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.

Skin care by washing with water is not inferior to washing with a cleanser in children with atopic dermatitis in remission in summer: WASH study.

BACKGROUND: Washing with water is not inferior to washing with soaps and detergents in children with atopic dermatitis (AD) in remission during the fall-winter seasons. We investigated whether this finding varies during summer based on the type of cleanser (soaps and detergents). METHODS: This evaluator-blinded, pragmatic, randomized, and non-inferiority study enrolled patients with AD whose eczema was controlled following regular steroid ointment application 2 days/week. For 8 ± 4 weeks, participants washed their upper and lower limbs with a cleanser on one side and with water alone on the other. Each participant chose either a weakly alkaline soap or an acidic detergent. The primary outcome was the Eczema Area and Severity Index (EASI) score at week 8 ± 4. RESULTS: The data of 43 of the 47 registered participants were analyzed. The median patient age was 44 (23-99) months; 28 and 15 participants chose weakly alkaline and acidic cleansers, respectively. At week 8 ± 4, EASI scores of the water and cleanser sides were 0.00 (0.00-0.40) and 0.15 (0.00-0.40), respectively (p = 0.74). The difference between both sides was 0.00 (-0.07 to 0.14); the limits of the 95 % confidence interval did not reach the pre-specified non-inferiority margin. No difference was observed in the median Patient-Oriented Eczema Measure score, number of additional steroid ointment applications, and occurrences of skin infections. There were no differences between the cleanser types in any of the results. CONCLUSIONS: We demonstrated that washing with water was not inferior to that with a cleanser in patients with AD in the maintenance phase during summer, regardless of the type of cleanser.

Diagnosis of non-immediate hypersensitivity to amoxicillin in children by skin test and drug provocation tests: A retrospective case-series study.

BACKGROUND: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. METHODS: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. RESULTS: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. CONCLUSIONS: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

Washing with water alone versus soap in maintaining remission of eczema.

BACKGROUND: There is no consensus on the use of soap in skin care for atopic dermatitis in Japan. Thus, this study aimed to evaluate the efficacy of soap to maintain eczema remission in atopic dermatitis patients during the fall-winter period in Japan. METHODS: This assessor-blinded, pragmatic randomized, non-inferiority study enrolled atopic dermatitis patients whose eczema was controlled by regular steroid ointment application less than or equal to 2 days / week (tacrolimus ointment was permitted). For 8 ± 3 weeks, participants washed their upper and lower limbs on one side with soap (soap side) and on the other side with water alone (water side). The primary outcome was an Eczema Area and Severity Index score at week 8 ± 3. RESULTS: Twenty-nine participants were analyzed. The Eczema Area and Severity Index scores at week 8 ± 3 of the water and soap sides were 0.0 (0.0-0.4) and 0.0 (0.0-0.4), respectively (P = 0.18). The difference between both sides was -0.02 (-0.11-0.08), and the limits of the 95% confidence interval did not reach the prespecified non-inferiority margin. The average Patient-Oriented Eczema Measure score was 1.27 ± 1.7 and 1.32 ± 1.8 for the water and soap sides, respectively (P = 0.92). The total number of additional steroid ointment applications was four (0-20) times and six (0-23) times, respectively (P = 0.98). Participants were categorized according to self-assessments of the usefulness of soap, with 2, 24, and 3 participants in the water-effective, invariant, and soap-effective groups, respectively. CONCLUSIONS: For children with controlled atopic dermatitis, washing with water alone was not inferior to washing with soap for maintaining remission of eczema during the fall-winter period in Japan.

Reference values for salivary cortisol in healthy young infants by liquid chromatography-tandem mass spectrometry.

