Positive Vasculitis Research Articles

A case of systemic lupus erythematosus with antineutrophil cytoplasmic antibodies, positive skin vasculitis, and concomitant combined thrombophilia.

A case of systemic lupus erythematosus with antineutrophil cytoplasmic antibodies, positive skin vasculitis, and concomitant combined thrombophilia.

Co-occurrence of Crescentic IgA Nephropathy and Borderline Positive ANCA-Associated Vasculitis: A Perilous Pairing!

Co-occurrence of Crescentic IgA Nephropathy and Borderline Positive ANCA-Associated Vasculitis: A Perilous Pairing!

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

A Rare Case of Double-antibody-positive Renal Vasculitis: Are we in a Hurry to Start Tuberculosis Medicines?

Double antibody positive renal vasculitis (anti GBM antibody and pANCA) is a rare form of small vessel vasculitis associated with poor outcome. It is difficult to decide which antibody is the precursor in these cases. We report here such a rare case of double antibody positive renal vasculitis which was started on anti tubercular medicine for a positive mantoux test and interferon gamma release assay. The possible reasons for these antibodies in this may be a complication of COVID-19 infection or vaccine, adverse drug effect of antitubercular medicines or a paradoxical reaction during the tuberculosis treatment. The patient could not survive beyond two months of diagnosis because of rapidly declining renal functions. This case highlights the importance of a meticulous clinical approach, supports two week tuberculosis medicines trial and an early and careful dealing of non responders during tuberculosis treatment especially in patients whose diagnosis is not microbiologically confirmed.

Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first β-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30days (n = 358, 55.68%). However, AEs were still possible after 1year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

#4600 MPO AND PR3 DUAL POSITIVE ANCA AND ANA: A CASE REPORT

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis has been thought to be a relatively rare disease, although it has been increasing in incidence recently likely due to improved testing and recognition. One of two main antigens are targeted in this condition, either proteinase 3 (PR3) or myeloperoxidase (MPO). Uncommonly, both antigens can be targeted in specific situations such as during levisamole use, propylthiouracil use, hydralazine use or infections. Herein, we illustrate a case of a patient who presented with progressively worsening kidney function in the setting of recent COVID booster. Method A 79 year old female with a history of hypertension, hyperlipidemia, acid reflux and hypothyroidism was admitted to our facility from her outpatient nephrologist due to abnormal labs. This was the first time the patient had seen a nephrologist, although she was told that her serum creatinine (SCr) was elevated to ∼3 mg/dL three months earlier. At that time, she noted blood tinged urine as well as frothiness of urine that had since resolved. She also endorsed a raised erythematous rash that also resolved. She did mention that she had increasing fatigue over the past week prior to presentation along with weight loss over the past few months. She denied ear pain, sinus pain, epistaxis, hemoptysis or specific joint pain. She denied any kidney stones or NSAID use. She was a former smoker, having quit decades ago. She denied any current tobacco or illicit drug use, including cocaine as well as any herbal supplements or medications that were not otherwise prescribed to her by a medical provider. She did note recent COVID booster prior to being told of a SCr ∼3 mg/dL. She had a repeat kidney function test one month prior to presentation, at which time she was told her SCr was 5 mg/dL. In our Emergency Department, SCr was elevated to 8.45 mg/dL with a BUN of 68 mg/dL. Computed tomography of the abdomen and pelvis ruled out any hydronephrosis or kidney stones. Urinalysis was revealing for 509 RBCs, 39 WBCs, WBC casts as well as granular casts. Spot urine protein to creatinine ratio was found to be elevated at 6925 mg/g. Serologies were pertinent for a positive ANA as well as ANCA. Interestingly, both MPO and PR3 titres were elevated at 72 AU/mL and 391 AU/mL, respectively. Kidney biopsy was performed and revealed a pauci-immune glomerulonephritis with crescents along with mixed interstitial inflammatory infiltrate (Figure 1). The diagnosis of dual positive ANCA glomerulonephritis was made. Computed tomography of the chest revealed scattered ground glass opacities and subpleural nodules which was consistent with a vasculitis. She started treatment with Rituximab and steroids on Day 5 of hospitalization. Results Although evidence linking ANCA vasculitis to COVID infection and vaccine has been starting to develop, the association with dual positive ANCA is something that has been elusive. Having titres for both MPO and PR3 ANCA is uncommon and has traditionally been attributed to very few causes; as COVID infection and vaccination has been a fairly recent development, this has not historically been considered a cause to think of in such patients. In the case presentation above, our patient had no other identifiable risk factors for presenting with a dual positive ANCA vasculitis. She did endorse recent booster vaccination which was subsequently followed by elevated SCr and positive serologies. Conclusion Dual positive ANCA vasculitis is an uncommon finding and should trigger a high clinical suspicion for implicated drugs, infections as well as COVID vaccination.

