Effects of Adalimumab Entering National Reimbursement on Medical Costs for Patients With Psoriasis:A 4-Year Single-Center Retrospective Study in China

Objective:Adalimumab(ADA)is expensive and rarely used among patients.However,its cost for moderate to severe chronic plaque psoriasis can now be reimbursed since its addition to the National Reimbursement Drug List(NRDL)in January 2020.Therefore,we conducted this study to estimate the medical cost of ADA and its influencing factors in patients with psoriasis using ADA and thus gain a better understanding of the effect of the NRDL adjustment in China.Methods:This retrospective study evaluated the medical cost of ADA before and after the addition of ADA to the NRDL(2018—2022)among 320 patients in a large professional dermatology specialty hospital.Descriptive analysis,Welch’s analysis of variance,and multiple regression analysis were used to evaluate the medical cost and influencing factors.Results:Before ADA was added to the NRDL,patients’mean total cost and ADA cost were¥24,243.56±16,346.53 and¥20,391.11±14,440.69,respectively.After ADA became covered by the NRDL,the above 2 expenses decreased to¥10,461.19±7,554.66 and¥8,775.27±7,092.16,respectively.This significant decrease in the cost of ADA resulted in a significant 110.5-times increase in ADA use.Statistically significant differences were found in the total cost,patient type(outpatient/inpatient),insurance status(yes/no),reimbursement status(before/after),and age.Medical insurance reimbursement(P<0.001,β=-0.468,before reimbursement=1,after reimbursement=2)was the most significant influencing factor,followed by patient type(P=0.018,β=-0.215,outpatient=1,inpatient=2)and age(P=0.0046,β=-0.174).Conclusion:Medical insurance reimbursement is the most important factor affecting patients’total cost of ADA by reducing the economic burden,enhancing the availability of ADA,and stimulating the need for treatment.

Development and Validation of Diagnostic Criteria for Elderly Atopic Dermatitis

Objective:Elderly atopic dermatitis(AD)is a newly identified subtype of AD.Whether specific diagnostic criteria are needed for elderly AD has been debated.This study aimed to propose diagnostic criteria for elderly AD and evaluate the sensitivity.Methods:A hospital-based study was conducted.We screened the clinical features of 1,312 patients with AD of different ages in 1 cohort and proposed a set of diagnostic criteria for elderly AD.The criteria were then validated in another cohort of 223 patients clinically diagnosed with elderly AD by dermatologists specialized in AD to examine the diagnostic sensitivity compared with other criteria by chi-square test.Results:Based on the patients’clinical features,a set of diagnostic criteria for elderly AD were proposed.The new diagnostic criteria showed significantly higher sensitivity than the classical diagnostic criteria(P<0.001),especially for mild and moderate AD(P<0.001).Of all 223 patients with elderly AD,93.3%fulfilled our criteria,while only 43.5%,65.5%,and 52.0%fulfilled the Hanifin and Rajka criteria,the Japanese Dermatology Academy criteria,and the United Kingdom Working Party criteria,respectively.Conclusion:The newly proposed criteria for elderly AD yielded high diagnostic sensitivity,particularly for mild and moderate AD.

Epidemiology of Leprosy in China,2021:An Update

Objective:Leprosy is an infectious diseases that remains a concerning public health issue.The infection of Mycobacterium leprae still exists at the county level in hard-to-access areas in southwest China.An accurate analysis of the prevalence of leprosy in various regions is necessary for the formulation of prevention and control strategies,so we conducted this study to describe the epidemiological characteristics of leprosy in China in 2021 and provide essential information for future national leprosy control and prevention strategies.Methods:We collected epidemiological data of leprosy from 31 provinces,autonomous regions,and municipalities of China(except for Hong Kong,Macao,and Taiwan)provided by the Leprosy Management Information System.We performed a comparative analysis of the epidemiological features of patients with leprosy including age,sex,geographical distribution,and grade of disability.Results:In total,374 newly detected leprosy cases were reported nationwide in China in 2021,giving an incidence rate of 0.27 per million population,which represented a decrease of 7.9%compared with 2020.Among the population with leprosy in 2021 that comprised 238 males(63.6%)and 136 females(36.4%),1.9%(7/374)were children younger than 15 years,92.8%(347/374)had multibacillary leprosy,and 18.2%(68/374)had grade 2 disability.More than half of the new leprosy cases(54.8%,205/374)were distributed in southwest China.There were 33 relapsed leprosy cases reported in 2021.By the end of 2021,there were 1,897 registered leprosy cases reported nationwide,giving a prevalence rate of 1.35 per million population.Conclusion:The leprosy epidemic in China shows a downward trend in terms of the prevalence and incidence rates.However,the high prevalence of leprosy in southwest China is still a matter of concern.

