Takayasu arteritis (TA) is a chronic vasculitis that affects the aortic arch and its primary branches. Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Patients diagnosed with both TA and UC have rarely been reported. The pathogenesis of TA and UC is uncertain, but cell-mediated mechanisms play an important role in both diseases, and a genetic factor is thought to have an effect on the coincidence of these two diseases. We herein report a 38-year-old female with TA who had a history of UC with optic neuritis. We believe that this is the first case of the coexistence of TA and UC in Korea.
Takayasu arteritis; Colitis, ulcerative; Optic neuritis
This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients.
Materials and Methods
We obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA).
Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11.
The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.
Rheumatoid arthritis; interleukin-6 family cytokines; interleukin-6; interleukin-11; leukemia inhibitory factor
Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. There are no generally accepted diagnostic criteria for PsA. Indeed, the diagnosis of this inflammatory arthritis is made by exclusion of other possible diseases and based upon immunologic, radiologic, and clinical features which are consistent with the diagnosis. Inflammatory arthritis in a patient with psoriasis can be an important clue for the diagnosis of PsA, but the possibility for diagnosis of other inflammatory arthritides ever remains. Herein we report a case of a female patient who was not diagnosed with PsA, but with rheumatoid arthritis, even though she had psoriasis.
Psoriasis; Arthritis, rheumatoid; Arthritis, psoriatic
To determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine.
Patients and Methods
This cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men.
Patients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p < 0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p < 0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p < 0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS.
Elevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.
Ankylosing spondylitis; bone mineral density; C-terminal telopeptide fragments of type I collagen; C-terminal telopeptide fragments of type II collagen; radiographic damage
To investigate whether serum amyloid A (SAA) levels are increased in patients with ankylosing spondylitis (AS) and whether its levels correlate well with AS disease activity.
Materials and Methods
Thirty-eight patients with AS and 38 age- and sex-matched control subjects were enrolled in this cross-sectional study. Their SAA levels were quantitatively measured by immunonephelometry. An established, self-administered instrument for evaluating disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI) was used to measure and acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), in patients with AS.
Patients with AS had a significantly higher mean SAA level than controls (9.52 ± 7.49 mg/L versus 2.73 ± 1.57 mg/L, p < 0.05), and the mean BASDAI score of patients with elevated SAA levels was significantly higher than that of patients with normal SAA levels (5.6 ± 1.3 versus 4.4 ± 1.5, p < 0.05). SAA levels showed significant correlations with BASDAI scores (r = 0.431, p = 0.007), ESR (r = 0.521, p = 0.001) and CRP levels (r = 0.648, p < 0.001). Additionally, the correlation between ESR and CRP levels also appeared significant (r = 0.703, p < 0.001). In those with normal ESR or CRP levels, SAA levels and BASDAI scores were elevated (p < 0.05) and showed a trend of positive correlation with one another.
Our data showed that SAA levels were increased in patients with AS and correlated well with disease activity. These findings suggest that SAA can be used as a valuable indicator of disease activity in AS.
Ankylosing spondylitis; bath ankylosing spondylitis disease activity index; acute phase reactants
Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-α and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8±14.4 vs. 22.2±6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (γ=0.671; γ=0.612; and γ=0.601, P<0.001, respectively), but not with serum TNF-α levels. Serum LRG levels in patients with an active disease status (DAS28≥2.6) were significantly higher than those in remission (DAS28<2.6) (36.45±14.36 vs. 24.63±8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-α and it may be a novel biomarker for assessing inflammatory activity in patients with RA.
Leucine-Rich Alpha-2-Glycoprotein; Arthritis, Rheumatoid; Disease Activity; Tumor Necrosis Factor-alpha
The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment.
We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 μg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy.
Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258).
Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Anti-inflammatory agents; non-steroidal; Rheumatic diseases; Complications; Rebamipide; Misoprostol
To investigate clinical implications of delta neutrophil index (DNI) to discriminate adult onset Still's disease (AOSD) from sepsis.
Materials and Methods
We reviewed the medical records of 13 patients with AOSD and 33 gender and age-matched patients with sepsis. In all subjects, microbial tests were performed to exclude or confirm sepsis. All laboratory data were measured two or three times during the first 3 days and represented by their mean levels. DNI was measured automatically by ADVIA 2120 for the first 3 days.
There were no significant differences in white blood cell counts, neutrophil proportion, erythrocyte sedimentation rate and C-reactive protein between two groups. AOSD patients had notably lower DNI than sepsis patients regardless of the presence of bacteremia or not. However, both DNI and ferritin were not significant independent factors for predicting sepsis in the multivariate logistic regression analysis. Meanwhile, the area under the receiver operating characteristic curve (AUROC) of DNI was slightly higher than that of ferritin. When we set DNI of 2.75% as the cut-off value for predicting sepsis, 11 (84.6%) of AOSD patients had a DNI value below 2.75% and 2 (15.4%) of them had a DNI over 2.75% (relative risk for sepsis 176).
We suggest that DNI may be a useful marker for differential diagnosis of AOSD from sepsis in the early phase as supplementary to ferritin.
Adult onset still's disease; delta neutrophil index; sepsis
We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients.
Purpura, Henoch-Schönlein; Child; Adult; Outcome; Prognostic Factor
Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Inflammation is thought to be an important factor in accelerated atherosclerosis in RA, whereas insulin resistance is a known risk factor for atherosclerosis in RA. We hypothesised that adipokines could be a link between inflammation, insulin resistance, and atherosclerosis in RA.
