The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation-a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan.

BACKGROUND: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus. METHODS: Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine's efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission. DISCUSSION: This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS. TRIAL REGISTRATION: ISRCTN: ISRCTN79334891. Registered 07 June 2021. EudraCT: 2018-001268-40. Registered 13 September 2019. CLINICALTRIALS: gov: NCT04316494. Registered 20 March 2020.

Hepatic and pulmonary involvement in a patient with PR3-ANCA vasculitis following SARS-CoV-2 vaccination: A case report.

We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.

A case of ANCA-associated vasculitis in a 16-year-old female following SARS-COV-2 infection and a systematic review of the literature.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare form of vasculitis in children. SARS-CoV-2, the virus that causes COVID-19 infection, seems to trigger autoimmunity and new-onset autoimmune disease in pediatric and adult patients. We present a case of new-onset AAV following COVID-19 infection in an adolescent patient, and we review the literature of AAV following COVID-19 infection. CASE PRESENTATION: An adolescent female with a history of asthma was diagnosed with mild COVID-19 infection and subsequently developed persistent cough, wheezing, hearing loss, arthralgias, and rash. Her imaging and laboratory workup showed pulmonary nodules and cavitary lesions, elevated inflammatory markers, negative infectious testing, and positive ANCA. She was treated with glucocorticoids, rituximab, and mycophenolate mofetil. At six-month follow-up, she had improvement in her symptoms, pulmonary function tests, imaging findings, and laboratory markers. CONCLUSIONS: We report the second case of new-onset anti-PR3, C-ANCA vasculitis and the fourth case of pediatric-onset AAV following COVID-19 infection. A systematic review of the literature found 6 cases of new-onset AAV in adults after COVID-19 infection. Pediatric and adult patients who develop AAV post COVID-19 infection have few, if any, comorbidities, and show marked radiographic and symptomatic improvement after treatment. There is increasing evidence for COVID-19-induced autoimmunity in children and our case highlights the importance of considering AAV in a child following a recent COVID-19 infection because timely treatment may improve clinical outcomes.

A Case Report of MPO-ANCA-Associated Vasculitis Following Heterologous mRNA1273 COVID-19 Booster Vaccination.

Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.

Antineutrophilic cytoplasmic antibody-associated vasculitis and the kidney.

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies that have emerged on the topic of ANCA-associated vasculitis with some historical context. The review also discusses how the adult data is relevant to pediatric patients. RECENT FINDINGS: Pediatric studies on AAV are lacking. Therapies targeted to the inflammatory cascade specifically implicated in AAV, such as MPO inhibitors and complement mediators, are emerging. The PEXIVAS study recently called into question the routine use of plasma exchange (PLEX) in severe AAV, with no difference in ESKD or mortality found between patients who did or did not receive PLEX. Longer maintenance duration of nearly 48 months is preferred as compared with shorter duration in patients who are not on dialysis because of higher relapse rates in children with AAV. SUMMARY: Current treatment in AAV includes corticosteroids, rituximab, and cyclophosphamide for induction. Maintenance therapy commonly consists of azathioprine or rituximab. Plasma exchange (PLEX) is no longer recommended for induction therapy for AAV but some experts still consider this as an option for patients who are not responding to therapy or have severe disease at presentation. However, emerging novel therapies may be on the horizon.

MPO-ANCA-positive Microscopic Polyangiitis Following COVID-19 Infection.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic disease that causes vasculitis in various organs. Although the cause of the onset is unknown, infection has been reported to be a causative factor. The subsequent cytokine storm triggered by the immune response against SARS-CoV-2 infection has been reported to lead to symptoms being more severe. We herein report our experience with the onset of AAV following COVID-19 infection. We also report the course of anti-SARS-CoV-2 serum antibody titers following induction therapy, which suggests that vaccination and education concerning standard precautions are necessary in patients who require immunosuppressive therapy, even after COVID-19 infection.

Case Report: ANCA-Associated Vasculitis Presenting With Rhabdomyolysis and Pauci-Immune Crescentic Glomerulonephritis After Pfizer-BioNTech COVID-19 mRNA Vaccination.

