Search

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.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.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.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.

Background Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. Methods To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Results Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Conclusions Our data unveil severity-specific immunological signatures perturbed in CKD patients.

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

The myositis autoantibodies have been widely used clinically in recent years for the identification of an autoantibody-associated clinical phenotype in dermatomyositis (DM) patients. However, correlations between myositis autoantibodies and clinical presentations in different populations are lacking, especially in Taiwan.To investigate the correlations among cutaneous manifestations, myositis autoantibodies, and systemic diseases, including interstitial lung disease (ILD) and internal malignancy.A retrospective study of patients with histopathologically confirmed cutaneous manifestations of DM was conducted during 2005 to 2020 in Taiwan. A commercial line blot immunoassay technique was used to detect myositis autoantibodies.A total of 88 DM patients were enrolled, with a mean age of onset of 49.4 years old. The most common systemic features were myositis (56.8%, 50/88), internal malignancy (22.7%, 20/88), dysphagia (19.3%, 17/88), and ILD (17%, 15/88). Among the enrolled patients, 32 patients received serum myositis autoantibodies examination. The most common autoantibodies were ANA (50.7%, 37/73), followed by anti-TIF1-γ (34.4%, 11/32) and anti-MDA5 (31.3%, 10/32) antibodies. Patients with Gottron sign (OR 5.6), arthritis (OR 23.35), or the presence of anti-MDA5 antibody (OR 11.14) were more susceptible to progressing to ILD, whereas patients with pruritus (OR 1.04), dysphagia (OR 6.73), and the presence of ANA (OR 6.29) had significantly higher risks of developing internal malignancies.Physicians should pay special attention to certain clinical features, which can help with the early detection of systemic diseases. Cancer screening and myositis autoantibodies examination should be conducted in all DM patients if applicable.

The purpose of this study was to analyze the clinical features, causative microorganisms, antibiotic susceptibility, and treatment outcomes in culture-proven microbial keratitis (MK) in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and to analyze the potential risk factors.We reviewed the medical records of all patients with SJS/TEN who attended our department between 2009 and 2018. Patients with a diagnosis of MK who underwent corneal cultures were enrolled. Demographics; clinical characteristics including ocular findings, treatment, time between onset of SJS/TEN and keratitis; changes in visual acuity; culture results; and antibiotic susceptibility were analyzed. Culture results from prior conjunctival swabs and keratitis were also compared.Sixteen eyes from 12 patients (mean age 40.1 ± 27.7 years) with MK were identified. These patients had the most severe ocular involvement in the acute stage and had more severe ocular complications (SOCs) in the chronic stage compared with patients with SJS/TEN without MK. There were 26 infection episodes during 4.4 ± 6.9 (1.0-25.8) years of follow-up. Oral nonsteroidal anti-inflammatory drugs accounted for half of the causative drugs. Severe dry eye was the most common predisposing factor, followed by topical steroid use, trichiasis, and lid margin keratinization. Staphylococcus was the most common pathogen, and over half of the gram-positive bacteria were resistant to oxacillin/methicillin. Fungal infections (notably Candida ) accounted for nearly one-third of the causative microorganisms. Culture reports from periodic conjunctival swabs were not consistent with those from corneal scrapings. Recurrence of infection was associated with inferior visual outcome.Patients with SJS/TEN with SOCs are subject to recurrent corneal infections, which are responsible for deterioration of vision. Identifying the risk factors and aggressive treatment as early as possible is pivotal for infection control.

Delayed drug hypersensitivity continues to contribute to major clinical problems worldwide. The clinical presentations of delayed drug hypersensitivity are diverse, ranging from mild skin rashes to life-threatening systemic reactions. The pathomechanism of delayed drug hypersensitivity involves human leukocyte antigens (HLA) presentation of drugs/metabolites to T cell receptors (TCR), resulting in T-cell activation. The pathogenesis of delayed drug hypersensitivity also has reactivation of the virus, and activation of many immune mediators. In this review, we discuss the immune pathogenesis, molecular interactions of HLA/drugs/TCR, and downstream signaling of cytotoxic proteins/cytokines/chemokines, as well as disease prevention and management for delayed drug hypersensitivity.

