All-cause and cause-specific mortality in patients with Behçet disease versus the general population.

BACKGROUND: The comparative risk of cause-specific mortality in patients with Behçet disease (BD) vs. the general population is not known. OBJECTIVES: To compare the risk of all-cause and cause-specific mortality in patients with BD vs. the general population. METHODS: Using data from the Korea National Health Insurance Service database for the period 2002-20, we conducted a cohort study comparing patients with BD with the general population, matched according to age and sex (1 : 4 ratio). We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analyses by age and sex were done. RESULTS: We included 24 669 patients with BD and 98 676 age- and sex-matched controls [mean (SD) age 40.5 (12.9) years; 34% male]. During a mean follow-up of 11.9 years, the incidence rate (IR) of death per 100 person-years was 0.36 in patients with BD and 0.29 in controls [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.20-1.38]. The risk of mortality was highest in the first year after BD diagnosis (HR 2.66, 95% CI 2.09-3.40). Patients with BD died more often in this period as a result of malignancy (HR 1.96, 95% CI 1.30-2.98); cardiovascular (HR 2.68, 95% CI 1.45-4.97), gastrointestinal (HR 3.50, 95% CI 1.35-9.07) and respiratory disease (HR 5.00, 95% CI 1.34-18.62); and infection (HR 3.33, 95% CI 1.02-10.92). Mortality as a result of neurological (HR 1.58, 95% CI 1.06-2.35) or genitourinary disease (HR 2.20, 95% CI 1.43-3.37) was also more common in patients with BD during the overall follow-up. Subgroup analyses showed consistent results. The risk of cardiovascular mortality vs. the general population was higher in younger patients (P = 0.006) and the risk of gastrointestinal mortality was increased in women vs. men (P = 0.04). CONCLUSIONS: This population-based cohort study revealed that the first year after diagnosis is the highest risk period for excess mortality in people with BD. The mortality burden in BD derives from a wide spectrum of organ involvement and should serve as a warning to clinicians about the systemic nature of the disease.

Behçet disease (BD) is a multisystem vasculitis (inflammation of the blood vessels) of unknown origin that commonly results in oral and genital ulcers, uveitis (eye inflammation) and skin lesions. BD is most prevalent in people from the Mediterranean to East Asia, affecting 0.4% of people in this area. Most lesions go away with time, but more severe forms that involve the cardiovascular and neurological systems can lead to death. It is estimated that people with BD have 1.4 times the risk of dying than the general population. Using large insurance databases in Korea, we investigated the risk of death in people with BD versus age- and sex-matched controls (i.e. people without the disease) from the general population. We found that patients with BD had a 28% greater risk of death than controls over 11.9 years of follow-up, with the highest risk being in first year after diagnosis. Top causes of death in people with BD included cancer, and cardiovascular, gastrointestinal, neurological, genitourinary, respiratory and infectious disease. Further analyses of the data showed that the risk of death in BD is affected by age and sex. In particular, younger patients were more susceptible to death as a result of cardiovascular disease and women were more susceptible to dying of gastrointestinal disease. Our study suggests that there could be an increased risk of death within the first year of being diagnosed with BD and highlights how BD is a systemic disease (i.e. the involvement of any internal organ system could lead to an increase in mortality). Finally, there were unique patterns of cause-specific deaths across subgroups of people with BD.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry.

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Comparative risk of infections between JAK inhibitors versus TNF inhibitors among patients with rheumatoid arthritis: a cohort study.

BACKGROUND: To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. METHODS: Using 2009-2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users. RESULTS: We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI. CONCLUSIONS: This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.

Risk-Benefit Analysis of Primary Prophylaxis Against Pneumocystis Jirovecii Pneumonia in Patients With Rheumatic Diseases Receiving Rituximab.

OBJECTIVE: To identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) outweighs the risk of adverse events (AEs). METHODS: This study included 818 patients treated with rituximab for rheumatic diseases, among whom 419 received prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) with rituximab, while the remainder did not. Differences in 1-year PJP incidence between the groups were estimated using Cox proportional hazards regression. Risk-benefit assessment was performed in subgroups stratified according to risk factors based on the number needed to treat (NNT) to prevent 1 case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication. RESULTS: During the 663.1 person-years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high-dose glucocorticoids (≥30 mg/day of prednisone or equivalent during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person-years) was 7.93 (95% confidence interval [95% CI] 2.91-17.25) in the subgroup receiving high-dose glucocorticoids compared with 0.40 (95% CI 0.01-2.25) in the subgroup without high-dose glucocorticoid use. Although prophylactic TMP/SMX significantly reduced the overall PJP incidence (HR 0.11 [95% CI 0.03-0.43]), the NNT to prevent 1 case of PJP (146) was higher than the NNH (86). In contrast, the NNT fell to 20 (95% CI 10.7-65.7) in patients receiving concomitant high-dose glucocorticoids. CONCLUSION: The benefit associated with primary PJP prophylaxis outweighs the risk of severe AEs in patients with rheumatic diseases receiving rituximab and concomitant high-dose glucocorticoid treatment.

