Case Presentation: A 54 year-old previously healthy man presented to the ED with two weeks of cough productive of “grey-green” mucus and slowly worsening dyspnea on exertion. His symptoms were accompanied by low-grade fevers, fatigue, poor appetite, and lightheadedness upon standing. His spouse was recently ill with symptoms of an upper respiratory infection. Review of systems was positive for yellowing of the skin and darkening of the urine; he denied orthopnea, chest pain, or abdominal pain.
The patient was afebrile with a heart rate of 120 beats per minute and an oxygen saturation of 91% on room air. He had jaundice of the sclera and skin, as well as rales at both lung bases. His white blood cell count was 30,000/µL with 87% neutrophils, hemoglobin (Hg) was 9.9 g/dL, MCV was 93 µm3, and reticulocyte index was 1.9. LDH was 723 U/L and haptoglobin was less than 8 mg/dL. Direct Coombs test was positive. Liver chemistries showed a total bilirubin of 8 mg/dL with a direct bilirubin of 1.1. Liver function tests were otherwise normal.

Portable chest x-ray was unremarkable. CT of the chest with angiogram showed diffuse tree-in-bud opacities without evidence of PE. CT of the abdomen demonstrated cholelithiasis without evidence of cholecystitis and a 2.9 cm hypodense liver lesion.

Nasopharyngeal nucleic acid amplification testing (NAAT) was positive for Mycoplasma pneumoniae and the patient was started on oral azithromycin. Over the next 48 hours, his Hg continued to downtrend, reaching a nadir of 6.9. He remained dyspneic and required 2L of oxygen by nasal cannula. Hematology was consulted given the severe hemolysis and concluded it was from the Mycoplasma infection. The patient symptomatically improved and was discharged after three days.

Discussion: Autoimmune hemolytic anemia (AIHA) is seen in up to 60% of patients with M. pneumoniae. Hemolysis is typically mild or subclinical; yet, inpatient providers are more likely to encounter severe cases of Mycoplasma-associated AIHA, as these patients often require an increased level of care and support. This patient’s presentation of indolent respiratory symptoms, recent sick contact, reticulonodular findings on chest imaging, and positive NAAT was strongly suggestive of Mycoplasma infection. Despite the “classic” presentation, the severe anemia led to unnecessary diagnostic uncertainty. Additional imaging revealed two incidental findings and resulted in further workup and anxiety. NAAT offers hospitalists a valuable tool for diagnosis considering its ease of use, rapid turnaround time, and published sensitivity of 62% and specificity of 95%. While a negative test does not preclude infection, a positive test is strongly supportive of it in the right clinical context.

Conclusions: Mycoplasma-associated AIHA is well-documented. While severe anemia is not typically seen, this case serves as a reminder of the spectrum of disease that can occur following infection. If clinical suspicion is high, NAAT offers hospitalists a valuable tool for diagnosis.