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.

A Transient Increase in the Serum ANCAs in Patients with SARS-CoV-2 Infection: A Signal of Subclinical Vasculitis or an Epiphenomenon with No Clinical Manifestations? A Pilot Study.

A relationship is emerging between SARS-CoV-2 infections and ANCA-associated vasculitis (AAV) because: (i) the pulmonary involvement of COVID-19 may mimic that observed in patients with AAV; (ii) the two diseases may occur together; (iii) COVID-19 may trigger AAV. However, few cases of AAV have been identified so far in COVID-19 patients. To define the frequency of ANCA autoimmunity in patients with SARS-CoV-2 infection, we analyzed the serum ANCAs and the serum PR3 and MPO antigens by immunoassays in 124 adult patients with a diagnosis of SARS-CoV-2 infection (16 were asymptomatic and 108 were hospitalized) and 48 control subjects. The serum ANCAs were significantly higher in the hospitalized patients compared with either the controls or the asymptomatic patients and increased with the progression of the COVID-19 severity. After one week of hospitalization, the values were significantly lower. In contrast, no differences emerged among the controls, asymptomatic and hospitalized patients for the PR3 and MPO serum levels. None of the patients had clinical signs of AAV with the exception of a severe pulmonary involvement. Further studies are necessary to define whether the increase in the serum ANCAs might mask subclinical vasculitis in a percentage of patients with SARS-CoV-2 infection or it is an epiphenomenon of SARS-CoV-2 infection with no clinical manifestations.

Pediatric P-ANCA vasculitis following COVID-19.

BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) are associated with a multisystem vasculitis affecting small blood vessels in the body. A handful of adult patients who developed vasculitis post-COVID-19 have been reported. Although SARS-CoV-2 has been shown to drive an exaggerated immune response in the pediatric population, such as in Multisystem Inflammatory Syndrome in Children (MIS-C), only one case of vasculitis following COVID-19 has been reported previously in children. CASE PRESENTATION: Seventeen-year-old male with a past medical history of COVID-19 pneumonia two months prior presented with acute kidney injury and diffuse alveolar hemorrhage. Rheumatologic workup revealed P-ANCA and Myeloperoxidase (MPO) positivity. Kidney biopsy showed necrotizing glomerulonephritis with limited immune complex deposition. Subsequently, he was treated with steroids and plasmapheresis, and ultimately started on cyclophosphamide. CONCLUSIONS: To our knowledge, this report presents the second reported pediatric case of P-ANCA/MPO vasculitis following COVID-19.

New onset ANCA-associated vasculitis in an adolescent during an acute COVID-19 infection: a case report.

BACKGROUND: SARS-CoV-2 has been found to be exquisitely adept at triggering autoimmunity and multiple new onset autoimmune diseases have been described as a post-infectious complication of COVID-19 infection in the adult population. Less has been described in the pediatric population, as infections are more likely to be asymptomatic and less severe. This case reports a previously healthy adolescent patient with new onset antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) diagnosed in the setting of acute COVID-19 infection. CASE PRESENTATION: A previously healthy adolescent male was diagnosed with COVID-19 pneumonia after presenting with infectious symptoms of fever, cough, congestion, and shortness of breath. After worsening of disease, he was found to have pulmonary nodules, atypical for COVID-19. Further imaging and laboratory workup showed elevated inflammatory markers, negative infectious testing, and positive antineutrophil cytoplasmic antibodies (ANCA) diagnostic for AAV. He was treated with pulse dose steroids followed by a prolonged taper and rituximab. Symptoms resolved and laboratory abnormalities improved over time. At six-month follow-up, lesions were much improved, laboratory markers were within normal limits, and patient remained asymptomatic off medications. CONCLUSIONS: This case is one of the first in the pediatric population to describe new onset AAV presenting with an acute, symptomatic COVID-19 infection. There is increasing evidence for COVID-19 induced autoimmunity in the pediatric population and pediatric care providers should be on high alert for new onset autoimmune disease in children afflicted by COVID-19.

