Pregnancy Outcomes Associated With Biologic Agent Exposure in Patients With Several Rheumatic Diseases and Inflammatory Bowel Diseases

Background@#This study aimed to analyze pregnancy outcomes based on biologic agents use in women using the nationwide population-based database. @*Methods@#The study used the claims database to identify women of childbearing age with several rheumatic (rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis) and inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) who had pregnancy-related codes between January 2010 and December 2019. We analyzed live births and adverse pregnancy outcomes based on the previous use of biologics. We also stratified the patients according to duration of biologic agent exposure before pregnancy and the use of biologics during pregnancy to analyze the pregnancy outcomes by subgroups. @*Results@#We identified 4,787 patients with pregnancy events. Among them, 1,034 (21.6%) used biologics before pregnancy. Live birth rate was not different between the biologics group and biologics naïve group (75.0% vs. 75.2%). Multivariate analyses showed that biologics use was associated with higher risk of intrauterine growth retardation (odds ratio [OR], 1.780) and lower risk of gestational diabetes mellitus (OR, 0.776) compared with biologics naïve. Biologics use during pregnancy was associated with higher risk of preterm delivery (OR, 1.859), preeclampsia/eclampsia (OR, 1.762), intrauterine growth retardation (OR, 3.487), and cesarean section (OR, 1.831), but lower risk of fetal loss (OR, 0.274) compared with biologics naïve. @*Conclusions@#Although there was no difference in live birth rate between the biologics group and biologics naïve group, biologics use seems to be associated with several adverse pregnancy outcomes, especially in patients with biologics during pregnancy. Therefore, patients with biologics during pregnancy need to be carefully observed for adverse pregnancy outcomes.

Use of Disease-modifying Antirheumatic Drugs After Cancer Diagnosis in Rheumatoid Arthritis Patients

Objective@#There is no recommendation for the use of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who developed cancer. We examined changes in the DMARDs prescription patterns associated with cancer diagnosis in RA patients. @*Methods@#We reviewed the medical records of 2,161 RA patients who visited rheumatology clinic between January 2008 and February 2017 and found 40 patients who developed cancer during RA treatment. In these patients, we examined DMARDs prescription patterns before and right after cancer diagnosis and at recent outpatient clinic visits. @*Results@#Before cancer diagnosis, methotrexate (MTX)-combined conventional synthetic DMARDs (csDMARDs) were most commonly prescribed (22, 55.0%) and biological DMARDs (biologics) in nine patients (22.5%). For cancer treatment, 19 patients received chemotherapy (including adjuvant chemotherapy) and 21 patients had surgery only. Right after cancer diagnosis, changes in the DMARDs prescription patterns were similar in discontinuation (13, 32.5%), switching (14, 35.0%), and maintenance (13, 32.5%). DMARDs were discontinued more frequently in the chemotherapy group (9/19, 47.4%) than the surgery only group (4/2, 19.0%) (p<0.05). Among the 13 patients who discontinued DMARDs, nine (69.2%) resumed DMARDs after a median of 5.5 months (interquartile range [IQR] 2.9, 18.3) due to arthritis flare. At a median of 4.6 years (IQR 3.3, 6.7) after cancer diagnosis, 25 patients were evaluated at recent outpatient clinic visits. Four patients received no DMARD, three MTX monotherapies, 11 csDMARDs combination therapies, and seven biologics. @*Conclusion@#A significant number of RA patients who developed cancer during RA treatment were still receiving DMARDs including biologics after cancer diagnosis.

Association of Uveitis with Radiographic Progression in Patients with Axial Spondyloarthritis: A Propensity Score Matching Analysis

OBJECTIVE: Acute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). However, the relationship between AAU and radiographic progression in axSpA remains unclear. Hence, we investigated whether the presence of AAU is associated with radiographic structural damage in patients with axSpA. METHODS: Clinical and radiographic data were obtained from 253 patients with axSpA. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Progression was defined as mSASSS worsening by ≥two units. Using propensity score (PS) matching, differences between patients with and without AAU were analyzed. RESULTS: The proportion of progressors among patients with AAU was lower than that of patients without AAU (13.6% vs. 29.5%, p=0.058). The rate of increase in mSASSS and number of syndesmophytes were lower in patients with AAU than patients without AAU (0.57±1.37 vs. 1.02±1.79, p=0.085 and 0.46±1.45 vs. 0.83±1.62, p=0.158). In multivariate regression analysis, presence of AAU was independently associated with slowed radiographic progression (odds ratio [95% confidence interval] 0.21 [0.07, 0.67], p=0.004). CONCLUSION: PS-matched axSpA patients with AAU showed significantly less radiographic progression than those without AAU.

