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.

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

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.

Atopic dermatitis: A global health perspective.

The International Society of AD (ISAD) organized a roundtable on global aspects of AD at the WCD 2023 in Singapore. According to the Global Burden of Disease (GBD) consortium, at least 171 million individuals were affected with AD in 2019, corresponding to 2.23% of the world population, with age-standardized prevalence and incidence rates that were relatively stable from 1990 to 2019. Based on the panel experience, most AD cases are mild-to-moderate. Without parallel data on disease prevalence and severity, the GBD data are difficult to interpret in many regions. This gap is particularly important in countries with limited medical infrastructure, but indirect evidence suggests a significant burden of AD in low-and-medium resource settings, especially urban areas. The Singapore roundtable was an opportunity to compare experiences in World Bank category 1 (Madagascar and Mali), 3 (Brazil, China) and 4 (Australia, Germany, Qatar, USA, Singapore, Japan) countries. The panel concluded that current AD guidelines are not adapted for low resource settings and a more pragmatic approach, as developed by WHO for skin NTDs, would be advisable for minimal access to moisturizers and topical corticosteroids. The panel also recommended prioritizing prevention studies, regardless of the level of existing resources. For disease long-term control in World Bank category 3 and most category 4 countries, the main problem is not access to drugs for most mild-to-moderate cases, but rather poor compliance due to insufficient time at visits. Collaboration with WHO, patient advocacy groups and industry may promote global change, improve capacity training and fight current inequalities. Finally, optimizing management of AD and its comorbidities needs more action at the primary care level, because reaching specialist care is merely aspirational in most settings. Primary care empowerment with store and forward telemedicine and algorithms based on augmented intelligence is a future goal.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique.

This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Healthcare Disparities in Atopic Dermatitis in Latin America: A Narrative Review.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, pruritic skin disease caused by a mixture of genetic, immunological, and environmental factors, characterized by periods of inflammation and remission. In Latin America (LA), the prevalence of AD ranges up to 25% in children and 1-3% in adults. The natural history of the disease for most patients is that AD goes into remission in adolescence and adult life. Only 10-30% of patients continue to have symptoms of the disease in adulthood. There are patients (3-4%) who have the onset of AD during adolescence or after adulthood. Those with limited access to healthcare services, such as diagnosis and treatment, have increased difficulties coping with AD. Healthcare disparities are a complex topic that include social, political, racial/ethnic, and geographical factors. Publications about healthcare disparities in AD in LA are scarce. As a result, recognizing and resolving healthcare inequalities is critical to improving the treatment and quality of life (QoL) of individuals with AD. METHODS: A panel of Latin American experts in dermatology and allergies was provided with a series of relevant questions to address before a multiday conference. During this conference, the entire group discussed and edited each narrative through numerous drafts and rounds of discussion until they reached a consensus. RESULTS: This paper examines the barriers to equal access to care and recommends realistic actions to overcome them. Inadequate disease knowledge, cultural and linguistic barriers, stigmatization, maldistribution of resources, absence of local clinical practice guidelines, arduous patient journey, and limited consultation time were identified as causes of health inequality. CONCLUSIONS: Among the suggested solutions are enhanced education for healthcare professionals, patients, and the general public, a focus on underprivileged communities, telemedicine and telementoring, translators, multidisciplinary teams, and local living clinical practice guidelines.

Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique

Abstract This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology.

BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology

Abstract: BACKGROUND: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. OBJECTIVES: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. METHODS: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. RESULTS/CONCLUSION: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. LIMITATIONS: Our work is a consensus statement, not a systematic review. CONCLUSION: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies.

Education of Patients with Atopic Dermatitis and Their Caregivers.

Atopic dermatitis (AD) is the most prevalent dermatological disease in the pediatric population. It is a chronic, pruritic, and inflammatory skin disorder, with a complex etiology involving genetic predisposition, skin barrier defects, and immune dysfunction. AD can be a challenge for patients, physicians, and caregivers and has a clear impact in patients' quality of life (QoL). Educational programs for patients with AD and their caregivers are effective in improving adherence, QoL, and clinical outcomes. Different models of educational programs exist and their structures depend on cultural, social, and economic factors. To improve existing programs, the educational team should go beyond the disease and have a broader view of the many aspects involved in the pathological process. These include psychological, environmental, social, financial, and cultural aspects. Patients and their caregivers should have a more realistic expectation about the treatment. Innovative methods and approaches like design thinking can create new and effective solutions for patients with AD and their caregivers.

