Short-term use of Soliris treats two cases of aHUS not tied to mutations

Disease triggered in the men either by rare infection or autoimmune condition

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by Andrea Lobo |

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Short-term use of Soliris (eculizumab) successfully treated atypical hemolytic uremic syndrome (aHUS) that had no genetic link in two young adults, one with a rare infection and the other with a rare autoimmune condition, according to a case report.

Both men lacked variants in complement genes that can be disease modifiers when aHUS is triggered in such circumstances and which can affect response to Soliris.

“In our study, patients did not have rare complement variants, which enabled rapid [Soliris] discontinuation with no long-term aHUS recurrence,” the scientists wrote, adding that “both patients required kidney replacement therapy and responded to [Soliris] with complete renal recovery.”

They also stressed that withdrawal from the treatment “should be tailored to the individual patient.”

The report, “Case report: Short-term eculizumab use in atypical HUS associated with Lemierre’s syndrome and post-infectious glomerulonephritis,” was published in the journal Frontiers in Medicine.

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Soliris treats aHUS in man likely triggered by kidney transplant

Use of Soliris when aHUS not tied to complement variants is ‘controversial’

aHUS is a type of thrombotic microangiopathy characterized by the formation of blood clots in small blood vessels.  The disease is caused by the abnormal activity of the complement cascade, a part of the immune system. While most patients have mutations in complement genes that make them prone to aHUS, their presence alone is usually not enough to cause aHUS to develop. An event trigger, such as an infection, usually is required.

Soliris, a complement inhibitor, is considered a main treatment for aHUS associated with mutations in complement genes, the report noted. Its effectiveness with nongenetic forms of aHUS, however, remains “controversial.”

Scientists in the U.S. described the cases of two young men with nongenetic aHUS who were effectively treated with Soliris.

The first was a 22-year-old African-American who came to a San Francisco-area hospital with complaints of a sore throat, headache, and back pain. A physical examination revealed an altered mental state, as well as a rapid heart rate, rapid breathing, and mildly high blood pressure. Laboratory tests suggested kidney disease, hemolytic anemia or anemia associated with red blood cell destruction, and a low platelet count.

He was initially thought to have thrombotic thrombocytopenic purpura (TTP) — another type of thrombotic microangiopathy — due to neurological symptoms. He started on therapeutic plasma exchange, a treatment that replaces a patient’s plasma, the liquid portion of blood, and on continuous kidney replacement therapy due to poor urine production.

Based on an ultrasound finding of a blood clot in an internal jugular vein of the neck and culture test results indicating a bacterial infection, the patient was diagnosed with Lemierre’s syndrome. This syndrome is a rare complication of an infection that involves a jugular vein clot. He was started on antibiotics.

Additional tests ruled out TTP as the cause of his symptoms, leading clinicians to suspect aHUS.

Genetic testing revealed the presence of a mutation in CFHR1-CFHR3 complement genes, but it was not considered disease-causing, because he had no commonly associated anti-complement factor H antibodies.

While showing some improvement, his kidney issues and anemia persisted. He then was started on Soliris, which rapidly improved his kidney function. Treatment was stopped after five doses.

The second patient was an 18-year-old Asian-American with a history of severe atopic dermatitis — an inflammatory skin condition commonly known as eczema, and characterized by the presence of inflamed and itchy skin lesions. He came to the hospital with an intermittent fever over the previous two weeks.

Physical examination revealed a low body temperature, mild rapid breathing, and high blood pressure. Due to these symptoms, he was admitted to the hospital for intravenous antibiotic treatment.

Laboratory tests indicated acute kidney injury, which was initially attributed to dehydration, and mild anemia. Six days after his admission, he began coughing up blood and clinicians noted the presence of blood in his urine. Together with a falling platelet count and respiratory distress, he was transferred to the intensive care unit.

He was treated with therapeutic plasma exchange and methylprednisolone to decrease inflammation.

Both men responded to treatment with 10 or fewer doses of Soliris

Further tests revealed low levels of the C3 complement protein and signs of a recent streptococcus bacterial infection, leading to a diagnosis of post-infectious glomerulonephritis or PIGN — an autoimmune response to infection that affects the tiny filter structures inside the kidneys. PIGN was confirmed through a kidney biopsy.

His worsening kidney function required the start of intermittent hemodialysis. Despite some improvement after one week of therapeutic plasma exchange and methylprednisolone, his declining kidney health, and worsening anemia and platelet counts led clinicians to suspect aHUS.

Soliris treatment was started and improved his kidney function and normalized his platelet count. Genetic testing revealed no mutations associated with aHUS, and treatment was stopped after 10 doses given over 15 weeks.

Both men had no recurrence of aHUS over six years of follow-up, and recent tests found normal blood cell counts and kidney function.

“Eculizumab can be effective in aHUS associated with rare infectious and autoimmune etiologies [causes] and potentially discontinued in the absence of rare complement [genetic] variants,” the scientists wrote.