Topical proactive therapy in dermatology. A scoping review.

The term 'proactive therapy' refers to a long-term management of clinically intact skin in previously disease-affected areas. This method was initially implemented in atopic dermatitis to maintain the remission and decrease the risk of exacerbations. Proactive therapy aims to limit the need for reactive treatment and improve the patients' quality of life. A proactive approach is likely to be adopted for other relapsing and inflammatory skin conditions in the future. This scoping review aims to identify dermatological conditions to be treated with the proactive approach, evaluate the available evidence for its efficacy and safety, as well as highlight the research gaps.

Multilocus-sequence typing reveals clonality of Staphylococcus aureus in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is exacerbated by Staphylococcus aureus, which is capable of displacing not only the physiological microbiota, but also other strains of its own species. Analyses of the molecular characteristics and relationships of S. aureus strains present in different microniches are lacking. OBJECTIVES: To determine, using multilocus sequence typing (MLST), the relationship of S. aureus isolates from the lesional and nonlesional skin and anterior nares of patients with AD, and to review the characteristics of the dominant clones. METHODS: Sixty-three individuals with active AD were enrolled. Ten patients with moderate-to-severe AD (SCoring of Atopic Dermatitis score ≥ 25) colonized by S. aureus in all analysed locations were included in the MLST analysis. RESULTS: The most prevalent sequence types were 7 (10/30 strains; 33.3%), 15 and 97 (both 5/30 strains; 16.7%) all of which were associated with the expression of adhesins and toxins promoting chronic microbial dysbiosis, skin barrier damage and inflammation. Six patients (60%) were carriers of clonal S. aureus strains at all analysed locations, three (30%) carriers in lesional and nonlesional skin, and one (10%) was a carrier in nonlesional skin and the anterior nares. CONCLUSIONS: The results imply that the identified S. aureus lineages are better adapted to dominate the microbiota in AD. Decontaminating the identified reservoirs of S. aureus (i.e. anterior nares and nonlesional skin) could reduce the severity of AD.

Enterotoxin Gene Cluster and selX Are Associated with Atopic Dermatitis Severity-A Cross-Sectional Molecular Study of Staphylococcus aureus Superantigens.

Staphylococcus aureus superantigens (SAgs) have been reported to aggravate atopic dermatitis. However, comprehensive analyses of these molecules in multiple microniches are lacking. The present study involved 50 adult patients with active atopic dermatitis. S. aureus was isolated from the lesional skin, nonlesional skin, and anterior nares. Multiplex-PCR was performed to identify genes encoding (1) selX (core genome); (2) seg, selI, selM, selN, selO, selU (enterotoxin gene cluster, EGC); and (3) sea, seb, sec, sed, see, tstH (classic SAgs encoded on other mobile genetic elements). The results were correlated to clinical parameters of the study group. selx and EGC were the most prevalent in all microniches. The number of SAg-encoding genes correlated between the anterior nares and nonlesional skin, and between the nonlesional and lesional skin. On lesional skin, the total number of SAg genes correlated with disease severity (total and objective SCORAD, intensity, erythema, edema/papulation, lichenification and dryness). Linear regression revealed that AD severity was predicted only by selx and EGC. This study revealed that selX and EGC are associated with atopic dermatitis severity. Anterior nares and nonlesional skin could be reservoirs of SAg-positive S. aureus. Restoring the physiological microbiome could reduce the SAg burden and alleviate syndromes of atopic dermatitis.

The Role of the Cutaneous Mycobiome in Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disorder characterized by eczematous lesions, itch, and a significant deterioration in the quality of life. Recently, microbiome dysbiosis has been implicated in the pathogenesis of atopic dermatitis. Changes in the fungal microbiome (also termed mycobiome) appear to be an important factor influencing the clinical picture of this entity. This review summarizes the available insights into the role of the cutaneous mycobiome in atopic dermatitis and the new research possibilities in this field. The prevalence and characteristics of key fungal species, the most important pathogenesis pathways, as well as classic and emerging therapies of fungal dysbiosis and infections complicating atopic dermatitis, are presented.

Sinoatrial conduction abnormalities - an underestimated cardiac complication in women with systemic sclerosis.