E021 A rare case of coexistence of ANCA-associated vasculitis and malignancy

Abstract Background/Aims A 65-year-old man, with a background of COPD, peripheral vascular disease and a neurostimulator in situ for chronic back pain, presented with a range of symptoms initially treated as lower respiratory tract infection in the community. He complained of bitemporal headache, jaw-pain, transient visual loss and had raised inflammatory markers (CRP 157 and ESR 105). He was subsequently treated as giant cell arteritis with 60mg prednisolone daily despite equivocal temporal artery ultrasound. He continued to have drenching sweats, arthralgia, epistaxis, shortness of breath and haemoptysis although inflammatory markers had normalised. Immunology revealed a strongly positive anti-PR3 antibody at > 8 units suggestive of granulomatosis polyangiitis. There was no convincing end organ evidence of vasculitis. CT-chest identified nodules and non-specific inflammatory changes but no cavitation or pulmonary haemorrhage. He was intolerant of steroids with significant insomnia and mood changes therefore they were rapidly tapered to 20mg daily. Methods He was readmitted to hospital on 20mg prednisolone with acute abdominal pain. CT abdomen-pelvis showed a lesion at the hepatic flexure suspicious for colon cancer, and this was confirmed on colonoscopy and biopsy. PET-CT at this time showed no evidence for active large vessel vasculitis. His prednisolone was tapered further and omitted prior to right hemicolectomy. Histology revealed definitive adenocarcinoma along with a focus of necrotising vasculitis and granulomas in the subserosa close to the tumour, with a distant granulomatous lesion at the resected appendix. He developed post-operative ileus and desaturated leading to a CTPA which did not show PE but identified progressive enlargement of the pulmonary nodules reported as suspicious of metastases. Throughout this time PR3 remained elevated and repeat PET-CT off steroids showed increased uptake at the aorta and right common iliac artery suggestive of active vasculitis. The FDG uptake and rate of enlargement of the pulmonary nodules was felt to be out of keeping with metastases and an inflammatory cause was suspected. Results Episodic pyrexia continued with no identifiable infective source and so a decision to commence oral prednisolone 40 mg was made. Repeat PET-CT 4 weeks later showed complete resolution of the inflammation in the aorta and right common iliac and reduction in size of the lung nodules. Unfortunately, the patient developed acute pancreatitis on steroids, so the prednisolone was reduced to 20mg with a view to induction therapy with cyclophosphamide. Conclusion This case highlighted multiple diagnostic challenges with clinical features of large vessel involvement in a patient with a positive ANCA and concomitant occult malignancy. Co-existence of a vasculitis and a neoplastic disease is rare. ANCA positive vasculitis is most commonly reported with haematological malignancies but less so in solid tumours, presenting as a paraneoplastic phenomenon. This case also highlighted the challenges in management when both conditions co-exist. Disclosure S. Ahmed: None. E. Pathan: None. P. Brown: None. J. Heaney: None. A. Pratt: None.

Association of HLA-class II alleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population.

