Targeted therapy for immune mediated skin diseases. What should a dermatologist know?

Abstract Background Molecularly targeted therapies, such as monoclonal antibodies (mAbs) and Janus Kinase inhibitors (JAKis), have emerged as essential tools in the treatment of dermatological diseases. These therapies modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. This review aims to provide an updated summary of targeted immune therapies for inflammatory skin diseases, considering their pathophysiology, efficacy, dosage, and safety profiles. Methods The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was conducted on PubMed over the past 10 years, focusing on randomized clinical trials, case reports, and case series related to targeted immune therapies in dermatology. Eligibility criteria were applied, and data were extracted from each study, including citation data, study design, and results. Results We identified 1360 non-duplicate articles with the initial search strategy. Title and abstract review excluded 1150, while a full-text review excluded an additional 50 articles. The review included 143 studies published between 2012 and 2022, highlighting 39 drugs currently under investigation or in use for managing inflammatory skin diseases. Study limitations The heterogeneity of summarized information limits this review. Some recommendations originated from data from clinical trials, while others relied on retrospective analyses and small case series. Recommendations will likely be updated as new results emerge. Conclusion Targeted therapies have revolutionized the treatment of chronic skin diseases, offering new options for patients unresponsive to standard treatments. Paradoxical reactions are rarely observed. Further studies are needed to fully understand the mechanisms and nature of these therapies. Overall, targeted immune therapies in dermatology represent a promising development, significantly improving the quality of life for patients with chronic inflammatory skin diseases.

Are behavioral interventions a better choice for atopic dermatitis patients? A meta-analysis of 6 randomized controlled trials

Abstract Background The treatment for atopic dermatitis (AD) has been the focus of clinical research, and behavioral intervention is considered an indispensable treatment method. To our knowledge, no relevant meta-analysis has evaluated the effects of behavioral interventions on atopic dermatitis. Objectives To evaluate the effects of behavioral interventions on atopic dermatitis. Methods The authors searched PubMed, EMBASE, and Cochrane CENTRAL to retrieve relevant RCTs (up to Feb 2022). The search strategy involved a combination of related keywords. The Cochrane Q and I2 statistics were used to assess heterogeneity. Results Six RCTs involving seven reports with 246 patients were included. The results suggested that behavioral interventions could relieve eczema severity (correlation coefficient [r = −0.39]; p < 0.001) and scratching severity significantly (r = −0.19; p = 0.017), while not affect itching intensity (r = −0.02; p = 0.840). A sensitivity analysis confirmed the robustness of the results. Study limitations An important limitation of this study was the insufficient number of RCTs and the limited sample size. In addition, the study lacked a control group receiving a type of intervention other than the experimental protocol. Another limitation was the short duration of follow-up. Conclusions This study suggests that behavioral interventions could be effective in treating atopic dermatitis by reducing eczema and scratching severity. Additionally, habit-reversal behavioral therapy may be more effective for treating atopic dermatitis.

Impacto de la implementación de la estrategia multimodal de la OMS para mejorar la higiene de manos en una Unidad de Cuidados Intensivos / Impact on implementation of multimodal of World Health Organization strategies to improve hand hygiene in an Intensive Care Unit

INTRODUCCIÓN: La higiene de manos (HM) es la principal medida para disminuir las IAAS, las que en las Unidades de Cuidados Intensivos (UCI) presentan una alta prevalencia. En Chile no existe información sobre el impacto de la estrategia multimodal de la OMS para la HM en adultos. El objetivo fue evaluar el impacto de la implementación de la estrategia en una UPC. METODOLOGÍA: Estudio longitudinal con evaluación pre y post-intervención, entre los años 2018 y 2021, en la UCI del Hospital del Trabajador (HT), Santiago, Chile. La implementación se evaluó con pautas de cumplimiento de HM, consumo de jabón y productos en base alcohólica (PBA). El impacto se midió con las tasas de neumonía asociada a ventilación mecánica (NAVM), infecciones del torrente sanguíneo asociadas a CVC (ITS- CVC) y del tracto urinario por CUP (ITU-CUP), y la incidencia anual de dermatitis. RESULTADOS: El cumplimiento de pautas aumentó de 91 a 96% (p < 0,05). El consumo total de productos para la HM aumentó de 0,17 a 0,31 L/día/cama y de PBA en 10%. Las tasas de IAAS pre y post-intervención fueron para NAVM de 10,3 y 8,4; ITS-CVC de 0,8 y 1,5 e ITU-CUP de 4,2 y 5,3 por 1.000 días de exposición. La incidencia anual de dermatitis disminuyó en 30% (p < 0,05). CONCLUSIONES: La implementación de la estrategia multimodal se asoció a una disminución de las tasas de NAVM y de dermatitis en la UCI del HT.

