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.     

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.     

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.     

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 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 sequence of pathologic events in a patient after thymectomy for myasthenia gravis

The case of a rare coexistence of myasthenia gravis (MG) with systemic lupus erythematosus (SLE) is described. MG was diagnosed prior to SLE which developed after thymectomy. The patient was affected by HCV viremia. Therefore, there were therapeutic problems. Metylase treatment was continued for several years and dopamine receptor agonist was effectively administered as adjunctive therapy in SLE.     

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.     

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.     

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     

Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis.

Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine.     

Coexistence of systemic lupus erythematosus and myasthenia gravis: two distinct populations of anti-DNA and anti-acetylcholine receptor antibodies

A woman with a four-year history of systemic lupus erythematosus (SLE) developed myasthenia gravis (MG). The clinical features of lupus disappeared slowly while the myasthenic syndrome became predominant. However, her serum was positive for anti-DNA and anti-acetylcholine receptor antibodies. Cross-reactivity between anti-DNA antibodies and anti-acetylcholine receptor antibodies was not demonstrated, suggesting the presence of two different populations. A cellular immunology profile was normal as expected in MG and in contrast to SLE. Conceivably, SLE and MG might represent two opposite extremes in the spectrum of autoimmune diseases.     

Subset specificity of antilymhocyte antibodies in systemic lupus erythematosus. II. Preferential reactivity with T4 + cells is associated with relative depletion of autologous T4 + cells

Using indirect immunofluorescence and flow cytometry, we determined the proportion and number of T3+, T4+, and T8+ cells in the peripheral blood of patients with systemic lupus erythematosus whose sera were positive for cold-reactive antilymphocyte antibodies versus values in patients whose sera were negative for these antibodies. There was a disproportionate reduction in T4+ peripheral lymphocytes when cold-reactive antilymphocyte antibodies preferentially cytotoxic for this subpopulation were present in autologous serum. The decrease in this subset was responsible for a reduction in the T4:T8 ratio; variation in the number and proportion of T8+ cells was insignificant. A similar, but autoantibody-independent, alteration in the T4+ subpopulation was found in patients who were receiving prednisone therapy. A relationship between T cell population abnormalities and systemic lupus erythematosus disease activity, per se, was not observed.     

Subset specificity of antilymphocyte antibodies in systemic lupus erythematosus

Using indirect immunofluorescence and flow cytometry, we determined the proportion and number of T3+, T4+, and T8+ cells in the peripheral blood of patients with systemic lupus erythematosus whose sera were positive for cold-reactive antilymphocyte antibodies versus values in patients whose sera were negative for these antibodies. There was a disproportionate reduction in T4+ peripheral lymphocytes when cold-reactive antilymphocyte antibodies preferentially cytotoxic for this subpopulation were present in autologous serum. The decrease in this subset was responsible for a reduction in the T4:T8 ratio; variation in the number and proportion of T8+ cells was insignificant. A similar, but autoantibody-independent, alteration in the T4+ subpopulation was found in patients who were receiving prednisone therapy. A relationship between T cell population abnormalities and systemic lupus erythematosus disease activity, per se, was not observed.     

Damaging effect of peripheral mononuclear cells of dermatomyositis on cultured human skin fibroblasts

When human skin fibroblasts were incubated with mononuclear cells (MNC) from 6 patients with dermatomyositis (DM), striking attachment of MNC around fibroblasts was observed. Simultaneously, cell number and 3H-thymidine incorporation of fibroblasts after 4 days of incubation were significantly decreased. MNC of normal subjects, of patients with systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, and other miscellaneous diseases with skin manifestations did not show this effect. MNC of patients with DM did not adhere to KYM-1 cells (human rhabdomyosarcoma cell-line) and did not inhibit cell proliferation of these cells. Our study strongly suggests that cell mediated injury of fibroblasts might play an important role in the pathogenesis of DM.     

Isoniazid-triggered pure red cell aplasia in systemic lupus erythematosus complicated with myasthenia gravis

A 47-year-old woman who had been treated for systemic lupus erythematosus (SLE) with myasthenia gravis (MG) was admitted to our hospital with acute onset of severe anemia after administration of isoniazid. Pure red cell aplasia (PRCA) was confirmed by elevated serum iron levels, reticulocytopenia and bone marrow aspiration showing a remarkable reduction of erythroblasts. Finally, cyclosporine A successfully improved PRCA. Although both SLE and MG have the potential complication of PRCA, we report here a case of isoniazid-triggered PRCA.     