Disease relapse remains a major problem in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations, HLA-DPB1*04:01 is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association between HLA-DRB1*09:01 and DQB1*03:03 with susceptibility to, and DRB1*13:02 with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association of DQA1*03:02, which is in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whether HLA-class II is associated with the risk of relapse in MPO-AAV. First, the association of HLA-DQA1*03:02 with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reported DRB1*09:01 and DQB1*03:03 were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (Puncorr) were corrected for multiple comparisons in each analysis using the false discovery rate method. The association of DQA1*03:02 with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: Puncorr=5.8x10-7, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40-2.16, MPA: Puncorr=1.1x10-5, OR 1.71, 95%CI 1.34-2.17). DQA1*03:02 was in strong linkage disequilibrium with DRB1*09:01 and DQB1*03:03, and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers of DRB1*09:01 (Puncorr=0.049, Q=0.42, hazard ratio [HR]:1.87), DQA1*03:02 (Puncorr=0.020, Q=0.22, HR:2.11) and DQB1*03:03 (Puncorr=0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DRβ1 (HLA-DRβ1_13S), including DRB1*13:02 carriers, showed longer relapse-free survival with nominal significance (Puncorr=0.010, Q=0.42, HR:0.31). By combining DQA1*03:02 and HLA-DRβ1_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (Puncorr=0.0055, Q=0.033, HR:4.02). HLA-class II is associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population.

Relapse of P-ANCA Positive Vasculitis with Pulmonary Hemorrhage in Hemodialysis Patient. Therapeutic Challenge

ANCA-Associated Vasculitis (AAV) is a multisystem small vessel disease with a high rate of morbidity (including renal failure and pulmonary involvement) and mortality

Severe eosinophilic granulomatosis with polyangiitis responding to a combination of rituximab and mepolizumab.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is a multisystem antineutrophil cytoplasmic antibody (ANCA) positive vasculitis, characterized by the presence of chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Although the most commonly involved organ is the lung, followed by the skin, EGPA can affect any organ system. Herein, we present the complicated case of an 18-year-old male patient with severe life-threatening EGPA, with central nervous system, cardiac and gasterointestinal involvement, which was resistant to initial treatment with glucocorticoids and cyclophosphamide. The patient responded well, achieving complete remission after the addition of rituximab and mepolizumab to glucocorticoids and cyclophosphamide.

Pulmonary renal syndrome: a clinical review.

The term "pulmonary renal syndrome" describes a clinical syndrome which is characterised by the presence of both diffuse alveolar haemorrhage and glomerulonephritis. It encompasses a group of diseases with distinctive clinical and radiological manifestations, as well as different pathophysiological processes. The most common diseases implicated are anti-neutrophil cytoplasm antibodies (ANCA)-positive small vessel vasculitis and anti-glomerular basement membrane (anti-GBM) disease. Prompt recognition is required as respiratory failure and end-stage renal failure can rapidly occur. Treatment includes a combination of glucocorticoids, immunosuppression, plasmapheresis and supportive measures. The use of targeted treatments has significantly reduced mortality. Thus, an understanding of pulmonary renal syndrome is essential for the respiratory physician.

A rare case of infliximab induced myeloperoxidase-cytoplasmic antineutrophil cytoplasmic autoantibody positive cutaneous vasculitis

<p>Drug-induced cutaneous vasculitis is a known autoimmune complication of tumor necrosis factor (TNF) inhibitors with many instances resulting in the production of newly formed antibodies. We report a 21-year-old female with a past medical history of Crohn’s disease controlled with infliximab who presented to dermatology with a purpuric rash and crusted plaques of her distal lower extremities. Biopsy of a lesion revealed perivascular lymphocytes, neutrophils and eosinophils, vessel wall damage, and dermal eosinophils consistent with a drug-induced vasculitis. Follow up labs assessing for antibodies revealed unusual findings of an elevated cytoplasmic-antineutrophil cytoplasmic autoantibody (C-ANCA) titer and myeloperoxidase (MPO) antibody level making this patient MPO-C-ANCA positive. The patient’s lesions were treated with both oral and topical steroids, colchicine, and transition of her infliximab to ustekinumab with subsequent improvement of her lesions and normalization of antibody titers.</p>

