Treatment advances have drastically improved survival rates among individuals with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in the past decade.1 However, these patients remain susceptible to a wide range of intersecting comorbidities that can greatly affect their functioning, quality of life, and mortality.1
“Some of these comorbidities are related to damage from the disease itself, like renal impairment, while other comorbidities are the result of therapies used to treat vasculitis,” explained Lindsay S. Lally, MD, rheumatologist at Hospital for Special Surgery in New York, New York. “High doses and prolonged use of glucocorticoids are particularly associated with development of high blood pressure, diabetes, and osteoporosis.”2
Daniel G. Arkfeld, MD, associate professor of clinical medicine at Keck School of Medicine at the University of Southern California in Los Angeles, added that the use of nonsteroidal anti-inflammatory drugs (NSAIDS) to reduce inflammation can lead to worse outcomes in kidney failure associated with AAV.
Complications Affect a Wide Range of Organ Systems
A search of the literature reveals various complications affecting a range of organ systems in patients with AAV.
A 2022 study detected pulmonary involvement in 50.9% of patients with newly diagnosed AAV,3 and other research has shown increased rates of cardiovascular disease in AAV. A population-based cohort study published in 2022 demonstrated a higher risk of stroke (7.0% vs 5.2%), atrial fibrillation (16.4% vs 11.5%), and congestive heart failure (20.8% vs 13.3%) in patients with AAV compared to those without AAV, and this risk was especially pronounced in the period shortly following AAV diagnosis.4
In a systematic review published in 2021, Mercuzot et al examined 103 articles published in MEDLINE over approximately 20 years and found an elevated risk of cardiovascular disease—especially coronary artery disease and thromboembolic events—in patients with AAV, as well as an increased risk of bronchiectasis, thyroid disease, and anxiety. In addition, the review showed that reductions in mental and physical components of health-related quality of life were associated with mood disorders, sleep impairment, fatigue, and unemployment.1
Patients with AAV may also experience dermatologic, neurologic, and infectious complications.5-7 As noted in a 2023 study, infections represent the top cause of death in the first year following AAV diagnosis and are a major ongoing contributor to mortality in this population.7
Prevalence rates of certain comorbidities may vary by AAV type. For example, one study of patients with AAV identified bronchiectasis in nearly 40% of patients, and all of these patients had anti-myeloperoxidase (anti-MPO) ANCA, which is typically associated with microscopic polyangiitis (MPA).8
Read more about the types of AAV
In other research, roughly 35% of patients with AAV presented with cutaneous manifestations, with a higher prevalence among patients with eosinophilic granulomatosis with polyangiitis (EGPA) compared to those with granulomatosis with polyangiitis (GPA) or MPA.5
Findings reported in 2021 revealed that central nervous system involvement was most common in patients with GPA (78%) compared to EGPA (19%) and MPA (2%), while peripheral nervous system involvement was most common among patients with EGPA (51%) compared to GPA (40%) and MPA (8.8%).6
Many of the comorbidities in AAV often overlap, as found in a 2023 study showing higher rates of cardiovascular events in AAV patients with pulmonary (HR, 1.50; 95% CI, 1.09-2.06) and kidney (HR, 3.02; 95% CI, 2.08-4.37) involvement.9 In a group of patients with both rheumatoid arthritis and AAV, the most commonly involved extra-articular organs were the kidneys (74.5%), lungs (51.1%), and skin (8.5%).10
Comorbidities Increase Importance of Early Diagnosis
These findings on comorbidities in AAV reinforce the importance of early diagnosis to minimize worsening of the disease and further damage to organ systems affected by AAV. “Close monitoring of patients during their treatment journey is critical to mitigate development of comorbidities, and this starts at diagnosis,” Dr. Lally said.
“Initial management of AAV is about inducing remission, and then in the long run, we have to deal with many areas affecting quality of life,” Dr. Arkfeld explained.
Taking steps to limit the use of steroids is among the most critical measures needed to reduce treatment-related comorbidities. Although steroids are needed acutely, they should be tapered as soon as possible, he advised. “This is very important, as steroids can cause weight gain, diabetes, stomach ulcers, steroid myopathy, and other effects.”
To that end, Dr. Lally noted there has been a shift in recent years toward efforts to decrease steroid exposure among patients with AAV.2 Providers may also “prescribe additional medications to reduce the risk of developing treatment-related comorbidities—for example, medications to protect from fracture or help reduce the risk of stomach ulcers” associated with steroid use.
