Absence Of Thymoma Research Articles

Myasthenia gravis complicated by pure red cell aplasia with clonal large granular lymphocytosis in the absence of thymoma: a rare case report and literature review

In 2013, a young woman during her early pregnancy was repeatedly hospitalized due to respiratory and swallowing difficulties. The pregnancy was terminated due to recurrent severe lung infections. She was later diagnosed with myasthenia gravis (MG) based on positive acetylcholine receptor antibodies. Her muscle weakness was subsequently well-controlled with pyridostigmine bromide, azathioprine, and prednisone. Notably, in the seventh year after her MG diagnosis (2021), the patient developed severe anemia (hemoglobin: 44 g/L). Bone marrow analysis revealed a rare combination of pure red cell aplasia (PRCA) with clonal expansion of large granular cells. Further examinations excluded thymoma. Considering the possibility of drug-induced PRCA, azathioprine was replaced with tacrolimus. Remarkably, the anemia resolved within 1 month, and her MG remained well-controlled. It is well-established that abnormal thymic hyperplasia within thymomas can alter the distribution and function of peripheral T lymphocytes, leading to the development of autoimmune diseases such as MG and PRCA. In this unique case without thymoma, we discussed the mechanisms and associations of PRCA with MG, medication, and clonal large granular T cells. This unique case highlights the unprecedented association of MG and PRCA without thymoma, underscoring the complexity of the disease spectrum. The patient’s subsequent successful delivery in June 2023 adds another dimension to the multifaceted clinical course, warranting attention and exploration into potential connections between these conditions.

Identification and validation of lncRNA mutation hotspot SNPs associated with myasthenia gravis susceptibility.

Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies that target the postsynaptic muscle membrane. Recent evidence suggests that genetic variants and long noncoding RNAs (lncRNAs) play crucial roles in the pathogenesis of MG. The purpose of this study was to investigate the associations between lncRNA-related single-nucleotide polymorphisms (SNPs) and MG susceptibility in Chinese populations. First, we identified lncRNA mutation hotspot regions based on the improved Kolmogorov‒Smirnov test and the cumulative hypergeometric distribution principle. Next, we further identified lncRNA mutation hotspot SNPs by calculating conservative scores. Finally, experiments were conducted to verify the associations between lncRNA mutation hotspot SNPs and MG susceptibility. A total of 82 patients with MG and 82 healthy controls were recruited for genotyping of lncRNA mutation hotspot SNPs using the SNaPshot technique. Quantitative real-time PCR was used to investigate lncRNA expression in 34 patients with MG and 37 healthy controls. In the multistep calculation, 14 candidate SNPs of 3 lncRNAs (AL031686.1, NONHSAT028539.2 and AC245014.3) in MG were identified as mutation hotspot SNPs. The genotyping results of the 14 SNPs in our study revealed no statistically significant differences in the frequencies of genotypes and alleles between patients with MG and controls. However, in the lncRNA AL031686.1, rs1000383 and rs6094353 were in perfect linkage disequilibrium (LD) and were associated with an increased risk of ocular MG. Additionally, rs6094347 was associated with an increased risk of ocular MG. Nevertheless, no SNP was found to be associated with factors such as sex, age, the presence or absence of thymoma, or the genetic model of MG. Further experiments revealed that NONHSAT028539.2 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with MG compared with those from healthy controls. In our study, we did not find an association between the 14 mutation hotspot SNPs of lncRNAs and susceptibility to MG. However, we observed that the rs6094347 and rs1000383/rs6094353 polymorphisms in the lncRNA AL031686.1 were associated with the risk of ocular MG.

BENEFITS OF THYMECTOMY IN MYASTHENIA GRAVIS

In recent years, thymectomy has become a widespread procedure in the treatment of myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild disease classification (Osserman classification 1, 2A). In absence of thymoma or hyperplasia,there was no relationship between age and gender in remission with thymectomy. In MG treatment,randomized trials that compare conservative treatment with thymectomy have started,recently.As with non-randomized trials, remission with thymectomy in MG treatment was better than conservative treatment with only medication.There are four major methods for the surgical approach:transcervical,minimally invasive,transsternal,and combined transcervical transsternal thymectomy. Transsternal approach with thymectomy is the accepted standard surgical approach for many years. In recent years, the incidence of thymectomy has been increasing with minimally invasive techniques using thoracoscopic and robotic methods.There are not any randomized, controlled studies which are comparing surgical techniques.However,when comparing non-randomized trials,it is seen that minimally invasive thymectomy approaches give similar results to more aggressive approaches.

