2019 Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases.

OBJECTIVE: To update and revise the diagnostic criteria for mixed connective tissue disease (MCTD) issued by the Japan Research Committee of the Ministry of Health, Labor, and Welfare (MHLW), a round table discussion by experts from rheumatology, dermatology, and pediatric medicine was conducted in multiple occasions. METHODS: The definition of MCTD, and items included in the diagnostic criteria were generated by consensus method and evaluation using clinical data of typical and borderline cases of MCTD, by applying to the diagnostic criteria for MCTD proposed in 1996 and 2004 by the Research Committee of MHLW. RESULTS: To the end, all committee members reached consensus. Then, the criteria were assessed in an independent validation cohort and tested against preexisting criteria. The revised criteria facilitate an understanding of the overall picture of this disease by describing the concept of MCTD, common manifestations, immunological manifestation and characteristic organ involvement. Conditions with characteristic organ involvement include pulmonary arterial hypertension, aseptic meningitis and trigeminal neuropathy. Even if the overlapping manifestations are absent, MCTD can be diagnosed based on the presence of the characteristic organ involvement. Furthermore, the criteria were validated for applicability in actual clinical cases, and public comments were solicited from the Japan College of Rheumatology and other associated societies. CONCLUSION: After being reviewed through public comments, the revised diagnostic criteria have been finalized.

High Dose Prednisolone Lowers Plasma Glycated Albumin Levels Compared to Actual Glycemic Control: A Retrospective Observational Study.

INTRODUCTION: Glycated hemoglobin (A1c) and glycated albumin (GA) are often used as indicators of glycemic control. In this study, we determined whether prednisolone (PSL) administration lowers plasma GA. METHODS: We investigated the factors affecting GA using multivariate analysis in 48 subjects with connective tissue diseases (CTDs). RESULTS: Multiple regression analysis of GA showed that the dose of PSL [ß = - 1.36; 95% confidence interval (CI) - 2.59 to - 0.14; p = 0.03], age (ß = 0.06; 95% CI 0.03-0.09; p < 0.001), body mass index (BMI) (ß = - 0.14; 95% CI - 0.28 to - 0.01; p = 0.042), and A1c (ß = 1.4; 95% CI 0.38-2.42; p = 0.008) significantly correlated with GA (adjusted R2 = 0.518). Moreover, GA levels adjusted for age, sex, BMI, plasma albumin (Alb) and creatinine (Cre), and A1c in the subjects taking ≥ 5 mg PSL was significantly lower than those in those taking < 5 mg PSL. Finally, the dose of PSL (as a continuous variable) was negatively correlated with GA adjusted for age, sex, BMI, Alb, Cre, and A1c. CONCLUSION: High dose (≥ 5 mg) PSL reduces GA concentration more than glycemia.

Stressors and rheumatoid arthritis: changes in stressors with advances in therapeutic agents.

The significance of evaluations of stressors in rheumatoid arthritis (RA) patients was investigated from the perspective of holistic medicine. The subjects were RA patients treated in the rheumatology outpatient clinic. They included 30 patients from 1987, 30 from 2002, and 137 from 2009. To investigate the specific causes of stress, the patients were asked the question, "What do you feel is your strongest stressor?" The same patients also underwent psychological testing and was examined the disease activity. Pain was the strongest stressor in RA patients in 1987, 2002, and 2009. However, the percentage of patients citing pain as their major stressor was decreasing with each year. CRP was significantly lower in 2009 than in 2002. CRP was also significantly lower in patients who used biologics than in patients who did not. In 2009, DAS28-CRP was significantly higher in patients whose largest stressor was pain than in patients whose largest stressor was another factor. In 2009, the values for both state anxiety and trait anxiety were significantly higher in patients who said that they had stressors than in those who said they did not. The strongest stressor in RA patients was pain. However, the percentage decreased over the years with lower disease activity from advances in therapeutic agents such as biologics. Meanwhile, stressors other than pain were the same or somewhat increased, and they were related to anxiety or depression. Understanding stressors in RA is thus important in treating RA patients.