Autoimmune conditions and primary central nervous system lymphoma risk among older adults

Primary central nervous system lymphoma (PCNSL) risk is highly increased in immunosuppressed individuals, such as those with human immunodeficiency virus infection and solid organ transplant recipients, but rates are increasing among immunocompetent older adults (age ≥65 years). We utilized data from a large, nationally-representative cohort of older adults in the United States and found that PCNSL is significantly associated with systemic lupus erythematosus, polyarteritis nodusa, autoimmune hepatitis, myasthenia gravis and uveitis. Immunosuppressive drugs given to treat these conditions may increase PCNSL risk, but these associations cannot explain the observed temporal increase in PCNSL rates, given the low prevalence of these conditions.     

Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of autoantibodies directed against an epitope of the glutamate/N-methyl-D-aspartic acid (NMDA) receptor subunit NR2A (which is highly expressed in human brain) in the sera of lupus patients, and to investigate the possible correlation of these antibodies with clinical and serological manifestations of systemic lupus erythematosus (SLE). METHODS: Sera were obtained from 109 consecutive SLE patients. Controls were 65 patients with myasthenia gravis, 19 with autoimmune polyendocrine syndrome type I (APS I), and 65 healthy donors. A 15 amino acid long peptide based on a sequence within the NR2A subunit of the NMDA/glutamate receptor was synthesised. Antibodies to this peptide were determined by enzyme linked immunosorbent assay. Antibodies against double stranded DNA (dsDNA) were measured by Chrithidia luciliae assay. Disease activity was determined using the SLE disease activity index (SLEDAI). RESULTS: Sera of 34/109 SLE patients (31%) reacted specifically with the NR2A peptide compared with only 4/65 myasthenia gravis patients (6.1%, p<0.001), 1/19 APS I patients (5.3%, p<0.02), and 3/65 healthy controls (4.6%, p<0.001). No correlation was found between the presence of NR2A and dsDNA or anti-cardiolipin specific autoantibodies. In addition, no significant correlation was observed between the presence of NR2A specific antibodies and the SLEDAI score or any lupus related clinical manifestations. CONCLUSIONS: A significant number of SLE patients (31%) have NR2A specific antibodies that do not correlate with anti-dsDNA antibodies. Additional studies of lupus patients with neurological disorders should elucidate the role of NR2A specific antibodies in lupus related CNS manifestations.     

The nonspecific clearance function of the reticuloendothelial system in patients with immune complex mediated diseases before and after therapeutic plasmapheresis

Summary The nonspecific clearance function of the reticuloendothelial system (RES) in six patients with immune complex mediated systemic vasculitis was determined by the evaluation of the disappearance rate of technetium 99m labelled microaggregated human serum albumin colloid (MHAC) injected IV before and after therapeutic plasma exchange. Three patients with systemic lupus erythematosus (SLE) and one patient with immune complex vasculitis (ICV) exhibited a significant clinical improvement after plasmapheresis which was paralleled by an accelerated MHAC elimination rate following plasma exchange therapy. One patient with ICV and unresponsive to plasma exchange showed delayed MHAC elimination. In one patient with myasthenia gravis (MG), the elimination rate was not altered by plasmapheresis. The data obtained indicate that nonspecific clearance of the RES may be one effect of plasma exchange therapy in patients with immune complex mediated diseases.     

Monozygotic twins with Klinefelter's syndrome discordant for systemic lupus erythematosus and symptomatic myasthenia gravis

Monozygotic twins with Klinefelter's syndrome were evaluated for two distinct illnesses. One subject had clinical and serologic evidence of systemic lupus erythematosus and no symptoms of muscle weakness. His identical twin had typical symptoms and laboratory evidence of myasthenia gravis. Antibodies to acetylcholine receptors were present in both subjects. These patients are discussed in relation to genetic, hormonal, and immunologic mechanisms involved in the pathogenesis of these two disorders.