Approach to Latent Tuberculosis Infection Screening Before Biologic Therapy in IBD Patients: PPD or IGRA?

2020 ◽  
Vol 26 (9) ◽  
pp. 1315-1318 ◽  
Author(s):  
Jana G Hashash ◽  
Carla Abou Fadel ◽  
Mohammad Hosni ◽  
Lara Hassoun ◽  
Zeina Kanafani ◽  
...  

Abstract The use of biological agents for the treatment of chronic inflammatory conditions such as inflammatory bowel diseases (IBD) has been on the rise.1,2 Current biological therapies include antitumor necrosis factor-α (anti-TNF-α), anti-interleukin-12/23, and anti-integrin agents. Before initiation of biological drugs, screening for Mycobacterium tuberculosis infection is required to avoid reactivation or worsening of disease after immunosuppression. It has been shown that anti-TNF-α treated patients have a 14-fold increased risk of tuberculosis (TB) infection/reactivation compared with healthy controls.3 The methods for screening for TB have evolved over time and vary from region to region.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S348-S349
Author(s):  
D Ogresta ◽  
A Bišćanin ◽  
V Tomašić ◽  
Z Dorosulić ◽  
D Kralj ◽  
...  

Abstract Background Mycobacterium tuberculosis infection (TB) causes a huge number of deaths in the world. A majority (95%) of infections remain asymptomatic, defined as latent tuberculosis (LTB). The estimated incidence rate of TB in Croatia is 10.6 cases per 100 000 inhabitants. Patients with inflammatory bowel diseases (IBD) usually require immunosuppressive therapies which puts them at higher risk for infection. LTB diagnosis and prophylactic treatment are recommended for all patients starting biologics. Methods A single-centre retrospective study in the continental part of Croatia included all IBD patients who started treatment with biologics and have presented with TB or LTB from January 2016 till September 2019. The aim was to evaluate the prevalence of LTB among patients with IBD before starting biologic therapy, and TB reactivation during treatment with biologics. All patients underwent Interferon Gamma Release Assay (IGRA) and X-ray. Active infection was excluded or diagnosed using clinical history, bronchoscopy, CT scan and sputum stain for Mycobacteria. Results Study population included 74 patients treated with biologics: 51% female, 73% Crohn’s disease (CD); 37% starting adalimumab, 29% infliximab, 19% ustekinumab and 15% vedolizumab. Prevalence of LTB was 8.1% (6 patients), and all patients underwent isoniazid prophylaxis for 9 months except one patient treated with conventional immunomodulatory therapy which failed prophylactic therapy with both isoniazid and rifampin (liver injury). Among patients with adequate chemoprophylaxis, two patients later on started with anti-TNF therapy (adalimumab), two patients with vedolizumab and one with ustekinumab. One patient with CD and negative LTB screening developed pulmonary TB during induction with infliximab (1 month after initiation); after successful treatment with conventional fourfold therapy, the patient was switched to vedolizumab. During the observational period (median 16 months), all IBD patients with LTB as well with cured TB were in clinical and biochemical remission, without signs of TB (re)activation. Conclusion Our study has demonstrated that prevalence of LTB among our IBD patients starting biologics was significant (8.1%). Treatment with vedolizumab, ustekinumab and anti-TNF (adalimumab) after isoniazid chemoprophylaxis appears to be safe during the observational period, without signs of TB reactivation.


2021 ◽  
Vol 16 ◽  
Author(s):  
Salma Athimni ◽  
Maroua Slouma ◽  
Rim Dhahri ◽  
Imen Gharsallah ◽  
Leila Metouia ◽  
...  

Background: Anti-tumor necrosis factor-α (TNF-α) is a life-changing treatment leading to quality-of-life improvement. Nonetheless, this treatment is associated with a high risk of infection, especially tuberculosis. Objective: Our study aimed to determine the frequency of active tuberculosis in our patients with chronic rheumatic disease and treated with TNF-α. Methods: We conducted a retrospective study including patients with Rheumatoid Arthritis and Spondylarthritis diagnosed according to ACR/EULAR 2009 criteria and ASAS 2010, respectively, and treated with biological agents for at least 6 months. We collected data regarding tuberculosis screening and the occurrence of active tuberculosis during follow-up. Results: 82 patients were included (37 men and 45 women). The mean age was 42 ± 3.4 years. At inclusion, no patient had a medical history of tuberculosis. The diagnosis of latent tuberculosis infection was established in 17 patients (20.7%). Prophylactic treatment was prescribed in all these cases for three months. Two cases (2.4%) of active tuberculosis occurred under biologic (infliximab). It was two severe forms of tuberculosis. The first case had miliary tuberculosis associated with hepatic and peritoneal involvement. The second one had pleural tuberculosis. These two patients received anti-tuberculosis therapy, and the biological treatment was interrupted. Given the high disease activity, the anti-TNF-α was restarted after 3 and 4 months. There was no recurrence of tuberculosis after 7 years of follow-up. Conclusion: The use of TNF-α blockers is associated with a risk of disseminated forms of tuberculosis. Tuberculosis screening, which is recommended before the biological onset, is also necessary under this treatment. Restarting the anti-TNF-α after appropriate treatment of tuberculosis seemed to be safe.


