Connective Tissue Diseases More Common in AAV Patients with Kidney Involvement Than Thought, Study Reports

More people with ANCA-associated vasculitis (AAV), including those with kidney involvement, also have connective tissue diseases (CTD) than is generally thought, especially among female patients. But the co-existence of a CTD was unlikely to worsen kidney disease or change overall disease outcomes, a study reports.

AAV patients with connective tissues diseases like systemic lupus erythematosus, rheumatoid arthritis, or Sjögren’s syndrome, however, are more likely to experience non-renal AAV relapses and more frequent episodes of venous thrombosis, or clots that form inside a blood vessel.

The study, “Patients with ANCA-Associated Glomerulonephritis and Connective Tissue Diseases: A Comparative Study from the Maine-Anjou AAV Registry,” was published in the Journal of Clinical Medicine.

AAV, an autoimmune disease marked by swollen and inflamed blood vessels (vasculitis), is caused by autoantibodies called ANCAs, or anti-neutrophilic cytoplasmic autoantibodies, that wrongly attack the walls of small vessels.

Some people develop an AAV subtype known as ANCA glomerulonephritis (ANCA-GN), which affects the small blood vessels in the glomeruli, the filtering units in the kidneys. This can cause blood and protein to leak into the urine and damage the kidneys, potentially resulting in kidney failure.

Cases in which ANCA-GN overlaps with other autoimmune connective tissue diseases (CTD) — disorders that damage body parts that connect body areas, like ligaments, blood vessels, bones, cartilage and skin — are known but thought to be rare.

Such overlap is most often found in small case reports or case series, which are insufficient to determine the frequency as well as the signs, symptoms, and outcomes associated with this condition.

A team led by researchers at the Université d’Angers, in France, reviewed the medical records of 106 with ANCA-GN patients enrolled in the Maine-Anjou Registry, and diagnosed between January 2000 and January 2018. All patients had follow-up data covering at least six months.

Their study focused on patients with new-onset or relapsing AAV (whose disease came back), who also had glomerulonephritis at the time of diagnosis. People with both a CTD and AAV were compared to a control group consisting of people with AAV only.

Data showed that 16 out of these 106 patients had a CTD when diagnosed with ANCA-GN (15.1% of the patients). On average, the CTD diagnosis preceded the onset of AAV by seven years, and 10 of these patients were on steroids or immunosuppressive treatment by the time they were diagnosed with AAV.

The most common CTDs were rheumatoid arthritis (5 patients), systemic sclerosis and Sjögren’s syndrome (4 patients each), and polymyalgia rheumatic (3 patients).

More women were in the CTD group (75%), compared to AAV-only patients serving as controls (30% female).

Between groups, there were no differences in the type of AAV — microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) — nor in the kind of ANCA antibodies involved — anti-myeloperoxidase (MPO) or anti-proteinase 3 (PR3).

Induction therapy, the first part of AAV treatment and one aimed at controlling the the disease and inducing remission, relied predominantly on cyclophosphamide. About one third of the patients were given plasma exchange.

Biopsies revealed a comparable degree of kidney disease between groups, with an identical number of damaged glomeruli.

Those in the CTD group tended to experience relapses more frequently, but this difference was not significant. However, patients with CTD also had higher rates of non-renal relapses compared to the control group (25% vs. 7.7%), and to experience more venous thrombotic events (31.2% vs. 10%).

No significant differences in other major issues, like severe infections requiring hospitalization, cardiovascular events, cancers, or mortality, were found between the CTD and control groups.

With 15.1% of patients studied showing a CTD diagnosis overlapping with an ANCA-GN diagnosis, these dual conditions are not exceptionally rare or “uncommon,” the researchers wrote, noting that CTDs generally impacted women but do not seem to affect AAV clinical presentation and severity.

“The main finding of this study is that, despite a higher rate of non-renal AAV relapse and venous thrombosis, CTD patients seem to have a comparable prognosis according to a composite criterion, including major events (deaths, severe infections, cancer, cardiovascular events and thrombotic events),” researchers wrote.