Application of Bioengineered Bacteria in Allergic Diseases

In recent years,increasing attention has been paid to bioengineered bacteria as vectors for the treatment of allergic diseases.The methods for preparing bioengineered bacteria that can express exogenous genes are improving.Research has focused mainly on application of bioengineered bacteria expressing recombinant allergens,hypoallergenic derivatives of allergens,T-cell epitope derivatives,cytokines,or as mucosal adjuvants to enhance immunotherapy effects.This strategy offers new ideas for the treatment of allergic diseases.This review summarizes recent advances in use of live bioengineered bacteria in allergic diseases as well as the challenges of using microorganisms(or their components)in immunotherapy.

Visual Clues for the Histopathologic Diagnosis of Psoriasis:A Retrospective Case-Control Study

Objective:The histopathologic diagnosis of psoriasis remains challenging.This study aimed to uncover clues for the histopathologic diagnosis of psoriasis in patients whose lesions required differentiation from other inflammatory skin disorders.Methods:A retrospective analysis was conducted between psoriasis biopsy sections and other inflammatory skin diseases sections.The psoriasis and control groups were compared regarding the pathological characteristics,including the?sign,hypogranulosis,and neutrophilic infiltration or pustules within the epidermis.We also summarized the clinical information and the classic and non-classic histologic features of psoriasis.Comparisons between psoriasis and control groups were performed using the c-square test.Results:Biopsy sections from 190 patients were analyzed.Of these patients,100 had a confirmed clinicopathological diagnosis of psoriasis,while 90 were diagnosed with an inflammatory skin disorder other than psoriasis(control group).The classic histologic features included the mound of parakeratosis(68.0%),confluent parakera tosis(42.0%),hypogranulosis(86.0%),regular psoriasiform hyperplasia(79.0%),Munro microabscess(85.0%),spongiform pustule of Kogoj(43.0%),suprapapillary plate thinning(87.0%),and dermal papilla capillary ectasia(98.0%).The?sign was present in 79.0%and 21.1%,respectively,of the lesional biopsy samples from the psoriasis and control groups(P<0.001).The combination of the?sign and neutrophil infiltration in the upper epidermis was present in 74.0%and 10.0%,respectively,of the lesional biopsy samples from the psoriasis and control groups(P<0.001).The combination of these 2 features had a sensitivity of 0.89 and specificity of 0.76 in distinguishing between the psoriasis and control groups.Conclusion:The?sign is a useful visual clue for the histopathologic diagnosis of psoriasis.However,for some inflammatory skin disorders that are very similar to psoriasis,such as pityriasis rubra pilaris,the combination of the?sign and neutrophil infiltration in the upper epidermis is needed to distinguish the condition from psoriasis.

Serum 25-Hydroxyvitamin D Level Might Be a Useful Indicator of Disease Severity in Obese Children With Atopic Dermatitis:A Case-Control Study

Objective:To assess the relationship between the severity of atopic dermatitis(AD)in children of varying weight categories and their serum 25-hydroxyvitamin D[25(OH)D]levels.Methods:The study population comprised 899 patients with AD and 854 age-and sex-matched controls.The Mann-Whitney U test and Kruskal-Wallis H tests were used to assess differences between groups,and Spearman correlation analysis was used to test correlation.Results:The 25(OH)D level in the AD group was M(Q_(25),Q_(75)),24.0(19.7,28.4)ng/mL,which was significantly lower than the control group(26.4[23.6,29.9]ng/mL;Z=-3.34,P=0.001).25(OH)D levels in children with AD were negatively correlated with body mass index(r=-0.30,P<0.001),Severity scoring of Atopic Dermatitis(SCORAD;r=-0.14,P<0.001),total immunoglobulin E(r=-0.13,P<0.001),and eosinophil(r=-0.08,P=0.017).There were statistically significant differences in 25(OH)D(H=18.46,P<0.001),total immunoglobulin E(H=9.13,P=0.010),eosinophil(H=67.17,P<0.001),and SCORAD(H=10.49,P=0.005)among groups with different body mass index classification.The 25(OH)D levels were 22.3(17.5,27.1)ng/mL in the overweight AD group and 22.3(17.6,25.7)ng/mL in the obese AD group,which were significantly lower than those in the normal-weight AD group(24.7[20.4,25.5]ng/mL;P=0.003,P=0.004).25(OH)D levels were negatively correlated with SCORAD in obese AD patients(r=-0.25,P=0.010).Conclusion:Vitamin D insufficient or deficient is obvious in children AD patients.The 25(OH)D levels in the overweight/obese AD group are significantly lower than those in the normal-weight AD group.Vitamin D level is negatively correlated with SCORAD in obese children with AD.

