p-ANCA Vasculitis Research Articles

Angiotensin II Type 2 Receptor Antibodies in Glomerular Diseases.

We evaluated the concentration of AT2R antibodies in 136 patients with primary and secondary glomerular diseases: membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (n = 25), systemic lupus erythematosus (n = 17), immunoglobulin A (IgA) nephropathy (n = 14), mesangial (non-IgA) proliferative nephropathy (n = 6), c-ANCA vasculitis (n = 40), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and compared it with a healthy control group (22 patients). Serum creatinine levels, proteinuria, serum albumin, and total protein concentrations were prospectively recorded for 2 years. The mean levels of AT2R antibodies in the lupus nephropathy group were significantly higher compared to the control group, 64.12 ± 26.95 units/mL and 9.72 ± 11.88 units/mL, respectively. There was no association between this level and the clinical course of the disease. The AT2R levels in other kinds of glomerular disease were no different from the control group. We found significant correlations between AT1R and AT2R in patients with membranous nephropathy (r = 0.66), IgA nephropathy (r = 0.61), and c-ANCA vasculitis (r = 0.63). Levels of AT2R antibodies in systemic lupus erythematosus are higher compared to other types of glomerulonephritis, vasculitis, and a healthy control group. Levels of AT2R antibodies correlate with AT1R antibodies in the groups of patients with membranous nephropathy, IgA nephropathy, and c-ANCA vasculitis. These kinds of AT2R antibodies have a stimulative effect on AT2R, but we have not found the influence of these antibodies on the clinical course of glomerular diseases.

S2310 Esophageal Manifestations of Paraneoplastic Pemphigus Vulgaris Associated With Gastric Neuroendocrine Tumor

Introduction: While pemphigus vulgaris (PV) typically affects the epidermis and oral mucosa, esophageal manifestations are uncommon. The primary symptoms accompanying this manifestation are dysphagia, odynophagia, and hematemesis. In this case report we examine the occurrence of esophageal pemphigus vulgaris associated with a gastric neuroendocrine tumor and note the endoscopic findings of esophagitis dessicans superficialis (EDS) within the esophagus. Case Description/Methods: A 63-year-old female with a history of P-ANCA vasculitis presented for evaluation of dyspnea, hypotension, fatigue, rash, and dysphagia. The patient was thought to have an infectious cause of these signs and symptoms, however given a lack of response to antibiotic and antifungal therapy within 48 hours the differential was broadened to include rheumatologic disease. The patient was treated with intravenous methylprednisolone and continued to experience dysphagia. Esophagogastroduodenoscopy was performed (Figure) and demonstrated a tongue ulceration and extensive desquamation in the distal esophagus appearing similar to a pseudomembrane. Extensive subepithelial hemorrhages were observed in the esophagus, however the gastric and duodenal mucosa were intact. Esophageal and gastric biopsies demonstrated staining for IgG reactive to desmoglein 3 consistent with PV. In addition, a well-differentiated neuroendocrine tumor (NET) in the stomach. The patient was subsequently treated with octreotide for her neuroendocrine tumor, as well as solumedrol and dapsone for her skin lesions. She also received a loading dose of rituximab. She received a second dose of rituximab 21 days after the loading dose and the corticosteroids were tapered as her symptoms of dysphagia gradually improved with immunosuppressive therapy. Discussion: Esophagitis dessicans superficialis has been described as sloughing of the superficial esophageal mucosa and is similar in appearance to the Nikolsky sign of external squamous epithelium seen with immunobullous diseases. Our patient presented with undiagnosed PV and had both esophageal and skin involvement with the concomitant gastric NET. The ultimate diagnosis of PV was confirmed based on the presence of antibodies to desmoglein 3 and it remains unknown if the gastric NET had any role in the development of PV. Clinicians should have a low threshold for endoscopic examination of patients for whom there is suspicion of immunobullous disease to facilitate rapid diagnosis and initiation of appropriate therapy.Figure 1.: Endoscopic images demonstrating tongue ulceration and extensive desquamation in the distal esophagus appearing similar to a pseudomembrane in addition to subepithelial hemorrhages.

