Positive Effects of Biologics on Osteoporosis in Rheumatoid Arthritis

Osteoporosis is a systemic skeletal disorder that causes vulnerability of bones to fracture owing to reduction in bone density and deterioration of the bone tissue microstructure. The prevalence of osteoporosis is higher in patients with autoimmune inflammatory rheumatic diseases, including rheumatoid arthritis (RA), than in those of the general population. In this autoimmune inflammatory rheumatic disease, in addition to known risk factors for osteoporosis, various factors such as chronic inflammation, autoantibodies, metabolic disorders, drugs, and decreased physical activity contribute to additional risk. In RA, disease-related inflammation plays an important role in local or systemic bone loss, and active treatment for inflammation can help prevent osteoporosis. In addition to conventional synthetic disease-modifying anti-rheumatic drugs that have been traditionally used for treatment of RA, biologic DMARDs and targeted synthetic DMARDs have been widely used. These agents can be employed more selectively and precisely based on disease pathogenesis. It has been reported that these drugs can inhibit bone loss by not only reducing inflammation in RA, but also by inhibiting bone resorption and promoting bone formation. In this review, the pathogenesis and research results of the increase in osteoporosis in RA are reviewed, and the effects of biological agents on osteoporosis are discussed.

The Impact of the Amendment of the Korean National Health Insurance Reimbursement Criteria for Anti-tumor Necrosis Factor-α Agents on Treatment Pattern, Clinical Response and Persistence in Patients With Rheumatoid Arthritis

Objective@#. To investigate the impact of the amendment of the Korean National Health Insurance (KNHI) reimbursement criteria for anti-tumor necrosis factor-α (TNF-α) agents based on from conventional clinical and laboratory measurements to disease activity score of 28 joints (DAS28) on treatment pattern, clinical response, and persistence rate in patients with rheumatoid arthritis (RA). @*Methods@#. This multicenter retrospective cohort study evaluated 148 RA patients eligible for the initiation of anti- TNF-α agents as the first-line biologics by either the past (n=95) or current (n=53) KNHI reimbursement criteria. Persistence was defined as the duration between the initiation and discontinuation of anti-TNFα agents. @*Results@#. In total, 106 (71.6%), 35 (23.6%), and 7 (4.7%) RA patients started treatment with adalimumab, etanercept, and infliximab, respectively. RA patients who received anti-TNF-α agents under the current reimbursement criteria had a significantly lower mean DAS28-erythrocyte sedimentation rate (ESR) (6.02 vs. 6.95, p＜0.001) and daily prednisolone-equivalent glucocorticoid dose (4.51 vs. 6.17 mg, p＜0.001) than those who received anti-TNF-α agents under the past reimbursement criteria. No significant differences in the 1-year remission rate defined by DAS28-ESR＜2.6 (17.9% vs. 30.2%, p=0.085) and the persistence rate (p=0.703) between the past and current reimbursement criteria was observed. @*Conclusion@#. Our data suggest that less active RA patients can receive reimbursement for anti-TNF-α agents under the current criteria, and the amendment of the KNHI reimbursement criteria may improve access to anti-TNF-α agents without affecting the treatment response and persistence rate.

Case of Raynaud Syndrome after the Use of Methimazole

Raynaud syndrome is a medical condition that causes pain, numbness, and changes in skin color at the distal extremities. Raynaud syndrome can be subdivided into primary Raynaud's and secondary Raynaud's. The former is diagnosed when the cause is unknown and the latter is caused by an underlying condition, such as connective tissue diseases, injury, smoking, or certain medications. Both cancer chemotherapy and β-blockers are relatively common causes of Raynaud syndrome but there are no reports of its association with methimazole administration. The authors encountered a 43-year old woman with hyperthyroidism who developed digital ulcers associated with Raynaud syndrome after a methimazole treatment. Her digital ulcers and Raynaud syndrome were improved after methimazole was replaced with propylthiouracil and conventional therapy. This paper reports this case along with a review of the relevant literature.

IgA nephropathy in a patient with ankylosing spondylitis well controlled with etanercept / 고신대학교의과대학학술지

Ankylosing spondylitis (AS) can involve the eye, gastrointestinal system, cardiopulmonary system, skin, kidneys, and spinal and peripheral joints. It is rarely accompanied by immunoglobulin A (IgA) nephropathy. Although IgA is involved in both AS and IgA nephropathy, the relationship between these diseases remains unclear. We detected hematuria and proteinuria in a 32-year-old male patient with ankylosing spondylitis that remained stable for 4 years through treatment with etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, and diagnosed IgA nephropathy through a renal biopsy. IgA nephropathy seems to be less commonly associated with AS disease activity or specific treatment such as TNF-α inhibitor use.