Molecular Characteristics of Cephalosporin-Resistant Neisseria gonorrhoeae Strains in China:A Retrospective Study

Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisseria gonorrhoeae(NG)strains isolated from China Gonococcal Antimicrobial Resistance Surveillance Programme(China-GRSP).Methods:In total,2,038 NG isolates were collected from the China-GRSP between 2015 and 2016.NG multiantigen sequence typing(NG-MAST),multilocus sequence typing(MLST),and NG sequence typing for antimicrobial resistance(NG-STAR)were used to determine characteristics and resistant determinants of cephalosporin-resistant isolates.The results are described as percentages.Results:Seventy-four(3.6%)cephalosporin-resistant isolates were confirmed.MLST_(ST7363)was the most prevalent MLST among cefixime-resistant(CFX-R)isolates,whereas MLST_(ST7365)(n=8)in was the most prevalent sequence type among ceftriaxone-resistant(CRO-R)isolates.CFX-R strains were mainly associated with penA-X(n=27,44.3%),penA-XIII(n=6,9.8%),penA-XVIII(n=5,8.2%),and CRO-R strains were mainly related to penA-XVIII(n=10,25.6%),penA-43(n=9,23.1%),penA-XIII(n=7,17.9%).Conclusion:The main conclusion of this study is that the predominant cephalosporin-resistant clones in China include locally emerged and imported linages.The CFX-R and CRO-R strains are primarily related to penA mutations,and their predominant genotypes are different.With the increase in international travel,tracking high-risk-resistant clones and identifying outbreaks and their associations with epidemiological characteristics are critical to improve public health.

Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

Objective:Heterogeneity of participants in clinical trials distorts intervention efficacy.However,factors associated with participant heterogeneity in randomized clinical trials(RCTs)focusing on systemic sclerosis(SSc)are not clear.We conducted this systematic review to establish normative standards for future research and help develop management guidelines.Methods:Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different countries.Risk of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ratios.Results:In total,261 trials met our inclusion criteria.The quality of SSc RCTs worldwide was relatively poor,with no trend of improvement in recent years,and only 12.2%were ranked as having a low risk of bias.Trials with a low risk of bias as well as single-center,single-country,or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center,multiple-country,or double-blind trials.Interestingly,trial registration and primary outcome definition contributed to high withdrawal.National income was also relevant;participant adherence in high-income countries,but not in upper-and lower-middle-income countries,was significantly altered by different variables.Conclusion:Overall,the risk of bias,national income,and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the results.Trials with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

Skin Microbiota and the Skin Barrier

The skin constitutes the primary barrier between the human body and the external environment.The skin microbiome plays an important role in the microecosystem on the skin surface and mediates multiple facets of the skin barrier function,including physical,chemical,microbial,and immune barriers.In this review,we discuss the host-microbiota interactions in barrier maintenance and disruption,implications for skin disorders such as atopic dermatitis,psoriasis,and rosacea,and the latest strategies for targeting the skin microbiota to improve the skin barrier.

Tinea of Vellus Hair Caused by Trichophyton violaceum in a Child:A Case Report

Introduction:Tinea of vellus hair is a rare dermatophytosis,caused by dermatophyte infection in the vellus hair.The clinical symptoms of tinea of vellus hair are more serious and the conventional topical treatment are often ineffective.Here,we report a case of tinea of vellus hair caused by Trichophyton violaceum in a child.Case presentation:A 7-year-old boy presented with a localized,scaly,and itchy erythema on his left cheek for two months.He once used a topical corticosteroid but without any clinical improvement,the erythema was progressively enlarging and spread to the left eyebrow.He denied any contact with animals.Direct microscopy found abundant spores and hyphae on the vellus hair;T.violaceum was identified by culture and PCR examination.The patient was diagnosed with tinea of vellus hair and cured after treating with oral terbinafine 125 mg/day and topical treatment for two weeks.There was no recurrence during the follow-up period.Discussion:The clinical symptoms of tinea of vellus hair are often atypical and easy to be misdiagnosed.Timely fungal examination is necessary for suspicious patients and confirmed patients should be treated with oral antifungal drugs.Conclusion:The diagnosis and treatment of tinea of vellus hair need to be paid more attention in clinical works.