Risk of Bloodstream Infection in Patients with Systemic Lupus Erythematosus Exposed to Prolonged Medium-to-High-Dose Glucocorticoids.

OBJECTIVES: This study aimed to investigate the incidence rate and risk factors of bloodstream infection (BSI) in patients with systemic lupus erythematosus (SLE) exposed to medium to high doses of glucocorticoids. METHODS: This study included 1109 treatment episodes with prolonged (≥4 weeks) medium-to-high-dose glucocorticoids (≥15 mg/day prednisolone) in 612 patients with SLE for over 14 years. Clinical features regarding systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), immunosuppressant use, and laboratory results were obtained from the electronic medical database. The primary outcome of this study was the 1-year incidence of BSI. The effect of clinical factors on the outcome was investigated using a generalized estimating equation. RESULTS: During a total of 1078.64 person-years, 30 cases of BSI occurred, with an incidence rate of 2.78 (95% confidence interval (CI) 1.88-3.97) per 100 person-years. Mortality rate of the treatment episodes with BSI was 16.7%, which was significantly higher than that in the other episodes (incidence rate ratio (IRR) 19.59, 95% CI 7.33-52.44). When the incidence rate of BSI was stratified by baseline glucocorticoid dose and SLEDAI-2K score, a higher incidence rate of BSI occurred as disease activity or baseline glucocorticoid dose increased. In the multivariable analysis, SLEDAI-2K ≥20 (adjusted IRR (aIRR) 4.66, 95% CI 2.17-10.00), initial baseline prednisolone ≥ 60 mg/day (aIRR 2.42, 95% CI 1.11-5.32), and cumulative prednisolone dose ≥15 mg/day during the previous 6 months (aIRR 2.13, 95% CI 1.03-4.40) significantly increased the risk of BSI. CONCLUSION: In patients with SLE exposed to prolonged medium-to-high-dose glucocorticoids, the 1-year incidence rate of BSI was significantly higher than previously reported in the general patients with SLE. Severe disease activity, and high-dose glucocorticoid treatment previously or at baseline increased the risk of BSI.

Performance of cut-offs adjusted with positive control band intensity in line-blot assays for myositis-specific antibodies.

The diagnostic performance of band intensity (BI) cut-offs, adjusted by a positive control band (PCB) in a line-blot assay (LBA) for myositis-related autoantibodies (MRAs) is investigated. Sera from 153 idiopathic inflammatory myositis (IIM) patients with available immunoprecipitation assay (IPA) data and 79 healthy controls were tested using the EUROLINE panel. Strips were evaluated for BI using the EUROLineScan software, and the coefficient of variation (CV) was calculated. Sensitivity and specificity, area under the curve (AUC), and the Youden's index (YI) were estimated at non-adjusted or PCB-adjusted cut-off values. Kappa statistics were calculated for IPA and LBA. Although inter-assay CV for PCB BI was 3.9%, CV was 12.9% in all samples, and a significant correlation was found between BIs of PCB and seven MRAs (all P < 0.05). At adjusted BI (aBI) > 10, the negative conversion rate of myositis-specific autoantibody (MSA)-positivity at BI > 10 was 11.5% in controls and 1.3% in patients. The specificity, AUC, and YI for MSAs at aBI > 10 or > 20 were higher than those at non-adjusted cut-off values. Additionally, AUC (0.720), YI (0.440), and the prevalence of MRAs with kappa > 0.60 (58.3%) were the highest at aBI > 20. The overall sensitivity and specificity for MSAs were 50.3% and 93.7% at aBI > 20, respectively, and 59.5% and 65.8% with BI > 10, respectively. The diagnostic performance of LBA can be improved using PCB-adjusted BIs. aBI > 20 is the optimal cut-off for IIM diagnosis using the EUROLINE LBA panel.

A Multicenter, Prospective, Randomized, Parallel-Group Trial on the Effects of Temporary Methotrexate Discontinuation for One Week Versus Two Weeks on Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis.

OBJECTIVE: This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after vaccination in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, prospective, randomized, parallel-group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021-2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4-fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination. RESULTS: The modified intent-to-treat population included 90 patients in the 1-week MTX hold group and 88 patients in the 2-week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1-week MTX hold group and 12.9 ± 3.3 mg/week in the 2-week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups. CONCLUSION: A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX.

