Development of interstitial pneumonia in a patient with rheumatoid arthritis induced by isoniazid for tuberculosis chemoprophylaxis.

Here, we report a 56-year-old patient with rheumatoid arthritis (RA) who had been treated with methotrexate and sulfuasalazine, but the disease activity remained high. Therefore, we planned TNF-blocker treatment for this patient. A tuberculin skin test was positive, we started anti-tuberculosis (TB) chemoprophylaxis with isoniazid (INH). However, liver dysfunction was appeared after 2 weeks from the start of INH. Therefore, we discontinued INH transiently and tried the desensitization of INH. However, interstitial pneumonia was developed 2 weeks after the re-start of INH, we decided to stop the INH prophylaxis. Interstitial pneumonia was improved by corticosteroid treatments. This case report shows that INH-induced IP can be occurred during the course of anti-TB chemoprophylaxis in patients with RA.

Serum levels of BAFF for assessing the disease activity of Takayasu arteritis.

OBJECTIVES: Takayasu arteritis (TA) is a chronic vasculitis that affects large elastic arteries. Monitoring of disease activity is crucial because the disease may progress despite treatment with glucocorticoids. Elevated levels of B cell activating factor belonging to TNF family (BAFF) have been observed in patients with autoimmune diseases. In this study, we investigated whether dysregulation of BAFF occurs in TA. METHODS: Serum levels of BAFF were measured in sera from 9 patients with TA including 6 patients with follow up after induction therapy. RESULTS: Circulating BAFF levels in TA patients were higher than in those in healthy subjects. The high levels of BAFF in active TA patients were decreased when the patients entered remission. CONCLUSIONS: To our knowledge, this is the first study to show elevated levels of BAFF in active TA patients. These findings suggest that this cytokine contributes to vasculitis in TA and raise the possibility that monitoring of serum BAFF might aid clinicians in making adequate treatment adjustments in TA patients.

Macrophagic myofascitis associated with rheumatoid arthritis.

Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremities. Magnetic resonance imaging showed evidence of myofascitis involving fascias of anterior tibialis muscle. Muscle biopsy showed a unique pathological pattern of MMF. MMF is known to be associated with vaccination containing aluminum. However, our case was not related to aluminum containing vaccinations and etiologies are unknown. The possible link needs to be discussed.

Serum amyloid A is a useful marker to evaluate the disease activity of Takayasu's arteritis.

Takayasu's arteritis (TA) is a rare large vessel vasculitis that is difficult to diagnose in the early stages. Therefore, it is also very difficult to manage and prevent irreversible vascular damage in TA. A 19-year-old female patient with back pain was examined using [(18)F]-FDG-PET to detect the source of inflammation. Specific accumulation of [(18)F]-FDG was observed in the thoracic and abdominal aorta, leading to the diagnosis of TA. Corticosteroid treatment resulted in clinical remission. However, the serum amyloid A (SAA) levels remained elevated. A follow-up scan showed residual uptake of [(18)F]-FDG in the thoracic aorta suggesting subclinical vascular inflammation. Methotrexate was combined with the corticosteroid, and the elevated levels of SAA became normalized. The present case suggests that monitoring serum levels of SAA and [(18)F]-FDG-PET could help clinicians to make adequate treatment adjustments in TA patients.

Successful treatment of refractory cardiac tamponade due to rheumatoid arthritis using pericardial drainage.

Rheumatoid pericarditis occurs in patients with rheumatoid arthritis (RA). However, cardiac tamponade due to rheumatoid pericarditis is rare; we describe a case of a 72-year-old man with a 6-year history of rheumatoid arthritis who developed rheumatoid pericarditis with recurrent cardiac tamponade. The patient experienced relapse of the cardiac tamponade despite treatment with pericardiocentesis. Therefore, the patient underwent surgical pericardial drainage. The patient was also subsequently treated with increasing doses of corticosteroid, methotrexate and leukocytapheresis. These treatments resulted in a successful outcome without any complication. This case suggests that in addition to immunosuppressive therapy, pericardial drainage should be considered in the treatment of life-threatening refractory cardiac tamponade caused by rheumatoid arthritis.

Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes.