Pure red cell aplasia and myasthenia gravis: a patient having both autoimmune conditions in the absence of thymoma

This is a patient who was presented initially with symptoms of malaise, tiredness and exertional dyspnoea and found to have a severe normocytic normochromic anaemia with low reticulocyte counts. Bone...

Thymectomy in Myasthenia Gravis.

In recent years, thymectomy has become a widespread procedure in the treatment of myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild disease classification (Osserman classification 1, 2A). In absence of thymoma or hyperplasia, there was no relationship between age and gender in remission with thymectomy. In MG treatment, randomized trials that compare conservative treatment with thymectomy have started, recently. As with non-randomized trials, remission with thymectomy in MG treatment was better than conservative treatment with only medication. There are four major methods for the surgical approach: transcervical, minimally invasive, transsternal, and combined transcervical transsternal thymectomy. Transsternal approach with thymectomy is the accepted standard surgical approach for many years. In recent years, the incidence of thymectomy has been increasing with minimally invasive techniques using thoracoscopic and robotic methods. There are not any randomized, controlled studies which are comparing surgical techniques. However, when comparing non-randomized trials, it is seen that minimally invasive thymectomy approaches give similar results to more aggressive approaches.

Elevated plasma interleukin-17A in a subgroup of Myasthenia Gravis patients

To better define the role of IL-17A in myasthenia gravis (MG), we assessed plasma concentrations in 69 adult patients with MG prior to initiation of immunosuppression and monitored their clinical course for the subsequent 2years with quantitative MG scores (QMGS) and Osserman classification. IL-17A was higher among patients than healthy control subjects. Early-onset women without thymoma had greater elevations of IL-17A. Logistic regression analysis indicated that the absence of thymoma rather than women gender or early-onset was the significant determinant associated with IL-17A elevation. Elevated IL-17A levels were associated with more severe MG. In summary, IL-17A has role in the pathogenesis of a subgroup of patients with early-onset women with MG with greater disease severity who are most likely to have thymic hyperplasia. This subgroup may be a target for IL-17 treatments, which are under development.

Prognostic factors of remission in myasthenia gravis after thymectomy.

Thymectomy has become an increasingly popular procedure for myasthenia gravis. Knowledge of factors associated with a good outcome (remission) or those most likely to benefit from surgery can help clinical decision-making. A systematic review search was conducted in Medline and Embase for English language studies from 1985 through to February 2014. Studies which evaluated variables associated with, or predictive of, remission in adult (≥18 years) myasthenic patients after thymectomy and using multivariable regression models were included. Statistical pooling was not appropriate due to methodological heterogeneity. From 128 potentially relevant studies, 18 reports of 19 studies met the inclusion criteria. Preoperative mild disease classification (i.e. studies reported this variable as Osserman classification 1, 2A or MGFA I-II) showed the most consistent association with remission. Evidence for several other prognostic factors was inconclusive, or no evidence was found. Gender, age and absence of thymoma (or hyperplasia) were not associated with remission following thymectomy. Patients with mild disease preoperatively may have a better chance of remission of MG after thymectomy.

Association of HLA-DQB1*05:02 and DRB1*16 Alleles with Late-Onset, Nonthymomatous, AChR-Ab-Positive Myasthenia Gravis

An association of several HLA alleles with myasthenia gravis (MG) has been reported. Aim of this work was to analyze the HLA allele profile in a survey of 76 unselected Italian MG patients and in a subgroup characterized by disease onset after the age of 50 years, absence of thymoma, and presence of antiacetylcholine receptor antibodies. We defined this subgroup by the acronym LOAb. Typing was performed at low resolution for HLA-A, -B, and -DRB1 loci with sequence-specific oligonucleotide probe (PCR-SSO); at high resolution for HLA-DQB1 locus by PCR with sequence-specific primers (PCR-SSPS). HLA allele frequencies were compared with 100 healthy controls. No correlation was observed between MG and the studied HLA class I alleles. On the contrary, a strong positive association was found for the HLA class II alleles DQB1∗05:02 (P c = 0.00768) and DRB1∗16 (P c = 0.0211) in the LOAb subgroup (n = 27) of MG patients. Association between DQB1∗05:02 and some subtypes of MG has been previously reported but not in patients with the LOAb characteristics. Therefore, the HLA allele DQB1∗05:02 might be considered as a susceptibility marker for LOAb among Italians.