Expertise Needed From Multidisciplinary Specialist Team
The management of comorbidities in AAV requires a multidisciplinary approach involving numerous specialists, such as renal specialists to address kidney involvement and pulmonologists to treat pulmonary necrotic lesions, according to Dr. Arkfeld. However, he said, “Rheumatology is the subspecialty that understands the systemic nature of AAV and should be managing the majority of these patients.”
Dr. Lally agrees: “While multidisciplinary care is important, rheumatologists have to play quarterback in identifying and managing these issues without just referring patients out to multiple other specialists,” she stated. “Being aware of comorbidities and making time during—and between—visits to address patient concerns is critical.”
In cases of severe disease resulting in damage to organs such as the kidneys, patients may experience depression and medical grief, Dr. Arkfeld added. For these patients, it is important to connect them to mental health resources including psychotherapists and support groups.
“At Keck, we often also employ our occupational therapists, who deal with many topics affecting quality of life in AAV patients and how to cope with these issues,” he said.
Much Work on AAV Remains
Among the areas requiring further research in AAV, Dr. Arkfeld cites the need to increase rates of early diagnosis, improve the accuracy of ANCA testing, develop new tests to identify ANCA-negative syndromes, and continue basic science research aimed at better understanding ANCA generation to inform new targets for treatment.
“We have made great strides in the treatment of AAV, and we now have treatment regimens that can effectively get the vast majority of our patients into remission,” Dr. Lally said. “The goal now has to be to minimize the toxicity of these therapies, which I do think starts with reduction of reliance on steroids.”
The approval of avacopan (Tavneos®), a novel agent for the treatment of AAV, by the US Food and Drug Administration in October 2021 represents a significant advancement towards this goal.11,12
“I think it’s also important to focus on the whole patient and recognize that disease remission does not translate to good quality of life, physically or emotionally,” she advised. “Understanding the impact of AAV diagnosis and treatments on our patients and working to optimize their quality-of-life outcomes is critical for doctors who work with this patient population.”
- Mercuzot C, Letertre S, Daien CI, et al. Comorbidities and health-related quality of life in patients with Antineutrophil Cytoplasmic Antibody (ANCA) – associated vasculitis. Autoimmun Rev. 2021;20(1):102708. doi:10.1016/j.autrev.2020.102708
- Floyd L, Morris A, Joshi M, Dhaygude A. Glucocorticoid therapy in ANCA vasculitis: using the Glucocorticoid Toxicity Index as an outcome measure. Kidney360. 2021;2(6):1002-1010. doi:10.34067/KID.0000502021
- Zhou P, Li Z, Gao L, et al. Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients. BMC Pulm Med. 2022;22(1):35. doi:10.1186/s12890-022-01829-y
- Massicotte-Azarniouch D, Petrcich W, Walsh M, et al. Association of anti-neutrophil cytoplasmic antibody-associated vasculitis and cardiovascular events: a population-based cohort study. Clin Kidney J. 2021;15(4):681-692. doi:10.1093/ckj/sfab229
- Abdel-Halim M, Mahmoud A, Ragab G. Cutaneous manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis. Vessel Plus. 2022;6:8. doi:10.20517/2574-1209.2021.40
- Hajj-Ali R, Butler R, Langford C, et al. Neurologic involvement in ANCA-associated vasculitis: data from multicenter longitudinal observational study. Arthritis Rheumatol. 2021; 73(suppl 9).
- Odler B, Riedl R, Gauckler P, et al; RAVE−ITN Research Group. Risk factors for serious infections in ANCA-associated vasculitis. Ann Rheum Dis. 2023;82(5):681-687. doi:10.1136/ard-2022-223401
- Néel A, Espitia-Thibault A, Arrigoni PP, et al. Bronchiectasis is highly prevalent in anti-MPO ANCA-associated vasculitis and is associated with a distinct disease presentation. Semin Arthritis Rheum. 2018;48(1):70-76. doi:10.1016/j.semarthrit.2017.12.002
- Moiseev S, Bulanov N, Crnogorac M, et al. Traditional and disease specific risk factors for cardiovascular events in ANCA-associated vasculitis: a multinational retrospective study. J Rheumatol. Published online January 15, 2023. doi:10.3899/jrheum.220851
- Wu H, Lu Y, Hu R, et al. Anti-neutrophil cytoplasmic antibody associated vasculitis in patients with rheumatoid arthritis. BMC Nephrol. 2022;23(1):155. doi:10.1186/s12882-022-02788-6
- US Food and Drug Administration. FDA approves add-on drug for adults with rare form of blood vessel inflammation. Published October 13, 2021. Accessed April 30, 2023.
- Soulsby WD. Journal club review of “avacopan for the treatment of ANCA-associated vasculitis”. ACR Open Rheumatol. 2022;4(7):558-561. doi:10.1002/acr2.11412