Pulmonary interstitial lesions in pemphigus mouse model: Verifying pemphigus may not be only limited to skin and mucosa.

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT-qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD.

DNA methylation of ITGB2 contributes to allopurinol hypersensitivity.

BACKGROUNDS: HLA-B*58:01 allele was strongly associated with allopurinol induced severe cutaneous adverse drug reaction (SCAR). However, HLA-B genotype is not sufficient to predict the occurrence of allopurinol-induced SCAR. OBJECTIVE: To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing. STUDY DESIGN: The study was designed as a retrospective case-control clinical study in multicenter hospitals across Taiwan, Mainland China, Malaysia and Canada. 125 cases of allopurinol-induced SCAR patients and 139 cases of allopurinol tolerant controls were enrolled in this study during 2005 to 2021. RESULTS: The results of genome-wide DNA methylation assay of 62 patients revealed that ITGB2 showed strong discriminative ability of allopurinol-induced SCAR in both HLA-B*58:01 positive and negative patients with AUC value of 0.9364 (95% CI 0.8682-1.000). In validation study, significant hypermethylation of ITGB2 were further validated in allopurinol-induced SCAR patients compared to tolerant controls, especially in those without HLA-B*58:01(AUC value of 0.8814 (95% CI 0.7121-1.000)). Additionally, the methylation levels of 2 sites on ITGB2 were associated with SCAR phenotypes. Combination of HLA-B*58:01 genotyping and ITGB2 methylation status could improve the prediction accuracy of allopurinol-induced SCAR with the AUC value up to 0.9387 (95% CI 0.9089-0.9684), while the AUC value of HLA-B*58:01 genotyping alone was 0.8557 (95% CI 0.8030-0.9083). CONCLUSIONS: Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*58:01 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR.

Photosensitivity is an important cause of refractory facial erythema in atopic dermatitis: A retrospective study of 82 Chinese patients.

BACKGROUND: Ultraviolet radiation can aggravate facial erythema in atopic dermatitis (AD) patients. OBJECTIVE: To investigate the photobiological testing results of Chinese AD patients with refractory facial erythema. METHODS: We conducted a retrospective analysis of 82 AD patients with refractory facial erythema who visited our department during 2004-2021. All of them completed phototesting and photopatch testing. RESULTS: 82 patients were enrolled in the study, and 53 (64.6%) were between 18 and 30 years old. 51.2% (42/82) had positive phototesting results and were considered photosensitive AD (PhAD) patients. One-third of them were both allergic to ultraviolet A and ultraviolet B. 65.9% (54/82) suffered from photoallergic contact dermatitis. Chlorpromazine (50.7%), potassium dichromate (13.2%), and thimerosal (11.8%) were the top three common photoallergens. Overall, 86.3% of AD patients with refractory facial erythema had direct photoallergy or photocontact allergy. PhAD patients had fewer allergic comorbidities than the other group (p = .007). More non-PhAD patients (55.0%) suffered from AD at 2-14 years old (p = .015). CONCLUSIONS: Photosensitivity contributes a lot to the facial lesions of AD patients, especially in their 20s. 86.3% of these patients had direct photoallergy or photocontact allergy. Therefore, AD patients with facial erythema should undergo phototesting and photopatch testing routinely.

Chronic actinic dermatitis: A 5-year clinical analysis of 488 patients in China.