The Diagnostic Reproducibility of Tomosynthesis for the Correlation between Acromiohumeral Distance and Rotator Cuff Size or Type

OBJECTIVE: To correlate the acromiohumeral distance (AHD) using tomosynthesis and rotator cuff (RC) pathology and various anatomical indices and to assess the diagnostic reproducibility of tomosynthesis for the evaluation of subacromial impingement. MATERIALS AND METHODS: A retrospective review of 63 patients with clinically suspected subacromial impingement was conducted. Two musculoskeletal radiologists independently measured the following quantitative data: the AHD on plain radiographs and the AHD at three compartments (anterior, middle, and posterior) using tomosynthesis, computed tomography (CT) arthrography, or magnetic resonance (MR) arthrography. To investigate the association between the AHD and RC pathology and various anatomical indices, we reviewed the arthroscopic operation record as the referenced standard. RESULTS: The size of rotator cuff tear (RCT) in full-thickness tears displayed a significant inverse correlation with the middle and the posterior tomosynthetic AHDs (p < 0.05). The results of an ANOVA revealed that the middle tomosynthetic AHD retained a significant association with the type of RCT (p = 0.042), and the posterior tomosynthetic AHD retained significance for the size of RCT in a full-thickness tear (p = 0.024). The inter-modality correlation exhibited significant agreement especially among the plain radiography, tomosynthesis, and CT or MR arthrography (p < 0.05). The intraobserver and interobserver correlation coefficients (ICCs) displayed excellent agreement (ICC = 0.896–0.983). The humeral head diameter and glenoid height were significantly correlated with patient height and weight. CONCLUSION: Acromiohumeral distance measurement using tomosynthesis is reproducible compared with other modalities.

Manifestations of Cervical Spine Involvement in Longstanding Ankylosing Spondylitis: Atlantoaxial Ankylosis and Atlantoaxial Subluxation

OBJECTIVE: To analyze radiologic findings of cervical involvement in ankylosing spondylitis (AS) patients, determine its association with structural severity and clinical variables, and to divide radiologic findings of atlantoaxial ankylosis (AAA) in AS patients into three anatomical components. METHODS: The study includes 150 AS patients with either AAA (62 patients) or atlantoaxial subluxation (AAS, 88 patients) who underwent plain radiography of the cervical spine on flexion at our tertiary center for rheumatic diseases. The study subjects' medical records were reviewed. Lateral plain radiographs of the cervical spine were analyzed by a musculoskeletal radiologist. We compared the results of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between AAS and AAA patients to determine if mSASSS was related to severity or duration of AS. RESULTS: The mean duration of illness in AS patients with AAA was 19.3 years, and in AAS patients 13.7 years (p<0.01). The mean total mSASSS of AS patients with AAA was 40.1, and of AAS patients 16.5 (p<0.001), and was positively associated with the development of AAA and AAS. The odds ratio (OR) of AAA development by cervical spine mSASSS change was higher (OR, 1.079) than the OR (1.049) of lumbar spine mSASSS even after adjusting for age, sex, and disease duration. CONCLUSION: Although AAA is described infrequently, we found from our data that it is another manifestation of cervical spine involvement in longstanding AS and is related to severity of AS reflected by higher cervical mSASSS.

Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

OBJECTIVES: To investigate the perception of and treatment pattern with regard to the four important issues in the management of lupus nephritis (LN), and to identify which parts of the LN treatment are difficult for physicians to carry out in clinical practice. METHODS: Four steps were carried out: pre-survey, LN symposium, post-survey, and meeting after the symposium.The two surveys were conducted with the same contents regarding renal biopsy, induction and maintenance treatment for class III and IV LN, and treatment for class V LN. The results of the first survey and the changes in opinion reflected in the second survey were comparatively analyzed. RESULTS: In the first survey, most of the respondent physicians replied that they would immediately conduct biopsy in the case of significant proteinuria. For the induction treatment of class III and IV LN, most of the respondent physicians selected high-dose cyclophosphamide. Mycophenolate mofetil and steroid combination therapy were selected for the maintenance treatment, and tacrolimus for the treatment of class V LN. There was a controversy in the drug selection, however, especially on the maintenance treatment of class III and IV LN and on the treatment of non-responsive class V LN. CONCLUSION: Some discrepancies were found in the treatment of LN in the real world. Although no recommendation was made for Korean LN patients in this study, the study results will help physicians select the most reasonable treatment for Korean LN patients based on experts' experiences and objective evidence.

Cytomegalovirus esophagitis presents as chest pain in a renal transplant recipient

No abstract available.

