Epidemiology Certain epidemiologic features of the disease are of clinical interest. Its prevalence is variously estimated to be from 43 to 84 per million persons and the annual incidence rate is approximately 1 per 300,000. The disease may begin at any age, but onset in the first decade is relatively rare (only 10 percent of cases begin in children younger than 10 years of age). The peak age of first symptoms is between 20 and 30 years in women and between 50 and 60 years in men. Under the age of 40, females are affected two to three times as often as males whereas in later life, the incidence in males is higher (3:2). Of patients with thymomas, the majority is older (50 to 60 years) and males predominate.
Familial occurrence of myasthenia is known, but it is rare. Many such cases prove to have one of the genetically determined myasthenic syndromes and not the acquired autoimmune form of disease (see further on). More common is a family history of one of the autoimmune diseases enumerated earlier. For example, in the series reported by Kerzin-Storrar and associates 30 percent had a maternal relative with a connective tissue disease, suggesting that myasthenia gravis patients inherit a susceptibility to autoimmune disease. Two of our patients have sisters with lupus. There have also been reports of the concurrence of myasthenia and multiple sclerosis, but this association is less certain. There is an increased representation of
HLA-B8 and -DR3 haplotypes, as occurs in other autoimmune diseases, which are discussed further on.
Myasthenia gravis, as the name implies, formerly had a grave prognosis, perhaps less so today but still associated with considerable morbidity. As mentioned, repeated or persistent activity of a muscle group exhausts contractile power, leading to a progressive paresis, and rest restores strength, at least partially. These features, concentrated in the palpebral, ocular, and the oro-facial-lingual muscles are the identifying attributes of the disease and their demonstration is usually enough to establish the diagnosis on clinical grounds.
The special vulnerability of the neuromuscular junctions in certain muscles gives myasthenia its highly characteristic clinical appearance. Usually the eyelids and the muscles of eye movement, and somewhat less often, of the face, jaws, throat, and neck, are the first to be affected. Infrequently, the initial complaint is referable to the limbs or to breathing. Specifically, weakness of the levator palpebrae or extraocular muscles is the initial manifestation of the disease in about half the cases, and these muscles are involved eventually in more than 90 percent. Ocular palsies and ptosis are usually accompanied by weakness of eye closure, a combination that is virtually always indicative of the disease although it may be observed in certain muscular dystrophies. Diplopia is quite common in myasthenia, but it does not correspond to the innervatory pattern of a nerve; instead, it is the result of asymmetrical weakness of several muscles in both eyes. As the disease advances, it spreads insidiously from the cranial to the limb and axial muscles, but there are instances of fairly rapid development, sometimes initiated by an infection, usually respiratory. In rare cases, the distal extremity muscles may be involved, such as the “myasthenic hand” described by Janssen and colleagues. Symptoms may first appear during pregnancy or, more commonly, during puerperium or in response to paralytic drugs used during general anesthesia.
In addition to special circulating autoantibodies, inflammatory thymic abnormalities of several types are closely connected with the disease, as elaborated further on, and weakness may begin months or years before or after removal of a thymoma.