Positive Antineutrophil Cytoplasmic Antibody Test Research Articles

The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern wasnot associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. IV Laryngoscope, 134:2609-2616, 2024.

Large vessel involvement in antineutrophil cytoplasmic antibody-associated vasculitis.

ANCA-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV. Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between 1 January 2000 and 31 December 2021 were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit. The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA, and 13 had c-ANCA and/or PR3-ANCA. Mean (s.d.) age at AAV diagnosis was 63.4 (12.79) years; 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a 1-year timespan. Twenty-five (69%) patients had histopathological confirmation of AAV diagnosis in a location other than temporal artery, aorta or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36) and methotrexate (18/36) were the most frequent treatments. This is the largest single-centre cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

The Role of Sural Nerve Biopsy in the Diagnosis of Vasculitis.

The diagnostic yield of sural nerve biopsy (SNB) in vasculitis is uncertain. Our aim was to document relevant characteristics of patients undergoing SNB in the investigation of vasculitis; determine the diagnostic yield; relate positive biopsy findings to patient demographic, laboratory, and clinical variables; and to calculate the rate of surgical complications. Patients with suspected vasculitis that underwent SNB as part of diagnostic evaluation at academic medical centers in Sweden and the United Kingdom were identified by searching local pathology databases and clinic registers. A structured review of medical case records and pathology reports was conducted. Histological findings were categorized as definite, probable, or no vasculitis in accordance with the 2015 Brighton Collaboration reinterpretation and update of the Peripheral Nerve Society guidelines for vasculitic neuropathy. Definite and probable findings were considered positive for vasculitis. Ninety-one patients that underwent SNB were identified (45% female). Forty (44%) patients showed histological evidence of vasculitis: 14 definite and 26 probable. A concomitant muscle biopsy conducted in 10 patients did not contribute to the diagnostic yield. Positive antineutrophil cytoplasmic antibody test, organ involvement other than the nervous system, and a longer biopsy sample were associated with a positive biopsy. The reported surgical complication rate was 15%. SNB of sufficient length is a useful procedure to confirm a diagnosis of vasculitis.

Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO detection in a large cohort tertiary center: lessons learnt from a real-life experience.

Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) are the best strategies for antineutrophil cytoplasmic antibodies (ANCA) detection. In a minority of subjects, ELISA-based ANCA testing may result in a borderline positive titre. Therefore, we assessed the clinical significance of such a result. This is a retrospective study, which included all subjects screened for ANCA subtypes (myeloperoxidase (MPO) or proteinase-3 (PR3)) with subsequent identification of borderline positive results, as determined by ELISA and retested using IIF. The demographic, clinical and laboratory data of subjects with borderline positive ANCA test results were extracted from their medical records. A total of 14,555 PR3/MPO-ANCA tests were performed with ELISA during the study period (2006-2016). Of the 14,555 PR3-ANCA antibody tests that were performed, 94 were borderline positive (titre 0.9-1.1), and of 14,555 MPO-ANCA antibody tests, 43 were borderline positive (titre 0.9-1.1). The male-to-female ratio was 1:1.08 and the mean age was 50.95±21.79 years. Four MPO-ANCA (9.30%) and 11 PR3-ANCA (11.70%) antibody borderline samples resulted positive on IIF testing. Subjects with borderline positive MPO-ANCA were found to have a poorer outcome in terms of renal failure and the requirement of dialysis. Subjects with borderline positive MPO-ANCA and positive p-ANCA (IIF) seem to have a less favorable outcome. Physicians should be aware of these findings and possibly perform a closer follow-up and routine screening for these subjects.

The clinical presentation and therapy of diseases related to anti-neutrophil cytoplasmic antibodies (ANCA).

Anti-neutrophil cytoplasmic antibodies (ANCA) are a family of autoantibodies that react with proteins predominantly expressed in cytoplasmic granules of polymorphonuclear neutrophil granulocytes (PMNs). ANCA was initially detected using indirect immunofluorescence, allowing for different patterns such as p-ANCA (perinuclear) and c-ANCA (cytoplasmic) to be distinguished. Today it is common to detect the antibodies by immunochemical assays such as ELISA using purified proteins as antigens. The strongest association with ANCA is found in the pauci-immune small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). There is compelling evidence that ANCA contributes to the pathogenesis in these conditions. ANCA also occurs in 30%-40% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) and anti-GBM disease, but is uncommon in other forms of vasculitis. ANCA with different specificities have been described with varying frequencies in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, endocarditis, chronic infections and hematopoietic malignancies. ANCA can also develop as an adverse event during pharmacological treatment. These entities are treated quite differently, with therapies ranging from immunosuppressive agents over antibiotics to simply removing the causative drug. A positive ANCA test thus requires a careful diagnostic work-up.