Keloid is a type of disfiguring pathological scarring unique to human skin. The disorder is characterized by excessive collagen deposition. Immune cell infiltration is a hallmark of both normal and pathological tissue repair. However, the immunopathological mechanisms of keloid remain unclear. Recent studies have uncovered the pivotal role of both innate and adaptive immunity in modulating the aberrant behavior of keloid fibroblasts. Several novel therapeutics attempting to restore regulation of the immune microenvironment have shown variable efficacy. We review the current understanding of keloid immunopathogenesis and highlight the potential roles of immune pathway-specific therapeutics.

Alterations in the gut microbiota composition and their associated metabolic dysfunction exist in psoriasis. However, the impact of biologics on shaping gut microbiota is not well known. This study aimed to determine the association of gut microorganisms and microbiome-encoded metabolic pathways with the treatment in patients with psoriasis. A total of 48 patients with psoriasis, including 30 cases who received an IL-23 inhibitor (guselkumab) and 18 cases who received an IL-17 inhibitor (secukinumab or ixekizumab) were recruited. Longitudinal profiles of the gut microbiome were conducted by using 16S rRNA gene sequencing. The gut microbial compositions dynamically changed in psoriatic patients during a 24-week treatment. The relative abundance of individual taxa altered differently between patients receiving the IL-23 inhibitor and those receiving the IL-17 inhibitor. Functional prediction of the gut microbiome revealed microbial genes related to metabolism involving the biosynthesis of antibiotics and amino acids were differentially enriched between responders and non-responders receiving IL-17 inhibitors, as the abundance of the taurine and hypotaurine pathway was found to be augmented in responders treated with the IL-23 inhibitor. Our analyses showed a longitudinal shift in the gut microbiota in psoriatic patients after treatment. These taxonomic signatures and functional alterations of the gut microbiome could serve as potential biomarkers for the response to biologics treatment in psoriasis.

The efficacy and safety of dupilumab have been reported previously based on data from controlled clinical trials. The GLOBOSTAD study extends the scope of these trials by providing real-world data. This analysis reports prior treatment usage in patients with atopic dermatitis (AD) initiating treatment with dupilumab in a real-world setting. This 5-year, international, multicentre, non-interventional study (GLOBOSTAD; NCT03992417) included patients ≥12 years-old with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) who initiated dupilumab treatment based on country-specific prescribing information. Data reported are for the population at baseline (N = 952, data cut-off: March 2022). At the study entry, the mean (standard deviation) Patient-Oriented Eczema Measure (POEM) score was 19.7 (6.4). POEM range is 0–28 and scores greater than 17 are consistent with severe or very severe disease. The mean (standard deviation) pruritus on the 0–10 Numerical Rating Scale (NRS) at study entry was 6.3 (2.1). Patient use of systemic treatments such as non-steroidal immunosuppressants (32.6%) and systemic corticosteroids (17.8%), as well as non-systemic treatments such as topical corticosteroids (47.2%) and calcineurin inhibitors (14.8%) in the 12 months preceding enrolment were reported. Ultraviolet phototherapy in the past 12 months was reported for 3.4% of patients. Patient-reported outcomes, including POEM and pruritus NRS, indicate a considerable burden of disease in patients with AD initiating dupilumab in the real world. A large proportion of patients from GLOBOSTAD reported the use of AD-specific systemic and non-systemic therapies prior to dupilumab initiation.