Staphylococcal enterotoxin B induces specific IgG4 and IgE antibody serum levels in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent inflammatory disease, with prevalence of about 10-20% in children and 1-3% in adults. Staphylococcus aureus is present in 80-100% of skin from atopic patients and is related to worsening of the disease by the action of enterotoxins. The aim of this study was to evaluate the profile of anti-Staphylococcus aureus enterotoxin B (SEB) antibody isotypes and IgG subclass levels in adult AD. METHODS: We selected 38 patients with AD, diagnosed by Hanifin and Rajka's criteria, aged between 18 and 65, and 26 healthy controls (HC). The severity of the disease was established according to the Eczema Area and Severity Index and patients graded as mild (28%), moderate (58%), and severe (14%). Sera were assessed for IgG subclasses, IgA, IgM, and IgE against SEB by ELISA. RESULTS: Elevated circulating IgE and IgG4 anti-SEB antibody levels associated with decreased IgA and IgM levels were detected in patients with AD, when compared to HC individuals. The severity of AD was related to low IgG1 and IgG3 levels and a high IgE antibody response to SEB. Interestingly, absence of IgG4 response to SEB was lower in patients with AD (2.63%), when compared to controls (34.6%), while a similar absence was detected for IgG1 and IgE antibodies (AD, 23.3 and 18.4% vs. HC, 38.5 and 19.2%). CONCLUSION: Our findings evidenced a contributing role for IgG4 and IgE antibodies in AD pathogenesis, which are triggered by staphylococcal superantigens.

Atopic dermatitis in adults: clinical and epidemiological considerations / Dermatite atópica em adultos: considerações clínicas e epidemiológicas

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory disease causing intense pruritus, and with typical clinical features. There are few epidemiological studies concerning AD in adults, as well as little information about its prognostic. The aim of this study was to evaluate the clinical and epidemiological course of adults with AD. METHODS: 80 patients aged above 18 years (mean age = 29 years) were selected (30 males and 50 females) and interviewed about hospitalization, systemic corticoid usage, age of AD onset, and personal and/or familial history of atopy. Disease severity was evaluated through the Scoring Atopic Dermatitis (SCORAD) tool. Laboratory examination included IgE serum levels and eosinophil blood count. RESULTS: 71 out of 80 patients referred association with respiratory symptoms (18 had asthma, 17 had rhinitis, and 36 had both conditions); nine out of 80 patients denied any respiratory disease. AD patients were divided in mild (n = 25), moderate (n = 30), and severe (n = 25); 56% had one or more hospitalizations due to AD. A positive association was found between IgE serum levels, eosinophil blood count, and disease severity. CONCLUSION: Adult AD represents a clinical challenge that needs to be better characterized, since it can be misdiagnosed and interferes with the patient's social and personal life. The association of skin and respiratory atopic disease is frequent, and laboratory parameters such as circulating IgE levels and eosinophil blood count may be helpful to assess disease severity.

OBJETIVO: Dermatite atópica (DA) é uma doenc¸a inflamatória crônica com prurido intenso e características clínicas típicas. Há poucos estudos epidemiológicos a respeito da DA em adultos, bem como pouca informação disponível sobre o seu prognóstico. O objetivo do presente estudo é avaliar as características clínicas e o curso epidemiológico dos adultos com DA. MÉTODOS: Foramselecionados 80 pacientes com idade acima de 18 anos (média de idade = 29 anos, 30 homens e 50 mulheres), que foram entrevistados sobre: internações, uso de corticóide sistêmico, idade de início da DA, história pessoal e/ou familiar de atopia. A gravidade da doença foi avaliada de acordo com o SCORing Atopic Dermatitis (SCORAD). A avaliação laboratorial incluiu dosagem sérica de IgE e contagem sanguínea de eosinófilos. RESULTADOS: 71 dos 80 pacientes referiram associação com sintomas respiratórios (18: asma, 17: rinite alérgica e 36: ambas as condições); nove dos 80 indivíduos negaram qualquer sintoma respiratório. Os pacientes com DA foram divididos em DA leve (n = 25), moderada (n = 30) e grave (n = 25); destes, 56% tiveram uma ou mais internações por conta da doença. Verificou-se uma associação entre níveis séricos de IgE, contagem sanguínea de eosinófilos e gravidade da doença. CONCLUSÃO: A DA do adulto representa um desafio clínico que necessita ser melhor caracterizado, uma vez que pode ser erroneamente diagnosticada, e interfere diretamente na vida social e pessoal dos pacientes. A associação entre manifestação respiratória e cutânea é frequente, e parâmetros laboratoriais como níveis de IgE circulante e contagem sanguínea de eosinófilos podem ser úteis para acompanhar a gravidade e evolução da doença.

Atopic dermatitis in adults: clinical and epidemiological considerations.

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory disease causing intense pruritus, and with typical clinical features. There are few epidemiological studies concerning AD in adults, as well as little information about its prognostic. The aim of this study was to evaluate the clinical and epidemiological course of adults with AD. METHODS: 80 patients aged above 18 years (mean age=29 years) were selected (30 males and 50 females) and interviewed about hospitalization, systemic corticoid usage, age of AD onset, and personal and/or familial history of atopy. Disease severity was evaluated through the Scoring Atopic Dermatitis (SCORAD) tool. Laboratory examination included IgE serum levels and eosinophil blood count. RESULTS: 71 out of 80 patients referred association with respiratory symptoms (18 had asthma, 17 had rhinitis, and 36 had both conditions); nine out of 80 patients denied any respiratory disease. AD patients were divided in mild (n=25), moderate (n=30), and severe (n=25); 56% had one or more hospitalizations due to AD. A positive association was found between IgE serum levels, eosinophil blood count, and disease severity. CONCLUSION: Adult AD represents a clinical challenge that needs to be better characterized, since it can be misdiagnosed and interferes with the patient's social and personal life. The association of skin and respiratory atopic disease is frequent, and laboratory parameters such as circulating IgE levels and eosinophil blood count may be helpful to assess disease severity.

