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Systemic lupus erythematosus (SLE) is frequently accompanied by gastrointestinal symptoms. Although all parts of the gastrointestinal tract may be affected, colonic involvement is quite rare. Colonic ulceration, particularly in the rectum, is associated with a high mortality rate in patients with SLE, despite immunosuppressive therapy. While a standard regimen for treating rectal ulcers as a complication of SLE has not been established, combination therapy with steroids and immunosuppressive agents is necessary because of the associated high mortality rate. In this report, we describe a patient with SLE whose condition was complicated with ulcerative lesions in the rectum and sigmoid colon; the lesions were successfully treated with a combination of corticosteroids and tacrolimus therapy. Tacrolimus could be a useful additional or alternative modality for treating rectal involvement in SLE.

A 59-year-old woman was referred to our hospital because of severe anemia and leucopenia. Although she developed mild arthralgia without the typical symptoms of systemic lupus erythematosus (SLE), positivity for anti-Sm antibodies led us to a diagnosis of late-onset SLE. Autoimmune hemolytic anemia (AIHA) and suppression of reticulocyte production were considered to have been involved in the etiology of severe anemia. Administration of oral prednisolone (PSL) resulted in a marked improvement of the hematological abnormalities. As late-onset SLE is rare and patients tend to show the typical symptoms less frequently, close attention should be focused on latent symptoms and immunological findings.

Supplemental Digital Content is available in the text, To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice. We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (

The case of an 18-year-old Japanese man with systemic lupus erythematosus (SLE) complicated by alveolar hemorrhage is described. The patient presented with fever, butterfly rash, and polyarthralgia, and was diagnosed with SLE. He suddenly developed alveolar hemorrhage during steroid pulse therapy. Treatment with plasmapheresis was initiated, with prompt clearing of the chest radiograph. This experience suggests that the prompt initiation of plasmapheresis should be considered for SLE patients with life-threating alveolar hemorrhage resistant to conventional immunosuppressive therapies.

SUMMARY COX plays an important role in inflammatory diseases such as rheumatoid arthritis. To determine the role of COX in Sjögren's syndrome (SS), we examined COX expression in the salivary glands of SS patients. We examined 15 patients with SS and two normal subjects. Labial salivary gland tissue samples were analysed immunohistochemically using anti-COX-1 and COX-2 antibodies. All biopsy samples from 15 patients with SS were stained for COX-1. In contrast, COX-1 immunostaining was not detected in normal salivary gland tissues. Co-expression of COX-1 and CD68 was confirmed by mirror section technique and double antibody immunostaining. This finding indicated that COX-1-expressing cells in SS salivary glands were infiltrating macrophages. In contrast to COX-1 staining, only a little COX-2 immunostaining was observed in salivary gland tissues from SS patients. These data suggest that COX-1 expression on infiltrating macrophages may contribute to the inflammatory process of salivary glands in SS.

Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.

We describe a 48-year-old woman with dermatomyositis complicated with interstitial pneumonia. The pulmonary lesion was refractory; however, several therapeutic regimens such as steriod pulse therapy or gamma globulin and cyclophosphamide, resolved the situation. Later she developed multiple brain abscesses thought to be responsible for immune depression; prolonged antimycotic therapy brought dramatic improvement. Brain abscess is a rare complication in such immuno-compromised cases; attention should be given to the possibility of deep mycosis, especially brain abscess.

Pulmonary vascular involvement in Behcet’s disease is a rare complication with a poor prognosis. We present an autopsy case of vasculo-Behcet’s disease complicated by pulmonary hemorrhage, possibly caused by rupture of pulmonary artery aneurysms. The patient was treated with a combination of high-dose steroids and pulse cyclophosphamide, but he died from massive hemoptysis. This case highlights the need for potent new therapies for patients with vasculo-Behcet’s disease refractory to conventional immunosuppressive therapy, such as a combination of steroids and cyclophosphamide.

We report the case of a patient with rheumatoid arthritis (RA) who showed a reduction in disease severity (from class IV to class II) after multi-joint surgery. The patient was a 61-year-old man with a history of RA, type-2 diabetes, chronic obstructive pulmonary disease, and nephrotic syndrome. He had been undergoing treatment for RA for the past 10 years, but his condition could not be appropriately controlled. In addition to generalized edema, marked destruction of the left elbow joint and knees was observed, and he was unable to move in bed (Steinbrocker classification: stage IV, class IV). In March 2009, he developed suppurative arthritis of the left elbow (methicillin-sensitive Staphylococcus aureus [MSSA] infection) and was referred to our institution, where the infection subsided after cleaning of the wound and administration of antibiotics. In March 2010, he underwent artificial joint replacement arthroplasty of the left elbow, followed by replacement arthroplasty of the right knee in July that year and of the left knee in November. As of December 2011, the patient showed no signs of inflammatory reactions and was able to walk using crutches (Steinbrocker classification: stage IV, class II). Recent advancements in pharmacotherapy have made it possible to control the advancement of joint destruction in RA. However, in this patient, because of the advanced stage of joint destruction, surgical methods were required to aid the patient in recovering his ability to walk.

