Naoki Mugii

Reduced red blood cell velocity in nail-fold capillaries as a sensitive and specific indicator of microcirculation injury in systemic sclerosis

OBJECTIVE To assess red blood cell velocity in finger nail-fold capillaries using video capillaroscopy in patients with SSc and other collagen diseases. METHODS This study included 127 patients with SSc as well as patients with SLE (n = 33), DM/PM (n = 21), RA (n = 13) and APS (n = 12), and 20 healthy subjects. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps. RESULTS The mean red blood cell velocity was significantly decreased in patients with SSc compared to healthy controls (63.0% reduction) and patients with other conditions. Mean blood velocity was similar between patients with dcSSc and lcSSc. Importantly, even SSc patients with normal or non-specific nail-fold video capillaroscopic (NVC) patterns or a scleroderma early NVC pattern exhibited a significantly lower red blood cell velocity compared to healthy controls (51.7 and 61.4% reduction, respectively) or patients with other conditions, despite normal or mild capillary changes. Patients with the scleroderma active and late NVC pattern showed a more decreased blood velocity (65.5 and 66.2% reduction, respectively). This reduced blood velocity was significantly associated with NVC findings, including capillary ramification and capillary loss. Although remarkably reduced velocity was observed in SSc patients with intractable digital ulcers (72.1% reduction), it was significantly improved by lipo-prostaglandin E(1) (lipo-PGE(1)) infusion. CONCLUSION Our results suggest that reduced blood velocity is a hallmark of SSc. Furthermore, measurement of red blood cell velocity may be useful in evaluating therapeutic effects on microcirculation.

Association between nail-fold capillary findings and disease activity in dermatomyositis

OBJECTIVE Although findings of nail-fold capillary changes and reduced red blood cell velocity in SSc patients are well established, studies in adult-onset DM patients are scarce. Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM. METHODS This study included 50 patients with adult-onset DM and 20 healthy subjects. A semi-quantitative rating scale was used to score capillaroscopy changes. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps. RESULTS Thirty-seven (74%) patients showed the scleroderma NVC pattern. Patients with the scleroderma pattern exhibited elevated serum creatine kinase levels more frequently and increased visual analogue scale of muscle disease activity. Scores of loss of capillaries were associated with muscle and global disease activity, whereas scores of haemorrhages were associated with skin disease activity. However, NVC findings were not significantly associated with lung involvement. The scores of irregularly enlarged capillaries, haemorrhages and loss of capillaries were reduced after stabilization of disease activity by treatment. The mean red blood cell velocity was not significantly reduced in DM patients compared with healthy controls and was not changed by treatment. CONCLUSION Our results suggest that changes in nail-fold capillaries reflect disease activity in DM. Furthermore, the differences found in red blood cell velocity may reflect somewhat distinct microcirculation injuries in DM and SSc.

Predictors of Exercise-Induced Oxygen Desaturation in Systemic Sclerosis Patients With Interstitial Lung Disease

BACKGROUND: The diffusion capacity of the lung for carbon monoxide (DLCO) is a good marker of disease severity in patients with idiopathic interstitial pneumonia, and is associated with oxygen saturation; however, little is known about DLCO in systemic sclerosis patients with interstitial lung disease. We studied potential predictors of exercise-induced oxygen desaturation in patients with systemic sclerosis. METHODS: Data were collected prospectively from 80 of 110 consecutive systemic sclerosis patients with normal oxygen saturation (> 95%) at rest, who could perform the 6-min walk test without physical discomfort, including leg pain. Pulmonary function tests and echocardiography were collected from all subjects. RESULTS: Thirty subjects showed a ≥ 4% decline in oxygen saturation during the 6-min walk test (desaturation group). The other subjects were assigned to the normoxic group. The percent-of-predicted values for FVC, FEV1, total lung capacity, DLCO, and DLCO/alveolar volume were lower, and FEV1/FVC was higher, in the desaturation group. Logistic regression analysis showed the percent-of-predicted DLCO as a highly accurate predictor of exercise-induced oxygen desaturation: the area under the receiver operating characteristic curve was 0.92 (cutoff point 56.3%, sensitivity 0.83, specificity 0.86). Five subjects over the cutoff point of the percent-of-predicted DLCO in the desaturation group could not be distinguished from the normoxic subjects with the lung-volume measurements or right-ventricular systolic pressure. CONCLUSIONS: The factor underlying exercise-induced oxygen desaturation appeared to be reduced percent-of-predicted DLCO, which was useful as a predictor in over 80% of the subjects.

Reduced hypoxia risk in a systemic sclerosis patient with interstitial lung disease after long-term pulmonary rehabilitation

Pulmonary rehabilitation is effective for improving exercise capacity in patients with interstitial lung disease (ILD), and most programs last about 8 weeks. A 43-year-old male patient with systemic sclerosis and oxygen saturation (SpO2) declining because of severe ILD was hospitalized for treatment of chronic skin ulcers. During admission, he completed a 27-week walking exercise program with SpO2 monitoring. Consequently, continuous walking distance without severe hypoxia (SpO2 > 90%) increased from 60 m to 300 m after the program, although his six-minute walking distance remained the same. This suggests that walking exercise for several months may reduce the risk of hypoxia in patients with ILD, even though exercise capacity does not improve.

