Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with chronic graft-versus-host disease (GVHD) developed myasthenia gravis (MG) 762 to 1,180 days after allogeneic bone marrow transplantation. Symptoms of MG were observed after taper or discontinuation of immunosuppressive treatment of chronic GVHD. All patients developed antibodies to acetylcholine receptor, and one had antibody formation to striated muscle. One patient died of complications of treatment of MG. The severity of disease underscores the importance of the differential diagnosis and the need for prompt therapy of this late complication after human bone marrow transplantation.
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PMID:Myasthenia gravis after allogeneic bone marrow transplantation: relationship to chronic graft-versus-host disease. 352 78

A 37-year-old Japanese man with chronic myeloid leukemia (CML) developed myasthenia gravis 29 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched brother. Proximal muscle weakness and bilateral ptosis occurred along with the exacerbation of chronic GVHD shortly after sudden cessation of cyclosporine (CYA) and prednisolone. The diagnosis of myasthenia gravis was made based on clinical symptoms and elevation of an anti-acetylcholine receptor antibody titer and all symptoms related to myasthenia gravis promptly diminished with the start of treatment for chronic GVHD. In most previously reported cases, the underlying disease was aplastic anemia (6 of 7 cases) and donors were of the opposite sex (6 of 7 cases). The haplotypes HLA B7 (3 of 5 cases), B35 (3 of 5 cases), and DR2 (3 of 3 cases) were common. All cases suffered from chronic GVHD. The present case had only chronic GVHD and HLA B7 as a background for myasthenia gravis after BMT. The abrupt cessation of immunosuppressive therapy may also be related to the development of myasthenia gravis after BMT.
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PMID:Myasthenia gravis after allogeneic bone marrow transplantation. 795 Nov 5

The change in immunological parameters was studied during the clinical course of a myasthenia gravis (MG) patient with chronic graft-versus-host disease (GVHD), which developed after bone marrow transplantation from an HLA-identical donor. Anti-acetylcholine receptor antibody gradually decreased in the patient treated with immunosuppressive agents, but was not detected in the donor. Lymphocyte numbers were low just before the onset of MG, increased abruptly within several days and then gradually decreased with treatment. The percentage of CD3+ and CD19+ lymphocytes was higher at onset than before, the percentage of CD4+ cells was higher at onset and gradually decreased with treatment, while CD8+ cells showed the lowest level just before onset and gradually increased during the clinical course. CD4+/CD45RA- cells also showed the highest levels at onset and a gradual decrease with treatment. Cellular, as well as humoral immune responses, might be associated with the pathogenesis of MG with chronic GVHD.
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PMID:Change of immunological parameters in the clinical course of a myasthenia gravis patient with chronic graft-versus-host disease. 867 93

Myasthenia gravis (MG) is a rare complication of allogeneic bone marrow transplantation (BMT). We present the 11th case in the medical literature, a 23-year-old female 100 months post-allogeneic bone marrow transplantation for acute myelogenous leukemia (AML). After discontinuation of immunosuppression for chronic graft-versus-host disease (GVHD) involving skin, gastrointestinal tract and lacrimal glands, the patient developed severe, progressive dysphagia initially attributed to esophageal candidiasis. With the development of muscle weakness, ptosis, and dysphonia the diagnosis of generalized myasthenia gravis was suspected, and confirmed by elevated anti-acetylcholine receptor antibody titer and a positive edrophonium challenge. Prednisone and pyridostigmine produced improvement, and thymectomy was performed without pathologic evidence of thymoma. Recurrent post-operative respiratory distress required transient mechanical ventilation. Twenty-seven months after diagnosis, the patient requires maintenance prednisone to control symptoms of myasthenia gravis. The clinical features of all reported cases of MG post-allogeneic BMT are reviewed, and universal features include an association with decreasing immunosuppression, the presence of other manifestations of chronic GVHD, anti-acetylcholine receptor antibodies, and the absence of an associated thymoma. HLA Cw1, Cw7 and DR2 were identified at frequencies significantly above that expected from HLA antigen prevalance studies, and may be markers for increased risk of developing MG post-allogeneic BMT. No statistically significant associations with HLA A2, B7, B35 or donor-recipient sex mismatch were present. Reinstitution of immunosuppression and standard therapies for myasthenia gravis were effective in the majority of cases. The role of thymectomy in this population remains unclear.
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PMID:Myasthenia gravis in association with allogeneic bone marrow transplantation: clinical observations, therapeutic implications and review of literature. 915 70

A 26-year-old man, affected by acute non-lymphocytic leukemia, received a bone marrow transplantation from his HLA identical sister. A mild (grade 1) acute graft-versus-host disease (GVHD) developed during the first month after BMT. A moderate (grade 2) muco-cutaneous GVHD was present from the 4th month on, in association with recurrent oral herpes simplex infection. A typical clinical and electromyographic picture of myasthenia gravis (MG) developed 46 months after BMT, requiring continuous medication with pyridostigmine. A high titer of antibiotics against the acetylcholine receptor was found in the serum of the patient but not in the serum of the donor. Since the donor had no evidence of MG or other autoimmune disorders, this is likely to be an autoimmune complication of chronic GVHD. Other cases described in the literature are reviewed: a recurrent expression or coexpression of some HLA antigens was recorded, indicating that some genetic factors could predispose to this acquired disorder.
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PMID:Myasthenia gravis after allogeneic bone marrow transplantation. A case report and a review of the literature. 932 79

