Reactivation Of Tuberculosis Research Articles

COMING OUT AFTER A DECADE OF HIDING: A 35-YEAR-OLD FEMALE WITH CHRONIC COUGH AND UNINTENTIONAL WEIGHT LOSS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Tuberculosis is one of the oldest infectious causes of death in adults, with archeological evidence of Potts disease in bones 9,000 years old. Incidence of tuberculosis in the United States continues to decline even though the pace of decline has slowed in the recent years. Most infections are diagnosed with exposures in the highly endemic, homeless, or prison population. Here we present a case of tuberculosis after a decade of possible exposure CASE PRESENTATION: A 35-year-old female with no prior medical history presented with one-year history of chronic productive cough with brown sputum associated with generalized weakness, dizziness, and shortness of breath. At an outside hospital, she was treated for bacterial pneumonia with continued worsening of symptoms. She also endorsed about 80 pounds of unintentional weight loss in the past year. She denied fever, chills, night sweat, chest pain, palpitations, heartburn, sick contacts, or hemoptysis. She denied any prior or current alcohol or illicit drug and was employed at a convenience store. She denied international traveling but admitted that she was incarcerated in 2010 for six months. She was born at term in the United States without any significant childhood illness. She denied family history of lung disease, tuberculosis, or malignancy. Work up showed extensive cavitary lesions in the left upper lobe and left lower lobe and some bronchiectasis. Sputum acid fact bacilli culture was positive. Human immunodeficiency was negative. Patient was diagnosed with pulmonary tuberculosis and started on appropriate treatment. DISCUSSION: Mycobacterium tuberculosis is most commonly transmitted by droplet nuclei from an infected person. The intimacy, duration of contact, the degree of infectiousness, and the shared environment in which contact takes place are all important determinants of the likelihood of transmission. The majority of active tuberculosis cases manifest soon after infection, rarely occurring more than two years of infection. Reactivation of latent tuberculosis is thought to occur later in life, when immunity wanes from natural aging or immunocompromised states. In our patient, the distinction between primary and reactivation tuberculosis is challenging as she has no recent risk of acquiring tuberculosis and reactivation in relatively young patient with no significant underlying medical problems is uncommon. CONCLUSIONS: In low transmission countries such as the United States, we usually see tuberculosis disease in elderly or in immigrants from high transmission area. Detecting and treating all tuberculosis patients is important to prevent outbreaks and untreated tuberculosis is often fatal. This case illustrates the importance of a wide differential during patient assessment. REFERENCE #1: Behr MA, Edelstein PH, Ramakrishnan L. Revisiting the timetable of tuberculosis. BMJ 2018; 362:k2738. REFERENCE #2: Cain KP, Haley CA, Armstrong LR, et al. Tuberculosis among foreign-born persons in the United States: achieving tuberculosis elimination. Am J Respir Crit Care Med 2007; 175:75. REFERENCE #3: Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L. 1., Jameson, J. L., & Loscalzo, J. (2015). Harrison's principles of internal medicine (19th edition.). New York: McGraw Hill Education. DISCLOSURES: No relevant relationships by Samapon Duangkham, source=Web Response No relevant relationships by Megan Hughes, source=Web Response No relevant relationships by Kenneth Iwuji, source=Web Response No relevant relationships by Cristina Morataya, source=Web Response No relevant relationships by Upama Sharma, source=Web Response No relevant relationships by Divya Vangipuram, source=Web Response No relevant relationships by Alexandra Wichmann, source=Web Response

The safety and efficacy of immunotherapy with anti-programmed cell death 1 monoclonal antibody for lung cancer complicated with Mycobacterium tuberculosis infection.

