Background: This study aimed to evaluate the association between the duration of workplace noise exposure and glucose metabolism status in a nationally representative Korean sample. Methods: This cross-sectional study included 3,534 participants aged ≥40 years without tinnitus or hearing loss from the Korea National Health and Nutrition Examination Survey (2018). The primary exposure was noise in the workplace and its duration. We divided the noise exposure group into four groups according to the duration of noise exposure (<3 years, 3–10 years, 10–20 years, and ≥20 years). The primary outcomes were fasting blood sugar (FBS), hemoglobin A1c (HbA1c), and pre-diabetes and diabetes diagnosed using FBS. Logistic and linear regression analyses were used to test the association between noise exposure and glycemic status. Results: After adjustment, HbA1c levels were significantly higher in the noise exposure than in the non-noise exposure group. HbA1c levels were significantly higher in those exposed to occupational noise for more than 20 years than in others. In the subgroup analysis among those who had been exposed to noise for >20 years, the non-aerobic physical activity group had significantly higher HbA1c levels than the physical activity group. Furthermore, among those who had been exposed to noise for >20 years, the without hearing protection group had significantly higher HbA1c levels than those using hearing protection. Conclusion The association between noise exposure and the prevalence of diabetes is unclear. However, our study clearly suggests that there is a relationship between elevated HbA1c levels and workplace noise exposure and that a long period of workplace noise exposure, no physical activity, and not wearing a hearing protection device could increase the risk of diabetes.

OBJECTIVES: To investigate the clinical findings upon initial diagnosis and extraglandular manifestations in Korean patients with primary Sjogren's syndrome (pSS). METHODS: We collected clinical and laboratory data from 238 pSS patients enrolled at Seoul National University Hospital, Seoul National University Bundang Hospital and Seoul Medical Center from March 2011 to December 2014. All patients met the American-European Consensus Group criteria for pSS. RESULTS: Upon initial diagnosis, sicca symptoms (xerophthalmia or xerostomia) as the chief complaint were only observed in 129 (54.2%) pSS patients, while extraglandular manifestation was more common as the chief complaint in male patients or those with younger age (<40 years) than female or older patients (both p<0.05). Extraglandular manifestations were found in 178 (74.8%) patients, with musculoskeletal manifestations being most common (53.8%). Peripheral neuropathy in pSS patients was associated with Raynaud phenomenon and elevated serum total immunoglobulin G (IgG) levels (both p<0.05). Serum beta2-microglobulin (beta2-M) levels were significantly correlated with European League against Rheumatism (EULAR) Sjogren's syndrome disease activity index, erythrocyte sedimentation rate and serum total IgG (all p<0.001), and were higher in patients with extraglandular manifestations than those without (p<0.05). Serum C3 levels were decreased in patients with extraglandular manifestation, compared to those without (p<0.05). Malignant lymphoma was found in Korean pSS patients (1.7%) and associated with elevated serum beta2-M levels (p<0.0001). CONCLUSION: Extraglandular manifestations were common in pSS patients and may be a diagnostic tool for male or younger pSS patients. Serum beta2-M levels can be useful markers for monitoring pSS patients.
beta 2-Microglobulin ; Consensus ; Diagnosis ; Erythrocyte Indices ; Female ; Humans ; Immunoglobulin G ; Lymphoma ; Male ; Peripheral Nervous System Diseases ; Raynaud Disease ; Rheumatic Diseases ; Seoul ; Sjogren's Syndrome*

Background: The D-dimer test is a screening tool for venous thromboembolism (VTE);however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear.Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients. Methods: SLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled.The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought. Results: The incidence of VTE was more common in SLE patients than controls (10.9% vs.4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (β = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K. Conclusion The D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE.

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Sjögren's syndrome is a systemic autoimmune disease characterized by sicca symptoms and extraglandular manifestations. Anemia, leukopenia, thrombocytopenia and lymphoproliferative disorders are well-known extraglandular, hematological complications of Sjögren's syndrome. These hematologic alterations are usually mild and respond well with steroid therapy. We report a case of a 52-year-old female patient who was initially presented with thrombocytopenia. The patient was then diagnosed with primary Sjögren's syndrome and initially treated with steroid. The patient's platelet count was decreased when steroid was tapered. The dose of steroid could be effectively reduced after combined medication with hydroxychloroquine.
Anemia ; Autoimmune Diseases ; Female ; Humans ; Hydroxychloroquine ; Leukopenia ; Lymphoproliferative Disorders ; Middle Aged ; Platelet Count ; Thrombocytopenia*

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.
Antibodies, Neutralizing ; Arthritis, Rheumatoid ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Humans ; Immunohistochemistry ; Interleukin-17 ; Interleukin-1beta ; Interleukin-23 ; Interleukin-23 Subunit p19 ; Joints ; Osteoarthritis ; RNA, Messenger ; RNA-Directed DNA Polymerase ; Synovial Fluid ; Synovial Membrane ; Tumor Necrosis Factor-alpha