Author(s):  
Anna Rita Corvino ◽  
Maria Grazia Lourdes Monaco ◽  
Elpidio Maria Garzillo ◽  
Elena Grimaldi ◽  
Giovanna Donnarumma ◽  
...  

Healthcare workers are at an increased risk of contracting Mycobacterium tuberculosis infection. Tuberculin skin test (TST) and interferon gamma release assay (IGRA) represent the available tests most used for the diagnosis of latent tuberculosis infection (LTBI). Different borderline zones have been proposed for defining conversions and reversions to improve the interpretation of the IGRA test results as part of serial testing. From 2012 to 2017, 5468 health students of an Italian University Hospital were screened for tuberculosis infection through the execution of the TST and, in case of positivity, of the QuantiFERON-TB® Gold In-Tube assay (QFT–GIT). The QFT–GIT is considered “borderline” with values from 0.35 to 0.99 IU/mL. Among the students who performed the QFT–GIT assay, 27 subjects presented a range of values defined as borderline. The QFT–GIT was repeated after 90 days on 19 subjects with borderline values and showed a negativization of the values in 14 students and a positive conversion in three cases, while for two students, a borderline value was also found for the second test, with a 74% regression of the borderline cases. The introduction of QuantiFERON borderline values is a useful assessment tool to bring out LTBI case candidates for chemoprophylaxis.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sofoklis Stavros ◽  
Despoina Mavrogianni ◽  
Myrto Papamentzelopoulou ◽  
Evaggelos Basamakis ◽  
Hend Khudeir ◽  
...  

Abstract Background Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, −238G > A, −308G > A and − 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women. Methods This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples. Results The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births. Conclusions This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, −238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.


2013 ◽  
Vol 1 ◽  
pp. 112-117 ◽  
Author(s):  
Jolanta Paluch-Oleś ◽  
Agnieszka Magryś ◽  
Maria Kozioł-Montewka ◽  
Arkadiusz Koszarny ◽  
Maria Majdan

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Hongpeng Zhao ◽  
Lixia Liu ◽  
Bo Liu ◽  
Yanmin Wang ◽  
Feng Li ◽  
...  

Polymorphisms in the tumor necrosis factor α (TNF-α) gene are emerging as key determinants of gastric diseases. The TNF-α-238G/A single-nucleotide polymorphism (SNP) is the most extensively studied. However, this association is inconsistent amongst different populations. We therefore conducted an updated meta-analysis to obtain a more precise estimate of the association of TNF-α-238G/A polymorphism with gastric cancer (GC) risk. A comprehensive search of PubMed, Embase, Chinese (CNKI and WanFang) databases was performed to identify relevant studies through 5 May 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Fourteen studies were included in our meta-analysis involving 2999 cases and 4685 controls. There was no significant association between TNF-α-238G/A polymorphism and GC risk in the overall populations. In the subgroup analysis, we found that TNF-α-238G/A polymorphism was associated with the increased risk of GC amongst Asians, especially in Chinese, but not in Caucasians. Subgroup analysis by genotyping methods revealed increased risk for other methods. In conclusion, our present meta-analysis shows that TNF-α-238G/A polymorphism is associated with the risk of GC in East Asian individuals.


Author(s):  
Beata Wańczyk-Dręczewska ◽  
Agnieszka O wczarczyk-Saczonek ◽  
Waldemar Placek

