Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.

Effect of tumor necrosis factor inhibitors on rheumatoid arthritis-induced peripheral neuropathy A cohort study

In this historical cohort study, 236 patients with primary rheumatoid arthritis were treated with the tumor necrosis factor inhibitors, etanercept or infliximab （n = 80）, or by conventional methods （n = 156）. Results revealed that 11 patients developed varying types of peripheral neuropathy at 1-2 years post-treatment （mean 16 months）. The incidence of peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 8.8% （7/80）, which was significantly higher than the conventional treatment group （2.6%; 4/156）. The relative risk of developing peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 3.41 （95% confidence interval： 1.03 11.31）. Comparison of the tumor necrosis factor inhibitors revealed that etanercept and infliximab had no significant difference in terms of inducing peripheral neuropathy. Experimental findings indicate that tumor necrosis factor inhibitors may increase the risk of peripheral neuropathy.

Cytomegalovirus colitis in a patient with Behcet’s disease receiving tumor necrosis factor alpha inhibitory treatment

Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.

Inflammatory bowel disease: An increased risk factor for neurologic complications

Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.

TNF inhibitors to treat ulcerative colitis in a metastatic breast cancer patient:A case report and literature review

Adalimumab (ADA) is a tumor necrosis factor (TNF) inhibitor, used for the treatment of inflammatory bowel disease. Previous studies have reported an increased risk of cancer following exposure to TNF inhibitors, but little has been reported for patients with cancer receiving TNF-inhibitor treatment. We present a female patient with metastatic breast cancer and ulcerative colitis (UC) who was treated with ADA. A 54-year-old African American female with a past history of left-sided breast cancer (BC) diagnosed at age 30 was initially treated with left-breast lumpectomy, axillary dissection, followed by chemotherapy and radiation therapy. Years after initial diagnosis, she developed recurrent, bilateral BC and had bilateral mastectomy. Subsequent restaging computed tomography (CT) scan demonstrated distant metastases to the bone and lymph nodes. Three years into her treatment of metastatic breast cancer, she was diagnosed with UC by colonoscopy. Her UC was not controlled for 5 mo with 5-aminosalicylates. Subcutaneous ADA was started and resulted in dramatic improvement of UC. Four months after starting ADA, along with ongoing chemotherapy, restaging CT scan showed resolution of the previously seen metastatic lymph nodes. Bone scan and follow-up positron emission tomography/CT scans performed every 6 mo indicated the stability of healed metastatic bone lesions for the past 3 years on ADA. While TNF-α inhibitors could theoretically promote further metastases in patients with prior cancer, this is the first report of a patient with metastatic breast cancer in whom the cancer has remained stable for 3 years after ADA initiation for UC.

MESANGIAL CELL PROLIFERATION INDUCED BY TNF-α IS DETERMINED BY LEVELS OF CYCLIN-KINASE INHIBITOR P27

Objective To investigate the role of cyclin-kinase inhibitor p27 on proliferation of mesangial cell(MC) induced by tumor necrosis factor α( TNF-α ). Methods The p27 protein of MC lysate was detected with western blotting analysis. The degree of MC proliferation was estimated through [^3H] thymidine incorporation. The effect of reducing p27 expression on MC proliferation was analysed with p27 antisense oligodeoxynucleotide (ODN). Results TNF-α(200000U/L) decreased p27 level to (0.6±0.1 ) from (1. 1±0.1 ) of MC lysate cultured in serum free DMEM for 24h ( P<0.01 ) and increased [^3H] thymidine incorporation to ( 2060±112 ) from (685±53) cpm/well( P<0.01 ). p27 antisense ODN transfection decreased p27 level of MC stimulated by TNF-α for 24h [(0.3±0.1 ) vs (0.6±0.1), P <0.01 ] and increased [^3H] thymidine incorporation [(2420±130) vs (2060±112) cpm/well, P <0.05]. Conclusion The decline of p27 protein maybe play an important role in MC proliferation induced by TNF-α.

Immunosuppressive therapies for inflammatory bowel disease

Inflammatory bowel disease (IBD) is comprised of Crohn&#x02019;s disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical course. For many years, the drug therapy was limited to sulfasalazine and related aminosalicylates, corticosteroids and antibiotics. Studies suggesting that the pathophysiology of these disorders relates to a disregulated, over-active immune response to indigenous bacteria have led to the increasing importance of immunosuppressive drugs for the therapy of IBD. This review details the mechanisms of action, clinical efficacy, and adverse effects of these agents.

Acute myocardial infarction in a young man with ankylosing spondylitis: A case report

BACKGROUND Ankylosing spondylitis(AS)is a chronic progressive inflammatory disease that mainly affects the spine and sacroiliac joints.To the best of our knowledge,AS with acute myocardial infarction(AMI)has rarely been reported.Here,we report an unusual case of AS with AMI in a young patient.CASE SUMMARY A 37-year-old man was admitted to the Department of Rheumatology and Immunology of our hospital on March 14,2020,for low back pain.Further evaluation with clinical examinations,laboratory tests,and imaging resulted in a diagnosis of AS.Treatment with a non-steroidal anti-inflammatory drug and a tumor necrosis factor inhibitor partially improved his symptoms.However,his back pain persisted.After 6 wk of treatment,he was admitted to the emergency room of another hospital in this city for sudden-onset severe chest pain consistent with a diagnosis of AMI.Angiography revealed severe narrowing of the coronary arteries.Surgical placement of two coronary stents completely relieved his back pain.CONCLUSION AS can cause cardiovascular diseases,including AMI.It is important to consider the cardiovascular risks in the management of AS.

Efficacy,safety,and cost-effectiveness of triple therapy in preventing relapse in rheumatoid arthritis:A randomized controlled trial(ESCoRT study)

Background:Biological agents,such as tumor necrosis factor inhibitors(TNFi),have been widely used in rheumatoid arthritis(RA)patients and greatly improved goal achievement.The aim of this study was to investigate whether conventional synthetic diseasemodifying anti-rheumatic drugs(csDMARDs)combination was better in reducing relapse than methotrexate(MTX)monotherapy,and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity(LDA)with TNFi and MTX therapy.Methods:RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks.Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups:(A)adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks;(B)maintaining TNFi and MTX for 60 weeks;and(C)maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks.The primary outcome was relapse.Results:A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized,with 24,21,and 22 patients in groups A,B,and C,respectively.The relapse rates of groups A and B during the entire 60 weeks were comparable[10/22(45.5%)vs.7/20(35.0%),χ^(2)=0.475,P=0.491],however,significantly lower than that of group C[10/22(45.5%)vs.17/20(85.0%),χ^(2)=5.517,P=0.019;7/20(35.0%)vs.17/20(85.0%),χ^(2)=11.035,P=0.004,respectively].Taking RMB 100,000 Yuan as the threshold of willingness to pay,compared to MTX monotherapy(group C),both TNFi maintenance and triple csDMARDs therapies were cost-effective,but triple csDMARDs therapy was better.Conclusion:For RA patients who have achieved LDA with TNFi and MTX,csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.Trial registration:ClinicalTrials.gov,NCT02320630.