BackgroundAnti-programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy has boosted the prognosis in advanced lung cancer. Meanwhile, accumulating cases showed the correlation between tuberculosis (TB) reactivation and anti-PD-1/PD-L1 immunotherapy. However, the safety and efficacy of anti-PD-1/PD-L1 immunotherapy for lung cancer complicated with TB infection could only be learned from real-world data.MethodsWe retrospectively analyzed 562 patients with advanced lung cancer who received anti-PD-1/PD-L1 immunotherapy at Shanghai Pulmonary Hospital from 2015 to 2019, including 13 patients with TB infection. Besides, relevant literature reviews were performed online to analyze the safety and efficacy of immunotherapy and to explore the appropriate treatment strategies in this specific population.ResultsIn our cohort, the initiation of anti-PD-1/PD-L1 immunotherapy was from June 2015 to December 2019. Among them, 13 patients had TB infection prior to immunotherapy including 11 latent TB and 2 active TB, and all of them were treated with anti-PD-1 immunotherapy. Patients with active TB infection were treated with concurrent anti-TB and anti-PD-1 treatments, and the remaining received either mono-immunotherapy or combined immunotherapy. Neither reactivation of latent TB nor progression of active TB was monitored in our cohort during immunotherapy. Severe immune-related adverse events (irAEs) were diagnosed in two patients. Treatment strategies such as discontinuation of immunotherapy and administration of corticosteroids were provided timely, and one with latent TB infection got gradually improved, but the other one with active TB died quickly. The median progression-free survival (PFS) was 5.5 months for tumor immunotherapy in our cohort. However, the PFS of immunotherapy was merely 2.1 and 2.2 months in lung cancer patients with active TB infection.ConclusionsImmunotherapy is relatively safe for lung cancer patients complicated with previously treated latent TB, and the efficacy of immunotherapy in this specified population is not inferior to that in lung cancer patients without TB infection. TB screening before anti-PD-1/PD-L1 immunotherapy is strongly recommended, and irAEs should be monitored more cautiously in lung cancer patients with active TB infection.

S2456 TB or Not TB? Miliary Tuberculosis in a QuantiFERON-Indeterminate Patient on Infliximab Therapy

Introduction: Miliary tuberculosis results from massive hematogenous dissemination of tuberculosis (TB) typically to the lung, bone, and less commonly to the gastrointestinal tract. It accounts for 2% of TB cases which may present as a life-threatening septic shock in the setting immunosuppression. Case Description/Methods: A 53-year-old Cuban male physician with moderate to severe ileocolic Crohn's disease and a history of travel to Cuba was recently initiated on Infliximab due to the failure of conventional therapy. Pretreatment Interferon-γ Release Assay (IGRA) QuantiFERON-TB Gold In-Tube, and tuberculin skin test were negative. Fourteen weeks later, he reported fever, emesis, and unintentional weight loss. Colonoscopy revealed severely inflamed mucosa of the right hemi-colon promoting escalation of infliximab dose with steroids for a presumed CD flare. Biopsy subsequently revealed numerous acid-fast bacilli. Therapy was immediately aborted, and he was then advised to initiate TB treatment. He returned eight days later with shock progressing to multiorgan failure. During emergent exploratory laparotomy, the small bowel and omentum were studded with white granulomatous nodules. He expired n the first postoperative day. Sputum, omentum, and abdominal wall cultures were all positive for Mycobacterium tuberculosis, and repeat IGRA was indeterminate. Discussion: Crohn’s disease (CD) is a chronic granulomatous inflammatory and destructive disease which follows a relapsing and remitting course. Infliximab therapy is initiated in moderate to severe stages however it carries with it an increased risk of reactivation of latent TB. IGRA testing before and during treatment is important during treatment with infliximab. It is difficult to surmise whether the subsequent hospital visits post infliximab initiation were due to worsening CD, or a manifestation of intestinal TB given the striking similarities. This patient’s insidious weight loss and rapid decline concomitant with the escalation of Infliximab and corticosteroid use points towards intestinal TB as the etiology of the symptoms. Despite the high sensitivity of IGRA testing, this patient’s travel history in an endemic area decreases the negative predictive value of the test. Diagnosis of miliary TB is challenging given its nonspecific presentation and limited diagnostic modalities. Therefore, patients continually exposed to endemic areas should prompt more frequent diagnostic re-evaluation prior to Infliximab escalation.