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, IL-1 beta and tumor necrosis factor (TNF-alpha) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, IL-1 beta and TNF-alpha in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and IL-1 beta on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and IL-1 beta could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than IL-1 beta or TNF-alpha. These responses were observed in a dose- responsive manner. In addition, IL-17 or IL-1 beta neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and IL-1 beta appears to upregulate the expression of IL-23p19 in RA-SFMC.
Antibodies, Neutralizing ; Arthritis, Rheumatoid ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Humans ; Immunohistochemistry ; Interleukin-17 ; Interleukin-1beta ; Interleukin-23 ; Interleukin-23 Subunit p19 ; Joints ; Osteoarthritis ; RNA, Messenger ; RNA-Directed DNA Polymerase ; Synovial Fluid ; Synovial Membrane ; Tumor Necrosis Factor-alpha

Gout is an inflammatory disorder in which urate crystals are deposited in the joints or soft tissues causing severe inflammation and pain. Urate crystals usually deposit in the joints, and sometimes in the extra-articular sites. A 67-year-old woman visited the otolaryngology clinic due to otalgia and discharge from the ear. She had experienced recurrent arthritis in the left second metatarsophalangeal joint from five years ago. She visited the otolaryngology clinic of our university hospital due to persistent inflammation in the ear canal despite treatment with antibiotics. An otoscopic examination showed a polyp-like mass near the eardrum. Computed tomography scan of temporal bone showed thickening of the eardrum and increased soft tissue density in the external ear canal. On histologic examination the polyp was finally found to be a urate crystal mass. She is now in a good state with urate lowering therapy. We report on a Korean case of tophaceous gout in the external ear canal that was misidentified as an inflammatory polyp.
Aged ; Anti-Bacterial Agents ; Arthritis ; Ear ; Ear Canal* ; Earache ; Female ; Gout* ; Humans ; Inflammation ; Joints ; Metatarsophalangeal Joint ; Otolaryngology ; Polyps* ; Temporal Bone ; Tympanic Membrane ; Uric Acid

Sorafenib is an oral multikinase inhibitor with clinical activity against hepatocellular carcinoma (HCC) and renal cell carcinoma. Administration of sorafenib carries a variety of adverse cutaneous reactions. Common adverse effects induced by sorafenib include hand-foot skin reactions, facial erythema, splinter subungual hemorrhage, and alopecia. Although erythema multiforme (EM) related to sorafenib has been reported, delayed-type cutaneous hypersensitivity reactions are rare in patients treated with sorafenib and there has been no case of Stevens-Johnson syndrome (SJS) reported so far. We recently experienced 3 cases of delayed-type cutaneous hypersensitivity related to administration of sorafenib. The first case was a 47-year female had targetoid erythematous rashes on her arms 12 days after starting sorafenib for HCC. The rashes spread from the arms to the trunk rapidly except for the hands and feet, and erosive lesions developed in the oral mucosa and lips. She was diagnosed as SJS. The second case was an 81-year-old male had maculopapular eruptions with multiple targetoid lesions on the trunk, arms, and legs 10 days after starting sorafenib for his HCC. There was no evidence of mucosal involvement. He was diagnosed with EM. The last one was a 20-year-old female developed generalized maculopapular eruptions in the whole body 10 days after starting sorafenib for the treatment of HCC. All 3 patients completely recovered after discontinuation of sorafenib.
Aged, 80 and over ; Alopecia ; Arm ; Carcinoma, Hepatocellular ; Carcinoma, Renal Cell ; Erythema ; Erythema Multiforme ; Exanthema ; Female ; Foot ; Hand ; Hemorrhage ; Humans ; Hypersensitivity* ; Hypersensitivity, Delayed ; Leg ; Lip ; Male ; Mouth Mucosa ; Skin ; Stevens-Johnson Syndrome ; Young Adult

OBJECTIVE: Interleukin (IL)-10 has been demonstrated to have anti-inflammatory and anti-tumour activity. Because aberrant angiogenesis is a significant pathogenic component of tumor growth and chronic inflammation, we investigated the effect of IL-10 on the production of vascular endothelial growth factor (VEGF) by the synovial fibroblasts derived from the patients with rheumatoid arthritis (RA). METHODS: Fibroblast-like synoviocytes (FLS) were cultured with transforming growth factor (TGF-beta) alone or with IL-10. The level of VEGF was measured by RT-PCR and enzyme-linked immunosorbent assay (using the 24, 48 and 72 h culture supernatants). The FLSs were cultured with TGF-b for 48 hr in the presence of PD98059 (an ERK inhibitor), curcumin and SP600125 (a JNK and Ap-1 inhibitor, respectively). The level of VEGF in the supernatants was measured by ELISA. Cell viability was assessed using MTT assay. The expressions of VEGF, ERK, AP-1 and IL-10 in the synovial tissue were quantified by immunohistochemistry. RESULTS: IL-10 exhibited the inhibitory effect on VEGF production when the FLSs were stimulated with TGF-beta. ERK and AP-1 inhibitors inhibited the TGF-beta induced VEGF production. Moreover, TGF-beta increased the phosphorylation of ERK and C-Jun, which was significantly inhibited by the IL-10. CONCLUSION: IL-10 may exert an antiangiogenic effect by inhibiting the ERK- and AP-1 mediated VEGF expression in rheumatoid synovial fibroblasts.
Anthracenes ; Arthritis, Rheumatoid ; Cell Survival ; Curcumin ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Flavonoids ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-10 ; Interleukins ; Phosphorylation ; Transcription Factor AP-1 ; Transforming Growth Factor beta ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A