Risk Analysis On Activation Of Latent Tuberculosis Infection In Patients With Rheumatic Diseases And Effect Of Prophylactic Therapy On Tuberculosis

Objective:To identify the risk factors on activation of latent tuberculosis infection in patients with rheumatic diseases during immunosuppressive therapy.To explore the efficacy and safety of 4-month rifampin and 6-month isoniazid prophylactic treatment regimen on latent tuberculosis infection in patients with rheumatic diseases.Methods:A 2-years study was conducted to evaluate the risk of activation of latent tuberculosis infection in patients with rheumatic diseases.990 patients with rheumatic disease who were admitted to the Department of Rheumatology and Immunology of the First Affiliated Hospital of Nanchang University from April2013 to January 2016 and excluded active tuberculosis were enrolled.All subjects were screened by IGRA test(T-SPOT.TB test)and then followed up regularly every 3months for 2 years.Of 232 patients with positive T-SPOT.TB,45 patients received different prophylactic therapies for latent tuberculosis infecion.Activation of tuberculosis,age,gender,comorbidity,diagnosis of rheumatic diseases,dosage of glucocorticoid,administration of immunosuppressive agent were collected in patients with positive T-SPOT.TB.Logistic regression analysis was performed to screen each variable.ROC curve was used to evaluate their predictive value.Of 45 patients who received prophylactic therapy,25 received 4-month rifampin therapy,the other for 6-month isoniazid therapy.The completion rate,clinical efficacy and toxicity were observed in these two groups.Results:In patients with rheumatic diseases,the IGRA-positive rates were 23.4%(232/990).2-years follow-up shows 4(0.52%)patients with negative IGRA developed into active tuberculosis and 13(7.06%)patients with positive IGRA developed into active tuberculosis,which pulmonary tuberculosis were 15 cases,1cases with vertebral tuberculosis and tuberculous pleurisy was 1 case,respectively.13 patients(76.47%)with active TB were undergoing prednisone with dosage of above 30 mg/d.Univariate analysis showed that age,administration of glucocorticoid,comorbidity of interstitial lung disease and cancer were significantly associated with tuberculosis activation(P<0.05),with the ORs of 0.956,18.113,5.312 and 10.182,respectively.Administration of glucocorticoid,comorbidity of cancer and interstitial lung disease entered the final logistic model,with the ORs of 17.864,4.544 and 12.042,respectively.Glucocorticoid dosage has best predictive value for the risk of activation of latent tuberculosis infection(AUC =0.768,p=0.001).Combination of the three risk factors was the better prediction for activation of latent tuberculosis infection(AUC=0.867,p=0.000)than any single risk factor.After 2 years of follow-up,24 patients completed treatment in the rifampin monotherapy group.One patient stopped treatment due to retinal hemorrhage.1patient died after one year of follow-up.In the isoniazid monotherapy group,90%(18/20)of the patients completed the treatment,1 patient stopped taking the drug due to elevated transaminase,and 1 patient dropout the treatment.None of these two groups had active tuberculosis.Conclusion:The incidence rate of active tuberculosis in patients with rheumatic diseases was much higher than general population.The incidence rate of active TB was much higher in RC patients with LTBI than in patients without LTBI.Dosage of glucocorticoid,comorbidity of malignant tumor and ILD are the risk factors of activation of latent tuberculosis infection in patients with rheumatic disease.Glucocorticoid dosage has best predictive value for the risk of activation of latent tuberculosis infection.Completion rates of the rifampin monotherapy group and isoniazid monotherapy group were high and major side effects were low in two therapies.