BACKGROUND/PURPOSE: Chronic actinic dermatitis (CAD) is a spectrum of diseases with chronic photosensitivity occurring mostly among middle-aged and older men. We seek to explore the characteristics and pathogenesis of CAD among the Chinese population. METHODS: The medical records of 488 CAD cases diagnosed by phototesting at Huashan Hospital, Fudan University from January 2014 to December 2018 were analyzed retrospectively. RESULTS: Among the 488 patients, 344 were male and 144 were female. 84.8% of the cases were over 40 years old at the age of onset, while the remaining with an early age of onset had a prevalence of atopic history of 21.6%. Up to 45.0% of the patients reported excessive sun exposure and outdoor activities before the initiation of symptoms. The typical skin lesions were erythema, papules and plaques laid predominantly in sun-exposed areas. 42.8% of the cases showed sensitivity to UVB only, 20.7% were both sensitive to UVA and UVB, and 18.2% had UVA sensitivity only. The most predominant photoallergens were chlorpromazine (80.1%), thimerosal (17.2%), potassium dichromate (12.7%), etc. The most prevalent patch test allergens were potassium dichromate (24.4%), thimerosal (20.5%), formaldehyde (16.8%), etc. CONCLUSIONS: CAD was more commonly seen in males over 40 years old. The action spectrum of Chinese patients is primarily in the UVB range. Exposure to excessive sunlight or contact allergens and photoallergens are important risk factors. Photobiology tests are essential in detecting photosensitivity and recognizing potential photosensitizers. Early avoidance of confirmed photoallergens and sun exposure may prevent photosensitive reactions from progressing into persistent photosensitivity.

Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid.

Routine systemic therapy for bullous pemphigoid (BP) has been challenged due to the inevitably adverse effects. According to the successful applications of dupilumab in BP cases reported, therefore, we investigate the real-life efficacy and safety of dupilumab combined with low-dose oral steroid for BP. A cohort of BP patients who received either dupilumab plus low-dose methylprednisolone (dupilumab group) or merely methylprednisolone (control group) was retrospectively reviewed. The time to disease control was investigated. Additionally, the control dose and cumulative dosage of steroids, Bullous Pemphigoid Disease Area Index (BPDAI) scores, pruritus scores, and adverse events were assessed. A total of 40 patients, with 20 in each group, were retrospectively studied. The time to disease control was shorter in the dupilumab group than the control group (14 days vs. 19 days, p = 0.043). When the disease was controlled, the control dose and cumulative dosage of methylprednisolone in the dupilumab group were substantially lower than those of the control (24.6 mg vs. 48.8 mg, 376.8 mg vs. 985.6 mg, both p < 0.01). Compared with the control, the percentage change from baseline in BPDAI scores and pruritus scores were both significantly reduced, and the adverse events were also less frequent in the dupilumab group. The combination therapy of dupilumab plus low-dose methylprednisolone exhibits superior efficacy and safety in comparison with the current first-line systemic therapy for BP.

The Efficacy and Safety of Fractional 1064 nm Nd:YAG Picosecond Laser Combined With Intense Pulsed Light in the Treatment of Atrophic Acne Scar: A Split-Face Study.

BACKGROUND AND OBJECTIVES: To evaluate the efficacy and safety of fractional 1064 nm Nd:YAG picosecond laser combined with intense pulsed light (IPL) in the treatment of atrophic acne scar with post-inflammatory erythema (PIE). © 2021 Wiley Periodicals LLC. STUDY DESIGN/MATERIALS AND METHODS: Seventeen patients received five sessions of treatment at weeks 0, 4, 8, 12, 16 and were followed up at week 28. One half of the face was randomly treated by fractional 1064 nm Nd:YAG picosecond laser combined with IPL (FxPico + IPL), and the other by IPL alone as a control. RESULTS: For the 15 patients who completed the study, the FxPico + IPL side demonstrated significant median Échelle D'évaluation clinique des cicatrices D'acné (ECCA) score improvement (P < 0.01), while IPL alone side did not (P = 0.1250). The pore counts for both sides decreased but more pore count reduction was seen on the FxPico + IPL side (P < 0.05). Better scar improvement was observed on the FxPico + IPL-treated side (P < 0.05) while no difference in erythema improvement was seen between the two sides. There was no difference between the two treatments in terms of overall satisfaction. Pain, erythema, edema, petechiae, crusting, reactive acneiform eruptions, and pruritus were common adverse effects and were mild to moderate. CONCLUSION: FxPico + IPL is an effective, efficient, and safe treatment regimen for atrophic acne scars complicated by PIE.

HLA-A*02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population.