DISSEMINATED HEMATOGENOUS TB PRESENTING AFTER SPONTANEOUS ABORTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Diagnosis of disseminated tuberculosis can be challenging, as symptoms can vary significantly and mimic other pathologies (1). Despite being rarely seen in pregnant or post-partum females, its high mortality and morbidity warrant prompt diagnosis and treatment with high clinical suspicion. CASE PRESENTATION: The patient is a 20-year-old female with past medical history of recent spontaneous abortion who presented with progressive dyspnea treated with antibiotics 2 months prior. Upon presentation, patient was hemodynamically stable with a GCS of 14. In the hours following admission, she decompensated quickly requiring intubation and vasopressors. CT chest revealed several bilateral cavitary lesions, the largest in the left upper lobe measuring 3.8 x 4.1cm. Transthoracic echocardiogram revealed an ejection fraction of 15-19% and left ventricular thrombosis. Bronchoscopy was preformed, resulting in Mycobacterium Tuberculosis (MTB) on PCR. Treatment was initiated with rifabutin, levofloxacin, pyrazinamide, ursodiol, and solumedrol. HIV was negative. Karius test was positive for cytomegalovirus, herpes simplex virus 1, MTB, and Candida albicans. Micafungin and valganciclovir were added to the treatment regimen. The patient's course was complicated requiring tracheostomy, multiple limb amputations, and extended ICU stay. The patient's condition slowly stabilized and she is currently pending discharge to a long-term care facility. DISCUSSION: In 2011, there were estimated to be more than 200,000 cases of active TB in pregnant females across the globe. While tuberculosis can be prevalent in pregnancy, the progressive disseminated hematogenous form is rare (1). Disseminated tuberculosis is a mycobacterial infection that either involves the blood, bone marrow, or liver; or involves two or more noncontiguous sites. Symptoms can vary significantly and resemble a variety of other pathologies (2). Less often, patients can present with acute respiratory failure, cholangitis, and hypotension (1). As the mortality of disseminated tuberculosis increases significantly with delay in treatment, a high clinical suspicion is required, particularly in countries where prevalence of TB is lower (2).The body's defense against tuberculosis is a cellular immune response. A physiological change in pregnancy results in the suppression of the T-helper 1 cells and has been thought to increase susceptibility to infection, reactivation, and spread of tuberculosis. After delivery, there is no suppression of the T-helper 1 cells and symptoms of tuberculosis can be exacerbated. It is hypothesized that after our patient's spontaneous abortion, the cellular immune response was reactivated and resulted in a pro-inflammatory response (1). CONCLUSIONS: Our case highlights the importance of considering disseminated tuberculosis as a differential in a post-partum patient presenting with respiratory symptoms with cavitary lesions. REFERENCE #1: 1. Barbosa, O. A., Teles, F. M., Maia, A. C. C., Pessoa, G. M. F., de Alencar, I. M., de Sousa, E. T., & Jorge Bezerra Simão, S. D. (2019). Disseminated hematogenous tuberculosis in puerperium—case report. Oxford Medical Case Reports, 2019(11), 479–481. https://doi.org/10.1093/omcr/omz116 REFERENCE #2: 2. Wang, J. Y., Hsueh, P. R., Wang, S. K., Jan, I. S., Lee, L. N., Liaw, Y. S., Yang, P. C., & Luh, K. T. (2007). Disseminated Tuberculosis. Medicine, 86(1), 39–46. https://doi.org/10.1097/md.0b013e318030b605 DISCLOSURES: No relevant relationships by Sarah Cheyney, source=Web Response No relevant relationships by Mary Reischmann, source=Web Response No relevant relationships by Crystal Verdick, source=Web Response

A case report of probable ocular tuberculosis following biologics

Biological drugs, especially anti-TNF-α agents, have revolutionized the treatment of chronic immune-inflammatory diseases, however complications include reactivation of tuberculosis and increased incidence of other infections. We report a 28-year-old male, on biological agents for HLA B27 positive spondyloarthropathy, inflammatory bowel disease and psoriasis, who presented with occlusive retinal perivasculitis. Following a thorough clinical examination and ocular and systemic investigation, a diagnosis of probable ocular tuberculosis (POTB) with tubercular retinal vasculitis (TRV) was made. Biologics were temporarily withdrawn and anti-tubercular therapy (ATT) initiated with good response. Patients on biologics need close monitoring, for ocular and systemic infections especially TB.