Angiotensin II Type 1 Receptor Antibodies Are Higher in Lupus Nephritis and Vasculitis than Other Glomerulonephritis Patients

Angiotensin II type 1 receptor (AT1R) antibodies are considered non-HLA (human leukocyte antigen) antibodies connected with humoral rejection after kidney transplantation. The role of AT1R antibodies in the pathogenesis of glomerular diseases and systemic vasculitis is unknown. We assessed the level of AT1R antibodies in 136 patients with different types of glomerulonephritis and systemic vasculitis and we observed kidney function and proteinuria, serum albumin and total protein levels for 2 years. The mean levels of AT1R antibodies were the following: 6.00 ± 1.31 U/ml in patients with membranous nephropathy (n = 18), 5.67 ± 1.31 U/ml with focal and segmental glomerulosclerosis (n = 25), 6.26 ± 2.25 U/ml with lupus nephropathy (n = 17), 10.60 ± 6.72 U/ml with IgA nephropathy (n = 14), 6.69 ± 2.52 U/ml with mesangial proliferative (non IgA) glomerulonephritis (n = 6), 6.63 ± 1.38 U/ml with systemic vasculitis (n = 56), including c-ANCA (anti-neutrophil cytoplasmic antibodies) vasculitis: 11.22 ± 10.78 U/ml (n = 40) and p-ANCA vasculitis: 12.65 ± 14.59 U/ml (n = 16). The mean AT1R antibodies level was higher in patients with lupus nephropathy and systemic vasculitis compared to glomerulonephritis groups. An inverse statistically significant correlation between AT1R antibodies and serum albumin (r = − 0.51) in membranous nephropathy group was also found. Prospective analysis of creatinine levels indicated an increase of creatinine levels during time among patients with higher AT1R antibodies levels in p-ANCA vasculitis. Lupus nephropathy and systemic vasculitis patients may have high levels of AT1R antibodies. AT1R antibodies may be associated with the severity of membranous nephropathy and the course of p-ANCA vasculitis, although influence of concomitant factors is difficult to exclude.

P-ANCA Systemic Vasculitis Induced by Brucellosis in an Elderly Male Patient

One of the most prevalent causes of vasculitis is bacterial infection. An infection that causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is uncommon and not reported frequently. We report a case of a 74-year-old male who presented with fever for ten days and was found to have brucellosis. Then, he was diagnosed with Guillain-Barré syndrome (GBS) and started on immunoglobulin (IVIG) for one week without a response. His fever was still persistent despite appropriate antibiotic therapy. Rheumatology evaluation revealed a history of multiple joint pain and swelling, elevated inflammatory marker, and a high titer of P-ANCA. Steroid therapy was started initially on the background of antibiotics therapy. His fever and other symptoms showed marked improvement after one week. However, P-ANCA titer was still elevated. The decision was made to treat the patient as a case of brucellosis-induced P-ANCA vasculitis. Azathioprine was added, and steroid was maintained for one month and then it was tapered gradually. All symptoms improved from the third month of follow-up except weakness from peripheral neuropathy with normalization of P-ANCA titer. His condition remained stable after six months of follow-up. Clinicians should be aware of the possibility of infection-induced vasculitis, particularly when patients' symptoms persist despite the appropriate use of antibiotics.

Case Report: Cyclophosphamide in COVID-19 – when an absolute contraindication is an absolute necessity

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and fraxiparine. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved. Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.

