Atopic Dermatitis Flares Research Articles

Colonization With Staphylococcus aureus in Atopic Dermatitis Patients: Attempts to Reveal the Unknown.

Atopic dermatitis (AD) patients are massively colonized with Staphylococcus aureus (S. aureus) in lesional and non-lesional skin. A skin infection may become systemic if left untreated. Of interest, the incidence of multi-drug resistant S. aureus (MRSA) in AD patients is higher as compared to a healthy population, which makes treatment even more challenging. Information on the specific genetic background of S. aureus accompanying and/or causing AD flares would be of great importance in terms of possible treatment option development. In this review, we summarized the data on the prevalence of S. aureus in general in AD skin, and the prevalence of specific clones that might be associated with flares of eczema. We put our special interest in the presence and role of staphylococcal enterotoxins as important virulence factors in the epidemiology of AD-derived S. aureus. Also, we summarize the present and potentially useful future anti-staphylococcal treatment.

Staphylococcal Hemolytic Potential Is Correlated with Increased Severity of Atopic Dermatitis in Children and Young Adults

Atopic dermatitis (AD) represents a complex intersection between skin barrier dysfunction, host immunologic response, and external factors such as allergenic triggers and the skin microbiome. However, the relative contributions of these factors are not clear. There is a surge in Staphylococcus aureus on the skin during flares of AD (Kong et al., 2012). S. aureus strains seen in AD flares are unique to the host and capable of eliciting varied immune responses (Byrd et al., 2017). No direct relationship between severity and in vitro toxin genotype has been established (Kim et al., 2009).

Practical Recommendations for the Topical Treatment of Atopic Dermatitis in South and East Asia

IntroductionThere is some evidence to suggest that the prevalence of atopic dermatitis (AD) in Asia is rising. We have therefore developed an algorithm for the topical treatment of AD throughout South and East Asia for use by primary care physicians, pediatricians and dermatologists.MethodsNine AD experts from South and East Asia and one from Europe developed the algorithm based upon treatment guidelines, relevant literature and local treatment practices. The algorithm outlines current best practice for the use of emollients, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with the intention of simplifying the treatment regimen of mild-to-moderate AD in South and East Asia.ResultsPatients with AD should bathe and cleanse affected skin to remove crusts and scales daily. Emollients should also be applied daily as a maintenance treatment. When selecting appropriate topical anti-inflammatory treatment for AD flares, several factors should be taken into consideration, including the patient’s age, attitude to treatment options and site of AD lesions. Given the concerns regarding the risk of skin atrophy with use of TCS, a TCI should be used to treat AD lesions in sensitive skin areas: pimecrolimus is recommended for mild-to-moderate AD in these locations, while tacrolimus should be considered for moderate and severe cases. Either pimecrolimus or tacrolimus is recommended for flares in other, non-sensitive body locations. A proactive or intermittent maintenance treatment strategy involving regular emollient use and twice-weekly application of a TCI to previously affected areas is encouraged to reduce the risk of flares.ConclusionsThe algorithm proposed here is intended to simplify the topical treatment of mild-to-moderate AD in daily practice in South and East Asian countries.

Healthcare utilization in Danish children with atopic dermatitis and parental topical corticosteroid phobia.

Atopic dermatitis (AD) is a prevalent relapsing inflammatory skin disease. There is currently little knowledge about healthcare utilization and medication use along with parental corticosteroid phobia in relation to severity of pediatric AD. To study the association between parental-reported healthcare utilization, medication use, and topical corticosteroid phobia and pediatric AD severity. The study population included all children in Denmark with a diagnostic code of AD (ICD-10 code, group L20) given at a hospital department of dermatology between 2014 and 2018. A questionnaire containing 158 response items was sent to the legal parents. We surveyed disease severity, AD treatment, corticosteroid phobia, and healthcare use along with other variables. Disease severity was assessed using the Patient-Oriented Eczema Measure tool, and corticosteroid phobia was assessed using the Topical Corticosteroid Phobia (TOPICOP) score. In total, 1343 (39%) parents completed the questionnaire and 95.3% were completed by the biological mother. Children's mean age was 8.9±4.5years, and 52.8% were boys. Severe AD was associated with a higher number of healthcare visits to GPs, private dermatologists, and hospital departments. Mean global TOPICOP score was 38.27±19.9%. There was a significant inverse linear trend between global TOPICOP score and parental educational level (Ptrend <.0005). The significant association between high global TOPICOP score and low parental educational level, resulting in delayed treatment of AD flares, indicates that improved family education ultimately may reduce healthcare expenses and burden of disease.

