Relapsing polychondritis coupling with cerebral amyloid deposit inducing cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Almost no abnormality including intracranial microbleeding was detected by cranial magnetic resonance image (MRI) at diagnosis. However, he developed a headache and hallucination after five months. Seven-month cranial MRI showed novel, multiple, intracranial microbleeding, especially in the bilateral but asymmetry posterior, temporal, and parietal lobes. 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow in the bilateral posterior lobes. After treatment, both of his neurological symptoms and increased cerebral blood flow improved to mild. Photon emission computed tomography using Pittsburgh compound B (PiB) for evaluation of brain amyloidosis at 12 months after onset showed an amyloid deposit in the bilateral frontal lobes, but a lack of uptake corresponded to the RP lesions. Our case suggests that inflammation coupled with an amyloid deposit, induced the multiple intracranial bleeding, and resulted in the lack of PiB uptake. Findings from our case show that inflammation including excess blood flow coupled with an amyloid deposit synergistically facilitate intracranial bleeding.

Difference in relapse-rate and clinical phenotype by autoantibody-subtype in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: To correlate the serotype specificity to myeloperoxidase (MPO) and proteinase-3 (PR3) with clinical characteristics in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Clinical characteristics and outcomes of patients with AAV in our division from 2005 to 2014 were retrospectively compared on the basis of ANCA subtype. RESULTS: We collected the data from 88 patients with MPO-ANCA vasculitis, and 17 with PR3-ANCA vasculitis. Patients with PR3-ANCA vasculitis were younger, and had higher involvement-rates in the eye, nose, and ear. In both MPO- and PR3-ANCA vasculitis, the most frequently involved organ was the respiratory system. Interstitial pneumonia was more frequent in MPO-ANCA vasculitis (52.3% versus 5.9%, p < 0.01), whereas nodular shadow was more frequent in PR3-ANCA vasculitis (9.1% versus 58.8%, p < 0.01). Multivariable Cox proportional hazard regression analysis showed that the hazard ratio of PR3-ANCA for relapse was 2.48 (95% confidence interval 1.14-5.42, p = 0.02). There was no difference in the survival and the progression to end-stage kidney disease and respiratory failure between the two vasculitides. CONCLUSION: MPO-ANCA vasculitis was a predominant form of AAV in Japan. Classification based on ANCA subtype would be clinically relevant in the prediction of organ involvement and relapse.

Prediction of the therapeutic response to methotrexate at 24 weeks by methotrexate-polyglutamates concentration in erythrocytes at 8 weeks in patients with rheumatoid arthritis.

OBJECTIVES: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate-polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy. METHODS: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naïve patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (ΔDAS28CRP). RESULTS: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1-5 were higher in patients with ΔDAS28CRP >1.2 than in those with ≤1.2. The cutoff value of MTX-PG1-5 to discriminate ΔDAS28CRP >1.2 from ≤1.2 at 24 weeks was 68.7 nM. Among 20 patients with MTX-PG1-5 > 50.6 nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p < 0.001). On the contrary, among the nine patients with MTX-PG1-5 ≤ 50.6 nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p = 0.500). CONCLUSIONS: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.

Risk factors correlated with immunosuppressant discontinuation in antineutrophil cytoplasmic antibody-associated vasculitis patients.

AIM: The use of an immunosuppressant is recommended as a treatment for remission induction in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the immunosuppressant is sometimes discontinued due to an adverse event. We sought to identify the cause and risk factors for immunosuppressant discontinuation in patients with AAV receiving remission induction treatment. METHODS: We retrospectively analyzed the cases of AAV patients treated in 2005-2016 with immunosuppressants to induce remission. We defined "discontinuation" as stopping, switching, or delaying immunosuppressant administration due to adverse events. We performed a multivariate analysis to identify risk factors for immunosuppressant discontinuation. RESULTS: We identified 50 patients treated with an immunosuppressant for remission induction: cyclophosphamide was used in 45 patients (90%), methotrexate in 4 (8%), and cyclosporine A in 1 patient (2%). Among them, 26 patients (52%) underwent discontinuation of the immunosuppressant. Infection and myelosuppression were the major causes of discontinuation. Multivariate Cox proportional hazards regression analysis revealed that a cumulative dose of prednisolone ≥ 2000 mg (hazard ratio [HR] =2.18, 95% confidence interval [CI] =1.37-3.70, P < .001), performance status of 3-4 (HR = 1.80, 95% CI = 1.07-3.03, P = .027), and oral cyclophosphamide (HR = 1.81, 95% CI = 1.11-2.97, P = .018) were independent risk factors correlated with immunosuppressant discontinuation. CONCLUSION: Physicians should be aware of risk factors predicting immunosuppressant discontinuation when treating AAV patients with an immunosuppressant.

Simultaneous Oculomotor and Facial Nerve Palsies in a Patient with Systemic Lupus Erythematosus and Sjögren's Syndrome.

A 70-year-old man with systemic lupus erythematosus (SLE) presented with simultaneous right oculomotor nerve palsy and right facial nerve palsy. Brain magnetic resonance imaging and cerebrospinal fluid analysis revealed no abnormality. Coexistent Sjögren's syndrome was diagnosed on the basis of anti-SS-A antibody positivity, salivary gland scintigraphy, and histological findings on minor salivary gland biopsy. As there was no obvious cause of multiple cranial neuropathies, we supposed that the palsies were induced by either of the underlying diseases. The patient was treated with a high-dose of prednisolone and intravenous cyclophosphamide, and both palsies recovered almost completely within two weeks.

Multicentric Reticulohistiocytosis with Dermatomyositis-like Eruptions.

A 68-year-old man presented with polyarthritis, proximal muscle weakness, and erythema of the face, arms, neck, and anterior chest that resembled the V-neck sign. Initially, dermatomyositis (DM) was considered because of the erythema, polyarthritis, and muscle weakness. He also had mediastinal and hilar lymphadenopathy on contrast-enhanced computed tomography. Unexpectedly, a biopsy of the forehead skin revealed numerous multinucleated giant cells. A biopsy of a solitary nodule on the dorsum of his right middle finger revealed similar multinucleated giant cells with ground-glass cytoplasm, leading to the diagnosis of multicentric reticulohistiocytosis (MRH). Although MRH is rare, it should be remembered that MRH can mimic DM.

Foot ulcers caused by rheumatoid vasculitis in a patient with rheumatoid arthritis undergoing etanercept treatment.

A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented with chronic ulcers on both feet while undergoing treatment with etanercept. Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor (TNF) agents are known to induce vasculitis, vasculitis can also be caused by active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF therapy must be evaluated carefully.