INTRODUCTION: Hand hygiene is the main measure to decrease infections related to healthcare and the Intensive Care Unit has a high prevalence. In Chile there aren't reports about the impact of the World Health Organization multimodal hand hygiene improvement strategy. AIM: To assess the implementation impact of this strategy at the ICU. METHODOLOGY: Longitudinal study with pre- and postintervention evaluation during the years 2018-2021 at ICU. The implementation was assessed against hand hygiene compliance guidelines, soap consumption and alcohol-based products. The impact was evaluated with the rates of ventilator-associated pneumonia (VAP), catheter related bloodstream infection (CRBSI) and catheter associated urinary tract infection (CAUTI) and the annual dermatitis incidence. RESULTS: The guidelines compliance increased from 91% to 96% (p < 0.05). The total product consumption increased from 0.17 to 0.31 Liters/day/bed. The use of alcohol-based products increased by 10%. HAI rates pre- and post-intervention were for VAP 10.3 and 8.4, CRBSI 0.8 and 1.5 and CAUTI 4.2 and 5.3. The annual dermatitis incidence decreased by 30.8% (p < 0.05). CONCLUSIONS: The strategy implementation benefited the decrease of VAP and the dermatitis prevention in ICU.

Guia prático para o uso de imunobiológicos em doenças alérgicas - ASBAI / Practical guide for the use of immunobiologic agents in allergic diseases - ASBAI

Os anticorpos monoclonais são uma nova classe de medicamentos que representa um marco na evolução da terapia de doenças alérgicas graves. Além de possibilitar uma terapia imunológica alvo específico, proporciona maior controle de sintomas, redução de exacerbações, melhoria da qualidade de vida e da segurança. A eficácia e a segurança dos anticorpos monoclonais no tratamento de doenças alérgicas estão bem documentadas nos estudos clínicos pivotais, de extensão e de vida real. No Brasil, estão licenciados atualmente pela Agência Nacional de Vigilância Sanitária (ANVISA) imunobiológicos para asma, dermatite atópica (DA), esofagite eosinofílica (EoE), granulomatose eosinofílica com poliangeíte (GEPA), rinossinusite crônica com pólipo nasal (RSCcPN), síndromes hipereosinofílicas (SHE) e urticária crônica espontânea (UCE). Com a incorporação do uso dessas novas terapias no dia a dia do médico alergologista e imunologista, naturalmente emergem aspectos práticos que exigem orientações práticas perante as evidências científicas mais atuais, a fim de se manter a boa prática médica, com uso criterioso e consciente pelo especialista capacitado. Assim, nesse guia prático, abordaremos os imunobiológicos aprovados até o momento para doenças alérgicas graves, com objetivo de auxiliar o especialista em Alergia e Imunologia na prescrição e manejo dessas medicações, incluindo indicações, contraindicações, monitoramento da eficácia e segurança, notificação de eventos adversos, bem como aspectos associados aos cuidados com vacinas, populações especiais, acesso, transporte, armazenamento e aplicação domiciliar.

Monoclonal antibodies are a new class of drugs that represent a milestone in the evolution of therapy for severe allergic diseases. In addition to allowing targeted immunologic therapy, they can improve symptom control, reduce exacerbations, and increase quality of life and safety. The efficacy and safety of monoclonal antibodies in the treatment of allergic diseases are well documented in pivotal, extension, and real-life clinical studies. In Brazil, immunobiologic agents are currently licensed by the National Health Surveillance Agency (ANVISA) for use in asthma, atopic dermatitis (AD), eosinophilic esophagitis (EoE), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), hypereosinophilic syndrome (HES), and chronic spontaneous urticaria (CSU). With the incorporation of these new therapies into the daily practice of the allergist and immunologist, practical aspects will naturally emerge and require practical guidelines in light of the most current scientific evidence in order to maintain good medical practice, with judicious and conscious use by a qualified specialist. Therefore, in this practical guide, we will address the immunobiologic agents currently approved for severe allergic diseases, aiming to assist allergy and immunology specialists in the prescription and practical management of these medications, including indications, contraindications, efficacy and safety monitoring, adverse event reporting, as well as health care factors associated with vaccination, special populations, access, transport, storage, and home use.

