[A case of giant cell arteritis after prednisolone dose reduction during treatment of polymyalgia rheumatica].

Giant cell arteritis (GCA) is closely associated with polymyalgia rheumatica (PMR). We herein report an 82-year-old woman who developed GCA during PMR treatment. She initially presented with shoulder pain and was diagnosed with PMR based on elevated serum C-reactive protein (CRP) levels and bursitis detected in both shoulders on ultrasonography (US). Treatment was initiated with a daily dose of 15 mg prednisolone (PSL), which led to rapid symptom alleviation, and the dosage was tapered to 1 mg/day. One month later, she developed myalgia extending from the lumbar region to the thigh and tenderness in the left temporal region. However, no abnormalities in the temporal artery were observed on US. Although the PSL dose was increased to 2 mg for relapse of PMR, the symptoms did not improve. One week later, she developed occipital pain with an increased CRP level of 9 mg/dL. She was diagnosed with GCA based on the 1990 ACR Classification Criteria. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) detected anomalous accumulations in the bilateral superficial temporal and vertebral arteries, but not in the larger vessels. We therefore diagnosed her with cranial-type GCA. At this time point, we repeated US and found a halo sign in the temporal artery. Although epithelioid and giant cells were not observed in the temporal artery biopsy, vascular inflammatory findings such as disruption of the internal elastic lamina and chronic inflammatory cell infiltration were noted. Symptoms improved immediately and CRP levels decreased after the PSL dose was increased to 30 mg daily. To mitigate the risk of steroid-induced diabetes, tocilizumab was introduced, and gradual tapering of PSL was implemented. In conclusion, we encountered a case of GCA that developed after PSL reduction during the course of PMR. PET/CT confirmed intracranial artery inflammation and facilitated a definitive diagnosis. Although PET/CT cannot be routinely performed for diagnose in Japan, we consider it useful as an adjunctive diagnostic tool.

[A case of methotrexate-associated diffuse large B-cell lymphoma with splenial lesions of the corpus callosum on brain MRI after complete remission with chemotherapy].

An 86-year-old woman in a wheelchair was accompanied by her husband and son as she visited our outpatient clinic due to disturbed consciousness and fever. Twenty-seven years earlier, she had been diagnosed with rheumatoid arthritis and had been treated with methotrexate (MTX) and low-dose prednisolone (PSL). She stopped taking MTX four years previously when she was diagnosed with diffuse large B cell lymphoma of the paranasal sinus. Her lymphoma went into remission after six cycles of systemic immunochemotherapy. MRI after hospitalization revealed a lesion in the splenium of the corpus callosum that was hyperintense on diffusion-weighted imaging and which had low apparent diffusion coefficient values. An analysis of the cerebrospinal fluid revealed no atypical cells. The MRI findings were atypical, but her consciousness disturbance improved, leading to the diagnosis of mild encephalitis/encephalopathy with a reversible splenial lesion, which would be associated with a transient consciousness disturbance with a good course. However, her consciousness worsened over the next 3 weeks. One month later, a contrast-enhanced MRI showed an enlarged lesion in the callosum as well as new lesions, and the diagnosis of secondary CNS lymphoma was made. Brain biopsy is often not feasible. Less invasive and highly accurate diagnostic methods are needed, such as the identification of a spinal fluid tumor marker.

Eustachian tube involvement in a patient with relapsing polychondritis detected by magnetic resonance imaging: A case report.