Therapeutic patient education in atopic dermatitis: worldwide experiences.

Therapeutic patient education (TPE) has proven effective in increasing treatment adherence and improving quality of life (QoL) for patients with numerous chronic diseases, especially atopic dermatitis (AD). This study was undertaken to identify worldwide TPE experiences in AD treatment. Experts from 23 hospitals, located in 11 countries, responded to a questionnaire on 10 major items. Patients in TPE programs were mainly children and adolescents with moderate to severe AD or markedly affected QoL. Individual and collective approaches were used. Depending on the center, the number of sessions varied from one to six (corresponding to 2 to 12 hours of education), and 20 to 200 patients were followed each year. Each center's education team comprised multidisciplinary professionals (e.g., doctors, nurses, psychologists). Evaluations were based on clinical assessment, QoL, a satisfaction index, or some combination of the three. When funding was obtained, it came from regional health authorities (France), insurance companies (Germany), donations (United States), or pharmaceutical firms (Japan, Italy). The role of patient associations was always highlighted, but their involvement in the TPE process varied from one country to another. Despite the nonexhaustive approach, our findings demonstrate the increasing interest in TPE for managing individuals with AD. In spite of the cultural and financial differences between countries, there is a consensus among experts to integrate education into the treatment of eczema.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting.

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity.

BACKGROUND: Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. OBJECTIVES: To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langeland's criteria. METHODS: Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. RESULTS: A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). CONCLUSION: Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.

Comparative effects of pimecrolimus cream vehicle and three commercially available moisturizers on skin hydration and transepidermal water loss.

BACKGROUND: Hydration and integrity of the horny layer is essential to normal skin function. OBJECTIVE: Comparison of the hydrating properties of three moisturizers with pimecrolimus cream vehicle. METHODS: Four test preparations (high-quality skin cream, cold cream emulsion, emollient oil, pimecrolimus cream vehicle) were applied to four different regions of the forearms and legs. Transepidermal water loss (TEWL) was assessed by evaporimetry at baseline, and 3 and 6 hours after arm application, and electrical capacitance was assessed by corneometry at baseline, and 1, 2, 3 and 6 hours after leg application. RESULTS: Corneometry assessment - in terms of efficacy in moisturizing the skin, test preparations were ranked (best to worst): high-quality skin cream (45.9 arbitrary units versus 75.3; p < 0.001) > pimecrolimus vehicle cream (46.6 versus 61.5; p < 0.001) > emollient oil (43.5 versus 54.8; p = 0.006) > cold cream emulsion (44.8 versus 49.9; p = 0.738). Untreated skin (control) had a mean capacitance of 44.8 units at baseline and 48.5 units at endpoint. Evaporimetry (assessment of TEWL) revealed no significant differences between control and any test preparation at any timepoint. CONCLUSIONS: Pimecrolimus cream vehicle has skin hydration properties comparable with highly effective commercially available products. No test preparation had a significant effect on TEWL.

Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion.

BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus (S. aureus); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin-18 (IL-18), an inflammatory cytokine, may play a role in the atopic skin inflammation. AIMS: To evaluate peripheral blood mononuclear cells (PBMC) proliferation response to staphylococcal enterotoxins A (SEA) and B (SEB) and the levels of IL-18 in adults with AD. METHODS: Thirty-eight adult patients with AD and 33 healthy controls were analysed. PBMC were stimulated with SEA and SEB, phytohemaglutinin (PHA), pokeweed (PWM), tetanus toxoid (TT) and Candida albicans (CMA). IL-18 secretion from PBMC culture supernatants and sera were measured by ELISA. RESULTS: A significant inhibition of the PBMC proliferation response to SEA, PHA, TT and CMA of AD patients was detected (P < or = 0.05). Furthermore, increased levels of IL-18 were detected both in sera and non-stimulated PBMC culture supernatants from AD patients (P < or = 0.05). CONCLUSIONS: A decreased PBMC proliferation response to distinct antigens and mitogens (TT, CMA, SEA and PHA) in adults with AD suggest a compromised immune profile. IL-18 secretion from AD upon stimulation was similar from controls, which may indicate a diverse mechanism of skin inflammation maintained by Staphylococcus aureus. On the other hand, augmented IL-18 secretion from AD sera and non-stimulated cell culture may enhance the immune dysfunction observed in AD, leading to constant skin inflammation.