Drug survival and the associated predictors in South Korean patients with rheumatoid arthritis receiving tacrolimus

BACKGROUND/AIMS@#To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care.@*METHODS@#2018-01-16: In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses.@*RESULTS@#TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039).@*CONCLUSIONS@#In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

Degos-Like Lesions Associated with Systemic Lupus Erythematosus

Degos disease, also referred to as malignant atrophic papulosis, was first described in 1941 by Köhlmeier and was independently described by Degos in 1942. Degos disease is characterized by diffuse, papular skin eruptions with porcelain-white centers and slightly raised erythematous telangiectatic rims associated with bowel infarction. Although the etiology of Degos disease is unknown, autoimmune diseases, coagulation disorders, and vasculitis have all been considered as underlying pathogenic mechanisms. Approximately 15% of Degos disease have a benign course limited to the skin and no history of gastrointestinal or central nervous system (CNS) involvement. A 29-year-old female with history of systemic lupus erythematosus (SLE) presented with a 2-year history of asymptomatic lesions on the dorsum of all fingers and both knees. The patient had only skin lesions and no gastrointestinal or CNS vasculitis symptoms. Her skin lesions were umbilicated, atrophic porcelain-white lesions with a rim of erythema. On the basis of clinical, histologic, and laboratory findings, a diagnosis of Degos-like lesions associated with SLE was made. The patient had been treated for SLE for 7 years. Her treatment regimen was maintained over a 2 month follow-up period, and the skin lesions improved slightly with no development of new lesions.

Effect of Rheumatoid Factor on Vascular Stiffness in General Population without Joint Symptoms / 고신대학교의과대학학술지

OBJECTIVES: The role of rheumatoid factor (RF) in vascular stiffness and cardiovascular risk in subjects without joint symptoms remains unclear. We investigated vascular stiffness in subjects without joint symptoms using pulse wave velocity (PWV), calculated Framingham risk scores (FRS), an estimator of cardiovascular risk, and analyzed whether vascular stiffness and FRS were affected by RF. METHODS: Two hundred forty-two subjects were included in this population-based study. RF was quantified with turbid immunometry using a cut-off of RF > 15 IU/ml to denote RF positivity. Information was then obtained on joint symptoms. Brachial-ankle PWV (baPWV) was measured using an automated device. RESULTS: Of the 242 subjects, 15 were RF-positive. RF-positive subjects without joint symptoms had a higher baPWV and FRS than RF-negative subjects without joint symptoms, but the difference did not reach statistical significance. However, when we stratified the subjects into two groups (group A – high RF: RF ≥ 40 IU/ml; group B – low RF: RF < 40 IU/ml), group A showed significantly higher baPWV (1640.7 ± 179.6 ㎝/s vs. 1405.7 ± 225.7 ㎝/s, P = 0.008) and FRS (25.7 ± 4.87 vs. 11.8 ± 9.6, P < 0.001). Multiple regression analysis was used to examine potential confounders, and RF exhibited significant but modest effects on baPWV (adjusted R-squared = 0.038, P = 0.030). CONCLUSIONS: In a sample of the general population without joint symptoms, higher levels of RF were associated with increased vascular stiffness, suggesting a pathophysiologic link between RF and endothelial dysfunction.

Gastrointestinal Risk Factors and Non-steroidal Anti-inflammatory Drugs Use in Rheumatoid Arthritis and Osteoarthritis Patients in Korea

