Inflammation is responsible for systemic bone loss in patients with seropositive rheumatoid arthritis treated with rituximab

Background/Aims@#We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). @*Methods@#Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. @*Results@#In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the develgroup with the second cycle but remained stable in the group with one cycle. @*Conclusions@#Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

A Rare Case of Limited Muscle Involvement in Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic vasculitis involving small- and medium-sized arteries, which presents with necrotizing inflammation. PAN occurs as a systemic disease or as a limited form confined to a single organ. Few cases have been reported with single organ involvement, and even fewer have been reported with skeletal muscle involvement. Herein, we report the ultrasonography and magnetic resonance imaging findings in a rare case of PAN with limited muscle involvement in a 66-yearold man.

A Rare Case of Limited Muscle Involvement in Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic vasculitis involving small- and medium-sized arteries, which presents with necrotizing inflammation. PAN occurs as a systemic disease or as a limited form confined to a single organ. Few cases have been reported with single organ involvement, and even fewer have been reported with skeletal muscle involvement. Herein, we report the ultrasonography and magnetic resonance imaging findings in a rare case of PAN with limited muscle involvement in a 66-yearold man.

Diagnostic Role of Parotid Computed Tomography for Identifying Sjögren’s Syndrome / 대한이비인후과학회지

Background and Objectives@#Sjögren’s syndrome (SS) is an autoimmune inflammatory disorder of exocrine glands characterized by dry mouth and eye. Recently, ultrasonography has become a valuable tool for the assessment of salivary gland involvement in SS although studies on the usefulness of salivary gland CT is rare. In this regard, we evaluated the diagnostic accuracy of parotid gland CT for SS.Subjects and Method A total of 91 patients with sicca symptoms took a parotid CT, a serology test, an ophthalmologic examination and a minor salivary gland biopsy. At the end, as a standard, we diagnosed the primary SS according to the new 2016 American College of Rheumatology/ European League Against Rheumatism classification criteria. The diagnostic value of parotid CT was compared by the McNemar test. @*Results@#Of the total of 91 patients with parotid CT, 37 (40.7%) patients met the SS classification criteria. On the parotid CT, heterogeneity of the parotid gland has the sensitivity of 74.1%, specificity of 70.3%, and accuracy of 71.4%. The abnormal fat tissue deposition showed the sensitivity of 74.1%, specificity of 81.3%, and accuracy of 79.1%. Diffuse calcification was seen in 1/91 SS patients (sensitivity 3.7%, specificity 100%, accuracy 71.4%). @*Conclusion@#Parotid CT is helpful for the diagnosis of SS. The presence of heterogeneity and fat tissue deposition are highly sensitive for the accuracy of SS. Diffuse calcification in bilateral parotid glands is highly specific for SS.

Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis

BACKGROUND/AIMS@#To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX)@*METHODS@#The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks.@*RESULTS@#Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile.@*CONCLUSIONS@#TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

Palisaded Neutrophilic Granulomatous Dermatitis in a Patient with Systemic Sclerosis-Rheumatoid Arthritis Overlap Syndrome

No abstract available.

Tumor Necrosis Factor Blockade Stimulates Circulating Osteoblastic Lineage Cells Activity while Reducing Circulating Osteoclasts

