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.

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.

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.

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.

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.

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.

Associations of HLA-A and HLA-B with vancomycin-induced drug reaction with eosinophilia and systemic symptoms in the Han-Chinese population.

Vancomycin is a commonly used antibiotic; however, it can cause life-threatening severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). A previous study has reported a strong association between HLA-A*32:01 and vancomycin-induced DRESS in European ethnicity. Herein, we aim to investigate the genetic predisposition of vancomycin-induced DRESS in the Han-Chinese population. In this study, we enrolled a total of 26 patients with vancomycin-induced DRESS, 1,616 general population controls, and 51 subjects tolerant to vancomycin. In vitro granulysin-based lymphocyte activation tests (LAT) were conducted among 6 vancomycin-induced DRESS patients who were concomitantly receiving other medicines. HLA-A and HLA-B genotypes were determined by sequencing-based typing. Our results found that vancomycin-induced DRESS was associated with HLA-A*32:01 [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 1.7-35.8; p-value = 0.035], HLA-B*07:05 (OR = 32.3, 95% CI = 2.8-367.7; p-value = 0.047), HLA-B*40:06 (OR = 4.7, 95% CI = 1.3-16.1; p-value = 0.036) and HLA-B*67:01 (OR = 44.8, 95% CI = 7.2-280.4; p-value = 0.002) when comparing the vancomycin-induced DRESS patients with the general population controls. LAT results showed that granulysin significantly increased in the vancomycin-induced DRESS patients upon vancomycin stimulation (4.7 ± 3.7 fold increased), but not upon other co-medicines. This study identified that, in addition to HLA-A*32:01, HLA-B*07:05, HLA-B*40:06, and HLA-B*67:01 were also genetic markers for vancomycin-induced DRESS in the Han-Chinese population. Associations of ethnic variances in HLA with vancomycin-DRESS were observed.

Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Implementation of NUDT15 Genotyping to Prevent Azathioprine-Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population.

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10-25 , odds ratio (OR) = 21.7, 95% confidence interval (95% CI) = 12.1-38.8) and NUDT15 rs746071566 (P = 4.2 × 10-9 , OR = 7.1, 95% CI = 3.7-13.7), but not TPMT, were associated with AZA-induced leukopenia and NUDT15 R139C variant shows the highest sensitivity with 92.5%. Furthermore, the targeted screening of 1,013 participants for NUDT15 R139C enabled those identified as carriers to use alternative immunosuppressants. This strategy resulted in a significant decrease in the incidence of AZA-induced leukopenia compared with historical incidence (incidence rate = from 7.6% decreased to 0.4%; P = 9.3 × 10-20 ). In conclusion, the NUDT15 R139C variant was strongly associated with AZA-induced leukopenia in Chinese patients. The genetic screening of NUDT15 R139C followed by use of alternative immunosuppressants in identified carriers effectively decreased the incidence of AZA leukopenia for patients with autoimmune disorders.

Clinical features and outcomes in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged < 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty-seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1-17 years); 51.1% were male. Thirty-three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often-implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3-42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long-term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post-inflammatory hypo-/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long-term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long-term sequelae requiring regular follow-up.

Psoriasis Patients with Specific HLA-Cw Alleles and Lower Plasma IL-17 Level Show Improved Response to Topical Lindioil Treatment.