MO003DISTAL RENAL TUBULAR ACIDOSIS IN PATIENTS WITH AUTOIMMUNE DISEASES

Abstract Background and Aims Distal renal tubular acidosis (DRTA) is characterized by hyperchloremic metabolic acidosis, with normal anion gap and with the inability to acidify the urine to a pH lower than 5.3. DRTA can evolve without symptoms and systemic acidosis, this form being defined as incomplete DRTA, that necessitates the use of a urinary acidification test like the Furosemide and Fludrocortisone test for establishing the diagnosis. There are several cases of type 1 DRTA reported in patients with autoimmune diseases, especially Sjögren syndrome and systemic lupus erythematosus (SLE), most of them being diagnosed due to severe symptoms caused by the associated hypokalemia. The prevalence of the DRTA in patients with autoimmune diseases is unknown, especially if we refer to the incomplete form. Method We conducted an observational prospective study in a selected cohort of 21 patients diagnosed with autoimmune diseases, who presented for evaluation in our clinic during December, 2020 and January, 2021. We included patients diagnosed with SLE, Sjögren syndrome, ANCA vasculitis, cryoglobulinemic vasculitis, who were submitted to Furosemide/Fludrocortisone test in our nephrology department. The urinary pH was evaluated hourly for 6 hours after the test began. The test was considered positive if the urinary pH did not decrease < 5.3. Results The study included 21 patients (16 females, 5 males, mean age 41.52 ± 17.58 years), diagnosed with SLE (13 patients, mean age 30.23 ± 10.34 years, eGFR 81.61±20.39 ml/min/1.73 m2), pANCA vasculitis (6 patients, mean age 60.83 ± 6.14, eGFR 40 ± 12.64 ml/min/1.73 m2), Sjogren syndrome (one 44 year-old patient, eGFR 39 ml/min/1.73 m2) and cryoglobulinemic vasculitis (one 69 year-old patient, eGFR 31 ml/min/1.73 m2). The test was positive for 4 patients out of 21 (3 females, one male; one with SLE, one with pANCA vasculitis, one with Sjogren syndrome and one with cryoglobulinemic vasculitis). Although 2 patients developed hypokalemia defined as a level of serum potassium lower than 3.5 mmol/l after the test and 1 patient augmented previous hypokalemia, there was not a significant change in kalemia (3.93 ± 0.32 mmol/l before the test vs 3.95 ± 0.49 mmol/l after the test, p=0.835). Although none of the patients developed metabolic alkalosis after the test, there was a significant increase in the level of serum bicarbonate (26.6 (2.2) mmol/l before the test vs 28.2 (2.7) mmol/l after the test, p=0.005) and also in the level of serum pH (7.36 ± 0.04 before the test vs 7.38 ± 0.04 after the test, p=0.018). None of the patients reported digestive or allergic side effects. It was interesting that the patients with vasculitis responded with delay to the treatment and urinary acidification under the pH of 5.3 occurred after a mean period of 3.2 hours in comparison to 1.5 hours in patients with SLE (p=0.014). Regarding the histological data, both the patients with vasculitis were elders, with an altered kidney function (both with a eGFR of 31 ml/min/1.73 m2) and severe tubular atrophy and interstitial fibrosis on kidney biopsy. The female patient with cryoglobulinemic vasculitis also had positive titers for antinuclear antibody, anti Ro-antibodies and anti-La antibodies. The patient with Sjögren syndrome was diagnosed with nephrocalcinosis and the kidney biopsy was not effectuated. The youngest patient with a positive test had preserved renal function, without tubular or interstitial lesions on kidney biopsy, but with a pattern of membranous lupus nephritis and with intense immunological activity (ANA, anti ds-DNA antibodies, anti RNP and Sm antibodies, antiphospholipid syndrome). Conclusion Incomplete DRTA was found in 4 out of 21 patients with autoimmune diseases, one with Sjogren syndrome and nephrocalcinosis, two with pANCA and cryoglobulinemic vasculitis with decreased eGFR and severe tubular atrophy and interstitial fibrosis and one young female with SLE.

Bilateral optic disc edema with preserved visual function not related to papilledema

Bilateral optic disc edema (ODE) with preserved visual function is typically a result of papilledema, but the causes of this finding in the absence of raised intracranial pressure have not been systematically evaluated. The goal of this study was to determine the causes of bilateral ODE with preserved visual function not related to intracranial hypertension to help in developing a differential diagnosis for this finding. We retrospectively reviewed 221 consecutive patients presenting to a tertiary neuro-ophthalmology practice over a period of 2 years. Four patients met the inclusion criteria with a mean age of 53 years (range 43 to 63), 2 patients were men and 2 were women. The final diagnoses were bilateral optic perineuritis secondary to p-ANCA vasculitis, bilateral incipient non-arteritic anterior ischemic optic neuropathy (NAION), hypertensive emergency, and intermediate uveitis. The patient with NAION developed an inferior altitudinal defect 4 months after presentation, but all other patients maintained normal visual function. The ODE resolved in all cases at a mean follow-up of 4.5 months (range 3 to 6 months). Optic disc edema with preserved visual function may not be related to papilledema, and this series indicates that optic perineuritis, incipient NAION, hypertensive emergency, and intermediate uveitis be considered in the differential diagnosis of these cases.