ACTIVE TB AFTER THE USE OF TOCILIZUMAB FOR COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Tocilizumab is a humanized anti-IL-6 receptor antibody and inhibits the binding of IL-6 to its receptors, associated with Th17 and Th22 cell differentiation which is critical for anti-mycobacterial activity. It is commonly used in patients with active rheumatoid arthritis. During the COVID-19 pandemic, tocilizumab has been widely used in severe COVID-19 infection with elevated markers of systemic inflammation. We report a case of active tuberculosis after the use of tocilizumab for COVID-19 pneumonia. CASE PRESENTATION: An 80-year-old Asian female with hypertension, coronary artery disease presented to the emergency department(ED) due to a one-day duration of fever, cough, and altered mental status. About three months prior to presentation, she had COVID-19 pneumonia requiring prolong hospitalization which was complicated by acute respiratory distress syndrome. She received tocilizumab, remdesivir, steroids and hydroxychloroquine for COVID-19 infection. Following the hospital stay, she was discharged to a long-term acute care facility, and then went home. She is originally from China and moved to the United States 50 years ago. In the ED she was febrile (100.4°F) and hypoxemic, subsequently placed on 4L of nasal cannula. The laboratory data was remarkable for leukocytosis and lactic acidosis. The chest radiograph showed bilateral reticular nodular patchy opacities. The patient was admitted and empiric antibiotics were started for possible pneumonia. Despite this treatment, her respiratory status deteriorated and she was intubated on day 4, with CT chest (figure1) revealing innumerable bilateral micronodules with centrilobular distribution and tree-in-bud opacities. There were also 2 large cavitary lesions in the right upper lobe. The sputum specimen was sent, which returned positive for Acid-Fast Bacillus. In addition, Mycobacterium tuberculosis PCR on sputum was positive. Therefore, the first-line anti-tuberculosis agents including rifampin, isoniazid, pyrazinamide, and ethambutol were started. The Mycobacterium tuberculosis Complex was isolated on sputum 3 weeks later. DISCUSSION: The data from clinical trials indicate that the use of tocilizumab is associated with a very low or absent risk of tuberculosis reactivation. However, this case highlights the judicious use of tocilizumab in patients who are at high risk of exposure or reactivation such as immigrants from endemic regions, IV drug users and health care workers, etc. In our case, the patient had other factors including severe COVID-18 infection, use of steroids, prolonged hospital stay, and malnutrition which might compromise the immune system, and predispose to active tuberculosis. CONCLUSIONS: We suggest that tests be performed to rule out latent tuberculosis in selected patients prior to tocilizumab use and monitor all patients for active tuberculosis during treatment. REFERENCE #1: Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180(3):1962-70. REFERENCE #2: Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics. Mediators Inflamm. 2017;2017:8909834. REFERENCE #3: Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148-51. DISCLOSURES: No relevant relationships by Goutham Dronavalli, source=Web Response No relevant relationships by Sungryong Noh, source=Web Response

Frequency of positivity of the tuberculin intradermorreaction test in a cohort of patients with rheumatoid arthritis

ResumenIntroducción. La artritis reumatoide es una enfermedad autoinmunitaria, crónica y deformante asociada con discapacidad. Quienes la padecen reciben inmunosupresores y tienen un gran riesgo de desarrollar tuberculosis. La prueba de intradermorreacción a la tuberculina se utiliza como tamización en quienes van a recibir terapia biológica. Objetivo. Evaluar la frecuencia de positividad en la prueba de intradermorreacción a la tuberculina en una cohorte de pacientes con artritis reumatoide.Materiales y métodos. Se hizo un estudio descriptivo de corte transversal de una cohorte de pacientes con artritis reumatoide a quienes se les practicó la prueba de tuberculina antes de iniciar la terapia biológica o en el momento del cambio de tratamiento. Los pacientes presentaban enfermedad moderada o grave y eran candidatos para iniciar o cambiar de terapia biológica. Se definió el valor de ≥6 mm como punto de corte para la positividad de la prueba y se hizo un análisis descriptivo de cada una de las variables. Resultados. Se incluyeron 261 pacientes con artritis reumatoide, 92 % de ellos eran mujeres, la edad promedio fue de 55 años (desviación estándar, DE=13,92) y el tiempo desde el diagnóstico era de 12,3 años (DE=8,54). La frecuencia de positividad de la prueba fue de 15,71 % (n=41). Nueve de los 41 pacientes positivos habían recibido la prueba previamente (entre 1 y 6 años antes), todos con resultado negativo; 18 (43,9 %) de ellos venían recibiendo tratamiento con glucocorticoides y todos los 41 (100 %) recibían metotrexate. Conclusiones. La frecuencia de positividad de la prueba de tuberculina en pacientes colombianos con artritis reumatoide fue de aproximadamente 16 %. Se recomienda optimizar las estrategias para detectar esta condición y darle un tratamiento oportuno y, así, disminuir el riesgo de reactivación de la tuberculosis.

