Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder

Myasthenia gravis is an antibody-mediated autoimmune disease at the neuromuscular junctions. It can be associated with many other autoimmune diseases. We report a case of acute presentation of autoimmune hepatitis with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder.     

Thymomes et maladies auto-immunes

The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection.     

Concomitant polymyositis and myasthenia gravis reveal malignant thymoma. A case report and review of the literature.

The frequency of thymona associated with autoimmune diseases has been reported to be increased, with 50% of thymoma patients also having myasthenia gravis (MG). Other autoimmune disorders, such as autoimmune erythroblastopenia and polymyositis (PM), have been less frequently associated with thymoma. The association of MG and PM with thymoma is rare. We here report the case of a 66-year-old woman whose concomitant MG and PM revealed malignant thymoma and review the other published cases of this association.     

Giant cell myositis and myocarditis revisited

Giant cell myositis (GCMm) and giant cell myocarditis (GCMc) are two rare autoimmune conditions. Among these, GCMc is a life-threatening disease with a 1-year mortality rate of 70%. Lethal ventricular arrhythmias, rapid evolution to heart failure and sudden death risk makes GCMc an emergency condition. It is thought to be mediated by T-cells and characterized by the presence of myofiber necrosis and giant cells in biopsies. Most commonly co-manifesting conditions with GCMm and/or GCMc are thymoma, myasthenia gravis and orbital myositis, all of which are treatable. As suspicion is the key approach in diagnosis, the physician following patients with thymoma with or without myasthenia gravis and with orbital myositis should always be alert. The fatal nature of GCMc associated with these relatively benign diseases deserves a special emergency attention with prompt institution of combined immunosuppressive treatment and very early inclusion of heart failure teams.Key words: giant cell myositis, giant cell myocarditis, thymoma/myasthenia gravis, orbital myositis     

THE THYMUS: EXPERIMENTAL PHYSIOLOGY,AND PATHOLOGY IN MAN

The thymus is an integral part of the immunological system. It is a site of intense lymphopoiesis, especially in early life. Neonatal thymectomy in mice causes runting and death due to gross immunological deficiencies. These deficiencies are determined by lymphopenia, and by lack of a lymphotrophic hormone secreted by the epithelial cells of the medulla; this hormone confers on lymphocytes the capacity to respond to antigenic stimulation. The thymus may be the main source of lymphoid cells carrying new or primary patterns of immune reactivity; it is thus “first-level” or “central” lymphoid tissue, which seeds cells to “second-level” or “peripheral” lymphoid tissues in the lymph nodes and spleen. Pathological lesions of the thymus in man include aplasia, hyperplasia, dysplasia and neoplasia. Gross aplasia characterizes the immunological deficiency diseases of infancy, including the lymphopenic type of congenital agammaglobulinæmia. Hyperplasia accompanies thyrotoxicosis. Dysplasia refers to the lymph follicle-germinal centre development in myasthenia gravis, probably an autoimmune disease, and to the proliferation in the medulla of spindle-epithelial cells in lupus erythematosus, an autoimmune disease. Neoplasia occurs as benign thymoma, which may be accompanied by extrathymic diseases which are possibly autoimmune in origin; these include myasthenia gravis, red cell aplasia, polymyositis, agammaglobulinæmia and lupus erythematosus. These diseases may in some way be caused by the thymoma; alternatively, the thymoma may represent the result of continuing hyperplasia of the thymus provoked by a primary autoimmune process. The place of thymectomy in the treatment of autoimmune disease is discussed. It is an established procedure in myasthenia gravis, and has been successful in two cases of autoimmune hæmolytic anæmia in infancy. We review our experience with thymectomy for three patients with systemic lupus erythematosus.     

La myasthénie du côté de l’interniste

Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis.     

Malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH

Patients with thymoma are likely to present with associated autoimmunologic disorders. The occurrence of syndrome of inappropriate antidiuretic hormone (SIADH) attributable to thymoma is extremely rare. We herein present an extremely rare case of a 59-year-old man patient who was discovered to have malignant thymoma associated with myasthenia gravis, Graves' disease, and SIADH. He was admitted for evaluation and treatment of hyponatremia (Na 125 mEq/l). SIADH was diagnosed, and thymoma was identified as its cause. The patient was also found to have both Graves' disease and myasthenia gravis. The hyponatremia was normalized with water restriction and 3% saline therapy before thymectomy. The thymic tumor was a Masaoka stage III thymoma that resulted in direct invasion to the wall of the innominate vein, but there was no finding of invasion to other mediastinal organs. Complete thymectomy with innominate vein graft was performed. Microscopic histopathology findings corresponded to those of a mixed-type thymoma and type B2. However, immunohistochemical stain for antidiuretic hormone was negative in the tumor cells. Adjuvant radiation therapy was employed postoperatively, and the patient's postoperative recovery was uneventful. He subsequently reached a euthyroid state. And the reversal to normal sodium and osmolality levels was continued after the tumor removal without any further management for hyponatremia. The observation of this interesting case and a literature review provided us with the opportunity to explore the pathogenesis and clinical aspects of thymoma-related autoimmune and/or endocrine disorders which must be suspected in patients with thymoma.     