OBJECTIVE: Although serum amyloid A (SAA) has been used as a marker of inflammation, its role in leucocyte recruitment and angiogenesis has not been well established in RA. CCL20 is a chemokine involved in the migration of CCR6-expressing Th17 cells. To study the contribution of SAA to the recruitment of Th17 cells, we investigated the effects of SAA on CCL20 production by RA synoviotytes. METHODS: Synoviocytes isolated from RA patients were stimulated with recombinant SAA and cellular supernatants were analysed by CCL20-specific ELISA. CCL-20 mRNA expression was analysed by RT-PCR. RESULTS: SAA is a most potent inducer of CCL20 secretion in RA synoviocytes compared with other inflammatory cytokines (IL-1beta, TNF-alpha and IL-17A). SAA stimulation induced CCL20 mRNA expression in RA synoviocytes, which was not affected by polymyxin B pre-treatment. SAA-induced CCL20 production was down-regulated by NF-kappaB inhibition and partially by c-jun N-terminal kinase (JNK) inhibition. SAA-induced CCL20 production was also suppressed by dexamethasone or FK506. CONCLUSION: These findings suggest that SAA may be implicated in the recruitment of lymphocytes, including CCR6-expressing Th17 cells, in RA synovium by up-regulating CCL20 production in synoviocytes.

Reactive arthritis which occurred one year after acute chlamydial urethritis.

A 30-year-old Japanese man developed dactylitis with sausage-like fingers in addition to balanitis and stomatitis. One year prior to these symptoms, acute chlamydial urethritis had been successfully treated by levofloxacin. On admission, Chlamydia trachomatis DNA was not detected in the urine sediment by PCR method, however, he was diagnosed to have reactive arthritis based on the clinical findings of asymmetric dactylitis, circinate balanitis, stomatitis and positivity for HLA B27 antigen. He was treated with methotrexate and his arthritis improved. The past chlamydial infection may have been involved in the pathogenesis of reactive arthritis in this patient.

Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes.

In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-kappaB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-kappaB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.

Acute hepatitis in a patient with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a hereditary syndrome characterized by recurrent episodes of fever and serositis. In this report, we describe a Japanese patient with FMF and Sjögren's syndrome, in whom acute elevations of transaminase occurred. The histological findings from the liver biopsy specimens demonstrated a nonspecific hepatitis, with liver cell necrosis and interlobular inflammatory cell invasion, without the presence of interface hepatitis or bile duct injury. This case underscores the possibility that MEFV mutations contribute to hepatic inflammation, as seen in this case, by way of an alteration of the pyrin function.

Acute dissecting thoracic aortic aneurysm in a patient with polymyalgia rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related disorders found in older patients, and vasculitis has been proposed as a part of the pathogenesis of PMR. We describe a female patient with PMR plus aortitis, both of which were well controlled on maintenance steroid therapy. Six months after the onset of her condition, however, she suddenly presented with chest pain. A diagnosis of dissecting aortic aneurysm was confirmed, and the aorta was successfully resected. Histology revealed infiltration of mononuclear cells including giant cells around the vaso vasorum with disruption of elastic lamina of the resected aorta. PMR or GCA may indicate an increased risk for aortic dissection in patients with normal erythrocyte sedimentation rate or C-reactive protein, and prompt recognition and therapy, not only during the active disease but also after symptoms of PMR have resolved, are needed.

Multicentric reticulohistiocytosis associated with ovarian cancer.

Multicentric reticulohistiocytosis (MR) is an uncommon disease characterized by joint and cutaneous manifestations. The diagnosis must be confirmed by histological evidence of typical histiocytes and multinucleated giant cells. Many conditions, including malignancy, have been described in association with MR. We herein report a female case of MR in whom partial improvement was obtained by steroid and low-dose methotrexate treatments. However, ovarian cancer was found and therefore a surgical resection and chemotherapy were performed. These treatments resulted in the complete resolution of the skin and joint symptoms. These findings support the close linkage between MR and malignancy and the efficacy of cytotoxic drugs for the treatment of MR.

Toll-like receptor expression in lupus peripheral blood mononuclear cells.

OBJECTIVE: To investigate expression of members of the Toll-like receptor (TLR) family in peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). METHODS: We analyzed PBMC from 14 patients with SLE and 15 healthy subjects. The surface expressions of TLR2 and TLR4 and intracellular expression of TLR9 on PBMC were analyzed by flow cytometry. RESULTS: Although TLR4 expressions on CD14+ monocytes were not significantly different between healthy subjects and patients with SLE, TLR2 expressions on monocytes were reduced in patients with SLE compared to healthy subjects. Intracellular TLR9 expression levels of CD19+ B lymphocytes were significantly elevated in patients with SLE. However, the TLR9 expression levels of plasmacytoid dendritic cells were not significantly different between these patients and healthy subjects. CONCLUSION: Our results show that human peripheral blood B cells express TLR9 and that its expression is increased in patients with SLE. This upregulated expression of TLR9 in B cells may be related to the abnormal B cell hyperactivity in patients with SLE.

