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.

Prevalence and Risk Factors of Hydroxychloroquine Retinopathy in Rheumatic Patients with Dry Eye Symptoms

Purpose@#Hydroxychloroquine is widely used for long-term treatment of rheumatic diseases, but the drug can trigger irreversible toxic retinopathy. We studied the prevalence of, and the risk factors for, hydroxychloroquine retinopathy in rheumatic patients with dry eye symptoms and we introduce a representative case. @*Methods@#We retrospectively studied a cohort of 133 rheumatological patients who had taken hydroxychloroquine for at least 12 months and who visited our ophthalmology clinic with dry eye symptoms from April 2016 to December 2021. Hydroxychloroquine retinopathy was diagnosed via fundus photography, spectral-domain optical coherence tomography, the Humphrey visual field test, autofluorescence fundus photography, and multifocal electroretinography. The principal outcomes were the prevalence of retinopathy at the first screening and the risk factors. @*Results@#Of the 133 patients, hydroxychloroquine retinopathy was diagnosed in seven (5.2%) at the first screenings. The Mann-Whitney U-test revealed that older age; higher daily doses; longer dosing duration; greater cumulative doses; and higher daily and cumulative doses/kg were statistically significant in terms of retinopathy development. On multivariate logistic regression analysis, the average daily dose (odds ratio [OR] 6.02; 95% confidence interval [CI] 1.64-22.12, 100 mg increments) and duration of dosing (OR 3.39; 95% CI 1.19-9.62, 5 years increments) remained statistically significant (P = 0.021, P = 0.007 respectively) @*Conclusions@#Ophthalmologists should enquire about any history of hydroxychloroquine therapy, and perform a retinal examination, when encountering dry eye in patients with rheumatic disease. Early detection of hydroxychloroquine retinopathy followed by discontinuation of hydroxychloroquine is the only way to prevent visual loss. High daily drug doses and long dosing durations are risk factors for retinopathy.

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

No abstract available.

Diagnosis and Treatment of Arthritis

Changes in the musculoskeletal system due to aging lead to muscle weakness, muscle atrophy, degenerative changes in joints and cartilage, and decreased bone density. Pain in the joints is a very common and subjective symptom. There are various causes, such as referred pain or neurological pain that make it difficult to diagnose correctly. Especially, in elderly patients, their detailed history and a physical examination are important for the diagnosis of arthritis, and consideration of the effects of underlying diseases and drugs is essential. In this review, we first describe the clinical approach to diagnosis of arthritis, and briefly describe the diagnosis and treatment of osteoarthritis, rheumatoid arthritis, and gout, which are common arthritis causing gait disorders in the elderly.

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.

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.

A Case Report of Renal Involvement in Adult-Onset Still's Disease over Age 70

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by spiking fever, arthralgia, salmon pink rash, neutrophilic leukocytosis, and multi-organ involvement. Although renal involvement may appear in some cases of adult Still's disease, onset over 70 years of age with renal involvement has not been described. We report a 73-years-old woman whose illness manifested with fever of unknown origin, massive proteinuria, and multiple lymph nodes enlargement. With proteinuria of 2,650 mg/day, a renal biopsy was performed, and histopathological evaluation yielded the diagnosis of chronic glomerulonephritis (CGN). After excluding infectious disease, malignancy, and other rheumatic disease, AOSD was diagnosed with symptoms including fever over 39.0degrees C for more than a week, leukocytosis, generalized lymphadenopathy, and negative autoantibodies. Proteinuria and fever were improved markedly by high dose glucocorticoids and methotrexate therapy.

Erratum: Correction of Title

This erratum is being published to correct of title.

Osteolysis of the Patella

No abstract available.

Adenocarcinoma Arising in a Duplication of the Cecum

Intestinal duplications are rare developmental abnormalities that may occur anywhere in the gastrointestinal tract. The possibility of a malignant change occurring in these duplications is very low. We present a case of adenocarcinoma arising in a duplication of the cecum. A 41-year-old male patient was admitted because of a palpable abdominal mass. Abdominal computed tomography revealed a 6-cm, peripheral wall-enhanced, round, cystic mass in the cecal area. Excision of the mesenteric mass and a right hemicolectomy was performed. Upon histologic examination, the patient was diagnosed with adenocarcinoma arising in a duplication of the cecum.

Dactylitis in a Patient with Psoriatic Arthritis Treated with Infliximab / 대한내과학회지

Dactylitis is a hallmark feature of psoriatic arthritis. It is usually managed with non-steroidal anti-inflammatory drugs and oral corticosteroids. Some cases have been treated successfully with intravenous corticosteroids or some disease-modifying antirheumatic drugs. Recently, inflximab has been reported as an effective treatment for dactylitis that is resistant to conventional treatment. This report describes a 37-year-old man with psoriatic arthritis who had multiple dactylitis on both thumbs and great toes. He was resistant to conventional treatment but was effectively treated with infliximab. This report highlights the effectiveness of infliximab for dactylitis, and the usefulness of blood pool imaging from bone scans as a method for determining treatment response.

A Case of Development of Sarcoidosis During Tumor Necrosis Factor-alpha Antagonist Therapy

Etanercept is a soluble receptor fusion protein that inhibits tumor necrosis factor-alpha(TNF-alpha). The receptor is used widely in the treatment of ankylosing spondylitis, rheumatoid arthritis, sarcoidosis and other indications. For sarcoidosis, it potentially suppresses granuloma formation with TNF-alpha blocking. On the other hand, recent studies have suggested that paradoxical sarcoidosis can be induced by TNF-alpha antagonists in some cases. A 42-year-old woman, who was treated with etanercept due to ankylosing spondylitis for 5 years, was admitted because of right suprahilar lymphadenopathy on chest radiography. Chest computed tomography revealed an enlargement of supraclavicular, paratracheal, mediastinal lymph nodes. She was diagnosed with sarcoidosis on the supraclavicular lymph node biopsy, which was non-caseating epithelioid cell granuloma and excluded from similar diseases. She was treated for sarcoidosis with prednisolone instead of etanercept.

Acquired Hemophilia in a Patient with Rheumatoid Arthritis / 대한류마티스학회지

Acquired hemophilia is a rare disease caused by an autoimmune reaction to coagulation factor VIII, The mortality rate of this disease is very high (8~22%). Clinical manifestations are different from congenital hemophilia. Various diseases are associated with acquired hemophilia, including autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis (RA), tumors, inflammatory bowel disease, psoriasis, asthma, diabetes, acute hepatitis B or C, and drug reactions. However, the underlying cause is unknown in approximately 50% of cases. A few cases of acquired hemophilia with RA have been published. However, no cases have been reported in Korea. We had a patient with longstanding RA and acquired hemophilia who was suffering from upper and lower extremity purpura with a deep intramuscular hematoma. The patient was successfully treated using cyclophosphamide combined with steroid.

A Case of Osteoid Osteoma Presenting with Hip Joint Pain / 대한류마티스학회지

No abstract available.