Patients with AAG often respond to intravenous immunoglobuli

Patients with AAG often respond to intravenous immunoglobulin or plasma exchange. If these therapies are inadequate, ongoing immune suppression with steroids, azathioprine, mycophenylate or rituximab have been shown to be effective in case reports. Our patient seemed initially resistant to steroid therapy although clearly benefited from the addition of azathioprine and is currently in remission, but it is unclear how long she will need to be treated. There is strong evidence that ganglionic α3-AChR antibodies are pathogenic. High titre antibodies are found almost exclusively in AAG, and patients with AAG can gain clinical improvements after removal of antibody with plasma exchange. Passive transfer of patient IgG induces dysautonomia in animals, and immunisation of ganglionic AChR induces AAG in rabbits. Ganglionic α3-AChR antibodies inhibit synaptic transmission and cause internalisation of synaptic ganglionic α3-AChR. The outcome in adults appears to be variable. Although many patients can have a monophasic course with spontaneous improvements, other patients may show a slowly progressive course similar to a degenerative autonomic neuropathy.
Introduction Myasthenia gravis (MG) is an acquired neuromuscular transmission disorder caused by immune-mediated damage to the postsynaptic endplate at the neuromuscular junction and characterized by fluctuating muscle weakness and fatigability [1]. The distribution of muscle involvement varies between patients and often changes along the disease course, ranging from mild isolated ocular involvement to severe generalised muscle weakness with bulbar symptoms and respiratory failure. In Western populations, 10–16% of patients with immune MG experience their first symptoms before 15years of age [2]. Despite differences in epidemiology and prognosis, the pathophysiology of juvenile-onset MG (JMG) is similar to adult-onset MG [3], suggesting a rationale for similar treatment approaches. Serum antibodies to the 449 receptor (AChR) are present in about 85% of patients with generalised MG and in 50% of those with ocular MG. Antibodies to muscle-specific kinase (MuSK) are detected in 30% of AChR antibody negative patients [4]. There is evidence supporting the essential role of the thymus in the immune process leading to AChR antibody production in MG [5]. The association between MG and thymic hyperplasia or thymoma has been recognised [6], although thymoma is uncommon in children [3]. Thymectomy has been employed in the treatment of MG since the 1940’s, initially based on the observed improvement of myasthenic symptoms in a patient who had undergone thymectomy for a thymic mass [7]. Following a substantial number of favourable reports, thymectomy has been widely accepted as a treatment option for non-thymomatous MG in adults [8], [9], [10] despite the lack of randomised controlled trials. An international multicentre, randomised controlled trial [11] to assess the effect of thymectomy on steroid requirement in MG, is still ongoing (Clinical trial number NCT00294658) [12], but entry is limited to adults. In JMG, the efficacy of thymectomy has been studied in historical case series [13]. In 19 reports with a total of 479 JMG patients who had thymectomy in childhood, symptomatic improvement was achieved in 68%, and medication was discontinued in 39%. However, these reports included heterogeneous groups of children with wide variation in factors Hydrolytic reaction may influence the response to thymectomy, including age at operation, surgical technique, concomitant use of other immune therapies, and duration of follow-up. Most notably, however, many series included AChR antibody negative children, some of whom may have been MuSK antibody positive or may have had unrecognised congenital myasthenic syndromes (CMS), necessarily unresponsive to thymectomy due to their genetic nature. Only two recent series have investigated the effect of thymectomy specifically in JMG [14], [15].