Large-vessel involvement in AAV tied to neurological manifestations
Risk of LVI 3 times higher for patients with neurological symptoms: Study
ANCA-associated vasculitis (AAV) patients with neurological manifestations are more than three times more likely to have large blood vessel involvement (LVI), according to a multicenter study in France and Belgium.
Data also showed that LVI most commonly affected the aorta — the large artery that delivers oxygen-rich blood to the body — and its branches.
“Clinicians should be aware of the occurrence of LVI in AAV,” the researchers wrote, adding that “standard AAV treatments appear to be effective in managing LVI, although relapses can happen.”
The study, “Large-vessel involvement in ANCA-associated vasculitis: a multicenter case-control study,” was published in Seminars in Arthritis and Rheumatism.
Researchers followed 26 AAV patients over 30 years
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. This leads to disease symptoms that include problems in the skin, lungs, kidneys, and nervous system.
Most cases are associated with the production of self-reactive antibodies, called ANCAs, that ultimately drive blood vessel inflammation. ANCAs typically target one of two enzymes: proteinase 3, or PR3, or myeloperoxidase, known as MPO.
But while AAV mainly affects small blood vessels, “there have been reports of large-vessel involvement (LVI), particularly of the aorta and its branches,” the researchers wrote.
To know more about the risk factors, clinical characteristics, and treatment of LVI in AAV, a team of researchers studied 26 AAV patients with such involvement. These patients were followed from 1991 to 2023 at 14 centers across France and Belgium, and through the French Vasculitis Study Group registry.
The patients’ mean age was 56 — ranging from 24 to 86 years — and slightly more than half (58%) were men.
Among the patients, 20 (more than 75%) had granulomatosis with polyangiitis (GPA), an AAV type associated with the formation of immune cell masses, or granulomas, mainly affecting blood vessels in the lungs, kidneys, and upper respiratory tract.
The remaining six patients (slightly fewer than 25%) had microscopic polyangiitis (MPA), which mainly affects the kidneys, and lacks granulomas.
All but one patient were positive for ANCAs, with those targeting PR3 detected in 14 patients and anti-MPO ANCAs in 11.
LVI was the first disease manifestation in nearly 70% of cases, while it occurred after an AAV diagnosis in the remaining eight patients, who had received previous standard AAV treatment.
In more than half of the patients (58%), LVI was detected incidentally during imaging for an AAV relapse. The remaining 11 patients had symptoms of LVI, most commonly pain affecting the back, abdomen, neck, or groin.
The aorta was the most frequently affected large blood vessel, in 69% of patients, and involved most frequently at the level of the chest. This was followed by the aorta’s upper branches (35%), and then equally the mesenteric arteries — derived from the aorta, they deliver blood to the gastrointestinal tract — and the lower limbs arteries, both at 19%.
Less frequently, the kidney arteries and those in the upper limbs were involved.
Imaging analysis revealed the thickening of blood vessels’ walls in 10 patients, mainly associated with inflammation and vessel narrowing. Aneurysms — bulges in blood vessel walls that can burst or rupture — were detected in five patients, mostly affecting mesenteric, pelvic, and kidney arteries.
When comparing the 26 patients with 52 age-, sex-, and AAV type-matched patients without LVI (used as controls), the team found that neurological involvement at the time of AAV diagnosis and previous neurological symptoms were risk factors for LVI, each increasing the risk by about three times.
LVI ‘strongly associated’ with neurological manifestations of AAV
At diagnosis, neurological involvement was present in 58% of patients and 27% of controls. It most commonly involved the nerves outside the brain and spinal cord (31% of cases vs. 19% of controls), those in the brain and spinal cord (23% vs. 2%), and headaches (19% vs. 12%).
No significant association was found between the occurrence of LVI and cardiovascular risk factors, cancer history, or smoking status.
Over follow-up, more AAV patients with LVI experienced relapses relative to controls (54% vs. 37 %), but this difference failed to reach statistical significance.
All 26 patients with LVI received corticosteroids as a first-line treatment, and most commonly in combination with an immunosuppressant (92%) such as cyclophosphamide (sold as Cytoxan, among others) and rituximab (sold as Rituxan, among others).
Evaluable data from 25 patients showed that 22 responded to treatment, while three experienced worse inflammation of the aorta wall or persistent AAV symptoms. For these cases, second-line treatment options included cyclophosphamide, rituximab, methotrexate, and a blood-cleaning procedure called plasma exchange.
Two patients experienced an LVI relapse four years after they received, and successfully responded, to treatment.
AAV is a rare cause of LVI, which seems to be more strongly associated with neurological manifestations of AAV.
“In our multicenter study of 26 patients, LVI predominantly affected the aorta and [its branches], with wall thickening, … inflammation, and aneurysms on imaging,” the researchers wrote.
“Many of our cases [had no symptoms of LVI], consistent with previous reports,” the team added, noting, however, that the detected LVI “manifestations generally responded well to a combination of corticosteroid plus an immunosuppressive agent.”
Altogether, the researchers concluded that “AAV is a rare cause of LVI, which seems to be more strongly associated with neurological manifestations of AAV.”
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