Tanshinone, a widely used Chinese patent medicine, has been confirmed to have various kinds of pharmacological effects although frequently causing cutaneous adverse drug reactions (cADRs). We aim to identify whether human leukocyte antigen (HLA) class I alleles are associated with tanshinone-induced cADRs in Han Chinese. The association study including 18 patients with tanshinone-induced cADRs, 67 tanshinone-tolerant volunteers, and two general population databases consisted of 10,689 and 169,995 healthy subjects was performed. The frequency of tanshinone-induced cADRs patients carrying HLA-A*02:01 was significantly higher when compared with the general control groups (OR = 6.25, Pc = 7.20 × 10-5; OR = 7.14, Pc = 8.00 × 10-6), and with the tolerant group (OR = 5.09, Pc = 0.024). The molecular docking assay confirmed high affinity of the ingredients of tanshinone towards HLA-A*02:01 (≤-7.5 kcal/mol). The result suggested HLA-A*02:01 may work as a promisingly predictive marker for tanshinone personalized therapy in Han Chinese.

HLA-C*12:02 is strongly associated with Xuesaitong-induced cutaneous adverse drug reactions.

Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown mechanisms of pathogenicity or risk factors. We aimed to verify whether human leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han Chinese population. We carried out an association study including 12 subjects with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of 12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received XST via intravenous drip. The carrier frequency of HLA-C*12:02 was significantly high compare to that of the control population (Pc = 4.4 × 10-4, odds ratio (OR) = 21.75, 95% CI = 5.78-81.88). Compared with that of the XST-tolerant group, the patients who received XST through intravenous drip presented a higher OR of cADRs (Pc = 0.011, OR = 27.00, 95% CI = 2.58-282.98). The results suggest that HLA-C*12:02 is a potentially predictive marker of XST-induced cADRs in Han Chinese, especially when XST is administered via intravenous drip.

Skin ulcers infected with conditional pathogenic strains treated with local hydrogen water packing in two pemphigus vulgaris patients: Case reports with follow-up for 2 months.

We are the first to report on a new, safe, and effective treatment of infections induced by conditional pathogenic strains with local wet packing with hydrogen water. The new treatment method may also shed light on the therapy of chronic, inflammatory skin ulcers.

Clinical, Viral and Genetic Characteristics of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in Shanghai, China.

DRESS is one of the most severe drug reactions. The aim of this retrospective study was to summarize the clinical presentation, genetic predisposition and prognostic factors of DRESS. A total of 52 patients with DRESS, who were inpatients at a medical referral centre in Shanghai, China, from January 2011 to December 2016, were analysed retrospectively. All the patients had skin eruption, 83% had liver involvement, and ≤10% had other organ involvement. Mean cost of hospitalization was US$5,511±3,050. The 3 most common causative agents were allopurinol (18/52; 35%), salazosulphapyridine (11/52; 21%) and carbamazepine (5/52; 10%). HLA-B*5801 and HLA-B*1302 were associated with allopurinol-induced DRESS. HLA-B*1301 was related to salazosulphapyridine-induced DRESS. The mortality rate was 6% (3/52). Epstein-Barr virus DNA was found in 10 patients (19%) and indicated a poor prognosis. Human herpes virus 6 DNA was detected in 17 patients (33%) and was associated with autoimmune sequelae. Due to its high medical cost and sometimes poor prognosis, prevention of DRESS should be a high priority.

Evaluation of narrow band ultraviolet B phototherapy in the treatment of chronic actinic dermatitis in Chinese patients.

Few studies have been conducted in chronic actinic dermatitis (CAD) treated with narrowband ultraviolet B (NB UVB) phototherapy, especially in Asian patients. We aim to evaluate the efficacy and safety of NB UVB phototherapy in Chinese patients with CAD. 19 CAD patients of Fitzpatrick skin phototype IV received NB UVB phototherapy in spring and treatments were given 3 times weekly with incremental dose and maintenance therapy was given twice weekly for 3-4 weeks. The mean initial, endpoint, and cumulative dose of NB UVB was 0.08, 0.33, and 6.0 J/cm2 , respectively. Patients totally received 27 times of treatments in average. 87.5% of previously ultraviolet B（UVB） sensitive patients and 75% of previously ultraviolet A（UVA） sensitive patients had normal or improved MED after phototherapy. The percentage of patients returned to normal UVB phototesting was higher than that of patients returned to normal UVA phototesting (68.8% vs. 37.5%). The mean 1-week DLQI and the need for using immunosuppressive agents and antihistamines were significantly reduced after treatment (p < .01 or p < .05). In conclusion, prophylactic NB UVB phototherapy is effective and safe in treatment of CAD in Chinese patients with Fitzpatrick skin phototype IV.

