Reliability and validity of the Korean version of the University of California–Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract instrument in patients with systemic sclerosis

Background/Aims@#Systemic sclerosis (SSc) is associated with a wide range of gastrointestinal (GI) changes. The University of California–Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) instrument is a self-administered GI assessment instrument for patients with SSc. We developed a Korean version of the UCLA SCTC GIT 2.0 instrument and evaluated its reliability and internal consistency. @*Methods@#The participants were 37 Korean patients with SSc. Translation and cross-cultural adaptation of the UCLA SCTC GIT 2.0 were performed according to international standardized guidelines. We evaluated reproducibility by calculating the intraclass correlation coefficients and assessed the internal consistency of the Korean version of the UCLA SCTC GIT 2.0. We assessed its construct validity by evaluating its correlations with the Short Form Health Survey version 2 and EQ-5D scores by means of Spearman correlation analyses. @*Results@#Patients with SSc were mostly women (89.19%) with a mean age of 52.2 years, median disease duration of 24 months, and median modified Rodnan total skin score of 4. The median total GIT score on the UCLA SCTC GIT 2.0 was 0.3. The UCLA SCTC GIT 2.0 Korean version showed excellent internal consistency (Cronbach’s α of total GIT score = 0.863). Most domains of the ULCA SCTC GIT 2.0 were correlated with those of the EuroQol (EQ)-5D score. @*Conclusions@#The Korean version of the UCLA SCTC GIT 2.0 has acceptable internal consistency, reliability, and validity. Therefore, it can be used to assess GIT involvement in Korean patients with SSc.

Intravenous Immunoglobulin Controls Th17 Cell-Mediated Osteoclastogenesis

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine–induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14⁺ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14⁺ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4⁺ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell–mediated osteoclastogenesis.

Mycophenolate Mofetil Overdose Induced Ventricular Tachycardia in a Patient with Systemic Lupus Erythematosus / 대한내과학회지

Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.

N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL in rheumatoid arthritis

BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.

Rheumatic complications in cancer patients treated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.

Magnetic resonance imaging-assessed synovial and bone changes in hand and wrist joints of rheumatoid arthritis patients

BACKGROUND/AIMS@#Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI.@*METHODS@#MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm's tenosynovitis score.@*RESULTS@#The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected.@*CONCLUSIONS@#This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.

N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL production in rheumatoid arthritis

In the article cited above, there was an error in the title.

Mycophenolate Mofetil Overdose Induced Ventricular Tachycardia in a Patient with Systemic Lupus Erythematosus / 대한내과학회지

Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.

New Classification Criteria for Primary Sjögren's Syndrome and Salivary Gland Ultrasonography / 대한내과학회지

Primary Sjögren's syndrome (pSS) is a chronic autoimmune inflammatory disorder characterized by lymphocytic infiltration of exocrine organs. Since 1965, several sets of classification criteria for pSS have been proposed by single experts or groups of multidisciplinary specialists. In 2002, the American-European Consensus Group proposed new classification criteria, which have been widely used in both clinical trials and routine clinical practice. In 2012, updated classification criteria were approved by the American College of Rheumatology (ACR). The existence of two different sets of criteria emphasized the need for an international consensus. Using methods consistent with those employed to develop recent ACR/European League Against Rheumatism (EULAR)-approved criteria, new ACR/EULAR classification criteria for pSS were developed and endorsed in 2016. Salivary gland ultrasonography (SGUS) is a new imaging tool used to detect salivary gland abnormalities in pSS patients. Several reports on the utility of SGUS for pSS diagnosis have appeared. This review focuses on the new 2016 ACR/EULAR classification criteria for pSS and the clinical application of SGUS in patients with pSS.

Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for patient with leptomeningeal metastasis of epidermal growth factor receptor mutant non-small cell lung cancer / 영남의대학술지

We report on a 64-year-old man with leptomeningeal metastasis (LM) from an epidermal growth factor receptor (EGFR)-mutated adenocarcinoma of the lung. He was treated with paclitaxel, cisplatin. After completion of chemotherapy, he complained of headache, nausea, and vomiting. EGFR-mutated tumor cells were identified from the cerebrospinal fluid (CSF). Second-line therapy with gefitinib, methotrexate was started. After receiving gefitinib for 4 weeks, he had no more headaches or vomiting. Eleven months after initiation of gefitinib, he developed headache and nausea. Chest computed tomography showed aggravation of bone metastasis. Third-line therapy was started with gemcitabine and carboplatin. Two weeks later, he experienced disorientation. After a fourth relapse within the central nervous system, the therapy was switched to erlotinib and significant improvement of LM was achieved. This case shows that LM can be diagnosed by detecting EGFR mutation in CSF and EGFR tyrosine kinase inhibitors are effective for LM from EGFR mutant non-small cell lung cancer.

Bilateral Ovarian Metastases from ALK Rearranged Non-Small Cell Lung Cancer / 결핵및호흡기질환

Anaplastic lymphoma kinase (ALK) rearrangement, is a kind of driver mutation, accounts for 3%-5% of non-small cell lung cancer (NSCLC). NSCLC patients harboring ALK fusion genes have distinct clinical features and good response to ALK inhibitors. Metastasis from lung cancer to the ovary has rarely been known. We report a case of a 54-year-old woman with bilateral ovarian metastases from ALK rearranged NSCLC. She underwent bilateral salpingo-oophorectomy for ovary masses, which were progressed after cytotoxic chemotherapy although primary lung mass was decreased. Histopathological examination of the ovary tumor showed characteristic adenocarcinoma patterns of the lung and ALK rearrangement.

Overtube-related Delayed Esophageal Perforation with Mediastinitis / 대한소화기학회지

Overtube provides a conduit for the passage of endoscope into the digestive tract. Esophageal perforation with mediastinitis is a rare overtube-related complication. Until now, no reports have been published regarding the esophageal perforation which developed many months after the original procedure using the overtube. A 56-year-old female visited our hospital complaining of chest pain and back pain that began 14 days ago. The patient underwent esophageal variceal ligation using the overtube 12 months earlier. She was diagnosed with esophageal perforation with mediastinitis which extended to intervertebral and epidural space. The cause of this condition was considered to have been related to the use of overtube. Management of delayed perforation remains controversial. Although surgical management might be the preferred mode of treatment, she underwent local N-butyl 2-cyanoacrylate injection therapy and temporary stent therapy with antibiotics due to high operative risk. Herein, we report a case of overtube-related delayed esophageal perforation with mediastinitis that was successfully treated by nonoperative management.