Hemorragia alveolar difusa secundaria a vasculitis asociada a ANCA

La hemorragia alveolar difusa (HAD) masiva es una complicación inusual de los pacientes con vasculitis ANCA, frecuentemente amenaza la vida y está asociada con una mortalidad de hasta el 100%. La información en la literatura acerca del tratamiento en casos refractarios y cuando el paciente se encuentra en diálisis es escasa. 
 Se presenta el caso de un paciente con vasculitis p-ANCA con compromiso renal y pulmonar en el escenario de síndrome pulmón-riñón, con múltiples recaídas de hemorragia alveolar a pesar de tratamiento con corticoide, azatioprina, ciclofosfamida y terapia de recambio plasmático. Se instauró manejo con anticuerpo monoclonal anti CD20 e inmunoglobulina, logrando resolución del episodio de hemorragia alveolar y permaneciendo sin actividad. Se resalta la utilidad del rituximab como estrategia terapéutica en casos refractarios

Bilateral optic perineuritis associated with p-ANCA vasculitis

A 69-year-old Chinese woman with underlying perinuclear anti-neutrophil cytoplasmic antibody associated with vasculitis (p-ANCA vasculitis) with no previous history of ocular involvement experienced one week of blurred vision in both eyes associated with pain. Ophthalmological evaluation demonstrated severe visual loss in both eyes, with pale optic discs but without other signs of ocular vasculitis. Magnetic resonance imaging (MRI) of the brain and orbit revealed bilateral enhancement of the optic nerve sheath with classical tram-track and doughnut signs. Intravenous methylprednisolone was given for five days and marked improvement of vision was seen. In patients with p-ANCA vasculitis, bilateral optic perineuritis (OPN) is uncommon but can be one of the treatable causes to be considered, with good response to prompt steroid treatment.

Diffuse alveolar hemorrhage: how relevant is etiology?

Diffuse Alveolar Hemorrhage (DAH) is a rare and potentially life-threatening clinical syndrome whose early recognition is essential. Characterization of patients with DAH and comparison of presentation and evolution of the disease according to etiology. We retrospectively reviewed the clinical records of patients admitted to our hospital over a 7-year period with DAH. Criteria for DAH (1+2): 1 - hemoptysis and/or pulmonary infiltrates and/or anemia (DAH triad); 2 - hemorrhagic bronchoalveolar lavage (BAL) or siderophagic alveolitis. DAH was grouped in immune and nonimmune and the course of disease was compared. We included 24 patients admitted with DAH, of which 11 had an immune cause: p-ANCA vasculitis (n=7), Systemic Lupus Erythematosus (n=2), c-ANCA vasculitis (n=1), Rheumatoid Arthritis (n=1) and 13 had a nonimmune cause: heart disease (n=6), amiodarone toxicity (n=2), clotting disorder (n=2), cannabis toxicity (n=1), S. aureus infection (n=1) and idiopathic (n=1). Patients with nonimmune DAH were significantly older than those with immune DAH (67.9±18.1 vs 56.6±18.8 years, p=0.042). DAH triad was observed in 54% of all patients, hemoptysis in 67%, anemia in 79%, and pulmonary infiltrates in all cases. Patients with immune DAH had more frequently pulmonary-renal syndrome (p<0.001), kidney failure (p=0.048), shock (p=0.049) and needed more frequently admition in ICU (p=0.039) and blood transfusion (p=0.043). Hospital length of stay was superior in immune group (29.5±20.0 vs 19.5±14.3 days, p=0.047). In-hospital mortality was exclusive to immune DAH (12.5%). Patients with DAH due to immune causes were significantly younger, had more severe presentations of the disease and worst outcomes.

Paquimeningitis y glomerulonefritis crescéntica en vasculitis p-ANCA: Reporte de caso

Las vasculitis asociadas a anticuerpos contra el citoplasma del neutrófilo configuran patologías multisistémicas caracterizadas por afectar pequeños vasos. Se ha reportado compromiso de sistema nervioso central en 2% a 8% de los casos, rara vez al inicio del cuadro clínico.&#x0D; Se reporta el caso de un hombre de 67 años de edad con vasculitis p-ANCA, quien debutó con proptosis, paquimeningitis y disfagia severa. Posteriormente deterioro renal, necesidad de hemodiálisis, ciclofosfamida y recambio plasmático terapéutico con lo cual alcanza criterios de remisión parcial y egresa de diálisis. Las vasculitis ANCA se relacionan con una amplia gama de signos y síntomas inespecíficos. La edad de aparición, creatinina inicial y requerimiento de diálisis, son factores pronósticos. El inicio oportuno del tratamiento es fundamental, requiriendo por tanto un alto índice de sospecha

Mesenteric vasculitis and ischaemia: every second counts

A 65-year-old woman with past medical history significant for Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (p-ANCA) vasculitis, peripheral arterial disease requiring left femoral-popliteal bypass, chronic anaemia, hypertension, hyperlipidaemia and hyponatraemia secondary to...