Manejo dos eventos adversos do dupilumabe na dermatite atópica e no prurigo nodular / Management of the adverse effects of dupilumab in atopic dermatitis and prurigo nodularis

A dermatite atópica (DA) e o prurigo nodular (PN) são doenças inflamatórias da pele que cursam com lesões variadas, como eczemas, pápulas e nódulos, acompanhados de intenso prurido e, nos casos graves, de importante prejuízo da qualidade de vida para os pacientes e seus familiares. O dupilumabe está aprovado no Brasil para o manejo das duas condições: DA moderada/grave e PN que não responde aos tratamentos tópicos. A eficácia e segurança do dupilumabe foram amplamente estabelecidas para ambas as condições em ensaios clínicos e estudos de vida real. Este artigo tem como objetivo revisar os principais eventos adversos (EAD) associados ao uso do dupilumabe em DA e PN, e auxiliar no seu manejo. Desde o início do uso da medicação, há alguns anos, os principais EAD reportados foram: a reação no local da injeção, a doença da superfície ocular (conjuntivite não infecciosa, blefarite, olhos secos), a eosinofilia e o eritema de face/pescoço. Outras manifestações também foram observadas em pacientes com DA em uso de dupilumabe, mas sem associação comprovada: psoríase, artralgia e alopecia areata. Apesar de muito infrequentemente levarem à suspensão do dupilumabe, é fundamental que os médicos prescritores deste medicamento para estas condições, dermatologistas e imunoalergistas, saibam detectar e manejar seus possíveis eventos adversos.

Atopic dermatitis (AD) and prurigo nodularis (PN) are inflammatory skin diseases characterized by various lesions such as eczema, papules, and nodules, with marked pruritus and, in severe cases, significant impairment of quality of life for patients and their families. Dupilumab is approved in Brazil for the management of both moderate/severe AD and PN that does not respond to topical treatments. The efficacy and safety of dupilumab have been extensively established for both conditions in clinical trials and real-world studies.This article aims to review the main adverse events (AEs) associated with the use of dupilumab in AD and PN and assist in their management. Since the introduction of dupilumab a few years ago, the main reported AEs have been injection site reactions, ocular surface disease (non-infectious conjunctivitis, blepharitis, dry eyes), eosinophilia, and facial/neck erythema. Other manifestations have also been observed in patients with AD on dupilumab, but without proven association: psoriasis, arthralgia, and alopecia areata. Although AEs very infrequently lead to discontinuation of dupilumab, it is crucial that physicians prescribing it for these conditions, dermatologists, and immunologists know how to detect and manage its possible adverse effects.

Síndrome da urticária de contato ­ uma revisão / Contact urticaria syndrome - a review

A síndrome da urticária de contato (SUC), a urticária de contato (UCO) e a dermatite de contato por proteínas (DCP) são entidades descritas sob o rótulo de reações cutâneas imediatas por contato. Geralmente as urticas surgem 20-30 minutos após a exposição por contato com uma substância, e desaparecem por completo em algumas horas, sem deixar lesão residual.Entretanto, a SUC pode apresentar sintomas generalizados graves. Estima-se uma prevalência, entre trabalhadores europeus, entre 5-10%, enquanto na população geral estima-se de que seja de 1-3%. Os mecanismos envolvidos na patogênese da SUC não foram totalmente elucidados. Uma abordagem inicial, para melhorar a sua compreensão, pode ser dividir esta condição em urticária não imunológica (UCNI) e imunológica (UCI). A primeira não necessita de sensibilização prévia ao alérgeno, enquanto a segunda necessita. O diagnóstico da SUC necessita de uma anamnese detalhada e exame físico seguido de teste cutâneo com as substâncias suspeitas. O afastamento do agente desencadeante é o melhor tratamento. Para isso é necessário o diagnóstico apropriado e precoce, a confecção de relatórios ocupacionais e o desenvolvimento de medidas preventivas.