INTRODUCTION: It has been claimed that patients with systemic sclerosis (SSc) have an increased risk of developing cardiac arrhythmias and atrioventricular conduction disorders, but it is unknown whether SSc may be a cause of sinoatrial conduction abnormalities. AIM: To establish the incidence of sinoatrial conduction abnormalities in patients with SSc and verify the relationship of these disorders with various clinical descriptors of SSc. MATERIAL AND METHODS: Forty women with systemic sclerosis of varying duration and severity underwent 24-hour ambulatory ECG monitoring. The occurrence of type I second-degree sinoatrial block (SA-block) and calculation of sinoatrial conduction time (SACT) were evaluated to establish the incidence of sinoatrial conduction abnormalities. The measurements of SACT were obtained using spontaneous atrial premature beats. The effect of various clinical descriptors on sinoatrial conduction abnormalities was assessed. RESULTS: The mean ± SD SACT for the 40 patients was 150 ±15 ms. Prolonged (> 150 ms) SACT was found in 20 patients. In 14 (35%) patients SA-block occurred during ambulatory ECG monitoring. The discriminant analysis identified the severity of SSc cutaneous manifestation as an independent marker for developing SA-block (p < 0.005) and SACT prolongation (p < 0.0002). CONCLUSIONS: Patients with SSc are at an increased risk of developing type I second-degree sinoatrial block and prolonged sinoatrial conduction time. The occurrence of these abnormalities is related to the severity of skin involvement. Therefore, cardiological diagnosis using 24-hour ambulatory ECG in this group of patients should be focused also on this type of disorders. Prospective, controlled studies are needed to assess their prognostic role.

The Influence of Microbiome Dysbiosis and Bacterial Biofilms on Epidermal Barrier Function in Atopic Dermatitis-An Update.

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.

The Propensity to Form Biofilm in vitro by Staphylococcus aureus Strains Isolated from the Anterior Nares of Patients with Atopic Dermatitis: Clinical Associations.

BACKGROUND: Atopic dermatitis is a chronic inflammatory dermatosis with complex pathogenesis. The skin microbiome in atopic dermatitis is dominated by Staphylococcus aureus which shows the ability to produce biofilm. OBJECTIVES: The aim of this work was to assess the influence of S. aureus biofilm on the course of atopic dermatitis. METHODS: Disease severity was evaluated based on the SCORAD index in 56 adult patients with atopic dermatitis. Microtiter plate assay of the propensity to form biofilm was performed on S. aureus strains isolated from the anterior nares, lesional skin, and nonlesional skin. Microbiological results were correlated to the clinical parameters and total IgE concentration. RESULTS: Biofilm-producing strains of S. aureus were identified in 76.3% (29/38) and 79.1% (34/43) of samples from the anterior nares and lesional skin, respectively (p > 0.05), and in 48.5% (16/33) of samples from nonlesional skin (p < 0.03). Patients colonized by biofilm-producing strains of S. aureus within the anterior nares showed statistically higher mean values of total and objective SCORAD and its components (extent, dryness), and of the largest extent of skin lesions during the flares in the last year when compared to patients colonized by non-biofilm-producing strains. Carriage of biofilm-producing S. aureus on lesional skin was associated with higher mean values of the extent of skin lesions during stable periods of the disease. CONCLUSIONS: The results of this study may suggest a relationship between the production of biofilm by S. aureus strains colonizing the anterior nares and the course of atopic dermatitis. Biofilm seems crucial for dispersal and persistent colonization of large areas of the skin by this pathogen. Destruction of S. aureus biofilm could positively affect the course of atopic dermatitis.

Biological drugs in the treatment of atopic dermatitis - current recommendations of the Polish Dermatological Society, the Polish Society of Allergology, the Polish Pediatric Society and the Polish Society of Family Medicine.

Atopic dermatitis (AD) is secondary to genetic, immunological and microbiological disorders as well as epidermal barrier defects, which are the main targets of therapy. The disease proceeds with periodic exacerbations. Its development and course are influenced by numerous environmental and individual factors. In recent decades, in industrialized countries, there has been a threefold increase in the incidence of AD. There is also an increasing number of cases resistant to topical treatment. Effective treatment of AD should provide control of clinical symptoms, prevent exacerbations and improve the quality of life of patients. The multifactorial etiopathogenesis and various endotypes and phenotypes of AD justify the tendency to optimize and personalize the therapy. Currently, we recommend the use of dupilumab for the treatment of patients from 12 years of age with moderate and severe atopic dermatitis, who do not respond to topical treatment.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part II. Systemic treatment and new therapeutic methods.

The treatment goal in atopic dermatitis is eliminating clinical symptoms of the disease, preventing exacerbations and complications, as well as improving patients' quality of life. In cases of severe atopic dermatitis and lack of response it is recommended to introduce systemic therapy. Patients ofter require multi-specialist consultations, and occasionally hospitalization. It is not recommended to use acupuncture, acupressure, bioresonance, homeopathy, or Chinese herbs in the treatment of atopic dermatitis.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part I. Prophylaxis, topical treatment and phototherapy.

