Disseminated tuberculosis after anti-TNF alpha treatment: Do not blindly trust the IGRA test.

INTRODUCTION: Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism. METHODS: We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis. RESULTS: The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis. CONCLUSION: Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.

Disseminated tuberculosis after anti-TNF alpha treatment: Do not blindly trust the IGRA test / Tuberculosis diseminada tras tratamiento anti-TNF alfa: no confíe ciegamente en la prueba IGRA

Introduction: Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism. Methods: We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis. Results: The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis. Conclusion: Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.(AU)

Introducción: El ensayo de liberación de interferón gamma (IGRA) se utiliza para detectar tuberculosis latente antes de los tratamientos biológicos en el contexto de sospecha de reumatismo inflamatorio. Métodos: Presentamos el caso de una mujer de 50 años con IGRA negativo antes de la introducción de adalimumab por presunta espondiloartritis axial. Resultados: El empeoramiento de los síntomas bajo tratamiento llevó a nuevas investigaciones y posteriormente se estableció el diagnóstico de tuberculosis (TB) diseminada con localizaciones pulmonar y óseas múltiples como espondilitis y sacroilitis. La historia de la paciente reveló una exposición pasada a la TB. Esta observación ilustra las limitaciones del IGRA en tal situación debido a su rendimiento variable para el diagnóstico de la TB activa. Conclusiones: El diagnóstico erróneo es frecuente en la TB ósea debido a signos inespecíficos. Llamamos la atención sobre la importancia de una evaluación de riesgo global antes de la introducción de un tratamiento biológico para la sospecha de reumatismo inflamatorio crónico, y recordamos los factores de riesgo para falsos negativos del IGRA. Puede ser necesario un curso de tratamiento prolongado después de la exposición al tratamiento anti-TNF-alfa.(AU)

Internal Jugular Vein Tumor Thrombus: A Tricky Question for the Thyroid Surgeon.

Internal jugular vein tumor thrombus is an extremely rare condition in thyroid carcinoma, but it does exist. Correlated with greater aggressiveness with a higher incidence of distant metastases at diagnosis and a higher recurrence rate, this important prognostic element should be systematically investigated by ultrasound operators in all patients presenting with thyroid carcinoma. The patient's follow-up must be careful. This can be a trap that surgeons must look for in their preoperative checklist. We report the case of a 58-year-old woman with an IJV thrombus associated with multiple bone metastases. She underwent successful surgical treatment, and postoperative pathology showed a poorly differentiated follicular carcinoma of the thyroid and a tumor thrombus in the internal jugular vein.

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use. In this review, we discuss rationale efficacy and safety evidence for the association of lenvatinib and pembrolizumab in ATC. First, we discuss preclinical rationale for pembrolizumab monotherapy, lenvatinib monotherapy and synergistic action of pembrolizumab and lenvatinib in the metastatic setting. We also discuss clinical evidence for immunotherapy and pembrolizumab in ATC through the analysis of studies evaluating immunotherapy, lenvatinib and pembrolizumab lenvatinib association in ATC. In addition, we discuss the safety of this association and potential predictive biomarkers of efficiency.

[Restatment. Mollaret's meningitis]. / la Méningite de Mollaret.

MOLLARET MENINGITIS Benign recurrent lymphocytic meningitis, also called Mollaret's Meningitis (MM), is a rare disease most commonly due to HSV-2 virus. Twenty to 30% of patients presenting a first meningitis due to HSV-2 will have recurrent meningitis. This pathology is characterized by recurrent attacks of sud-den onset meningitis with complete recovery, and intervals, free of any symptoms. The majority of patients do not report a history of genital herpes. The diagnosis is based on the clinic and analysis of the cerebrospinal fluid (CSF), which shows aseptic lymphocytic meningitis. A positive PCR for HSV-2 allows a diagnosis with certainty. Facing a negativ PCR, the diagnosis of MM is established after excluding other causes of recurrent lymphocytic meningitis. The pathophysiology is not well known but is linked to the reactivation of the HSV-2 virus located in the sacral ganglia of sensory neurons in a latent state after the primary genital infection. Treatment of a first episode of MM with HSV-2 is based on antivirals. But no treatment has been shown to be effective in reducing the duration of recurrences or the frequency of recurrences. The prognosis is excellent with a tendency to a spontaneous decrease of the frequency of recurrences over time. It is important to know this pathology, in order to avoid diagnostic wandering and the multiplication of invasive examinations.

LA MÉNINGITE DE MOLLARET La méningite récurrente lymphocytaire bénigne, ou méningite de Mollaret (MM), est une maladie rare le plus souvent attribuée au virus HSV2. Elle concerne 20 à 30 % des patients ayant fait une première méningite à HSV2. Cette pathologie se caractérise par la récurrence de syndromes méningés francs et d'apparition brutale, d'évolution spontanément favorable, espacés d'intervalles libres de tout symptôme. La majorité des patients ne rapporte pas d'antécédent d'herpès génital. Le diagnostic repose sur la clinique et l'analyse du LCR, qui montre une méningite lymphocytaire aseptique. Une PCR positive pour HSV2 pose le diagnostic de certitude. Face à une PCR négative, le diagnostic de MM est établi après exclusion des autres causes de méningite récurrente lymphocytaire. La physiopathologie est peu connue mais serait liée à la réaction du virus HSV2, localisé dans les ganglions sacrés des neurones sensitifs à l'état latent après la primo-infection génitale. Le traitement d'un premier épisode de MM à HSV2 repose sur les antiviraux, mais aucun traitement n'a démontré son efficacité pour réduire la durée ou la fréquence des récurrences. Le pronostic est excellent, avec une tendance à la diminution spontanée de la fréquence des récurrences au cours du temps. Il est important de connaître cette pathologie afin d'éviter une errance diagnostique et la multiplication d'examens invasifs.

Neutralizing antibody response to SARS-CoV-2 persists 9 months post symptom onset in mild and asymptomatic patients.

OBJECTIVE: A better understanding of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is critical to predict its dynamics within the general population and its impact on the vaccination strategy. This study assessed the persistence of neutralizing antibody (Nab) activity and SARS-CoV-2 serology in serum samples of mild and asymptomatic patients 9 months post symptom onset (PSO) in a primary care context among immunocompetent adults. METHODS: A longitudinal cohort of crew members (CMs) exposed to coronavirus disease 2019 (COVID-19) during an outbreak of SARS-CoV-2 on the French aircraft carrier 'Charles de Gaulle' in April 2020 was created. CMs infected with COVID-19 and with positive serology at the end of quarantine were tested 9 months PSO. Samples were collected 18 and 280 days PSO. For each patient, both serology and serum viral neutralizing activity were performed. RESULTS: In total, 86 CMs were analysed. Samples were collected 18 and 280 days PSO. The seroconversion rates were 100% and 93% (82/86) at 18 and 280 days PSO, respectively, and 72.7% of patients exhibited persistent Nab activity at 9 months, regardless of disease severity. CONCLUSION: Nab activity persists for up to 9 months following asymptomatic/mild COVID-19 among young adults, regardless of serological results.

Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19.

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.