Revisiting the safety of topical calcineurin inhibitors in patients with atopic dermatitis

Topical calcineurin inhibitors (TCI) have emerged from the shadow of topical corticosteroids as another first-line remedies for treating acute flares of atopic dermatitis (AD). The effectiveness of TCI in maintenance therapy is also undeniable. The wider use of TCI increases the relevance of the issue of their safety. The adherence of physicians and their patients to the treatment with TCI is constrained by a controversial FDA black box warning against these drugs based on the theoretical risk of skin tumors, especially lymphoma. This warning, formulated in 2005, has been repeatedly refuted. However, there have been studies that at least partially supported cautious use of TCI. In recent years, the results of large cohort prospective studies clarifying the issue of oncological safety of TCI have been published. The review highlights the results of various studies with optimistic, pessimistic and balanced conclusions regarding the safety of TCI, primarily their effect on tumorigenesis, in order to better inform physicians about the benefit/risk balance when using these drugs in AD patients. The data presented in this review indicate that there is no increased risk of melanoma and other forms of skin cancer in TCI users, but these data do not completely rule out the risk of skin lymphoma. However, the very low level of potential risk to an individual patient gives physicians the right to neglect this risk when choosing TCI as a treatment option for AD.

Randomized double‐blind cross‐over trial of bath additive containing tannic acid in patients with atopic dermatitis

AbstractSkin care against aggravating factors is important to prevent skin lesions from flare‐up in the treatment of atopic dermatitis (AD). Tannic acid (TA), a natural polyphenolic and protein‐denaturing agent, has activity to denature antigens relevant to the AD flare. To assess the efficacy of a bath additive containing TA (TA‐bath additive) on pruritus of AD, we carried out a randomized double‐blind trial, in which 21 patients with AD completed the blinded sequential treatments with the TA‐bath additive and a bath additive without TA (placebo‐bath additive) in a cross‐over manner. A significant improvement of pruritus was observed in the afternoon and night by using the TA‐bath additive and in the afternoon by the placebo‐bath additive in patients with AD. No superiority of the TA‐bath additive to the placebo was revealed in the overall patient cohort. However, the added TA in the bath additive exerted its efficacy especially on itch at night in patients with mild‐to‐moderate disease. Bathing by using the series of the bath additive with TA and that without TA improved AD skin lesions throughout this study. No adverse effects related to the use of the TA‐ and placebo‐bath additives were observed. In conclusion, the bath additive containing TA may help skin care of patients with itch and skin lesions of the mild AD.

Rosmarinus officinalis L. (Rosemary) Extracts Containing Carnosic Acid and Carnosol are Potent Quorum Sensing Inhibitors of Staphylococcus aureus Virulence.

Staphylococcus aureus is an opportunistic pathogen and a common cause of skin infection. S. aureus also plays a role in the pathogenesis of the chronic inflammatory skin disease, atopic dermatitis. S. aureus virulence involves activation of the quorum sensing agr operon. In this paper, we show that the diterpene carnosic acid, present in R. officinalis L. (rosemary) leaves, is a specific inhibitor of S. aureus agr expression as low as 5 μM. Carnosol and rosmarinic acid are two other phytochemicals present in rosemary leaves. Carnosol, but not rosmarinic acid, is also a potent agr expression inhibitor. Natural rosemary extracts containing carnosic acid and carnosol inhibit S. aureus agr expression, both in luciferase reporter strains and in wild type strains isolated from patients with atopic dermatitis. Specific inhibition of S. aureus virulence using topical formulations of rosemary extract may offer a practical approach to preventing and treating flares of atopic dermatitis.

