Bacterial lung infection sparks CAD, kidney injury for woman
Rare case began with mild cough and sore throat
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A woman in her 50s developed cold agglutinin disease (CAD) and kidney injury as rare complications of a bacterial lung infection caused by Mycoplasma pneumoniae (M. pneumoniae), according to a case report.
Although these infections can trigger the production of cold agglutinins, the self-reactive antibodies that cause CAD, in up to 20% of cases, the severe red blood cell destruction (hemolysis) inside blood vessels and acute kidney injury experienced by the woman are rare.
The case “represents an unusual and clinically significant manifestation of Mycoplasma-associated [CAD],” the researchers wrote, noting that “clinicians should consider cold agglutinin-mediated hemolysis in patients with dark urine and [acute kidney injury] following respiratory infection.”
The study, “Severe Intravascular Hemolysis and Acute Kidney Injury Triggered by Mycoplasma-Associated Cold Agglutinin Disease: A Case Report,” was published in Clinical Medicine Insights: Case Reports.
CAD is marked by the production of cold agglutinins, self-reactive antibodies that bind to red blood cells at cold temperatures, causing them to stick together. This activates the complement pathway, a component of the immune system, that ultimately leads to hemolysis and anemia (low levels of red blood cells).
‘Exceedingly rare’ combination
Hemolysis in CAD most often occurs outside blood vessels, in the liver. In severe cases, it can occur within blood vessels, a condition known as intravascular hemolysis.
CAD is classified as primary when it occurs for unknown reasons, and secondary — also known as cold agglutinin syndrome (CAS) — when triggered by an underlying condition or infectious agent, such as M. pneumoniae.
While this bacterium is best known for causing mild respiratory infections, rare cases of life-threatening CAD-related hemolysis or acute kidney injury have been reported. “The combination of Mycoplasma pneumoniae-triggered CAS with intravascular hemolysis and [acute kidney injury] is exceedingly rare,” the researchers wrote.
The pair of researchers, in Egypt and Syria, reported the case of a 59-year-old woman who developed CAD-related intravascular hemolysis and acute kidney damage secondary to an M. pneumoniae lung infection.
The woman was admitted to the emergency department after experiencing progressive weakness, dizziness, and dark brown urine for one week. She also had yellowing of the skin and the whites of the eyes, and low urinary output. She said that two weeks earlier, she had a mild cough and sore throat, which went away on their own.
Physical examination revealed high blood pressure and a fast heart rate.
Laboratory tests showed acute kidney injury, with high levels of creatinine and urea nitrogen, and signs of intravascular hemolysis. These included low blood levels of hemoglobin (the protein that carries oxygen in red blood cells), high blood levels of the hemolysis markers bilirubin and lactate dehydrogenase (LDH), and blood in the urine.
A Coombs test, which assesses for the presence of antibodies and/or complement proteins bound to red blood cells, showed the woman was positive for bound C3d, a complement protein. She also had high levels of cold agglutinins. These findings confirmed a CAD diagnosis.
Analysis of possible infections demonstrated a recent M. pneumoniae infection, “indicating a likely triggering factor,” the researchers wrote.
The woman was admitted to the intensive care unit for close monitoring and comprehensive management, including being placed in a warm room and with all fluids and blood products being administered intravenously (into the vein) via a blood warmer to prevent further hemolysis. She received a blood transfusion of warmed red blood cells, which raised her hemoglobin levels without signs of hemolysis aggravation.
Due to worsening kidney function, continuous kidney replacement therapy was initiated on day two, which gradually increased her urinary output. It was discontinued on day eight as kidney function “showed signs of recovery,” the researchers wrote.
Given her high cold agglutinin levels and hemolysis severity, the woman received a single dose of rituximab (sold as Rituxan, with biosimilars available) on day 4 to reduce the production of self-reactive antibodies. Rituximab is designed to kill B-cells, the immune cells that produce antibodies, including cold agglutinins.
She also received an antibiotic to treat the lung infection.
By day 10, hemoglobin levels had stabilized, and LDH and creatinine levels had decreased. The woman was discharged in stable condition, with follow-up appointments scheduled. Hemolysis markers normalized over two to four weeks, and kidney function recovered within four to eight weeks.
“Our case joins the few reported instances of life-threatening Mycoplasma pneumoniae-CAS,” the researchers wrote. “Massive intravascular hemolysis can theoretically precipitate acute [kidney tube] injury from [hemoglobin] casts and iron deposition, which may explain any [kidney] dysfunction seen in these patients.”
The “early recognition and supportive interventions—particularly warmed transfusions and [kidney] support—were critical to recovery,” they wrote.
