Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature.

Although the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM.

A retrospective study of SARS-CoV-2 antibodies in children with allergies.

BACKGROUND: The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children are continually changing. We conducted a survey of pediatric allergy patients attending our department to determine the prevalence of antibodies against SARS-CoV-2 in children. METHODS: A retrospective study was performed among children aged <11 years, referred to a pediatric allergy department between February 2020 and January 2022 with a chief complaint of allergy. The data of children with blood examination findings were retrospectively studied. Qualitative testing for anti-SARS-CoV-2 IgG and IgM antibodies was performed using a SARS-CoV-2 rapid antibody test. Participants were retested 1 year later to evaluate changes in antibody levels. RESULTS: In total, 310 patients with a median age of 26 months (interquartile range: 11.6-58.4 months) and male/female ratio of 1.31 were included. A total of 32 patients tested positive for anti-SARS-CoV-2 IgG or IgM antibodies. No differences were observed in the severity of allergic disease. The prevalence of antibodies was higher among children enrolled in preschool or school (odds ratio: 13.19, 95% confidence interval; 2.30-249.7). A total of 66.7% of patients underwent follow-up testing. The antibody positivity rate increased between the first and second testing, but this was not related to the number of medical visits or the severity of allergic disease. CONCLUSION: Antibody prevalence in children was low but increased during the study period. The majority of children who tested positive for SARS-CoV-2 antibodies did not have a history of coronavirus disease 2019, suggesting that most infections were subclinical.

Promoting awareness of terminology related to unmet medical needs in context of rheumatic diseases in Japan: a systematic review for evaluating unmet medical needs.

To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes.

Evidence of off-label inhalation therapy on pediatric asthma practice in Japan.

BACKGROUND: In Japan, many asthma inhalers do not have formal approval for use in the pediatric population because of the lack of domestic data. In real-world settings, however, numerous off-label medications are prescribed. Currently, the nature of off-label prescriptions of asthma inhalers on pediatric patients in Japan remains unclear. METHODS: Using public open-source national medical claims data, we investigated the real-world descriptive epidemiology of off-label prescriptions for asthma inhalers for pediatric patients. We obtained the number of off-label prescriptions of formulations for patients aged 0-14 years from anonymously summarized prescription data for a 7-year period starting from April 2014. The actual prescription numbers and their chronology over time were then analyzed. RESULTS: In 2019, 143,439 asthma inhalers were used off label in children and adolescents. Overall, 96.1% were inhaled corticosteroids (ICSs) or long-acting beta stimulants (LABAs), and 3.9% were high-dose ICS. Of ICSs and LABAs, 18.8% were off-label prescriptions. The total number of off-label ICS/LABA prescriptions and their percentage relative to the overall formulations gradually decreased but a notable disparity was observed among inhaler types. CONCLUSIONS: There was a surprisingly large number of off-label prescriptions of asthma inhalers in the pediatric population in Japan. The proper use of ICSs/LABAs and expansion of insurance coverage should be advocated to reduce off-label use.

Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea.

STUDY OBJECTIVES: Poor adherence to continuous positive airway pressure (CPAP) has been a critical issue in treating obstructive sleep apnea. Because long-term CPAP adherence may be established shortly after treatment begins, early intervention is essential. This study aimed to identify the potential factors affecting CPAP therapy adherence during diagnostic polysomnography and auto CPAP titration polysomnography. METHODS: This retrospective observational study included 463 patients with obstructive sleep apnea who underwent consecutive diagnostic polysomnography and titration polysomnography. We recorded their demographic, anthropometric, and lifestyle factors and obtained self-reported comments regarding their sleep status following both polysomnography evaluations. CPAP adherence was evaluated following 3 months of treatment. RESULTS: A total of 312 patients (67.4%) fulfilled the criteria for good adherence. Each patient's CPAP adherence was categorized as "poor" (< 4 hours/night or <70% of nights), "good" (≥ 4 hours/night and ≥ 70% of nights), or "excellent" (≥ 6 hours/night and ≥ 80% of nights). There were no significant differences in arterial oxyhemoglobin saturation measured by pulse oximetry and apnea-hypopnea index during diagnostic polysomnography among 3 groups. The polysomnographic evaluations indicated that patients with better adherence displayed more significant improvements in sleep parameters, including apnea-hypopnea index, sleep efficacy, sleep latency, and sleep architecture, which were correlated with an improvement in self-reported sleep quality. CONCLUSIONS: Polysomnographic evaluations enabled CPAP adherence prediction and a comparison of self-reported sleep quality with and without CPAP; CPAP adherence led to improvements in polysomnographic parameters. Our findings suggest that titration polysomnography and self-reported sleep improvement with CPAP could be used for adherence prediction in clinical practice. CITATION: Shirahata T, Uchida Y, Uchida T, et al. Improvement of sleep parameters by titration polysomnography could predict adherence to positive airway pressure therapy in obstructive sleep apnea. J Clin Sleep Med. 2023;19(8):1465-1473.

