A Potential Alternative Therapy for MPO-ANCA Vasculitis with IVIG in a Patient with COVID-19
1Family Medicine Department, Rutgers Robert Wood Johnson, New Brunswick, New Jersey
2CentraState Medical Center, Freehold, New Jersey
Khan R, Zafar M, Leuzzi B. A potential alternative therapy for MPO-ANCA vasculitis with IVIG in a patient with COVID-19. Consultant. 2023;63(5):e2. doi:10.25270/con.2022.10.000001
Received April 21, 2022. Accepted August 5, 2022. Published online September 30, 2022.
The authors report no relevant financial relationships.
Resham Khan, MD, Rutgers Robert Wood Johnson, 125 Paterson Street, New Brunswick, NJ, 08901 (firstname.lastname@example.org)
A 76-year-old woman with a past medical history of duodenal ulcer perforation and repair in 2015 via ex-laparotomy, hypertension, stage IV chronic kidney disease, and gastroesophageal reflux disease was admitted for COVID-19 in the setting of acute kidney injury and was found to have myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) vasculitis and received a rare alternative treatment with intravenous immunoglobulin (IVIG) infusions.
The presenting patient is a 76-year-old woman with a history of duodenal ulcers status post perforation, subsequent repair via ex-laparotomy, multiple gastrointestinal bleeds, chronic anemia, and chronic kidney disease stage IV. The patient’s underlying cause of chronic kidney disease is severe anemia with underlying glomerulonephritis. She was admitted to the emergency department (ED) for cough, fever, and generalized weakness with right lower lobe infiltration seen on chest radiograph. Her COVID-19 polymerase chain reaction (PCR) test came back positive. Several weeks prior to this, the patient had undergone a renal biopsy due to worsening renal function with no clear etiology. After the renal biopsy, the patient began using chronic oral steroids for trial purposes while her biopsy results were pending.
The patient’s baseline creatinine level prior to admission was noted to be 1.9-2.0 mg/dL. On the day of admission, the patient was noted to have a creatinine level of 2.7 mg/dL, blood urea nitrogen test (BUN) level of 76 mg/dL, and glomerular filtration rate (GFR) of 17 ml/min, which only slightly improved the next day. On the second day following admission, the patient’s creatinine jumped to 3.1 mg/dL, BUN of 82 mg/dL, and GFR of 15 ml/min. Additional labs revealed the patient had positive anti-nuclear antibody (ANA) with ANA titers of 1:640 and a homogenous pattern. The patient’s C3/C4 complements and double-stranded DNA were within normal limits. Her myeloperoxidase antibody returned and was elevated at 31.9 AI. Urinalysis demonstrated proteinuria and microscopic hematuria. The next day, the patient’s renal biopsy results showed “focal crescentic MPO ANCA vasculitis with mild interstitial fibrosis”. The patient underwent abdomen and pelvis computed tomography scans, the results of which showed that her “kidneys are normal in appearance except for bilateral round low densities consistent with cysts, including a 4+ cm cyst anterior in the left lower pole.”
The standard treatment for this patient would have been cyclophosphamide or rituximab, but considering the patient’s current COVID-19 infection and the fear of immunosuppression, we focused on alternative treatment options.6 Given that there have been some studies suggesting IVIG as an alternative treatment for ANCA-vasculitis, a five-dose IVIG regimen was trialed in correspondence with Nephrology, Rheumatology and Hematology/Oncology teams. We administered 0.4 mg/kg per dose. Based on prior retrospective studies, this treatment was expected to stabilize the patient’s renal function for at least 3 months.1,2 During this hospitalization, the patient received five total doses of IVIG daily along with oral prednisone 40mg daily. Immediately after receiving the first infusion of IVIG, the patient’s creatinine improved, decreasing from 3.1 mg/dL to 2.9 mg/dL to 2.2 mg/dL in the span of 4 days. Subsequent visits in the outpatient setting and hospital demonstrated that the patient’s creatinine had stabilized in the range of 1.8-2.2 mg/dL. The next month, when myeloperoxidase antibodies were drawn, they had decreased from 31.9 AI the month prior to 5.9 AI.
Of note, the patient had received a 200 mg IV loading dose of remdisivir once followed by 100 mg IV daily for 4 days, making a total of 5-day course of the treatment. The patient was not vaccinated against COVID-19 given her immunocompromised state.
