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.     

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.     

An interplay of genetic and environmental factors in familial hepatitis and myasthenia gravis

A family is described in which there occurred two cases of the lupoid type of active chronic hepatitis with cirrhosis, one of chronic persistent hepatitis, and one of myasthenia gravis. The two cases of lupoid hepatitis were in the proposita, a schoolgirl aged 16 years, and her great-aunt aged 69 years whom she had never met. The case of myasthenia gravis was that of the father. The whole family, except the great-aunt, had been exposed to an epidemic of infectious hepatitis five years previously, and the girl and her brother had contracted this disease. The schoolgirl later developed active chronic hepatitis while her brother had chronic persistent hepatitis without immunological concomitants.APART FROM COINCIDENCE, SOME COMBINATION OF THREE PROCESSES WAS REQUIRED TO ACCOUNT FOR THE ILLNESSES IN THIS FAMILY: a genetic predisposition to chronic liver disease in particular, a genetic predisposition to autoimmune reactions in general, and a ;triggering' effect of infection with the hepatitis virus.     

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.     

Short-term interferon therapy for chronic hepatitis C patients with low viral load

BACKGROUND/AIMS: To evaluate the usefulness of high-dose short-term interferon therapy prospectively in 32 chronic hepatitis C patients with a low viral load showing the rapid disappearance of hepatitis C virus RNA after the start of interferon therapy. METHODOLOGY: Each patient was confirmed with a low hepatitis C virus RNA level less than 1.0 Meq/mL before the start of interferon therapy regardless of hepatitis C virus genotypes. High-dose short-term interferon therapy was defined as administration of natural interferon alpha 10 MU/day for 14 weeks (daily for 4 weeks then three times a week for 10 weeks). This course of treatment was carried out only in cases with the rapid disappearance of hepatitis C virus RNA at 2 weeks after the start of interferon. RESULTS: Sustained virological response was observed in 30 of 32 patients (93.8%) who received high-dose short-term interferon therapy. One patient who received 24 weeks interferon administration relapsed and became a non-responder. One patient refused to continue this therapy. CONCLUSIONS: High-dose short-term interferon therapy might be useful when combining the selection of patients according to pretreatment hepatitis C virus RNA levels and testing virus presence at an early point after the start of interferon therapy.     

Pericarditis in myasthenia gravis

Myasthenia gravis is an autoimmune disorder with antibodies to the acetylcholine receptors (Ach R) in skeletal muscles. Myocardial involvement can present as a myocarditis or with arrhythmias. To our knowledge, there is no documentation in the literature of pericardial involvement in myasthenia gravis. We report the presence of pericardial effusion and atrioventricular conduction block in a patient with myasthenia gravis that responded appropriately to immunosuppressive therapy and plasma exchanges.     

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.     

Pericarditis due to interferon-alpha therapy during treatment for chronic hepatitis C

Pericarditis due to interferon alpha therapy during treatment for chronic hepatitis C. We report a patient with pericarditis during therapy with interferon alpha 2b for chronic hepatitis C viral infection. We review interferon alpha therapy and hepatitis C virus side-effects on the cardiovascular system.     

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.     

Current Trends in the Management of Myasthenia Gravis: Plasmapheresis and Immunosuppressive Therapy

Summary: Current trends in the management of myasthenia gravis: Plasmapheresis and immunosuppressive therapy. J. D. Pollard, A. Basten, J. E. Hassall, H. Kronenberg, R. Cobcroftand R. Dawkins, Aust. N.Z. J. Med ., 1980, 10, pp. 212–217.
In recent years a considerable body of evidence has accumulated to demonstrate autoimmune mechanisms in myasthenia gravis. This evidence has important implications for the aetiology, diagnosis and management of the disease
The primary abnormality in myasthenia gravis is related to the presence of antibody which reacts with the acetylcholine receptor. Measurement of this IgG antibody in the serum has become the most reliable diagnostic adjunct to the edrophonium test, and in an individual patient, the level of the serum antibody relates closely to the clinical indices. In cases of myasthenia where control with anticholinesterase drugs is unsatisfactory, methods to lower the antiacetylcholine receptor antibody are indicated: these may include thymectomy, immunosuppressive therapy or plasmapheresis
Two patients with very severe disease are described in whom all types of therapy were used and in whom survival depended ultimately on the use of plasmapheresis. These patients illustrate the importance of receptor antibody in the clinical manifestations of myasthenia gravis and in its management     