Background Drug reaction with eosinophilia and systemic symptoms (DRESS) is an intractable drug hypersensitivity disease with high mortality. The current standard treatment requires high-dose and long-term systemic corticosteroids, which may lead to adverse effects and intolerability of patients. Objective To evaluate the efficacy and safety of cyclosporine in patients with corticosteroid-dependent DRESS or intolerance to systemic corticosteroids. Methods A retrospective review of 8 patients with corticosteroid-dependent DRESS who were treated with cyclosporine as an alternative treatment owing to suboptimal response to regular doses of systemic corticosteroids for at least 3 weeks, flare-ups when tapering corticosteroids, or experiencing intolerable adverse effects of corticosteroids. Results In all 8 patients (4 women and 4 men; age range, 15-75 years), either intractable skin eruptions, persistent eosinophilia, or elevated liver function was noted after at least 3 weeks of treatment with systemic corticosteroids. The patients had marked cutaneous improvement and normalization of liver function and eosinophil count after adding cyclosporine, and the systemic corticosteroid treatment was smoothly tapered down. The mean dosage of cyclosporine was 1.68 ± 0.73 mg/kg/d, and the mean duration of cyclosporine treatment was 76.13 ± 35.64 days. Their serum eosinophil counts, serum alanine aminotransferase levels, and serum thymus and activation-regulated chemokine levels were all elevated at baseline and then significantly decreased during the recovery stage after cyclosporine therapy (P Conclusion Cyclosporine is an effective and safe therapeutic alternative as a steroid-sparing agent for corticosteroid-dependent DRESS. Further prospective randomized controlled studies are required to confirm these preliminary results.

Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm (41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl .

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Introduction Variants in the low-density lipoprotein receptor–related protein 10 (LRP10), linked to inherited forms of α-synucleinopathies, have been reported. Nine variants of LRP10 were identified in the first such report, and subsequent studies have identified possible pathogenic variants in patients with sporadic Parkinson's disease (PD). Few studies have investigated the role of LRP10 in PD. We sought to validate the role of this gene in Taiwanese patients with PD. Methods In total, 1277 individuals were included in this study (669 had PD and 608 were controls). The entire LRP10 coding exons and exon–intron boundaries were sequenced in 103 probands with early-onset PD or familial PD. We then genotyped the newly identified variants from the 103 patients and previously reported potential pathogenic variants in our cohort. The frequencies of variants were analyzed. Results Five new and possibly pathogenic variants were identified initially. In total, 14 potentially pathogenic variants (including nine previously reported and five newly identified variants) were analyzed thereafter. We did not find any significant associations between any variant and the risk of PD. However, c.1424+5delG was identified in a patient with sporadic PD who was diagnosed as having PD and dementia and who had prominent psychiatric symptoms. Conclusion Although we identified a patient with sporadic PD and dementia carrying a c.1424+5delG variant, our data did not provide sufficient evidence to support the role of LRP10 in PD in Taiwanese adults.

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.

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

Yin-Ku Lin,1,2 Ching-Ya Wang,3,4 Yu-Huei Huang,3,4 Ya-Ching Chang,3,4 Chun-Bing Chen,3– 9 Chuang-Wei Wang,3,5– 7,&ast; Rosaline Chung-Yee Hui,3,4,&ast; Wen-Hung Chung3,5– 12,&ast; 1Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; 2School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan; 4College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; 6Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Linkou, Taiwan; 7Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, People’s Republic of China; 8Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; 9Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; 10Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 11School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 12Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan&ast;These authors contributed equally to this workCorrespondence: Wen-Hung Chung, Chang Gung Memorial Hospital, Linkou Branch, No. 5, Fusing St, Taoyuan, 333, Taiwan, Tel +886 3-3281200 #8495, Fax +886 3-3281200 #2206, Email wenhungchung@yahoo.com; chung1@cgmh.org.twPurpose: 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&ast;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&ast;01:02 (P = 0.01, OR: 0.28). Patients who were HLA-Cw&ast;06:02-positive or HLA-Cw&ast;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&ast;06:02 or HLA-Cw&ast;01:02 alleles and plasma IL-17 levels are predictive markers of treatment response to Lindioil ointment in patients with psoriasis.Keywords: HLA-Cw&ast;06:02, HLA-Cw&ast;01:02, indigo naturalis, Lindioil, IL-17, psoriasis

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.

