Mycoplasma pneumoniae linked to rare case of acquired angioedema
Report suggests cold agglutinins triggered a temporary C1-inhibitor deficiency
A young man in Greece developed acquired angioedema, one of the rarest forms of angioedema, as a complication of Mycoplasma pneumoniae infection — the bacterium best known for causing lung infection, or pneumonia — according to a recent case report.
While being treated for pneumonia, the man suddenly developed swelling on the left side of his face that didn’t respond to anti-inflammatory or allergy medicines. A diagnosis was confirmed after blood tests showed abnormally low levels and poor function of complement proteins, including C1 esterase inhibitor (C1-INH), C1q, and C4.
His symptoms resolved quickly after treatment with Firazyr (icatibant), a therapy approved for on-demand management of swelling attacks in people with hereditary angioedema.
“While a detailed and thorough assessment for the presence of associated comorbidities remains essential in all cases of acquired angioedema, clinicians should also consider infectious triggers, particularly when initial investigations are unrevealing,” the researchers wrote, emphasizing that prompt recognition of the cause is critical to guide treatment and prevent future attacks.
The case, “Acquired Angioedema Related to Transient C1- Inhibitor Deficiency Triggered by Mycoplasma pneumoniae Infection: A Case Report,” was published in the Allergy/Immunology section of MDPI.
How acquired angioedema develops
Angioedema occurs when blood vessels leak fluid into the deeper layers of the skin or mucous membranes that line internal organs, causing sudden swelling attacks. These can affect almost any part of the body, including the face, hands, airways, or digestive tract.
In acquired angioedema, these attacks occur when C1-INH levels become too low. This can happen when the body makes antibodies that neutralize C1-INH, or when the complement cascade — a protein network that supports immune defenses — becomes overactive due to cancer or other illnesses. When that happens, the body uses up too much C1-INH.
As C1-INH is depleted, components of the classical complement pathway — including C1q and C4 — are also consumed, resulting in their low blood levels, which may help with diagnosis. Low C1-INH also allows bradykinin, a signaling molecule that makes blood vessels leaky, to build up and cause swelling.
“Infectious triggers are rarely encountered, and the underlying mechanisms have yet to be completely clarified,” the researchers wrote.
Here, researchers in Greece described the “unique case” of a 19-year-old man, with no prior medical records, who developed acquired angioedema as a complication of Mycoplasma pneumoniae infection.
Pneumonia symptoms lead to unexpected swelling
The man first went to the emergency department after a week of fever and painful mouth ulcers that began with a dry cough. A chest X-ray suggested early lung infection, but his condition worsened despite antibiotic treatment.
He was transferred to a larger hospital, where doctors started him on glucocorticoids — common anti-inflammatory medications — and antihistamines, which are often used for allergic reactions. When his condition didn’t improve, he was admitted to the internal medicine department, where a CT scan confirmed pneumonia in the right lower lung.
He was given levofloxacin, an antibiotic commonly used to treat community-acquired pneumonia, and lab tests identified Mycoplasma pneumoniae infection. A biopsy of his mouth ulcers showed only general inflammation with no clear cause, which improved with local anti-inflammatory treatment.
Blood tests revealed low C4 levels and the presence of cold agglutinins — antibodies often linked to infections that bind to red blood cells at low temperatures and activate the complement system.
On the third day in hospital, he suddenly developed swelling on the left side of his face, but without itching, hives, or swelling of the tongue or throat.
“This presentation, alongside the low C4 levels and the lack of clinical response to the administration of [glucocorticoids] and antihistamines, raised strong clinical suspicion of acquired angioedema,” the researchers wrote.
Targeted therapy quickly resolves swelling attack
After treatment with a single dose of Firazyr — a therapy which blocks bradykinin from binding to its receptor — the swelling resolved within a few hours. Follow-up blood tests confirmed low levels and poor function of C1-INH, along with reduced C1q, consistent with acquired angioedema.
Following this episode, the man improved steadily. His fever subsided, his need for oxygen support decreased, and he was discharged in good condition.
At a one-month follow-up, his blood tests were normal, and cold agglutinins had disappeared. He also hadn’t experienced any new swelling attacks. Additional scans and lab tests ruled out autoimmune disease and cancer — both common causes of acquired angioedema. Based on his negative family history and the lack of recurrent symptoms, doctors confirmed a diagnosis of acquired angioedema.
The researchers suggested cold agglutinins may have triggered excessive complement activation, leading to the consumption of C1-INH and ultimately driving the swelling attacks.
“This case report adds to the limited evidence that infectious causes, such as Mycoplasma pneumoniae, can act as precipitating factors for [acquired angioedema], even in previously healthy patients without traditional risk factors,” the researchers wrote. “Timely detection and elimination of the underlying trigger are essential for optimal management and prevention of recurrent [angioedema] attacks, while the use of targeted agents such as bradykinin receptor antagonists is crucial for preventing life-threatening complications in acute episodes.”
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