Chinese Expert Consensus on the Diagnosis and Treatment of Adult Dermatomyositis (2022)

Dermatomyositis,an idiopathic inflammatory myopathy,is characterized by distinctive skin manifestations,proximal muscle weakness,and multiple organ involvement and can be accompanied by malignancies.To provide a reference for dermatologists and clinicians in other relevant fields of clinical practice,experts from the Dermatology Branch of the China International Exchange and Promotion Association for Medical and Health Care and the National Clinical Research Center for Dermatologic and Immunologic Diseases developed this consensus on the diagnosis and treatment of adult dermatomyositis using Chinese and international literature and expert advice.

Clinical Application of Platelet-Rich Fibrin in Dermatology

Platelet-rich fibrin(PRF)is a second-generation platelet concentrate obtained from autologous blood.PRF is composed of abundant platelets,leucocytes,and a high concentration of various growth factors and fibrinogen.The composition and three-dimensional structure of PRF enable it to effectively make cells migrate and proliferate,playing an important role in tissue repair.Furthermore,the easy preparation and low cost of PRF make it a good treatment option.Numerous articles have been published about the application of PRF in clinical practice,however,the application of PRF in dermatology has not been comprehensively reviewed.The objective of this review article was to discuss various applications of PRF in dermatology,including healing chronic wounds,treating androgenic alopecia,skin rejuvenation,autologous fat transplantation,and treating vitiligo.PRF is a promising dermatologic treatment,but lacks a standardized protocol regarding its methods of attainment and use,which needs more investigations.

The Immune Function of Keratinocytes in Anti-Pathogen Infection in the Skin

Keratinocytes,located in the outer part of human skin,are the main epidermal cell type and play an essential role in skins defense against infection.Besides creating a physical barrier between the environment and the internal body,keratinocytes exert powerful immune function in anti-pathogen infection in the skin.At the recognition stage,pattern recognition receptors(PRRs)expressed by keratinocytes sense pathogen-associated molecular patterns(PAMPs)existing in pathogens.Toll like receptors(TLRs)are the most important PRRs in keratinocytes.Other PRRs such as dectin-1 and nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs)are also found to participate in this process.Activated PRRs enhance the secretion of cytokines,chemokines and the production of antimicrobial peptides(AMPs).Proinflammatory cytokines tumor necrosis factor-α,interleukin(IL)-1α,IL-6,IL-1βand IL-18,chemokines(C-X-Cmotif)ligand(CXCL)1,CXCL2,CCL20,CCL2 and IL-8,AMPs human β-defensin(HBD)2,HBD3 and LL37 are the main molecules expressed in this procedure.Thymic stromal lymphopoietin(TSLP),IL-36γ,IL-17 family member IL-17C and anti-inflammatory cytokine IL-10 can also be secreted.Some molecules produced by keratinocytes such as ribonuclease 5 and 7,S100 proteins own antimicrobial properties.Keratinocytes defense responses can be regulated by internal and external factors.This review summarizes recent advances on the innate immune function of keratinocytes against infection,promoting the finding of a new direction for avoiding severe skin infection as well as the potential treatment of keratinocyte-associated inflammatory dermatosis.

Guidelines for the Diagnosis and Treatment of Rosacea in China(2021 Edition)

Rosacea is a chronic inflammatory skin disease that primarily affects the centrofacial areas and mainly manifests as recurrent flushing and erythema.In recent years,there has been progress in the understanding of the diagnosis and treatment of rosacea.Therefore,a group of dermatological experts updated the guidelines based on the 2016 expert consensus statement on rosacea diagnosis and treatment in China.These new guidelines propose diagnostic criteria for rosacea at different sites to further standardize the diagnosis and treatment of rosacea in China.

Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China(2020)#

Atopic dermatitis(AD)is a common disease clinically characterized by chronic recurrent eczematous lesions,dry skin,and pruritus.AD can negatively impact patients’quality of life.The prevalence of AD in China has been increasing during the past few decades.Based on the most recent advances in the treatment of AD,we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition,epidemiology,pathogenesis,clinical classification,diagnosis,prevention,and treatment of AD.

