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.

Risk factors for intolerance of oral 5-aminosalicylic acid preparations in pediatric ulcerative colitis.

BACKGROUND: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC. METHODS: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared. RESULTS: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group. CONCLUSIONS: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

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.

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.

Clinical significance of interleukin-18 for the diagnosis and prediction of disease course in systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate the clinical significance of serum IL-18 levels for the diagnosis of systemic JIA (s-JIA) and to predict the disease course of s-JIA. METHODS: Overall, 116 patients with s-JIA, 151 with other diseases and 20 healthy controls were analysed. Serum IL-18 levels were measured longitudinally in 41 patients with s-JIA from active phase through remission phase. Serum IL-18 levels were quantified via enzyme-linked immunosorbent assay and the results were compared with clinical features and the disease course of s-JIA. RESULTS: The serum IL-18 level cut-off value for differentiation of s-JIA from other diseases was 4800 pg/ml. In patients with a monocyclic course, serum IL-18 levels steadily decreased during the inactive phase and low levels were sustained during remission. In contrast, in patients with a chronic course, elevated serum IL-18 levels were sustained even during the inactive phase. In patients with a polycyclic course, serum IL-18 levels were elevated during disease flares and normalized during the inactive phase. The serum IL-18 level cut-off value for diagnosis of remission in s-JIA was 595 pg/ml. CONCLUSION: Serum IL-18 levels of >4800 pg/ml may be useful for differentiating between s-JIA and other diseases. Monitoring of serum IL-18 levels might be useful for predicting the disease course and assessing remission in s-JIA.

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg.

BACKGROUND/OBJECTIVES: Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. METHODS: This cross-sectional, case-control study included children ˂ 6 years old with moderate-severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg-specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. RESULTS: Of the 57 patients (age range, 2 months to 5 years; median, 22 months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two-thirds of dermatologists, was significantly associated with FLG mutation (P = 0.002, OR = 6.98, 95% CI = 2.1-23.7), and this association was observed especially in children over 2 years. Cross-shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white-specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3 IU/mL, P < 0.05). CONCLUSIONS: Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.

Risk factors for hypersensitivity reactions to tocilizumab introduction in systemic juvenile idiopathic arthritis.

OBJECTIVES: The objective of this study is to identify risk factors for hypersensitivity reaction (HSR) to tocilizumab (TCZ) in systemic juvenile idiopathic arthritis (sJIA). METHODS: Clinical records of 40 patients with sJIA administered TCZ at one center were retrospectively reviewed. Patients were divided into HSR or non-HSR groups depending on the presence of HSR between the first and third TCZ administrations; clinical and laboratory assessments, including serum cytokine profile, were compared. RESULTS: Five patients displayed HSR following the third TCZ administration. They were significantly younger, shorter, and lighter, with a higher peak body temperature than non-HSR patients following the third administration. Their serum C-reactive protein (CRP) level was undetectable following the first administration but detectable by the third administration. Before the third administration, the white blood cell counts and serum levels of CRP and sTNFRII were significantly higher in the HSR group than in the non-HSR group. The serum levels of interleukin-18 and -6 before the third TCZ administration were higher and lower than those before the first administration in the HSR and non-HSR groups, respectively. CONCLUSION: Patients with sJIA having a younger age, shorter stature, and lighter weight and those showing increased disease activity in the early period of TCZ administration may be at higher risk of TCZ-induced HSR.

Pharmacokinetics of mycophenolate mofetil in juvenile patients with autoimmune diseases.

Objectives: This study aimed to determine the association between the dosage and pharmacokinetics of mycophenolate mofetil (MMF) in juvenile patients with autoimmune diseases.Methods: Totally, 29 patients were administered oral MMF. The blood concentrations of mycophenolate acid (MPA) at seven points, the area under the time-concentration curve (MPA-AUC0-12h), the peak concentration (Cmax), and the time to peak concentration (Tmax) were measured. To obtain a dose-normalized MPA-AUC0-12h value, the actual measured MPA-AUC0-12h value was divided by the dose value of the morning administration corrected for body weight (BW) or body surface area (BSA). The patients were classified into three age groups (group 1, ≤10 years; group 2, >10-≤15 years; and group 3, >15 years), and pharmacokinetic parameters were compared among the groups.Results: In total, we obtained 37 measurements. The actual measured MPA-AUC0-12h values and the MPA-AUC0-12h values corrected for dose per BW and Tmax were lower in young patients. The MPA-AUC0-12h values corrected for dose per BSA and Cmax were comparable among all the groups.Conclusion: In patients with juvenile autoimmune diseases, determining MMF administration dosage according to BSA may facilitate MPA-AUC0-12h value prediction.

Clinical subsets of juvenile dermatomyositis classified by myositis-specific autoantibodies: Experience at a single center in Japan.

Objectives: This study investigated the association between myositis-specific autoantibodies (MSAs) and clinical subsets of juvenile dermatomyositis (JDM) in Japanese patients. Methods: Twenty-one patients at a single center who developed initial or relapsed JDM from 2011 to 2016 were analyzed. Serum concentrations of MSAs against TIF1-γ, MDA5, NXP2, Mi-2, ARS, and SAE were measured by enzyme-linked immunosorbent assays. Clinical symptoms and laboratory data were obtained from clinical records. Clinical characteristics were compared in patients with autoantibodies against TIF1-γ, MDA5, and NXP2. Results: Of the 21 patients, 20 (95.2%) were positive for one or more MSAs, including nine (42.9%), five (23.8%), six (28.6%), and one (4.8%) positive for anti-TIF1-γ, anti-MDA5, anti-NXP2, and anti-Mi-2 autoantibodies. No patient was positive for anti-ARS or anti-SAE autoantibodies. The frequency of diffuse cutaneous lesions was higher in patients with anti-TIF1-γ autoantibodies. Anti-MDA5 autoantibody-positive patients had features of interstitial lung disease on chest computed tomography. Severe muscle damage at disease onset was significantly associated with positivity for anti-NXP2 autoantibodies. Conclusion: Similar to findings in Western countries, the clinical characteristics of JDM in Japanese may differ for each type of MSAs.