Therapeutic Efficacy and Safety of Methotrexate in Moderate-to-Severe Atopic Dermatitis: A Retrospective Study of Korean Patients at Tertiary Referral Hospital.

BackgroundMethotrexate (MTX) has been prescribed to suppress atopic dermatitis (AD) symptoms and flares in moderate-to-severe cases.ObjectiveThe purpose of this study was to evaluate the therapeutic efficacy and safety of MTX as well as the suppressive activity of MTX to reduce flares in moderate-to-severe AD patients.MethodsPatients with moderate-to-severe AD who were treated with MTX at the Chonnam National University Hospital were retrospectively studied.ResultsTotal 102 patients (79 males, 23 females) with a median age of 22.0±10.3 years were studied. The median initial dose of MTX was 10.3±2.6 mg/week, and the MTX-weekly dose was increased by 2.5 to 5 mg at an interval of 2 to 4 weeks to a maximum dose of 17.5±2.7 mg/week. The median maintenance dose was 11.7±2.1 mg/week; the median duration of treatment with MTX was 34.0±38.8 weeks. The initial response was noted after 5.8±3.7 weeks. Of the 102 patients, 60.8% (62/102) showed successful treatment response and 39.2% (40/102) showed mild or no improvement. MTX therapy effectively suppressed the frequency of AD flares by more than 50% in 71.1% (32/45) of the patients who responded among the MTX responders group. The most common adverse events were transient liver abnormality (5.9%, 6/102) and gastrointestinal discomfort (3.9%, 4/102), but no serious adverse events occurred.ConclusionOur results reveal that MTX is a relatively safe drug to control moderate-to-severe AD with satisfactory therapeutic efficacy and inhibitory activity against AD flares.

The improvement of infantile atopic dermatitis during the maintenance period: A multicenter, randomized, parallel controlled clinical study of emollients in Prinsepia utilis Royle.

In order to investigate the effect of daily emollient treatment on infantile atopic dermatitis (AD) during the maintenance period, a total of 309 children younger than 2 years with moderate AD (155 and 154 in the treatment and control groups, respectively) were enrolled in this multicenter, randomized, parallel controlled clinical trial. Subjects were topically treated with desonide cream and emollients in Prinsepia utilis Royle for 2-4 weeks before entering the maintenance period and then differentially treated with either emollients for treatment or none for control. The cumulative maintenance rate, time to flare and improvement of eczema area and severity index (EASI) and infant's dermatitis quality of life index (IDQOL) were evaluated. Results showed that the cumulative maintenance rate of the treatment group (60.5%, 95% CI 50.0-69.4%) was significantly higher than that of the control group (23.5%, 95% CI 15.2-33.0%) (p < .001). The median time to flare in the treatment group was 90 days (interquartile range, IQR 28-90), which was significantly longer than that in the control group (28 days [IQR 18-67]) (p < .001). At Week 4 in the maintenance period, the EASI and IDQOL scores of the treatment group were lower than those of the control group. In conclusion, the application of emollients during the maintenance period of infantile AD can significantly reduce the risk of AD flares, prolong the time to flare and improve the clinical symptoms.

Topical tacrolimus in adult atopic dermatitis: a consensus based on a 15-year experience.

