Prompt treatment leads to full recovery in severe aHUS case: Report
Patient received Soliris after developing complications in several organs
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A woman with atypical hemolytic uremic syndrome (aHUS) developed severe complications affecting the kidneys, brain, and heart, but recovered without lasting neurological damage after prompt treatment that included the complement blocker Soliris (eculizumab), a study showed.
The complement cascade is a part of the immune system that is abnormally activated in aHUS. A mutation in the complement factor H (CFH) gene was later identified in the woman.
“Early clinical recognition and prompt initiation of complement [suppressor therapy] were central to the favorable outcome, while intensive blood pressure control and comprehensive supportive care may have contributed to neurological recovery,” researchers wrote.
The study, “A case report of atypical hemolytic uremic syndrome with a CFH mutation complicated by recurrent posterior reversible encephalopathy syndrome,” was published in Medicine.
Soliris blocks key complement protein
AHUS is a type of thrombotic microangiopathy (TMA), a group of diseases marked by blood clots in small blood vessels that block blood flow and cause red blood cell destruction (hemolysis), kidney damage, and low platelet levels. Platelets are the tiny cell fragments in blood that help it to clot.
In aHUS, abnormal activity of the complement cascade causes blood clot formation and related symptoms. While most patients have inherited mutations in genes that encode proteins of the complement cascade, a triggering event such as an infection is typically necessary for developing aHUS. Mutations in the complement factor H (CFH) gene are often linked to more severe aHUS.
In this report, a team of researchers in Japan described the case of a 32-year-old woman whose CFH-related aHUS led to severe organ dysfunction, including of the heart and brain. It was successfully treated with Soliris, a therapy approved for aHUS that blocks the complement protein C5.
The woman had been healthy except for painful menstrual periods, and had no family history of blood or kidney disease. For two months, she had worsening fatigue and poor appetite, which worsened after a COVID-19 infection one month before admission. The day before visiting the hospital, she developed shortness of breath while resting.
Laboratory tests at a previous facility showed anemia (lower-than-normal red blood cells), thrombocytopenia (lower-than-normal platelets), and severe acute kidney disease, meaning her kidneys had suddenly stopped functioning properly. She was therefore referred to the researchers’ hospital.
Patient had complications affecting the kidneys, heart, and brain
Examination showed high blood pressure, swelling throughout her body, pale eyelids caused by anemia, and purple skin spots caused by bleeding under the skin. A blood smear showed many schistocytes (broken red blood cell fragments), suggesting blood clots in small blood vessels and the presence of a TMA.
Urine tests showed the presence of red blood cells and proteins, consistent with severe kidney damage. Because of these findings, she was admitted to the intensive care unit for close monitoring and treatment.
On her first night in the hospital, she had a generalized tonic-clonic seizure, which causes full-body shaking and loss of consciousness. She then stopped breathing and needed a breathing machine.
Continuous dialysis, which removes waste and excess fluid from the blood, was started because her kidneys were no longer working.
Plasma exchange, a blood-filtering procedure meant to clear the blood of potentially harmful substances, was started on the third day. Although she briefly improved enough to come off the breathing machine, she developed severe cardiomyopathy, a disease that affects the heart muscle. Heart ultrasound showed that her heart was pumping poorly.
On the sixth day at the hospital, the woman developed involuntary eye movements. Brain scans showed widespread lesions consistent with severe posterior reversible encephalopathy syndrome (PRES), which can cause seizures, confusion, and vision problems, but often improves with prompt treatment.
This case highlights that CFH mutation-positive aHUS can be complicated by severe multiorgan dysfunction, including cardiomyopathy and recurrent PRES. Early clinical diagnosis and prompt initiation of complement [blockage], combined with intensive blood pressure control, resulted in complete neurological recovery and favorable outcomes.
Doctors carefully controlled her blood pressure because high blood pressure can worsen PRES. After other possible causes were excluded, the woman was diagnosed with aHUS without waiting for results from genetic testing.
Treatment with Soliris was started immediately. The woman’s condition gradually improved, and she was discharged from the intensive care unit on day 14. However, after about 10 days, she had another seizure. A brain MRI revealed new brain lesions, “suggestive of recurrent PRES,” the researchers wrote.
Even though schistocytes remained in the blood for some time, continued treatment with Soliris, plasma exchange, dialysis, strict blood pressure control, and intensive supportive care steadily improved her status.
Later, her anemia and thrombocytopenia eased, and dialysis was no longer needed. Genetic testing more than a month after her hospitalization confirmed a disease-causing CFH mutation.
She left the hospital on day 69 without lasting neurological problems. She continues outpatient treatment with Ultomiris (ravulizumab), a longer-acting complement suppressor.
“This case highlights that CFH mutation-positive aHUS can be complicated by severe multiorgan dysfunction, including cardiomyopathy and recurrent PRES,” the researchers wrote. However, “early clinical diagnosis and prompt initiation of complement [blockage], combined with intensive blood pressure control, resulted in complete neurological recovery and favorable outcomes.”
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