Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis

BACKGROUND/AIMS@#To analyze clinical characteristics of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA), especially in patients with poor prognosis.@*METHODS@#Seventy-seven RA patients with ILD and 231 age, sex, and disease duration-matched RA patients without ILD were enrolled in this retrospective study. Epidemiologic, clinical, and laboratory information were obtained through a medical chart review. Logistic regression analysis was used to estimate the risk of mortality in RA patients with ILD.@*RESULTS@#Compared to the RA without ILD group, the RA with ILD group had significantly higher titers of rheumatoid factor and the anti-cyclic citrullinated peptide (p = 0.001 for both), higher levels of C-reactive protein (CRP) at the time of RA diagnosis (p = 0.014), and a higher erythrocyte sedimentation rate (p = 0.022) and CRP levels (p < 0.001) throughout the 10-year follow-up period. These patients also received a higher mean daily dose of corticosteroids (p < 0.001). In the subgroup analysis of RA patients with ILD, 28 patients (36.4%) died during follow-up. Multivariate analysis revealed that older age at the time of ILD diagnosis was significantly associated with mortality. Usual interstitial pneumonia (UIP) subtype on high-resolution computed tomography (HRCT) was also suggested as a poor prognostic factor.@*CONCLUSIONS@#The survival of RA patients with ILD is adversely affected by age at the time of ILD diagnosis. RA-ILD patients diagnosed after age 65 or with a UIP subtype on HRCT may have a poor prognosis.

Elderly Patients Exhibit Stronger Inflammatory Responses during Gout Attacks

Gout attacks are often accompanied by systemic inflammatory response. The aim of the retrospective study was to compare gout patients in different age groups in terms of their clinical features at gout attacks. Patients, who were treated for gout attack in two tertiary medical centers between January 2000 and April 2014, were divided into young (≤ 50 years), middle-aged, and elderly (> 65 years) groups. Patients in three age groups were compared in terms of presence of fever (> 37.8°C), C-reactive protein (CRP) levels, and erythrocyte sedimentation ratio (ESR) at the gout attacks. Monocytes, which were isolated from 10 consecutive patients who previously experienced gout attacks, were stimulated with monosodium urate (MSU) crystals and cytokine production was measured by flow cytometry. Among 254 patients analyzed in this study, 48 were young, 65 were middle-aged, and 141 were elderly. The elderly patients were more likely to have fever (51.1%) during the attack than the young (20.8%) and middle-aged (30.8%) patients (P < 0.001 by χ² test). They were also more likely to have higher ESR and CRP levels than the young patients (P = 0.002 for ESR, P < 0.001 for CRP). Patients' age correlated significantly with CRP and ESR levels (both P < 0.001). After stimulation with MSU, the production of interleukin-1β by monocytes increased with patients' age (r = 0.670, P = 0.03). In conclusion, gout attacks in elderly patients are associated with fever and higher ESR and CRP levels, often resembling a septic arthritis.

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

OBJECTIVE: Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). METHODS: This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. RESULTS: For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. CONCLUSION: We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.

Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi-System Inflammation without Infectious or Autoimmune Evidence

Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs.

A Case of Relapsing Polychondritis Improved by Infliximab Treatment

Relapsing polychondritis is an episodic, systemic inflammation of the cartilage with unknown autoimmune etiology. It leads to the destruction of cartilaginous structures of the ear, eye, nose, respiratory tract, joints, skin, and heart valve, and its presented symptoms are diverse. It can be improved mainly by corticosteroid or immunosuppressive agents. Recently, the use of biologic agents (TNF inhibitors, rituximab, tocilizumab et al) was reported from abroad. However, there is no reported case of relapsing polychondritis, which is treated by biologic agents in Korea. We report this first case of refractory relapsing polychondritis, which was improved with a treatment of Infliximab.