Atopic dermatitis (AD) is one of the most common cutaneous inflammatory diseases both in adults and in children. It is a chronic, remitting-relapsing dermatitis, primarily managed by dermatologists, but also by allergists and primary care physicians. Due to coexistence of comorbidities, often a multidisciplinary team is required. Topical calcineurin inhibitors (TCIs - i.e. tacrolimus and pimecrolimus) are a class of steroid-sparing, anti-inflammatory agents that have been shown to be efficacious for the treatment of AD acute flares and in maintenance therapy. In particular, the application of tacrolimus ointment twice daily reduces AD severity and pruritus. Moreover, maintenance therapy with an intermittent application of tacrolimus to recurrent skin sites (proactive therapy) decreases frequency and severity of relapses. Many studies have also assessed the efficacy of TCIs in disorders other than AD. Although US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a "black box warning" regarding the possible cancerogenic activity of these drugs, there is currently no strong evidence of an increased rate of malignancy in treated patients, and observational data from postmarketing surveillance studies have shown no safety concerns. A panel of dermatologists have thoroughly discussed the use of tacrolimus in AD after 15-year experience. The experts focused on AD flare treatment, maintenance therapy and management of side effects. Consensus was reached on some areas of interest, namely the stages of AD in which tacrolimus is recommended, the amount of drug to be applied, how to manage side effects, and how to improve patient's compliance. Moreover, the panel of experts recommended to perform randomized clinical trials to confirm the efficacy of tacrolimus off-label use, which led to successful outcomes in other skin diseases.

M319 ATOPIC DERMATITIS AND THE RISK OF FOOD AVOIDANCE: AN UNFORTUNATE CASE OF FOOD ALLERGY

Frequently, patients with atopic dermatitis (AD) avoid otherwise tolerated foods due to concerns for possible flares of AD, or sensitization found on blood and/or skin prick testing (SPT). Most studies in patients with AD demonstrate poor predictive value when comparing food allergy (FA) testing and immediate reactions during oral food challenge (OFC). Furthermore, avoidance of some foods carries a risk of developing IgE-mediated FA.

Staphylococcus aureus and the Cutaneous Microbiota Biofilms in the Pathogenesis of Atopic Dermatitis.

Biofilm is the dominant mode of growth of the skin microbiota, which promotes adhesion and persistence in the cutaneous microenvironment, thus contributing to the epidermal barrier function and local immune modulation. In turn, the local immune microenvironment plays a part in shaping the skin microbiota composition. Atopic dermatitis (AD) is an immune disorder characterized by a marked dysbiosis, with a sharp decline of microbial diversity. During AD flares biofilm-growing Staphylococcus aureus emerges as the major colonizer in the skin lesions, in strict association with disease severity. The chronic production of inflammatory cytokines in the skin of AD individuals concurs at supporting S. aureus biofilm overgrowth at the expense of other microbial commensals, subverting the composition of the healthy skin microbiome. The close relationship between the host and microbial biofilm resident in the skin has profound implications on human health, making skin microbiota an attractive target for the therapeutic management of different skin disorders.

The infantile cutaneous microbiome: A review.

Recent focus on the neonatal intestinal microbiome has advanced our knowledge of the complex interplay between the intestinal barrier, the developing immune system, and commensal and pathogenic organisms. Despite the parallel role of the infant skin in serving as both a barrier and an interface for priming the immune system, large gaps exist in our understanding of the infantile cutaneous microbiome. The skin microbiome changes and matures throughout infancy, becoming more diverse and developing the site specificity known to exist in adults. Delivery method initially determines the composition of the cutaneous microbiome, though this impact appears transient. Cutaneous microbes play a critical role in immune system development, particularly during the neonatal period, and microbes and immune cells have closely intertwined, reciprocal effects. The unique structure of newborn skin influences cutaneous microbial colonization and the development of dermatologic pathology. The development of the infantile skin barrier and cutaneous microbiome contributes to future skin pathology. Atopic dermatitis flares and seborrheic dermatitis have been linked to dysbiosis, while erythema toxicum neonatorum is an immune response to the establishment of normal bacterial skin flora. Physicians who care for infants should be aware of the impact of the infantile skin microbiome and its role in the development of pathology. A better understanding of the origin and evolution of the skin microbiome will lead to more effective prevention and treatment of pediatric skin disease.