Invited Commentary

We read with interest the study by Liu and associates [1Liu Z. Feng H. Yeung S.-C.J. et al.Extended transsternal thymectomy for the treatment of ocular myasthenia gravis.Ann Thorac Surg. 2011; 92: 1993-1999Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. Optimal treatment of ocular myasthenia gravis (MG) is still a controversial issue with no agreement among surgeons and neurologists. There is no doubt that patients with thymoma should undergo surgery, whatever the MG stage is; however, many doubts still persist regarding the indication for surgery for those with pure ocular MG. This dilemma is related to several factors. At this stage, some natural remissions (approximately 30% of cases) occur without surgery. In addition, most of the patients with ocular MG remain at this stage with symptoms easily controlled by medical treatment. Furthermore, the variability in diagnosis, type of medical treatment, length of time before referral for surgery, preparation for surgery, and type of surgical approach has made MG (in particular ocular MG) difficult to study. In the last two decades, an increasing number of reports have sustained the potential role of surgery, even at the early stage of MG. The results are even more crucial in the era of thoracoscopic and robotic thymectomy. Proponents of thymectomy generally agree that the duration of symptoms before surgery is a predictor for outcome, with better results in patients reporting symptoms for less than 1 year. However, this does not match with the guidelines proposed by neurologists: they suggest a period of medical treatment not shorter than 1 year in the absence of thymoma. The results of surgical treatment of ocular MG should be popularized among neurologists to encourage the debate and eventually increase referrals to thoracic surgery units. It could also help to alleviate neurologists' historical reluctance to withdraw medications after surgery in patients without symptom; this is usually reported as one of the factors contributing to lower cure rates. We must admit that phase II studies are interesting and encouraging, but they are not persuasive from the scientific point of view. We now need phase III studies in patients with ocular MG involving surgeons and neurologists; this will be the only way to identify the best treatment for ocular MG. Extended Transsternal Thymectomy for the Treatment of Ocular Myasthenia GravisThe Annals of Thoracic SurgeryVol. 92Issue 6PreviewThe optimal treatment for ocular myasthenia gravis (OMG) remains controversial. We conducted a review of the long-term clinical outcomes of Chinese patients with OMG after extended transsternal thymectomy (ETT) to determine the efficacy of this procedure as a treatment for OMG. Full-Text PDF

Neuromyotonia and myasthenia gravis in the absence of thymoma

European Journal of NeurologyVolume 13, Issue 7 p. e5-e5 Neuromyotonia and myasthenia gravis in the absence of thymoma A. Antelli, A. Antelli Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorK. Spengos, K. Spengos Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorT. Zambelis, T. Zambelis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorD. Pandis, D. Pandis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorG. Tsivgoulis, G. Tsivgoulis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorV. Zis, V. Zis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this author A. Antelli, A. Antelli Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorK. Spengos, K. Spengos Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorT. Zambelis, T. Zambelis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorD. Pandis, D. Pandis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorG. Tsivgoulis, G. Tsivgoulis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this authorV. Zis, V. Zis Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, GreeceSearch for more papers by this author First published: 23 June 2006 https://doi.org/10.1111/j.1468-1331.2006.01271.xCitations: 1 Konstantinos Spengos, Vas. Sofias 82, 11528 Athens, Greece (tel.: +30 6946 466216; fax: +30 210 6742604; e-mail: [email protected]). Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume13, Issue7July 2006Pages e5-e5 RelatedInformation