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.

Background: Nonablative lasers are popular alternatives for atrophic acne scar treatment in Asia. Objectives: We aimed to compare the efficacy and safety between 1550-nm nonablative fractional laser (NAFL) and 755-nm picosecond laser with diffractive lens array (DLA) in Asian patients. Methods: Twenty-three patients with atrophic acne scars received three sessions of split-face treatment with 1550-nm NAFL on one side and 755-nm picosecond laser with DLA on the other side. Sessions were applied at 8-week interval. Blinded dermatologists assessed efficacy through baseline and follow-up photographs. Results: A greater improvement in atrophic facial acne scars was observed on the 1550-nm NAFL side than on the 755-nm picosecond laser side (P < 0.05). Pain was significantly more severe on the 1550-nm NAFL side than the 755-nm picosecond laser side (P < 0.05). Adverse effects on the 1550-nm NAFL side included prolonged erythema, acneiform eruptions, superficial crusting, and postinflammatory hyperpigmentation. Only transient erythema was observed on the 755-nm picosecond laser side. Conclusion: Although the 1550-nm NAFL showed superior efficacy to the 755-nm picosecond laser with DLA for the treatment of atrophic facial acne scars, the latter was associated with fewer adverse effects and may be the best choice for those who request “little-to-no down-time” treatments.

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.

Adverse drug reactions (ADR) remain the major problems in healthcare. Most severe ADR are unpredictable, dose-independent and termed as type B idiosyncratic reactions. Recent pharmacogenomic studies have demonstrated the strong associations between severe ADR and genetic markers, including specific HLA alleles (e.g., HLA-B*15:02/HLA-B*57:01/HLA-A*31:01 for carbamazepine-induced severe cutaneous adverse drug reactions [SCAR], HLA-B*58:01 for allopurinol-SCAR, HLA-B*57:01 for abacavir-hypersensitivity, HLA-B*13:01 for dapsone/co-trimoxazole-induced SCAR, and HLA-A*33:01 for terbinafine-induced liver injury), drug metabolism enzymes (such as CYP2C9*3 for phenytoin-induced SCAR and missense variant of TPMT/NUDT15 for thiopurine-induced leukopenia), drug transporters (e.g., SLCO1B1 polymorphism for statin-induced myopathy), and T cell receptors (Sulfanilamide binding into the CDR3/Vα of the TCR 1.3). This mini review article aims to summarize the current knowledge of pharmacogenomics of severe ADR, and the potentially clinical use of these genetic markers for avoidance of ADR.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe mucocutaneous bullous disorders characterized by widespread skin and mucosal necrosis and detachment, which are most commonly triggered by medications. Despite their rarity, these severe cutaneous adverse drug reactions will result in high mortality and morbidity as well as long-term sequela. The immunopathologic mechanisms is mainly cell-mediated cytotoxic reaction against keratinocytes leading to massive skin necrolysis. Subsequent studies have demonstrated that immune synapse composed of cytotoxic T cells with drug-specific human leukocyte antigen (HLA) class I restriction and T cell receptors (TCR) repertoire is the key pathogenic for SJS/TEN. Various cytotoxic proteins and cytokines such as soluble granulysin, perforin, granzyme B, interleukin-15, Fas ligand, interferon-γ, tumor necrosis factor-α have been as mediators involved in the pathogenesis of SJS/TEN. Early recognition and immediate withdrawal of causative agents, and critical multidisciplinary supportive care are key management of SJS/TEN. To date, there is yet to be a sufficient consensus or recommendation for the immunomodulants of the treatment in SJS/TEN. Systemic corticosteroids remain one of the most common treatment options for SJS/TEN, though the efficacy remain uncertain. Currently, there is increasing evidence showing that cyclosporine and TNF-α inhibitors decrease the mortality of SJS/TEN. Further multicenter double-blinded, randomized, placebo-controlled trials are required to confirm the efficacy and safety.