Tolerability and Efficacy of a Medical Device Repairing Emollient Cream in Children and Adults with Mild to Moderate Atopic Dermatitis.

IntroductionRegular emollient application is recommended for managing atopic dermatitis (AD). Although many emollients are available, only AD-tested medical device repairing emollient creams (MDRECs) can be recommended for treating and preventing AD skin lesions. Here, we evaluated the tolerability and benefit of a new MDREC in an open-label study in infants, young children, and adults with mild to moderate AD.MethodsSubjects (or their parents or guardians) were instructed to apply the MDREC to AD lesions or areas of dry skin twice daily for 3 weeks. Investigators assessed tolerability and AD severity at days 1, 8, and 22. Subjects assessed AD severity weekly, recorded any adverse events, and reported their satisfaction with the MDREC at day 22.ResultsSixty-one subjects (19 infants, 22 children, and 20 adults) were included and 59 completed the study. At inclusion, 49% of the infants and young children and 15% of the adults were experiencing flares of AD. At day 22, the local tolerability of the MDREC was judged by the investigators as excellent in all the children and in 18 of the 20 adult subjects (90%). All adverse events were mild and transient. Investigator- and subject-assessed AD severity progressively decreased at each assessment for each age subgroup.ConclusionThis study shows that the MDREC was well tolerated when applied to AD skin lesions in infants, young children, and adults and suggests this product can be used daily to control the signs and symptoms of AD.FundingLaboratoires Dermatologiques Ducray, Pierre Fabre Dermo-Cosmétique.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid-containing preparation (Atopiclair® ), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once-daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE.

Proactive maintenance therapy of canine atopic dermatitis with the anti-IL-31 lokivetmab. Can a monoclonal antibody blocking a single cytokine prevent allergy flares?

Once the signs of canine atopic dermatitis (AD) are controlled, the proactive application of topical glucocorticoids can delay disease flares. We wished to determine if the proactive administration of the anti-IL-31 lokivetmab would prevent or delay flares of canine AD. We tested this strategy in four Maltese-beagle atopic dogs before enrolling 21 dogs with spontaneous AD. In our acute AD model, house dust mite (HDM)-sensitized dogs were injected once with lokivetmab. After seven days, an HDM suspension was applied epicutaneously, and both skin lesions and pruritus manifestations were quantified for 24h. In a second study, 21 dogs with spontaneous AD controlled with anti-allergic drugs were treated with lokivetmab per manufacturer's recommendations; all anti-allergic drugs were discontinued within four weeks after the first injection. All dogs were followed prospectively for at least one year and the time-to-flare (TTF) of AD after the last day of anti-allergic treatment was determined. In the experimental study, one injection of lokivetmab prevented nearly all expected allergen-induced pruritus manifestations but not skin lesion development. In dogs with spontaneous AD, the median TTF after lokivetmab proactive therapy was 63days. One-fourth of dogs did not exhibit a flare for at least one year while receiving lokivetmab monotherapy. Although lokivetmab seems more effective to prevent pruritus than skin lesions in dogs with experimental AD' it also can delay disease flares in some dogs with the spontaneous disease. Studies are needed to identify those patients most likely to respond to such a proactive regimen.

Economic value of atopic dermatitis prevention via partially-hydrolyzed whey-based infant formula (PHF-W) use in high-risk, non-exclusively breastfed, Indonesian urban infants: results of a cost-effectiveness model