BACKGROUND: Relapsing polychondritis (RP) is a rare inflammatory disease involving the systemic cartilage, such as the auricle, trachea, and bronchiole, among others. A patient with RP shows variable symptoms based on the involved cartilage. CASE SUMMARY: A 72-year-old Japanese woman with a history of redness of the bilateral auricles for 3 d was referred to a clinician. The clinician prescribed antibiotics to the patient; however, the symptoms worsened; thus, she was referred to our hospital. Head and neck magnetic resonance imaging (MRI) showed edematous auricle with remarkable contrast, fluid collection in the bilateral mastoid cells, suggesting otitis media. The eustachian tube (ET) on the right side was also edematous with contrast enhancement. The patient was suspected of RP according to the diagnostic criteria. A biopsy of the auricular cartilage was performed by an otorhinolaryngologist, confirming pathological proof of RP. Treatments with steroids were immediately administered thereafter. CONCLUSION: We highlight a rare case of RP with radiologically confirmed involvement of ET in the MRI.

COVID-19 survivors with calcineurin-inhibitors-treated rheumatoid arthritis.

We report two cases recovered from coronavirus disease 2019 with rheumatoid arthritis which had been in remission or low disease activity by taking calcineurin inhibitor (CNI). Both cases had moderate to severe pneumonia treated with intravenous dexamethasone or in the severe case remdesivir in addition to it. These cases suggest that the use of CNI may have affected the improvement of severe pneumonia.

[An elderly man presenting polyarthritis diagnosed as chronic tophaceous gout].

An 85-year-old man was admitted to our hospital for swollen and painful bilateral lower legs and a high fever. He was initially diagnosed with acute cellulitis and treated with antibiotics. Several days after the improvement of his swollen legs, he complained of both shoulder and arm pain. The laboratory data at this time were as follow: C-reactive protein 10.7 mg/dL, uric acid 8.7 mg/dL, and creatinine 1.07 mg/dL. Both rheumatoid factor and anti-CCP antibody were negative. Whole-body gallium scintigraphy showed a high pathological accumulation in both the shoulders and left wrist. As polymyalgia rheumatica was suspected, oral prednisolone (PSL) of 10 mg/day was started. The patient's shoulder pain improved and he was discharged. However, he was hospitalized twice in the next month because of left shoulder, left knee, right arm, and right wrist pain. During the third hospitalization, we found a subcutaneous nodule on right toe. Aspiration material from the nodule was a white paste, showing acicular crystals under the microscope. According to these findings, the nodule was diagnosed as a tophaceous nodule, and recurrent episodes of polyarthritis were diagnosed as chronic tophaceous gout. Low-dose PSL was continued and febuxostat was added. This patient had multiple risk factors for chronic tophaceous gout: obesity, a habit of drinking, diabetes mellitus, hyperlipidemia, congestive heart failure, and interruption of allopurinol treatment. We herein discuss the clinical course of the patient, the interruption of allopurinol treatment and polypharmacy in elderly patients.

Chylothorax in POEMS syndrome.

Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a multisystemic syndrome that is associated with plasma cell disorder. Pleural effusion is a common manifestation of POEMS syndrome, but the association of POEMS syndrome with chylothorax has not been reported. We report on a 61-year-old female patient who initially presented with dyspnea and bilateral leg edema. Importantly, the patient had normal renal function. Her chest X-ray and computed tomographic imaging showed bilateral pleural effusion, and her chest drainage revealed chylothorax. Detailed examination failed to reveal the definitive cause of the chylothorax. She received several treatments for chylothorax, namely, a low-fat diet or fasting, total parenteral nutrition, a somatostatin analog (octreotide), thoracic duct ligation by video-assisted thoracic surgery, and pleurodesis. However, further examination revealed endocrinopathy, monoclonal plasma cell disorder, peripheral neuropathy, and elevation of the serum level of vascular endothelial growth factor. The patient's condition was consequently diagnosed as POEMS syndrome. Eventually, her chylothorax was controlled by pleurodesis, and she was transferred to another hospital for stem cell transplantation. Herein, we report on the apparent first case of POEMS syndrome with chylothorax. In some cases of idiopathic chylothorax, the underlying primary disease may be latent, such as in the present patient. POEMS syndrome is rare, but this syndrome should be included in the differential diagnosis of chylothorax with unexplained etiology.

Associations between vascular calcification, arterial stiffness and bone mineral density in chronic hemodialysis patients.