Atopic dermatitis is a chronic and recurrent inflammatory dermatosis with concomitant intensive pruritus, and is diagnosed both in children and adults. Atopic dermatitis-patients are predisposed to have bacterial, viral and fungal skin infections; they also suffer from an increased risk of developing food allergies (especially, at an infantile age), allergic rhinitis, or bronchial asthma (a so-called atopic march). Currently, an increasing atopic dermatitis incidence constitutes a serious medical problem that regards not only dermatology and allergology, but also paediatrics, and family medicine. The basis for atopic dermatitis treatment and prophylaxis is restoration of epidermal barrier functions by means of tailored emollients. Atopic dermatitis therapies should effectively eliminate clinical symptoms of the disease, prevent exacerbations as well as complications, and improve patients' quality of life.

Nasal Colonization by Staphylococci and Severity of Atopic Dermatitis.

BACKGROUND: Skin colonization by Staphylococcus aureus (SA) correlates with increased severity of atopic dermatitis (AD). The role of nasal SA carriage and coagulase-negative staphylococci (CNSs) in AD is unclear. OBJECTIVE: The aim of this study was to assess the influence of colonization of lesional/nonlesional skin and the anterior nares by SA and CNSs on AD severity in 63 adult patients. METHODS: Disease severity was assessed with SCORAD index. The total immunoglobulin E (IgE) concentration was determined using the enzyme-linked immunosorbent assay method. The prevalence and abundance of staphylococci were assessed with the combination of bacterial culture and mass spectrometry. RESULTS: The prevalence values of SA within the skin (lesional/nonlesional) and anterior nares were 79.4%/61.9% and 69.8%, respectively (vs 5.6% and 13.9%, respectively in controls, P < 0.0001). The carriage of CNSs in all niches was associated with lower mean IgE concentration (1164.66 ± 1010.36 vs 1762.99 ± 1059.15, P < 0.0213; 1166.9 ± 1006.4 vs 2152.7 ± 759.2, P < 0.0063; 1022 ± 1100 vs 1925 ± 880.8, P < 0.0044, respectively). The abundance of SA correlated with the extent of skin lesions and total IgE (ρ = 0.42, P = 0.0007; ρ = 0.488, P < 0.0001; ρ = 0.312, P < 0.2; and ρ = 0.402, P = 0.0007; ρ = 0.403, P < 0.002; ρ = 0.287, P < 0.03, respectively). CONCLUSIONS: Atopic dermatitis severity correlates with both cutaneous and nasal colonization by SA. Staphylococcus aureus seems to promote TH2-type response, whereas CNS probably limits this process. Preventive measures within the anterior nares should be considered for AD patients.

Is Itch Intensity in Atopic Dermatitis Associated with Skin Colonization by Staphylococcus aureus?

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic skin condition of unclear pathogenesis. Patients with AD are predisposed to colonization by Staphylococcus aureus due to deficiencies in the mechanical and immunological functions of the skin barrier. Recent studies indirectly show that S. aureus may aggravate disease flares in AD. AIMS: The aim was to assess the relationship between S. aureus skin colonization and itch intensity in patients with AD. MATERIALS AND METHODS: The SCORAD index components reflecting itch intensity (excoriations, subjective evaluation of pruritus, and sleep loss) were assessed in 33 adult patients with AD. Swabs were taken from lesional and nonlesional skin. The prevalence and abundance of S. aureus were assessed. Statistical analysis was performed to correlate the microbiological results with the clinical parameters. The control group consisted of 36 healthy volunteers. RESULTS: Lesional and nonlesional skin showed a high frequency of S. aureus colonization when compared with controls (81.8% and 57.6% vs 5.6%, respectively, P < 0.0001). The mean concentration (points) of S. aureus was 2.01 ± 1.25, 1.06 ± 1.14, and 0.11 ± 0.46, respectively (P < 0.0001). S. aureus abundance on lesional/nonlesional skin positively correlated with excoriations and sleep loss (rho = 0.69, P < 0.00001; rho = 0.44, P < 0.01; rho = 0.41, P < 0.02; and rho = 0.34, P < 0.05, respectively). The mean values of excoriations were higher in patients colonized by S. aureus than in patients without S. aureus carriage. CONCLUSION: S. aureus skin colonization may be one of the factors aggravating itch in AD. It may be hypothesized that restoring the natural composition of the skin microbiome may reduce pruritus intensity.

Can evaluation of specific immunoglobulin E serum concentrations of antibodies to aeroallergens in atopic dermatitis patients replace skin prick tests method in clinical practice?