国产与进口干扰素治疗急性和慢性丙型肝炎疗效比较

目的 了解国产干扰素是否同样具有进口干扰素的临床疗效并探讨在急性期用干扰素进行抗病毒治疗的疗效。方法 本文对81例慢性丙型肝炎病人分组使用国产干扰素贝尔芬、安福隆和进口干扰素干扰能进行了临床疗效及毒副作用对比观察。在此基础上,应用干扰素α(国产或进口干扰素均可)治疗32例急性丙型肝炎并与81例慢性丙型肝炎进行了对比研究。结果 国产干扰素贝尔芬、安福隆和进口干扰素干扰能在临床疗效和药物不良反应等方面均无显著性差异(P值均>0.05)。对急性丙型肝炎的早期抗病毒治疗,在近期疗效上可以很好地抑制病毒的复制。结论 国产干扰素价格低,但同样具有进口干扰素的临床疗效,有推广使用的价值。在急性期应用干扰素α进行抗病毒治疗,可以达到病毒的消除并阻断其向慢性化的发展。     

Myasthenia gravis and hyperthyroidism: two cases

It is well known that hyperthyroidism occurs in approximately 2 to 17.5% of patients with myasthenia gravis. Hyperthyroidism may influence the clinical course of myasthenia gravis. We report the cases of two patients, a 53-year-old man and an 18-year-old woman, who had both severe myasthenia gravis and hyperthyroidism due to Graves' disease. Myasthenia gravis affected in particular facio-ocular areas with diffuse myopathy and signs of neuromuscular block on the electromyogram. In one patient, the diagnosis of thyroid disease was made three months before the diagnosis of myasthenia gravis while in the other, thyroid disease was recognized four months after myasthenia gravis. Myasthenia gravis worsened after the development of hyperthyroidism in the second patient. Both patients were given anti-cholinesterase drugs. One underwent thymectomy. Radioiodine used for the treatment of hyperthyroidism improved the symptoms of myasthenia gravis in the first patient. The association of myasthenia gravis and hyperthyroidism is more than a coincidence; our cases illustrate the difficult diagnosis and management of these diseases. Clinicians should look for myasthenia gravis in hyperthyroid patients and vice versa, especially when symptoms of myasthenia gravis or hyperthyroidism worsen.     

Coexistence of Myasthenia Gravis and Hashimoto's Thyroiditis in a Chinese Woman

Summary: The coexistence of myasthenia gravis and Hashimoto's thyroiditis has rarely been described. A 64-year-old Chinese woman with myasthenia gravis and Hashimoto's thyroiditis is described. The literature on the occurrence of Hashimoto's thyroiditis and myasthenia gravis is briefly reviewed. The relationship between myasthenia gravis and thyroid dysfunction is outlined. It is suggested that the association of myasthenia gravis with Hashimoto's thyroiditis (a long-known autoimmune disease) provides further support to the hypothesis that myasthenia gravis may be an auto-immune disorder.     

Response to pegylated interferon alpha-2b and ribavirin in children with chronic hepatitis C

GOALS: The purpose of this communication is to report our observations on the treatment of a diverse group of adolescent patients who were chronically infected with hepatitis C and received pegylated interferon and ribavirin. BACKGROUND: The currently accepted optimal therapy for adults with chronic hepatitis C is weekly injections of pegylated interferon and twice daily oral ribavirin. Information on interferon alone or in combination with ribavirin for chronic hepatitis C in children is limited. There is no published information on pegylated interferon and ribavirin in pediatric patients who previously failed interferon therapy. REPORT: Ten patients 11 to 18 years old received weekly pegylated interferon and twice daily ribavirin for hepatitis C. Treatment continued for 48 weeks, except for 1 patient with hepatitis C virus type 3a who was treated for 24 weeks and 1 patient who did not complete the course of treatment. The period of observation continued from November 2002 to December 2004. Within this group were 3 pediatric patients who had previously failed interferon therapy for hepatitis C. RESULTS: All but 1 patient had a viral response (no detectable virus) at some time during or after the treatment. Three patients achieved sustained viral response (no detectable virus 6 mo after the therapy). One patient who previously failed interferon therapy was among the sustained responders. CONCLUSIONS: In response to treatment with pegylated interferon and ribavirin, children and adolescents with chronic hepatitis C achieve results similar to those seen in adults. Previous antiviral therapy does not preclude positive response to pegylated interferon and ribavirin.     