Although utility of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been rehearsed in large vessel vasculitides, it is not known if small vessel vasculitides are also associated with increased FDG uptake. Hereby described is a 64-year-old female patient with prolonged fever and splenomegaly, which was depicted as a hot area in FDG-PET. Splenectomy disclosed microaneurysms, giant cell granuloma, perivascular leukocytic infiltration with fibrinoid necrosis, consistent with granulomatous angitis. Serum myeloperoxidase-antineutrophil cytoplasmic antibody was positive. The present case illustrates that vasculitides affecting small vessels present increased FDG uptake as do those affecting large vessels.

We describe a 45-year-old man with neurosarcoidosis complaining of bell-shaped tightening and pain with sensory disturbance of superficial and deep sensations. The patient showed subacute progressive sensory impairment in bilateral C7-Th12 dermatomes. Triceps and patellar tendon reflexes were decreased. Chest X-ray revealed bilateral hilar lymphadenopathy without pleural effusion. There was abnormal accumulation of gallium in the bilateral hilar lymph nodes, parotid glands, and lacrimal glands on scintigraphy. Examination of bronchoalveolar lavage fluid showed an elevated CD4/CD8 ratio. Transbronchial lung biopsy showed non-caseating granulomas with many epitheloid cells and occasional Langhans giant cells without any necrotic lesion. The tuberculin reaction was negative, and elevation of serum lysozyme and IgG level were seen. These findings fulfilled the clinical criteria for sarcoidosis. Spine MRI demonstrated no abnormality. Studies of short-latency somatosensory evoked potentials showed delayed N13 latency and absent N19 and N28 potentials bilaterally. A nerve conduction study revealed no abnormality. The patient's muscle strength was normal through the entire clinical course. Therefore, we consider that his sensory impairment was caused by peripheral neuropathy, especially in the dorsal root region. Neurosarcoidosis is important for differentiating bell-shaped sensory impairments of all modalities.

In December, 2001, a 67-year-old woman was given a diagnosis of having systemic sclerosis and organizing pneumonia. Steroid treatment improved her condition, and she received no further medication for approximately three years thereafter. In October 2005, she visited Kurume University Hospital because of cough and fever. Chest X-ray film and high-resolution computed tomography (HRCT) showed bilateral patchy consolidation with air-bronchogram sign and ground-glass opacities, predominantly in the right lower lung field, suggesting relapse of organizing pneumonia. However, bronchoalveolar lavage fluid (BALF) analysis showed an increase of neutrophils (79%) and the CD4/CD8 ratio (4.04). Streptococcus dysgalactiae subsp. equisimilis (beta-hemolytic, Lancefield group G) was detected by bacterial culture of the BALF. Treatment with sulbactam sodium/ampicillin sodium (SBT/ ABPC) rapidly improved her symptoms. The patchy consolidations on chest X-ray and HRCT also disappeared after the treatment. On the basis of these clinical and bacteriological findings, we diagnosed the patient as having bacterial pneumonia caused by Streptococcus dysgalactiae subsp. equisimilis.

Background Disease-modifying antirheumatic drugs (DMARDs) are known to inhibit radiographic progression in patients with rheumatoid arthritis (RA). Their effects are supposed to be different according to clinical condition, however, there have been few epidemiological reports of longitudinal investigation in RA patients captured in daily practice. Objectives To determine prognostic factors of radiographic progression (RRP) in patients with RA in clinical practice for achieving treat to target strategy. Methods We performed a Japanese multicenter prospective study on biological DMARDs (bDMARDs)-naive 887 RA patients with moderate to high disease activity or with radiographic bone erosion, treated with conventional synthetic DMARDs (csDMARDs) at study entry. We observed longitudinally these patients for 1 year and assessed Disease Activity Score in 28 joint (DAS28-ESR) every 3 months. RRP was defined as yearly progression of modified total Sharp score (mTSS) >3.0U. Furthermore, we divided into two groups based on disease duration ( Results RRP was found in 9.2% of patients. Multiple step-wise regression analysis revealed that disease duration (OR=0.92, 95% CI 0.86 to 0.99), time-integrated DAS28-ESR during 1 year (OR=1.04, 95% CI 1.01 to 1.06), CRP at baseline (OR=1.24, 95% CI 1.07 to 1.43), and introduction of bDMARDs (OR=0.12, 95% CI 0.03 to 0.55) are independent variables to predict the development of RRP. Intriguingly, our subgroup analysis has revealed that time-integrated DAS28-ESR during 1 year is not a significant predictor for RRP in early RA and the protective effect of bDMARDs toward RRP is evident in early RA patients. Conclusions RRP in RA patients treated with DMARDs is closely associated with persistent disease activity or early introduction of bDMARDs. Among early RA patient, subclinical RRP should be considered regardless of integrated disease activity. Disclosure of Interest None declared