OBJECTIVE: The aim of this study was to examine and compare the gastrointestinal (GI) risk factors and treatment patterns of rheumatoid arthritis (RA) and osteoarthritis (OA) patients in Korea. METHODS: This was a cross-sectional, observational study on RA and OA patients taking non-steroidal anti-inflammatory drugs (NSAIDs) for at least 1 month. A total of 1,896 patients (981 RA patients, 915 OA patients) were recruited from 20 university hospitals. Data were collected through medical records and patient surveys. GI risk factors included age, prolonged (over 3 months) or high-dose use of NSAIDs, alcohol drinking, smoking, use of aspirin, anticoagulants or glucocorticoids, comorbidities, and history of Helicobacter pylori infection or other GI complications. Treatment patterns were classified according to groups using, selective cyclooxygenase (COX)-2 inhibitors+/-gastro-protective agents, non-selective COX-2 inhibitors+proton pump inhibitor, or non-selective COX-2 inhibitors+/-other gastro-protective agents. RESULTS: GI risk factors were highly present in both RA and OA patients. The proportion of prolonged use of NSAIDs, smoking, and glucocorticoid use were higher in RA patients (p<0.001). The proportion of comorbidities and use of aspirin were higher in OA patients (p<0.001). The remaining GI risk factors were present in similar proportions in both groups. Use of selective COX-2 inhibitors or gastro-protective agents was higher in RA patients. CONCLUSION: Prolonged use of NSAIDs and concomitant glucocorticoid use were higher in RA patients, while comorbidities and concomitant aspirin use were predominant in OA patients. These results will provide insights for use in development of future guidelines for proper selection of NSAIDs and effective prevention of GI complications in arthritis patients.

Discovery of Splenic Sarcoidosis Concurrent with the Diagnosis of Ovarian Cancer: A Case Report

Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by noncaseating epithelioid granuloma formation. Although the relationship between sarcoidosis and malignancy has been noted in recent decades, there are few case reports describing the concurrent diagnosis of sarcoidosis and malignancy. Herein, we describe a case of biopsy-proven splenic sarcoidosis mimicking metastasis at the time of ovarian adenocarcinoma. Imaging studies including positron-emission tomography-computed tomography were not useful for differentiating sarcoidosis from malignancy. Thus, our case highlights the importance of histopathological examination to rule out nonmalignant conditions before the diagnosis of metastatic disease is made.

Successful Treatment of Newly Developed, Intractable Digital Ulcers and Gangrene with Bosentan in Systemic Sclerosis

In systemic sclerosis, digital ulcers and gangrene are somewhat common clinical characteristics of obliterative vasculopathy. These manifestations increase morbidities, such as pain, infections, and acroosteolysis. However, patient responses to the appropriate treatments are often inadequate. We treated a patient with systemic sclerosis who had a refractory digital ulcer and gangrene with bosentan, an endothelin receptor antagonist, and observed improvement. Here we systematically review this case.

A Case of Essential Thrombocythemia in a Patient with Ankylosing Spondylitis Concomitantly Treated with Adalimumab

Extreme thrombocytosis in patients with ankylosing spondylitis (AS) is rarely reported. Because the relationship between high disease activity and increased platelet counts is somewhat contradictory, severe thrombocytosis in AS patients can be secondary to infection, iron deficiency anemia, drug administration, and hematologic malignancies. Essential thrombocythemia (ET) is a rare acquired stem cell neoplasm characterized by overproduction of platelets by megakaryocytes in the bone marrow in the absence of other causes of thrombocytosis. There is no report in the literature regarding the association between AS and ET. We report on a case of a 34-year-old Korean man with active AS diagnosed as JAK2V617F mutation negative ET during adalimumab treatment.

A Case of Thyrotropin (TSH)-Secreting Pituitary Adenoma in a Patient with Ankylosing Spondylitis / 대한내과학회지

A thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, with an incidence of one case per million. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton. Extra-articular manifestations, such as anterior uveitis, may also be prominent features in AS but little is known about the association between AS and thyroid diseases including TSH-secreting pituitary adenomas. We present a case study of a 26-year-old male AS patient who was diagnosed with a TSH-secreting pituitary adenoma using a thyrotropin releasing hormone stimulation test, measurement of the TSH alpha-subunit, and magnetic resonance imaging, and subsequently treated with a transsphenoidal tumor resection.

A Case of Improved Leukocytoclastic Vasculitis after Successful Treatment of Hepatocellular Carcinoma and Membranous Obstruction of Inferior Vena Cava

Vasculitis is a heterogeneous group of diseases that destroy blood vessel walls by inflammation. Approximately half of vasculitis cases are idiopathic, but sometimes associated with genetic factors, medicines, chronic infection, autoimmune diseases, and malignancies. Although the mechanism remains unclear, vasculitis secondary to malignancy, also known as paraneoplastic vasculitis, has been reported. It is generally associated with hematologic malignancies rather than solid malignancies and commonly presents as leukocytoclastic vasculitis or polyarteritis nodosa. We experienced a case of leukocytoclastic vasculitis in a patient with hepatocellular carcinoma and membranous obstruction of the inferior vena cava. Here, we report this case with a brief review of literature.