The common carotid artery (CCA) intima-media thickness (IMT), CCA resistive index (RI), and carotid plaques were measured by ultrasonography in 192 patients with RA. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). Serum adiponectin, leptin, resistin, tumor necrosis factor-α, and interleukin (IL)-6 concentrations were determined.
The CCA RI was associated with CCA IMT and the estimated total plaque volume after adjustment for conventional CV risk factors. Among adipokines, resistin and IL-6 were correlated with inflammatory parameters. Leptin and leptin:adiponectin (L:A) ratio were correlated with metabolic risk factors, including HOMA-IR. And L:A ratio was related to the CCA RI after adjustment for conventional and nonconventional CV risk factors, including HOMA-IR, erythrocyte sedimentation rate and C-reactive protein.
L:A ratio was associated with HOMA-IR and carotid RI. L:A ratio might be an independent factor for predicting cardiovascular risk in patients with RA.
Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/µL. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/µL after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.
Cyclophosphamide; Systemic Lupus Erythematosus; Thrombocytopenia
Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αΜ (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.
The authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.
The A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5).
These findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.
We identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values.
We consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated.
The median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001).
The cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.
We aimed to determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in a large group of Korean patients with Behçet's disease (BD), with and without joint involvement, and to compare these findings with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Materials and Methods
We tested 189 patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM rheumatoid factor in serum. We reviewed the medical records of patients with BD to investigate their personal and clinical characteristics as well as their laboratory test results.
Anti-CCP antibodies were detected in seven of the 189 BD patients (3.7%), at a mean titer of 30.6±44.4 U/mL, in 86 of the 105 RA patients (81.9%) with a mean titer of 198.8±205.7 U/mL, and in nine of the 36 SLE patients (25%) with a mean titer of 180.4±113.9 U/mL. One of the seven anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular joint involvement, and the other two patients (28.6%) had oligoarticular involvement.
We determined the prevalence of anti-CCP antibodies in a large group of Korean BD patients with and without joint involvement. Negative anti-CCP test in patients with BD may help to differentiate BD from RA and SLE, all of which present with similar clinical features.
Behçet's disease; joint involvement; anti-cyclic citrullinated peptide antibody; rheumatoid factor; systemic lupus erythematosus; rheumatoid arthritis
Retroperitoneal fibrosis (RPF) is a rare disease with unclear etiology, which is characterized by chronic non-specific inflammation of the retroperitoneum. This study was performed to investigate the clinical characteristics, laboratory findings, radiologic findings, treatment and outcome in Korean patients with RPF. We retrospectively reviewed medical records of 27 RPF patients who were admitted to Yonsei University Medical Center between 1998 and 2009. Twenty-two patients (81%) were male. The mean age at diagnosis was 56 yr. Nine patients had identifiable risk factors of RPF and three patients had combined autoimmune diseases. Acute phase reactants were elevated in most patients. Rheumatoid factor was positive in 3 of 16 patients (19%) and antinuclear antibody in 4 of 17 (24%). Five of 6 patients who were taken positron-emission tomography showed positive uptake. Glucocorticoids were used in 16 patients (59%) and four of them received combination therapy with azathioprine. After immunosuppressive treatment, the levels of acute phase reactants dropped, and the size of mass also decreased in most patients. In conclusion, the clinical characteristics of RPF in Korean patients are similar with other series except for higher proportion of male. Some patients with RPF have autoimmune features. The effect of immunosuppressive treatment on RPF is good.
Retroperitoneal Fibrosis; Autoimmune Diseases; Immunosuppression
The aim of this study was to assess the prevalence and the common type of malignancies in Korean patients with polymyositis (PM) and dermatomyositis (DM) and to evaluate the differences of clinical and laboratory findings between patients with malignancy and those without malignancy. Forty-one Korean patients, who were diagnosed as PM or DM, were enrolled in this study. They fulfilled the Bohan and Peter's criteria for a definite diagnosis of PM and DM. Patients with PM were 25 and those with DM were 16. Eleven out of 41 patients (26.8%) had malignancies. The malignancy was diagnosed simultaneously or later in 81.8% of patients with inflammatory myopathy (IM). The breast cancer was the most common malignancy. In this study, forty three years old as a screening age for malignancy had 88.9% sensitivity and 50.2% specificity. The serum levels of creatine kinase (CK) were significantly lower in patients with malignancy than those without malignancy.
Dermatomyositis; polymyositis; malignancy
To determine whether MRI is able to demonstrate the effect of radiation synovectomy after the intra-articular injection of holmium-166-chitosan complex for the treatment of rheumatoid arthritis of the knee.
Materials and Methods
Fourteen patients aged 36-59 years were treated with 10-20 mCi of holmium-166-chitosan complex. A criterion for inclusion in this study was the absence of observable improvement after 3- or more months of treatment of the knee with disease-modifying anti-rheumatic drugs. MR images were acquired both prior to and 4-months after treatment. Clinical evaluation included the use of visual analog scales to assess pain, and the circumference of the knee and its range of motion were also determined. MR evaluation included measurement of the volume of synovial enhancement and wall thickness, the amount of joint effusion, and quantifiable scoring of bone erosion, bone edema and lymph nodes.
Visual analog scale readings decreased significantly after radiation synovectomy (p < 0.05). MRI showed that joint effusion decreased significantly (p < 0.05), and that the volume of synovial enhancement tended to decrease, but to an insignificant extent (p = 0.107).
The decreased joint effusion noted at 4-month follow-up resulted from radiation synovectomy of the rheumatoid knee by means of intra-articular injection of holmium-166-chitosan complex.
Knee, MR, Rheumatoid arthritis, Radiation synovectomy