OBJECTIVE: This study examines the effects of tumor necrosis factor (TNF) blockade on markers of bone metabolism in peripheral blood from active rheumatoid arthritis (RA) patients. METHODS: Eighteen patients (16 women, 2 men) aged 50 years (range 37-63 years), with persistently active RA (mean disease duration 7 years) were studied. Most took methotrexate (mean dose 12.5 mg) and all except one received corticosteroid (mean dose 5.7 mg). Four were treated with etanercept, eight received adalimumab and six received infliximab. Before and six months after taking TNF blockers, blood was sampled to obtain peripheral blood mononuclear cells (PBMCs), and serum bone turnover markers and acute phase reactants were measured. PBMCs were seeded and cultured to produce osteoblastic lineage cells and osteoclasts. RESULTS: The formation of calcified nodules by osteoblastic lineage cells from PBMC increased from 205.7±196.3 µmol/well at the baseline to 752.5±671.9 µmol/well after TNF blockade (p<0.024). The serum levels of bone formation markers, including bone specific alkaline phosphatase and osteocalcin also increased. The number of circulating osteoclasts and area of bone resorption pits made by osteoclasts were reduced after TNF blockade. CONCLUSION: The activity of circulating osteoblastic lineage cells increased after TNF blockade, whereas peripheral osteoclastogenesis tended to be suppressed. This is the first study of cultured human peripheral osteoblastic lineage cells in RA patients. Given that peripheral bone formation is difficult to study using radiologic methods, culture of these cells may provide a new modality for studying bone metabolism in RA.

Bone Mineral Density Measurement Intervals for Rheumatoid Arthritis Patients Not Treated for Osteoporosis / 대한내과학회지

BACKGROUND/AIMS: Osteoporosis occurs more frequently in rheumatoid arthritis (RA) patients than in healthy individuals. This study investigated the appropriate bone mineral density (BMD) measurement interval and risk factors associated with osteoporosis for RA patients. METHODS: A retrospective study was performed on 511 RA patients aged more than 40 years old who had undergone BMD testing more than once and who had normal BMD or osteopenia at the baseline BMD test and no history of any fracture of the spine or femur. The subjects were categorized into four subgroups: normal BMD (T-score > -1), mild (-1 ≥ T-score > -1.5), moderate (-1.5 ≥ T-score > -2), and advanced (-2 ≥ T-score > -2.5) osteopenia. The BMD testing interval was defined as the estimated time for 10% of the RA patients to make the transition to osteoporosis without osteoporotic fracture or the administration of any osteoporosis drug. RESULTS: The observation period was 2,214 patient-years, with an average of 4.3 years. The estimated BMD testing interval was more than 10 years for normal, 4.3 years for mild, 2.5 years for moderate, and 1.5 years for advanced osteopenia in each of the RA patient groups. CONCLUSIONS: Our study indicated that in normal or osteopenic RA groups, a baseline BMD T-score is the most important factor in estimating the interval in which osteoporosis is predicted to occur. In addition, we recommend that the BMD measuring interval should be greater than 10 years in normal BMD RA patients, 4 years in mild, 2 years in moderate, and 1 year in advanced osteopenic RA patients on the basis of L-spine BMD.

A Case Report of SAPHO Syndrome Treated with Oral Alendronate

SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis is rare compared to other spondyloarthropathies. It is also difficult to diagnose, and treatment methods have not yet been fully identified. Approximately 72% of patients are diagnosed with at least one other disease before a final diagnosis of SAPHO syndrome. In addition, SAPHO syndrome is subject to a delayed diagnosis period of 4.5 to 9.1 years. Medications such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and tumor necrosis factor inhibitors are used in treatment of SAPHO syndrome. Bisphosphonate is also used for refractory SAPHO syndrome; however, most reports on this relate to intravenous injection of medication. The authors experienced and subsequently reported on a case involving a patient with SAPHO syndrome accompanied by fracture and infection of the left second finger who was treated with the oral biphosphonate, alendronate.

A Case of Eosinophilic Granulomatosis with Polyangiitis Presenting with Subarachnoid Hemorrhage and Mononeuritis Multiplex

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, is an anti-neutrophil cytoplasmic antibody associated vasculitis, accompanied by asthma, hypereosinophilia, nonfixed pulmonary infiltrates, and sinusitis. Peripheral neuropathy is common in patients with EGPA; however, a few cases of EGPA with central nervous system (CNS) involvement have been reported. A 45-year-old female referred for right side weakness and posterior neck pain was diagnosed as EGPA with subarachnoid hemorrhage and mononeuritis multiplex. She was effectively treated with a high dose glucocorticoid, cyclophosphamide, and intravenous immunoglobulin. EGPA with CNS involvement is uncommon and causes significant morbidity and mortality. Therefore more rapid and accurate diagnostic evaluation may be required. EGPA should be considered in patients with neurological symptoms and hypereosinophilia.