Diet and Folk Medicines for Rheumatic Diseases

Notwithstanding recent advances in the field of treatment of rheumatic diseases, patients still have a significant interest in complementary and alternative medicine for various reasons. The purpose of this review is to investigate the effect of certain dietary components or folk medicines on the pathogenesis or outcome of rheumatic diseases. The data used in the study were mainly selected from the references searched by MEDLINE. Among the variety of dietary components and folk medicines investigated, omega-3 fatty acid, alcohol, and vitamin D showed negative correlation with the risk of rheumatoid arthritis. Specifically, omega-3 fatty acids appeared to be somewhat helpful for treatment of rheumatoid arthritis. Although some of the items showed a positive effect through this study, it failed to establish definitive evidence for the overall effect of diet and folk medicines in rheumatic diseases. In the future, further understanding of mechanisms and clinical utility should be acquired through numerous systematic and scientific research studies.

Usefulness of Ultrasonography in Differential Diagnosis between Ruptured and Unruptured Epidermal Cysts / 대한피부과학회지

BACKGROUND: An epidermal cyst is a common keratin-filled epithelial-lined cyst. The treatment of choice for epidermal cysts is surgical excision. If the cyst becomes ruptured, inflamed, or infected, then incision and drainage together with oral antibiotic therapy or intralesional steroid injection treatment is required. Identification of ruptured and unruptured cysts is important for treatment decisions. OBJECTIVE: The purpose of this study was to evaluate the usefulness of ultrasonography in the diagnosis of epidermal cysts, and to analyze distinctive features that can differentiate between ruptured and unruptured epidermal cysts. METHODS: We reviewed the clinical and sonographic features of pathologically confirmed epidermal cysts from 2 subgroups of 66 patients: 30 with unruptured cysts and 36 with ruptured cysts. The sonographic features used in the analysis included tumor size, margin, shape, tumor texture, posterior echo, internal debris, and lesion vascularity on color Doppler sonography. RESULTS: The mean long diameter of the cysts was 10.95 mm in the unruptured cyst group and 12 mm in the ruptured cyst group. Some sonographic features, including heterogenous and hypoechoic echo texture, posterior echo enhancement, and internal hyperechoic and hypoechoic debris, showed no significant differences between the groups (p>0.05). The unruptured cyst group showed cysts with significantly higher frequencies of a well-circumscribed margin, an ovoid shape, and no vascular flow (p<0.05). In contrast, the ruptured cyst group usually had cysts with a poorly defined or slightly poorly defined margin, an irregular shape, peripheral vascular flow, and mild or moderate flow vascularity. CONCLUSION: The results of this study indicate that ultrasonography is helpful in differentiating between ruptured and unruptured epidermal cysts.

Usefulness of Ultrasonography in Differential Diagnosis between Ruptured and Unruptured Epidermal Cysts / 대한피부과학회지

BACKGROUND: An epidermal cyst is a common keratin-filled epithelial-lined cyst. The treatment of choice for epidermal cysts is surgical excision. If the cyst becomes ruptured, inflamed, or infected, then incision and drainage together with oral antibiotic therapy or intralesional steroid injection treatment is required. Identification of ruptured and unruptured cysts is important for treatment decisions. OBJECTIVE: The purpose of this study was to evaluate the usefulness of ultrasonography in the diagnosis of epidermal cysts, and to analyze distinctive features that can differentiate between ruptured and unruptured epidermal cysts. METHODS: We reviewed the clinical and sonographic features of pathologically confirmed epidermal cysts from 2 subgroups of 66 patients: 30 with unruptured cysts and 36 with ruptured cysts. The sonographic features used in the analysis included tumor size, margin, shape, tumor texture, posterior echo, internal debris, and lesion vascularity on color Doppler sonography. RESULTS: The mean long diameter of the cysts was 10.95 mm in the unruptured cyst group and 12 mm in the ruptured cyst group. Some sonographic features, including heterogenous and hypoechoic echo texture, posterior echo enhancement, and internal hyperechoic and hypoechoic debris, showed no significant differences between the groups (p>0.05). The unruptured cyst group showed cysts with significantly higher frequencies of a well-circumscribed margin, an ovoid shape, and no vascular flow (p<0.05). In contrast, the ruptured cyst group usually had cysts with a poorly defined or slightly poorly defined margin, an irregular shape, peripheral vascular flow, and mild or moderate flow vascularity. CONCLUSION: The results of this study indicate that ultrasonography is helpful in differentiating between ruptured and unruptured epidermal cysts.

