Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model

Atopic dermatitis, a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. In this study, we examined the efficacy of ointment containing NF-kB decoy oligodeoxynucleotides (ODN) on atopic dermatitis lesions in NC/Nga mice, which are characterized by the spontaneous onset of atopic dermatitis in conventional conditions. Topical administration of NF-kB decoy ODN twice a month resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. Reduction of the atopic skin condition by NF-kB decoy ODN was accompanied by a significant decrease in migration of mast cells into the dermis and an increase in apoptotic cells. Here, we demonstrated the successful treatment of atopic dermatitis with ointment containing NF-kB decoy ODN in a mouse model, promising new therapy for atopic dermatitis.     

Starvation reduces allergen-induced skin wheal responses and plasma substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome

The effect of starvation on allergen-induced skin wheal responses and plasma neuropeptide levels was not previously reported. Starvation for 24 h reduces allergen-induced skin wheal responses and plasma levels of substance P and vasoactive intestinal peptide in patients with atopic eczema/dermatitis syndrome, but not in control subjects. These results may have implications for the pathophysiology of the atopic eczema/dermatitis syndrome.     

CKLF1拮抗肽C19在小鼠特应性皮炎中的作用研究

目的探讨趋化素样因子1(CKLF1)拮抗肽C19局部皮下注射对特应性皮炎小鼠模型的作用。方法用卵清蛋白(OVA)经皮致敏BALB/c小鼠建立特应性皮炎模型。将60只BALB/c小鼠随机分成特应性皮炎组、对照组、预防组和治疗组,每组15只。观察小鼠致敏局部皮肤及组织病理改变。以ULSTM荧光标定技术检测各组总RNA中micro RNA的表现图谱。结果 1与对照组及预防组相比,皮炎组小鼠局部皮肤出现红斑、鳞屑等皮损,治疗组小鼠皮损经治疗后红斑、水肿减轻,鳞屑减少。小鼠局部皮损组织病理学显示,经CKLF1拮抗肽C19预防或治疗后,小鼠表皮增厚、细胞间水肿、真皮血管扩张充血及炎性细胞浸润均较轻。2以ULSTM荧光标定技术检测各组总RNA中micro RNA的表现图谱,通过鉴定各组间上调与下调的特定micro RNA基因,筛选调节炎症细胞因子特定靶基因表达的micro RNA,初步分析发现,经CKLF1拮抗肽C19局部外用治疗或预防后,小鼠皮损中部分调节炎症细胞因子特定基因表达的micro RNA上调。结论 CKLF1拮抗肽C19可能在预防或治疗特应性皮炎中具有重要作用,为了解及探索治疗特应性皮炎的多肽类药物提供了新途径。     

Pruni cortex ameliorates skin inflammation possibly through HMGB1-NFκB pathway in house dust mite induced atopic dermatitis NC/Nga transgenic mice

Pruni cortex, the bark of Prunus jamasakura Siebold ex Koidzumi, has been used in the Japanese systems of medicine for many years for its anti-inflammatory, antioxidant and antitussive properties. In this study, we investigated the effect of pruni cortex on atopic dermatitis NC/Nga mouse model. Atopic dermatitis-like lesion was induced by the application of house dust mite extract to the dorsal skin. After induction of atopic dermatitis, pruni cortex aqueous extract (1 g/kg, p.o.) was administered daily for 2 weeks. We evaluated dermatitis severity, histopathological changes and cellular protein expression by Western blotting for nuclear and cytoplasmic high mobility group box 1, receptor for advanced glycation end products, nuclear factor κB, apoptosis and inflammatory markers in the skin of atopic dermatitis mice. The clinical observation confirmed that the dermatitis score was significantly lower when treated with pruni cortex than in the atopic dermatitis group. Similarly pruni cortex inhibited hypertrophy and infiltration of inflammatory cells as identified by histopathology. In addition, pruni cortex significantly inhibited the protein expression of cytoplasmic high mobility group box 1, receptor for advanced glycation end products, nuclear p-nuclear factor kappa B, apoptosis and inflammatory markers. These results indicate that pruni cortex may have therapeutic potential in the treatment of atopic dermatitis by attenuating high mobility group box 1 and inflammation possibly through the nuclear factor κB pathway.     