A Case of a Glomus Tumor in the Hand Associated with Raynaud's Disease / 대한내과학회지

Although it is difficult to reach a diagnosis in patients who complain of pain or sensitivity to cold in their hands, Raynaud's phenomenon is most often suspected in such cases. Symptoms of Raynaud's phenomenon include pallor, cyanosis, and redness following cold exposure. Glomus tumors can also increase patients' sensitivity to cold. In this case, our patient complained of symptoms indicative of Raynaud's phenomenon. Although treatment of Raynaud's phenomenon improved the symptoms, pain persisted in the fourth finger of the left hand. We diagnosed the patient with a glomus tumor and, after surgical treatment, the patient's symptoms improved. Here, we have also reviewed and discussed a number of reports of glomus tumors associated with Raynaud's disease. Diagnosing a glomus tumor in the hand may take some time, and the diagnosis could be further delayed if accompanied by Raynaud's phenomenon. Although glomus tumors are rare, we suggest that clinical awareness is important for early diagnosis and treatment.

Digital Thermography of the Fingers and Toes in Raynaud's Phenomenon

The aim of this study was to determine whether skin temperature measurement by digital thermography on hands and feet is useful for diagnosis of Raynaud's phenomenon (RP). Fifty-seven patients with RP (primary RP, n = 33; secondary RP, n = 24) and 146 healthy volunteers were recruited. After acclimation to room temperature for 30 min, thermal imaging of palmar aspect of hands and dorsal aspect of feet were taken. Temperature differences between palm (center) and the coolest finger and temperature differences between foot dorsum (center) and first toe significantly differed between patients and controls. The area under curve analysis showed that temperature difference of the coolest finger (cutoff value: 2.2degrees C) differentiated RP patients from controls (sensitivity/specificity: 67/60%, respectively). Temperature differences of first toe (cutoff value: 3.11degrees C) also discriminated RP patients (sensitivity/specificity: about 73/66%, respectively). A combination of thermographic assessment of the coolest finger and first toe was highly effective in men (sensitivity/specificity : about 88/60%, respectively) while thermographic assessment of first toe was solely sufficient for women (sensitivity/specificity: about 74/68%, respectively). Thermographic assessment of the coolest finger and first toe is useful for diagnosing RP. In women, thermography of first toe is highly recommended.

Prevention of Comorbidity and Acute Attack of Gout by Uric Acid Lowering Therapy

The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA) or =6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Safety and Efficacy Evaluation for the Addition of Either Etanercept or Leflunomide in Korean Rheumatoid Arthritis Patients Inadequately Responding to Methotrexate

OBJECTIVE: To compare the safety and efficacy associated with the addition of etanercept (ETN) with that of leflunomide (LEF) in Korean rheumatoid arthritis (RA) patients, who inadequately respond to methotrexate (MTX) in a randomized, open-label study. METHODS: Twenty-nine subjects suffering moderate to severe RA, despite MTX treatment were randomly assigned to a combination therapy with either ETN or LEF. The primary end-point was the proportion of subjects achieving American College of Rheumatology (ACR20) criteria at week 16. RESULTS: Ninety percent (n=18) of the ETN+MTX group (n=20) and 22.2% (n=2) of the LEF+MTX group (n=9) achieved an ACR20 response (p=0.001). All patients (n=20) in the ETN+MTX group showed moderate or good EULAR response as compared with 55.6% (n=5) in the LEF+MTX group (p=0.012). All of the ETN+MTX subjects completed the study without adverse events. Adverse events occurred in 77.8% (n=7) of cases in the LEF+MTX group; significantly elevated serum AST/ALT levels in 6 subjects and mild neutropenia (ANC < 1,500/microL) in 1 subject. CONCLUSION: The ETN+MTX combination therapy was effective and safe, whereas the LEF+MTX combination therapy resulted in moderate efficacy in only half of the cases, and was accompanied by a high rate of adverse events. Elevated AST/ALT was the most common adverse event causing dose adjustment or discontinuation of therapeutic agent in the LEF+MTX group.