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

PULMONARY LIMITED SERONEGATIVE GRANULOMATOSIS WITH POLYANGIITIS VASCULITIS

A rare case report of granulomatosis with polyangiitis presenting with thrombus of the ascending aorta

Granulomatosis with polyangiitis (GPA) is a rare multisystem autoimmune antineutrophil cytoplasmic antibodies (ANCA) positive vasculitis that, in rare cases, can affect the aorta causing aortitis, aneurysm and rupture. A 50-year-old man presented with acute onset central chest pain, vomiting and

MO478: The Epidemiology of Anca-Associated Vasculitis at a Single Centre Over Two Decades

Abstract BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) refers to a group of conditions in which the end result is systemic injury of small blood vessels, resulting in damage to distinct organ systems including the lung, kidneys, ear, nose and throat. A characteristic, although not exclusive feature, is the development of anti-neutrophil cytoplasmic antibodies (ANCA) against specific proteins within the neutrophil-leucocyte proteinase 3 (PR3) and myeloperoxidase (MPO). The incidence varies according to geographic location but is ∼20 cases/million/year. The age of onset is usually between 45–75 years old, with a male: female ratio of 1:1. Without treatment, it is life-threatening; the aim of treatment is to induce remission with a strong immunosuppressive induction regimen followed by a maintenance phase. The risk of relapse remains. Here, we assessed the epidemiology of AAV >2 decades at our centre (Salford Royal Hospital, UK) with particular reference to severity of disease at presentation, ANCA positivity and outcomes. METHOD Patients with a diagnosis of AAV (either granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA)) were identified from our database between January 2000 and December 2021 (see Figure 1). Diagnosis was based on clinical features, ANCA result and kidney biopsy findings. A total of 47 were excluded and demographic data, co-morbidities, laboratory values (including baseline creatinine, eGFR, proteinuria, ANCA positivity), treatment given and outcomes were collected in the remaining sample. Analysis determined (i) basic demographic description of our cohort, (ii) median baseline creatinine, eGFR and proteinuria, (iii) those with an initial requirement for renal replacement therapy (RRT) at presentation, (iv) ANCA positivity rates and (v) outcomes including progression to RRT and mortality. RESULTS The evaluable cohort totalled 369 patients (see Table 1). Of these, 194 were male (52.6%), and the median age at presentation was 73 (IQR 60–82) years; 91.9% were Caucasian. Median baseline creatinine was 165 µmol/L (93–338), eGFR 33 mL/min/1.73 m2 (15–66) and proteinuria 98 g/mol (25–258). ANCA was measured in 363 (98.4%), of which c-ANCA and or PR3 positivity was seen in 142 (39.1%), and p-ANCA and or MPO positivity was seen in 148 (40.8%). In a small number, atypical ANCA was seen (1.9%) or ANCA was obscured by anti-nuclear factor (ANF) (2.8%). An immediate requirement for RRT at presentation was seen in 26 (7%). Progression to RRT at any time point over the follow up period was observed in 86 (23.3%), with the first RRT modality being haemodialysis in 64 (17.3%), peritoneal dialysis in 20 (5.4%) and transplant in 2 (0.5%). A total of 147 patients (39.8%) died over the follow-up period. A combined outcome of progression to RRT or death was seen in 191 (51.8%). CONCLUSION We show that patients present with AAV at an advanced age and with significant renal involvement (median baseline eGFR of 33 mL/min/1.73 m2 in our study). The distribution of PR3 and MPO positive vasculitis is similar, although there were a significant number of ANCA negative patients in our cohort. There were differences in concordance between c-ANCA and PR3 positivity, along with p-ANCA and MPO positivity, which may be explained by historical differences in testing. There remains a significant risk of progression to the requirement for RRT or death: 51.8% observed over our follow-up period of two decades.