ANCA-Associated Vasculitis Following Pfizer-BioNTech COVID-19 Vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world. As of the end of June 2021, there were approximately 181 million confirmed cases and more than 3.9 million deaths across the globe. The colossal impact of coronavirus disease 2019 (COVID-19) is driving the biggest vaccination campaign in human history. All 3 vaccines authorized for emergency use by the US Food and Drug Administration (Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson) have been thoroughly studied and found to be safe and effective in preventing severe COVID-19 cases. While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown. Rare side effects continue to surface as millions of people receive COVID-19 vaccines around the world, as compared with the thousands enrolled in the clinical trials. We report a case of new-onset renal-limited ANCA-associated vasculitis (AAV) in a 78-year-old woman with previously normal kidney function after receiving the Pfizer-BioNTech COVID-19 vaccine. The patient developed acute kidney injury with proteinuria and microscopic hematuria with many dysmorphic red blood cells in the urine. Anti-myeloperoxidase antibody titer was elevated. Kidney biopsy showed pauci-immune crescentic necrotizing glomerulonephritis. Kidney function improved after treatment with steroids and rituximab. Our patient had normal routine laboratory testing before the vaccination. Although this case cannot demonstrate a causal relationship between COVID-19 vaccination and AAV, ongoing surveillance for similar complications would be prudent as worldwide vaccination efforts continue.

ANCA associated glomerulonephritis in tuberculosis: a paradoxical reaction.

We present a case of antineutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis in the context of treatment of pulmonary tuberculosis (TB). A 42-year-old woman was treated for drug-susceptible pulmonary TB and represented with paradoxical worsening of symptoms and radiological features. She was HIV negative. A severe acute kidney injury with features of glomerulonephritis was evident on admission. Perinuclear ANCA and antimyeloperoxidase antibodies were present in serum and renal biopsy was consistent with ANCA-associated vasculitis. The patient was successfully treated with both antituberculous therapy and immunosuppression (corticosteroids and mycophenolate mofetil) with subsequent clinical improvement and amelioration of renal function. We propose this is the first case that describes the association between paradoxical reactions during TB treatment and ANCA-associated glomerulonephritis.

ANCA-associated vasculitis after COVID-19.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are systemic autoimmune diseases that may lead to renal failure due to the infiltration of mononuclear cells and the destruction of small- and medium-sized blood vessels. It has been shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger the presentation or exacerbation of autoimmune diseases. Crescentic glomerulonephritis (GN) has rarely been reported in patients with Coronavirus disease-2019 (COVID-19). We present rare two cases with AAV after a recent diagnosis of COVID-19. The first case was 26-year-old male patient, who was presented with acute kidney injury after COVID-19. Serum creatinine increased and active urine sediment was seen. Serological evaluation showed anti-myeloperoxidase antibody was at a level of 80.6 U/mL. Kidney biopsy showed necrotizing GN with cellular crescents. Methylprednisolone, cyclophosphamide and plasma exchange were administered. He was discharged with hemodialysis. Second case was a 36-year-old female who was hospitalized because of fever, cough and dyspnea. After she was diagnosed with COVID-19, she had total hearing loss, with cavitary lesions on bilateral lung parenchyma and an acute kidney injury. Serological evaluation showed an elevated anti-proteinase-3 with a level of 1:32. Kidney biopsy showed necrotizing GN with cellular crescents. Renal function improved after methylprednisolone and cyclophosphamide treatment. With a systematic review of the literature, we found four cases of new-onset AAV due to COVID-19. Herein, we discuss two cases and provide a literature review on cases of new-onset pauci-immune GN after COVID-19 infection.

Acute ANCA Vasculitis and Asymptomatic COVID-19.

We describe the presentation and diagnosis of a child with newly diagnosed antineutrophil cytoplasmic antibody-associated vasculitis and associated diffuse alveolar hemorrhage who was positive for coronavirus disease 2019 immunoglobulin G antibodies, indicative of a previous asymptomatic infection. Results of multiple polymerase chain reaction tests coinciding with the start of symptoms were negative, indicating that acute infection was not the cause of the patient's symptoms. Coronavirus disease 2019-induced autoimmune diseases have been described in adults, but this case report represents the first case described in a pediatric patient.