Background: Early nutritional intervention with partially-hydrolyzed whey-based formula (PHF-W) instead of standard cow’s milk formula (CMF) has been found to reduce the risk of atopic dermatitis (AD) development in non-exclusively breastfed infants with familial heredity of AD.Objective: To estimate the 6-year economic impact of this nutritional intervention in non-exclusively breastfed Indonesian urban infants with family history of AD.Methods: A mathematical model simulated AD incidence and burden of using PHF-W vs. CMF in the target population from birth to age 6. The model integrated literature, current cost and market catalogues, and expert clinician opinion. Modeled outcomes included AD risk, time spent post-AD diagnosis, days without flare, quality-adjusted life-years, and costs.Results: Using PHF-W instead of CMF resulted in an estimated absolute 14% (95% CI: 4%, 23%) AD risk reduction, a 0.69 year (95% CI: 0.26, 1.13) per-child reduction in time spent post-AD diagnosis, a 38 (95% CI: 12, 67) increase in days without AD flare, and a 0.046 gain in quality-adjusted life-years. The AD-related 6-year cost estimates when feeding high-risk urban infants with PHF-W were Indonesian Rupiah (IDR) 8,695,057 (95% CI: IDR 4,519,447, IDR13,995,605) and IDR13,139,569 (95% CI: IDR 7,098,794, IDR 19,216,068) per child, respectively, resulting in a net per-child difference of IDR 4,444,512 (95% CI: IDR1,893,080, IDR 8,557,946) favoring PHF-W.Conclusion: PHF-W for the first 17 weeks of non-exclusively breastfed Indonesian urban infants with a hereditary risk of AD demonstrated a reduction in AD incidence, increased days without flare, and increased quality-adjusted life-years and net cost reductions.

Atopy and Sensitization to Allergens Known to Cause Systemic Contact Dermatitis.

Atopic dermatitis (AD) associated with respiratory atopy may represent a form of systemic contact dermatitis (SCD), whereby AD flares after ingestion or inhalation of allergens. The aim of the study was to compare the prevalence of positive patch tests to allergens known to cause SCD in AD patients with and without respiratory atopy. This is a retrospective study of patients with AD patch tested to 23 allergens known to cause SCD. Positive patch tests were compared between AD patients with and without respiratory atopy, stratified by age and wet or dry work occupation. Children and adolescents, but not adults, with AD and respiratory atopy were more likely than age-matched AD patients without respiratory atopy to have positive patch tests to these allergens (odds ratio, 2.33; 95% confidence interval, 1.13-4.79). Moreover, AD patients with respiratory atopy and engaging in wet work, but not dry work, occupations were more likely than AD patients without respiratory atopy to have positive patch tests to allergens known to cause SCD (odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Thus, respiratory atopy and wet work are associated with sensitization to allergens known to cause SCD in patients with AD, and patch testing may be valuable in identifying systemic triggers of dermatitis in these patients.

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

BACKGROUNDAtopic 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.OBJECTIVESThe aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis.METHODSEighteen 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/CONCLUSIONThe 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.

Staphylococcus aureus from atopic dermatitis skin accumulates in the lysosomes of keratinocytes with induction of IL-1α secretion via TLR9.

Staphylococcus aureus (S.aureus) is frequently detected in the skin of patients with atopic dermatitis (AD), and involved in the flare of AD. There are some evidence-specific strains of S.aureus affect the severity of AD. However, the mechanism of predominant colonization and the aggravation of dermatitis by certain strains of S.aureus in the patients with AD are still unknown. To reveal the characteristics of S.aureus from patients with AD (S.aureus-AD), we analyzed the interaction of S.aureus-AD and keratinocytes in comparison with those of S.aureus laboratory strains (S.aureus-stand.). We stimulated HaCaT cells, keratinocyte cell line, and human epidermal keratinocytes by heat-killed S.aureus strains, then evaluated immune response of keratinocytes by ELISA, immunofluorescence staining, and flow cytometry. Upon incubation with keratinocytes, three out of four strains of heat-killed S.aureus-AD were strongly agglutinated inside the cytoplasm. In the cells, they are located in lysosomes and promoted the secretion of interleukin-1α (IL-1α). These reactions were not observed by any of four strains of S.aureus-stand. and S.epidermidis and were abolished by the treatment of S.aureus with proteinase K. Moreover, the IL-1α secretion was diminished by the inhibition of Toll-like receptor 9 (TLR9). S.aureus-AD accumulates in lysosome of keratinocytes by means of bacterial cell wall proteins and induces IL-1α via TLR9.