AIM: The aim of our study was to examine the associations between vascular calcification, arterial stiffness and bone mineral density (BMD) in chronic hemodialysis (HD) patients. METHODS: The study subjects were 83 (70 men and 13 women) HD patients. All patients had computed tomography (CT) to determine aortic calcification index (ACI), pulse wave velocity (PWV) using a volume-plethysmographic apparatus, and BMD estimated by digital image processing (DIP). RESULTS: Patients, 84.3% male, 38.6% diabetic, had a mean age of 59.3 +/- 11.2 years. In univariate linear regression analysis, ACI correlated positively with age (r = 0.586, P < 0.0001), dialysis vintage (r = 0.47, P = 0.002), pulse pressure (r = 0.311, P = 0.004), C-reactive protein (CRP) (r = 0.226, P = 0.0397) and PWV (r = 0.422, P < 0.0001). There was no significant association between ACI and serum markers of mineral metabolism. There was also a positive association between PWV and systolic blood pressure (P = 0.0004) or pulse pressure (P < 0.0001), and a trend towards greater PWV with increasing age (r = 0.494). In multivariate regression analysis only increasing age, pulse pressure, serum levels of albumin and CRP were significantly associated with ACI and PWV. Mean BMD on DIP was 2.7 +/- 0.4 mmAL. ACI was inversely correlated with BMD (r = -0.234, P = 0.0331). CONCLUSIONS: Vascular calcification is closely associated with arterial stiffness in HD patients. BMD is inversely correlated with ACI, suggesting that measurement of hand BMD by DIP is a useful tool for assessment of renal bone disease in these patients.

[Liver involvement in primary Sjogren's syndrome].

PURPOSE: To determine the prevalence of liver involvement in patients with primary Sjogren's syndrome (SS) and to evaluate the association of this complication with other extra-glandular manifestations and serologic markers. METHODS: We examined 155 Japanese patients (150 women and 5 men, mean age 66.6 years) who met the European Epidemiology Center Criteria for primary SS. Liver involvement was considered present when abnormal liver function tests (AST, ALT, ALP, GTP, or bilirubin) were detected more than three times. RESULTS: 20 patients (13%) had liver involvement including 2% with clinically overt liver disease. The causes of liver involvement were primary biliary cirrhosis (PBC) 6, autoimmune hepatitis (AIH) 2, hepatitis C virus (HCV) infection 2, concurrence of AIH and HCV infection 1, fatty liver 1. In 8 patients, the cause remained unclear. Of 6 patients complicated with PBC, four patients had PBC-specific antimitochondrial antibodies (AMA). Liver dysfunction was transient in two patients. Hepatocelluar carcinoma developed in a patient whose liver involvement was due to AIH and HCV. Patients with liver involvement were more likely to have cutaneous and neurological manifestations, when compared to SS without liver involvement. A positive antinuclear antibody, rheumatoid factor, and anticentromere antibody were also associated with liver involvement. Other autoantibodies did not correlate with the prevalence of liver involvement. CONCLUSION: Although symptomatic liver involvement is rare in SS patients, asymptomatic liver involvement is common. Clinicians must be aware of the possibility of liver involvement so that it can be treated as soon as possible.

[Effect of pneumonia on clinical course and prognosis after hip fracture].