BACKGROUND: Sampling of salivary cortisol is non-invasive and important for the evaluation of the hypothalamic-pituitary-adrenal axis function and stress levels. However, the reference values for salivary cortisol measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy infants are unclear. The aim of this study was to establish the reference values for salivary cortisol levels in healthy infants. METHODS: This study was a prospective observational cohort study following the participants until the age of 6 months. We analyzed 71 healthy, full-term infants at age 1 month between December 2017 and March 2018. We repeated saliva sampling every month, measured the salivary cortisol levels in the early morning by LC-MS/MS, and took the subjects' medical history by questionnaire. RESULTS: The minimum, 25th, 50th, 75th percentile, and maximum salivary cortisol levels were 0.08, 1.11, 2.21, 5.18, and 30.35 nmol/L, respectively. CONCLUSIONS: We established the reference values for salivary cortisol in young infants using LC-MS/MS.

Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Evidence is accumulating that early consumption is more beneficial than is delayed introduction as a strategy for primary prevention of food allergy. However, allergic reactions caused by early introduction of such solid foods have been a problematic issue. We investigated whether or not early stepwise introduction of eggs to infants with eczema combined with optimal eczema treatment would prevent egg allergy at 1 year of age. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled infants 4-5 months of age with eczema from two centres in Japan. Exclusion criteria were being born before 37 weeks of gestational age, experience of ingestion of hen's eggs or egg products, history of immediate allergic reaction to hen's eggs, history of non-immediate allergic reaction to a particular type of food, and complications of any severe disease. Infants were randomly assigned (block size of four; stratified by institution and sex) to early introduction of egg or placebo (1:1). Participants in the egg group consumed orally 50 mg of heated egg powder per day from 6 months to 9 months of age and 250 mg per day thereafter until 12 months of age. We aggressively treated participants' eczema at entry and maintained control without exacerbations throughout the intervention period. Participants and physicians were masked to assignment, and allocation was concealed. The primary outcome was the proportion of participants with hen's egg allergy confirmed by open oral food challenges at 12 months of age, assessed blindly by standardised methods, in all randomly allocated participants who received the intervention. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000008673. FINDINGS: Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0·222 [95% CI 0·081-0·607]; p=0·0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0·221 [0·090-0·543]; p=0·0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0·022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. INTERPRETATION: Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent hen's egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy. FUNDING: Ministry of Health, Labour and Welfare, and National Centre for Child Health and Development, Japan.

Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction.

Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.

Predictors of initial oral food challenge outcome in food protein-induced enterocolitis syndrome.

Background: There is a paucity of data on predictors of clinical history in oral food challenge (OFC) outcome for the initial diagnosis of food protein-induced enterocolitis syndrome (FPIES). Objective: This study aimed to identify predictors for the diagnosis of FPIES. Methods: The study included patients who underwent OFC to diagnose FPIES from 2010 to 2021. Patients with a positive OFC result were classified as belonging to the FPIES group, and those with negative OFC result within 120 days from the last symptomatic episode were classified as belonging to the no-allergy (NA) group. Background factors were analyzed in the groups. Results: A total of 50 OFCs to 12 different foods were conducted in 50 patients. Of those 50 patients, 30 were classified as belonging to the FPIES group. No significant difference was observed between the FPIES and NA groups with respect to background factors, including the features of symptomatic episodes and examinations of immediate-type allergy. A history of asymptomatic ingestion was observed in 23 of 24 and 13 of 19 patients in the FPIES and NA groups, respectively; thus, it was significantly more common in patients with FPIES. The diagnostic rate of patients with fewer than 3 symptomatic episodes was 52%, and that of patients with 3 episodes or more was 75%, not considering a patient without available data. Conclusions: A definite diagnosis of FPIES should be based on OFC, as there are no predictors for OFC positivity other than a history of asymptomatic ingestion. The absence of asymptomatic ingestion history was a negative predictor for the diagnosis of FPIES.

Fluid control in elderly patients with nocturia.