Comparative risk of blindness and vision-threatening ocular comorbidities in patients with Behçet's disease versus the general population.

OBJECTIVE: To compare the risk of blindness and vision-threatening ocular comorbidities in patients with Behçet's disease (BD) vs the general population. METHODS: Using 2002-2017 Korea National Health Insurance Service database, we did a population-based cohort study comparing newly diagnosed BD patients and age- and sex-matched non-BD controls at a 1:5 ratio. The primary outcome was blindness, defined as a best-corrected visual acuity of ≤20/500 in the better-seeing eye. Secondary outcomes were vision-threatening ocular comorbidities (cataract, glaucoma and retinal disorders) that require surgical interventions and incident uveitis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. We performed subgroup analyses by sex and BD diagnosis age. RESULTS: We included 31 228 BD patients and 156 140 controls. During a follow-up of 9.39 years, the incidence rate of blindness per 1000 person-years was 0.24 in BD and 0.02 in controls with an HR of 10.73 (95% CI 7.10, 16.22). The HR for secondary outcomes was 2.06 (95% CI 1.98, 2.15) for cataract surgery, 5.43 (4.57, 6.45) for glaucoma surgery and 2.71 (2.39, 3.07) for retinal surgery. The HR of incident uveitis was 6.19 (95% CI 5.83, 6.58). Males suffered a disproportionately higher risk of blindness than females due to greater severity rather than a lower incidence of uveitis. The risk of uveitis and blindness decreased as BD diagnosis age increased. CONCLUSIONS: In this large population-based cohort study, BD patients compared with the general population have a 10.73-fold risk of blindness in 10 years and also a substantially higher risk of diverse ocular comorbidities that pose potential threats to vision.

Association between sarcopenia defined as low lean mass by dual-energy X-ray absorptiometry and comorbidities of rheumatoid arthritis: Results of a nationwide cross-sectional health examination.

BACKGROUND: To examine the association between sarcopenia and comorbidities among patients with rheumatoid arthritis (RA). METHODS: We selected RA patients and age- and sex-matched non-RA controls at a 1:5 ratio from 2008-2011 Korea National Health and Nutrition Examination Survey database. Sarcopenia was defined by appendicular skeletal muscle mass. After investigating associations between sarcopenia and individual comorbidities among RA patients, we performed a stratified analysis comparing three subgroups (RA/sarcopenia, RA/non-sarcopenia, non-RA/sarcopenia) versus a non-RA/non-sarcopenia subgroup to evaluate interactive as well as independent effects of sarcopenia and RA on comorbidities. Health-related behaviors (exercise, smoking, drinking, and diet) were also examined. The weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, sex, and income. RESULTS: We included 400 RA patients and 2,000 non-RA controls (mean age 57.4 years, 79.6% female). Sarcopenia was observed in 20.5% of RA and 19.3% of non-RA group. Among RA patients, sarcopenia was associated with obesity (OR 2.61, 95% CI 1.42-4.83), dyslipidemia (3.09, 1.37-6.99), diabetes (2.07, 0.99-4.33), chronic obstructive pulmonary disease (18.77, 2.40-146.55), and hepatitis B ever-infection (8.69, 1.15-65.58). Among three stratified subgroups, only a RA/sarcopenia subgroup was associated with such comorbidities, cardiovascular diseases, and depression compared to a non-RA/non-sarcopenia subgroup. Health-related behaviors were comparable between patients with and without sarcopenia. CONCLUSIONS: In this nation-wide cross-sectional study, a wide spectrum of comorbidities were preferentially found among RA patients with sarcopenia than without, suggesting that sarcopenia is significantly associated with RA-related comorbidities. Particular attention should be paid to comorbidities of sarcopenic RA patients.

Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat.

BACKGROUND: To re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat. METHODS: Using 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat. CONCLUSION: In this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

Initial methotrexate dosage is not associated with an increased risk of liver toxicity in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study is to determine whether an initial methotrexate (MTX) dosage is associated with an increased risk of liver toxicity in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 730 RA patients who started MTX treatment between 2004 and 2019 at the rheumatology clinic at Seoul National University Hospital. The patients were divided into three groups according to the initial dosage of MTX they received: low (MTX ≤ 7.5 mg/week), intermediate (MTX 10-12.5 mg/week), and high (MTX ≥ 15 mg/week) dosage groups. Hepatotoxicity, defined as elevations in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels more than twofold above the upper limit of normal (2 × ULN), was examined during 90 days of MTX treatment. Predictors of hepatotoxicity were identified using logistic regression analyses. RESULTS: Of the 730 patients, 10 (1.4%) patients developed hepatotoxicity. The rate of hepatotoxicity was not different between the three MTX dosage groups. Univariate logistic regression analyses showed that the risk of hepatotoxicity was not higher in the intermediate MTX dosage group (odds ratio (OR): 0.89, 95% confidential interval (CI): 0.20-4.00, p = 0.877) or in the high MTX dosage group (OR: 1.23, 95% CI: 0.24-6.14, p = 0.804) than in the low MTX dosage group. Multivariate logistic regression analyses showed that elevated baseline AST and/or ALT levels above ULN and concomitant leflunomide use were associated with MTX hepatotoxicity. CONCLUSION: The initial MTX dosage is not associated with increased hepatotoxicity in RA patients. KEY POINTS: • An initial methotrexate (MTX) dosage is not associated with liver toxicity in patients with rheumatoid arthritis (RA). • RA patients with a baseline liver function test (LFT) abnormality or receiving concomitant leflunomide treatment should be monitored closely for LFT abnormalities during the early phase of MTX treatment.