Contact urticaria syndrome (CUS), contact urticaria, and protein contact dermatitis (PCD) are entities described under the umbrella term of immediate contact skin reactions (ICSR). Generally, hives appear 20-30 minutes after contact with the offending substance, and disappear completely in a few hours, without leaving residual lesions. However, the CUS may be associated with severe systemic symptoms. A prevalence of 5-10% has been estimated among European workers; in the general population it is 1-3%. The mechanisms involved in CUS pathogenesis have not been fully elucidated. An initial approach to improving its understanding involves dividing this condition into non-immune and immune contact urticaria. The former does not require prior sensitization to the allergen, while the latter does. Diagnosis of CUS is established by a detailed history and physical examination, followed by skin tests with suspected substances. Removal of the triggering agent is the best treatment. This requires early proper diagnosis, occupational reporting, and development of preventive measures.

Dermatite de contato alérgica por flores: a importância do teste de contato personalizado / Allergic contact dermatitis to flowers: the importance of personalized patch testing

A dermatite de contato por plantas é um problema ocupacional muito comum. Flores e folhas são relatadas como causadoras de dermatite irritativa primária, tanto química como mecânica, dermatite de contato alérgica e fitofotodermatites. Frente à variedade de plantas potenciais causadoras de dermatoses e o modo como foi concluído o diagnóstico, relatamos um caso de dermatite de contato alérgica pelo gênero Chrysanthemum em uma paciente florista que buscou seu diagnóstico por mais de 10 anos. Fragmentos das pétalas e folhas de manuseio mais frequente pela paciente foram utilizados para confecção de um teste de contato personalizado que permitiu a conclusão diagnóstica e correta condução da paciente. Assim, ressaltamos a importância da realização do teste de contato personalizado, em especial nos casos suspeitos de dermatite de contato alérgica, onde o teste (bateria padrão) resultou negativo e/ou as substâncias suspeitas não se encontraram contempladas.

Plant contact dermatitis is a very common occupational problem. Flowers and leaves are reported to cause primary irritant dermatitis (both chemical and mechanical), allergic contact dermatitis, and phytophotodermatitis. Given the variety of plants that could potentially cause dermatoses and the way in which the diagnosis was established, we report a case of allergic contact dermatitis caused by the genus Chrysanthemum in a florist who had sought a diagnosis for more than 10 years. Fragments of the petals and leaves most frequently handled by the patient were used to create a personalized patch test that allowed conclusive diagnosis and, finally, appropriate management. We highlight the importance of carrying out personalized patch testing, especially in cases of suspected allergic contact dermatitis in which the standard test battery was negative and/or did not cover the suspected substances.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

Research progress of tralokinumab for the treatment of moderate and severe atopic dermatitis / 中国基层医药

Tralokinumab is a selective interleukin-13 inhibitor developed by LEO Pharma in Denmark. It was granted approval by the US Food and Drug Administration on December 27, 2021, for the treatment of patients aged 18 years or older with moderate to severe atopic dermatitis whose disease is refractory to or cannot be fully controlled by local prescription therapy. This article presents a comprehensive review of the recent research progress in the treatment of moderate to severe atopic dermatitis with tralokinumab.

Research progress on immunologic skin diseases in China / 中国免疫学杂志

Immunologic skin diseases encompass a spectrum of immune system-mediated autoimmune or inflammatory skin conditions,such as lupus erythematosus,psoriasis,atopic dermatitis,and vitiligo.Immunologic skin diseases are characterized by an unclear pathogenesis,complex disease processes,diverse clinical manifestations,and treatment difficulties,thereby presenting sig-nificant diagnostic and therapeutic challenges.Notably,Chinese researchers have achieved numerous innovative research findings on immunologic skin diseases in recent years.Over the past decade,Chinese scholars have contributed 11 919 SCI papers to the field of immune dermatosis,with more than 10 being published in the world's leading medical journals.These publications include one in Sci-ence,one in Nature,two in Cell,three in The New England Journal of Medicine,two in The Lancet,and one in Nature Medicine,as well as four in Immunity.Here,we aim to present a comprehensive summary of Chinese research progress pertaining to the pathogene-sis,diagnosis and treatment of immunologic skin diseases.

