Arteritis

Two pathologists (SH and PS) evaluated the kidney biopsies and were blinded to clinical data. Within a kidney biopsy, infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. The total cortical inflammation including areas of interstitial fibrosis and tubular atrophy, subcapsular and perivascular cortex including nodular infiltrates were considered. In addition, each glomerulus was scored separately for the presence of necrosis, crescents, and global sclerosis. Based on these scorings, histopathological subgrouping according to Berden et al. into focal, crescentic, mixed, or sclerotic classes was performed (6 (link)). Furthermore, the ANCA renal risk score (ARRS), according to Brix et al. into low, medium, or high risk, was calculated (7 (link)). The total renal chronicity score including global/segmental glomerular sclerosis (score 0: <10%, 1: 10-25%, 2: 26-50%, 3: >50%), interstitial fibrosis (score 0: <10%, 1: 10-25%, 2: 26-50%, 3: >50%), tubular atrophy (score 0: <10%, 1: 10-25%, 2: 26-50%, 3: >50%), and arteriosclerosis (score 0: intimal thickeninglink)). Kidney biopsies were also evaluated analogously to the Banff scoring system for allograft pathology, as described previously (25 (link)). In brief, Banff score lesions include interstitial inflammation (i), tubulitis (t), arteritis (v), glomerulitis (g), interstitial fibrosis (ci), tubular atrophy (ct), arteriolar hyalinosis (ah), peritubular capillaritis (ptc), total inflammation (ti), inflammation in areas of IFTA (i-IFTA) and tubulitis in areas of IFTA (t-IFTA) (25 (link)). Systematic histological scoring of tubular injury lesions was evaluated as previously described (26 (link), 27 (link)). In brief, epithelial simplification and tubular dilation, non-isometric cell vacuolization, cellular, red blood cell (RBC), and hyaline casts were given a score ranging from 0 to 4 as a percentage of the total affected cortical area of the biopsy (score 0: <1%, 1: ≥1-10%, 2: ≥10-25%, 3: ≥25-50%, 4: >50%).

A retrospective review of the medical records of dogs diagnosed with non-infectious, non-erosive, idiopathic IMPA and SRMA from two referral institutions during the period between 2017 and 2021 was performed. The terms used as identifiers during the search were: “immune-mediated polyarthritis,” “steroid-responsive meningitis arteritis,” “meningitis,” “arthritis,” “polyarthritis,” “SRMA,” “IMPA.” Patients were included if they were diagnosed with non-infectious, non-erosive, idiopathic (primary) IMPA or SRMA and CRP was measured at the time of presentation. Ethical approval was granted by the Research Ethics Committee at the University of Glasgow with a reference number EA39/20.
A diagnosis was made based on consistent medical history, physical, neurological and orthopedic examination, and clinicopathologic findings (results of hematology, serum biochemical analysis for IMPA and SRMA, and thoracic and abdominal imaging for IMPA). These were coupled with the results of routine analysis of CSF collected from the cerebellomedullary or lumbar cistern. For those patients identified for the purposes of the study with SRMA, fluid analysis revealed neutrophilic or mixed neutrophilic and monocytic pleocytosis with no visible organisms, and lack of toxic neutrophils (1 (link), 2 (link)). Patients diagnosed with IMPA were identified for the purposes of the study as those whose results of synovial fluid analysis indicated neutrophilic inflammation in two or more joints.
Other diagnostic tests performed in an attempt to rule out other causes of CSF pleocytosis (imaging of the vertebral column, PCR assays to detect Toxoplasma gondii, Neospora caninum, canine distemper virus in CSF, CSF culture and serum T. gondii and N. caninum antibody titers) or secondary IMPA (echocardiography, serologic and PCR assays to detect vector-borne disease, serologic testing for Bartonella sp. infection, joint radiography, and microbial culture of blood, synovial fluid, or urine samples) were performed at the discretion of the attending clinician, taking into consideration patient demographic and historical factors, physical examination findings, preliminary test results, and client finances. Dogs were excluded if they had incomplete medical history, no definitive diagnosis or had undergone corticosteroid treatment prior to diagnosis. Additionally, dogs with SRMA were excluded if they had neurological deficits.
Data retrieved from the medical records was as follows: breed, age, body weight, gender, neutered status, month of presentation, history, physical and neurologic examination findings, CRP values at the time of diagnosis, CSF routine analysis and joint cytology results, imagining modalities performed and results, infectious disease testing, and final diagnosis.
CRP was measured quantitatively in 142 dogs (84%) and semi-quantitatively in 27 dogs (16%). For the purposes of statistical analysis semi-quantitative results were replaced as follows: 2.5 mg/L instead of <5, 150 mg/L instead of >100 mg/L, and 250 mg/L instead of >200 mg/L. The CRP serum concentration was measured using species-specific immunoturbidimetric assay for canine CRP (Gentian Canine CRP Immunoassay, Gentian AS, Moss, Norway) in one of the hospitals and using IDEXX Catalyst^® CRP Test (a sandwich immunoassay, IDEXX, USA) in the other. The two assays were compared and considered to provide accurate and consistent results (26 ). The reference range for CRP was <10 mg/L.