The Relationship between Nutritional Status and Latent Tuberculosis in Routine Hemodialysis

BACKGROUND: Malnutrition in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) interferes with the natural and adaptive immune response, consequently, increasing the latent tuberculosis (TB) reactivation. AIM: This study therefore aims to determine the relationship between nutritional status and latent TB in routine HD, using interferon gamma release assays (IGRA), to screen for latent TB. METHODS AND STUDY DESIGN: This study has an analytical observation cross-sectional design, and was conducted on 120 CKD-HD patients aged 18 years and above, and has been undergoing HD twice weekly for over 3 months, without malignancy, human immunodeficiency virus/acquired immunodeficiency syndrome, history of TB, or radiological evidence at the HD Unit of the Dr. Hasan Sadikin Hospital, Bandung, Indonesia, between March and May 2020, and not currently receiving immunosuppressant or TB therapy. In addition, the age, gender, history of Bacille Calmette-Guerin vaccine, CKD etiology, length of HD, HD adequacy, TB contact history, number of family members, smoking status, body mass index, albumin, malnutrition inflammation score, triceps skinfold thickness (TST), biceps skinfold thickness, suprailiac skinfold thickness (SIST), mid-upper arm circumference (MAC), and normalized protein catabolic rate between positive and negative IGRA groups, of each patient, were determined. RESULTS: In this study, all the patients met the inclusion and exclusion criteria. Based on the IGRA test, 47 patients (39.17%) tested positive, and 68 (56.67%) tested negative, while the results for the remaining 5 (4.16%) were indeterminate. The malnutrition inflammation score (MIS) score with positive IGRA 23.3 (20.0–26.7) was discovered to differ insignificantly (p value of 0.252) from the negative counterpart 20.0 (16.7–28.4). Meanwhile, in the HD adequacy assessment based on urea reduction rate, a statistically significant difference (p = 0.042) occurred between the positive 70.45 (65.70–76.61) and negative 74.15 (70.71–77.33) IGRA groups. In the smoking status, the positive and negative IGRA were discovered to differ significantly (30 (63.8% vs. 28 (41.2% p = 0.017) OR 2.521 (1.172–5.425). However, in the history of contact with TB patients, the positive and negative IGRA did not differ significantly (4.3% vs. 11.8% p = 0.160). Furthermore, there was a significant difference in TST and MAC, between MIS >5 and MIS ≤5 (p < 0.05). CONCLUSION: The assessment of nutritional status level, TST, MAC, smoking status, and adequate HD is crucial for CKD patients with routine HD, as these factors present risks of latent TB.

Extracellular Matrix-Induced GM-CSF and Hypoxia Promote Immune Control of Mycobacterium tuberculosis in Human In Vitro Granulomas.

Several in vitro cellular models have been developed with the aim to reproduce and dissect human granulomatous responses, the hallmark of tuberculosis (TB) immunopathogenesis. In that context, we compared two- (2D) versus three-dimensional (3D) granuloma models resulting from infection of human peripheral blood mononuclear cells with M. tuberculosis (Mtb) in the absence or presence of a collagen-based extracellular matrix (ECM). Granuloma formation was found to be significantly enhanced in the 2D model. This feature was associated with an earlier chemokine production and lymphocyte activation, but also a significantly increased bacterial burden. Remarkably, the reduction in Mtb burden in the 3D model correlated with an increase in GM-CSF production. GM-CSF, which is known to promote macrophage survival, was found to be inherently induced by the ECM. We observed that only 3D in vitro granulomas led to the accumulation of lipid inclusions within Mtb. Our data suggest that a hypoxic environment within the ECM could be responsible for this dormant-like Mtb phenotype. Furthermore, exposure to a TNF-α antagonist reverted Mtb dormancy, thereby mimicking the reactivation of TB observed in rheumatic patients receiving this therapy. To conclude, we showed that only in vitro granulomas generated in the presence of an ECM could recapitulate some clinically relevant features of granulomatous responses in TB. As such, this model constitutes a highly valuable tool to study the interplay between immunity and Mtb stress responses as well as to evaluate novel treatment strategies.