INTRODUCTION: Positive skin prick tests (SPT) results with protein allergens are the minor Hanifin and Rajka's atopic dermatitis (AD) criterion. In adults, they mainly concern aeroallergens. The inflammation of skin often prevents SPT, but does not exclude the assessment of serous specific immunoglobulin E (sIgE) concentrations. AIM: To assess usefulness of testing AD patients to aeroallergens with SPT and sIgE concentrations, and the correlation of these results and the clinical AD course. MATERIAL AND METHODS: In 286 AD patients, total IgE and sIgE (14 aeroallergens) were measured. SPTs were performed with 17 aeroallergens. The AD severity was determined depending on the concurrent co-existence of asthma, allergic rhinitis, extensive skin flares and severe itching. RESULTS: 59.1% and 66.1% of patients have had positive results of sIgE and SPT, respectively (p > 0.05). The concentration of total IgE has positively correlated with the number of positive sIgE results (rho = 0.588, p < 0.001) and their intensity (rho = 0.592, p < 0.001). Among the patients with at least one high positive sIgE score, severe AD patients have been dominant (59.8% vs. 40.2%, p < 0.04). Among the patients with positive results without any high scores, the percentages are 21.6 and 78.4, respectively (p < 0.001). CONCLUSIONS: The compatibility of SPT results and IgE concentrations indicates that the two methods equally assess aeroallergy in AD patients. The assessment of sIgE concentrations is especially advisable in patients with an elevated total IgE level. The obtained results may suggest that presence of a high specific IgE level of antibodies to aeroallergens may be the factor predicting a severe clinical AD course.

Staphylococcus aureus: an underestimated factor in the pathogenesis of atopic dermatitis?

Atopic dermatitis is a common, recurrent pruritic dermatosis with a complex pathogenesis. It has been associated with disordered patterns of immunological response and impaired epithelial barrier integrity. These features predispose the patients to robust colonization of skin lesions by Staphylococcus aureus. Virulence factors of S. aureus (e.g. superantigens, α- and δ-toxin, protein A) have been shown to exacerbate and perpetuate the course of atopic dermatitis. Novel therapeutic options with potential for restoring natural microbiome composition are being elaborated and may enter clinical practice in the future.

Atopic and Non-atopic Eczema.

Atopic dermatitis is a common term used in the medical literature, but according to The Nomenclature Review Committee Of The World Allergy Organization the name which should be used is eczema. Eczema is divided into two subtypes: atopic and non-atopic. These subtypes differ in the level of total immunoglobulin E (IgE) in serum, response to allergens in skin prick tests, and detection of specific IgE antibodies. Non-atopic eczema is characterized by a low level of total IgE, negative skin prick tests, and undetectable specific IgE antibodies. It is estimated that 10-45% cases of eczema are non-atopic ones. In recent studies, other features differentiating these two subtypes have been identified, such as female predominance in non-atopic eczema. A more severe course, damage of the epidermal barrier, predominance of Th2 (T helper cells 2) response, and a lower positive reaction to metal patch tests are the characteristics of the atopic subtype. In our opinion, new diagnostic criteria taking into account the non-atopic subtype of eczema need to be established.

MiRNA in atopic dermatitis.

MicroRNAs are relatively new molecules that have been widely studied in recent years as to determine their exact function in the human body. It is suggested that microRNAs control approx. 30% of all genes, making them one of the largest groups that control the expression of proteins. Various functions of miRNAs have already been described. In skin diseases, there are more and more studies describing an altered expression of microRNAs in the skin or serum. Relatively little is known about the function of these molecules in atopic dermatitis, which prompted us to gather current reports on this subject.

Expression of vascular endothelial growth factor and other cytokines in atopic dermatitis, and correlation with clinical features.

BACKGROUND: Vascular endothelial growth factor (VEGF) was found increased in the stratum corneum of patients with atopic dermatitis (AD). However, its potential pathogenic role(s) in AD needs further clarification. OBJECTIVE: The aim of this study was to determine whether VEGF serum levels correlate with other selected cytokine levels and features of AD. METHODS: VEGF and other cytokine levels were measured in 83 patients with AD and in a control group and then correlated with clinical and laboratory parameters of AD. RESULTS: The mean serum concentrations of VEGF and tumor necrosis factor α were significantly higher in patients with AD than in the control group, whereas the mean interleukin eight serum level was lower. VEGF concentrations correlated with the severity of AD as expressed by SCORAD index and objective SCORAD. CONCLUSION: VEGF could be regarded as a potentially important mediator in the pathogenesis of AD, as VEGF levels correlate somewhat with AD severity.