Purpose: Lindioil, a medicine refined from indigo naturalis (a herb used in Chinese medicine), is effective in treating severe psoriasis; however, responses vary across individual patients. We aim to investigate genetic predispositions associated with treatment response to topical Lindioil among patients with psoriasis and correlations with plasma cytokine patterns. Patients and Methods: We enrolled 72 psoriasis patients treated with Lindioil ointment and analyzed the human leukocyte antigen class C (HLA-Cw) genotypes and plasma cytokine expression patterns. We developed regression models of treatment response, defined as Psoriasis Area and Severity Index (PASI) 75, to examine correlations among HLA-Cw alleles, cytokine levels, and treatment response to Lindioil. Results: Patients harboring HLA-Cw*06:02 were significantly more likely to respond to Lindioil (P = 0.02, odds ratio [OR]: 6.88), whereas Lindoil was ineffective in those harboring HLA-Cw*01:02 (P = 0.01, OR: 0.28). Patients who were HLA-Cw*06:02-positive or HLA-Cw*01:02-negative had better PASI scores and body surface area (BSA) improvement (73.3% vs 44.4%, P<0.001) following an 8-week treatment period. Psoriasis patients achieving PASI 75 after 8 weeks presented with lower baseline plasma interleukin-17 (IL-17) levels than those who did not achieve PASI 75 (PASI 75: 11.28 pg/mL vs PASI <75: 15.82 pg/mL, P = 0.05). Conclusion: Our findings suggest that the presence of the HLA-Cw*06:02 or HLA-Cw*01:02 alleles and plasma IL-17 levels are predictive markers of treatment response to Lindioil ointment in patients with psoriasis.

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.

Case of vitiligo universalis as a sequela of drug-induced hypersensitivity syndrome.

Drug-induced hypersensitivity syndrome (DIHS) is a type of severe drug adverse reaction with high morbidity and mortality. DIHS patients have been reported to subsequently develop autoimmune disease, which may be followed by end-organ decompensation. We report a 47-year-old woman who presented with fever, generalized maculopapular eruption, facial edema and eosinophilia with liver function impairment after taking celecoxib and sulfasalazine for 1 month. The patient was diagnosed with definite DIHS. The patient was treated with immunosuppressants including systemic corticosteroid for approximately 1.5 years due to recurrent episodes. Reactivation of human herpesvirus 6 and possible reactivation of cytomegalovirus were detected. Generalized hypopigmentation of the skin and leukotrichia were noted 4 months after the onset of DIHS. Histopathological examination confirmed the diagnosis of vitiligo. Some spontaneous repigmentation was noted 4 years after DIHS without specific treatment. Further immunoserology study showed elevated plasma C-X-C motif chemokine 10 level, which is related to vitiligo activity, in our patient. The occurrence of widespread vitiligo after DIHS is an extremely rare condition. This case provides an important reminder for physicians to monitor such severe complications after DIHS.

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.

Effectiveness and safety of secukinumab for psoriasis in real-world practice: analysis of subgroups stratified by prior biologic failure or reimbursement.

BACKGROUND: Little is known about the treatment outcomes of secukinumab in clinical practice, which differ from those in clinical trials. The effectiveness of biologics may differ in psoriasis patients with previous biologics exposure. The objective of this study was to investigate the real-world effectiveness and safety of secukinumab therapy and analyze subgroups stratified by reimbursement or prior biologic failure. METHODS: This retrospective multicenter study collected data from a cohort of 118 consecutive patients who received secukinumab treatment between December 2015 and March 2018. Effectiveness was evaluated by degree of improvement in the Psoriasis Area and Severity Index (PASI) scores. Adverse events and reasons for discontinuation were also recorded. RESULTS: The mean PASI improvement rate at weeks 4, 12, 24, and 36 was 63.5%, 77.7%, 78.7%, and 76.0%, respectively. Compared with reimbursed patients, nonreimbursed patients had a significantly lower baseline PASI and a shorter mean disease duration of psoriasis; they were more frequently biologic-naïve, had used less prior traditional antipsoriatic drugs and were more likely to be treated with secukinumab 150 mg. The effectiveness of secukinumab in nonreimbursed patients was superior despite higher discontinuation rates. Compared with patients without prior biologic failure, patients with prior biologic failure had a significantly lower mean PASI improvement at weeks 12, 24, 36, and 48. The decline in response rates to secukinumab tended to be more pronounced for patients who failed ustekinumab than tumor necrosis factor-α inhibitors. Moreover, the number of prior biologic failures was associated with a decreased response rate and increased likelihood of secondary loss of effectiveness of secukinumab therapy. CONCLUSION: In a real-life clinical setting, the characteristics of nonreimbursed patients receiving secukinumab treatment differed from those of reimbursed patients. The PASI improvement for secukinumab was substantial but lower than that in clinical trials. The number and classes of prior biologic failures impact the treatment response to secukinumab.

The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

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.