Acute miliary tuberculosis in pregnancy after in vitro fertilization and embryo transfer: a report of seven cases

BackgroundWhile miliary tuberculosis (TB) in pregnancy is rare after in vitro fertilization and embryo transfer (IVF-ET), it poses a serious threat to the health of pregnant women and their fetuses. The present study aimed to describe the clinical features of miliary TB and pregnancy outcomes of patients after IVF-ET.MethodsData of infertile patients who received IVF-ET at Peking University Third Hospital between January 2012 and December 2017 were retrospectively analyzed. Patients who developed miliary TB during pregnancy were identified, and clinical characteristics of miliary TB were described.ResultsOut of 62,755 infertile women enrolled, 7137 (11.4 %) showed signs of prior pulmonary TB on chest X-ray (CXR). Among the 15,136 women (mean age: 33.2 ± 5.0 years) who successfully achieved clinical pregnancy, seven patients aged 28–35 years had miliary TB during pregnancy, with two patients having a complication of TB meningitis. All these patients presented with fever. Notably, old TB lesions were detected on CXR in six patients before IVF-ET; nevertheless, no anti-TB therapy was administered. Furthermore, salpingography revealed oviduct obstruction in all patients (7/7). Patients received anti-TB therapy following a diagnosis of miliary TB and were clinically cured. However, pregnancy was terminated due to spontaneous (4/7) and induced (3/7) abortion.ConclusionsTB reactivation, mostly as miliary TB and TB meningitis, is severe in pregnant women after IVF-ET and deleterious to pregnancy outcomes. Signs of prior TB on CXR may be risk factors for TB reactivation during pregnancy.

The risk of tuberculosis infection in 410 Saudipatients receiving adalimumab therapy.

BACKGROUND: Adalimumab is a fully humanized monoclonal antibody inhibitor of tumor necrosis factor-a used to treat various autoimmune disorders. Adalimumab poses a risk for tuberculosis (TB) infection, especially in countries where TB is endemic.OBJECTIVE: Determine the rate of TB infection after adalimumab therapy in Saudi Arabia.DESIGN: Medical record review.SETTINGS: Tertiary care center in Riyadh.PATIENTS AND METHODS: Demographic and clinical data were retrieved from the electronic healthcare records of all patients who received adalimumab treatment from 2015 to 2019.MAIN OUTCOME MEASURES: Occurrence of TB after adalimumab therapy.SAMPLE SIZE: 410 patients (median ([QR] age, 37 [28], range 4–81 years), 40% malesRESULTS: Rheumatoid arthritis was the most frequent indication (n=153, 37%). The patients were followed for a mean of 36 (8.9) months. No case of TB infection or reactivation was observed. An inter-feron-gamma release assay (IGRA) was requested in 353/391 (90.3%) patients, prior to initiating therapy. The IGRA was positive in 26 cases (6.6%). The IGRA-positive patients received isoniazid prophylactically. Bacterial infectious complications of adalimumab therapy occurred in 12 (2.9%) patients. Urinary tract infection was the most frequent complication (culture requested in 48 patients, positive in 8).CONCLUSION: Adalimumab treatment was not associated with a risk of TB disease or TB reactivation in our cohort over the follow-up observation period. No TB reactivation occurred with adalimumab therapy when TB prophylaxis was used. The positive IGRA rate in patients on adalimumab treatment was low (7%).LIMITATIONS: Single center and one geographical area in Saudi Arabia.CONFLICT OF INTEREST: None.

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).

Efficacy and safety of rituximab in autoimmune pancreatitis type 1: our experiences and systematic review of the literature

Introduction Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. Patients and methods Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. Results Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11–43% and the relapse-free period during follow-up (range 2–173 months) ranged from 38–94%. Conclusions Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.

Immune control of Mycobacterium tuberculosis is dependent on both soluble TNFRp55 and soluble TNFRp75.

