Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet's disease in Japan.

BACKGROUND: We hypothesized that Behçet's disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD. METHODS: A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups. RESULTS: A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters. CONCLUSIONS: In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely "mucocutaneous", "mucocutaneous with arthritis", "neuro", "GI", and "eye."

Radiological images of interstitial pneumonia in mixed connective tissue disease compared with scleroderma and polymyositis/dermatomyositis.

OBJECTIVE: Little has been reported on the radiological and pathological findings of interstitial pneumonia in mixed connective tissue disease (MCTD). There may be possible difference in treatment response and prognosis between the imaging patterns of systemic sclerosis (SSc)-like and polymyositis/dermatomyositis (PM/DM)-like. The purpose of this study was to examine whether the radiological images of interstitial pneumonia in MCTD presented SSc-like or PM/DM-like pattern, and to assess whether the imaging patterns corresponded to clinical and pathological features. MATERIALS AND METHODS: This retrospective study included 29 patients with interstitial pneumonia who underwent surgical lung biopsy; 10 with SSc, 10 with PM/DM, and 9 with MCTD. High resolution computed tomography (HRCT) images were classified as SSc, PM/DM, or the other pattern by two radiologists independently without clinical information. The pathology of the lung specimens from MCTD patients were evaluated and compared with the imaging pattern. RESULTS: The concordance rate between clinical diagnosis and radiological pattern was 100% in SSc patients, and 80% in PM/DM patients. Among patients with MCTD, imaging patterns were classified as SSc pattern in 4 (MCTD-SSc), PM/DM pattern in 4 (MCTD-PM/DM) and other in one. The imaging patterns did not always correlate with the clinical findings in MCTD patients. Pathologically, plasma cell infiltration and organizing pneumonia were relatively more frequent in MCTD-PM/DM, and smooth muscle hyperplasia was relatively more frequent in MCTD-SSc. CONCLUSION: HRCT images in MCTD patients can be classified as SSc pattern or PM/DM pattern. MCTD-SSc and MCTD-PM/DM were corresponded to similar pathological findings of SSc and PM/DM.

Gastrocnemius Myalgia as a Rare Initial Manifestation of Crohn's Disease.

The initial symptoms of Crohn's disease (CD) sometimes present as extraintestinal lesions, which can be a diagnostic challenge for physicians. Painful legs, known as "gastrocnemius myalgia syndrome", are rare complications that often precede abdominal manifestations. We herein report the case of a 38-year-old man who presented with bilateral leg myalgia lasting for 4 months. Magnetic resonance imaging showed abnormal intensity, and a muscle biopsy revealed inflammatory cell infiltration. Abdominal symptoms appeared three months after the myalgia onset, and the diagnosis of CD was confirmed later by endoscopic and radiological findings. To our knowledge, this is the first description of gastrocnemius myalgia syndrome in Japan.

Continuous evolution of clinical phenotype in 578 Japanese patients with Behçet's disease: a retrospective observational study.

BACKGROUND: It has been suggested that the phenotypes of Behçet's disease (BD) in Japan are changing. To ask whether the evolution of BD holds true in recent-onset cases in Japan, we performed a retrospective study. METHODS: We reviewed the records of 578 patients with BD who met the 1987 revised diagnostic criteria of the Behçet's disease research committee of Japan. The patients were divided into three groups based on the date of disease onset. We compared the demography, clinical features, and treatments among them with or without adjustment for the observation period. Patients having oral ulcers, genital ulcers, regional skin involvement, and uveitis are categorized as having complete-type BD, and the associated factors were determined by univariate and multivariate logistic regression analyses. RESULTS: Male patients had a higher propensity for uveitis and central nervous system (CNS) involvement, whereas female patients had higher rates of genital ulcers and arthritis. We found a significant trend in reduction of complete-type, genital ulcer, HLA-B51 carriers, and increment of gastrointestinal BD over time. Multiple regression analysis identified HLA-B51 positivity, earlier date of disease onset, and younger age of onset as independently associated with complete-type BD. Although treatments had been also chronologically changed, the causative relationship between therapeutic agents and phenotypical changes was not determined from the study. CONCLUSION: The present study revealed that phenotypical evolution was characterized by decreased incidence of the complete type and increment of gastrointestinal involvement in Japanese patients with BD during the last 30 years.

Life events, emotional responsiveness, and the functional prognosis of patients with rheumatoid arthritis.

BACKGROUND: Stressors may differently affect human physiological systems according to the host properties relevant to psycho-behavioral processes that the stressors invoke. In a Japanese multicenter cohort study of patients with rheumatoid arthritis (RA), we examined if major life events differently contribute to the patients' functional prognosis according to their ability to identify emotions as manifest feelings when encountering the events (emotional responsiveness). METHODS: 460 patients with RA completed a self-administered baseline questionnaire about psychosocial factors including emotional responsiveness. Two years later, they checked on a list of positive/negative personal events that happened during the two-year study period. Rheumatologists evaluated their functional status at baseline and follow-up using the ACR classification system. RESULTS: In a multiple logistic regression model that included baseline demographic, disease activity/severity-related, therapeutic, and socioeconomic factors as covariates, none of the counts of positive, negative, or all life events was associated with the functional status at follow-up. In the subgroup with poor emotional responsiveness, however, these life event counts were all associated with a poorer functional prognosis (odds ratio of ACR class 3-4 vs. 1-2 associated with one increment in the all life-event count = 2.39, 95 % confidence interval = 1.27-4.48, p = .007), while no such relationship was evident for the rest of the patients. CONCLUSIONS: Major life events, whether positive or negative in nature, may have an impact on the disease course of patients with RA when the patient has poor emotional responsiveness to the event(s).

Rational/antiemotional behaviors in interpersonal relationships and the functional prognosis of patients with rheumatoid arthritis: a Japanese multicenter, longitudinal study.

BACKGROUND: The repression of negative emotions is a personality factor that received considerable attention in the 1950-60s as being relevant to the onset and course of rheumatoid arthritis (RA). Despite subsequent, repeated criticisms of the cross-sectional nature of the earlier studies, even to date few prospective studies have been reported on this issue. This multicenter study prospectively examined if "rational and antiemotional" behavior (antiemotionality), characterized by an extreme tendency to suppress emotional behaviors and to rationalize negative experiences in conflicting interpersonal situations, is associated with the functional prognosis of patients with RA. METHODS: 532 patients with RA who regularly visited one of eight hospitals/clinics in Japan in 2000 were recruited for study. All completed a self-administered baseline questionnaire about lifestyle and psychosocial factors including antiemotionality. Two years after, 460 (mean age, 56.1 years; 54 men and 406 women) of 471 patients who continued to visit the clinics agreed to take the follow-up questionnaire. The functional status of the patients was evaluated by rheumatologists based on the ACR classification system. RESULTS: A multiple logistic regression model that included baseline demographic, disease activity/severity-related, therapeutic, and socioeconomic factors as covariates found a tendency toward higher antiemotionality to be related to poorer functional status at follow-up. This relationship was not explained by lifestyle factors. CONCLUSIONS: Antiemotionality may be a prognostic factor for the functional status of patients with RA. This finding sheds light on a seemingly forgotten issue in the care of patients with RA.