One winter afternoon, Matthew, a 30-year-old clerk with an unremarkable past medical history, presents with symptoms of generalized malaise, weakness with dry cough and increasing dyspnea. He's been suffering from flu-like symptoms such as aches and pains, fever and muscle cramps over the past 10 days. In fact, he went to the emergency department 5 days ago but was sent home with the assurance that he only had a viral syndrome. The following day, he noted discolouration of his urine to dark orange. His appetite has been poor for a week but he denies any nausea, vomiting or diarrhea. He also doesn't have abdominal or chest pain, nor does he declare any joint pain, skin rash or hair loss.
Further inquiry reveals that his son recently had the chicken pox and that they had their furnace cleaned 3 weeks prior to the onset of symptoms. They also got a cat and a dog in the past 3 months. Matthew isn't on any medications and he doesn't smoke. While he drinks socially, he denies any drug use.
Physical examination reveals a listless young man with icterus. He's afebrile and cervical and axillary lymph nodes are normal. On chest exam, you find a resonant chest with fair air entry bilaterally and few crackles at the right lung base. Heart sounds are normal without any murmurs or added sounds. Abdominal examination is unremarkable and non-tender; there's no hepatomegaly or splenomegaly. There's also no pedal edema. Neurologic exam is non-focal.
A urinalysis shows a pH of 6.0, specific gravity of 1.015, 1+ protein, 1+ blood, 2+ bilirubin, 4+ urobilinogen and 0-5 WBC/HPF. Chest x-ray reveals bilateral interstitial infiltrate, more prominent in the right lower lung. An urgent abdominal ultrasound the next morning is unremarkable, however. Specifically, there's no evidence of hepatobiliary pathology. Hemoglobin has dropped to 67 g/L. What's your diagnosis?
The clinical picture of a febrile illness with persistent dry cough, increasing dyspnea, progressive anemia, mainly indirect hyperbilirubinemia, interstitial infiltrate on chest x-ray and a history of furnace cleaning a few weeks prior to the onset of symptoms raises the possibility of an interstitial pneumonia. Mycoplasma or Legionella are the main suspects, with Mycoplasma taking the lead because the progressive anemia with indirect hyperbilirubinemia suggests that a hemolytic process is occurring. Cold agglutinins and mycoplasma serology were requested, and the cold agglutinins came back strongly positive with a titre of 1:2,048. Direct antiglobulin test (DAT)-IgG was negative but DAT-CD3 was weakly positive.
Matthew was started on intravenous erythromycin and steroids. Within 48 hours, his symptoms improved and hemoglobin stabilized. He was discharged home 5 days later on oral erythromycin for another 5 days and tapering doses of steroids. Six weeks later, his hemoglobin is back at 142 g/L and his cold agglutinin is 1:30. The weather might have worsened the hemolysis as the cold agglutinins are more likely to precipitate and cause hemolysis at colder temperatures. Mycoplasma IgG antibody is now found to be positive; hepatitis serology is negative. Final diagnosis: cold agglutinin-induced hemolytic anemia, likely secondary to Mycoplasma interstitial pneumonia.
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