Myasthenia gravis and premature ovarian failure

Myasthenia gravis is believed to be an autoimmune disorder that results from antibodies directed against acetylcholine receptors. Not infrequently, it is associated with other autoimmune diseases, and, recently, several cases have been reported of coexistent premature ovarian failure. A 25-year-old nullgravida woman with myasthenia gravis became amenorrheic and then had ovarian failure with increased gonadotropin and negligible estrogen levels. Other endocrine functions were normal. An in vitro assay demonstrated the presence, in serum, of an inhibitor of binding to the luteinizing hormone (LH) receptor that suggested the possibility of a similar autoimmune process underlying the myasthenia gravis and premature ovarian failure. This could be the first case in which both disorders occurred with evidence for an LH receptor antagonist.     

Case Report of Thymoma Tumor Reduction Following Plasmapheresis

For thymoma, multidisciplinary antitumor strategy is composed of surgery, chemotherapy, and radiotherapy. Meanwhile, ∼20% to 25% of patients with thymoma have myasthenia gravis and plasmapheresis is recommended for thymoma-associated myasthenia gravis.We report a case that a 40-year-old woman with thymoma experiencing tumor relapse after surgery showed significant response to plasmapheresis.This is the first case of thymoma responded to plasmapheresis, which may guide the study of the etiology and pathogenesis of thymoma.     

Pancreatic Cancer in a Patient with Myasthenia Gravis

Myasthenia gravis has been associated with several diseasessuch as hyperthyroidism and malignancy (thymoma,lung carcinoma) but so far no reports have demonstrated arelationship between this disease and pancreatic disease.We report a 66-year-old man with myasthenia gravis diagnosedon the basis of clinical symptoms (eyelid ptosis),typical abnormalities on repetitive nerve-stimulation tests,and the presence of Ach-R antibodies in the serum. The responseto anticholinesterasic agents (pyridostigmine) wasgood, but after 1 year, he developed pancreatic cancer andmyasthenia gravis symptoms recurred. After surgery andchemotherapy, myasthenia gravis symptoms disappeared.Some months later, the patient had a recurrence of pancreaticcancer after relapse of myasthenia gravis.     

Pleural dissemination of thymoma showing tumor regression after combined corticosteroid and tacrolimus therapy

We present the case of an elderly woman with myasthenia gravis who had pleural dissemination of thymoma reduced by treatments with a moderate dose of corticosteroids and a conventional dose of tacrolimus. A maintenance dose of prednisolone for myasthenia gravis could not shrink the size of the disseminated thymoma, but prednisolone (>30 mg daily) succeeded in reducing the size of the tumor. Moreover, a combination with tacrolimus enabled the daily dose of prednisolone to be tapered off without recurrence of myasthenia gravis, and the disseminated thymoma almost disappeared. A moderate or higher dosage of corticosteroids with tacrolimus may, in some cases, be an effective procedure for pleural dissemination of thymoma. Treatment should be undertaken on a trial basis for patients not indicated for surgery, radiotherapy, or chemotherapy.     

自身免疫多内分泌腺病综合征Ⅲ型合并重症肌无力一例报道及人类白细胞抗原基因分析

1型糖尿病合并自身免疫性甲状腺疾病是自身免疫多内分泌腺病综合征(APS)Ⅲ型最常见的类型,但重症肌无力合并APS Ⅲ型罕见报道。本研究对1例先后出现眼肌型重症肌无力、1型糖尿病、桥本甲状腺炎的APS Ⅲ型合并重症肌无力的男性患者进行了人类白细胞抗原(HLA)基因分析及文献回顾11例APSⅢ合并重症肌无力,发现HLA-D...     

Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.     

Giant cell myositis associated with concurrent myasthenia gravis: a case-based review of the literature

The term “giant cell myositis” has been used to refer to muscle diseases characterized histologically by multinucleated giant cells. Myasthenia gravis is an autoimmune neuromuscular junction disorder. The rare concurrence of giant cell myositis with myasthenia gravis has been reported; however, the clinical and histological features have varied widely. Here, we present such a case and a review of the literature. An 82-year-old woman admitted for subacute, progressive, proximal muscle weakness developed acute-onset dysphagia, dysphonia, and respiratory distress 5 days after admission. Laboratory findings were positive for acetylcholine receptor binding antibodies and striational muscle antibodies against titin. Muscle biopsy demonstrated widespread muscle fiber necrosis with multinucleated giant cells, consistent with giant cell myositis. She died despite treatment with pulse methylprednisolone and plasma exchange. A literature review of the PubMed and Scopus databases from 1944 to 2020 identified 15 additional cases of these co-existing diagnoses. We found that giant cell myositis with myasthenia gravis primarily affects female patients, is typically diagnosed in the 6–7th decades, and is characterized by the presence of thymoma. Muscle histology predominantly shows giant cell infiltrate without granulomas. The onset of myasthenia gravis symptoms may precede, follow, or coincide with symptoms of myositis. Treatment with thymectomy, anticholinesterase inhibitors, or immunosuppressive therapy may lead to favorable clinical outcomes.

