Anti-tumor Necrosis Factor-alpha Inhibitors Research Articles

Neurosarcoidosis-Induced Winging Scapula: Efficacy of Infliximab Treatment in Addressing Multifaceted Challenges.

Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or alongside other systemic symptoms. Here, we describe the case of a 45-year-old male with a history of recurrent sinusitis refractory to antibiotics, who presented to the emergency department with sinus congestion and dysphagia. Clinical examination revealed left lower motor neuron facial palsy and enlarged submandibular salivary glands. Despite obtaining negative results from various antibody panels, the patient exhibited elevated Angiotensin Converting Enzyme levels of 83 nmol/kg/min. Additionally, computed tomography chest scans revealed bilateral hilar and mediastinal lymph node enlargement, findings consistent with sarcoidosis. Otorhinolaryngology evaluation for dysphagia confirmed left vocal cord palsy. Following a negative infectious disease workup, submandibular salivary gland biopsy confirmed sarcoidosis. Treatment with mycophenolate mofetil and oral steroids led to gradual improvement in salivary gland swelling, dysphagia, and facial palsy. However, worsening left shoulder pain prompted further investigation, revealing winging of the left scapula on repeat examination. Magnetic resonance imaging (MRI) of the cervical spine revealed a six mm hyperintensity in the left dorsal cord at the C5 level, suggesting possible neurosarcoidosis vs. demyelinating disease. Subsequently, the patient was prescribed anti-tumor necrosis factor alpha inhibitor infliximab. Subsequent MRI of the cervical spine, conducted six months after initiating Infliximab therapy, indicated resolution of the lesions. This positive outcome was supported by the patient's report of symptom improvement, notably reduced shoulder pain and improvement in left scapular winging. This case underscores the unusual co-occurrence of Bell's palsy and vocal cord palsy in the same patient, along with the potential contribution of neurosarcoidosis to the winged scapula. Additionally, it sheds light on the positive response of neurosarcoidosis to Infliximab therapy.

Prevalence of Latent Tuberculosis Infection Among Rheumatology Patients and Management Practices in the United Arab Emirates: A Single-Center Retrospective Cohort Study.

Introduction Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis (TB) infection using interferon-gamma release assays (IGRAs). Variability in the management of latent and indeterminate IGRA results across institutionslimited long-term outcome data. A retrospective study was conducted at Tawam Hospital, United Arab Emirates, to investigate the incidence and management protocols associated with positive and indeterminate IGRAresults, as well as TBinfection, among patients with rheumatic conditions. Methods A single-center retrospective observational study was performed at Tawam Hospital, Abu Dhabi, UAE. Ethical approval for this study was obtained from the Tawam Human Research Ethics Committee. Laboratory records and the hospital's electronic medical system were used to obtain information about IGRA results over a 12-year period (April 2010-April 2022). The hospital's electronic medical system was used to obtain patient information and subsequent management approaches of positive and indeterminate IGRAs.Moreover, long-term follow-up data were collected to determine the risk of TB reactivation in the cohort. Results We found a total of 1,012 positive and 223 indeterminate IGRA test results within the 12-year period. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were women (n = 24, 61.5%) and UAE nationals (n = 22, 56.4%), and their mean age was 38.6 years. Systemic lupus erythematosus was the most prevalent rheumatologic condition (n = 21, 53.8%). Thirteen (33.3%) were on disease-modifying anti-rheumatic drugs (DMARDs) and 26 (66.7%) were on corticosteroids during IGRA testing. A total of eight patients (20.5%) received anti-TB medications. In the positive IGRA group, the mean age was 55.7 years and the female-to-male ratio was 3:1. The most common rheumatologic condition was rheumatoid arthritis (n = 69, 56%). Sixty-five (52.8%) patients were on conventional DMARDs, 43 (34.9%) were on corticosteroids during IGRA testing, and 74 (60%) received anti-TB medications. Two cases (1.6%) of active TB infections were detected among patients with positive IGRA tests, both of whom were receiving anti-tumor necrosis factor alpha inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Long-term data on the risk of TB activation in positive and indeterminate IGRA results for rheumatological conditions are low. It is recommended to reassess the choice of using anti-TNF-α, with a positive IGRA result if no other feasible alternatives can be offered. Our findings stress the importance of age, underlying diseases, and immunosuppressive treatments in interpreting IGRA results and guiding patient management. A large multicenter study is needed to understand the differences and outcomes of such patients in TB endemic and nonendemic geographical areas.