Treatment with Rituximab in a Patient with Refractory Felty Syndrome and Low Rheumatoid Arthritis Disease Activity: A Case Report

Felty syndrome (FS) is a rare manifestation in rheumatoid arthritis (RA) characterized by neutropenia and splenomegaly. Treatment for FS is not well established because there has been no randomized controlled study. A few recent reports found rituximab effective in patients with refractory FS. According to those reports, most patients with RA and FS had active arthritis. Here we report a case of a patient with glucocorticoid dependent and disease-modifying anti-rheumatic drugs (DMARDs) refractory FS and quiescent RA who was successfully treated with rituximab.

Rituximab Treatment for the Patients with Refractory Inflammatory Myopathy

OBJECTIVE: To assess the efficacy and safety of rituximab (RTX) on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. METHODS: Four inflammatory myopathy patients who had been refractory to glucocorticoids, one or more immunosuppressive therapies and intravenous immunoglobulin were treated on an open-label basis. Each patient received two 500 mg doses of RTX 2 weeks apart in one cycle. In one patient who did not respond after the first cycle of RTX, the infusion schedule was modified by the physician. We measured muscle enzyme including CPK, LDH and assessed muscle strength individually to evaluate RTX response. Additionally anti-CD19 antibody was measured. RESULTS: Three patients responded to the first cycle of RTX treatment with improvements in muscle enzyme and muscle strength, and then maintained physical function over the duration of several infusion cycles. In one patient, muscle enzyme did not decrease after the first cycle of RTX, and a high dose glucocorticoid was given. After modifying the treatment schedule with monthly RTX infusion, his muscle enzyme level and muscle strength improved. Anti-CD19 antibody decreased after RTX generally, but responses were variable. Herpes zoster infection occurred in two patients. CONCLUSION: Rituximab may be a therapeutic choice in refractory inflammatory myopathy. However a further trial is needed to confirm the efficacy and prove the safety.

Rituximab Treatment in a Case of Dermatomyositis Accompanied by Thrombotic Thrombocytopenic Purpura / 대한내과학회지

Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease known to be related with infection, toxin, pregnancy and autoimmune disease. Autoimmune disease-related TTP is rare, difficult to diagnose and can rapidly become fatal if left untreated. We report the case of a 59 year-old Korean female with TTP associated with dermatomyositis flare. The patient was suspected to have amyopathic dermatomyositis and was treated with moderate doses of oral glucocorticoids. One month later, muscle weakness developed with dermatomyositis flare, and the patient showed confusion, acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia. She was diagnosed with TTP associated with dermatomyositis flare. After prompt plasmapheresis treatment with high dose glucocorticoid therapy, her confusion, thrombocytopenia and anemia were improved. However, oliguric renal failure and myopathy remained, and thrombocytopenia and anemia recurred. After starting additional rituximab treatment, the clinical manifestation of dermatomyositis and TTP improved markedly.

Visceral fat and body weight are reduced in overweight adults by the supplementation of Doenjang, a fermented soybean paste

Various forms of fermented soybean products are well documented for their health benefits. The efficacy of anti-obesogenic effect of Doenjang, one of the most commonly used seasonings in Korean cuisine, has been reported only in animal models; thus, an evaluation of Doenjang needs to be conducted in human studies. We aimed to test the hypothesis that Doenjang supplementation reduces body weight and changes body composition in overweight adults. A total of 51 overweight adults participated in this study. A group of males with BMI > or = 23 kg/m2 and waist to hip ratio (WHR) > or = 0.90, and a group of females with BMI > or = 23 kg/m2 and WHR > or = 0.85 were randomly assigned to either a Doenjang supplement (9.9 g dry/day) group or a placebo group for a 12-week randomized, double-blind and placebo-controlled study. Anthropometric parameters, abdominal fat distribution by computerized tomography (CT) and blood components were measured before and after the intervention period. After the 12-week study, the Doenjang supplementation group had significant reductions in body weight (kg), body fat mass (kg) and body fat (%) compared to the placebo group, the supplementation of Doenjang resulted in a significant reduction in visceral fat (cm2), although no changes were observed in total and subcutaneous fat are as (cm2), serum lipid profiles and dietary intakes. The present study demonstrated that daily supplementation of 9.9 g dry/day of Doenjang for 12 weeks reduces body weight and visceral fat in overweight adults.