Improved prognosis in Norwegian patients with glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies.

BackgroundGlomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased mortality and a high risk of end-stage renal disease (ESRD). Here, we investigated whether the prognosis has improved over the last 25 years.MethodsPatients were identified in the Norwegian Kidney Biopsy Registry. We included all patients with pauci-immune crescentic glomerulonephritis and a positive ANCA test from 1988 to 2012. Deaths and ESRD in the cohort were identified through record linkage with the Norwegian Population Registry (deaths) and the Norwegian Renal Registry (ESRD). Outcomes of patients diagnosed in 1988–2002 were compared with outcomes of patients diagnosed in 2003–12.ResultsA cohort of 455 patients with ANCA-associated glomerulonephritis was identified. The mean follow-up was 6.0 years (range, 0.0–23.4). During the study period, 165 (36%) patients died and 124 (27%) progressed to ESRD. Compared with patients diagnosed in 1988–2002, those diagnosed in 2003–12 had higher mean initial estimated glomerular filtration rates (37 versus 27 mL/min/1.73 m2) and lower risk of ESRD (1-year risk: 13 versus 19%; 10-year risk: 26 versus 37%). The composite endpoint, ESRD or death within 0–1 year after diagnosis, was reduced from 34 to 25%. In patients over 60 years old, 1-year mortality fell from 33 to 20%.ConclusionsIn Norwegian patients with ANCA-associated glomerulonephritis, prognosis was significantly better in 2003–12 compared with 1988–2002. This improvement was probably partly due to a shorter diagnostic delay, and better therapeutic management in older patients.

Imaging of Pulmonary Vasculitis

The presence of pulmonary vasculitis can be suggested by a clinical presentation that includes diffuse pulmonary hemorrhage, acute glomerulonephritis, chronic refractory sinusitis or rhinorrhea, imaging findings of nodules or cavities, mononeuritis multiplex, multisystemic disease, and palpable purpura. Serologic tests, including the use of cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and perinuclear ANCA, are performed for the differential diagnosis of the diseases. A positive cytoplasmic ANCA test result is specific enough to make a diagnosis of ANCA-associated granulomatous vasculitis if the clinical features are typical. Perinuclear ANCA positivity raises the possibility of Churg-Strauss syndrome or microscopic polyangiitis. Imaging findings of pulmonary vasculitis are diverse and often poorly specific. The use of a pattern-based approach to the imaging findings may help narrow the differential diagnosis of various pulmonary vasculitides. Integration of clinical, laboratory, and imaging findings is mandatory for making a reasonably specific diagnosis.

Antineutrophil Cytoplasmic Antibody–Associated Active Scleritis

To determine whether antineutrophil cytoplasmic antibody (ANCA) testing provides prognostic information in evaluating scleritis. Retrospective medical record review of patients evaluated at a tertiary care center from January 1, 1995, to June 30, 2006, was performed to compare clinical features, treatments, and associated systemic disease in patients who test positive for ANCA vs patients whose ANCA tests are negative. Among 78 patients identified, 14 tested positive for ANCA. Patients with positive ANCA test results were more likely to have an associated systemic disorder (10 of 14 or 71%) than were patients who tested negative for ANCA (26 of 64 or 41%; P = .04), and the disorder was more likely to have been diagnosed as a result of scleritis work-up (2 of 10 or 20% vs 19 of 26 or 73%; P = .007). Patients with positive ANCA test results had significantly more ocular complications (21 of 14 or 86% vs 20 of 64 or 31%; P < .001), including keratopathy (5 of 14 or 36% vs 6 of 64 or 9%; P = .02), visual acuity of 20/50 or worse (8 of 14 or 57% vs 11 of 64 or 17%; P = .001), and vascular pannus (3 of 14 or 21% vs 1 of 64 or 2%; P = .02). Aggressive therapy, such as chronic systemic corticosteroids (9 of 14 or 64% vs 9 of 64 or 14%; P < .001) and alkylator therapy (8 of 14 or 57% vs 7 of 64 or 11%; P < .001), was more likely to be recommended for patients who tested positive for ANCA. A substantial subset of patients with scleritis are also positive for ANCA. These patients are more likely to have severe ocular disease and undiagnosed primary vasculitic disease, thereby requiring more aggressive therapy. An ANCA test may be useful in the evaluation and treatment of patients with scleritis.

