Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers

Lefeuvre, Claire; Payet, Christine; Fayet, Odessa-Maud; Maillard, Solène; Truffault, Frédérique; Bondet, Vincent; Duffy, Darragh; Montpréville, Vincent de; Ghigna, Maria-Rosa; Fadel, Élie; Lupo, Audrey; Alifano, Marco; Validire, Pierre; Gossot, Dominique; Béhin, Anthony; Eymard, B.; Berrih‐Aknin, Sonia; Panse, Rozen Le

doi:10.1016/j.jaut.2019.102337

Cited by 42 publications

(40 citation statements)

References 47 publications

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“…Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images. Other risk factors for the development of MG in patients with thymoma include (I) detection of AChR autoantibodies, (II) development of B1 or B2 thymoma subtypes, (III) presence of ectopic thymic germinal centers, (IV) local invasiveness of thymoma, and (V) females under 50 years old (9). The patient in this case had two of the risk factors listed.…”

Section: Case Presentationmentioning

confidence: 85%

New diagnosis of myasthenia gravis presenting as myasthenic crisis after radical thymectomy: a case report

Nayak¹,

Shargall²

2021

Curr Chall Thorac Surg

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Myasthenia gravis (MG) is a well-known paraneoplastic syndrome associated with thymomas. It occurs secondary to the production of autoantibodies against acetylcholine receptors (AChR). This results in the reduced delivery of action potentials that generate muscular contractions. In its most extreme form, MG can present as a crisis resulting in respiratory failure requiring invasive ventilatory support. There are several known risk factors for patients with known MG to develop a post-operative crisis after thymectomy.It is recommended that patients diagnosed with thymoma be evaluated for MG prior to resection. However, most guidelines do not make any recommendations regarding screening with AChR antibody tests if there are no signs or symptoms of MG. In this case report, we present a patient with an incidental finding of a large anterior mediastinal thymoma with no signs or symptoms of MG. The patient subsequently develops bulbar symptoms and dyspnea necessitating readmission to hospital 2 weeks after surgery. This eventually culminated in cardiorespiratory arrest. This was confirmed to be secondary to a myasthenic crisis via AChR autoantibody testing. The patient was treated with intravenous immunoglobulin (IVIG), pyridostigmine and prednisone with good effect. The onset of myasthenic crisis after a surgical insult in known MG patients has been well documented. However, the development of myasthenic crisis in an asymptomatic patient with no history of MG has not previously been shown. This case report illustrates the need for more sensitive screening tools to detect MG in patients with thymoma. The routine use of AChR autoantibody testing as a screening tool in patients with thymoma even when asymptomatic and/or deemed low risk may help clinicians better prepare for possible MG flairs. Furthermore, surgeons should have a low threshold to suspect MG in patients after thymectomy regardless of time elapsed since surgery.

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Section: Case Presentationmentioning

confidence: 85%

New diagnosis of myasthenia gravis presenting as myasthenic crisis after radical thymectomy: a case report

Nayak¹,

Shargall²

2021

Curr Chall Thorac Surg

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“…In human patients with MG, studies have revealed conflicting data on optimal outcome and age of MG onset, but most recent studies have revealed a better outcome with older age 23,24 . However, most data on outcome in relation to age in human MG pertain to MG associated with thymoma or thymectomy 22,25 …”