Variable levels of apoptotic signal-associated cytokines in the disease course of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND/OBJECTIVES: Keratinocyte death is a hallmark of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Apoptotic signal-associated cytokines, such as TNF-α, sFasL, granulysin, sTRAIL and IFN-γ have been reported to participate in keratinocyte apoptosis. However, their levels are variable, which hampers the elucidation of the role of these cytokines. We sought to determine whether cytokine levels vary with disease course. METHODS: The serum cytokine levels of 24 patients and blister fluid of 10 were analysed by enzyme-linked immunosorbent assay on the first day of their admission to hospital and were evaluated at different time points in the disease course. Meanwhile, surface markers (CD3, CD4, CD8, CD1a, CD14, CD16+56 and CD68) of blister fluid cells were measured by flow cytometry. RESULTS: The concentrations of all cytokines in the serum and blister fluid were higher than those in the controls and were more elevated in the blister fluid than in the serum. Moreover, sTRAIL, IFN-γ and TNF-α quantities were relatively stable, while those of sFasL and granulysin decreased rapidly in the disease course. On the first day, CD8+ T and natural killer cells were predominant in the blister fluid but their relative percentage diminished gradually, while that of CD14+ cells increased. CONCLUSION: Our study confirmed there are high but variable levels of these cytokines in SJS/TEN, especially in the early phase and different tendencies are manifested in the disease course.

HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients.

OBJECTIVE: Tetanus antitoxin (TAT) is an effective antitetanus medicine, but may sometimes cause adverse drug reactions such as rapid-onset anaphylactic shock and late-onset cutaneous adverse drug reactions, including exanthematous drug eruptions (EDE). Human leukocyte antigen (HLA) class I alleles are strongly associated with different types of cutaneous adverse drug reactions. This study aimed to assess whether there is an association between TAT-induced EDE and HLA-A, HLA-B, and HLA-C alleles in the Chinese Han population. PATIENTS AND METHODS: We carried out an association study in 15 patients with TAT-induced EDE and two groups of general Han Chinese patients. Allele-level genotypes of the HLA-A, HLA-B, and HLA-C genes of each patient were determined using the PCR-sequence-specific oligonucleotides method. RESULTS: The carrier frequency of HLA serotype A2 was significantly higher in the TAT-induced EDE patients than in the general Han Chinese study participants from the human major histocompatibility complex database [n=283, odds ratio (OR)=6.93; P=0.0061]. Particularly, the carrier frequency of three A2 alleles, including HLA-A*02:01, HLA-A*02:06, and HLA-A*02:07, is significantly higher than that of the control group (OR=14.40; P=2.4×10). Furthermore, HLA-B*39:01 was in complete linkage disequilibrium with HLA-A*02:06 in the case patients. Consequently, the distribution of the HLA-A*02:06/-B*39:01 haplotype was also significantly different in the cases and the controls (OR=105.00; P=0.0024). CONCLUSION: The HLA-A*02:06/-B*39:01 haplotype is a potential genetic marker for the TAT-induced EDE. Furthermore, the HLA-A2 serotype, especially three alleles A*02:01, A*02:06, and A*02:07, was identified to be associated with the TAT-induced EDE in the Han Chinese population for the first time.

Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.

Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions.

Detection of HLA-B*58:01 with TaqMan assay and its association with allopurinol-induced sCADR.

BACKGROUND: The HLA-B*58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B*58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B*58:01 and to investigate the association of HLA-B*58:01 with allopurinol-induced sCADR in a Han Chinese population. METHODS: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B*58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B*58:01-positive DNA template. RESULTS: The new method successfully identified HLA-B*58:01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B*58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLA-B*58:01 was significantly higher in the sCADR group than in the control group (p<0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p=0.1547). CONCLUSIONS: HLA-B*58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B*58:01 detection prior to allopurinol therapy.

