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Background: Vaccination to prevent hepatitis B (HB) virus infection is important for children undergoing immunosuppressive treatment. Information on the efficacy of HB vaccination in children with rheumatic diseases undergoing immunosuppressive therapy is scarce., Methods: Children with rheumatic diseases administered HB vaccine during immunosuppressive treatment between May 2013 and September 2016 were enrolled. Patients were vaccinated three times (primary series). Those who remained seronegative after the primary series received a secondary series of vaccinations. Patient baseline characteristics and treatment details from the medical records were retrospectively investigated. The proportion of patients that was seropositive for HB virus antibody after primary-and secondary series of vaccinations was calculated. Associations between immunosuppressants and serostatus were evaluated., Results: Fifteen of 26 patients (58%) produced anti-hepatitis B surface antibody (anti-HBs) after the primary vaccinations. Eight of 10 patients (80%) taking methotrexate and 3 of 11 (27%) taking mycophenolate mofetil (MMF) were seropositive. Multivariate analysis adjusted for dosage of prednisolone per body weight. Multivariate analysis showed MMF was a factor impeding seroconversion (odds ratio 0.093, 95% confidence interval 0.014-0.615). In six of seven patients (86%) who received a secondary series of vaccinations, anti-HBs were produced., Conclusions: MMF may impede seroconversion after a primary series of HB vaccinations, thus requiring secondary series of vaccinations in pediatric patients with a rheumatic disease undergoing immunosuppressive therapy., (© 2020 Japan Pediatric Society.)

An 8-year-old girl was presented to our clinic with fever, arthritis in her left knee, a necrotic right fifth toe, and multiple large deep-seated ulcerations. She was diagnosed with pyoderma gangrenosum. Treatment with corticosteroids alone was ineffective for her skin lesions, and therefore combination immunosuppressant therapy was administered. Her skin lesions rapidly improved, enabling discontinuation of the corticosteroid therapy and avoiding systemic infection through the ulcers. Combination immunosuppressant therapy may be a treatment option for patients with severe, rapidly progressive pyoderma gangrenosum.

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-AUC 0-12h ), the peak concentration ( C max ), and the time to peak concentration ( T max ) were measured. To obtain a dose-normalized MPA-AUC 0-12h value, the actual measured MPA-AUC 0-12h 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-AUC 0-12h values and the MPA-AUC 0-12h values corrected for dose per BW and T max were lower in young patients. The MPA-AUC 0-12h values corrected for dose per BSA and C max were comparable among all the groups. Conclusion: In patients with juvenile autoimmune diseases, determining MMF administration dosage according to BSA may facilitate MPA-AUC 0-12h value prediction.

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.

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.

Interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency (OMIM #607676) is a rare primary immunodeficiency of innate immune defect. We identified 10 patients from 6 families with IRAK4 deficiency in Japan, and analyzed the clinical characteristics of this disease. Nine patients had homozygous c.123_124insA mutation, and 1 patient had c.123_124insA and another nonsense mutation (547C>T). Umbilical cord separation occurred on the 14th day after birth or thereafter. Two patients had no severe infections owing to the prophylactic antibiotic treatment. Severe invasive bacterial infections occurred before the age of 3 in the other 8 patients. Among them, 7 patients had pneumococcal meningitis. Five patients died of invasive bacterial infection during infancy, although intravenous antibiotic treatment was started within 24 hours after onset in 4 patients among them. Analysis of cerebrospinal fluid of the patients who had fatal meningitis revealed very low glucose levels with only mild pleocytosis. The clinical courses of invasive bacterial infections were often rapidly progressive despite the early, appropriate antibiotic treatment in IRAK4 deficiency patients. The early diagnosis and appropriate prophylaxis of invasive bacterial infections are necessary for the patients., Competing Interests: None of the authors have any conflicts of interest to disclose.