Spinal arachnoiditis and cyst formation with subarachnoid haemorrhage

We present the case of a 58-year-old lady with p-ANCA vasculitis who suffered a WFNS grade 1 subarachnoid haemorrhage (Fisher grade 1) secondary to a ruptured left posterior inferior cerebellar artery aneurysm and then developed a rare complication of radiologically progressive spinal arachnoiditis despite maintained clinical response to definitive treatment measures.

P-ANCA pachymeningitis presenting with isolated “optic neuropathy”

Isolated bilateral optic neuropathy is an exceedingly rare presentation of perinuclear-antineutrophil cytoplasmic autoantibody (p-ANCA) vasculitis. We report one such case with MRI documentation of a compressive mechanism mediated by pachymeningitis. A 69-year-old woman had a 6-month history of progressive visual failure caused by bilateral optic neuropathy. Cranial MRI showed diffuse contrast enhancement of the dura mater extending to the perioptic sheaths bilaterally with encasement of the optic nerves. Extensive laboratory study showed increased levels of p-ANCA titres and autoimmune markers. Corticosteroid treatment improved both visual acuity and the neuroradiological signs of active pachymeningitis. In conclusion, our case demonstrates that bilateral optic neuropathy may be the presenting symptom of p-ANCA-associated pachymeningitis, whose causative role may be demonstrated by MRI.

Eye Manifestations in Patients with Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Case Series and Literature Review

To report and summarize eye manifestations of patients with perinuclear pattern antineutrophil cytoplasmic antibody [pANCA, myeloperoxidase (MPO)-ANCA]-associated vasculitis. The medical records of four consecutive patients with pANCA (MPO-ANCA) vasculitis who showed eye manifestations were retrospectively reviewed. In addition, the medical literature databases, PubMed and Japana Centra Revuo Medicina for Japanese literature, were searched for pANCA vasculitis patients with eye manifestations. Three of the four patients treated at the Okayama University Hospital showed unilateral or bilateral scleritis. In the literature review, eight of the 27 patients showed ocular surface manifestations such as scleritis and peripheral keratitis. Other frequent eye presentations were posterior segment manifestations such as central or branch retinal vein occlusion, optic neuropathy, and acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Systemically, the most frequent manifestations were glomerulonephritis in the present patients as well as in the patients reported in the past studies. Ocular surface manifestations and posterior segment manifestations were major eye presentations in patients with pANCA-associated vasculitis. ANCA testing including both pANCA and cytoplasmic pattern antineutrophil cytoplasmic antibody would help establish a systemic diagnosis in patients with eye manifestations such as scleritis, retinal vein occlusion, optic neuropathy, or APMPPE.

Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis

A 75-year-old man suffered from perinuclear antineutrophil cytoplasm antibody (p-ANCA)-associated vasculitis with mild renal involvement. Three years later, he suddenly experienced an anuric acute renal failure due to anti-glomerular basement membrane (GBM) disease. Antibodies to myeloperoxydase were continuously present at a high titer in the patient's serum while serum anti-GBM antibodies were only detected at the time of the acute renal failure. A substantial proportion of patients with anti-GBM glomerulonephritis simultaneously display ANCAs whose pathogenic role is not clear. In our case, ANCAs were supposed to be of pathogenic importance because they may have uncovered the Goodpasture antigen. This case report lends further support to the concept that p-ANCA vasculitis may trigger anti-GBM disease.

Alpha 1-Antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis: genetic and clinical implications.

A high incidence of alpha 1-antitrypsin (AAT) deficiency has been reported in patients with C-ANCA systemic vasculitis in association with antibodies against proteinase-3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C-ANCA or P-ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C-ANCA vs. P-ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C-reactive protein (PCR) (P < 0.001), with a less severe renal involvement or a minor risk of death, and, in one tested patient, with a novel point mutation (TCGA-->TCAA) at the enhancer-promoter region of the AAT gene. Low AAT serum levels did not correlate with either type/titre of autoantibody or distribution/severity of the vasculitis process. In the case-control study, high AAT levels emerged as a major determinant of progression towards end-stage renal failure [odds ratio 3 (95% CI 1.1-8.4)]. These results indicate: (a) a high incidence of the PiZ gene of AAT in systemic vasculitis irrespective of the type of autoantibodies; (b) a novel form of AAT deficiency associated with the normal PiM phenotype becoming manifest only during acute illness; (c) dysregulation of the acute-phase response affecting selectively AAT or both AAT and PCR; (d) correlation between low plasma levels of AAT and less severe renal involvement or risk of death.