The association between HLA-B variants and amoxicillin-induced severe cutaneous adverse reactions in Chinese han population.

Background: Amoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs. Methodology: Four patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins. Results: Compared with AMX-tolerant controls, a significant association of HLA-B*15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68-1275.67; p = 7.34 × 10-3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10-4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis. Conclusion: Our findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMX-induced SCAR still needs to be further explored in larger cohort studies and other ethnic populations.

Epidemiological Insights into Autoimmune Bullous Diseases in China: A Comprehensive Analysis.

OBJECTIVE: This study aims to conduct an extensive analysis of autoimmune bullous diseases, particularly pemphigus vulgaris and bullous pemphigoid, in Shanghai, China, from 2016 to 2023. It seeks to understand the demographic profiles, comorbidities, mortality rates, risk factors, and socioeconomic impacts associated with autoimmune bullous disease. METHODS: A cross-sectional study design was employed, enrolling 1,072 patients. Diagnostic measures included clinical manifestations, histopathology, direct immunofluorescence, and serologic tests. The study also involved a detailed socioeconomic analysis and evaluation of occupational risks. RESULTS: The findings highlight a significant occupational risk in industries requiring enhanced safety measures, with a notable prevalence of autoimmune bullous disease among workers in these sectors. A considerable portion of the patients were from low-income backgrounds with limited literacy, indicating the economic burden of autoimmune bullous disease. A key discovery of the study is the potential pathological link between autoimmune bullous disease and interstitial lung disease. CONCLUSION: This research, one of the first comprehensive studies on autoimmune bullous disease in China, underscores the need for targeted healthcare strategies and further investigation into autoimmune bullous disease, particularly its relationship with interstitial lung disease.

Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy.

Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is mainly based on the systemic use of corticosteroids, but long-term use of corticosteroids results in a series of side effects. Type 2 inflammation is an immune response largely mediated by group 2 innate lymphoid cells, type 2 T helper cells, eosinophils, and inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13. Among patients with BP, the levels of immunoglobulin E and eosinophils are significantly increased in the peripheral blood and skin lesions, suggesting that the pathogenesis is tightly related to type 2 inflammation. To date, various targeted drugs have been developed to treat type 2 inflammatory diseases. In this review, we summarize the general process of type 2 inflammation, its role in the pathogenesis of BP and potential therapeutic targets and medications related to type 2 inflammation. The content of this review may contribute to the development of more effective drugs with fewer side effects for the treatment of BP.

Efficacy and Safety of Hydrogen Therapy in Patients with Early-Stage Interstitial Lung Disease: A Single-Center, Randomized, Parallel-Group Controlled Trial.

Purpose: Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD. Patients and Methods: A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis. Results: The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in DLCO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV1, FEV1/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (P=0.706). Conclusion: Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.

An association study of HLA with levofloxacin-induced severe cutaneous adverse drug reactions in Han Chinese.

Levofloxacin-induced severe cutaneous adverse drug reactions (LEV-SCARs) remain unexplored. An association study of human leukocyte antigen (HLA) alleles with LEV-SCARs among 12 patients, 806 healthy subjects, and 100 levofloxacin-tolerant individuals was performed. The carrier frequencies of HLA-B∗13:01 (odds ratio [OR]: 4.50; 95% confidence interval [CI]: 1.15-17.65; p = 0.043), HLA-B∗13:02 (OR: 6.14; 95% CI: 1.73-21.76; p = 0.0072), and serotype B13 (OR: 17.73; 95% CI: 3.61-86.95; p = 4.85 × 10-5) in patients with LEV-SCARs were significantly higher than those of levofloxacin-tolerant individuals. Molecular docking analysis suggested that levofloxacin formed more stable binding models with HLA-B∗13:01 and HLA-B∗13:02 than with non-risk HLA-B∗46:01. Mass spectrometry revealed that nonapeptides bound to HLA-B∗13:02 shifted at several positions after exposure to levofloxacin. Prospective screening for serotype B13 (sensitivity: 83%, specificity: 78%) and alternative drug treatment for carriers may significantly decrease the incidence of LEV-SCARs.