A 34-year-old woman comes to the office with several months of vision problems, difficulty chewing, and trouble speaking. The symptoms fluctuate, but the patient has noticed that they are worse after a long day. She works as a telemarketer and has been putting in increasingly long hours to meet her quotas. Regarding her symptoms, she says, "It's probably just exhaustion; an ice pack to my face seems to help." During physical examination, the patient is asked to keep her eyes focused on a spot on the ceiling, and after 2 minutes, her vision becomes blurry. The remainder of the examination is normal. Further evaluation shows that the patient's symptoms are reversible on administration of an acetylcholinesterase inhibitor. The pathogenesis of this patient's disease is most similar to which of the following conditions?

Question

A 34-year-old woman comes to the office with several months of vision problems, difficulty chewing, and trouble speaking.  The symptoms fluctuate, but the patient has noticed that they are worse after a long day.  She works as a telemarketer and has been putting in increasingly long hours to meet her quotas.  Regarding her symptoms, she says, "It's probably just exhaustion; an ice pack to my face seems to help."  During physical examination, the patient is asked to keep her eyes focused on a spot on the ceiling, and after 2 minutes, her vision becomes blurry.  The remainder of the examination is normal.  Further evaluation shows that the patient's symptoms are reversible on administration of an acetylcholinesterase inhibitor.  The pathogenesis of this patient's disease is most similar to which of the following conditions?

Quizplus · Accepted Answer

This patient's clinical findings of intermittent diplopia, difficulty chewing, and speech problems (especially at the end of the day) suggest a diagnosis of myasthenia gravis (MG). MG is caused by impaired functioning of nicotinic cholinergic receptors at the neuromuscular junction due to interference by IgG autoantibodies. The diagnosis can be confirmed with administration of an anticholinesterase agent (eg, edrophonium), which increases the amount of acetylcholine at the neuromuscular junction. Acetylcholinesterase activity decreases at lower temperatures, so application of an ice pack can also improve symptoms caused by weakness of superficial muscles (eg, ptosis). MG is a form of type II hypersensitivity, which is characterized by IgM and/or IgG autoantibodies that bind to cell surface antigens and/or extracellular matrix components. Among the available options, only Goodpasture syndrome is due to the production of autoantibodies (directed against the glomerular basement membrane). These antibodies cause inflammatory destruction of the basement membrane in the lung alveoli and renal glomeruli. (Choice A) Atopic dermatitis is a chronic, pruritic, eczematous skin condition that almost always begins in childhood. The pathogenicity involves several factors, including skin barrier abnormalities, defects in innate immunity, and a T_H2-skewed immune response. (Choice B) The pathogenesis of contact dermatitis (type IV hypersensitivity reaction) involves cutaneous exposure to small foreign molecules (haptens) that bind to skin proteins. These proteins are subsequently processed by antigen-presenting Langerhans cells that transport the modified proteins to lymph nodes and promote the development of hapten-specific T cells. With continued hapten exposure, sensitized T cells produce inflammatory cytokines at the exposure site, causing the characteristic eczematous skin changes. (Choice D) Most patients with acute hypersensitivity pneumonitis have specific serum IgG antibodies that precipitate bacterial or fungal antigens found in inhaled organic dust particles. This causes interstitial alveolitis and bronchiolitis via immune complex and complement deposition in vessel walls (type III hypersensitivity mechanism). (Choice E) The pathogenesis of poststreptococcal glomerulonephritis involves granular deposition of immune complexes containing group A streptococcal antigens, IgG, and C3 in the glomerular basement membrane and mesangium. It is a type III, immune complex-mediated, hypersensitivity response. Educational objective: Myasthenia gravis results from an autoimmune type II (antibody-mediated) hypersensitivity reaction against skeletal myocyte surface acetylcholine receptors. Goodpasture syndrome similarly involves autoantibodies against basement membrane collagen in the renal glomeruli and lung alveoli.

A 34-Year-Old Woman Comes to the Office with Several Months