Evaluation of the clinical cutoff level of serum (1 --> 3)-beta-D-glucan in patients with connective tissue diseases complicated by deep fungal infections.

Serum (1 --> 3)-beta-D-glucan levels and clinical findings were evaluated in 229 inpatients with connective tissue diseases (CTDs) during the period between June and October 2004. The mean serum (1 --> 3)-beta-D-glucan level was 129.7 +/- 207.6 pg/mL in patients with a definitive diagnosis of fungal infections and 10.5 +/- 8.6 pg/mL in patients without fungal infections. Analysis of the diagnostic sensitivity/specificity for various (1 --> 3)-beta-D-glucan cutoff levels gave the best results for a cutoff level of 15 pg/mL, with a sensitivity of 92.3% and specificity of 81.3%. This level was therefore determined to be the optimal cutoff in patients with CTDs.

[Two cases with ankylosing spondylitis using infliximab (case report)].

Case 1 was a 46-year-old man who developed neck pain in addition to pain and swelling in the limb joints in 1975. The patient was diagnosed with ankylosing spondylitis (AS) in 1983 based on detection of sacroiliitis on X-ray as well as a positive result for HLA B-27. Following administration of non-steroidal anti-inflammatory drugs (NSAIDs) and sulfasalazine (SSZ), methotrexate (MTX) was substituted at doses up to 17.5 mg/week in addition to concomitant prednisolone (PSL) (7.5 mg/day). However, no favorable response was obtained. As pain and inflammatory response improved following initiation of infliximab (IFX) in April 2005, PSL was discontinued and MTX was reduced to 10 mg/week. Case 2 was a 57-year-old man who experienced limitation of neck mobility in 1975. The patient was diagnosed with AS in 1989 based on detection of cervical ankylosis and sacroiliitis on X-ray and was given NSAIDs. After developing pain and swelling in the limb joints in 1994, the patient was given PSL (10 mg/day), bucillamine, MTX (8 mg/week), and leflunomide but did not improve. Arthritis in the limbs showed short-term improvement following initiation of IFX in May 2005. These findings demonstrate that IFX is a treatment option for AS refractory to conventional treatment.

[Pulmonary arterial hypertension with connective tissue diseases].

Pulmonary arterial hypertension (PAH) occurs in about 5% of connective tissue disease (CTD) patients. Performing echocardiography, the incidence is much higher at 9.5%, thus confirming the presence of asymptomatic PAH. In 32% of MCTD with PAH, PAH was diagnosed within one year of MCTD diagnosis. Therefore, it is necessary to screen for PAH by echocardiography after the diagnosis of CTD, irrespective of the existence of PAH-related signs and symptoms. The treatments of PAH with CTD are different from those of idiopathic PAH in that the immunosuppressive therapy is expected to alleviate PAH with CTD.

Multiple perforated ulcers of the small intestine associated with allergic granulomatous angiitis: report of a case.

Although allergic granulomatous angiitis (AGA) is occasionally associated with gastrointestinal lesions, multiple perforated ulcers of the gastrointestinal tract are uncommon. We report herein a case of AGA associated with multiple perforated ulcers that erupted in the small intestine during corticosteroid therapy. A 31-year-old Japanese man was admitted to our hospital with epigastralgia, edema of the bilateral lower extremities, and general malaise. He had a persistent high fever, abdominal pain, and watery diarrhea. Laboratory data showed remarkable eosinophilia. The abdominal pain became exacerbated after the administration of oral prednisolone. Physical examination indicated positive signs of peritoneal irritation in the entire abdomen, and abdominal computed tomography scanning showed intra-abdominal free air, suggesting generalized peritonitis due to intestinal perforation. Laparotomy revealed multiple perforated ulcers in the jejunum and ileum. Histological examination indicated remarkable eosinophilic infiltration in the surrounding area of the small arteries and arterioles located in the submucosal layer, which was compatible with AGA. Although the association of intestinal perforation with AGA is relatively infrequent, intensive perioperative management is essential to ensure a favorable clinical outcome, particularly during the period on corticosteroid therapy.