How to avoid misdiagnosis of rosacea / 中华皮肤科杂志

In recent years, with the in-depth research on rosacea, dermatologists′ understanding of rosacea has gradually increased. However, misdiagnosis and overdiagnosis emerge as a tendency because some doctors roughly equate erythema with rosacea, neglecting the differential diagnosis with other similar skin problems. This article discusses clinical manifestations and diagnostic criteria of rosacea, elaborates on how to make a correct diagnosis, and lists key points in differential diagnosis between rosacea and other skin diseases, with a view to providing a reference for clinicians in the treatment of rosacea, and to reducing its misdiagnosis and overdiagnosis.

Effects and Mechanisms of Zhenxin Anshen Prescription on 1-Chloro-2,4-Dinitrobenzene-Induced Atopic Dermatitis Mice Based on ORAI1/NFAT Signaling Asix / 中药新药与临床药理

Objective To investigate the effects and mechanisms of Zhenxin Anshen Prescription(composed of Os Draconis,Ostreae Concha,Lophatheri Herba,Drynariae Rhizoma,Poria)on mice with atopic dermatitis(AD)based on the calcium channel regulator 1(ORAI1)/nuclear factor of T-cells(NFAT)signalling axis.Methods Thirty-six BALB/c mice were randomly divided into a blank control group,a model group,a Cetirizine group(1.3 mg·kg-1)and a Zhenxin Anshen Prescription group(36.36 g·kg-1),with nine mice in each group.AD mouse model was established using 1-chloro-2,4-dinitrobenzene(DNCB)induction.The drug was administered by gavage once a day for 2 weeks.At the end of drug administration,the area of skin lesions was measured and the severity of skin lesions was scored;spleen mass was measured and spleen index was calculated;pathological changes of skin lesion tissues were observed by HE staining;interleukin 4(IL-4),IL-13 and thymic stromal lymphopoietin(TSLP)in serum were detected by ELISA;and the protein expression levels of ORAI1,calmodulin phosphatase A(CaN)and nuclear factor of T cells 2(NFAT2)were detected by Western Blot.Results Compared with the blank control group,the skin lesion score of mice in the model group was significantly increased(P＜0.01),the skin lesion area was significantly enlarged(P＜0.01);the thickness of the epidermis and dermis were significantly increased(P＜0.01),hyperkeratosis of the epidermis,hypertrophy of the stratum spinosum,and infiltration of inflammatory cells such as eosinophils and lymphocytes can be seen in the dermis;the splenic index and serum IL-4,IL-13,TSLP levels were significantly increased(P＜0.01);protein expression levels of CaN,NFAT2,ORAI1 were significantly increased in the skin lesion tissues(P＜0.01).Compared with the model group,the dermatitis score of mice in the Zhenxin Anshen Prescription group was significantly decreased(P＜0.01),the lesion area was significantly reduced(P＜0.01),the epidermal and dermal thicknesses(P＜0.01),the hyperkeratosis of epidermis was alleviated,the spinous layer was slightly hypertrophic,and there was a small amount of inflammatory cell infiltration in the dermis;the splenic index and the levels of serum IL-4,IL-13,and TSLP were significantly decreased(P＜0.01);the protein expressions levels of CaN,NFAT2,and ORAI1 in the skin lesion tissues were significantly decreased(P＜0.01).Conclusion Zhenxin Anshen Prescription can ameliorate dermatopathological injury in DNCB-induced AD mice,and the mechanism may be related to its ability to inhibit the protein expressions of ORAI1,CaN and NFAT2,reduce the levels of serum type 2 inflammatory factors TSLP,IL-4 and IL-13,and ameliorate cutaneous inflammation and itching through immunomodulation.

A Preliminary Proteomic Study of Peitu Qingxin Granules for the Treatment of Atopic Dermatitis / 中药新药与临床药理

Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P＜0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P＜0.05,P＜0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.