A 20-year-old man with aplastic anemia developed myasthenia gravis (MG) 7 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched sister. Proximal muscle weakness (predominant in the lower limbs) and dysphagia occurred without any other sign of graft-versus-host disease (GVHD), 1 month after cessation of immunosuppression with cyclosporine. The diagnosis of MG was based on clinical symptoms and on neurophysiologic investigations showing a significant increase of the Jitter in single-fiber electromyography and a significant decremental response during repetitive stimulation at slow rates, but antibodies against the acetylcholine receptor (AchRab) were negative. All clinical and neurophysiological signs normalized within 1 month of treatment with low-dose prednisolone and pyridostigmine, and the patient is perfectly well 1 year after cessation of all therapy. All cases of BMT-associated MG previously published are reviewed in comparison with ours. The originality of this new observation is that this case is the only one not associated with chronic GVHD and negative for AchRab. Alternatively, MG may have been the sole manifestation of chronic GVHD in this patient.
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PMID:Myasthenia gravis without chronic GVHD after allogeneic bone marrow transplantation. 970 30

Ocular problems are common in recipients of stem cell transplantation (SCT), but ptosis is rarely reported and investigated. Among 346 consecutive SCT recipients, severe bilateral ptosis was noticed or reported in six cases (five women and one man), all with acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD). On univariate analysis, both aGVHD (P=0.001) and cGVHD (P<0.001) were associated with post SCT ptosis, while a trend was shown for female sex (P=0.086). The median level of anti-acetylcholine receptor antibody was significantly higher in ptosis cases than controls with cGVHD (student's t-test, P=0.01). Antistriated muscle antibody was detected in three cases and was not significantly different from controls (Fisher's exact test, P=0.29). Tensilon tests were uniformly negative. However in five cases, single fibre electromyogram at frontalis muscle showed irregular recruitment effort, suggesting localized neuromuscular transmission defect reminiscent of ocular myasthenia gravis (MG). Two patients were observed, while three patients did not respond to mestinon or steroids treatment and one patient underwent aponeurosis advancement surgery. Transplant physicians and ophthalmologists should be aware of the problem of post SCT ptosis, which may be related to alloimmune causes of neuromuscular transmission block. Diagnosis can be difficult to confirm even with invasive SF-EMG testing. Most cases warrant conservative treatment due to chronicity, benign course and poor response to medication.
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PMID:Immunological and electrophysiological investigations of severe ptosis after bone marrow transplantation. 1524 30

A 51-year-old man developed progressive debilitating limb and respiratory muscle weakness while undergoing treatment for chronic graft-versus-host disease secondary to allogeneic bone marrow transplant for mantle cell lymphoma. He had a normal serum creatine kinase level and acetylcholine receptor antibodies were negative. Electromyography showed a severe, nonirritable myopathy and a sensory motor axonal polyneuropathy. A muscle biopsy showed a necrotizing, vacuolar myopathy with many fibers containing autophagic and red-rimmed vacuoles, suggestive of an amphiphilic drug myopathy. The patient's strength and function improved significantly after discontinuation of hydroxychloroquine.
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PMID:Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft-versus-host disease. 1579 21

Myasthenia gravis (MG) is commonly regarded as the prototype of an antibody-mediated, organ-specific autoimmune disease. Antibodies against the acetylcholine receptor (AChR) on the muscle endplate trigger its typical clinical manifestations of weakness and fatiguability. T-B cell interactions are thought to play a crucial role in the pathogenesis of MG. OX40 (CD134), a costimulatory molecule that is expressed on activated CD4+ T-cells, might contribute to the development or pathogenesis of immune-mediated diseases such as rheumatoid arthritis and graft-versus-host disease. In the present study, we investigated the expression of OX40 on CD4+ T-cells from patients with MG and healthy individuals. Results from 36 MG patients and 28 healthy controls revealed that more freshly isolated CD4+ T-cells from MG patients expressed OX40 than cells from healthy individuals. High levels of antibodies against the AChR, thymic hyperplasia and onset at an early age were associated with elevated expression of OX40. Upon activation by various concentrations of anti-CD3 antibodies, CD4+ T-cells from MG patients showed a tendency toward higher levels of OX40 expression than cells from healthy individuals. Given the role of OX40 in the immune system, we conclude that OX40 might contribute to the development of MG.
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PMID:Expression of OX40 (CD134) on CD4+ T-cells from patients with myasthenia gravis. 1636 41

A 17-year-old male underwent a second bone marrow transplantation using a 6/8 allele HLA-matched unrelated donor. On day 100 after transplantation, steroid treatment for chronic graft-versus-host disease (GVHD) was started. On day 766, the patient experienced general fatigue, followed by double vision, ptosis, and dysphagia on day 810. Based on the positivity of the acetylcholine receptor antibody and a waning electromyography pattern, he was diagnosed with GVHD-related myasthenia gravis (MG). On day 861, we initiated plasmapheresis (PE), followed by the administration of intravenous immunoglobulin (IVIg) ; this treatment attenuated the bulbar symptoms of MG. Although the steroid treatment was continued, we restarted the administration of tacrolimus. On day 2,739 after transplantation, we stopped the steroid treatment, and the patient remained in remission for MG following the cessation of the steroid treatment on day 2,897. This case suggests that PE followed by IVIg could be an effective therapeutic alternative for MG associated with GVHD.
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PMID:[Durable remission attained with plasmapheresis and intravenous immunoglobulin therapy in a patient with acute exacerbation of GVHD-related myasthenia gravis]. 2987 33


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