Methodology and didactics of training children and adolescents in topical treatment of atopic dermatitis

There are increasing numbers of education programmes for children and young people with atopic dermatitis. These also include directions for the treatment of atopic dermatitis. However, the methods to be followed and the treatment to be applied are usually not clearly defined or explained. Presented are the key aspects of the local treatment of atopic dermatitis to be taught to children. The introduction of a basic therapeutic concept helps sort out which are the best preparations to use, some with and others without active ingredients. The interactions between basic care, active ingredients and skin conditions are explained in such a way that children can understand them.     

Thymic stromal lymphopoietin: master switch for allergic inflammation

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL) 7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses. TSLP is highly expressed by keratinocytes in skin lesions of patients with atopic dermatitis and is associated with dendritic cell activation in situ, suggesting that TSLP might be a master switch for allergic inflammation at the epithelial cell-dendritic cell interface. New reports now establish a direct link between TSLP expression and the pathogenesis of atopic dermatitis and asthma in vivo, and begin to reveal the molecular mechanisms underlying TSLP-induced allergic inflammation.     

Contact allergens in moisturizers in preventative emollient therapy – A systematic review

BackgroundResults of preventative emollient therapy on atopic dermatitis and food allergy trials are inconsistent. In addition to the ingredients considered beneficial, the moisturizers may contain potentially harmful haptens. This study aimed to assess the prevalence of haptens in moisturizers used in studies to prevent atopic dermatitis or food allergy and assess their correlations to the trial results.MethodsA systematic search of studies investigating the role of emollient usage in preventing atopic dermatitis or food allergy in infants was performed from inception to December 2020. Haptens were identified based on the nine common patch test series (European, American, and Australian).Results12 clinical trial studies were included in the review. In total, 16 different emollients were applied as an intervention. The vast majority (75%) of preparations contained at least one hapten from which several substances pose high allergic or irritant potential. Quantitative data synthesis of the findings regarding food allergy and atopic dermatitis prevention was not possible due to the significant heterogeneity of preparations used.ConclusionsCareful selection of emollient should consider the absence of potentially harmful ingredients, particularly when used in youngest children. Chronic skin exposure to haptens promotes the development of allergic contact dermatitis and moreover, via deterioration of the skin barrier and subclinical inflammation, may facilitate epicutaneous sensitization and promote atopic dermatitis; however further research is needed to validate our suppositions.     

Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.     

Phytotherapy in paediatric skin disorders – A systematic literature review

ObjectivesAlthough skin disorders in children and adolescents are increasingly treated with phytotherapies in practice, there are very few studies investigating this topic, and no systematic review exists that summarizes the current state of research. This review examines which herbal medicines show to be effective to treat atopic dermatitis, diaper dermatitis, and skin lesions or wounds.MethodsClinical studies were searched according to PRISMA-guidelines in the medical databases of PubMed, EMBASE, and CINAHL and summarised in a systematic review.ResultsAmong the 429 articles screened, 17 studies with a total of 2358 participants were identified that suited our inclusion criteria. Thereof seven studies each on the treatment of atopic dermatitis and skin lesions or wounds and three on diaper dermatitis. The phytotherapeutics investigated were based on the following herbs: Evening primrose, blackcurrant, polypodium leucotomos, calendula, aloe vera, chamomile, comfrey, hamamelis, olive, hypericum, neem, white oak, and myrrh. They have mainly been analysed in randomized controlled trials, but also in (long-term) observational studies, prospective trials and case series.ConclusionsBased on the application of the Jadad score, eight out of 17 of the studies examined were of low quality. Yet we found some indication that evening primrose oil may be effective for treating atopic dermatitis in children, while comfrey appears to have a positive effect on wound healing. Interestingly, none of the studies found positive effects for treating skin disorders with aloe vera or chamomile.     

Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease

IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis–like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL‑36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels—all of which were abrogated in IL-36R–deficient mice or anti-IL‑36R–blocking antibody–treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL‑36 cytokines in human atopic dermatitis skin and in IL‑36 receptor antagonist–deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL‑36 responses represent a key mechanism and potential therapeutic target against allergic diseases.     

Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum

Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.The smallpox vaccine consists of live vaccinia virus (VACV) and is considered the gold standard of vaccines, as it has led to the complete eradication of a lethal infectious disease from the human population. Recent fears that smallpox might be deliberately released in an act of bioterrorism have led to renewed efforts to better understand the disease mechanism and to develop a safer vaccine. Approximately 50% of US residents were born after the regular smallpox vaccination was discontinued in 1972. Thus, these unimmunized people are vulnerable to smallpox. The population landscape is very different between now and 36 yr ago, with two-to-three times more frequent incidence of atopic dermatitis in the current population (1). Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia infection (2).Atopic dermatitis is a chronic inflammatory skin disease (3). The etiology of this disease is multifactorial, and involves complex interactions between genetic and environmental factors. The skin in a preatopic dermatitis state has been postulated to have hypersensitivity to environmental triggers, resulting from a defective skin barrier that allows the penetration of allergens and microbial pathogens (4). The acute phase is characterized by eczematous skin lesions with an infiltration of Th2 cells. The chronic phase is characterized by lichenification of skin and an infiltration of Th1 cells. As recent studies have established IL-17– and IL-22–producing CD4⁺ T cells as a distinct class of helper T cells (Th17), Th17 cells are also implicated in the acute but not the chronic phase (5, 6). Despite the progress in our understanding of atopic dermatitis pathogenesis (7) and immune responses to VACV (8), it is not understood why atopic dermatitis patients are susceptible to developing eczema vaccinatum (9).In this study, we have established a mouse model of eczema vaccinatum using a strain of mice that are prone to develop eczematous skin lesions, characterized their immune responses to VACV infection, and showed the importance of NK cells in early suppression of VACV-induced severe eczema vaccinatum–like skin lesions.     

The effective management of atopic dermatitis in school-age children

The terms atopic eczema and atopic dermatitis (AD) are synonymous. In this article, the latter term is used. AD can affect all age groups but is most commonly associated with children. It is a dry-skin condition, the severity of which can vary from person to person. It is not contagious. In mild forms of the condition the skin is dry, hot and itchy, while in more severe cases the skin can be broken, raw and bleeding, or produce vesicles and papules that may become eroded.     

Atopic dermatitis-like symptoms in HR-1 hairless mice fed a diet low in magnesium and zinc

We aimed to develop an animal model for atopic dermatitis. HR-1 hairless mice fed a diet with reduced magnesium and zinc levels were compared with mice fed a standard diet. Skin dryness and wrinkle-like changes, scratching behaviour, decreased skin water content, increased transepidermal water loss and raised blood immunoglobulin E levels were seen in the group receiving the reduced magnesium and zinc diet compared with control mice. There were no significant differences in body weight or the weight of the major organs between the two groups. Haematological examination in both groups was normal apart from increased immunoglobulin E levels in mice fed a reduced magnesium and zinc diet. These mice may be useful models of atopic dermatitis; preparation of the animals is not particularly time consuming, the reproducibility is 100%, and atopic dermatitis symptoms occur even in a specific pathogen-free environment.     