Thymectomy in the treatment of ocular myasthenia gravis

Thymectomy is an effective and accepted treatment for myasthenia gravis, but thymectomy for ocular myasthenia gravis (Osserman stage I) is controversial. To assess the efficacy and propriety of thymectomy for the treatment of ocular myasthenia gravis. We conducted a review and follow-up of all patients who had thymectomy for the treatment of ocular myasthenia gravis between 1970 and 1998 at the University of California, Davis, Medical Center, and the University of Rome, "La Sapienza," Rome, Italy. Patient response to thymectomy was categorized as follows: cured, patients who became symptom-free and required no further medication; improved, patients who required less medication and whose symptoms were less severe; unchanged, patients whose symptoms and medications were the same; worse, patients who had more severe symptoms, needed more medication, or died. Sixty-one patients (mean age 37 years; range 14-73 years) were followed up for a mean duration of 9 years (range 0.5-29 years). Ocular myasthenia gravis with mixed and cortical thymomas, stages I to IV, occurred in 12 patients, and ocular myasthenia without thymomas occurred in 49 patients. Transsternal thymectomy (n = 55) and transcervical thymectomy (n = 6) resulted in cure in 31 (51%) patients, improvement in 12 (20%) patients, no change in 16 (26%) patients, and worsening of symptoms (including 1 postoperative death) in 2 patients. Patient outcomes were statistically independent of the duration of preoperative symptoms (mean 9.5 months), patient age, or the presence or absence of thymoma. In patients with ocular myasthenia, 70% were cured or improved after thymectomy; in the subgroup of patients with ocular myasthenia and thymoma, 67% were cured or improved. Thymectomy is an effective and safe treatment for patients with ocular myasthenia gravis.

Myasthenia gravis with ocular involvement in older patients

There has been little previous study reporting the eye findings and presentation of elderly patients with myasthenia gravis. The purpose of this study was to review the findings and course of myasthenia gravis after the sixth decade of life. Retrospective observational case series. The authors reviewed the clinical records of 27 patients with onset of myasthenia gravis at age 60 years or more who were seen at a tertiary care academic ophthalmology centre in Houston between January 1992 and March 1999. The diagnosis of myasthenia gravis was based on conventional clinical and laboratory criteria. Twenty patients (74%) were men. Of the 16 patients who underwent testing for anti-acetylcholine receptor antibodies, 11 (69%) were seropositive. Concurrent thyroid disease was found in seven patients (26%), including five (71%) of the seven women. No patient had thymoma. Sixteen patients (59%) manifested generalized symptoms during follow-up; 12 did so within 1 year of disease onset. Patients responded well to both anticholinesterase and corticosteroid therapy. At the most recent follow-up visit 18 patients (67%) were clinically improved, and no patient was clinically worse. Myasthenia gravis in this study was characterized by a male predominance, high rate of concurrent thyroid disease, high rate of progression to mild generalized symptoms, absence of thymoma, good response to medical therapy and minimal life-threatening complications. Clinicians should consider the diagnosis of myasthenia gravis in an older patient presenting with diplopia or ptosis.

Immunosuppressive treatment of ocular myasthenia gravis.

Myasthenia gravis (MG) is caused by autoantibodies against proteins at the neuromuscular junction. This autoimmune process leads to abnormal fatiguability and weakness of striated muscle. Ptosis and diplopia are among the most common manifestations of MG. The term "ocular MG" (OMG) as opposed to "generalised MG" (GMG) is used to define the clinical subtype of MG with isolated eye muscle weakness. Although OMG may appear to cause only moderate disability, it can significantly impair the patient's activities of daily living and progress to generalised myasthenia. Therefore, a clear management plan should be installed early in these patients. Since prospective treatment trials have not been performed, basic management strategies for OMG have to be deduced from retrospective studies, trials in GMG, and generally accepted clinical experience. Cholinesterase inhibitors are used in all types of MG, but are often less helpful in OMG. In the absence of thymoma, thymectomy is usually not considered in OMG, although a few studies have described histological abnormalities in thymuses from patients with OMG. Corticosteroids are of great short term benefit in most patients with OMG but potential adverse effects limit their long term use. Azathioprine is needed to reduce long term corticosteroid adverse effects, but this agent requires about 6 months to be effective. In summary, OMG has a good prognosis in most patients, with corticosteroids and azathioprine being the major treatment options. The challenges for the clinician are to recognise the condition despite the large number of differential diagnoses, to minimise the patient's symptoms using the therapies available and to carefully limit potentially hazardous therapeutic efforts, especially in mild or even uncertain cases.