Tumor Necrosis Factor-Alpha Inhibitors and Cardiovascular Risk in Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune disease that, if untreated or poorly controlled, can cause significant morbidity in terms of loss of physical function and higher mortality due to higher cardiovascular risk. The standard of care for this disease is the use of disease-modifying antirheumatic drugs (DMARDs). However, patients unable to reach low disease activity or remission and patients unable to tolerate conventional DMARDs will be switched to biologic therapy, a subset of which includes anti-tumor necrosis factor-alpha inhibitors. Since tumor necrosis factor-alpha inhibitors (TNFi) inhibit the inflammatory cascade, they also play an essential role in dampening the progression of atherosclerosis and altering the risk of cardiovascular outcomes in RA.In this study, we assessed the risk of cardiovascular diseases, namely, congestive heart failure, nonfatal myocardial infarction, cerebrovascular disease, and coronary artery disease. We carried out the analysis by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted a literature search utilizing the following databases: PubMed, Science Direct, and Cochrane Library. Using the search strategy, we found a total of 19 articles that fit the inclusion and exclusion criteria, in addition to passing the risk of bias assessment. This is composed of three systematic reviews with meta-analyses, three randomized control studies, four narrative reviews, and nine cohort studies. In this systematic review, it was found that treatment with TNFi causes a corresponding reduction in the risk of cardiovascular events. This review encourages further dissection into the inner workings of TNFi in reducing the risk of cardiovascular disease among patients with RA.

Pure peripheral spondyloarthritis, is it exceedingly rare? A real-world experience from an Indian tertiary care hospital

Background: Peripheral spondyloarthritis (pSpA) is usually associated with psoriasis, inflammatory bowel disease, or preceding infection (called reactive arthritis). Pure pSpA is a clinical entity wherein there are enthesitis, dactylitis, or arthritis, without any of the above-associated conditions. We aimed to describe the clinical, laboratory, radiological, and management profile of pure pSpA, among patients with pSpA presenting to the rheumatology outpatient department. Materials and Methods: In this retrospective, observational study, medical records of all the patients diagnosed as pSpA by a rheumatologist, between January 1, 2016, and December 31, 2018, were included. Among these, thirty patients qualified to be called pure pSpA, and we reported their demographic characteristics (age and sex), clinical features (onset of disease, clinical signs, and symptoms), laboratory parameters (erythrocyte sedimentation rate, hemoglobin, and C-reactive protein), radiological findings, and treatment pattern. Results: Thirty patients fulfilled the criteria for pure pSpA. The mean age (standard deviation) of the patients at onset was 32 ± 5.8 years. The mean disease duration before diagnosis was 9.7 months. Arthritis, enthesitis, and dactylitis were present in 29 (96.7%), 8 (26.7%), and 9 (30%) patients, respectively. Eighteen (60%) patients had monoarthritis, while 11/30 (36.7%) had oligoarthritis, at presentation. HLA B27 was positive in 24/30 (80%) patients. Seven patients (23.3%) had bilateral sacroiliitis on imaging and two (6.7%) had unilateral sacroiliitis. Twenty patients (66.7%) required conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while two (6.7%) required biological DMARDs in the form of anti-tumor necrosis factor-alpha inhibitors. Conclusion: Pure pSpA is a relatively rare clinical disease which presents with either a mono or oligoarthritis and shows good treatment response to csDMARDs.

Advances in Management of Intestinal Behçet's Disease: A Perspective From Gastroenterologists.

Intestinal Behçet's disease (intestinal BD) is a rare chronic inflammatory disorder of the intestine that is characterized by recurrent intestinal manifestations with other systemic features of BD. Intestinal BD is diagnosed when a typically shaped ulcer is observed in the gastrointestinal tract, and the clinical findings meet the diagnostic criteria for BD. Owing to the small number of patients, intestinal BD is easily underestimated. On the other hand, but it often requires surgical treatment because of severe complications, including intestinal perforations or massive bleeding. The same treatment strategies used for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are used for intestinal BD. 5-Aminosalicylic acids, corticosteroids, and immunomodulators are considered conventional therapies, but a considerable number of patients eventually become unresponsive to these pharmaceutical treatments. Recently, biologic agents, such as anti-tumor necrosis factor-alpha inhibitors, have also been suggested as a new treatment option for intestinal BD. This article reviews the pathogenesis and diagnosis of intestinal BD and the current treatment strategies that are expected to be useful for rheumatologic specialists.

