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.     

MYASTHENIA GRAVIS : CLINICAL,SEROLOGICAL AND HISTOLOGICAL STUDIES IN RELATION TO THYMECTOMY

In 10 cases of myasthenia gravis correlative studies were made by means of autoimmune serological tests, electromyography, thymic X-ray examination (pneumomediastinography) and assessment of thymic morphology in relation to the effects of thymectomy (nine cases) and thymic irradiation (one case). The 10 patients were placed in three groups, namely (a) three young females with a non-involuted thymus showing “thymitis” and negative results to serological tests who derived benefit from thymectomy, (b) four older females with thymic atrophy and positive results to serological tests who for the most part gained no benefit from thymectomy, and (c) three males with thymomas and positive results to serological tests who obtained benefit from thymectomy in two instances. The presence of the characteristic autoantibody—the myoid antibody which reacted with thymic myoid cells and skeletal muscle—was helpful in diagnosis but did not appear to be related to neuromuscular block, neither was it of value in predicting the response to thymectomy. Electromyography with the decamethonium test showed, with one exception, the characteristic myasthenic responses irrespective of the patient's age, the presence or absence of myoid antibody, or the nature of the microscopic lesion in the thymus. The radiographic outline of the thymus as determined by pneumomediastinography correlated well with the size and shape of the resected thymus. The typical histological appearance in the thymus of abundant cortex and prominent medullary germinal centres and lymphocytosis was termed “thymitis” ; it was characteristic of the thymus of patients in group (a) and the residual thymus of patients with thymoma in group (c). Our clinical observations could be correlated with experimental studies, indicating that myasthenia gravis is associated with a destructive “autoimmune thymitis”. It is suggested that “thymitis” is associated with the release from the medulla of an uncharacterized humoral agent which causes neuro-muscular block.     

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.     

A case of systemic lupus erythematosus complicated by pure red cell aplasia and idiopathic portal hypertension after thymectomy

Abstract

We describe a 49-year-old woman who presented in 2002 with pure red cell aplasia (PRCA), systemic lupus erythematosus (SLE), and idiopathic portal hypertension (IPH) that developed following a thymectomy. She underwent a thymectomy at 40 years of age to treat myasthenia gravis. PRCA developed 3 years after the thymectomy and she was successfully treated with cyclosporin. Systemic lupus erythematosus and IPH were diagnosed 6 years later. We conclude that immunological dysfunction resulting from the thymectomy contributed significantly to the subsequent development of PRCA, SLE, and IPH in this patient. This is the first report to describe this extremely rare occurrence.     

A case of dermatomyositis associated with thymic abnormalities]

A case of dermatomyositis (DM) associated with thymic cyst with lymphoid follicle formations has been reported. A 57-year-old man developed polyarthralgia, muscle weakness, heliotrope rash and Gottron's sign. Laboratory findings showed elevated values of creatine-phosphokinase, aldolase and transaminase. He was diagnosed as DM and was treated with prednisolone 50 mg/day. Muscle weakness was improved immediately, although rash persisted unchangeably. He was examined for coexistence of malignant tumor which had been reported frequently as associated with DM. Enlargement of thymus was found by computer tomography and then thymectomy was performed. In his thymus, lymphoid follicle formations, which are as often encountered in other autoimmune diseases, were found. So far, the beneficial effect of thymectomy on the improvement of immunological abnormalities not only in patients with myasthenia gravis but also in patients with other autoimmune diseases has been recognized. In this case, intractable rash in DM improved after thymectomy. Further study needs to clarify the relationships between DM and thymic abnormalities.     

Lupus érythémateux aigu systémique après thymectomie

Thymectomy has a broad indication for the treatment of myasthenia gravis. Occurrence a few months or years after thymectomy of a number of autoimmune diseases including systemic lupus erythematosus in myasthenic patients is very rare. We report a 51-year-old woman who developed a systemic lupus 1 year after the thymectomy.     

Thymoma associated with pure red-cell aplasia: clinical features and prognosis

As information on the clinical features and prognosis of thymoma complicated by pure red-cell aplasia is limited, follow-up data on thymoma patients who had a thymectomy between 1954 and 1999 were analyzed retrospectively. Six of 166 cases were complicated by pure red-cell aplasia. In 3 of these, the pure red-cell aplasia appeared after surgical intervention. Remission was observed in 2 patients who underwent extended thymectomy. The other 4 patients subsequently died from pure red-cell aplasia. The outcome in patients with pure red-cell aplasia was poorer than that in the entire group of patients with thymoma and in those with thymoma complicated by myasthenia gravis. The possible onset of pure red-cell aplasia after thymectomy should be kept in mind during follow-up.     

Acute systemic lupus erythematosus after thymectomy for myasthenia. Sequential study of lymphocyte subpopulations

A 35 year-old woman developed severe systemic lupus erythematosus 9 years after thymectomy for myasthenia gravis. "Seric Thymic Factor" (STF) was low; T helpers subset, T helpers/T suppressors ratio and to a lesser extent T suppressors subset were decreased. Suppressor cell function investigated by Concanavaline A lymphocyte reactivity was low. Under cyclophosphamide, plasmapheresis and steroids all clinical and biological symptoms improved but STF remained low; T helpers, T suppressors subsets and T helpers/T suppressors ratio increased but did not reach the normal range. Statistical and immunological arguments suggest that the association between systemic lupus erythematosus and myasthenia gravis did not occur only by chance. Moreover, thymectomy might have played a role by decreasing the number and function of some subpopulations of lymphocytes.     

