Approved treatment helps girl recover from severe aHUS, report shows
Ultomiris led to rapid improvements in kidney function, platelet counts
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Treatment with Ultomiris (ravulizumab) led to rapid blood and kidney recovery in a 12-year-old girl with atypical hemolytic uremic syndrome (aHUS) associated with a rare genetic mutation, according to a case report.
The girl developed acute kidney failure, thrombocytopenia (low counts of platelets, small cell fragments that help the blood to clot), and hemolysis (red blood cell destruction) following an influenza A (H1N1) infection.
According to researchers, “this is the first reported case in Colombia of aHUS associated with a rare … variant of CD46, triggered by influenza A (H1N1), and successfully treated with [Ultomiris].”
The case was described in “Influenza A(H1N1) triggered atypical hemolytic uremic syndrome in a child with homozygous CD46 variant successfully treated with ravulizumab: a case report,” published in CEN Case Reports.
Testing revealed the H1N1 virus
AHUS is caused by abnormal activity of the complement pathway, a part of the immune system, which results in blood clotting in small blood vessels, known as thrombotic microangiopathy (TMA). The disease is marked by hemolysis, thrombocytopenia, and kidney damage.
While most people with aHUS have mutations in genes that regulate the function of the complement pathway, a triggering event, such as an infection, is also necessary to develop the disease.
In their report, researchers described the case of a 12-year-old girl with a rare mutation in the CD46 gene. The girl was admitted to the emergency department after four days of fever, chills, abdominal pain, diarrhea, dry cough, and bleeding from the lining of the mouth and nose. At the first evaluation, the clinicians also found yellowing of the whites of her eyes, small areas of bleeding in the eyes, and bruising on her lower lip and limbs.
Blood tests showed microangiopathic hemolytic anemia, in which red blood cells are destroyed as they pass through small blood vessels, along with thrombocytopenia and acute kidney injury. The girl also presented with complement system impairment and elevated D-dimer, a sign of blood clot formation. Together, these findings were suggestive of TMA.
Further tests also revealed the H1N1 virus, and the Escherichia coli bacterium, which is able to cause disease in the digestive tract, for which she received treatment with antiviral medication and antibiotics. However, testing was negative for Shiga toxin-producing E. coli, a trigger of the typical form of hemolytic uremic syndrome.
Platelets counts increased within 3 days of receiving Ultomiris
The girl’s condition worsened rapidly, affecting several organs, including the liver and pancreas. She was admitted to the pediatric intensive care unit (ICU), where she received therapeutic plasma exchange, a treatment that removes and replaces the liquid part of the blood, for seven days. She also received red blood cells and platelet transfusions.
During the ICU stay, she developed acute respiratory failure requiring ventilatory support for nine days, and hypertension (high blood pressure), which was treated with a combination of treatments. She also underwent four sessions of hemodialysis, a procedure that helps filter blood when the kidneys are not working properly.
Despite treatment, her blood and kidney abnormalities were not resolved. She was eventually diagnosed with aHUS, after excluding Shiga toxin-associated disease and finding normal activity of ADAMTS13, an enzyme whose severe deficiency is associated with another form of TMA.
Due to the condition’s severity and lack of response to plasma exchange, she started treatment with Ultomiris (1,200 mg), an antibody therapy that targets the complement protein C5. Within three days of receiving the first dose, her platelet counts increased, and the levels of lactate dehydrogenase, a marker of hemolysis, decreased.
This case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy [and] highlights how infections can act as triggers that unmask underlying genetic susceptibility.
The girl received a second, maintenance dose of Ultomiris (2,700 mg) about two weeks later and no longer needed daily red blood cell or platelet transfusions.
She was discharged after 33 days. About three months later, her kidney function, platelet counts, and hemoglobin levels returned to normal. Hemoglobin is the protein that carries oxygen in red blood cells. The girl continued receiving Ultomiris every eight weeks and remained in clinical remission, with no reported relapses.
Genetic testing identified a rare disease-causing mutation in both copies of the gene that encodes the CD46 protein, which helps regulate the complement system. The researchers noted that such a CD46 mutation “is clinically relevant, as it is associated with an increased risk of relapse after discontinuation of complement inhibition.”
According to the researchers, “this case underscores the importance of early C5 inhibition in complement-mediated thrombotic microangiopathy.” It also “highlights how infections can act as triggers that unmask underlying genetic susceptibility,” they wrote.
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