Relationship between serum resistin concentrations and inflammatory markers in patients with type 2 diabetes mellitus.

To examine whether serum resistin concentrations are associated with metabolic or inflammatory markers in patients with type 2 diabetes mellitus, we examined serum concentrations levels and metabolic or inflammatory markers in 56 patients with type 2 diabetes mellitus and 41 healthy subjects. Serum levels of resistin, serum amyloid A, and soluble vascular cell adhesion molecule-1 were measured by enzyme-linked immunosorbent assay. Serum resistin levels were significantly elevated in diabetic patients compared with those in healthy subjects. Serum resistin concentrations did not correlate with body mass index; however, there was a significant positive correlation between resistin and soluble vascular cell adhesion molecule-1 in diabetic patients. Based on the present results, we conclude that resistin appears to be associated with vascular inflammatory markers in patients with type 2 diabetes mellitus.

HLA-DRB1*04 alleles in Japanese rheumatoid arthritis patients with AA amyloidosis.

OBJECTIVE: To compare the HLA-DRB1 shared epitope (SE) alleles in Japanese patients with rheumatoid arthritis (RA) and amyloid A (AA) amyloidosis versus those without AA amyloidosis. METHODS: The HLA-DRB1 alleles were genotyped for 91 RA patients without AA amyloidosis, 33 RA patients with AA amyloidosis, and 63 control subjects. HLA-DRB1 typing was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization method. RESULTS: Although a significant difference was not observed, the frequency of SE genotype was higher in RA patients with AA amyloidosis than in those without AA amyloidosis. All SE-positive RA patients with AA amyloidosis had *04 alleles (*0401, *0405, *0410), and a significant association of the presence of a double dose of *04 SE alleles with AA amyloidosis (OR 4.0, 95% CI 1.91-13.99) was observed. CONCLUSION: Our data suggest that presence of double *04 SE is associated with a higher risk of developing AA amyloidosis in Japanese patients with RA.

Idiopathic portal hypertension associated with systemic sclerosis and Sjögren's syndrome.

We report a patient with idiopathic portal hypertension (IPH) associated with systemic sclerosis (SSc) and Sjögren's syndrome. A 72-year-old Japanese woman was admitted to our hospital because of Raynaud's phenomenon, sclerodactyly, and dyspnea. The patient had splenomegaly, esophageal varices in the absence of extrahepatic portal obstruction, and cirrhosis of the liver. Immunological studies revealed positive anti-nuclear antibodies and high titers of anti-Scl-70, anti-SS-A, anti-centromere, and anti-mitochondrial M2 antibodies. Histological examinations of the liver biopsy specimen revealed stenosis and loss of small portal veins without findings of primary biliary cirrhosis. The patient was diagnosed as having IPH associated with SSc and Sjögren's syndrome. These observations suggest an immunological role in the pathogenesis of IPH.

FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by interleukin-1beta in rheumatoid synovial fibroblasts.

The aim of this study was to determine whether FK506, which has been shown to be effective for the treatment of refractory RA, affects the synthesis of matrix metalloproteinases (MMPs) in rheumatoid synovial fibroblasts. Synovial fibroblasts isolated from rheumatoid synovium were incubated in 6-well culture plates for 24 h with FK506 and interleukin-1beta, alone and in combination. Samples of supernatants were assayed by ELISA or immunoblottings using anti-MMP-13 specific antibodies. In addition, synovial fibroblasts pretreated with FK506 were stimulated with IL-1beta for 10 min and cellular lysates were subjected to anti-phospho-specific mitogen-activated protein kinase (MAPK). Unstimulated synovial fibroblasts produced low levels of MMP-3 and 13. IL-1beta-induced substantial output of these MMPs into cell supernatants. FK506 had no detectable effects on IL-1beta-induced MMP-2 induction. FK506, however, significantly suppressed MMP-13 production from IL-1beta-stimulated synovial fibroblasts. FK506 also prevented IL-1beta-stimulated JNK activation and transcriptional activation of AP-1 in these cells. Our results indicate that FK506 is capable of regulating MMP-13 synthesis via JNK pathway in rheumatoid synonvium.