Extended Thymectomy for Myasthenia Gravis Patients: A 20-Year Review

Since 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated. Three hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point. Remission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome. Extended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Coexistence of rheumatoid arthritis, myasthenia gravis, and pemphigus superficialis

Abstract d -Penicillamine (DP) is widely used nowadays in the treatment of rheumatoid arthritis, despite its well known side effects of an autoimmune nature, often associated with specific histocompatibility antigens (HLA). We report the case of a woman, suffering from rheumatoid arthritis (RA), treated with DP, who developed myasthenia gravis (MG) and pemphigus foliaceus (PF) and whose phenotype has only antigens usually associated with pemphigus. This may be the second published case of concurrent pemphigus and myasthenia gravis induced by d -penicillamine therapy, in the absence of thymoma.

Coexistence of rheumatoid arthritis, myasthenia gravis, and pemphigus superficialis⋆

Abstract d‐Penicillamine (DP) is widely used nowadays in the treatment of rheumatoid arthritis, despite its well known side effects of an autoimmune nature, often associated with specific histocompatibility antigens (HLA). We report the case of a woman, suffering from rheumatoid arthritis (RA), treated with DP, who developed myasthenia gravis (MG) and pemphigus foliaceus (PF) and whose phenotype has only antigens usually associated with pemphigus. This may he the second published case of concurrent pemphigus and myasthenia gravis induced by d‐penicillamine therapy, in the absence of thymoma.

Thymectomy for myasthenia gravis.

1. Results of 19 thymectomies in patients with myasthenia gravis, performed during the period from August 1961 to July 1964, were reported. 2. Based on the severity of symptoms, the cases were divided into the following three groups. Grade I included four cases of a localized myasthenia with ocular symptoms. Grade II included six cases of moderately advanced generalized myasthenia with not only ocular but also bulbar symptoms. Grade III included nine cases of far advanced generalized myasthenia with muscular weakness of neck, trunk, and extremities beside the ocular and bulbar symptoms. 3. Routine laboratory examination did not reveal any pathognomonic findings or confirm any difference among Grades I, II and III. On the contrary, examinations directly connected with muscle functions, such as per cent vital capacity, Tensilon test, Curare test and electromyographic study, showed an apparent difference among the three groups. This classification is advantageous not only for decision of indication for surgery, but also for pre-and postoperative management. 4. Out of 19 cases, five males and one female were accompanied with thymoma. They belonged to Grade III and myasthenic symptoms wereextensive and grave. 5. Indication for surgery was concluded in: 1) the cases with thymoma, 2) the cases of Grade III, regardless of the presence or absence of thymoma, and 3) the cases of Grade II, where conservative treatment was not effective or caused severe side-effect. 6. Anterior mediastinum was entered through sternal splitting method. The whole thymus including the cervical portion should be excised, preserving the pleura and phrernic nerves as much as possible. 7. The most important measure for postoperative respiratory crisis is the maintenance of airway, and prophylactic tracheotomy is far superior to delayed forced tracheotomy. The indication for tracheotomy was decided in: 1) the cases of Grade III, and 2) the cases of Grade II whose per cent vital capacity were less than 59 per cent. Furthermore, 3) the cases of Grade II, where there was an increase in inspiratory capacity at preoperative Tensilon test even though per cent vital capacity was more than 50 per cent should be included. Tracheotomy is unnecessary for Grade I cases. 8. Follow-up results of 17 cases, excluding two recent cases, were: marked improvement in six cases, improvement in seven, and no change in four. The symptoms were improved in 76.5 per cent in total, and unchanged in two of Grade I and in two of Grade III with thymoma. No deaths related to surgery nor myasthenic deaths were observed. Results of female cases were better than those of male cases, and four of six cases with thymoma showed marked improvement. 9. Objection to thymeetomy for myasthenia gravis is mainly due to apprehension for risk of surgical intervention. So far as thymectom.y is performed as safely as the other mediastinal surgeries in co-operation with internists, anesthesiologists, surgeons and nursing members, thymectomy is the treatment of choice for this grave disease, in which otherwise only symptomatic therapy is possible.