2463 Infliximab Drug-Induced Autoimmune Hepatitis in Patient With Crohn's Ileocolitis

INTRODUCTION: Infliximab is an anti-tumor necrosis factor alpha inhibitor commonly used in the treatment of Crohn's disease. It is known to produce mild elevations in liver enzymes, however, severe damage and marked elevations in transaminases related to drug-induced autoimmune hepatitis (AIH) are rare. We present a case of a patient with Crohn's disease who recently began infliximab and presented with severe infliximab-induced autoimmune hepatitis. CASE DESCRIPTION/METHODS: A 37-year-old man with Crohn's ileocolitis, diagnosed at age 28 and recently inducted with infliximab, presented with fatigue, weakness, and epigastric pain. He had previously been on 6-mercaptopurine, adalimumab, and ustekinumab, but had most recently been on azathioprine (AZT) and began infliximab two months prior to presentation. Approximately one month prior to presentation, he developed elevated transaminases with aspartate transaminase (AST) and alanine transaminase (ALT) in the 300s, so AZT was discontinued as this was thought to be the cause. Despite discontinuation of AZT, his liver function tests (LFTs) rose dramatically, prompting hospitalization. Labs on admission revealed a hepatocellular pattern with total bilirubin 7.1, AST 2153, ALT 2931, alkaline phosphatase 156, and international normalized ratio 1.25. Notably, antinuclear antibody was positive 1:1280, smooth muscle antibody was weakly positive, and cytomegalovirus (CMV) IgM was elevated. Hepatobiliary scan and magnetic resonance cholangiopancreatography were consistent with hepatocellular disease. Core liver biopsy revealed active hepatitis with moderate activity (interface moderate), cholestasis, and an infiltrate of eosinophils and plasma cells. CMV staining was negative. Overall, the testing was consistent with drug-induced AIH. Infliximab was stopped and steroids were begun, resulting in normalization of LFTs. DISCUSSION: Infliximab has been implicated in mild cases of hepatotoxicity, and therefore, it is recommended to check LFTs before and after beginning the medication. There are very few reports of severe AIH that have been linked specifically to infliximab, as cases of hepatotoxicity are often secondary to reactivation of viral hepatitis or CMV infections, or related to other biologic therapies. This is a rare case of infliximab-induced AIH, and it is an important consideration in patients with elevated LFTs after starting this drug. Treatment involves cessation of infliximab and treatment with steroids, which usually leads to resolution of the hepatitis.

Management of microscopic colitis: challenges and solutions.

Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by nonbloody diarrhea in the setting of normal appearing colonic mucosa. MC has two main subtypes based on histopathologic features, collagenous colitis and lymphocytic colitis. Management of both subtypes is the same, with treatment goal of reducing the number of bowel movements and improving consistency. First-line treatment involves counseling the patient about decreasing their risk factors, like discontinuing smoking and avoiding medications with suspected association such as NSAIDs, proton pump inhibitor, ranitidine, and sertraline. Starting loperamide for immediate symptomatic relief is used as an adjunct to therapy with glucocorticoids. Budesonide is considered first-line treatment for MC given its favorable side effect profile and good efficacy, though relapse rates are high. Systemic glucocorticoids should be reserved to patients unable to take budesonide. In glucocorticoid refractory disease, medications that have been tried include cholestyramine, bismuth salicylate, antibiotics, probiotics, aminosalicylates, immunomodulators, and anti-tumor necrosis factor-alpha inhibitors. More research is needed for the creation of a systematic stepwise approach for relapsing and refractory disease.

Pulmonary Tuberculosis.

