A case report, a case who developed limited cutaneous scleroderma and pulmonary hypertension 8 years after diagnosis of anti-centromere antibody-positive Sjögren syndrome.

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (DLCO, 17%) and desaturation (69%) after a 6-minute walk test. She was also diagnosed as having limited cutaneous systemic sclerosis (lcSSc) because she had developed finger sclerosis. The six-minute walk distance had improved by 54 m 3 months after commencing treatment with tadalafil. Clinicians should be alert to the possibility of patients with ACA-positive SS developing lcSSc and PAH during their clinical course.

Differences in Adherence Barriers to Inhaled Medicines between Japanese Patients with Chronic Obstructive Pulmonary Disease and Asthma Evaluated using the "Adherence Starts with Knowledge 20" (ASK-20) Questionnaire.

Objective This multicenter, cross-sectional, non-interventional trial aimed to investigate adherence barriers to inhaled medicines when compared with oral medicines in Japanese patients with chronic obstructive pulmonary disease (COPD) and asthma. Methods The self-reporting "Adherence Starts with Knowledge 20" (ASK-20) questionnaire was administered for adherence barriers of inhaled and oral medicines to outpatients with regular clinic attendance. Results Patients with COPD and asthma reported different adherence barriers to inhaled medicines. Independent adherence barriers [odds ratio (95% confidence interval)] to inhaled medicines relative to those for oral medicines among patients with COPD and asthma were those related to item Q8 [ "I know if I am reaching my health goals"; 2.49 (1.39-4.47); p=0.0022] and item Q2 [ "I run out of my medicine because I do not get refills on time"; 2.69 (1.26-5.75); p=0.0127], respectively. Among patients with poor adherence to only inhaled medicines, those with COPD and asthma recognized item Q3 [ "consuming alcohol and taking medicines"; 6.63 (1.27-34.7); p<0.05] and item Q1 [ "forget to take medicines only sometimes"; 4.29 (1.83-10.0); p<0.05], respectively, were recognized as independent adherence barriers to inhaled medicines. The total ASK-20 scores and total barrier counts in patients with poor adherence to inhaled medicines were significantly higher than in those without poor adherence among patients with asthma (p=0.0057) but not those with COPD (p>0.05). Conclusion These results will aid in personalizing education on adherence to inhaled medicines among patients with COPD and asthma.

Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family.

Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant hereditary SPG caused by mutations in the SPAST gene. We studied the four-generation pedigree of a Japanese family with autosomal dominant hereditary SPG both clinically and genetically. Twelve available family members (ten affected; two unaffected) and two spouses were enrolled in the study. The clinical features were hyperreflexia in all four limbs, spasticity of the lower extremities, impaired vibration sense, mild cognitive impairment confirmed by the Wechsler Adult Intelligence Scale-Third Edition, and peripheral neuropathy confirmed by neurophysiological examinations. All four female patients experienced miscarriages. The cerebrospinal fluid tau levels were mildly increased in two of three patients examined. Linkage analyses revealed the highest logarithm of odds score of 2.64 at 2p23-p21 where the SPAST gene is located. Mutation scanning of the entire exonic regions of the SPAST gene by direct sequencing revealed no mutations. Exonic copy number analysis by real-time quantitative polymerase chain reaction revealed heterozygous deletion of exons 1 to 4 of the SPAST gene. Breakpoint analysis showed that the centromeric breakpoint was located within intron 4 of SPAST while the telomeric breakpoint was located within intron 3 of the neighboring DPY30 gene, causing a deletion of approximately 70 kb ranging from exons 1 to 3 of DPY30 to exons 1 to 4 of SPAST. To our knowledge, this is the first report of SPG4 associated with partial deletions of both the SPAST and DPY30 genes. The partial heterozygous deletion of DPY30 could modify the phenotypic expression of SPG4 patients with this pedigree.

Primary systemic amyloidosis presenting as angina pectoris due to intramyocardial coronary artery involvement: a case report.

We describe a 76-year-old Japanese woman with primary systemic amyloidosis who presented with angina pectoris associated with ST-segment and T-wave abnormalities resulting from intramyocardial coronary artery amyloidosis. The patient was admitted to our hospital because of dyspnea and pretibial edema 7 years after the diagnosis of variant angina. A diagnosis of primary systemic amyloidosis (AL amyloid protein) was made after examination of gastric and endomyocardial biopsy specimens. The patient died of progressive, uncontrolled heart failure 3 months later. An autopsy study demonstrated only mild-to-moderate atherosclerosis in the epicardial coronary arteries. However, histological examination of the heart revealed diffuse stenoses and obstructions in the intramural coronary arteries by amyloid deposits. This patient had small-vessel coronary disease with ST-segment changes and angina caused by cardiac amyloidosis. A correct diagnosis of ischemic heart disease due to primary amyloidosis is important for estimation of the prognosis and for appropriate management.