Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects

BackgroundAntineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV.ObjectiveWe investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval.MethodsIn this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI).ResultsThe positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10–2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77–2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20–2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24–3.96) after adjusting for confounders.ConclusionsSerum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

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.

Vasculitis and Breast Cancer: Mind the Hint

Diffuse alveolar haemorrhage related to an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis is an extremely rare form of presentation of breast cancer. Here we report the case of a 77-year-old woman with a histological diagnosis of a papillary ductal carcinoma of the breast presenting with a diffuse alveolar haemorrhage secondary to a perinuclear ANCA-associated vasculitis. To our knowledge, this is the first case ever reported of a diffuse alveolar haemorrhage related to an ANCA-associated small vessel vasculitis as a form of presentation of breast cancer. The therapeutic approach of this paraneoplastic vasculitis included the use of corticosteroids and plasmapheresis, a very useful technique to remove endothelial aggressors (circulating antibodies) as a strategy to earn time for a proper therapeutic decision specifically directed for disease modification, but that can also be associated with several severe adverse effects, which are illustrated in our case.

Polyangiitis overlap syndrome: a novel presentation of microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis

Polyangiitis overlap syndrome (POS) is a diagnostic term coined by Leavitt and Fauci that characterises patients with overlapping features of more than one vasculitis. Prior case studies of antineutrophil cytoplasmic antibodies (ANCA)-associated POS have only been published in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis alongside proteinase-3/cytoplasmic (C)-ANCA positivity. We present a case of a 60-year-old woman with dyspnoea, hemoptysis, positive perinuclear-ANCA and renal biopsy demonstrating evidence of microscopic polyangiitis. In addition, our patient also had asthma, mononeuritis multiplex, eosinophilia and migratory pulmonary infiltrates, thus fulfilling the criteria for EGPA. This novel case report suggests that POS is not limited to C-ANCA positivity and has variable presentations.

A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment

Acute kidney injury (AKI) is a common presentation which can result from a number of different underlying pathological processes. Haematological malignancies, particularly multiple myeloma (MM), are known to frequently present with AKI. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare condition which can cause crescentic glomerulonephritis (GN), resulting in AKI. We present the case of a 60-year-old man who presented with clinical features suggestive of AAV in the context of blood tests which demonstrated AKI and positive perinuclear ANCA (p-ANCA) and anti-myeloperoxidase (anti-MPO) titres. Further investigations demonstrated an underlying diagnosis of MM. A renal biopsy was ultimately required to determine the cause of AKI, a cast nephropathy. This case is the first to our knowledge which demonstrates a rare situation in which myeloma kidney is associated with positive p-ANCA and anti-MPO titres, without any evidence of a crescentic GN. It highlights the importance of following up on all investigations sent in the context of AKI, even when a potential diagnosis seems evident. Furthermore, it demonstrates the role of renal biopsy in confirming a diagnosis in the context of AKI with multiple differential diagnoses.

Eosinophilic granulomatosis with polyangiitis in a Nigerian woman

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss Syndrome, is a systemic autoimmune disease that is usually associated with asthma and eosinophilia. It is a rare condition associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of a 52-year-old Nigerian woman who presented with bilateral leg swelling with multiple ulcers, background history of allergic rhinitis and chronic sinusitis since adolescence. There were also associated symptoms of peripheral neuropathy, weight loss, peripheral blood eosinophilia and positive perinuclear ANCA and she was previously managed for rheumatoid arthritis and asthma. She fulfilled the American College of Rheumatology criteria for EGPA and was treated with glucocorticoids and methotrexate which led to significant improvement of her symptoms.

Antineutrophil Cytoplasmic Antibody Frequency in Chronic Hepatitis B Patients

Background. Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients.Methods. A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays.Results. ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P= 0.6 andP= 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P= 0.009 andP= 0.005, resp.).Conclusions. In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions.

Sinonasal Involvement in Systemic Vasculitides and Cocaine-Induced Midline Destructive Lesions: Diagnostic Controversies

Multiple systemic diseases produce various clinical manifestations in the sinonasal area. They usually appear as difficult-to-diagnose disease processes with slow, atypical clinical courses. The aim of this study was to evaluate the sinonasal manifestations of systemic vasculitides, highlighting key points for diagnosis and differential diagnosis with other pathological entities, especially cocaine-induced midline destructive lesions (CIMDL). A retrospective study was performed of 10 patients treated in our hospital during the last 5 years with an initial diagnosis of systemic vasculitides with sinonasal involvement: eight patients with granulomatosis with polyangiitis (GPA; new nomenclature for Wegener granulomatosis) and two patients with Churg-Strauss syndrome (CSS). The study variables were clinical presentation, nasal endoscopy results, maxillofacial scan results, nasal biopsy results, erythrocyte sedimentation rate, and autoimmune antibody levels. The definitive diagnosis was GPA in six (60%) patients, CSS in two (20%) patients, and CIMDL in two (20%) patients. Nasal symptoms were similar in all patients, but nasal polyps were present in only one patient with CSS. Systemic manifestations were absent in patients with CIMDL. Likewise, peripheral eosinophilia was observed only in the two patients with CSS. Specific positive biopsy specimens were obtained in six patients (all six patients with GPA, one with CSS, and one with CIMDL). Antineutrophil cytoplasmic antibodies (ANCA) were positive in all patients with GPA (proteinase 3 antigen in five patients and myeloperoxidase in one patient), and perinuclear ANCA was positive in one patient with CIMDL; however, this patient showed an undefined pattern. Finally, the response to treatment was adequate in all patients excluding those with CIMDL. GPA and CIMDL syndromes pose a difficult differential diagnosis because they have common clinical, serological, and histological presentations. Negative histological results do not exclude the diagnosis of sinonasal vasculitides. The absence of systemic manifestations and the lack of response to treatment will lead to the confirmation of CIMDL syndrome in a cocaine user. Otolaryngologists play an important role in the early and differential diagnosis of these diseases.