Thymoma-associated systemic lupus erythematosus, exacerbating after thymectomy. A case report and review of the literature

SIR, Myasthenia gravis (MG), pure red cell aplasia and acquiredhypogammaglobulinaemia are well recognized to be associatedwith thymoma, but systemic lupus erythematosus (SLE) can alsobe a manifestation of thymoma. The literature on the featuresof thymoma-associated SLE and the effect of thymectomy on SLEdisease activity is conflicting. A 76-yr-old Caucasian woman presented with malaise and weightloss of 10 kg over the past 6 months. Clinical examination atthat time revealed a low body weight of 46 kg and a body lengthof 160 cm. Laboratory examination showed     

Autoimmune disorders and paraneoplastic syndromes in thymoma

Thymomas are counted among the rare tumour entities which are associated with autoimmune disorders (AIDs) and paraneoplastic syndromes (PNS) far more often than other malignancies. Through its complex immunological function in the context of the selection and maturation of T cells, the thymus is at the same time highly susceptible to disruptive factors caused by the development and growth of thymic tumours. These T cells, which are thought to develop to competent immune cells in the thymus, can instead adopt autoreactive behaviour due to the uncontrolled interplay of thymomas and become the trigger for AID or PNS affecting numerous organs and tissues within the human body. While myasthenia gravis is the most prevalent PNS in thymoma, numerous others have been described, be they related to neurological, cardiovascular, gastrointestinal, haematological, dermatological, endocrine or systemic disorders. This review article sheds light on the pathophysiology, epidemiology, specific clinical features and therapeutic options of the various forms as well as courses and outcomes of AID/PNS in association with thymomas. Whenever suitable and backed by the limited available evidence, the perspectives from both the thymoma and the affected organ/tissue will be highlighted. Specific issues addressed are the prognostic significance of thymectomy on myasthenia gravis and other thymoma-associated AID/PND and further the impact and safety of immunotherapies on AID and PND relating to thymomas.     

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.

     

A patient with thymoma and four different organ-specific autoimmune diseases

This is the first report of a patient with four organ-specific autoimmune diseases; myasthenia gravis, type 1 diabetes mellitus, autoimmune hepatitis and Hashimoto's thyroiditis. The clinical history suggests a relationship with a non-removed thymoma. Not only the thymoma seems to have triggered these four diseases, the dramatic progressive course with an active autoimmune hepatitis and high concentrations of multiple autoantibodies was probably also associated with non-removal of the thymoma. Thymectomy should be performed in myasthenia gravis patients with thymoma and associated autoimmune diseases.     

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。     

Experience with surgery for thymoma associated with pure red blood cell aplasia. Report of three cases

We present three cases of thymoma associated with pure red blood cell aplasia in which thymomectomy and thymectomy were performed. Case 1, a patient with pure red blood cell aplasia and hypogammaglobulinemia, was treated after surgery with immunosuppressive agents. She did not show any remission and died eight months after the operation. Case 2, a patient with pure red blood cell aplasia alone, showed transient erythropoiesis only in the early post-operative period and died one year and seven months after the operation. Patient 3 had pure red blood cell aplasia alone before surgery and was treated after surgery with prednisolone and fluoxymesterone. He showed good remission from the aplasia after these treatments; however, myasthenia gravis appeared seven months after the operation. These results seem to show that such combined therapy as applied in case 3 may be effective for some of the patients with pure red blood cell aplasia and thymoma; however, the effects of thymomectomy or thymectomy (or both) are still controversial for the treatment of pure red blood cell aplasia.     

TYPE 1 CRYOGLOBULINAEMIA ASSOCIATED WITH A THYMIC TUMOUR: SUCCESSFUL TREATMENT WITH PLASMA EXCHANGE

Thymic tumours are associated with a wide range of autoimmuneand haematological disorders, notably myasthenia gravis, redcell aplasia, and systemic lupus erythematosus. An associationwith cryoglobulinaemia has only once been reported previously.In this report we describe a 60-yr-old male patient with a spindlecell thymoma, treated surgically, who also had type 1 cryoglobulinaemia,with severe peripheral circulatory impairment with digital ulcerationand a mononeutitis multiplex. The patient has been successfullytreated with prednisolone, immunosuppression and plasma exchange. KEY WORDS: Cryoglobulinaemia, Thymoma, Plasma exchange, Immunosuppression, Tumour, Corticosteroids     

Development of systemic lupus erythematosus after thymectomy for myasthenia gravis. Studies of suppressor cell function

Systemic lupus erythematosus developed in an 18-year-old man three years after thymectomy for myasthenia gravis. The patient had considerable defects in suppressor cell function that seemed to be partially reversed in vitro by the addition of thymic hormone.     

A pair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post-thymectomy

We describe a pair of monozygotic twins who are concordant for myasthenia gravis but discordant for systemic lupus erythematosus (SLE). SLE developed in twin 1 18 years post-thymectomy and has been characterized by recurrent transverse myelitis and optic neuritis. Twin 2 remains well post-thymectomy, except for a skin rash and persistent leukopenia. Both twins have developed autoimmune thyroid disease. We review genetic and environmental factors of importance in the pathogenesis of SLE and discuss the possible role of thymectomy in the etiology of the disease.     

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.