Clinicopathological features of graft versus host disease-associated myositis.

BACKGROUND AND OBJECTIVE: Chronic graft versus host disease (GVHD)-associated myositis targeting skeletal muscle is a relatively rare but potentially debilitating complication following allogeneic hematopoietic stem cell transplantation (HSCT). We reviewed the clinicopathological features of GVHD-associated myositis among patients receiving allogeneic HSCT to elucidate the cellular pathogenesis. METHODS: We retrospectively reviewed clinical data and muscle biopsy results from 17 consecutive patients diagnosed with GVHD-associated myositis at our institution between 1995 and 2019. Immunostaining findings of GVHD-associated myositis were compared to those of patients with anti-tRNA-synthetase antibody-associated myopathy (ASM) (n = 13) and dermatomyositis (DM) (n = 12). RESULTS: The majority of patients with GVHD-associated myositis showed subacute or chronic progression of mild to moderate limb weakness together with elevated serum creatine kinase. These patients also exhibited mild C-reactive protein elevation but were negative for myositis-related autoantibodies. Programmed death-1 (PD-1)-positive cells were observed in muscle interstitium adjacent to myofibers expressing human leukocyte antigen (HLA)-DR. The interstitium was also HLA-DR-positive, similar to biopsy samples from ASM patients but not DM patients. The proportions of HLA-DR-positive muscle fibers and PD-1-positive interstitial cells were significantly higher in GVHD and ASM samples than DM samples. The PD-1-positive cells were mostly CD-8-positive lymphocytes. DISCUSSION: GVHD-associated myositis is characterized by HLA-DR-positive myofibers and infiltration of PD-1-positive lymphocytes. These features distinguish GVHD-associated myositis from DM but not from ASM.

[A case of anti-acetylcholine receptor antibody-positive ocular myasthenia gravis with anti-titin antibody and anti-Kv1.4 antibody positive inflammatory myopathy].

An 84-year-old man was diagnosed with anti-acetylcholine receptor (AChR) antibody-positive ocular myasthenia gravis (OMG) at the age of 77 and received treatment. The patient was referred to our department with swelling and pain in his right upper arm, which had spread to other limbs. His serum anti-AChR antibody and creatine kinase levels were elevated, and MRI of the limbs displayed signal changes suggesting inflammation in the several muscles. Despite showing no sign of thymoma, he was positive for serum anti-titin and anti-Kv1.4 antibodies. We performed a muscle biopsy, which led to a diagnosis of inflammatory myopathy (IM). IM associated with OMG is relatively mild. Age-related immune dysregulation may cause both OMG and IM. Evaluation of disease activity with serum anti-AChR antibody levels, and assessment of prognosis with examining anti-striational antibodies are necessary for appropriate management of IM associated with MG.

Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.

OBJECTIVE: Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses. METHODS: In this retrospective observational study, we analyzed biopsied muscle samples from 14 sIBM patients and six non-diseased subjects to identify metabolic profiles. Frozen muscle samples were used to measure metabolites with cation and anion modes of capillary electrophoresis time of flight mass spectrometry. We validated the metabolic pathway altered in muscles of sIBM patients through RNA sequencing and histopathological studies. RESULTS: A total of 198 metabolites were identified. Metabolomic and transcriptomic analyses identified specific metabolite changes in sIBM muscle samples. The pathways of histamine biosynthesis and certain glycosaminoglycan biosynthesis were upregulated in sIBM patients, whereas those of carnitine metabolism and creatine metabolism were downregulated. Histopathological examination showed infiltration of mast cells and deposition of chondroitin sulfate in skeletal muscle samples, supporting the results of metabolomic and transcriptomic analyses. INTERPRETATION: We identified alterations of several metabolic pathways in muscle samples of sIBM patients. These results suggest that mast cells, chondroitin sulfate biosynthesis, carnitine, and creatine play roles in sIBM pathophysiology.

Clinical implication of denervation in sporadic inclusion body myositis.

INTRODUCTION: Sporadic inclusion body myositis (sIBM) is often accompanied by signs suggestive of denervation on electromyography (EMG), which mimics neurogenic disorders. Hence, the current study aimed to assess reinnervation after denervation in sIBM and its clinical impllcation. METHODS: We retrospectively examined consecutive muscle biopsy specimens collected from 109 sIBM patients who were referred to our institution for diagnostic muscle biopsy from 2001 to 2018. Reinnervation after denervation in sIBM patients was assessed via muscle biopsy and EMG. The levels of acetylcholine receptor subunit γ (Chrng) and muscle-specific kinase (MuSK) mRNA, which are markers of denervation, were examined using real-time polymerase chain reaction. Response to treatment was defined as an increase of grade 1 or higher in two or more muscle groups as assessed using the Medical Research Council scale. RESULTS: In total, 93 (85.3%) of 109 sIBM patients had reinnervation after denervation on histological examination and/or EMG. The mean disease duration before biopsy was significantly longer in patients with reinnervation after denervation than in those without (p < 0.00001). Patients with denervation had significantly higher levels of Chrng and MuSK mRNA than those without. The proportion of patients who responded to immunosuppressive therapies was smaller in the patients with denervation than those without (p < 0.05). However, there was no significant difference regarding time from onset to using a walking aid between the two groups. DISCUSSION: Reinnervation after denervation is associated with disease duration and short-term response to therapy in individuals with sIBM.

Hereditary Angioedema Type 1 with Recurrent Dizziness.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient's hands and fingers appeared mild. Laboratory examinations revealed a low C4 and C1 inhibitor (INH) activity. A direct sequencing analysis of C1INH revealed a pathogenic gene mutation. Based on these results, she was diagnosed with hereditary angioedema (HAE) type 1. These findings indicate that HAE can cause recurrent dizziness, and it should therefore be included in the differential diagnosis in patients with recurrent neurologic symptoms, even in the absence of severe edema.

Effectiveness of levodopa treatment for diabetic chorea with reduced striatal accumulation in dopamine transporter SPECT: a case report.

We report the case of a 77-year-old woman with diabetic chorea, which presented as hemiballism of the right limbs. Initial blood examination revealed that sugar and hemoglobin A1c levels were 732 mg/dl and 12.2%, respectively. Thus, a diagnosis of hyperglycemic hyperosmolar syndrome was made at a previous hospital. Ballism of the right limbs developed after 10 days and progressively worsened. After a month, the patient was admitted to our hospital. Brain MRI (axial T1-weighted imaging) revealed a high-signal-intensity area in the left striatum. Dopamine transporter SPECT demonstrated reduced 123I-ioflupane binding in the bilateral striatum with left side predominance. Although haloperidol and risperidone were ineffective for her involuntary movement, chlorpromazine had a little effect. Levodopa and gabapentin combination treatments were effective in decreasing the symptoms. It was considered that dopamine antagonist was the medical treatment for diabetic chorea and that levodopa could worsen neurological symptoms such as chorea-ballism. However, in our case, levodopa treatment was effective.