Sequential MS treatments trigger aHUS in woman: Case study
Researchers urge continuous monitoring during MS therapy switches
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The sequential use of immune-modulating medications to treat multiple sclerosis (MS), an inflammatory disease that affects the brain and spinal cord, triggered atypical hemolytic uremic syndrome (aHUS) in a 48-year-old woman, according to a case study.
This case highlights “the importance of continuous clinical and laboratory monitoring in patients receiving sequential immunomodulatory therapies, facilitating early recognition of unexpected adverse events,” the authors wrote.
The case study, “Complement-mediated thrombotic microangiopathy presenting as atypical hemolytic uremic syndrome during disease-modifying therapy for multiple sclerosis,” was published in Neurological Sciences.
MS often treated with a series of different medications over time
AHUS is a rare disease caused by the abnormal activity of the complement cascade, a part of the immune system, which leads to the formation of tiny blood clots in small blood vessels. While it’s frequently linked to genetic mutations that regulate the complement cascade, the disease often requires a triggering event, such as an infection, pregnancy, cancer, or certain medications.
The disease has three hallmark symptoms: hemolytic anemia (red blood cell destruction), thrombocytopenia (low levels of platelets, the cell fragments that help blood clot), and acute kidney failure.
In this case, aHUS was triggered by medications used to treat multiple sclerosis, an autoimmune disease in which the immune system causes damage to certain parts of the brain, spinal cord and the optic nerve. MS is often treated with a series of different medications over time, particularly if a drug isn’t working adequately or is causing side effects.
The 48-year-old woman had been diagnosed with relapsing-remitting MS, a type of MS marked by attacks of new or worsening symptoms followed by periods of partial or complete recovery, eight years earlier. She experienced facial numbness, blurred vision, lack of balance, weakness, vertigo, and double vision.
She was first treated with dimethyl fumarate, a common MS medication (sold as Tecfidera and available as generics). Nine months later, her platelet count dropped substantially. As there were new signs of inflammatory disease on MRI scans, her treatment was switched to fingolimod (sold as Gilenya and also available as generics), another MS drug.
While on fingolimod, at month 14, she developed a widespread case of shingles (herpes zoster) affecting a large area of skin on her chest. Fingolimod was stopped, and she was treated with the antiviral drug acyclovir, which resolved the infection.
Because MRI scans still showed disease activity, she was then switched to cladribine (sold as Mavenclad), a drug that works by temporarily reducing the number of certain immune cells that drive inflammatory attacks.
Complement-mediated thrombotic microangiopathy consistent with aHUS may represent a rare but serious complication occurring during disease-modifying therapy for MS. Early recognition and prompt complement inhibition may be critical for preventing irreversible organ damage and improving clinical outcomes.
Her first year on cladribine was uneventful with no relapses. However, nine days after her first dose of the second year of cladribine treatment, she developed diarrhea, fever, jaundice (yellowing of the skin and whites of the eyes), and reduced urine output.
Blood tests showed thrombocytopenia, kidney injury, and signs of hemolytic anemia. Based on these findings, she was diagnosed with aHUS.
Doctors ruled out other possible causes of her symptoms, including a bleeding condition called thrombotic thrombocytopenic purpura. Genetic testing found no disease-causing mutations, suggesting her condition was not inherited.
Cladribine was stopped, and she was started on the approved aHUS therapy Soliris (eculizumab), which stabilized her condition. She was followed for 13 months without any MS relapses or new MRI activity.
The authors proposed what they called a “multi-hit model.” In this case, the combination of several prior MS treatments, the shingles infection, the acyclovir treatment, and the immune changes triggered by cladribine may have together contributed to the abnormal complement activation and blood vessel damage.
They emphasize that patients on sequential MS therapies should be monitored closely so that unusual complications like aHUS can be caught early.
“Complement-mediated thrombotic microangiopathy consistent with aHUS may represent a rare but serious complication occurring during disease-modifying therapy for MS,” the researchers concluded. “Early recognition and prompt complement inhibition may be critical for preventing irreversible organ damage and improving clinical outcomes.”
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