Therapeutic effect of Xiaofeng Zhiyang granules on acute itching in mice with atopic dermatitis by decreasing leukotriene / 药学实践与服务

Objective To establish a mice model of atopic dermatitis with acute itching and investigate the antipruritic effect and its mechanism of Xiaofeng Zhiyang granules（XFZYG）. Methods A mice model of atopic dermatitis was prepared by induction method. Mice were sensitized by calcipotriol and ovalbumin (OVA) applying to the right ear daily for 10 days, and then stimulated by OVA injected intradermally into the right cheek to resulting in acute itching. These mice were divided into 5 groups: blank control group, model group, low dose (7.2 g/kg) and high dose (14.4 g/kg) of XFZYG, and positive control group (montelukast 5 mg/kg). Drugs were administered by gavage at 12 h and 30 min before stimulation. The leukotriene levels in the serum of the mice were measured by Elisa and the basophil ratio and activation status in the blood were measured by flow cytometry. Results The mean number of scratches in the model group was 56 between 30 min and 60 min after stimulation, while the mean number of scratches in the low and high dose of XFZYG groups were 42 and 23 respectively, which were significantly lower than those in the model group （P<0.05）. The serum leukotriene levels and the proportion of basophils in the low and high dose of XFZYG groups were significantly lower than those in the model group (P<0.05). Conclusion XFZYG had certain therapeutic effect on acute itching of atopic dermatitis in mice, and the mechanism of its action was related to the reduction of leukotriene level and basophil ratio in serum of mice with atopic dermatitis .

Clinical Efficacy and Regulation of Skin Microbiota in Children with Atopic Dermatitis and Damp-heat Accumulation Syndrome Treated with Zhaqu Xiaofeng Powder （楂曲消风散） / 中医杂志

ObjectiveTo assess the clinical efficacy and regulation of skin microbiota in children with atopic dermatitis and damp-heat accumulation syndrome treated by Zhaqu Xiaofeng Powder （楂曲消风散， ZXP）. MethodsNinety children were randomized into a treatment group and a control group， each with 45 children. The treatment group received ZXP orally， while the control group received levocetirizine hydrochloride syrup， both for 4 weeks. The atopic dermatitis severity index （SCORAD）score， visual analog scale （VAS）score for itching， children dermatology life quality index （CDLQI）score， and traditional Chinese medicine syndrome score were assessed before and after 2- and 4-week treatment. Simultaneously， adhering to the principles of sample size in microbial sequencing， 25 children were randomly selected from each group （total 50 children）； skin samples were collected before and after treatment， and skin specimen DNA was extracted for 16S rRNA gene amplifier sequencing； the skin microbiota levels were detected， and the distribution of bacteria， diversity of flora， and differences between groups were compared. ResultsThere were five drop-outs in each group， and 40 cases in each group were included in final analysis. After 2- and 4-week treatment， both groups showed a significant reduction in SCORAD scores， VAS scores， and CDLQI scores， and more reductions were shown after 4-week treatment than 2-week treatment （P＜0.01）. The SCORAD score， VAS score， and CDLQI score of the treatment group were significantly lower than those in the control group after 4-week treatment （P＜0.01）. The scores of upset， thirsty， poor appetite， short red urine， and dry stool were reduced in the treatment group （P＜0.05）， while the scores of thirsty， poor appetite， short and red urine decreased after treatment （P＜0.05）. After 4 weeks of treatment， among the differential genera with abundances ＞0.5% in the treatment group， The cumulative relative abundances of Staphylococcus aureus， Streptococcus_mitis， Escherichia coli and Gemella_haemolysans in the treatment group were downregulated after treatment； in the control group， there was a relative cumulative decrease in the abundance of Streptococcus_mitis. The control group had reduced relative abundance of Streptococcus_mitis， Escherichia coli， Staphylococcus aureus and Gemella_haemolysans， after treatment （P＜0.05）. Alpha diversity analysis revealed an increase in both Chaol index and Shannon index after treatment （P＜0.05）， while there was no significant difference in Chaol index and Shannon index in the control group before and after treatment （P＞0.05）. Higher Chaol index and Shannon index were found in the treatment group （P＜0.05）. Beta diversity analysis showed that there were significant differences in the microbial community structure at the lesion site between the treatment group and the control group before treatment. The microbial community structure in the treatment group was similar after treatment， while there was no significant change in the microbial community structure in the control group before and after treatment. There were significant structure differences of key bacteria genus in both groups before and after treatment. ConclusionZXP used in the treatment of pediatric atopic dermatitis （AD）with the syndrome of damp-heat accumulation， has shown efficacy in reducing the severity of skin lesions， alleviating itching， and enhancing the quality of life in children. This modulation aims to decrease the abundance of pathogenic bacteria while promoting the colonization of beneficial bacteria， thereby altering the skin microbiota and contributing to the treatment of pediatric AD.