Silica and Connective Tissue Disorders: The Important Role of the Dermatologist

Dermatological manifestations of connective tissue diseases (CTDs) are common and frequently precede other symptoms. Thus, dermatologists may be the first clinicians to diagnose these disorders. Silica exposure is an acknowledged cause of several CTDs, but this is under-appreciated by clinicians, who may also be unaware of the wide range of jobs in which silica exposure can occur. The CTDs associated with silica exposure include systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis and overlap syndromes. Silica-related systemic sclerosis (Si-SSc) is associated with a specific antibody profile and more severe disease. Silicosis has re-emerged worldwide recently due to several new workplace exposures, including a new type of silicosis (artificial stone (AS) silicosis), which is associated with a particularly high rate of auto-antibody formation. Dangerous work practices are still occurring. This article summarises recent literature on the topic of the resurgence of silicosis and silica-induced CTDs and reminds dermatologists of the importance of taking a thorough occupational history in all patients. Early intervention in CTDs and reduction in dust exposure can reduce risk and improve prognosis. Treatment options are rapidly improving.

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

Can propylthiouracil induce autoimmune-related immunotoxicity?

Introduction. The use of propylthiouracil can be associated with mild adverse reactions, but severe complications such as agranulocytosis and vasculitis can also be seen. Direct toxicity and immune-mediated induction of anti-neutrophile cytoplasmic antibodies have been described as possible mechanisms responsible for agranulocytosis. The majority of vasculitis is antimyeloperoxidase antibodies associated, but the exact mechanism for anti-neutrophile cytoplasmic antibodies-associated vasculitis as an adverse effect of propylthiouracil treatment is still unclear. Case report. We presented a 61-year-old female patient with Graves? disease who experienced a fever and throat pain two weeks after propylthiouracil therapy was initiated. Agranulocytosis alongside basal left-sided pneumonia was noted. Propylthiouracil was discontinued, and the treatment with broad-spectrum antibiotics was started, as well as Lugol?s solution, methylprednisolone, and granulocyte-colony stimulating factor. Further course of treatment was complicated by the occurrence of a generalized erythematous-papillomatous rash. The patient was diagnosed with agranulocytosis and antimyeloperoxidase, anti-neutrophile cytoplasmic antibodies positive vasculitis as an adverse effect of propylthiouracil. Conclusion. Patients presenting with concomitant agranulocytosis and anti-neutrophile cytoplasmic antibodies-associated vasculitis as a complication of propylthiouracil therapy for Graves? disease are rare in clinical practice. Prompt discontinuation of the antithyroid drug is of great importance to reduce damage to target organs. Similarities in the pathogenesis of both conditions could be the potential explanation for these two adverse events occurring at the same time, which points out the need for a deeper understanding of this topic.

Herpes Zoster Precipitating First Attack of Neuromyelitis Optica along with Perinuclear Anti-Neutrophilic Cytoplasmic Antibody Positive Vasculitis.

Herpes Zoster Precipitating First Attack of Neuromyelitis Optica along with Perinuclear Anti-Neutrophilic Cytoplasmic Antibody Positive Vasculitis.

Compromiso gastrointestinal inusual en paciente pediátrico con vasculitis asociada a anticuerpos anticitoplasma de neutrófilos. Reporte de un caso

Vasculitis is characterized by presenting inflammation of the wall of blood vessels, one type of these diseases are those associated with anti-neutrophil cytoplasm antibodies. They usually occur in adulthood and are rare in childhood. The disease generally affects the lung, kidney, and skin, with gastrointestinal involvement being rare. Here we describe the case of a pediatric patient with gastrointestinal bleeding secondary to ANCA positive vasculitis. Endoscopy revealed patchy erythematous lesions and wall hematoma at the level of the colon. Although we report a fairly infrequent clinical condition, it is not without complications. We believe it is appropriate to suspect it, first of all, intestinal involvement where the underlying inflammatory process is not clear, even more so when it involves other organs.