Dermatitis bullosa caused by the immune checkpoint inhibitor camrelizumab:A case report

BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.

Targeted therapy outcomes in acrodermatitis continua of Hallopeau: A systematic review

Dear Editor,Acrodermatitis continua of Hallopeau(ACH),a rare and chronic variant of pustular psoriasis,is characterized by atrophic skin changes,sterile pustules,onychodystrophy,and osteolysis of the distal phalanges of the fingers and toes.Given the absence of international consensus guidelines and comprehensive clinical studies of high methodological rigor,the management of ACH primarily relies on antipsoriatic therapeutic approaches and empirical evidence derived from scattered case reports.With the development of biologics and small-molecule drugs,targeted therapies hold some promise for the future of its successful management[1].Here we summarize treatment outcomes of targeted therapies for ACH.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Xylooligosaccharides Alleviate Inflammatory Dermatoses and Related Depression-Like Behaviors in Atopic Dermatitis Mice Induced by 2,4-Dinitrofluorobenzene

Objective:To investigate the influence of xylooligosaccharides on skin inflammation,behavioral characteristics,neurotransmitters,and gut flora in a mouse model of atopic dermatitis(AD)induced by 2,4-dinitrofluorobenzene(DNFB).Methods:The AD mouse model was created by administration of DNFB for 14 consecutive days.The scoring atopic dermatitis index,enzyme-linked immunosorbent assay(ELISA),histopathology,and immunohistochemical analyses were used to assess inflammation and depression-like behaviors.Furthermore,high-throughput 16S rRNA gene sequencing was used to determine the composition of fecal microbiota.Results:Xylooligosaccharides treatment reduced the number of scratches and skin thickness,mast cell infiltration and the levels of immunoglobulin(Ig)E and T-helper cytokines compared with the AD model group.Meanwhile,xylooligosaccharides treatment reduced the immobility time of mice in the forced swimming test and increased the total movement distance and movement distance in the center area in the open-field test.Furthermore,5-hydroxytryptamine and dopamine expression in the brain was increased following xylooligosaccharides treatment.Using network pharmacology,Gene Ontology analysis showed that the targets were mainly enriched in phosphatase binding and the regulation of leukocyte differentiation,which ameliorated AD mainly through the hypoxia inducible factor-1 and phosphatidylinositide 3-kinase-protein kinase B pathways.16S rRNA gene sequencing,diversity indices,and gut microbial taxonomic composition analysis showed DNFB-induced changes in intestinal microbiota diversity in AD mice.Comparative analysis indicated that xylooligosaccharides intake improved the gut microbiome by dramatically enhancing the concentration of Lactobacillus while decreasing the concentration of Bacteroides in mice.Conclusion:Xylooligosaccharides reduce inflammatory dermatosis and related depression-like behaviors via regulating intestinal homeostasis,having medicinal value as a nutritional and functional ingredient.

Outcome of Nurses with Occupational Dermatitis

Background: Occupational dermatitis is considered as the second most common occupational disease. It accounts for 25% of all lost workdays. Several international studies reported a prevalence of occupational dermatitis in healthcare workers between 17% and 55%. This study aims to identify factors that affect the professional outcome of nurses suffering from occupational dermatitis. Methods: This was a multicenter cross-sectional study concerning nurses declared having occupational dermatitis in the central region of Tunisia. A synoptic sheet related to socio-professional and administrative data was completed. A self-administered Questionnaire going over medical and occupational characteristics was completed during a direct interview. Results: The study involved forty nurses working in four public hospitals in the center of Tunisia. Only 37 workers were included in the study. A professional reclassification was introduced among 19 workers (51% of study population). Work-station adaptation was requested in 14 cases (38%). Exposure to allergens in the workplace was eliminated in 20 cases. Two study participants were transferred to other departments (5.4%) and three people retired (8.1%). A statistically significant association was found between professional reclassification and a history of allergic manifestations (p = 0.003). Similarly, a significant association was found between professional reclassification and the allergic agent (p = 0.014). Workstation layout was significantly associated with a history of allergic manifestations (p = 0.039), the palm hand location (p = 0.04), professional eviction (p Conclusion: This study identified the main factors influencing the occupational outcome of nurses suffering from occupational dermatitis. This outcome depended on a history of atopy (especially allergic rhinitis) and sensitization to allergens (thiuram mix).