OBJECTIVES: To investigate the pathophysiology of nocturnal polyuria associated with aging. METHODS: Fifty patients (mean age 67.7 years, range 50-87) with nocturia were recruited for this prospective study. Patients were classified into nocturnal polyuria (NP) and non-nocturnal polyuria (non-NP) groups based on records of their frequency-volume charts. A hypertonic saline infusion test was carried out to evaluate individual osmotic and volume control. RESULTS: In the NP group, there was a significantly increased nocturnal diuretic rate compared with the daytime diuretic rate. In the non-NP group, there was a significantly decreased nocturnal diuretic rate compared with the daytime rate. There was also a positive correlation between systolic blood pressure and nocturnal diuretic rate, and a negative correlation between systolic blood pressure and daytime diuretic rate in those with NP, but no correlation in those without NP. Thus, a close relationship between diuretic rates and systolic blood pressure was seen in NP patients. Moreover, a slight overall shift upward from the physiological range of plasma osmolality relative to arginine vasopressin after hypertonic saline loading was seen in those with NP compared with those without. An altered circadian rhythm was also seen in diurnal plasma arginine vasopressin levels in patients with and without NP. CONCLUSIONS: Patients with nocturnal polyuria are likely to have a more hypervolemic or vasoconstrictive condition. It is considered that non-osmotic control takes on a greater meaning in patients with nocturnal polyuria, though osmotic control contributes less to diuresis within the physiological plasma osmolality range with aging.

Detrusor contractility and overactive bladder in patients with cerebrovascular accident.

OBJECTIVES: A retrospective analysis of urodynamic studies was conducted to investigate detrusor contractility following cerebrovascular accident. METHODS: Fifty-seven patients (34 men and 23 women) who were rehabilitated following cerebrovascular accident were included in the analysis. Subjects with maximum contractile power values less than 10 W/m(2) in men and 8 W/m(2) in women, in the absence of bladder outlet obstruction, were defined as having detrusor underactivity. RESULTS: A significantly lower maximum value of detrusor contractile power and a larger residual urine volume, particularly more prevalent in women than in men, appeared unexpectedly after cerebrovascular accident. Patients with underactivity had significantly lower maximum and average flow rates, lower contractile power, and an increased postvoid residual relative to their normal counterparts. The prevalence of underactivity was 35% in the men and 43% in the women. Furthermore, 67% of the men and 80% of the women with underactivity had overactive bladder symptoms. On the other hand, detrusor underactivity was observed in 8 (35%) of 23 overactive bladder patients in the men and 8 (42%) of 19 in the women. CONCLUSIONS: Post-cerebrovascular accident patients presented various patterns of detrusor contractility. Specific attention to the possible occurrence of detrusor underactivity in these patients is essential for the successful management of overactive bladder syndrome.

Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy: a multicenter, investigator-blinded, randomized, parallel group controlled trial (PACI Study)-protocol for a randomized controlled trial.

BACKGROUND: Atopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis. METHODS: This study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N = 650) 7-13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen's egg allergy at the age of 28 weeks. DISCUSSION: This is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis.Trial registration UMIN-CTR: UMIN000028043.

Factors Associated with Development of Food Allergy in Young Children after Liver Transplantation: A Retrospective Analysis of 10 Years' Experience.

BACKGROUND: Although development of food allergy after liver transplantation is most commonly described in young children, little is known about identification of young liver-transplant recipients who are at risk of food allergy. OBJECTIVE: This study aimed to identify the types of food allergy and the risk factors for the development of food allergy after liver transplantation. METHODS: This was a retrospective analysis of pediatric liver transplant recipients in our organ transplantation center during 2005-2015. Relevant data of all patients who underwent liver transplantation were extracted from the center's database and the medical records. Differences in patients' characteristics were evaluated for associations between food allergy and potential risk factors. Logistic regression models were used to calculate adjusted odds ratios. RESULTS: We obtained the data of 206 patients under 36 months of age, 42 (20.4%) of whom developed food allergy after liver transplantation. The allergy was IgE-mediated-only in 30 (71.4%) and non-IgE-mediated-only in 10 (23.8%). Multivariate analysis found eczema at liver transplantation to be a significant risk factor (adjusted odds ratio [aOR] 2.41, 95% confidence interval [CI] 1.14-4.77, P < .05). Eczema increased the risk of developing IgE-mediated food allergy after liver transplantation (aOR 3.13, 95% CI 1.41-6.93, P < .01), whereas no significant association was observed with non-IgE-mediated food allergy. CONCLUSIONS: We identified eczema at liver transplantation as a significant risk factor for the development of IgE-mediated food allergy after liver transplantation, but not non-IgE-mediated food allergy. Our findings may contribute to a better understanding of the susceptible subgroup requiring special caution and to the establishment of effective strategies for prevention.