Tuberculosis presents a global health challenge, and tumour necrosis factor (TNF) signalling is required for host immunity against Mycobacterium tuberculosis (Mtb). TNF receptor shedding, however, compromises effective immunity by reducing bioactive TNF through the formation of inactive complexes. In this study, we first compared the effect of total soluble TNF receptors using a transgenic p55ΔNS /p75-/- murine strain on host protection during a low-dose aerosol Mtb H37Rv challenge. We report that the presence of membrane-bound TNFRp55 alone in the absence of TNFRp75 results in superior control of a primary Mtb infection where p55ΔNS /p75-/- hyperactive dendritic cells displayed an increased capacity to induce a hyperactive Mtb-specific CD4+ T-cell response. p55ΔNS /p75-/- dendritic cells expressed a higher frequency of MHCII and increased MFIs for both CD86 and MHCII, while CD4+ T cells had higher expression of CD44 and IFN-γ. Next, the relative contributions of soluble TNFRp55 and soluble TNFRp75 to host protection against either primary Mtb infection or during reactivation of latent tuberculosis were delineated by comparing the experimental outcomes of control C57BL/6 mice to transgenic p55ΔNS /p75-/- , p55ΔNS and p75-/- mouse strains. We found that soluble TNFRp55 is redundant for immune regulation during the chronic stages of a primary Mtb infection. However, TNFRp55 together with soluble TNFRp75 has a crucial role in immune regulation of reactivation of latent tuberculosis.

Role of resuscitation promoting factors in reactivation of latent tuberculosis during high glucose conditions employing human granuloma in vitro model

BackgroundDiabetes aggravates the risk of tuberculosis (TB) through impairment of immunity which may lead to the activation of latent tuberculosis (LTBI). LTBI serves as a homeostatic state where host does not develop any symptoms of the disease as host immune system assist in the containment of infection leading to granuloma formation. However, the compromised immunity imbalances this equilibrium which further leads to reactivation of LTBI. The aim of this study was to assess if hyperglycemia like conditions contribute towards activation of latent tuberculosis. Material/methodsIn vitro granuloma model was developed using peripheral blood monocytic cells (PBMCs) under normal and high glucose conditions and the characteristics of dormancy i.e. tolerance towards rifampicin, loss of acid fastness were monitored. Further, activation was assessed by expression analysis of various resuscitation promoting factors rpfA-E. ResultsGranuloma formation was not observed in the presence of high glucose. The gene expression of hspX was downregulated whereas the expression of rpfA-E genes was upregulated under high glucose conditions after 48 h of glucose treatment. The expression of rpfD gene remained upregulated till 72 h of glucose treatment. ConclusionHigh glucose concentrations impede the granuloma formation and may lead to activation of latent tubercle bacilli through resuscitation promoting factors. Thus, rpfs represent an important targets for new interventions that can abate the burden from co-pathogenesis of tuberculosis and diabetes.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Incidence of Infections and Second Cancers in Philadelphia Chromosome-Negative Patients with Myeloproliferative Neoplasms Treated with Ruxolitinib