Preparation of anti-canine interleukin-31 receptor alpha polyclonal antibody and evaluation of its therapeutic efect in canine atopic dermatitis

Canine atopic dermatitis(CAD)is a prevalent genetically susceptible infammatory and pruritic allergic skin condition afecting not only the health of dogs but also the quality of life of their owners.Interleukin-31(IL-31)and interleukin-31 receptor alpha(IL-31RA)are essential for the development of pruritus in primates and mice.Hence,it is expected that inhibiting IL-31RA will be an efective approach to alleviate pruritus.The purpose of the study was to produce anti-canine IL-31RA polyclonal antibodies(anti-IL-31RA pAbs)and evaluate their efcacy in inhibiting house dust mite(HDM)-evoked pruritic responses.Dogs were immunized with antigens formed by IL-31RA recombinant short peptides coupled to BSA to produce anti-IL-31RA pAbs.The CAD model was developed by using HDM allergen stimulation,and the efects of IL-31RA pAbs on the reduction of pruritus in CAD model dogs were examined.The Canine Atopic Dermatitis Extent and Severity Index(CADESI)-4 and pruritus Visual Analog Scale(pVAS)were utilized to evaluate pruritic responses,and skin tissue samples were collected from the inguinal area for pathological assessment of skin infammatory cell infltration.The results showed that anti-IL-31RA pAbs with high titers(1:128,000)and specifcity were efectively produced.In the CAD model group,the severity of skin damage,pruritus score,infammatory cell infltration and level of infammatory factors were considerably elevated.Anti-IL-31RA pAbs relieved pruritic behavior and dermatitis in dogs compared to placebo-treated dogs.In conclusion,anti-IL-31RA pAbs efectively suppressed CAD in vivo and are anticipated to be an efective novel treatment for pruritic skin disorders such as CAD.

Blue Cap Is Effective and Safe for the Treatment of Atopic Dermatitis in Children

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Treatment of AD is based on skin barrier repair and reduction of inflammation. We analyzed the efficacy and safety of activated piroctone olamine (APO)—Blue Cap—in children with AD. Materials and Methods: An open-label interventional clinical study was carried out at three clinical centers in Serbia. A total of 58 patients with AD, aged between 3 and 18 years were included and treated with Blue Cap Foam (100 ml;CATALYSIS S.L. Madrid)—Activated Piroctone Olamine—applied twice a day in the affected areas with eczema for 30 days and final assessment at 45 days from baseline. Photographic documentation, clinical evaluation, therapy effectiveness and safety questionnaires were assessed at baseline, 15, 30 and 45 days. Results: Our results demonstrated a significant reduction in signs (erythema, scaling, infiltration, excoriations, xerosis) and symptoms (pruritus) at weeks 2 and 4 of the study. At the end of the study, most patients had moderate (28.6%) to great (62.5%) disappearance of manifestations and moderate (25%) to great (71.4%) skin quality improvement. The effect and tolerability of the therapy were evaluated as very good in 66.1 % and 67.9% and good in about 14.3% and 17.9%, assessed by the investigator and patient, respectively. Three patients experienced a burning sensation at the beginning of the study, the side-effects were resolved as the patients continued applying the foam. After two weeks of cessation of the investigated foam, a significant percentage of patients experienced worsening in the final assessment done by the investigator as well as the participant. In the final assessment, a significantly high percentage (57.1%) of patients had a total reduction of manifestation, and a significant number of participants considered the applied product as treatment success, assessed by the investigator (62.5%) as well as the participants (66.4%). Conclusions: Blue Cap is effective and safe in children with AD, although further large-scale randomized controlled trials should confirm our study findings.

Psychosocial and Socioeconomic Barriers to Treatment Adherence in Pediatric Atopic Dermatitis

Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

Preprocessing and Efficacy Analysis of Comprehensive Anti-Inflammatory Treatment for Lymphedema in Patients with Irritating Contact Dermatitis

Objective: To explore the pre-treatment and efficacy analysis of comprehensive anti-inflammatory treatment for lymphedema in patients with irritating contact dermatitis. Method: Convenience sampling method was used to observe the skin of 160 patients with upper limb lymphedema admitted to the lymphedema outpatient department of our hospital. They were divided into an observation group (80 cases) and a control group (80 cases), and both groups received a course of comprehensive anti-inflammatory treatment (20 treatments). The control group received routine skin care;On the basis of the control group, the observation group received pre-treatment of the affected limb skin: Laofuzi herbal ointment was applied externally to the prone areas of irritating contact dermatitis (such as the upper arm, inner forearm, and cubital fossa). Result: The incidence of irritating contact dermatitis in the observation group was significantly lower than that in the control group (P 0.05). Patients in the observation group felt significantly better in terms of comfort, skin moisture, and itching relief after being wrapped with low elasticity bandages than those in the control group (P Conclusion: Preventive treatment can effectively reduce the incidence of irritating contact dermatitis, prolong the time of stress treatment, thereby increasing efficacy and improving patient compliance.