Long-term follow-up of patients with chronic hepatitis C treated with alpha-interferon.

We reanalyzed the results of a pilot study of recombinant alpha-interferon therapy for chronic non-A, non-B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long-term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransferase levels in two patients who had relapses in disease when interferon was stopped. During a follow-up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long-term beneficial responses to alpha-interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum.     

Klinisch-pathologische Studie zur Klassifikation und Prognose von 57 Thymustumoren

Summary The most important prognostic determinants of the thymomas are the gross findings at operation (= the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas.Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymomaassociated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.

     

A comparative clinical and pathological study on the classification and prognostic features of 57 thymomas. II. prognostic features (author's transl)]

The most important prognostic determinants of the thymomas are the gross findings at operation (equal to the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas. Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymoma-associated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.     

In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor

A monoclonal antibody to I-A gene products of the immune response gene complex attenuates both humoral and cellular responses to acetylcholine receptor and appears to suppress clinical manifestations of experimental autoimmune myasthenia gravis. This demonstrates that use of antibodies against immune response gene products that are associated with susceptibility to disease may be feasible for therapy in autoimmune conditions such as myasthenia gravis.     

Antiphospholipid syndrome during pegylated interferon alpha-2a therapy for chronic hepatitis C

A great variety of autoimmune side effects have been reported during interferon alpha therapy. The presence of anticardiolipin antibodies during interferon alpha therapy in chronic hepatitis C has also been reported. There are no reports on the occurrence of antiphospholipid syndrome in patients with chronic hepatitis C while on pegylated interferon alpha therapy. We report a case of a 46-year-old man who developed antiphospholipid syndrome 12 weeks after starting pegylated interferon alpha plus ribavirin for chronic hepatitis C. The clinical presentation of antiphospholipid syndrome was primary adrenal insufficiency secondary to bilateral adrenal haematoma and subclavian vein thrombosis. A pathogenic role of pegylated interferon alpha as a trigger factor for antiphospholipid syndrome development is suggested.     

Incidence of hepatocellular carcinoma in chronic hepatitis C after interferon therapy

BACKGROUND/AIMS: We investigated the rate of occurrence and the risk factors for hepatocellular carcinoma in chronic hepatitis C patients who received interferon therapy. METHODOLOGY: We followed 413 chronic hepatitis C patients for more than 6 years after interferon therapy and assessed the following patient characteristics: age, sex, platelet count, response to interferon, hepatitis C virus RNA level, hepatitis C virus genotype, liver histology, and changes in serum alanine aminotransferase levels. RESULTS: Hepatocellular carcinoma was found in 21 patients after interferon therapy. The factor most related to the occurrence of hepatocellular carcinoma was changes in serum alanine aminotransferase levels (univariate analysis, P < 0.0001; multivariate analysis, P = 0.0013), followed by age (univariate analysis, P = 0.0003; multivariate analysis, P = 0.0029). A significant difference was observed in the platelet count and response to interferon based on univariate analysis alone (P = 0.0096, P = 0.0241, respectively), however no significant differences were noted in the other factors. The course of serum alanine aminotransferase levels following interferon therapy rather than the eradication of hepatitis C virus was found to be the factor most profoundly involved in liver carcinogenesis. CONCLUSIONS: Even if interferon therapy fails to eradicate the hepatitis C virus, maintaining low serum alanine aminotransferase levels post-interferon therapy would reduce the risk of hepatocellular carcinoma in chronic hepatitis C.