Introduction: The introduction of biological therapy has revolutionized the treatment of psoriasis. Due to its immunosuppressive effect, the following side effects might occur: injection-site reactions, exacerbation of autoimmune diseases, increased risk of malignant tumors and infections, including tuberculosis (TB). Aim: The aim of this report is to present a case of a patient who developed TB during tumornecrosis factor α (TNF-α) inhibitor therapy. Case study: A 52-year-old man was admitted to the Dermatology Clinic for re-qualification for biological treatment with adalimumab. The patient was treated with cyclosporin A and lefludomide combined with methotrexate with no effect and the adalimumab therapy was initiated with complete remission of psoriatic lesions. The patient was suspended in the drug program because of TB. TNF-α inhibitor therapy was resumed after antimycobacterial treatment, during which lymphadenopathy was observed and serous TB was confirmed. Three months after the treatment, the patient was rehospitalized because of suspicion of TB relapse. It was decided to requalify the patient for biological therapy after completion of antimycobacterial treatment. Due to the high risk of TB recurrence, switch to the interleukin-17 inhibitor was decided. Results and discussion: The proper qualification and thorough testing before biological treatment ensures patients’ safety and satisfactory therapeutic effect. It should be remembered that during longterm therapy with TNF antagonists, both reactivation of latent TB as well as new infection are serious problems. Therefore, regular tests should be performed, especially in countries with high prevalence of this disease. Conclusions: In patients who develop TB, particularly recurrent, switching to a drug with a different mechanism should be considered.


Author(s):  
Lindsey S Lawrence ◽  
Amer Heider ◽  
Andrew A M Singer ◽  
Haley C Neef ◽  
Jeremy Adler

Abstract Background Granulomatous intestinal inflammation may be associated with aggressive Crohn’s disease (CD) behavior. However, this has not been confirmed, and it is unknown if associated disease complications are preventable. Methods This is a retrospective cohort of patients younger than 21 years at CD diagnosis (November 1, 2005 to November 11, 2015). Clinical information was abstracted, including dates of starting medications and the timing of perianal fistula or stricture development, if any. Diagnostic pathology reports were reviewed, and a subset of biopsy slides were evaluated by a blinded pathologist. Patients were excluded if perianal fistula or stricture developed within 30 days after CD diagnosis. Medications were included in analyses only if started >90 days before development of perianal fistula or stricture. Results In total, 198 patients were included. Half (54%) had granulomas at diagnosis. Granulomas were associated with a greater than 3-fold increased risk of perianal fistula (hazard ration [HR] = 3.24; 95% confidence interval CI], 1.40–7.48). Immunomodulator and anti-tumor necrosis factor-α (anti-TNF) therapy were associated with 90% (HR, = 0.10; 95% CI, 0.03–0.42) and 98% (HR, = 0.02; 95% CI, 0.01–0.10) reduced risk of perianal fistula, respectively. Patients with granulomatous inflammation preferentially responded to anti-TNF therapy with reduced risk of perianal fistula. The presence of granulomas was not associated with risk of stricture. Immunomodulator and anti-TNF therapy were associated with 96% (HR, = 0.04; 95% CI, 0.01–0.22) and 94% (HR, = 0.06; 95% CI, 0.02–0.20) reduced risk of stricture, respectively. Conclusions Granulomas are associated with increased risk of perianal fistula but not stricture. Steroid sparing therapies seem to reduce the risk of both perianal fistula and stricture. For those with granulomas, anti-TNF-α therapy greatly reduced the risk of perianal fistula development, whereas immunomodulators did not.


Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 530 ◽  
Author(s):  
Eugenie Mussard ◽  
Sundy Jousselin ◽  
Annabelle Cesaro ◽  
Brigitte Legrain ◽  
Eric Lespessailles ◽  
...  

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S271-S271
Author(s):  
Eun Ju Choo ◽  
Se Yoon Park

Abstract Background We investigated the prevalence of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) and analyzed its risk factors in a tertiary care university hospital in South Korea in a population with intermediate tuberculosis (TB) burden. Methods A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant. QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay and chest radiography were performed to investigate the rate of LTBI. Results A total of 1,429 participants, 213 (14.9%) doctors and 988 (69.1%) nurses and 228 (16.0%) others were enrolled. The mean age of the subjects was 33.0 years old, and 1,175 (82.2%) were female. Of the participants, 94.5% had received BCG vaccine. QFT-GIT assays were positive for 156 subjects (10.9%). Of the 213 doctors, 28 (13.1%) were positive by QFT-GIT, and among the 988 nurses, 94 (9.5%) had positive QFT-GIT results. Experience of working in hospital was significantly associated with positive LTBI test results by QFT-GIT assay. Gender and duration of employment as an HCW were significantly associated with having a positive QFT-GIT result in univariate analyses. In multivariate analyses, duration of employment as an HCW (>15 years) (odds ratio, 1.98; 95% confidence interval, 1.14–3.43) was independently associated with increased risk of a positive QFT-GIT result. Conclusion A high prevalence of LTBI was found among our HCWs. Considering the association between the experience of working in hospital and high risk of LTBI. The risk for tuberculosis infection among HCWs was higher than general population, which suggests that stricter preventive strategies against nosocomial tuberculosis infection should be implemented. Disclosures All authors: No reported disclosures.


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