Advancements in the application of natural extracts for atopic dermatitis treatment

Atopic dermatitis,a common chronic inflammatory skin disease,has an unclear etiology and may involve multiple factors such as genetic predisposition,immune abnormalities,and impaired skin barrier function.Currently,there is no specific medication available for the complete cure of atopic dermatitis.The current treatment approaches mainly focus on symptom relief and control rather than curative treatment.Some commonly used medications for atopic dermatitis,such as topical corticosteroids and immunosuppressants,may have certain adverse reactions and side effects.This review summarizes the research progress on natural extracts in the treatment of atopic dermatitis,aiming to provide a foundation for the development of safe and side-effectfree medications.

Correlation Analysis Between Children with Atopic Dermatitis and Asthma and Factors Affecting Intestinal Flora

Objective:In order to reveal the potential association between intestinal flora and atopic dermatitis with asthma,the study compares the changes in intestinal flora before and after treatment with antibiotics in children and explores the risk factors for the disease development in children.The differences between asthma-controlled children and healthy children were also analyzed to investigate whether there was a correlation between the level of control and intestinal flora in asthmatic children.Methods:367 children with atopic dermatitis and asthma were selected,and the control group was healthy children who did not have other skin diseases.Fecal samples were collected from healthy children and children with asthma,and the intestinal flora was tested at Beijing Nebula Medical Testing Laboratory Co.At the same time,50 children were selected according to the inclusion and exclusion criteria to take amide antibiotics during hospitalization,and stool samples were collected before and after taking antibiotics.Results:The proportion of Gram-positive cocci increased and the proportion of Gram-positive bacilli decreased after the administration of antibiotics in children with atopic dermatitis and asthma(P<0.05),and no significant difference was shown in the gender and age of the children(P>0.05).The proportion of family history of atopic dermatitis with asthma was higher in the experimental group(P<0.05).Conclusion:The use of antibiotics in children with atopic dermatitis with asthma showed a positive correlation with changes in intestinal flora.The use of antibiotics may lead to changes in intestinal flora and increase the risk of atopic dermatitis with asthma.Antibiotic use in infancy and childhood is also recognized as a risk factor for atopic dermatitis with asthma.Therefore,the use of antibiotics should be minimized in preventing and treating atopic dermatitis with asthma.

drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease

The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of

Practical guidelines for diagnosis and early management of drug-induced liver injury

The spectrum of drug-induced liver injury （DILI） is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method （CIOMS/RUCAM） scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, and total bilirubin （T-Bil）. However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.

Study on the therapeutic mechanisms of pseudolaric acid in mice with allergic contact dermatitis

Objective:To study the therapeutic mechanisms of pseudolaric acid on allergic contact dermatitis in mice.Methods:A total of 50 BALB/C mice were selected and randomly divided into control group,model group,and treatment A,B,C groups with 10 rats in each group.ACD model was established in model group,and treatment A,B,C groups but not in control group.Model group received no treatment,but treatment A,B,C groups were treated with external application of the concentration of 0.1%,0.2% and 0.4% of the pseudolaric acid for the lesions of ear skin.And the weight gain and the swelling degree of the mice' ear were recorded,weight of thymus and spleen were measured.Spleen suspension was prepared to test T lymphocyte and B lymphocyte levels of mice in five groups.Changes in serum IFN-ed through the enzyme linked immunosorbent assay(ELISAγ,IL-4 and IL-10 levels were test).Results:The weight gain of mice in model group were significant lower than those of mice in the control group and the treatment A,B,C groups(P<0.05).Weight gain of mice in treatment A,B groups were significant lower than that of control group(P<0.05),but the difference in weight gain between treatment C group and control group showed no significant difference(P>0.05).The swelling degree and the weight of mice ears in model group were significant higher than those of mice in control group and treatment A,B,C groups(P<0.05).Swelling degree and the weight of mice ears of treatment A,B,C groups were obviously higher than that of control group(P<0.05).The swelling degree and weight of mice' ears in treatment A,B,C groups were decreased with the increase of the drug dosage,but comparison between A,B and C group showed statistically differences(P<0.05).The thymus and spleen index of mice in model group were significant higher than those of the other four groups(P<0.05),among the four groups,thymus and spleen index of treatment A and B group were higher than control group and treatment C group(P<0.05).The stimulation index of T and B cells of mice in model group was significantly higher than the rest four groups(P<0.05).The serum IFN-γ level of mice in control group and treatment A,B and C group was obviously lower than that of mice in model group(P<0.05).The serum IFN-γ level of mice in treatment A,B and C group were decreased with the increasing of the drug dosage,and the level of C group was obviously lower than that of A and B group(P<0.05).Conclusion:The pseudolaric acid has anti-inflammation and immune adjustment the effects showing a remarkable therapeutic effects for the ACD mice.

Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the Pub Med database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals(including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agentseither as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.

Drug-induced liver injury:Is it somehow foreseeable?

The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.

Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.