Warrington, Kenneth J.

Introduction: Periaortitis is a rare inflammatory condition with both infectious and non-infectious aetiologies, often presenting a diagnostic challenge. A comprehensive evaluation—including history, physical examination, imaging, and a broad infectious work-up—is essential, as negative blood cultures do not rule out infection, and premature use of glucocorticoids may be harmful in cases of infectious periaortitis. Case description: We report the case of a 70-year-old man presenting with flank pain and periaortitis, in whom positron emission tomography/computed tomography (PET/CT) scan revealed moderate-to-severe 18F-fluorodeoxyglucose (FDG) uptake. Despite negative cultures, a Karius test and urine antigen confirmed Streptococcus pneumoniae as the causative agent. The patient underwent successful open surgical repair of a mycotic pararenal abdominal aortic aneurysm, followed by targeted antibiotic therapy. Discussion: Pneumococcal periaortitis is a rare condition with few reported cases, though S. pneumoniae has been implicated in various vascular infections including mycotic aneurysms, and diagnostic challenges persist, especially when blood cultures are negative. The Karius SpectrumTM, despite its cost and limited guidance for use, and FDG-PET/CT imaging have emerged as helpful tools in identifying infectious aetiologies, with high maximum standardized uptake value values favouring infection over autoimmune causes, as seen in this case. Conclusion: Infectious periaortitis should be suspected when there is a high uptake of FDG on PET/CT prompting an infectious disease work-up which may include a Karius test.

Objective To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

Abstract Introduction: Idiopathic CD4 lymphocytopenia is a disorder with CD4 counts below 200 cells/mm3 or less than 20% of total lymphocytes without an acquired or genetic cause. Case Summary: A 41-year-old female with history of Celiac disease complicated by hyposplenism developed fevers, weight loss, sicca symptoms, widespread erythematous rash, sinusitis, multifocal pneumonia refractory to antibiotics and pulmonary embolism. Workup demonstrated isolated weakly positive PR3 antibody of 1.2 (reference range < 1.0), CD4 count of 78 with negative ANA, ENA, HIV, CMV, EBV, HTLV, fungal, mycobacterial testing and mildly low IgM. PET-CT noted FDG avidity in the paranasal sinuses, lung opacities and salivary glands. Sinus biopsy showed chronic inflammation and fibrosis. Sputum cultures were positive for MSSA and Pseudomonas. Lung biopsy noted fibrinous organizing pneumonia. Skin biopsy demonstrated pauci-inflammatory vacuolar interface dermatitis with discontinuous weak granular deposition of C3 on basement membrane. A small-intestinal biopsy noted villous blunting and polymorphous T cell infiltration of the lamina propria. Bone marrow biopsy redemonstrated polytypic T cells with inverted CD4:CD8 ratio, but neither harbored an abnormal T cell population. Treatment for presumptive GPA was undertaken with corticosteroids, Rituximab, and Avacopan with transient improvement. CRP was elevated at 65.1 mg/dL (reference range < 5.0mg/dL). However, CD4 count had increased to 260 (reference range 365-1437) with 20% CD4 cells, low B cells, normal CD8 and NK cells, and IgG4 levels elevated at 180 mg/dL (reference range 2.4-121.0). LDH was elevated at 455 U/L (reference range 122-222) but flow cytometry, SPEP, and FLC ratio were unremarkable. Rhinoscopy demonstrated purulence, nasal septal perforation, and crusting of the larynx and subglottis. Salivary gland biopsy noted chronic sialadenitis without malignancy. Repeat CD4 count was 93. Given recurrent, refractory pulmonary infections, IVIG was considered, but prior to administration the patient developed worsening hypoxemia and pressor requirements and was transitioned to comfort cares. Discussion: It is crucial to rule out conditions causing lymphopenia, such as severe sarcoidosis, Sjogren's, IgG4-related disease, cutaneous T cell lymphoma, and splenectomy. While common complications include opportunistic infections, invasive cancers and autoimmunity, their absence may be explained by normal CD3 and CD8 counts. Despite complications, mortality is generally not increased, although baseline CD4 counts of less than 150 cells/mm3 may predict death. Decreases in CD4 counts in the setting of rising immunoglobulin levels may represent antibody production against lymphocytes. While evidence on the use of IVIG is limited, it may be beneficial when hypogammaglobulinemia or life-threatening infections are present.

Abstract The session on other forms of vasculitis included a masterful review on IgG4-related disease (IgG4-RD) following which two research studies evaluating therapeutic agents and one study on histopathologic findings of IgG4-RD were presented. Peyronel F., et al. discussed the results of a prospective multicentre randomized clinical trial evaluating methotrexate for patients with retroperitoneal fibrosis. Methotrexate, in combination with a tapering regimen of glucocorticoids, was effective in inducing remission and allows use of lower cumulative prednisone doses. Hobbelink J., et al. evaluated the histopathologic scoring system from the ACR/EULAR Classification criteria for IgG4-RD. Their study found that these criteria were able to distinguish patients with confirmed and suspected IgG4-RD. Trivioli G et al. retrospectively evaluated rituximab in adult-onset IgA Vasculitis (IgAV) and crescentic IgA Nephropathy (cIgAN). Rituximab resulted in high rate of renal response in IgAV but remission rates in cIgAN remained lower with poorer renal outcomes compared with IgAV.