Introduction:This is a retrospective, case-control study evaluating the incidence of infections and second cancers in Philadelphia-chromosome negative (Ph-) myeloproliferative neoplasm (MPN) patients treated with ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor approved for treating patients with polycythemia vera (PV), primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (PET-MF), and post-polycythemia vera myelofibrosis (PPV-MF) [1]. These patients are at significant risk for infections and second cancers when treated with long-term ruxolitinib. Similar observations have been reported in the COMFORT-II clinical trial findings, which studied ruxolitinib use in myelofibrosis (MF) patients [2], and have real-world clinical implications.Methods:128 MPN patients treated with ruxolitinib were studied and matched with 122 control patients based on gender, disease subtype, and age at the beginning of an MPN treatment (± 5 years). All evidence of infections and second cancers during this treatment regimen were recorded.Results:MPN patients whose mean age was 67.2±11.2 years when starting ruxolitinib treatment were studied, among whom myelofibrosis (38.3%) and PV (33.6%) were the leading subtypes. Of patients in the ruxolitnib cohort, 60/128 (46.9%) presented with ≥1 infection and a second cancer occurred in 13/128 (10.2%) patients. Of patients in the control cohort, 37/122 (30.3%) presented with ≥1 infection and a second cancer occurred in 6/122 (4.9%) patients. The difference of these proportions was significant for both infections (p=0.0072, RR=1.5456) and second cancers (p=0.0006, RR=2.0651) (Graph 1). Types of infections and cancers are summarized in Table 1a, Table 1b, and Table 2 . Of note, 2 patients treated with ruxolitinib had tuberculosis (TB) reactivations and 1 patient had pulmonary aspergillosis. All 13 of the patients that were diagnosed with a second cancer after being treated with ruxolitinib were found to have ≥1 skin cancer.Stratification of the incidence of these events by gender shows a trend for females treated with ruxolitinib with a higher relative risk (RR) of developing cancer than males of the same cohort (RR: 6.8971 for females, 0.4385 for males) (Table 3) . Serial upper respiratory infections (URIs) and urinary tract infections (UTIs) were of higher incidence in the ruxolitinib cohort than in the control cohort. In the ruxolitinib cohort, 7/21 (33.3%) and 5/12 (41.7%) experienced serial URIs and UTIs, respectively. In the control cohort, 1/9 (11.1%) and 0/8 (0.0%) experienced serial URIs and UTIs, respectively. 29/128 (22.7%) of the ruxolitinib cohort and 14/123 (11.4%) of the control cohort developed ≥2 different types of infections (p=0.0217, RR=1.9905).When compared to the control cohort, patients in the ruxolitinib cohort were found to have a higher incidence of recurring neutropenia (ruxolitinib: 35/128 (27.3%), control: 22/123 (17.9%), p=0.0782, RR=1.5288). The ruxolitnib cohort had a higher incidence of elevated ferritin than the control cohort (ruxolitinib: 26/128 (20.3%), control: 6/123 (4.9%), p=0.0010, RR=4.1641). Elevated ferritin could be a factor contributing to the increased risk of developing certain types of infections owing to iron overload [3].Conclusions:Long-term ruxolitinib treatment in Ph- MPN patients has resulted in an increased risk of infections and second cancers when compared to a matched control cohort. Those patients also had significantly higher ferritin levels which may contribute to the increased risk of certain infections. The risk of secondary cancer was much higher in the ruxolitinib group and especially in females. The significant proportion of ruxolitinib-treated patients who developed skin cancer (13/128, 10.2%) emphasizes the importance of skin cancer screening in these patients. [Display omitted] DisclosuresRitchie:Astellas Pharma: Other: Research funding to my institution; NS Pharma: Other: Research funding to my institution; Bristol-Myers Squibb: Other: Research funding to my institution; Celgene: Consultancy, Other: Travel, Speakers Bureau; Pfizer: Consultancy, Other: Research funding to my institution; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Other: Research funding to my institution, and travel, Speakers Bureau. Roboz:Cellectis: Research Funding; AbbVie, Agios, Amgen, Amphivena, Array Biopharma Inc., Astex, AstraZeneca, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Novartis, Onconova, Pfizer, Roche Pharmace: Consultancy. Lee:Amgen: Consultancy; Baxalta: Consultancy; Alexion Pharmaceuticals: Consultancy; Clinipace: Consultancy.

Preventing Infectious Complications of Immunomodulation in COVID-19 in Foreign-Born Patients.

Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10903-021-01225-4.

Overuse of Tuberculosis Surveillance Testing in Patients With Inflammatory Bowel Disease Compared to Non-IBD Patients on Biologic Therapy.

Biologic treatment for moderate to severe inflammatory bowel disease (IBD) places patients at risk for infectious complications. Tuberculosis (TB) infection and reactivation can lead to serious morbidity and mortality for immunosuppressed patients. As a result, guidelines recommend screening for TB before starting biologic treatment, but a paucity of data remains on the utility of surveillance testing. We performed a retrospective chart review at a single academic center evaluating both IBD and non-IBD patients on biologic therapy. The primary outcome was to determine the number of subsequent surveillance tests performed after initial screening for latent TB in both patient groups. A total of 188 patients (147 IBD and 41 non-IBD patients) on biologic therapy were included. Screening for TB before biologic treatment was performed in 56% of non-IBD patients versus 83% for patients with IBD (P = 0.0003). Of the total cohort, 65% had at least 2 follow-up surveillance tests for TB. Three or more surveillance tests were performed in 40% of patients with IBD versus only 13% for non-IBD patients (P = 0.0132). A total of 7 patients (4%) had an abnormal surveillance test. No patients were confirmed to have a diagnosis of TB or underwent treatment. Patients on biologic therapy unnecessarily undergo surveillance testing for TB. Patients with IBD on biologic therapy are screened annually for TB at a higher rate compared to non-IBD patients. Standardization of care among patients on biologic therapy is necessary to avoid excessive testing in areas with a low incidence of TB.

Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn\u2019s disease

Crohn’s disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30–396) months; median follow-up duration-42 (range 8–180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2–96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.