Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy.

BACKGROUND: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. OBJECTIVES: This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. METHODS: This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. RESULTS: This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P = .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. CONCLUSIONS: This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

Increased plasma miR-24 and miR-191 levels in patients with severe atopic dermatitis: Possible involvement of platelet activation.

BACKGROUND: Platelets are involved in the pathomechanisms of atopic dermatitis (AD). This study aimed to elucidate the levels of platelet-related miRNAs, (miR-24 and miR-191) in the plasma of AD patients and their relationships with the disease severity and laboratory data. METHODS: miRNAs were detected in the subjects plasma using specifically primed quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with severe AD had significantly higher plasma miR-24 or miR-191 levels than the patients with mild AD, the urticaria patients, and the healthy volunteers. The plasma miR-24 and miR-191 levels of the AD patients were correlated with their serum thymus and activation-regulated chemokine levels. In addition, plasma miR-24 and miR-191 levels were correlated with their plasma levels of platelet factor 4 and ß-thromboglobulin. CONCLUSION: Our findings imply that miR-24 and miR-191 may be involved in the pathomechanisms responsible for the worsening of AD, possibly through their effects on platelet activation.

Patch testing with the Japanese baseline series 2015: A 4-year experience.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

Effects of constant light exposure on allergic and irritant contact dermatitis in mice reared under constant light conditions.

Environmental light levels can affect physiological functions, such as general activity, body temperature and metabolism. Irregular lifestyles, such as those involving exposure to light during the night, can exacerbate the clinical symptoms of several inflammatory skin diseases. However, the effects of constant light exposure on immune responses are not fully understood. This study aimed to elucidate the effects of constant light exposure on two major types of skin reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). BALB/c mice were kept under constant light conditions or a normal light and dark cycle, and their ACD and ICD responses were assessed after the topical application of 2,4,6-trinitro-1-chlorobenzene and croton oil, respectively, to the ear skin. Interestingly, in both ACD and ICD, the ear-swelling response and local leukocyte infiltration were aggravated by constant exposure to light, which has previously been shown to severely disturb the behavioural rhythms of mice. In ACD, these findings were accompanied by increases in the numbers of degranulated mast cells and eosinophils. These results suggest that constant light exposure intensifies allergic and non-allergic skin inflammation.

Atopic Dermatitis: Identification and Management of Complicating Factors.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.

Platelets are important for the development of immune tolerance: Possible involvement of TGF-ß in the mechanism.

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6-trinitro-1-chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti-platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti-platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3+ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low-dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)-ß1. Interestingly, platelet depletion reduced plasma TGF-ß1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF-ß1 during platelet depletion in mice with LZT. Administration of anti-TGF-ß antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF-ß1.

Influence of topical steroids on intraocular pressure in patients with atopic dermatitis.

BACKGROUND: Topical corticosteroids (TCS) can induce adverse effects, such as skin atrophy. Although TCS can cause increases in intraocular pressure (IOP), the effects of daily TCS use on IOP have not been fully elucidated. We evaluated the clinical doses of TCS and the change in the IOP during the daily treatment of atopic dermatitis (AD). METHODS: We collected clinical data on a total of 65 patients who were diagnosed with AD and underwent 2 or more IOP measurements at our hospital. RESULTS: Mean monthly facial steroid volumes of ≤11.8 g and ≤15.0 g of TCS were applied to 90% of the patients aged 2-12 years and those aged ≥13 years, respectively. During the treatment, there were no TCS-related increases in IOP in any patient. CONCLUSIONS: Our study suggests that TCS might not cause increases in IOP at the abovementioned doses. However, the IOP of steroid responders is known to be highly responsive to steroids. Therefore, patients who have steroids applied to their eyelids had better undergo regular IOP measurements at ophthalmological clinics.

Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin lesions.

BACKGROUND: Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients. METHODS: We measured the serum IL-21 levels of adult AD patients and healthy control subjects using an enzyme-linked immunosorbent assay. RESULTS: The adult AD patients exhibited significantly higher serum IL-21 levels than the healthy control subjects. A comparison of the patients' serum IL-21 levels based on the clinical severity of their AD revealed that the patients with severe AD demonstrated significantly higher serum IL-21 levels than those with mild AD and the healthy control subjects. The serum IL-21 levels were significantly correlated with the skin severity score, and especially with the degree of acute lesions such as erythema and edema/papules. The serum IL-21 level was not associated with laboratory markers, such as the serum IgE level, the serum thymus and activation-related chemokine level, blood eosinophilia, and the serum lactate dehydrogenase level. CONCLUSIONS: These results suggest that IL-21 might be involved in the pathogenesis of AD, especially the development of acute skin lesions.

Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency.

BACKGROUND: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature. However, recent studies of affected mothers identified four missense mutations in the solute carrier family 30 member 2 gene (SLC30A2), which encodes the zinc transporter, ZnT2. METHODS: Genetic analyses of SLC30A2/ZnT2 in three Japanese mothers secreting low-zinc milk (whose infants developed TNZD) were performed. The effects of identified mutations were examined in a cell-based assay. Furthermore, 31 single-nucleotide polymorphisms (SNPs) in SLC30A2/ZnT2 were evaluated for their potential involvement in low-zinc levels in milk. RESULTS: Each mother had a different novel heterozygous mutation in SLC30A2/ZnT2. One mutation reduced splicing efficiency of the SLC30A2/ZnT2 transcript, and all ZnT2 mutants were defective in zinc transport and were unstable in cells. Moreover, four SNPs caused a significant loss of zinc-transport activity, similar to that in disease-causing ZnT2 mutants. CONCLUSION: Our results indicate that many SLC30A2/ZnT2 mutations cause or potentially cause TNZD. Genetic information concerning TNZD pathogenesis is limited, and our results suggest that the TNZD frequency may be higher than previously thought.