Transcription and Secretion of Interleukin-1β and HMGB1 in Keratinocytes Exposed to Stimulations Mimicking Common Inflammatory Damages

Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P<0.05).Transcription of HMGB1 was inhibited in all 3 types of stimulation(P<0.05),but secretion was increased after exposure to UVB irradiation and co-stimulation by TNF-α and IFN-γ(P<0.05).We observed no change in the secretion level of HMGB1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).

Alleviating Skin Barrier Disruption,Skin Inflammation,and Pruritus:A Moisturizing Spray Containingβ-Glucan and Panthenol

Objective:Inflammatory skin diseases were proved to be associated with dry skin-induced pruritus.However,the relationship between skin inflammation,skin barrier function,and pruritus remains unclarified.The present study aimed to explore this relationship using an acetone-ether-water(AEW)mouse model,and to investigate the anti-itch effects of the combined application ofβ-glucan and panthenol in a moisturizing spray in this mouse model.Methods:A dry skin-induced chronic pruritus mouse model was established by repeated AEW treatment of the skin.The pruritic behavior,skin barrier function,and expression of molecules related to pruritus and inflammation in topical lesions were measured.The effects of a spray containingβ-glucan and panthenol were observed.Thet test and one-way analysis of variance were used to evaluate differences between groups.Results:AEW treatment triggered spontaneous scratching with significantly increased numbers of scratching bouts,and disrupted the skin barrier with a significant increase in transepidermal water loss values and a significant decrease in filaggrin gene(FLG)expression(allP<0.01).AEW treatment also significantly increased the expression of NOD-like receptor family pyrin domain containing 3,apoptosis-associated speck-like protein containing a CARD,caspase-1,interleukin-1β,and tumor necrosis factor-α,as well as the pruritus-associated molecules nerve growth factor,cathepsin S,and thymic stromal lymphopoietin in the skin(allP<0.01).Application of the spray containingβ-glucan and panthenol significantly alleviated these responses,resulting in a reduced number of scratching bouts in 1 hour,reduced transepidermal water loss values,increased filaggrin mRNA expression,and reduced mRNA levels of NOD-like receptor family pyrin domain containing 3,apoptosis-associated speck-like protein containing a CARD,caspase-1,interleukin-1β,tumor necrosis factor-α,cathepsin S,thymic stromal lymphopoietin,and nerve growth factor in skin lesions(allP<0.05).Conclusion:The present results suggest a relationship between damaged skin barrier function,pruritus,and inflammation.Addingβ-glucan and panthenol to moisturizing skincare products may alleviate pruritus induced by dry skin,improve the damaged skin barrier function,and reduce the inflammatory state in local skin areas.

The Power of Molecular Genetics in Understanding Heritable Skin Disorders: Introduction to the Special Theme on Genodermatosis

Among the over 7,000 heritable disorders,at least 1,000 of them have cutaneous manifestations.Some of these conditions are exclusively limited to the skin,thus being non-syndromic,while some of them are associated with a number of extracutaneous manifestations,that is,they are syndromic,with protean manifestations.These conditions,heritable skin diseases,display a tremendous collection of phenotypes as well as a broad spectrum of severity and the overall outcome.In most severe forms,some of these conditions are lethal at the early stages of life,while at the other end of the spectrum they may present with a relatively minor skin involvement primarily of cosmetic concern,with no effect on the longevity of the affected individuals.Considering the plethora of clinical manifestations,frequently with overlapping clinical features and complex classification schemes often riddled with eponyms,the heritable skin disorders frequently pose a diagnostic challenge for practicing dermatologists.

Updated review of IL-17 inhibitors for psoriasis treatment

Introduction Psoriasis is a chronic,immune-mediated inflammatory skin disease.The pathogenic characters of psoriasis are remarkable proliferation,unusual differentiation and immune activation of keratinocytes,accompanied with disorderly immune system[1].Psoriasis patients suffered from tremendous psychosocial burden,and remarkable reduction of physical activity and quality of life[2].

Eccrine Spiradenoma of the Forehead: A Case Report

Introduction Condyloma acuminatum(CA),also known as genital warts,is an anogenital warty growth caused by some types of the human papilloma virus(HPV).CA is usually found within the anal or genital area,but it occasionally presents in the oral,respiratory,conjunctival,nasal,or nipple region.We herein report a rare case of a 29-year-old Chinese woman with a tiny CA on her nipple,which was diagnosed through dermoscopy.With noninvasion and convenience,dermoscopy is valuable for the early diagnosis of tiny CA that is unable to be discerned by the naked eye.