Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

BACKGROUND: Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. METHODS: We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. RESULTS: There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. CONCLUSIONS: PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.

Monitoring liver function among patients who initiated anti-tuberculosis drugs in Taiwan, 2000-2011.

OBJECTIVE: To investigate adherence to liver function monitoring as recommended in Taiwan's tuberculosis (TB) diagnosis and treatment guidelines for newly diagnosed TB patients. DESIGN: Retrospective cohort study of the National Health Insurance Research Database (NHIRD), Taiwan, 2000-2011. METHODS: From the NHIRD, we identified 11 397 newly diagnosed TB patients who initiated anti-tuberculosis treatment between 2000 and 2011 and categorised these into three groups: completely, partially and non-adherent. Logistic regression was used to explore potential factors associated with the adherence rate. RESULTS: The completely adherent rate increased from 0.5% in 2000 to 9.2% in 2011, while the non-adherent rate decreased from 17.5% to 1.2%. Compared to the non-adherent group, patients with a history of liver disease (OR 4.36, 95%CI 1.92-9.87) and viral hepatitis (OR 9.39, 95%CI 1.47-60.19), as well as patients whose prescribing physicians were specialists in chest (OR 4.59, 95%CI 1.91-11.05), TB (OR 2.55, 95%CI 1.01-6.40) and infectious diseases (OR 3.93, 95%CI 1.08-14.31), had higher odds of being completely adherent to the guidelines. CONCLUSION: Our findings could serve as an important reference for developing effective strategies to improve adherence to guidelines and prevent patients from developing anti-tuberculosis drug-associated hepatotoxicity.

Risk of tuberculosis in rheumatoid arthritis patients on tumour necrosis factor-alpha inhibitor treatment in Taiwan.

OBJECTIVES: To quantify the incidence of tuberculosis (TB) in rheumatoid arthritis patients undergoing treatment with tumour necrosis factor-alpha inhibitors (TNFi). DESIGN: In a retrospective cohort study conducted using data from Taiwan's National Health Insurance claims databases, rheumatoid arthritis patients notified during the period 2006-2008 were recruited and classified based on types of TNFi treatment received. Active TB was the primary outcome. TB risk was estimated using Cox's proportional hazard model. The TB screening rate within 30 days of initiating treatment with TNFi was examined. RESULTS: Respectively 5079 and 829 patients were included in the non-TNFi and TNFi groups. Active TB rates were respectively 1411.3 and 679.5 events per 100,000 person-years in patients treated with adalimumab and etanercept. Significant TB risk was noted in patients treated with TNFi (aHR 4.87, 95%CI 2.14-11.06). No significant difference in active TB was observed between the TNFi subgroups (etanercept as reference, aHR 1.89, 95%CI 0.40-6.04). Only 8.7% (n = 9) of TNFi users underwent screening for TB before the first dose of TNFi. CONCLUSIONS: Patients on TNFi have a significantly greater risk of active TB than non-TNFi patients in the Taiwanese population. No difference in TB risk between the two available TNFi groups was noted. Screening for TB before initiating treatment with TNFi should be implemented.

There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade.

Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E virus.

Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern China. However, the evaluation of antibodies to HEV during consecutive time periods after infection has not been reported. We utilized enzyme immunosorbent assay (ELISA) to defect IgM and IgG anti-HEV in consecutive serum specimens from patients with acute hepatitis E and compared that data with detection rates of IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be detected as early as 4 days after onset of disease symptoms in some patients. The detection rate of IgM anti-HEV is significantly higher in specimens collected within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks after onset (67.6%) (P < 0.005). IgM anti-HEV had a similar pattern to IgM anti-HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti-HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P < 0.005). One should be cautioned against making a diagnosis of HEV infection solely by the currently available assays for IgG anti-HEV. In conclusion, IgM anti-HEV can be used as a reliable and sensitive marker for recent HEV infection, but serum specimens should be collected within 4 weeks after onset of symptoms to avoid false-negative results. In contrast, we should be aware of the failure to develop IgG anti-HEV in some patients. These patients carry the risk of reinfection.