Significance of antineutrophil cytoplasmic antibody in adult patients with Henoch-Schönlein purpura presenting mainly with gastrointestinal symptoms

To test the clinical significance of antineutrophil cytoplasmic antibody (ANCA) in evaluation of adult Henoch-Schonlein purpura (HSP) patients presenting mainly with abdominal symptoms. Twenty-eight consecutive HSP patients who presented predominantly with abdominal symptoms were enrolled in this study. Control subjects included 27 age- and sex-matched patients with peptic ulcer disease, colon cancer, acute gastroenteritis, irritable bowel syndrome and colonic polyps. ANCA was measured by indirect immunofluorescence (IIF) in all patients, and follow-up ELISA was performed in patients with positive IIF tests. ANCA was detected in 9 HSP patients by IIF (2 were positive for c-ANCA and 7 were positive for p-ANCA). No ANCA was found in the control group. The sensitivity and specificity of a positive ANCA test (either c- or p-ANCA) were 32.1% and 100% respectively. Only one out of the 9 patients with positive ANCA by IIF had positive ANCA by ELISA and the antigen was myeloperoxidase (MPO). The patients positive for ANCA had higher HSP clinical scores, and were more likely to have renal function impairment. Patients with late purpura development were also associated with more severe clinical manifestations. A positive ANCA test is associated with more severe symptoms in HSP. After inflammatory bowel disease is excluded, a positive ANCA test provides a clue to the diagnosis of HSP presenting predominantly with abdominal symptoms.

Poor Renal Outcome of Antineutrophil Cytoplasmic Antibody Negative Pauci-immune Glomerulonephritis in Taiwanese

Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

Wegener’s granulomatosis mimicking a parotid abscess

We present the case of a previously healthy 59-year-old man who was under treatment for scleritis and episcleritis when he developed a parotid-gland swelling and pus-producing sinus. On surgical exploration, the features were those of a parotid abscess, but the lesion not only failed to heal post-operatively but increased in size very significantly. There was also severe necrotizing keratitis of the eyes. Due to clinical suspicion and a positive antineutrophil cytoplasmic antibodies test, Wegener's granulomatosis was diagnosed and the patient successfully treated with cyclophosphamide and steroids. Previously, a number of cases of Wegener's granulomatosis causing salivary-gland swelling have been reported in the literature; this is the first case in which the disease has masqueraded as a parotid abscess.

Evaluation of patients with scleritis for systemic disease

Objective To evaluate the relationship between associated medical conditions and scleritis—particularly, the timing of the diagnosis of these diseases. Design Retrospective case series. Participants Patients with scleritis presenting to a single center over an 18-year period. Methods Medical records were reviewed for the presence of an associated infectious or rheumatic disease and for the timing of the diagnosis of the systemic disease relative to the presentation for evaluation of the scleritis. Main outcome measures Presence of an associated medical condition and timing of diagnosis relative to that of scleritis. Results In a series of 243 patients with scleritis, 44.0% had an associated medical condition: 7.0%, an infection, and 37.0%, a rheumatic disease. The most frequent infection was herpes zoster, and the most frequent rheumatic disease was rheumatoid arthritis, present in 4.5% and 15.2% of patients, respectively. Of the 107 patients with an underlying disease, 77.6% had a previously diagnosed disease, 14.0% had their conditions diagnosed as a result of the initial evaluation, and 8.4% developed a systemic disease during follow-up. Systemic vasculitis was less likely to have been previously diagnosed than other rheumatic diseases (59.1% vs. 83.8%, P = 0.015) and more likely to be diagnosed by the initial diagnostic evaluation (27.3% vs. 8.8%, P = 0.027). Ten patients (4.1%) had a positive antineutrophil cytoplasmic antibody (ANCA) test result without clinical evidence of a systemic vasculitis. Four of 5 patients with a positive cytoplasmic ANCA test result but no clinical evidence of systemic vasculitis required immunosuppressive drugs for control of the scleritis, whereas 1 of the 5 patients with a positive perinuclear ANCA test result required immunosuppressive drugs. Among patients with no evident systemic disease after the initial diagnostic evaluation, the rate of occurrence of a rheumatic disease was 4% per person-year. Conclusions Although associated systemic diseases are frequent among patients with scleritis, the majority are previously diagnosed. Systemic vasculitis is less likely than other rheumatic diseases to have been previously diagnosed. Because vasculitis is a potentially life-threatening disorder, it should be a focus of the diagnostic evaluation.