Study on the Effect of Fuhe Decoction （敷和汤） with Different Doses of Suanzaoren （Ziziphus jujuba） on IgE Levels and Intestinal Flora in Atopic Dermatitis Model Mice / 中医杂志

ObjectiveTo investigate the effect of Fuhe Decoction （敷和汤） with different doses of Suanzaoren （Ziziphus jujuba） for atopic dermatitis （AD）. MethodsForty-eight female BALB/c mice were randomly divided into normal group， model group， loratadine group， and Fuhe Decoction groups with high， medium， and low doses of Fuhe Decoction （Fuhe Decoction high-， medium-， and low-dose groups）， with eight mice in each group. The AD model was prepared by continuous stimulation with 2，4-dinitrofluorobenzene （DNFB） in all groups but the normal group. After modelling， the Fuhe Decoction high-， medium- and low-dose groups were given 24， 18 and 15 g/（kg·d） of Fuhe Decoction， the loratadine group was given 0.001 g/（kg·d） of loratadine dry suspension， and the normal group and the model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 14 days. The number of scratches within 10 min and the score of skin lesions were observed on the 7th and 14th days of modelling and on the 7th and 14th days of drug administration， respectively； serum immunoglobulin E （IgE） was detected by ELISA； the histopathological and morphological changes of the skin were observed by HE staining； and the diversity and abundance of intestinal flora were detected by 16S rRNA sequencing of fecal matter from the colon of the mice. ResultsCompared with the normal group， mice in the model group on the 7th day and the 14th day of modelling and the 7th day， the 14th day of gavage showed increased scratching within 10 min and higher skin lesion scores （P＜0.05）， with hyperkeratotic or incomplete epidermis， marked thickening of spiny cells， and a large number of inflammatory cells infiltrated in the mice after gavage； serum levels of IgE elevated （P＜0.05）， and the abundance of Bacillota decreased， that of the Bacteroidota and bacteria elevated， and relative abundance of Lactobacillus spp. and Prevotella spp. decreased， and relative abundance of Anaplasma spp. and Treponema spp. increased （P＜0.05）. Compared with the model group， the number of scratches within 10 min and the skin lesion scores of mice in the loratadine group and the Fuhe Decoction medium- and high-dose groups decreased on the 7th day and the 14th day of gavage （P＜0.05）， serum IgE reduced， and the bacteria reduced in the loratadine group， the abundance of Bacteroidesmus spp. increased and Bacteriodesmus spp. decreased in the medium-dose group of Fuhe Decoction， the abundance of Bacteriodesmus spp. decreased in the loratadine group， the abundance of Bacteriodesmus spp. decreased， and that of both Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction medium-dose group （P＜0.05）. Compared with the loratadine group， the skin lesion scores increased in Fuhe Decoction low-dose group， and the number of scratching increased in the Fuhe Decoction low- and high-dose groups on the 7th day and the 14th day of gavage； the IgE content increased in Fuhe Decoction low-dose group， the Bacillota increased and the Bacteroidota decreased， the Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction middle-dose group， and Anopheles spp. increased in Fuhe Decoction high-dose group after gavage （P＜0.05）. ConclusionFuhe Decoction can improve the clinical symptoms of AD， regulate the relative abundance of intestinal flora to correct the disorders of the bacterial flora， among which the effect of Fuhe Decoction medium-dose group is optimal and comparable to that of the loratadine group， and the reduction of serum IgE inflammatory response may be one of its mechanisms of action.