Association between Vitamin D Deficiency and Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis

OBJECTIVE: The present study determined if vitamin D deficiency is a potential risk factor for increased carotid intima-media thickness (CIMT) in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study analyzed 50 consecutive female RA patients without cardiovascular disease history at the Pusan National University Hospital between September and December of 2013. CIMT was measured using a high-resolution ultrasonography. Serum 25-hydroxy vitamin D (25-OHD) levels were assessed by radioimmunoassay, and vitamin D deficiency was defined as serum 25-OHD levels <20 ng/mL. Stepwise multivariable linear regression analyses were performed to evaluate the association between vitamin D deficiency and increased CIMT. RESULTS: The median 25-OHD level (inter-quartile range) was 14.0 (11.0~20.7) ng/mL, and 74% of patients had vitamin D deficiency. The mean+/-standard deviation of CIMT was 0.58+/-0.08 mm. RA patients with vitamin D deficiency had significantly higher CIMT than those without this feature (0.59+/-0.07 vs 0.54+/-0.05, p=0.028). In univariable linear regression models, vitamin D deficiency (beta(SE)=0.047 (0.021), p=0.028), older age (beta(SE)=0.003 (7.2(-4)), p<0.001) and higher disease activity score 28-erythrocyte sedimentation rate (beta(SE)=0.021 (0.010), p=0.034) and Korean version of health assessment questionnaire score (beta(SE)=0.051 (0.015), p=0.002) were significantly associated with increased CIMT. Vitamin D deficiency remained statistically significant in multivariable regression models after adjusting for confounders. CONCLUSION: Vitamin D deficiency was associated with increased CIMT in female RA patients. Our finding suggests that hypovitaminosis D can be a risk factor for atherosclerosis in RA patients.

A Case of Tjalma Syndrome Coincidentally Accompanied by an Ovarian Teratoma Successfully Treated with Intravenous Immunoglobulin-G Adjunctive Therapy

Tjalma or pseudo-pseudo Meigs' syndrome is a clinical condition that is characterized with ascites, pleural effusion, and increased serum CA-125 levels in patients with systemic lupus erythematosus (SLE) without the presence of ovarian tumor. On the other hand, Meigs' and pseudo-Meigs' syndromes represent the same manifestations with ovarian tumor. In this case report, we present a 43-year-old SLE patient suffering from Tjalma syndrome with the coexistence of incidental ovarian teratoma, who was successfully treated with intravenous immunoglobulin-G adjunctive therapy after inadequate response to surgical excision of the ovarian tumor, steroid, and cyclophosphamide pulse therapy.

Case of Secondary Amyloidosis in a Patient with Ankylosing Spondylitis Refractory to TNF-alpha Inhibitors / 대한내과학회지

Secondary amyloidosis occurs in patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The major therapeutic approach to secondary amyloidosis involves controlling the underlying inflammatory disease. Tumor necrosis factor-alpha (TNF-alpha) inhibitors have revolutionized the treatment of rheumatic diseases; in many cases dramatic clinical improvement of secondary amyloidosis due to AS has been observed in response to treatment with these agents. However, the development of secondary amyloidosis associated with AS refractory to treatment with TNF-alpha inhibitors has been infrequently reported. Here, we described a case of a 37-year-old male patient with longstanding AS who was diagnosed with secondary amyloidosis due to high disease activity despite treatment with etanercept, adalimumab and infliximab.

Henoch-Schonlein Purpura in a Patient with Ankylosing Spondylitis after Infliximab Therapy / 대한내과학회지

Tumor necrosis factor alpha (TNF-alpha) inhibitors are used widely to treat patients with active rheumatoid arthritis and ankylosing spondylitis (AS). Although various cutaneous reactions can occur as side effects of TNF-alpha inhibitors, systemic vasculitis requiring withdrawal of the agent and immunosuppressive drugs is rare. A 59-year-old male with AS who had been treated with infliximab for 60 months visited us with complaints of palpable purpura on both legs and severe abdominal pain. Abdominal computed tomography showed diffuse wall thickening of the proximal jejunum and ileum and a skin biopsy revealed leukocytoclastic vasculitis. The patient was diagnosed with Henoch-Schonlein purpura (HSP). Infliximab was discontinued and systemic steroid therapy at 0.5 mg/kg resulted in prompt resolution of the HSP. Here, we report the first case of HSP in a patient with AS after infliximab treatment.