Ｓｔｒａｗｂｅｒｒｙ ｇｕｍが診断の契機となったＷｅｇｅｎｅｒ肉芽腫症の１例

Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous inflammation of the respiratory tract, kidneys, and other organs. The most characteristic oral manifestation of WG is an unusual form of hyperplastic gingivitis. Because the clinical appearance of the affected gums resembles overripe strawberries, the gingivitis is referred to as “strawberry gums”. We report a case of WG showing typical strawberry gums with middle ear and nasal involvement. A 43-year-old woman was referred to our department because of gingival swelling after an operation for otitis media, which had not been diagnosed as WG at that time. The gingival surface appeared granular, resembling over-ripe strawberries. A gingival biopsy specimen showed microabscesses and multinucleate giant cells, characteristic findings of strawberry gums. The clinical appearance and histopathological findings suggested a diagnosis of WG. The diagnosis was supported by a positive anti-neutrophil cytoplasmic antibody test (cANCA). The patient responded to treatment with steroids and immunosuppressants, and the strawberry gums disappeared. The typical findings of strawberry gums were the initial diagnostic sign of WG.

Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists

Background: Various forms of Churg-Strauss syndrome have been reported in association with the use of leukotriene receptor antagonists in asthmatic patients. Objective: Our purpose was to increase awareness that different forms of the Churg-Strauss syndrome occur in patients not receiving leukotriene modifiers. Methods: We searched for all the cases of Churg-Strauss syndrome that were seen in the University of Rochester Medical Center, New York, in the past 4 years. Results: We identified 7 patients, 6 of whom fulfilled the American College of Rheumatology criteria for the classification of Churg-Strauss syndrome. None of them used leukotriene receptor antagonists. All had asthma and sinus disease. The duration and severity of their asthma varied considerably. In the majority of the patients the features of Churg-Strauss syndrome became obvious as the systemic corticosteroid dose was being tapered or discontinued, although 3 patients had not been receiving maintenance oral corticosteroids at disease onset. Three patients had positive antineutrophil cytoplasmic antibodies test result (perinuclear pattern). There was histologic documentation of vasculitis in 4 patients. Five of 7 patients responded to high-dose corticosteroid treatment. Conclusion: Our 7 cases are similar to the various forms of Churg-Strauss syndrome that have been reported in association with the leukotriene receptor antagonists. Complete or incomplete forms of this syndrome can become apparent in asthmatic patients as systemic corticosteroids are being tapered but can also occur in patients with mild asthma of short duration who use only inhaled corticosteroids. (J Allergy Clin Immunol 1999;104:1060-5.)

Wegener's granulomatosis: A meta-analysis of 349 literary case reports

We report the results of a meta-analysis of 349 patients with Wegener's granulomatosis (WG) that were described in the literature from 1979 onward. We describe the patients in terms of diagnosis (granulomas present or absent in biopsy samples from various organs, results of the anti-neutrophil cytoplasmic antibody (ANCA) test) and of the clinical impact of renal involvement. Furthermore, we report the incidence of histopathologic lesions that were found in 134 renal biopsy samples. Before and after the development of the ANCA test, the percentage of patients in whom WG was diagnosed with histologically proven granulomas is the same. However, after 1987 the diagnosis of the group without granulomas is frequently supported by a positive ANCA test result. For the entire group we found that patients without renal involvement (N = 82) were reported to have lower erythrocyte sedimentation rate (ESR), lower white blood cell count (WBC), less anemia, less hypertension, less occurrence of joint symptoms, and less multi-organ involvement than patients with renal involvement (N = 267). The most frequently reported lesion in the renal biopsy samples was extracapillary proliferation (70%), followed by fibrinoid necrosis of the glomerular tuft (54%). Renal granulomas were reported in only 7 biopsy samples.

Metastatic Crohn's disease. Report of 3 cases with special reference to histopathologic findings

Metastatic Crohn's disease is a rare, often unrecognized cutaneous disorder lacking definite histopathologic criteria. The purpose of this study was to document clinicopathologic and immunologic findings in 3 patients with metastatic Crohn's disease. The histopathologic findings are evaluated in correlation to those reported in the literature in an attempt to better define the histopathologic features. None of the patients showed signs of depressed cell-mediated immune response as evaluated with skin tests and T-cell subtyping of blood samples. One of the patients had antineutrophil cytoplasmic antibodies. Polymerase chain reaction, a highly efficient method of amplifying low levels of specific DNA sequences, did not show mycobacterial DNA in the samples studied. Granulomas of the sarcoid type with numerous foreign body and Langhans giant cells were the dominating features. In accordance with previous results, we found vascular involvement in 2 cases, manifested as granulomatous perivasculitis in both. We also found necrobiotic areas in all 3 cases. We propose that both necrobiosis and granulomatous perivasculitis be added to the histopathologic characteristics of metastatic Crohn's disease. Patients may even have a positive antineutrophil cytoplasmic antibody test result.