Atopic dermatitis

Atopic dermatitis is a common, chronic skin condition characterized by xerosis, pruritus, and inflammation. Numerous factors place individuals at increased risk for developing this disease. T-helper cells and their cytokines, in addition to immunoglobulin E and eosinophils, play a major role in the pathogenesis of atopic dermatitis. Various hypotheses including the "hygiene hypothesis" and the "keratinocyte apoptosis hypothesis" have been proposed. Diagnosis is based on clinical criteria rather than objective testing. Allergic reactions to several triggers including foods may exacerbate symptoms. Treatment for atopic dermatitis consists of avoidance of triggers and administration of emollients, steroids, and topical immune response modifiers such as tacrolimus. Further research is necessary to better understand this disease.     

Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch

Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not in non-lesional or normal skin. Substances were applied in the same skin area before and 3 h after administration of placebo or antihistamine (olopatadine hydrochloride: H1-receptor-blocker). Intensities of itch and pain sensation and areas of flare and wheal were measured. All the substances induced significantly more intense itch in lesional skin than in non-lesional skin of patients. Even bradykinin, which evoked only weak itch and pain of similar intensities in non-lesional skin of patients and in healthy volunteers, induced intense itch in lesional skin, while the simultaneously increased pain did not suppress the itch sensation, indicating central sensitization. Histamine- and substance P-induced itch was almost completely suppressed by antihistamines, whereas bradykinin- and serotonin-induced itch was not. This suggests that substance P is a histamine-dependent pruritogen also in lesional skin under sensitized conditions but that bradykinin and serotonin are histamine-independent pruritogens in lesional skin. It is concluded that serotonin and bradykinin, classic endogenous algogens, can turn into potent histamine-independent pruritogens in lesional skin of atopic dermatitis.     

Atopic dermatitis: an overview

Atopic dermatitis, also known as atopic eczema, is a chronic pruritic skin condition affecting approximately 17.8 million persons in the United States. It can lead to significant morbidity. A simplified version of the U.K. Working Party's Diagnostic Criteria can help make the diagnosis. Asking about the presence and frequency of symptoms can allow physicians to grade the severity of the disease and response to treatment. Management consists of relieving symptoms and lengthening time between flare-ups. Regular, liberal use of emollients is recommended. The primary pharmacologic treatment is topical corticosteroids. Twice-daily or more frequent application has not been shown to be more effective than once-daily application. A maintenance regimen of topical corticosteroids may reduce relapse rates in patients who have recurrent moderate to severe atopic dermatitis. Pimecrolimus and tacrolimus are calcineurin inhibitors that are recommended as second-line treatment for persons with moderate to severe atopic dermatitis and who are at risk of atrophy from topical corticosteroids. Although the U.S. Food and Drug Administration has issued a boxed warning about a possible link between these medications and skin malignancies and lymphoma, studies have not demonstrated a clear link. Topical and oral antibiotics may be used to treat secondary bacterial infections, but are not effective in preventing atopic dermatitis flare-ups. The effectiveness of alternative therapies, such as Chinese herbal preparations, homeopathy, hypnotherapy/biofeedback, and massage therapy, has not been established.     

Staphylococcus aureus isolation from the lesions,the hands,and anterior nares of patients with atopic dermatitis

Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can exacerbate the disease. Some patients with atopic dermatitis may act as a reservoir for S. aureus transmission to others. This study compared S. aureus colonization in atopic dermatitis patients and their caregivers with control patients and their caregivers. Quantitative cultures were obtained from the lesions, clinically normal skin, hands, and anterior nares of 100 patients with atopic dermatitis, 100 controls with other cutaneous disorders, and 200 caregivers. The AD patients had significantly greater presence of S aureus from lesional and clinically normal skin, as well as the hand. Significantly increased carriage of S. aureus was found in the anterior nares of caretakers of AD patients compared with control caretakers. Topical corticosteroid use did not affect recovery of S. aureus. There was a significant correlation between recovery of S. aureus from lesional skin and recovery from the anterior nares and hands. The nares and hands may be important reservoirs and vectors for autotransmission of S. aureus to lesional skin and for transmission to patients with AD.     

