A 23-year-old woman is evaluated due to 10 days of nonproductive cough, low-grade fever, headache, and malaise. The patient has no other medical problems and takes no medications. Lung examination reveals scattered rales. Chest x-ray reveals bilateral patchy areas of consolidation. She has mild anemia and an elevated serum lactate dehydrogenase level. The patient is treated for presumed Mycoplasma pneumonia with azithromycin. Two months later, her symptoms and the anemia have resolved. Which of the following best explains the resolution of this patient's anemia?
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Mycoplasma pneumoniae is a common cause of tracheobronchitis and walking pneumonia. It attacks the respiratory epithelium by binding to an oligosaccharide (I-antigen) that is also present on the surface of erythrocytes. This leads to the formation of cross-reacting IgM antibodies that attach to red blood cells, activate the complement system, and cause erythrocyte lysis.
The cross-reacting antibodies are called cold agglutinins because they bind to erythrocytes in areas where the blood temperature is below core body temperature (eg, distal extremities, nose). Most patients with cold agglutinins are asymptomatic, but some develop manifestations of intravascular hemolytic anemia such as elevated reticulocyte count and lactate dehydrogenase level. IgM titers usually begin to fall approximately 4 weeks after initial infection leading to a resolution of the hemolytic anemia (within 8 weeks).
Other extrapulmonary manifestations of M pneumoniae include Stevens-Johnson syndrome, joint pain, encephalitis, cardiac rhythm disturbances, and bullous myringitis.
(Choice A) M pneumoniae is an atypical bacterium; it has a plasma membrane composed of cholesterol (unlike most bacteria) and no cell wall. The lack of a cell wall makes this pathogen resistant to beta-lactam antibiotics.
(Choice B) Malaria and babesiosis are associated with intraerythrocytic organisms that can cause cell lysis and anemia. However, these pathogens usually cause high fever and more severe clinical syndromes. In addition, azithromycin monotherapy is not an effective cure for these infections.
(Choice D) Iron deficiency anemia, which is most commonly due to blood loss, can often be improved by replenishing body iron stores (eg, oral iron supplementation). Chronic infection or inflammatory conditions can be associated with anemia of chronic disease, which is due to impaired utilization of iron (not absolute iron deficiency).
(Choice E) Enzyme deficiencies that cause anemia include glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency. Infection and medications that cause oxidative stress (eg, sulfonamides, antimalarial agents) can cause hemolysis in patients with G6PD; however, G6PD is an X-linked disorder (it is seen in men).
Educational objective:
Mycoplasma pneumoniae binds an oligosaccharide on the respiratory epithelium that is also present on erythrocytes, leading to the generation of cross-reacting IgM antibodies (cold agglutinins). Patients with M pneumoniae infections often develop mild, transient hemolytic anemia that resolves as IgM antibody titers decline (6-8 weeks after infection begins).