Extensive Thrombosis in a Patient with Familial Mediterranean Fever, Despite Hyperimmunoglobulin D State in Serum: First Adult Case in Korea

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis, or erysipelas-like erythema. It is known to occur mainly among Mediterranean and Middle Eastern populations such as non-Ashkenazi Jews, Arabs, Turks, and Armenians. FMF is not familiar to clinicians beyond this area and diagnosing FMF can be challenging. We report a 22-yr old boy who presented with fever, arthalgia and abdominal pain. He had a history of recurrent episodes of fever associated with arthalgia which would subside spontaneously or by antipyretics. Autosomal recessive periodic fever syndromes were suspected. Immunoglobulin D (IgD) level in the serum was elevated and DNA analysis showed complex mutations (p.Glu148Gln, p.Pro369Ser, p.Arg408Gln) in the MEFV gene. 3D angio computed tomography showed total thrombosis of splenic vein with partial thrombosis of proximal superior mesenteric vein, main portal vein and intrahepatic both portal vein. This is a case of FMF associated with multiple venous thrombosis and elevated IgD level. When thrombosis is associated with elevated IgD, FMF should be suspected. This is the first adult case reported in Korea.

Effects of Gout Web based Self-management Program on Knowledge Related to Disease, Medication Adherence, and Self-management

PURPOSE: This study was conducted to examine the changing patterns of knowledge related to disease, medication adherence, and self-management and to determine if outcomes were more favorable in the experimental group than in the comparison group through 6 months after providing a web-based self-management intervention. METHODS: A non-equivalent control group quasi-experimental design was used and 65 patients with gout, 34 in experimental group and 31 in comparison group, were selected from the rheumatic clinics of two university hospitals. Data were collected four times, at baseline, at 1 month, 3 months, and 6 months after the intervention. RESULTS: According to the study results, the changing patterns of knowledge and self-management were more positive in the experimental group than in the control group, whereas difference in the changing pattern of medication adherence between two groups was not significant. CONCLUSION: The results indicate that the web-based self-management program has significant effect on improving knowledge and self-management for middle aged male patients with gout. However, in order to enhance medication adherence, the web-based intervention might not be sufficient and other strategies need to be added.

Erratum: Correction of Title

This erratum is being published to correct of title.

Induction of Remission is Difficult due to Frequent Relapse during Tapering Steroids in Korean Patients with Polymyalgia Rheumatica

Polymyalgia rheumatica is an inflammatory disease affecting elderly and involving the shoulder and pelvic girdles. No epidemiological study of polymyalgia rheumatica was conducted in Korea. We retrospectively evaluated patients with polymyalgia rheumatica followed up at the rheumatology clinics of 10 tertiary hospitals. In total 51 patients, 36 patients (70.6%) were female. Age at disease onset was 67.4 yr. Twenty-three patients (45.1%) developed polymyalgia rheumatica in winter. Shoulder girdle ache was observed in 45 patients (90%) and elevated erythrocyte sedimentation rate (> 40 mm/h) in 49 patients (96.1%). Initial steroid dose was 23.3 mg/d prednisolone equivalent. Time to normal erythrocyte sedimentation rate was 4.1 months. Only 8 patients (15.7%) achieved remission. Among 41 patients followed up, 28 patients (68.3%) had flare at least once. Number of flares was 1.5 +/- 1.6. The frequency of flare was significantly lower in patients with remission (P = 0.02). In Korea, polymyalgia rheumatica commonly develops during winter. Initial response to steroid is fairly good, but the prognosis is not benign because remission is rare with frequent relapse requiring long-term steroid treatment.

Osteolysis of the Patella

No abstract available.