A Case of Overlap Syndrome of Systemic Sclerosis and Cryoglobulinemic Vasculitis With Central Nervous System Involvement.

Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.

Congenital syphilis presenting with a generalized bullous and pustular eruption in a premature newborn.

Congenital syphilis occurs when Treponema pallidum crosses the placenta during pregnancy or from contact with an infectious genital lesion during delivery. Cutaneous manifestations of congenital syphilis are relatively common, occurring in approximately 30% to 70% of patients. Maculopapular lesions, vesiculobullous lesions, condylomata lata lesions, annular lesions, and erythema multiforme-like targetoid lesions have been reported. We report on a premature newborn with congenital syphilis who presented with generalized bullous and pustular eruption and desquamation at birth.

Porokeratotic eccrine ostial and dermal duct nevus showing partial remission by topical photodynamic therapy.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon, benign dermatosis and is characterized by asymptomatic grouped keratotic papules and plaques with a linear pattern on the extremities. Various treatments, including topical steroids, topical calcipotriol, topical 5-fluorouracil, retinoid, cryotherapy, and carbon dioxide laser ablation have been tried for PEODDN, but the results were unsatisfactory. Recently, topical photodynamic therapy (PDT) has been shown to be effective for various cutaneous disorders. We report a case of PEODDN showing partial remission with PDT using topical 5-aminolevulanic acid in a 4-year-old girl.

A case of tuberculosis cutis orificialis with perianal involvement.

Tuberculosis cutis orificialis (TCO) is a rare manifestation of cutaneous tuberculosis that is caused by auto-inoculation of mycobacteria in patients with advanced internal tuberculosis. TCO occurs in oral, perianal, or genital mucosa and adjacent skin. The tongue is the most frequently affected site, but the perianal area can also be affected. A 39-year-old male presented with a 4-month history of painful ulcers on the perianal area. The histopathologic findings revealed granulomatous infiltrates composed of epithelioid cells and Langhans-type giant cells in the dermis, and a few acid-fast bacilli noted on Ziehl-Neelsen staining. The polymerase chain reaction (PCR) was positive for Mycobacterium tuberculosis and the chest X-ray showed findings consistent with active pulmonary tuberculosis in both upper lung zones. The skin lesion showed complete resolution 2 months after the start of treatment with antituberculosis agents. We report a case of TCO with perianal involvement in a patient with underlying active pulmonary tuberculosis.

Epigallocatechin-3-gallate suppresses galactose-alpha1,4-galactose-1beta,4-glucose ceramide expression in TNF-alpha stimulated human intestinal epithelial cells through inhibition of MAPKs and NF-kappaB.

Intestinal epithelial cells (IECs) have been known to produce galactose-alpha1,4-galactose-beta1,4-glucose ceramide (Gb3) that play an important role in the mucosal immune response. The regulation of Gb3 is important to prevent tissue damage causing shiga like toxin. Epigallocatechin-3-gallate (EGCG) has been studied as anti-carcinogenic, anti-oxidant, anti-angiogenic, and anti-viral activities, and anti-diabetic. However, little is known between the expressions of Gb3 on IECs. The aim of this study was to examine the inhibitory effect of EGCG, a major ingredient of green tea, on Gb3 production via mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) in the TNF-alpha stimulated human colon epithelial cells, HT29. To investigate how Gb3 is regulated, ceramide glucosyltransferase (CGT), lactosylceramide synthase (GalT2), and Gb3 synthase (GalT6) were analyzed by RT-PCR in HT 29 cells exposed to TNF-alpha in the presence or absence of EGCG. EGCG dose-dependently manner, inhibits TNF-alpha induced Gb3 expression by blocking in both the MAPKs and NF-kappaB pathways in HT29 cells. TNF-alpha enhanced CGT, GalT2 and GalT6 mRNA levels and EGCG suppressed the level of these enzymes enhanced by TNF-alpha treatment.