Section: Discussionmentioning

confidence: 99%

Clinical features and outcome of acquired myasthenia gravis in 94 dogs

Forgash

Chang

Mittelman

et al. 2021

Veterinary Internal Medicne

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Background Factors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited. Hypothesis/Objectives Of dogs with MG, advancing age and comorbid neoplasia are associated with poor long‐term prognosis and low rates of remission. Animals Ninety‐four client‐owned dogs with MG diagnosed by acetylcholine receptor antibody (AChR Ab) assay between 2001 and 2019 from a university clinic and 3 private clinics in the United States. Methods Cases were retrospectively evaluated and data were collected to determine clinical signs, treatment, and response to therapy defined by means of a clinical scoring rubric. Immunological remission was defined as a return of the AChR Ab concentration to <0.6 nmol/L. Multivariable binary logistic regression analysis was used to identify clinical criteria predicting remission. Results An anticholinesterase drug was used to treat 90/94 (96%) dogs, which in 63/94 (67%) was the sole treatment; other drugs included immune modulators. Clinical remission (lack of clinical signs ≥4 weeks after treatment cessation) was observed in 29 (31% [95% confidence interval (CI): 22.4‐40.8%]) dogs, clinical response (lack of clinical signs on treatment) in 14 (15% [95% CI: 9.0‐23.6%]) dogs, clinical improvement (on treatment) in 24 (26% [95% CI: 17.8‐35.2%]) dogs, and no clinical improvement in 27 (29% [95% CI: 20.5‐38.6%]) dogs. Immunological remission was observed in 27/46 (59%) dogs, with clinical remission in all 27. Younger age (P = .04) and comorbid endocrine disease (P = .04) were associated with clinical remission. Initial AChR Ab concentration (P = .02) and regurgitation (P = .04) were negatively associated with clinical remission. Conclusions and Clinical Importance Clinical remission in MG is less likely in older dogs and dogs presenting with regurgitation or high initial AChR Ab concentration, but more likely in younger dogs and dogs with comorbid endocrine disease.

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“…They include: the lack of a functional medulla expressing AIRE; the reduction, or absence, of tolerogenic myoid cells; the reduced expression of HLA class II molecules; and the failure of Treg generation, which ultimately leads to autosensitization to AChR, and other locally expressed muscle antigens, and defective negative T-cell selection [14,49,50]. Recently, a higher proportion of GCs was abnormally found in nonneoplastic thymic tissue adjacent to thymoma in MG patients compared to thymoma patients without MG, suggesting that B-cell dysregulation characterizes not only thymic hyperplasia but also thymoma-associated MG, and that GCs may represent a risk factor for the development of MG in thymoma patients [51].…”

Section: Role Of the Thymus In Mg Pathologymentioning

confidence: 99%

Epstein-Barr Virus in Myasthenia Gravis: Key Contributing Factor Linking Innate Immunity with B-Cell-Mediated Autoimmunity

Bortone¹,

Scandiffio²,

Cavalcante³

et al. 2021

Infectious Diseases

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Epstein-Barr virus (EBV), a common human herpes virus latently infecting most of the world’s population with periodic reactivations, is the main environmental factor suspected to trigger and/or sustain autoimmunity by its ability to disrupt B-cell tolerance checkpoints. Myasthenia gravis (MG) is a prototypic autoimmune disorder, mostly caused by autoantibodies to acetylcholine receptor (AChR) of the neuromuscular junction, which cause muscle weakness and fatigability. Most patients display hyperplastic thymus, characterized by ectopic germinal center formation, chronic inflammation, exacerbated Toll-like receptor activation, and abnormal B-cell activation. After an overview on MG clinical features and intra-thymic pathogenesis, in the present chapter, we describe our main findings on EBV presence in MG thymuses, including hyperplastic and thymoma thymuses, in relationship with innate immunity activation and data from other autoimmune conditions. Our overall data strongly indicate a critical contribution of EBV to innate immune dysregulation and sustained B-cell-mediated autoimmune response in the pathological thymus of MG patients.

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Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers

Cited by 42 publications

References 47 publications

New diagnosis of myasthenia gravis presenting as myasthenic crisis after radical thymectomy: a case report

New diagnosis of myasthenia gravis presenting as myasthenic crisis after radical thymectomy: a case report

Clinical features and outcome of acquired myasthenia gravis in 94 dogs

Epstein-Barr Virus in Myasthenia Gravis: Key Contributing Factor Linking Innate Immunity with B-Cell-Mediated Autoimmunity

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