). The mean age of onset was 65.9 years, and disease duration ranged from 2 months to 20 years. Diabetes was the most common comorbidity, and extremities were the most frequent sites of involvement. The lesions presented as papuloplaque, verrucous, cicatricial, targetoid, or mixed types. The dermoscopic features were variable, including red dots, white vague areas, black globules, and sand-like patterns. Among 10 Fonsecaea isolates further identified by sequencing the ITS regions of ribosomal DNA, nine were F. monophora and one was F. nubica. All but one patient received either systemic antifungal agents, surgical excision, or both. Surgical excision achieved a higher complete remission rate than the other forms of treatment did.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

BACKGROUND: Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: To investigate the clinicopathology, risk factors, and prognostic factors of MEN. METHODS: We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). RESULTS: Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. LIMITATIONS: The study was limited by the small sample size. CONCLUSION: MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Predicting the Time to Relapse Following Withdrawal from Different Biologics in Patients with Psoriasis who Responded to Therapy: A 12-Year Multicenter Cohort Study.

BACKGROUND: For patients with psoriasis, discontinuation of biologics following remission has become more common in daily practice. OBJECTIVE: We aimed to identify predictors and construct a predictive model for time to relapse following withdrawal from biologics. METHODS: This 12-year, multicenter, observational cohort study was performed in six dermatology centers between February 2011 and February 2024. We identified biological treatment episodes in patients with moderate-to-severe psoriasis and included only treatment episodes in which a clinical response (≥ 50% reduction in Psoriasis Area and Severity Index score [PASI 50] from baseline) was achieved and the patient withdrew from biological therapy with a well-controlled status (PASI < 10 and ≥ 50% improvement in PASI from baseline). The primary outcome was time to relapse, which was defined as the period from the last biologic administration to relapse. An extended multivariate Cox proportional hazards analysis (Prentice-Williams-Peterson Gap time model) was used to predict relapse and generate a predictive model. RESULTS: This study screened 1613 biological treatment episodes, and 991 treatment episodes were enrolled. The time to relapse decreased significantly as the number of previous withdrawals from biological treatment increased (p < 0.001). Similarly, the time to relapse decreased significantly as the number of previous biologics used increased (p < 0.001). The maximum PASI improvement during biological treatment decreased and the PASI score at withdrawal of biological treatment increased in parallel as the number of prior withdrawals from biologics increased. The time to relapse following withdrawal was longest for interleukin (IL)-23 inhibitors (IL-23i), followed by the IL-12/23i, IL-17 inhibitors (IL-17i), and tumor necrosis factor-α inhibitors. After adjustment, multivariate Cox regression identified the following significant predictors of relapse following withdrawal: the mechanisms of action of biologics (hazard ratio [HR] for IL-17i vs IL-12/23i, 1.59; HR for IL-23i vs IL-12/23i, 0.60), number of previous withdrawals from biological treatment (HR 1.23; 95% confidence interval [CI] 1.13‒1.33), time to achieve PASI 50 (HR 1.01; 95% CI 1.00‒1.02), maximum PASI improvement on biologics (HR 0.98; 95% CI 0.98‒0.99), and PASI at the end of therapy (HR 1.03; 95% CI 1.01‒1.05). The model had good predictive and discriminative ability. CONCLUSIONS: These results have the potential to help physicians and patients make individualized treatment decisions; information on the risk of relapse of psoriasis at specific timepoints following the withdrawal of biologics is particularly valuable for patients considering discontinuation of biologics or as-needed biologic therapy. However, the benefit and risk of repeated withdrawals of biologics should be carefully weighed, as the treatment efficacy and duration of remission decline as the number of withdrawals increases.

Clinical Characteristics and Disease Burden of Patients with Moderate-to-Severe Generalized Pustular Psoriasis Flares in Taiwan.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. METHODS: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008-December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. RESULTS: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87-61.78), 14.08 (95% CI 3.04-65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08-0.54) and 0.07 (95% CI 0.006-0.78), respectively. CONCLUSIONS: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes.

An Evaluation of Skin and Immunological Responses after Using a Novel Cross-Linked Porcine-Based Dermal Injectable Collagen with Lidocaine for Nasolabial Fold Correction.

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing.

Evaluation of Collagen Dermal Filler with Lidocaine for the Correction of Nasolabial Folds: A Randomized, Double-Blind, Multicenter Clinical Trial.

Purpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection. Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05). Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.

High Diversity of Fusarium Species in Onychomycosis: Clinical Presentations, Molecular Identification, and Antifungal Susceptibility.

Fusarium are uncommon but important pathogenic organisms; they cause non-dermatophyte mould (NDM) onychomycosis. Patients typically respond poorly to treatment owing to Fusarium's native resistance to multiple antifungal drugs. However, epidemiological data for Fusarium onychomycosis are lacking in Taiwan. We retrospectively reviewed the data of 84 patients with positive Fusarium nail sample cultures at Chang Gung Memorial Hospital, Linkou Branch between 2014 and 2020. We aimed to investigate the clinical presentations, microscopic and pathological characteristics, antifungal susceptibility, and species diversity of Fusarium in patients with Fusarium onychomycosis. We enrolled 29 patients using the six-parameter criteria for NDM onychomycosis to determine the clinical significance of Fusarium in these patients. All isolates were subjected to species identification by sequences and molecular phylogeny. A total of 47 Fusarium strains belonging to 13 species in four different Fusarium species complexes (with Fusarium keratoplasticum predominating) were isolated from 29 patients. Six types of histopathology findings were specific to Fusarium onychomycosis, which may be useful for differentiating dermatophytes from NDMs. The results of drug susceptibility testing showed high variation among species complexes, and efinaconazole, lanoconazole, and luliconazole showed excellent in vitro activity for the most part. This study's primary limitation was its single-centre retrospective design. Our study showed a high diversity of Fusarium species in diseased nails. Fusarium onychomycosis has clinical and pathological features distinct from those of dermatophyte onychomycosis. Thus, careful diagnosis and proper pathogen identification are essential in the management of NDM onychomycosis caused by Fusarium sp.

Association between peripheral vascular endothelial dysfunction and livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) is a disease characterized by multiple painful and recurrent ulcerations on the feet, accompanied by atrophic scars. Many researchers suggest that a hypercoagulable status is the pathogenetic factor for LV. However, the cause of LV remains elusive. OBJECTIVE: We sought to determine if endothelial dysfunction is present in patients with LV. METHODS: This prospective study included 16 patients with LV and active ulcers and 16 matched control subjects. We reviewed detailed clinical parameters, including antinuclear antibody, high-sensitivity C-reactive protein, protein C, protein S, homocysteine, anti-SSA, anti-SSB, anticardiolipin antibody, and serum lipid profiles. Flow-mediated vasodilation of the brachial artery was used as an indicator of vascular endothelial function using high-resolution 2-dimensional ultrasonic imaging. RESULTS: Blood pressure, blood biochemistry, high-sensitivity C-reactive protein, and homocysteine were not significantly different in patients with LV and control subjects. Nitroglycerin-mediated vasodilation was not significantly different in patients with LV and control subjects. However, flow-mediated vasodilation was much less in patients with LV than in the control group (3.58 ± 2.32% vs 7.51 ± 2.40%, P < .001). LIMITATIONS: The study was performed at a single site with a limited sample size. CONCLUSION: Peripheral vascular endothelial dysfunction was demonstrated in patients with LV by reduction of brachial flow-mediated vasodilation.