Atopic dermatitis. Special clinical complications

Atopic dermatitis is a common disease of childhood that remits with age. Its pathogenesis is still uncertain; histamine seems important but the role of IgE is uncertain. The condition presents with several clinical features, none of which alone is pathognomonic. In some patients, particularly infants, several observations may be needed to discover the chronic nature of the disease. Most patients with atopic dermatitis have excessive skin dryness and hand dermatitis; many have superficial pustular staphylococcal infection. Management focuses on measures that reduce trigger factors, such as skin irritant exposure, emotional stress, and infection. Therapeutic agents include emollient creams, corticosteroid creams and ointments, and oral antihistamines. Exposure to summer sunshine is important in control.     

Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone

BACKGROUND: Playing video games causes physical and psychological stress, including increased heart rate and blood pressure and aggression-related feelings. Use of mobile phones is very popular in Japan, and frequent ringing is a common and intrusive part of Japanese life. Atopic eczema/dermatitis syndrome is often exacerbated by stress. Stress increases serum IgE levels, skews cytokine pattern towards Th2 type, enhances allergen-induced skin wheal responses, and triggers mast cell degranulation via substance P, vasoactive intestinal peptide and nerve growth factor. MATERIALS AND METHODS: (1). In the video game study, normal subjects (n = 25), patients with allergic rhinitis (n = 25) or atopic eczema/dermatitis syndrome (n = 25) played a video game (STREET FIGHTER II) for 2 h. Before and after the study, allergen-induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, and in vitro production of total IgE, antihouse dust mite IgE and cytokines were measured. (2). In the mobile phone study, normal subjects (n = 27), patients with allergic rhinitis (n = 27) or atopic eczema/dermatitis syndrome (n = 27) were exposed to 30 incidences of ringing mobile phones during 30 min. Before and after the study, allergen-induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor were measured. RESULTS: Playing video games had no effect on the normal subjects or the patients with allergic rhinitis. In contrast, playing video games significantly enhanced allergen-induced skin wheal responses and increased plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome. Moreover, playing video games enhanced in vitro production of total IgE and anti-house dust mite IgE with concomitant increased production of IL-4, IL-10 and IL-13 and decreased production of IFN-gamma and IL-12 in the patients with atopic eczema/dermatitis syndrome. However, exposure to frequently ringing mobile phones significantly enhanced allergen-induced skin wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome, but not in the normal subjects or the patients with allergic rhinitis. CONCLUSION: Playing video games enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor, and skewing of the cytokine pattern toward Th2 type in the patients with atopic eczema/dermatitis syndrome. In addition, exposure to frequently ringing mobile phones also enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor Collectively, high technology causes stress, which in turn may aggravate symptoms of atopic eczema/dermatitis syndrome.     

Antibacterial effect of beta-thujaplicin on staphylococci isolated from atopic dermatitis: relationship between changes in the number of viable bacterial cells and clinical improvement in an eczematous lesion of atopic dermatitis

Beta-thujaplicin (hinokitiol) is a tropolone-related compound purified from the wood of Chamaecyparis obtusa, SIEB: et Zucc. and Thuja plicata D. Don. All Staphylococcus aureus isolates were inhibited by beta-thujaplicin with MICs of 1.56-3.13 mg/L. However, a paradoxical zone phenomenon occurred, with each isolate producing regrowth at higher beta-thujaplicin concentrations. Other antimicrobial agents showed a wide range of MICs. The combination of beta-thujaplicin and zinc oxide inhibited the paradoxical zone phenomenon, and enhanced killing activity against clinically isolated staphylococci. Large numbers of viable bacterial cells, especially S. aureus cells, were detected in the skin surface of atopic dermatitis, in comparison with those in healthy volunteers. The number of cells increased as the severity of the skin condition worsened. Topical application of beta-thujaplicin resulted in a reduction in the number of bacterial cells on the skin surface, and an improvement in skin condition after treatment. The results of this study suggest that the degree of reduction in the number of viable bacterial cells in an eczematous lesion of atopic dermatitis is related to the degree of improvement in skin condition.