     

Hyperparathyroidism, chemodectoma, thymoma, and myasthenia gravis.

Of two patients with hyperparathyroidism, one had an associated chemodectoma, and the other had a thymoma and myasthenia gravis. There is a possible relationship to the multiple endocrine neoplasia syndromes.     

胸腺瘤伴重症肌无力患者瘤组织中Bcl-2和Fas的表达水平

目的 探讨凋亡相关基因bcl-2、Fas在胸腺瘤伴重症肌无力患者瘤组织中的表达状况及其临床意义。方法经手术治疗的25例胸腺瘤伴重症肌无力患者的肿瘤组织标本为病例组，25例先天性心脏病患者手术时切取的正常胸腺组织标本为对照组，通过免疫组化的方法检测两组标本中Bcl-2和Fas蛋白的表达水平。结果胸腺瘤中Bcl-2及Fas表达水平均显著高于对照组，经Ridit分析两者差异均有统计学意义（U值分别为2．645、3．200，P均〈0．05），但Bcl-2和Fas的表达水平与胸腺瘤患者的重症肌无力Ossermen分型、术前病程、年龄及性别等临床因素均无显著相关。结论 Bcl-2和Fas在胸腺瘤伴重症肌无力的发病中可能具有重要作用。     

A case of post-thymomectomy myasthenia gravis after extrapleural pneumonectomy for invasive thymoma which necessistated long-term mechanical ventilation]

The patient was a 58-year-old male with invasive thymoma which had disseminated in the left thorax and was histologically a polygonal cell type lesion. While the serum value of anti-acetylcholine receptor antibody was high before surgery, there were signs of myasthenia gravis. After preoperative chemotherapy, a thymectomy and left panpleuropneumonectomy were conducted. Forty days after surgery, the patients suffered post-thymomectomy myasthenia gravis, which necessitated mechanical ventilation for 6 months. Despite steroid therapy and 17 plasmapheresis procedures the tidal volume increased by little more than 200-250 ml during that time. The causes of ventilatory failure, therefore, were probably decreased pulmonary function due to extrapleural pneumonectomy and the myasthenia gravis. According to the literature, polygonal cell type thymomas with high serum levels of anti-acethycholine receptor antibody have higher incidences of post-thymomectomy myasthenia gragvis than other ones. Therefore, the risk of post-thymomectomy myasthenia gravis should be kept in mind when extrapleural pneumonectomy for invasive thymoma is being considered, especially in the cases of this type.     

Newly diagnosed multiple sclerosis in a patient with ocular myasthenia gravis: A case report

Rationale:Patients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by antibodies, they are likely to occur together. However, since multiple sclerosis is an autoimmune disease that is not mediated by a specific antibody, it has fewer immune mechanisms in common with myasthenia gravis than neuromyelitis optica spectrum disease. We encountered a case of newly developed multiple sclerosis in a patient with myasthenia gravis.Patient concerns:A 46-year-old man was diagnosed with ocular myasthenia gravis 6 years ago and had been taking pyridostigmine to control his symptoms.Diagnosis:The patient developed right optic neuritis, and multiple sclerosis was suspected based on the brain magnetic resonance imaging findings. However, the required diagnostic criteria were not met.Interventions:Disease-modifying therapy was not initiated, and clinical progression of the disease was monitored.Outcomes:One year after the onset of optic neuritis, the patient developed myelitis and was diagnosed with multiple sclerosis, prompting treatment with disease-modifying therapy.Lessons:When optic neuritis occurs in patients with myasthenia gravis, careful evaluation is necessary while considering the possibility that it may be the first symptom of a demyelinating central nervous system disease. Therefore, it is important to conduct shorter-interval monitoring and symptom screening for patients with neurological autoimmune diseases, such as myasthenia gravis, even if multiple sclerosis is not initially suspected, to achieve early detection of multiple sclerosis.     

Gm and Km allotypes in autoimmune diseases.

The associations or linkages between the polymorphisms of the Gm and Km immunoglobulin allotypes and the susceptibility to autoimmune diseases, including diseases with immuno-pathological pathogenesis are reported in this review. These diseases include multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, Crohn's disease, coeliac disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. Immunoglobulin allotypes are described as well as the statistical methods used to analyse the data.