As the world deals with the COVID-19 pandemic, vaccination remains vital to successfully end this crisis. However, COVID-19-vaccine-induced immediate hypersensitivity reactions presenting with potentially life-threatening systemic anaphylactic reactions are one of the reasons for vaccine hesitancy. Recent studies have suggested that different mechanisms, including IgE-mediated and non-IgE-mediated mast cell activation, may be involved in immediate hypersensitivity. The main culprits triggering hypersensitivity reactions have been suggested to be the excipients of vaccines, including polyethylene glycol and polysorbate 80. Patients with a history of allergic reactions to drugs, foods, or other vaccines may have an increased risk of hypersensitivity reactions to COVID-19 vaccines. Various strategies have been suggested to prevent hypersensitivity reactions, including performing skin tests or in vitro tests before vaccination, administering different vaccines for the primary and following boosters, changing the fractionated doses, or pretreating the anti-IgE antibody. This review discusses the current trends, potential mechanisms, and prevention strategies for COVID-19-vaccine-induced immediate hypersensitivity reactions.

The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance.Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method.Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time.Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.

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.

Cutaneous manifestations resembling Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients with acute graft-versus-host disease (aGVHD); however, the clinicopathological characteristics of SJS/TEN-like aGVHD remain unexplored.To investigate the clinicopathology, complications, and outcomes of patients with SJS/TEN-like aGVHD.We analyzed a multicenter cohort of patients with aGVHD between 2000 and 2021.We analyzed 31 patients with aGVHD, including SJS/TEN-like (n = 15) and non-SJS/TEN-like (n = 16). Patients with SJS/TEN-like aGVHD had significantly more extensive erythema and skin detachment/mucositis. SJS/TEN-like aGVHD was significantly associated with higher aGVHD grading and systemic complications, including pancytopenia, leukopenia, anemia, severe thrombocytopenia, coagulation abnormality, hepatitis, diarrhea, renal dysfunction, and bacteremia. A significantly lower hemoglobin/red cell distribution width ratio was identified in SJS/TEN-like aGVHD. Histopathology showed significant severe dyskeratosis and interface change. Patients with SJS/TEN-like aGVHD had lower 2-month survival rates and 5.35-fold higher 5-year mortality rates than those with non-SJS/TEN-like aGVHD. Total mortality rates of patients with SJS/TEN-like aGVHD reached 80% during follow-up; sepsis predominated the causes of death.Retrospective, nonrandomized study with a small sample size.SJS/TEN-like aGVHD is associated with multiple systemic complications and high mortality. Early recognition, differential diagnosis from drug-induced-SJS/TEN, and appropriate treatment are critical.

Nasal microbiota is crucial for the pathogenesis of allergic rhinitis (AR), which has been reported to be different from that of healthy individuals. However, no study has investigated the microbiota in nasal extracellular vesicles (EVs). We aimed to compare the microbiome composition and diversity in EVs between AR patients and healthy controls (HCs) and reveal the potential metabolic mechanisms in AR.Eosinophil counts and serum immunoglobulin E (IgE) levels were measured in patients with AR (n = 20) and HCs (n = 19). Nasal EVs were identified using transmission electron microscopy and flow cytometry. 16S rRNA sequencing was used to profile the microbial communities. Alpha and beta diversities were analyzed to determine microbial diversity. Taxonomic abundance was analyzed based on the linear discriminant analysis effect size (LEfSe). Microbial metabolic pathways were characterized using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUst2) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.Eosinophils, total serum IgE, and IgE specific toPatients with AR had distinct microbiota characteristics in nasal EVs compared to that in HCs. The metabolic mechanisms of the microbiota that regulate AR development were also different. These findings show that nasal fluid may reflect the specific pattern of microbiome EVs in patients with AR.