We encountered a 39-year-old female patient with systemic lupus erythematosus (SLE) in whom thrombotic thrombocytopenic purpura (TTP) recurred. The patient was successfully treated with corticosteroid in combination with immunosuppressive agents. Because TTP complicating SLE is more resistant to treatment than idiopathic TTP, prompt diagnosis and efficacious initial treatment are critical.

A 23-year-old woman presented with recurrence of lupus cystitis, which had been in remission under daily administration of a single corticosteroid over a period of 8 years. She was treated with increased doses of corticosteroid and immunosuppressants, i.e., cyclosporin, cyclophosphamide, azathioprine, and salazosulfapyridine, but the cystitis remained active. Since her condition became critical by the complication of intestinal pseudo-obstruction, tacrolimus was administered. This agent induced a remission promptly without significant adverse events in this patient, suggesting an efficacy to lupus cystitis refractory to corticosteroid and other immunosuppressants.

Pneumomediastinum as a complication of interstitial pneumonia with leakage of air into the mediastinum or subcutaneous tissues is a rare complication of dermatomyositis (DM). Herein we report a case of pneumomediastinum complicating polymyositis (PM), which is usually associated with DM. A 61-year-old man was hospitalized in our department because of deterioration of interstitial pneumonia. Treatment with high-dose corticosteroid and cyclosporin A steadily improved his interstitial pneumonia. Two weeks later, he developed subcutaneous emphysema and chest X-ray showed pneumomediastinum. Both subcutaneous emphysema and pneumomediastinum improved gradually without any additional treatment.

To investigate whether erythromycin (EM) can suppress the expression of cyclooxygenase-2 (COX-2) in rheumatoid synovial cells, and determine the mechanisms involved. Methods. Synovial tissues were obtained from 25 patients with rheumatoid arthritis (RA). Rheumatoid synovial cells were cultured with or without EM (0.1-1000 nM) in the presence of interleukin 1beta (IL-1beta) for various times. Protein expression of COX-2, and phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) were detected by Western blot. COX-2 messenger RNA (mRNA) was detected by RT-PCR. DNA binding activity of nuclear factor kappa B (NF-kB) was detected by ELISA. Results. IL-1beta-stimulated synovial cells expressed COX-2 protein. EM suppressed the IL-1beta-induced COX-2 protein expression in a dose-dependent manner and inhibited IL-1beta-induced p38 MAPK phosphorylation, which was correlated with COX-2 expression in synovial cells. In contrast, EM had no effect on DNA binding activity of NF-kB and ERK1/2 expression.Our results indicated that EM downregulated COX-2 expression by inhibiting the p38 MAPK cascade, but had no effect on NF-kB or ERK1/2, in rheumatoid synovial cells.

Cyclooxygenase (COX) plays a pivotal role in the inflammatory process of inflammatory arthropathies. Inflammatory cytokines induce COX-2 expression in osteoblasts of inflamed joints, followed by osteoclast activation. The inhibition of COX-2 expression could help prevent prostaglandin E2 secretion, followed by osteoclast activation for bone destruction and resorption. We examined whether the antioxidant N-acetylcysteine (NAC) inhibited COX-2 expression induced in the human osteoblastic cell line MG63 by interleukin-1beta (IL-1beta). According to Western blot and reverse transcription-polymerase chain reaction (RT-PCR) test results, NAC inhibited IL-1beta-induced COX-2 expression in protein and messenger RNA. We also demonstrated immunohistochemically that NAC inhibited NFkappaB nuclear translocation. These results suggested that NAC inhibited both COX-2 expression and NFkappaB nuclear translocation in MG63, which in turn indicated that NAC could inhibit the inflammatory process involved in bone resorption by regulating COX-2 expression at the level of transcription.

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.

Background/Aims: Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. Methodology/Principal Findings: In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1β) gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1β-511 (C/T) and IL-1 receptor antagonist (IL-1Ra) variable number of tandem repeat (VNTR) polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1β -511 (C/T), IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%), and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5%) in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p = 0.001) in FMF patients compared with healthy subjects. Conclusions/Significance: Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5′-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms) of SAA1 gene, are associated with susceptibility to FMF in the Japanese population., PLoS ONE, 8(2), e55227; 2013