Myeloperoxidase ANCA-associated vasculitis is a small vessel vasculitis, characterized by multisystem inflammation, affecting multiorgan systems including the kidneys.5,6 Collections of lymphocytes, monocytes, and macrophages can form granulomas.5,6Additionally, the development of autoantibodies to neutrophil-derived myeloperoxidase suggests an autoimmune component to the pathogenesis of this disease.1,2,5 While the use of cyclophosphamides and steroids have been effective, there are studies that show up to 50% of patients can relapse within 2 years if therapy is not sustained.5,6 With sustained therapy, there are potential adverse effects of long-term immunosuppressive therapy including but not limited to, cardiovascular dysfunction, decreased immunity and increased susceptibility to infections, reduced fertility or infertility, bladder/kidney damage, and ocular damage.4 Research supports IVIG binding to ANCA, prohibiting it from binding to its antigen.1,2,5,6,7 Further evidence shows IVIG has the potential in inhibiting the ANCA-antigen induced activation of the immune system.6 IVIG does not suppress the immune system.1,2,8
While immunosuppressive and cyclophosphamide therapy is the standard therapy for ANCA-vasculitis, there have only been a few studies suggesting IVIG as an alternative treatment option.1,2,4,5 Given our patient’s positive results with IVIG of halting the progression of worsening renal function, we believe this case is clinically relevant and provides further evidence supporting the use of IVIG as an alternative therapy for ANCA-vasculitis.4
Still, there have been a few rare cases reported of patients developing ANCA-vasculitis after a recent diagnosis of COVID-19 infection as it has been seen to trigger autoimmune disease.3 Indeed, our patient had an active COVID-19 infection in conjunction with worsening renal function secondary to ANCA-vasculitis. If Rituximab was administered, there would have been B-cell depletion causing interruption in humoral immunity in the setting of COVID-19. Furthermore, if another standard therapy such as cyclophosphamide was used, this could have potentially been fatal during an active COVID-19 infection.6 Therefore, since immunosuppressive therapy could not be used, we started IVIG infusions, which halted the worsening of her renal assisting in treating the patient’s ANCA-vasculitis.
Since being treated with five infusions of IVIG, the patient’s renal function has stabilized. Evidenced by subsequent hospital visits and outpatient visits, it is noted that the patient’s renal function has stabilized with a baseline creatinine of 2.2-2.5 ml/dL. The patient has not received any other therapy for ANCA-vasculitis, and so we can attribute this stabilization to IVIG infusions.4 During subsequent visits, the patient has declined further treatment with the standard therapy of rituximab for fear of immunosuppression.
A potential disadvantage of using IVIG infusions for the treatment of ANCA-vasculitis is the potential relapsing of symptoms. Given the limited used of IVIG in ANCA-vasculitis, there is not enough definitive data showing that patients may not be affected by ANCA-vasculitis in the future. To evaluate this, the continuous outpatient follow-up for patients after receiving IVIG treatments to check renal function, symptoms, and other lab work is of utmost significance to ensure no worsening of any organ system due to the ANCA-vasculitis.
Given the limited evidence of IVIG being a successful alternative therapy for ANCA-vasculitis, this case is an important example of IVIG preventing a patient from worsening renal function during an active COVID-19 infection.
- Carvalho, J. Intravenous immunoglobulin quickly lowers disease activity in AAV patients, review study finds. ANCA Vasculitis News. Published August 20, 2019. Accessed April 14, 2022. https://ancavasculitisnews.com/2019/08/20/intravenous-immunoglobulin-ivig-therapy-quickly-lowers-disease-activity-in-aav-study-says/
- Crickx E, Machelart I, Lazaro E, et al. Intravenous immunoglobulin as an immunomodulating agent in antineutrophil cytoplasmic antibody-associated vasculitides: A French nationwide study of ninety-two patients. Arthritis Rheumatol. 2016;68(3):702-712. doi:10.1002/art.39472
- Duran T, Turkmen E, Dilek M, Sayarlioglu H, Arik N. ANCA-associated vasculitis after COVID-19. Rheumatol Int. 2021;41:1523-1529. doi:10.1007/s00296-021-04914-3
- Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin therapy. Front Immunol. Published online June 8, 2018. Accessed April 14, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008653/
- Muso E, Ito-Ihara T, Ono T, et al. Intravenous immunoglobulin (IVIg) therapy in MPO-ANCA related polyangiitis with rapidly progressive glomerulonephritis in Japan. J Infect Dis. Accessed April 14, 2022. https://www.niid.go.jp/niid/images/JJID/57/S17.pdf
- Ito-Ihara T. Ono T, Nogaki F, et al. Clinical efficacy of intravenous immunoglobulin for patients with MPO-ANCA-associated rapidly progressive glomerulonephritis. Nephron Clin Pract. 2006;102:35-42. doi:10.1159/000088313
- Jayne DRW, Chapel H, Adu D, et al. Intravenous immunoglobulin for anca‐associated systemic vasculitis with persistent disease activity. QJM. 2000;93(7):433-439. doi:10.1093/qjmed/93.7.433
- Pego PM, Câmara IA, Andrade JP, Costa JM. Intravenous immunoglobulin therapy in vasculitic ulcers: a case of polyarteritis nodosa. Autoimmun Highlights. 2013;9:95-99. https://autoimmunhighlights.biomedcentral.com/articles/10.1007/s13317-013-0048-5
- What is the role for intravenous immunoglobulin in treating vasculitis? Vasculitis Foundation. Published online December 1, 2012. Accessed April 14, 2022. https://www.vasculitisfoundation.org/mcm_faq/what-is-the-role-for-intravenous-immunoglobulin-in-treating-vasculitis/