Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid-induced myopathy.

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered.

Results of the guideline-based treatment for pemphigus: a single-centre experience with 84 cases.

BACKGROUND: The Japanese guidelines for the management of pemphigus (JG) were published in 2010. However, further progress in the treatment of pemphigus requires their validation. OBJECTIVES: To examine the efficacy and safety of treatments based on the JG. METHODS: A retrospective study of 84 Japanese patients with moderate to severe pemphigus, who were initially treated in accordance with the JG and then followed up for >2 years, was performed in a single centre. Treatment typically consisted of 0.5-1 mg prednisone (PSL)/kg/day accompanied by 100 mg azathioprine/day as a steroid-sparing agent. RESULTS: In 83 of the 84 patients (98.8%), complete remission on minimal therapy (≤10 mg PSL/day and concomitant immunosuppressive agent) was achieved. The time between initiation of therapy and remission was 13.9 ± 9.4 months. In 78 patients (92.9%), remission was accomplished within the 2-year follow-up. The 32 patients with recalcitrant disease (38.1%) received additional treatment. Relapse occurred in 12 patients (14.3%) either during tapering of the PSL dose (six patients) or after achieving remission (six patients). Adverse events, mostly liver enzyme elevation, infections and diabetes, occurred in 67 patients (79.8%). One patient (1.2%) died during the observation period after gastrointestinal haemorrhage. CONCLUSIONS: Our results suggested that the elderly and patients requiring additional therapies were at higher risk of adverse events, including severe infections, and should thus be monitored carefully. This study provided clinical data that could inform revised guidelines and contribute to the evaluation of future novel therapies.

Prevalence of Smqnr and plasmid-mediated quinolone resistance determinants in clinical isolates of Stenotrophomonas maltophilia from Japan: novel variants of Smqnr.

Stenotrophomonas maltophilia is an important pathogen in healthcare-associated infections. S. maltophilia may contain Smqnr, a quinolone resistance gene encoding the pentapeptide repeat protein, which confers low-level quinolone resistance upon expression in a heterologous host. We investigated the prevalence of Smqnr and plasmid-mediated quinolone resistance (PMQR) determinants in S. maltophilia isolates from Japan. A total of 181 consecutive and nonduplicate clinical isolates of S. maltophilia were collected from four areas of Japan. The antimicrobial susceptibility profiles for these strains were determined. PCR was conducted for Smqnr and PMQR genes, including qnrA, qnrB, qnrC, qnrS, aac(6')-Ib and qepA. PCR products for Smqnr and aac(6')-Ib were sequenced. For the S. maltophilia isolates containing Smqnr, pulsed-field gel electrophoresis (PFGE) was performed using XbaI. Resistance rates to ceftazidime, levofloxacin, trimethoprim-sulfamethoxazole, chloramphenicol and minocycline were 67.4%, 6.1%, 17.7%, 8.8% and 0%, respectively. The minimum inhibitory concentration required to inhibit the growth of 50% and 90% of organisms were 0.5 and 2 mg/L for moxifloxacin but 1 and 4 mg/L for levofloxacin, respectively. Smqnr was detected in 104 of the 181 S. maltophilia isolates (57.5%), and the most frequent was Smqnr6, followed by Smqnr8 and Smqnr11. Eleven novel variants from Smqnr48 to Smqnr58 were detected. The 24 Smqnr-containing S. maltophilia isolates were typed by PFGE and divided into 21 unique types. Nine S. maltophilia isolates (5.0%) carried aac(6')-Ib-cr. No qnr or qepA genes were detected. This study describes a high prevalence of Smqnr and novel variants of Smqnr among S. maltophilia from Japan. Continuous antimicrobial surveillance and further molecular epidemiological studies on quinolone resistance in S. maltophilia are needed.

[A 78-year-old woman who had an onset of seizure and right hemiparesis at the age 77].

We report a 78-year-old woman who had an onset of convulsion and right hemiparesis at the age 77. She had been well until October 28th of 1990 when she suddenly developed a seizure starting in her right face with secondary generalization. She was admitted to Saitama Kyodo Hospital where neurologic examination revealed confusion with slight right hemiparesis; deep reflexes were exaggerated on the right side; otherwise neurologic examination was unremarkable. Cranial CT scan revealed an iso-density mass in the left motor area with extensive edema extending into left anterior frontal as well as parietal regions; by contrast enhancement, a homogeneous enhancement of the tumor was noted. She was treated with glycerol and phenytoin, and she became alert two days after her admission. The diagnosis of metastatic brain tumor was entertained; extensive malignancy survey was performed, however, no primary tumor was found. As neurosurgical procedure was refused, she was discharged on December 16th of 1990. She noted worsening of her right hemiparesis in the end of February, 1991, and she was admitted again on March 18th of 1991. On neurologic examination, she was disoriented to time and place; she was apparently demented. Her right hemiparesis was more advanced and she was unable to walk. Her hospital course was complicated by disturbance of consciousness and pneumonia, and she died on August 22nd of 1991. The patient was discussed in a neurological CPC. Opinions were divided between meningioma and a metastatic brain tumor. Other possibilities raised included malignant lymphoma and glioblastoma multiforme. As edema was very extensive on CT, many participants thought that it might be a metastatic brain tumor.(ABSTRACT TRUNCATED AT 250 WORDS)