A case of bunashimeji mushroom-induced hypersensitivity pneumonitis diagnosed by inhalational provocation test in a hospital room.

A 66-year-old woman was admitted to our hospital with a 2-month history of dry cough and exertional dyspnea. She had worked as a mushroom farmer and had been exposed to mushroom for more than 40 years. The patient showed elevated levels of KL-6 (2966 U/mL) and surfactant protein D (410 ng/mL), and computed tomography of the chest revealed ground-glass opacities and fine nodular shadows in both lungs, suggesting mushroom-induced hypersensitivity pneumonitis. Pulmonary function testing revealed decreases in forced vital capacity (78% of predicted) and carbon monoxide diffusing capacity (67% of predicted). The inhalational provocation test was positive for bunashimeji mushrooms. Precipitating antibody was only identified for spores or bodies of bunashimeji mushrooms, and lymphocyte stimulation testing with spores or bodies of bunashimeji mushrooms also yielded positive results. Bunashimeji mushroom-induced hypersensitivity pneumonitis was therefore diagnosed. Radiological findings and pulmonary function were improved by corticosteroid therapy and the patient has since remained healthy with allergen avoidance.

Atrophic autoimmune thyroiditis complicated with systemic lupus erythematosus.

Atrophic autoimmune thyroiditis (AAT) is a type of autoimmune thyroiditis that causes hypothyroidism without thyroid enlargement. AAT is distinguished from Hashimoto's disease (HD) by the absence of thyroid enlargement. AAT is rare in children and clinically characterised by severe primary hypothyroidism. Autoimmune thyroiditis, especially HD, is commonly complicated with systemic lupus erythematosus (SLE). Here, we reported the patient with AAT as the initial presentation of SLE complicated with generalised myxoedema, whose presentation was a diagnostic challenge. This patient illustrates the importance of the early recognition of an atypical presentation of SLE patients with autoimmune thyroiditis. It is possible that similar cases have existed in the past but have been overlooked as HD. A large-scale study is necessary to clarify the reality of AAT in SLE.

Pure red cell aplasia accompanied by COVID-19 successfully treated using cyclosporine.

A 67-year-old Japanese man was admitted to our hospital with severe coronavirus disease 2019 (COVID-19) in March 2020. Mechanical ventilation was initiated 8 days after admission, due to severe respiratory failure. Multiple severe complications such as liver dysfunction, arrhythmia, brain infarction, and venous thromboembolism were also observed. We initially diagnosed Coombs test-positive warm autoimmune hemolytic anemia. Corticosteroids proved ineffective and anemia worsened with severe erythroid hypoplasia (0.5% erythroblasts in bone marrow), so we diagnosed pure red cell aplasia (PRCA). We also identified massive infiltration of cytotoxic T-lymphocytes expressing CD8, granzyme B, and perforin in bone marrow. Systemic cyclosporine was started, with full resolution of anemia and no need for blood transfusions after 4 weeks. We believe that this represents the first report of COVID-19-associated PRCA successfully treated using cyclosporine.

Predicting the presence and severity of obstructive sleep apnea based on mandibular measurements using quantitative analysis of facial profiles via three-dimensional photogrammetry.

BACKGROUND: In obstructive sleep apnea (OSA), the upper airway is obstructed during sleep due to obesity and/or posterior collapse of the tongue root. Maxillofacial morphological abnormalities increase the risk of OSA in the Asian population. This study sought to elucidate whether three-dimensional (3D) photogrammetry measurements correlate with the severity of OSA irrespective of sex and degree of obesity. METHODS: A prospective pilot study was performed, in which 37 consecutive adult patients (M/F = 28/9) underwent polysomnography and 3D photogrammetry in the supine position for the diagnosis of OSA. Measurements obtained from 3D photogrammetry included mandibular width (Mw), mandibular length (Ml), mandibular depth (Md), mandibular width-length angle (Mwla), and mandibular area (Ma). The effects of sex and body mass index (BMI) on the measurements and their association with the apnea-hypopnea index (AHI) were statistically analyzed. The inter-rater reliability of the measurements was evaluated using intraclass correlation coefficients (ICC). RESULTS: Mwla (R = 0.73, p < 0.01), Mw (R = 0.39, p < 0.05), and Md (R = -0.34, p < 0.05) were significantly correlated with the severity of OSA. On multivariate analysis, Mwla (p < 0.01) and Md (p < 0.05) remained independent factors for AHI after adjusting for sex, age, BMI, and neck circumference. In addition, diagnosability analysis revealed that Mwla was useful for identifying the presence of OSA (AHI ≥5) (cutoff: 78.6°, sensitivity: 0.938, specificity: 0.800, area under the curve: 0.931). The ICC was >0.9, showing high reliability. CONCLUSIONS: This study suggests that Mwla measured using 3D photogrammetry can predict the presence of OSA and correlates with the severity of OSA, independent of obesity and sex.

Tacrolimus as an alternative treatment for patients with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in patients with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively analysed 27 patients with JIA who received tacrolimus therapy at the Department of Pediatric Rheumatology of the Tokyo Medical and Dental University between April 2019 and August 2020. We collected background and clinical characteristics at the time of add-on tacrolimus therapy initiation (baseline; Month 0) and after 3, 6, and 12 months. The primary outcome was successful medication reduction after 12 months. Patients requiring reduced and additional treatments were assigned as 'did not require additional treatment patients' and 'required additional treatment patients', respectively. The Wilcoxon signed-rank test was used to evaluate the continuous distribution of laboratory data and Juvenile Arthritis Disease Activity Score-27 at 3, 6, and 12 months relative to baseline values. Statistical significance was set as p < .05. RESULTS: Among the 27 included cases, 17 patients were classified as did not require additional treatment patients, and there was a significant improvement in Juvenile Arthritis Disease Activity Score-27 scores in this group (p < .05). No patients presented tacrolimus-related adverse events throughout the study period. CONCLUSION: Tacrolimus is an effective and safe therapeutic alternative for approximately 60% of patients with JIA.

The Benefits and Respective Side-Effects of PE Therapy for Intractable Kawasaki Disease.

Kawasaki disease (KD) is a vasculitis syndrome that frequently develops coronary artery lesions (CALs). In the treatment of KD, the utility of high-dose intravenous immuno-globulin (IVIG) therapy has already been clarified, and it has been established as the first-line treatment method. However, since approximately 10% of patients are refractory to this IVIG therapy and 2.6% of all patients have coronary sequelae, 500 children with KD still remain every year in Japan. In this disease, it is necessary to calm inflammation within 10 days of onset in order to suppress CALs caused by a large amount of persistent inflammatory cytokines. Indeed, the early suppression of inflammation is an effective means of suppressing the onset of CALs. Here, we describe the pathophysiology of Kawasaki disease and plasma exchange (PE), which is a therapeutic method that can calm the hyper-cytokine state of this disease. The treatment result of PE for IVIG-refractory Kawasaki disease is outstanding, and an extremely large effect can be expected if it can be started before the appearance of CALs. It seems that it should always be considered as one of the powerful additional treatments in the future.