Search

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population.

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.

Pathogenic MEFV variants cause pyrin-associated autoinflammatory diseases (PAADs), which include familial Mediterranean fever (FMF), FMF-like disease, and pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). The diagnosis of PAADs is established by clinical phenotypic and genetic analyses. However, the pathogenicity of most MEFV variants remains controversial, as they have not been functionally evaluated. This study aimed to establish and validate a new functional assay to evaluate the pathogenicity of MEFV variants. We transfected THP-1 monocytes with 32 MEFV variants and analyzed their effects on cell death with or without stimulation with Clostridium difficile toxin A (TcdA) or UCN-01. These variants were classified using hierarchical cluster analysis. Macrophages were obtained from three healthy controls and two patients with a novel homozygous MEFVP257L variant, for comparison of IL-1β secretion using a cell-based assay and a novel THP-1-based assay. Disease-associated MEFV variants induced variable degrees of spontaneous or TcdA/UCN-01-induced cell death in THP-1. Cell death was caspase-1 dependent and was accompanied by ASC speck formation and IL-1β secretion, indicating that pathogenic MEFV variants induced abnormal pyrin inflammasome activation and subsequent pyroptotic cell deaths in this assay. The MEFV variants (n = 32) exhibiting distinct response signatures were classified into 6 clusters, which showed a good correlation with the clinical phenotypes. Regarding the pathogenicity of MEFVP257L variants, the results were consistent between the cell-based assay and the THP-1-based assay. Our assay facilitates a rapid and comprehensive assessment of the pathogenicity of MEFV variants and contributes to a refined definition of PAAD subtypes.

Pathogenic MEFV variants cause pyrin-associated autoinflammatory diseases (PAADs), which include familial Mediterranean fever (FMF), FMF-like disease, and pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). The diagnosis of PAADs is established by clinical phenotypic and genetic analyses. However, the pathogenicity of most MEFV variants remains controversial, as they have not been functionally evaluated. This study aimed to establish and validate a new functional assay to evaluate the pathogenicity of MEFV variants.We transfected THP-1 monocytes with 32 MEFV variants and analyzed their effects on cell death with or without stimulation with Clostridium difficile toxin A (TcdA) or UCN-01. These variants were classified using hierarchical cluster analysis. Macrophages were obtained from three healthy controls and two patients with a novel homozygous MEFVDisease-associated MEFV variants induced variable degrees of spontaneous or TcdA/UCN-01-induced cell death in THP-1. Cell death was caspase-1 dependent and was accompanied by ASC speck formation and IL-1β secretion, indicating that pathogenic MEFV variants induced abnormal pyrin inflammasome activation and subsequent pyroptotic cell deaths in this assay. The MEFV variants (n = 32) exhibiting distinct response signatures were classified into 6 clusters, which showed a good correlation with the clinical phenotypes. Regarding the pathogenicity of MEFVOur assay facilitates a rapid and comprehensive assessment of the pathogenicity of MEFV variants and contributes to a refined definition of PAAD subtypes.

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.

The objective of this study is to identify risk factors for hypersensitivity reaction (HSR) to tocilizumab (TCZ) in systemic juvenile idiopathic arthritis (sJIA).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.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.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.

Objectives To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. Methods Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient’s data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. Results The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter’s criteria and Tanimoto’s criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron’s sign. Conclusion Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome characterised by recurrent episodes of urticarial rash and fever. Diagnosis is based on characteristic clinical...

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.

Diffuse alveolar hemorrhage (DAH) is a rare disease characterized by dyspnea, cough, hemoptysis, and new alveolar infiltrates. Among the various underlying disorders, vasculitis is believed to play a significant role in the pathogenesis of DAH. Here we report the first case of a patient with Down syndrome who developed DAH secondary to anti-neutrophil cytoplasmic antibody-associated vasculitis. This case highlights the significance of vasculitis as well as pulmonary hypoplasia and vulnerability associated with Down syndrome in the development of DAH.

粘液産生モデルの移植気管と正常気管の電気生理学的特性の違いを検討した。電位差測定時，粘膜側の環流溶液をかえることにより，粘膜面に存在するNa+チャンネル，およびCl-チャンネルの機能を調べた。環流溶液は以下の(1)～(5)を用いて検討した。(1)HEPES溶液，(2)HEPES溶液＋アミロライド100μM，(3)HEPES溶液＋アミロライド100μM＋Cl-フリー（Cl-の代わりに145mM gluconateを用いた），(4)HEPES溶液＋アミロライド100μM＋Cl-フリー＋CPT-cAMP 200μM＋フォルスコリン10μM，(5)HEPES溶液。結果：(1)の平常状態の環流液を用いた時には，移植気管のほうが正常気管に比べ，電位差は高い傾向を認めたが有意差は認めなかった。また，溶液を(2)～(5)へ変化させた時の電位変化は，移植気管においても保たれていた。以上より，移植気管においてもNa+およびCl-チャンネルの電位変化の検討が行えると考えられた。

Diffuse alveolar hemorrhage (DAH) is a rare disease characterized by dyspnea, cough, hemoptysis, and new alveolar infiltrates. Among the various underlying disorders, vasculitis is believed to play a significant role in the pathogenesis of DAH. Here we report the first case of a patient with Down syndrome who developed DAH secondary to anti-neutrophil cytoplasmic antibody-associated vasculitis. This case highlights the significance of vasculitis as well as pulmonary hypoplasia and vulnerability associated with Down syndrome in the development of DAH.