[A case of retroperitoneal bronchogenic cyst].

A 59-year-old hypertensive man was referred to our hospital with a retroperitoneal cystic tumor, measuring 6 cm in diameter that was detected by an ultrasound examination during routine check-up 2 years before coming to our department. During the 2-year follow-up, the cystic tumor gradually increased in size. The patient also became hypertensive with slightly elevated urine levels of noradrenaline and dopamine, while the plasma catecholamines and their metabolites in the urine were within the normal range. Computed tomographic scanning and magnetic resonance imaging revealed a dumbbell-shaped retroperitoneal cyst with dense fluid, measuring 7 x 3.5 x 3 cm in diameter, in the left supra-adrenal and sub-diaphragmatic regions. He underwent extirpation of the cystic tumor with suspicion of adrenal endocrine cystic tumor. The histopathological diagnosis was a bronchogenic cyst, which is an extremely rare developmental anomaly in the retroperitoneal space. We herein report this rare case of retroperitoneal bronchogenic cyst and present a brief review of the previously reported 30 Japanese cases.

The impact of radical prostatectomy on patient well-being: a prospective urodynamic study focused on detrusor function.

Prostate cancer is common in aged men and radical prostatectomy is established as a therapeutic measure. However, to date there is little information about its impact on voiding function. We conducted a prospective clinical study to elucidate the impact of radical prostatectomy on voiding function in 17 patients with prostate cancer, by urological evaluation including filling and voiding cystometry (pressure flow study). The patients who were estimated as having weak detrusor function including very weak detrusor function at 3 months postoperatively had significantly more frequent urinary incontinence compared with the others (p < 0.05). Of 8 patients who showed urinary incontinence for more than 3 months, 7 (88%) patients developed weak detrusor function at 3 months after operation, but 4 of them were estimated as having normal detrusor function preoperatively. These patients revealed reduced maximum flow rate and significantly increased quality of life score compared with the other patients (p < 0.05). An initially reduced bladder compliance disclosed a tendency to a rapid return to normal with time after surgery. Detrusor overactivity itself and neoadjuvant antiandrogen therapy were not related to prolonged postoperative urinary incontinence. The present study indicates that caution is required when administering medication that could potentially affect detrusor function, regardless of the type of preoperative detrusor function, in patients with persistent urinary incontinence or a reduced urinary stream. Particular emphasis is laid on the importance of urodynamic assessment of post-prostatectomy detrusor function and appropriate management modalities based on the results.

[A case of primary transitional cell carcinoma of the prostate].

A 77-year-old man was referred to our hospital with a complaint of dysuria and right ischiodynia. He had had a hemi-thyroidectomy for thyroid cancer and right cervical lymphadenectomy three years and one year, respectively, before this visit. Prostate cancer was strongly suspected by transrectal examination with prostate specific antigen (PSA) elevated to 77.8 ng/ml. Pathological diagnosis of prostate biopsy specimen was transitional cell carcinoma with grade 3 malignancy and negative staining for PSA. Endoscopic examination showed a normal appearance of bladder and prostatic urethral epithelium. Urine cytology showed no malignant cells. However, immunostaining for PSA revealed that the cervical lymph node specimen resected before was moderately differentiated adenocarcinoma of prostate. He had multiple metastases to mediastinal and retroperitoneal lymph nodes and right ischium. Endocrine therapy (goserelin acetate depot, bicalutamide) and systemic chemotherapy (methotrexate, epirubicin, cisplatin) were performed combined with irradiation to right ischium metastasis. Two months later, he showed a complete response in PSA and partial response in lymph node metastases, but died of cancer 13 months later.