Clinical comprehensive evaluation of three oral Janus kinase inhibitors for atopic dermatitis / 中国药房

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

Observation of acute clinical manifestations of cosmetology-related ocular damage / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the acute clinical manifestations of cosmetology-related ocular damage(COD).METHODS:Retrospective study. A total of 53 cases(89 eyes)with ocular damage caused by cosmetology from April 2016 to October 2021 were collected. The clinical features were analyzed, including age, gender, affected eye(s), clinical manifestations, injury cause, treatment procedures, and prognosis.RESULTS: All 53 patients were female, aged 22-45 years, with an average age of 28.4±6.7 years. Monocular injuries were observed in 17 patients, and binocular injuries in 36 patients. The same eye could exhibit two or more ocular damage simultaneously. The primary cosmetology procedures causing COD were eyeliner tattooing(38 eyes; 43%), eyelash extensions(18 eyes; 20%), removal of false eyelashes(11 eyes; 12%), mascara application(8 eyes; 9%), double eyelid surgery(6 eyes; 7%), and others(8 eyes; 9%). Major ocular damages included corneal damage(56 eyes; 63%), eyelid contact dermatitis(26 eyes; 29%), conjunctivitis(19 eyes; 21%), reactive eyelid edema(13 eyes; 15%), ocular surface foreign bodies(12 eyes; 14%), bacterial infection of the palpebral margin(10 eyes; 11%), and others(5 eyes; 6%). These 5 eyes included 1 eye(1%)with central retinal artery occlusion caused by periocular injection of hyaluronic acid. The majority of patients(74 eyes)recovered within 1-2 wk with appropriate treatment, while filamentosa keratitis appeared in 3 eyes and the eye with central retinal artery occlusion had poor prognosis.CONCLUSIONS: COD predominantly occurs in young and middle-aged females with cosmetology experience. The most common cosmetology procedure leading to COD is eyeliner tattooing, and corneal damage is the most significant type of COD. COD can be effectively prevented and treated, resulting in a generally favorable prognosis.

Research progress of TCM treatment of atopic dermatitis based on gut-brain-skin axis / 国际中医中药杂志

Based on the introduction of gut-brain-skin axis, this article discussed the relationship between psychological behavior, intestinal flora, and atopic dermatitis. By combing the literature on the treatment of atopic dermatitis with TCM, it is found that TCM therapy can regulate the relative abundance of intestinal flora, participate in immune metabolism and restore skin barrier function by intervening in the gut-brain-skin axis, so as to achieve the purpose of treating atopic dermatitis.

Clinical Observation on Modified Shehuang Ointment for the Treatment of Facial Seborrheic Dermatitis / 广州中医药大学学报

Objective To observe the clinical efficacy of modified Shehuang Ointment(mainly composed of Cnidii Fructus,Phellodendri Chinensis Cortex,and Zanthoxyli Pericarpium)for the treatment of facial seborrheic dermatitis(SD).Methods Seventy-two patients with facial SD were randomly divided into observation group and control group,with 36 patients in each group.Both groups of patients were given oral use of Acrivastine Capsules and Vitamin B6 Tablets,and additionally,the observation group was given topical application of modified Shehuang Ointment and the control group was given topical application of 2%Ketoconazole cream.The course of treatment covered 4 weeks.The changes of clinical symptom scores and dermatology life quality index(DLQI)scores in the two groups were observed before and after treatment,and the clinical efficacy and safety of the two groups were also evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 88.89%(32/36),and that of the control group was 72.22%(26/36).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the clinical symptom scores of erythema,scales,grease,rash area,itchiness and other clinical symptoms of the patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the clinical symptom scores of the observation group were significantly lower than those of the control group,the differences being statistically significant(P＜0.05).(3)After treatment,the DLQI scores of patients in the two groups were significantly lower than those before treatment(P＜0.05),and the DLQI scores in the observation group were significantly lower than those in the control group after treatment,the difference being statistically significant(P＜0.05).(4)During the treatment period,no significant adverse reactions occurred in the two groups of patients,with high safety.Conclusion The conventional western medicine treatment combined with topical application of modified Shehuang Ointment exerts certain effect in the treatment of facial SD,which can effectively relieve the clinical symptoms and improve the quality of life of patients.