Treatment with Soliris (eculizumab) is an effective strategy to manage atypical hemolytic uremic syndrome (aHUS) even when manifested with atypical neurological symptoms, a rare case reported by Turkish researchers suggests.
The case was described in the study, “An adult case of atypical hemolytic uremic syndrome presented with posterior reversible encephalopathy syndrome: Successful response to late-onset eculizumab treatment,” published in the journal Hematology Reports.
Soliris is a complement inhibitor discovered, developed, and marketed by Alexion. It works by blocking the signals of the immune system’s complement pathway that, when activated in an uncontrolled manner, contributes to the development of rare and serious diseases such as paroxysmal nocturnal hemoglobinuria (PNH), aHUS, and generalized myasthenia gravis (gMG).
aHUS is a progressive disorder linked to a high risk of permanent renal damage caused by dysregulation of the complement system — a set of more than 20 blood proteins that form part of the body’s immune defenses. About 60-70% of aHUS patients carry mutations in genes that encode those complement regulatory proteins.
Extra-renal manifestations occur in about 20% of patients. They most commonly involve the central nervous system — with altered consciousness, seizures, and focal neurologic deficits — and the gastrointestinal system, with diarrhea.
A Turkish team presented the case of a 29-year-old woman who had aHUS that manifested as a rare neurological condition called posterior reversible encephalopathy syndrome (PRES).
She was admitted to the hospital with a six-month history of headaches and vomiting without diarrhea. She previously had anemia, with normal renal function and no signs of altered brain structures.
An initial physical evaluation showed that she had peripheral edema (swelling due to accumulation of fluids) and she said she had been urinating less.
Blood tests showed she had 12.8 and 4.4 times the normal levels of creatinine and urea, respectively, suggesting she had impaired renal function. This was confirmed by the 15 times lower kidney filtration rate and increased levels of protein in the urine. She also had low hemoglobin levels.
Overall, her lab results indicated that she had renal insufficiency with tissue damage and signs of anemia caused by destruction of red blood cells.
To understand whether her symptoms were being triggered by the immune system, researchers analyzed the levels of circulating antibodies commonly associated with autoimmune disorders, which were found to be negative. Also, the levels of complements C3 and C4 proteins, as well as C5, were within normal range.
Genetic analysis of complement genes showed that she had two mutations on the complement factor H activator and one on the CFHR5 genes, which have been associated with aHUS. They also detected a new mutation in the C3 gene, but it is unknown whether it could contribute to the development of the disease.
Based on these findings she started on hemodialysis and plasmapheresis (blood filtration to remove harmful antibodies) to restore blood analysis back to normal, and she took steroid therapy to regulate her immune system’s activity.
Despite the treatment, she started to experience seizures with uncontrolled hypertension. The seizures could not be controlled with antiepileptic agents, such as Valium (diazepam) and Depacon (valproate sodium), and she required ventilation assistance upon the seizures.
She was then scheduled for a chronic hemodialysis program and twice-daily plasmapheresis, and started to receive anti-hypertensive therapy to control her blood pressure.
Brain scanning after the seizure revealed some alterations consistent with a diagnosis of posterior reversible encephalopathy syndrome.
“Neurological involvement [such as PRES] is the most common extra-renal complication and a major cause of mortality and morbidity [in] aHUS,” researchers said.
About one month after admission, she started treatment with Soliris — weekly intravenous infusions of 900 mg for four weeks followed by a maintenance dose of 1,200 mg every 14 days.
Her renal functions and blood parameters showed progressive improvement upon treatment with Soliris. After three months her brain scans were back to normal and by the fourth month her renal function had improved.
She was kept on chronic Soliris therapy for 24 months and continued treatment with two anti-hypertensive agents.
In cases of aHUS with continuing hematologic, renal, or other clinical manifestations, treatment with Soliris should be considered, the team said.
“Even when [Soliris] treatment is initiated late, it should be taken into consideration that [it] can cause a dramatic response in these patients,” the researchers stated.