Thymoma with Myasthenia Gravis in Adolescent

Thymomas are exceedingly rare in the first 20 years of life, Thymic lesions comprise approximately 2–3% of all pediatric mediastinal tumors and include thymic cysts, hyperplasia, carcinoma, and thymomas. Fewer than 30 cases in children have been described in the literature. Thymomas in adults are commonly associated with other diseases, the most frequent being myasthenia gravis. However, this association has been rarely reported in childhood. These tumors are typically aggressive, with poor outcomes. We report a case of thymoma associated with myasthenia gravis in a 16-year-old girl and review the literature

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis : a subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.651); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68) and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Flow cytofluorimetric analysis of anti-LRP4 (LDL receptor-related protein 4) autoantibodies in Italian patients with Myasthenia gravis

Background: Myasthenia gravis (MG) is an autoimmune disease in which 90% of patients have autoanti-bodies against the muscle nicotinic acetylcholine receptor (AChR), while autoantibodies to muscle-specific tyrosine kinase (MuSK) have been detected in half (5%) of the remaining 10%. Recently, the low-density lipoprotein receptor-related protein 4(LRP4), identified as the agrin receptor, has been recognized as a third autoimmune target in a significant portion of the double sero-negative (dSN) myasthenic individuals, with variable frequency depending on different methods and origin countries of the tested population. There is also convincing experimental evidence that anti-LRP4 autoantibodies may cause MG. Methods: The aim of this study was to test the presence and diagnostic significance of anti-LRP4 autoantibodies in an Italian population of 101 myasthenic patients (55 dSN, 23 AChR positive and 23 MuSK positive), 45 healthy blood donors and 40 patients with other neurological diseases as controls. All sera were analyzed by a cell-based antigen assay employing LRP4-transfected HEK293T cells, along with a flow cytofluorimetric detection system. Results: We found a 14.5% (8/55) frequency of positivity in the dSN-MG group and a 13% frequency of co-occurrence (3/23) in both AChR and MuSK positive patients; moreover, we report a younger female prevalence with a mild form of disease in LRP4-positive dSN-MG individuals. Conclusion: Our data confirm LRP4 as a new autoimmune target, supporting the value of including anti-LRP4 antibodies in further studies on Myasthenia gravis

On the origin of <i>Halipeurus heraldicus</i> on Round Island petrels: cophylogenetic relationships between petrels and their chewing lice

Lice phylogenetic relationships have often been used to elucidate host relationships and vice versa. In this study, we investigate the louse genus Halipeurus which parasitizes bird hosts in the families Procellariidae, Hydrobatidae and Pelecanoididae. The presence of two lice species on Pterodroma arminjoniana in different breeding grounds (Halipeurus heraldicus on Round Island, off Mauritius in the Indian Ocean and Halipeurus kermadecensis on Trindade Island in the Atlantic Ocean) has led to some confusion in the distribution of Pt. arminjoniana and its close relatives Pt. heraldica and Pt. neglecta. By using a cophylogenetic approach that incorporates uncertainties in phylogenetic reconstructions, we show significant overall coevolution between Halipeurus lice and their hosts. However, the study also indicates that the presence of H. heraldicus on Pt. arminjoniana and Pt. neglecta on Round Island and on Pt. heraldica on Gambier Island are the result of a host switch whereas H. kermadecensis is the ancestral parasite of Pt. arminjoniana. This suggests that H. kermadecensis was lost during or after colonisation of Round Island by Pt. arminjoniana. We conclude that cophylogenetic analyses are central to inferring the evolutionary history and biogeographical patterns of hosts and their parasites

Schizophrenia is a TH2 dominant autoimmune disease possibly against acetylcholine receptors of CNS

Schizophrenia is a very common psychiatric disorder. However, its etiology and pathogenesis is still unknown. Current theory saying that neurotransmitter imbalance such as serotonin or dopamine only provides limited effectiveness in schizophrenia treatment by drugs changing serotonin and dopamine concentration. Despite of such treatment, majority of schizophrenia patients still have very poor prognosis. Thus, the neurotransmitter imbalance theory is not correct. Here, I propose that schizophrenia is actually a TH2 dominant autoimmune disorder. The candidate of autoantigen could be acetylcholine receptors of CNS. My theory can explain the positive as well as negative symptoms of schizophrenia. By microarray analysis of PBMCS, one-tenth of the total 519 significantly expressed genes are immune-related genes. Among them, TH2 related genes are significantly up-regulated including IL-4, histidine decarboxylase, aldehyde dehydrogenase, CCR9, IgE Fc receptor, GATA2, serotonin receptor, phospholipase A2, and prostaglandin D2 synthase. Besides, TH1 and TH17 related genes are down-regulated including CXCL5, cathepsin C, and neutrophil related S100 binding proteins. The new theory sheds a light to better control this detrimental illness. Anti-inflammatory agents could be used to manage schizophrenia in the near future

Audio-vestibular symptoms in systemic autoimmune diseases

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menière’s disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases

Thymoma metastatic to liver and pancreas: case report and review of the literature

A 71-year-old man presented with a thymic mass involving the superior vena cava. A mediastinoscopical biopsy initially suggested a diagnosis of type A thymoma. After neoadjuvant chemotherapy, the patient underwent en-bloc thymectomy and vascular resection for a pathology-confirmed type B3 thymoma involving the superior vena cava, the left brachiocephalic vein and the distal part of the right brachiocephalic vein. Adjuvant radiotherapy was administered. Two years after the primary surgery, abdominal computed tomography (CT) and whole body fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans showed a single hepatic lesion that was treated with wedge liver resection. Pathological examination confirmed metastatic type B3 thymoma. Almost 4 years later, abdominal CT and 18-FDG PET revealed a 2.9-cm solid mass involving the body of the pancreas. Distal pancreatectomy with lymph node dissection was performed. Pathological examination showed a pancreatic metastasis from a type B3 thymoma, without lymph node involvement. The patient is alive and free of disease 6 months after the pancreatectomy (68 months after the initial thymectomy surgery). Intra-abdominal recurrence and pancreatic metastases are very uncommon manifestations of thymoma, but this event should be kept in mind when an abdominal mass is seen during follow-up