This review on pulmonary tuberculosis includes an introduction that describes how the lung is the portal of entry for the tuberculosis bacilli to enter the body and then spread to the rest of the body. The symptoms and signs of both primary and reactivation tuberculosis are described. Routine laboratory tests are rarely helpful for making the diagnosis of tuberculosis. The differences between the chest X ray in primary and reactivation tuberculosis is also described. The chest computed tomography appearance in primary and reactivation tuberculosis is also described. The criteria for the diagnosis of pulmonary tuberculosis are described, and the differential is discussed. The pulmonary findings of tuberculosis in HIV infection are described and differentiated from those in patients without HIV infection. The occurrence of tuberculosis in the elderly and in those patients on anti-tumor necrosis factor alpha inhibitors is described. Pleural tuberculosis and its diagnosis are described. Efforts to define the activity of tuberculosis and the need for respiratory isolation are discussed. The complications of pulmonary tuberculosis are also described.

Development of miliary tuberculosis related to anti‐tumor necrosis factor‐alpha inhibitor therapy for pustular psoriasis

Development of miliary tuberculosis related to anti‐tumor necrosis factor‐alpha inhibitor therapy for pustular psoriasis

Localized Cutaneous Cryptococcus albidus Infection in a 14‐Year‐Old Boy on Etanercept Therapy

Immune-modulating medications, such as the tumor necrosis factor-alpha inhibitors, are establishing a niche in the dermatologic therapeutic armamentarium as novel, effective, and relatively safe alternatives in the treatment of numerous inflammatory dermatoses. The benefits of anti-tumor necrosis factor-alpha inhibitor therapy are well known. However, these agents are also associated with an increased risk of infectious complications--most commonly granulomatous infections with mycobacteria and fungi. We present a teenaged boy with localized, cutaneous Cryptococcus albidus infection on the scalp which occurred after he began etanercept for refractory psoriasis. The infection resolved after a course of fluconazole. This is the second report of localized, cutaneous C. albidus infection, but the first occurring in association with etanercept therapy. Our patient's findings remind us that extra vigilance is imperative in monitoring patients on immunosuppressive regimens and that any persistent, nonhealing lesion in these patients should prompt evaluation for potential infection, not only from common and typical pathogens but also from more unusual, atypical ones.

Effects of infliximab and etanercept, two types of anti-tumor necrosis factor-alpha inhibitor on serum level of matrix metalloproteinase 3 expression in patients with ankylosing spondylitis

To evaluate the effect of Infliximab and Etanercept two types of anti-tumor necrosis factor-alpha (TNF-alpha) inhibitors, on the serum level of matrix metalloproteinase 3 (MMP-3) in the pathogenesis of ankylosing spondylitis (AS). 47 patients with AS, 40 males and 7 females, aged 17 - 51, were treated with Infliximab (5 mg/kg i.v at weeks 0, 2, and 6); and 26 patients with AS were treated with Etanercept (25 mg, twice a week for 12 weeks). Clinical data including Bath AS indices (BASDAI and BASFI) and sera were collected at baseline and other different times. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. Serum levels of MMP-3 were measured with MMP-3 ELISA kits. Two, six, and ten weeks after Infliximab treatment the levels of ESR, CRP, and serum MMP-3 of the AS patients were all significantly lower than the baseline level (all P < 0.01), and the serum MMP-3 levels were all significantly correlated with ESR (all P < 0.05). In the Etanercept group 1, 2, 4, 8, and 12 weeks after treatment the levels of serum MMP-3, ESR, CRP, BASDAI, and BASFI were all significantly lower than the baseline levels (all P < 0.01); before the treatment ESR was significantly correlated with CRP (r = 0.80, P < 0.01), BASDAI was significantly correlated with BASFI (r = 0.48, P < 0.05), and MMP-3 was significantly correlated with ESR (r = 0.74, P < 0.01) and with CRP (r = 0.72, P < 0.01); and 12 weeks after the treatment significant correlation still existed between ESR and CRP (r = 0.40, P < 0.05), BASDAI and BASFI (r = 0.89, P < 0.01), and MMP-3 and ESR (r = 0.43, P = 0.029), however, there was no significant correlation between CRP and serum level of MMP-3 (r = 0.37, P = 0.061). Infliximab and Etanercept, 2 anti-TNF-alpha inhibitors, not only significantly decrease the ESR and CRP, but also decrease the serum level of MMP-3 of patients with AS. MMP-3 is involved in the pathogenesis and disease activity of AS. MMP-3 is also a potentially useful marker of AS disease activity and useful parameter to assess the effectiveness of anti-TNF-alpha inhibitor in treatment of AS.