Limitations to the 6-minute walk test in dermatomyositis with interstitial lung disease in comparison with idiopathic interstitial pneumonia.

Although the relationship between muscle strength and exercise capacity has been demonstrated in dermatomyositis without lung dysfunction, little is known about the association between exercise capacity and interstitial lung disease in dermatomyositis. Eleven patients with dermatomyositis with interstitial lung disease without the manifestation of muscle weakness and 12 patients with idiopathic interstitial pneumonia underwent the 6-minute walk test (6MWT). PaO2, creatine kinase, percentage predicted 6MWT distance (6MWD%), and SpO2 at rest were similar between patients. Percentage predicted vital capacity, carbon monoxide diffusing capacity (DLCO%), and SpO2 after 6MWT were higher and exertional dyspnea was lower in patients with dermatomyositis than in patients with idiopathic interstitial pneumonia. SpO2 after 6MWT was positively correlated with 6MWD% in patients with dermatomyositis, while DLCO% and PaO2 were positively correlated with 6MWD% in patients with idiopathic interstitial pneumonia. Lung dysfunction in dermatomyositis might not be a major limitation factor in exercise capacity.

The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease

The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe) scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002), and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease.

Clinical significance and usefulness of rehabilitation for systemic sclerosis

Systemic sclerosis is a multisystem connective tissue disorder characterized by excessive fibrosis of the skin and internal organs. Impairments in skin, the musculoskeletal system, and respiratory system require rehabilitation therapy because they may lead to disabilities and reduce the quality of life in daily activities. Rehabilitation for systemic sclerosis mainly comprises two distinct approaches that include local and global rehabilitation. Local rehabilitation is applied to maintain and/or improve hand and face functions, while global rehabilitation includes aerobic and resistance exercises. Although few high-quality randomized clinical trials have been conducted to date, previous studies indicated the effectiveness of rehabilitation therapy for decreasing local and systemic disabilities, resulting in improved quality of life. Rehabilitation for systemic sclerosis needs to be regularly and constantly performed at home as well as in hospitals. Physicians involved in the treatment of systemic sclerosis need to consider rehabilitation, and skilled physiotherapists and occupational therapists also play a crucial role in evaluating and treating systemic sclerosis patients.

Cardiopulmonary factors affecting 6-min walk distance in patients with idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies involve skeletal muscles and can be associated with interstitial lung disease and/or heart dysfunction, which may reduce exercise capacity. We aimed to clarify cardiopulmonary factors affecting the 6-min walk distance in patients who were able to walk without leg pain or fatigue. Twenty-three patients with inactive adult idiopathic inflammatory myopathies, and 18 age- and gender-matched healthy controls were evaluated for hemodynamic responses using noninvasive impedance cardiography during the 6-min walk test. The patients were also examined by the pulmonary function test for forced vital capacity and diffusing capacity for carbon monoxide (DLCO), and by echocardiography for left ventricular ejection fraction and right ventricular systolic pressure. Interstitial lung disease was diagnosed in 19 patients using high-resolution computed tomography. There was no difference in 6-min walk distance or cardiac output after walking between the patients and healthy controls. However, stroke volume during the 6-min walk test was significantly lower in the patients than in healthy controls, suggesting malfunction in the heart. Moreover, the increased heart rate matched the cardiac output. Spearman’s correlation analysis demonstrated a correlation between 6-min walk distance and stroke volume, cardiac output after walking and DLCO, but not left ventricular ejection fraction or right ventricular systolic pressure, as this study lacked the patients with pulmonary hypertension. In conclusion, impaired DLCO due to interstitial lung disease was suggested to be a fundamental parameter affecting exercise capacity, in addition to heart involvement, in patients with idiopathic inflammatory myopathies.

Long-term follow-up of finger passive range of motion in Japanese systemic sclerosis patients treated with self-administered stretching

Abstract Objective: Severe skin sclerosis in patients with systemic sclerosis (SSc) can result in a loss of hand function. The aim of this study is to examine the long-term changes of finger passive range of motion (ROM) in Japanese SSc patients treated with self-administered stretching. Methods: This is a single-center, retrospective, observational cohort study. Forty-three Japanese patients with SSc were given instructions on self-administered stretching. ROM was assessed using a goniometer on their first visit and after 1 year, 3 years, 5 years and 9 years. Hand function was assessed by the Health Assessment Questionnaire disability index (HAQ-DI) at their first visit and after 9 years. Results: Total passive ROM significantly improved in each finger after 3 years of finger stretching. Most patients (37 of 43 patients, 86%) improved or maintained total passive ROM and hand function within 9 years after their first visit. However, significant improvement of total passive ROM was lost in 6 of 43 SSc patients (14%) 9 years after their first visit. The HAQ-DI also was increased in these six patients. Multivariable analyses revealed that re-elevation of modified Rodnan total skin thickness score during the clinical course (OR = 5.260e + 7, 95% CI 1.52e + 150–uncalculated p = .0096) was the independent factor associated with deterioration of total passive ROM at 9 years. Conclusion: Patients with progressive skin sclerosis during the clinical course need multimodality therapy to maintain finger joint motion, since the effect of self-administered stretching is limited in these patients.

Diagnostic criteria, severity classification and guidelines of systemic sclerosis: Guideline of SSc

Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side‐effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence‐based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc.