High prevalence of latent tuberculosis using the QuantiFERON-TB Gold Plus test in Takayasu arteritis

Objectives: This study aims to investigate latent tuberculosis using the QuantiFERON-TB Gold Plus method in patients with Takayasu arteritis (TA). Patients and methods: This case-control study included 22 patients with TA (3 males, 19 females; median age: 36.5 years; IQR, 32 to 50 years), 22 healthy individuals (3 males, 19 females; median age: 38.5 years; IQR, 32.5 to 50 years), and 66 patients with diffuse connective tissue diseases (DCTDs) (4 males, 62 females; median age: 41 years; IQR, 29.8 to 54 years). Two control groups were formed: (i) age- and sex-matched healthy individuals and (ii) patients with other DCTDs. Epidemiological data were collected, and the QFT-Plus test was performed. The QFT-plus positivity was compared among the groups. Results: A higher prevalence of QFT-Plus positive cases was observed in the TA group (8/22) than in the healthy control group (1/22) (p=0.020) or in the group with other DCTDs (3/66) (p=0.001). There was a statistically significant difference in the past pulmonary tuberculosis prevalence between the TA and DCTD groups (p=0.013). Conclusion: The prevalence of latent tuberculosis in TA patients (36.4%) was higher than that in both control groups and higher than the prevalence of latent tuberculosis among the general Brazilian population. Although a positive association was found, it is not possible to establish a direct cause-effect relationship. Given the increasing use of anti-cytokine therapies in TA, it is necessary to thoroughly screen patients with TA before initiating immunosuppressive therapy to avoid tuberculosis reactivation.

Analyzing Tuberculosis Reactivation in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Treated with Biological Therapy Using Machine Learning Methods

This study is based on the consideration that the patients with rheumatoid arthritis and ankylosing spondylitis undergoing biological therapy have a higher risk of developing tuberculosis. The QuantiFERON-TB Gold test result was the output of the models and a series of features related to the patients and their treatments were chosen as inputs. A distribution of patients by gender and biological therapy, followed at the time of inclusion in the study, and at the end of the study, is made for both rheumatoid arthritis and ankylosing spondylitis. A series of classification algorithms (random forest, nearest neighbor, k-nearest neighbors, C4.5 decision trees, non-nested generalized exemplars, and support vector machines) and attribute selection algorithms (ReliefF, InfoGain, and correlation-based feature selection) were successfully applied. Useful information was obtained regarding the influence of biological and classical treatments on tuberculosis risk, and most of them agreed with medical studies.

COVID-19 and chronic diabetes: the perfect storm for reactivation tuberculosis?: a case series

Background The coronavirus disease 2019 pandemic is predicted to have a net negative effect on tuberculosis control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues such as the lockdown of tuberculosis services affect all patients, while biosocial factors have a differential impact on an individual’s risk for tuberculosis or adverse tuberculosis outcomes. Case presentation We report three Hispanic cases of incident tuberculosis (two males, 43 and 44 years old; one female, 49 years old) after resolution of coronavirus disease episodes. Coincidentally, all cases shared a common risk factor: a chronic history poorly controlled diabetes. Conclusions Our findings alert to the threat posed by the synergy between coronavirus disease and diabetes, on tuberculosis reactivation. In medium- to high-risk settings for tuberculosis, we recommend implementation of routine screening for latent tuberculosis infection in these cases, and preventive tuberculosis treatment in those who are positive.

Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report

Background Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. Case presentation A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. Conclusion To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Systemic corticosteroids for management of ‘long-COVID’: an evaluation after 3 months of treatment

Some patients even 4 weeks after Corona Virus Disease 2019 (COVID-19) remain to be symptomatic and are known as “long-COVID”. In the present study we performed the follow up evaluation at 3 months of long-COVID patients, after treatment with systemic steroids. During the study duration, out of the 4,542 patients managed in the outpatient department of the particular unit, there were 49 patients of Long-COVID. The patients having abnormal computed tomography (CT) alongwith resting hypoxia or exertional desaturation were treated with systemic steroid (deflazacort) in tapering doses for 8-10 weeks. We retrospectively analysed the clinical and radiological findings of these patients at first presentation and at about 3 months of follow up visit. On follow up, all the 49 long-COVID patients showed improvement. The occurrence of breathlessness decreased from 91.83% to 44.89% (p<0.001) and cough from 77.55% to 8.16% (p<0.001). Twenty-four patients were prescribed systemic steroids. Out of these, nearly 58% patients had MMRC grade 4 breathlessness, which decreased to < 2 MMRC in about 86% of these patients. MMRC grade (median) decreased from 3 to 1 (p<0.001). Majority of patients who were tachypnoeic and hypoxic at rest (n=7) showed improvement (71%), post-treatment with corticosteroids. Occurrence of normal chest X-ray increased from 12% to 71% (p<0.001). All these patients had abnormal CT thorax initially, and post-treatment 25% had normal CT thorax. Hence, we conclude that systemic steroids are helpful in hastening recovery of select subset of long-COVID patients. Simultaneously, we should be cautious of immunosuppressive effects of steroids like tuberculosis reactivation, especially in tuberculosis endemic countries. These findings have therapeutic implications and may serve as guidance for future approach to the management of ‘long-COVID’ with pulmonary sequalae.

1410. Isoniazid Therapy for Latent Tuberculosis Infection in Patients with Cancer Treated with Checkpoint Inhibitors Immunotherapy

Background Data on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI. Methods We performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy. Results We identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days. Conclusion Our data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy. Disclosures Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Prevention of Tuberculosis Reactivation

It is not known if screening for latent tuberculosis infection (LTBI) is useful for reducing the risk of tuberculosis reactivation among people at risk (no evidence was found). In people with LTBI, providing treatment for the latent infection may be helpful for preventing the development of active tuberculosis disease. (In addition, LTBI treatments do not appear to increase the risk for hepatotoxicity.) Treatment effectiveness may depend on the specific LTBI treatment regimen used. For people at an increased risk for tuberculosis ― including those from areas with high rates of tuberculosis ― guidelines recommend screening and treatment for LTBI, as this may help prevent TB reactivation. Treatment is recommended for those who are 65 years old or younger and with a positive LTBI result (recommendation from 1 high-quality guideline).

A Case of Crohn’s Disease with Cardiac Tamponade Caused by Tuberculous Pericarditis: Assessment of a Rare Phenomenon

A 28-year-old woman was hospitalized for cardiac tamponade caused by tuberculous pericarditis. She was taking ustekinumab (UST) for Crohn’s disease. UST is not considered to significantly increase the risk of developing serious infections, including tuberculosis. However, there is still a risk of Mycobacterium tuberculosis reactivation. Therefore, for patients on concurrent UST and antituberculosis medication, a close collaboration among specialists in infectious diseases, cardiology, and gastroenterology is necessary.