The records of 38 elderly patients with hip fracture admitted to our hospital between January and December 2002 were retrospectively reviewed to determine the incidence and outcomes of medical complications. The mean age was 84.5 +/- 6.83 years old, 32 women and 6 men. 27 patients (71%) suffered from dementia. Of the 38 patients, 33 (86.8%) had one and more underlying diseases: hypertension 29, cerebrovascular episode 7, congestive heart failure 5, diabetes mellitus 4, gastric ulcer or chronic gastritis 3, ischemic heart disease 4, depression 2. Three patients had a past history of hip fracture. Fourteen patients (37%) developed medical complications after hip fracture, most frequently pneumonia (64%). Other complications were dizziness, nausea, congestive heart failure, choledocholithiasis, and GI tract bleeding. Eight patients who suffered pneumonia cancelled elective surgery. Severity of pneumonia was mild in 2, moderate in 5, and severe in 2. Both cases with severe pneumonia died in hospital. Patients with pneumonia (pneumonia group) were significantly older and had more severe dementia than patients without pneumonia (non-pneumonia group). Although there were no significant differences in physical ability between the two groups before admission, physical ability on discharge was lower in the pneumonia group. The pneumonia group had a significantly longer mean hospital stay than the non-pneumonia group. Our results suggest that the prevention of pneumonia is necessary to improve the outcome of hip fracture.

[A case of non-specific interstitial pneumonia in patient with microscopic polyangiitis].

Non-specific interstitial pneumonia developed as an initial manifestation in a patient with microscopic polyangiitis. A 62-year-old man was admitted to our hospital in March 2001, because of fever and intermittent myalgia of lower extremities. Chest X-ray had revealed reticular shadows in the bilateral middle and lower lung fields since 1996. Just before admission, the patient had been diagnosed as having nonspecific interstitial pneumonia (NSIP) from the specimen obtained by video-assisted thoracoscopic surgery (VATS) in another hospital. Physical examination on admission revealed bilateral episcleritis. Laboratory data showed elevated levels of CRP and KL-6, polyclonal gammaglobulinemia, positive rheumatoid factor and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Sensory and motor nerve conducting velocities were delayed in left peroneal nerve, but not other nerves, suggesting mononeuropathy. Biopsied specimens of the left quadriceps revealed vasculitis of arteioles. In spite of positive proteinuria and hematuria, no pathological lesion was found in the kidney. From all of these findings, the patient was diagnosed as having microscopic polyangiitis (MPA) without renal involvement. Methylprednisolone pulse therapy followed by intravenous cyclophosphamide pulse therapy improved his clinical conditions such as pyrexia, cough, myalgia, episcleritis and respiratory symptoms with decreased titer of serum MPO-ANCA. Thereafter, the dose of prednisolone was successfully tapered to 10 mg/day without clinical relapse. In the present patient who developed demonstrated non-specific interstitial pneumonia as an initial manifestation of MPA, VATS provided useful diagnostic and prognostic information, leading to an appropriate therapeutic choice.

[Clinical assessment of microscopic polyangiitis in elderly patients].

OBJECTIVE: To evaluate the influence of the age at disease onset on the clinical symptoms, laboratory findings, treatment, and complications of microscopic polyangiitis (MPA). PATIENTS: From 1999 to 2001, we encountered 4 MPA patients with disease onset at age 65 or older (average 77.3, all were female: the elderly group). For comparison, 4 MPA patients with disease onset a 64 years or younger (average 44.7, two were male: the non-elderly group) were used. RESULTS: There was no statistically significant difference in clinical features between the two groups. All patients in the elderly group were referred to our hospital, because of fever of unknown origin or suspicion of connective tissue disease. The elderly group had a longer duration from the first admission to the start of treatment. Renal biopsies were done in all of the non-elderly group and one of the elderly group. The diagnosis of the other 3 patients of the elderly group was based on muscle or nerve biopsy, showing necrotizing vasculitis. At the time of diagnosis, antibodies to myeloperoidase (MPO-ANCA) were positive in 7 of 8 patients (87.5%). 2 patients of the non-elderly group were died of heart failure and hepatic failure by cyclophosphamide (CYC). The other 6 patients achieved substantial improvement. CONCLUSIONS: Muscle or nerve biopsy helped clinical management of elderly patients when renal biopsies could not be done. IVCY was relatively safe and effective treatment for MPA in elderly as well as non-elderly patients.

[Two cases of limited cutaneous nodular amyloidosis with primary Sjögren's syndrome].

We described two female patients with primary Sjögren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sjögren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sjögren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sjögren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.

Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM.

RanBPM is a RanGTP-binding protein required for correct nucleation of microtubules. To characterize the mechanism, we searched for RanBPM-binding proteins by using a yeast two-hybrid method and isolated a cDNA encoding the ubiquitin-specific protease USP11. The full-length cDNA of USP11 was cloned from a Jurkat cell library. Sequencing revealed that USP11 possesses Cys box, His box, Asp and KRF domains, which are highly conserved in many ubiquitin-specific proteases. By immunoblotting using HeLa cells, we concluded that 921-residue version of USP11 was the predominant form, and USP11 may be a ubiquitous protein in various human tissues. By immunofluorescence assay, USP11 primarily was localized in the nucleus of non-dividing cells, suggesting an association between USP11 and RanBPM in the nucleus. Furthermore, the association between USP11 and RanBPM in vivo was confirmed not only by yeast two-hybrid assay but also by co-immunoprecipitation assays using exogenously expressed USP11 and RanBPM. We next revealed proteasome-dependent degradation of RanBPM by pulse-chase analysis using proteasome inhibitors. In fact, ubiquitinated RanBPM was detected by both in vivo and in vitro ubiquitination assays. Finally, ubiquitin conjugation to RanBPM was inhibited in a dose-dependent manner by the addition of recombinant USP11. We conclude that RanBPM was the enzymic substrate for USP11 and was deubiquitinated specifically.

An autopsy case of intravascular lymphomatosis with dermatomyositis.

A 62-year-old man was admitted to hospital with general malaise, arthralgia, edema, and high-grade fever. He was diagnosed as dermatomyositis because of typical skin rashes and muscle weakness. His symptoms were improved by high-doses of prednisolone and cyclosporin A, with the exception of the skin rash over the back. High-grade fever developed again when tapering prednisolone. His condition deteriorated gradually. Paresthesia, hypothyroidism, metabolic acidosis, and disseminated intravascular coagulopathy occurred, and he died eight months after the first admission. Postmortem examination revealed intravascular proliferation of atypical mononuclear cells in the lumens of small vessels in all organs. Intravascular lymphomatosis (B cell type) was diagnosed.

[Case of eosinophilic fasciitis with change of serum Th 1/Th 2 cytokine level which correlated with disease activity].

A 25-year-old female who had right knee and ankle joint swelling with arthralgia in July 1999, was diagnosed as having eosinophilic fasciitis (EF) based on typical skin sign and the result of muscle biopsy. Treatment was started with 20 mg of oral prednisolone per day. Her symptoms had subsided but they later recurred as the prednisolone dose was gradually tapered. We measured her serum cytokine levels during the course. Her serum IFN-gamma increased and IL-4 decreased after the treatment compared with those levels prior to treatment. And the cytokine levels reverted to pre-treatment status when she had a relapse. The cytokine balance seems to play some role in the etiology of EF.

[Patient with intravascular lymphomatosis: Changes with time in concentrations of serum cytokines].

Serum cytokines were evaluated in a patient with intravascular lymphomatosis (IVL). A 62-year-old man was admitted to our hospital for his general malaise, arthralgia, and high-grade fever. He was diagnosed as dermatomyositis, initially. His symptoms were improved by high dose of corticosteroid and immunosuppressive therapy. However his condition deteriorated gradually, and died ten months after the onset of symptoms. Postmortem examination revealed IVL (B cell type). The serum concentrations of inflammatory cytokines, IL-6 and TNF-alpha, were elevated. Level of serum IFN-y was high only at the end of his illness. Serum IL-2 was not detected during the course. Serum IL-4 was slightly elevated. Elevated CRP and hypoalbuminemia might be related to the elevation of these inflammatory cytokines. The clinical diagnosis of IVL is usually difficult because of the absence of specific clinical manifestations and laboratory findings. The time course and/or concentrations of serum cytokines could be a key to make an early diagnosis.