A Case of Chronic Arthritis Due to Mycobacterium intracellulare after Trauma / 결핵및호흡기질환

While nontuberculous mycobacterium (NTM) infections are recently on the rise, arthritis caused by NTM is hardly reported in Korea. NTM arthritis has no distinctive clinical characteristics from chronic arthritis. Tuberculosis of the joint specifically produces similar clinical and pathologic presentations to NTM arthritis, so it is not easy to distinguish between them. We report a case of Mycobacterium intracellulare in an arthritis patient after trauma and surgical repair of the injury. At the beginning, the patient was diagnosed as tuberculous tenosynovitis through pathology without microbiologic evidence. The final diagnosis was made after subsequent recurrences for several years. The misdiagnosis and delayed diagnosis led to irreversible joint destruction and functional impairment. NTM infection must be included in the differential diagnosis of chronic arthritis at the outset.

An Endobronchial Lipoma Treated by Bronchoscopic Excision / 대한내과학회지

A 68-year-old man presented with partial atelectasis of the right middle lobe on chest X-ray. Computed tomography of the chest revealed a hypodense mass in the middle lobe. Bronchoscopy showed a round mass obstructing the right middle lobe bronchus, and a biopsy specimen revealed only chronic inflammation. The tumor was removed using rigid bronchoscopy, and a diagnosis of endobronchial lipoma was made. An endobronchial lipoma is a very rare benign tumor that may cause parenchymal lung damage due to bronchial obstruction and subsequent pneumonia. We report this case to emphasize the role of endoscopic treatment in the management of endobronchial lipoma.

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.

Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis

Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.

Measurement of Interleukin-33 (IL-33) and IL-33 Receptors (sST2 and ST2L) in Patients with Rheumatoid Arthritis

The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 +/- 464.0 pg/mL) than in healthy controls (96.0 +/- 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1beta (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naive RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.

Synchronous development of KIT positive acute myeloid leukemia in a patient with gastrointestinal stromal tumor

We report a case of synchronous occurrence of KIT-positive acute myeloid leukemia (AML) and gastrointestinal stromal tumor (GIST). A 63-year-old woman was hospitalized for dizziness, and abdominal computed tomography revealed an exophytic gastric mass and hepatic metastasis. The patient was diagnosed with GIST and was administered imatinib (400 mg/day) for the metastatic unresectable tumor. After 2 weeks of imatinib treatment, the patient developed pancytopenia, which persisted even after the drug was discontinued, thereby necessitating bone marrow biopsy. Biopsy examination indicated AML, and karyotyping revealed a complex karyotype. We did not observe point mutations at residues D816 and N822 of KIT. Therefore, the patient received standard induction chemotherapy, but on the 18th day after completion of chemotherapy, she died of septic shock and multi-organ failure. Since KIT plays an important role in both GIST and AML, we consider that both these malignancies may have been associated with each other.

A Case of Hypertrophic Cranial Pachymeningitis Presenting with Scleritis in a Patient with Undifferentiated Connective Tissue Disease

Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been reported to be infrequently associated with systemic autoimmune disorders such as Wegener's granulomatosis, rheumatoid arthritis, sarcoidosis, Behcet's disease, Sjogren syndrome, and temporal arteritis. Here, we report a case of HCP initially presented with scleritis and headache in a patient with undifferenciated connective tissue disease (UCTD). HCP was initially suspected on brain magnetic resonance imaging and defined pathologically on meningial biopsy. Immunologic studies showed the presence of anti-RNP antibody. After high dose corticosteroid therapy, the patient's symptoms and radiologic abnormalities of brain were improved. Our case suggested that HCP should be considered in the differential diagnosis of headache in a patient with UCTD presenting with scleritis.

Utility of B-type Natriuretic Peptide in Patients with Acute Respiratory Distress Syndrome / 결핵및호흡기질환

BACKGROUND: B-type natriuretic peptide (BNP) has been shown to be strong mortality predictors in a wide variety of cardiovascular syndromes. Little is known about BNP in patients with acute respiratory distress syndrome (ARDS). We studied whether BNP can predict mortality in patients with ARDS. METHOD: Echocardiographic study was done to all patients with ARDS, and we excluded patient with low ejection fraction (less than 50%) or showing any features of diastolic dysfunction. 47 patients were enrolled between December, 2003 and February, 2006. Parameters including BNP were obtained within 24h hours at the time of enrollment. RESULT: Mean BNP concentrations and APACHE II scores differed between the survivors and nonsurvivors (BNP, 219.5 +/- 57.7 pg/mL vs 492.3 +/- 88.8 pg/mL; p=0.013, APACHE II score, 17.4 +/- 1.6 vs 23.1 +/- 1.3, p=0.009, respectively). With the use of the threshold value for BNP of 585 pg/mL, the specificity for the prediction of mortality was 94%. The threshold value for APACHE II of 15.5 showed sensitivity of 87%. 'APACHE II + 11xlogBNP' showed sensitivity 63%, and specificity 82%, using threshold value for 46.14. CONCLUSION: BNP concentrations and APCHE II scores were more elevated in nonsurvivors than survivors in patients with ARDS who have normal ejection fraction. BNP can predict mortality. Further study should be done.