Citations

Objective Diffuse alveolar hemorrhage (DAH) is a life‐threatening presentation of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Patients with AAV are at an increased risk of venous thromboembolic events (VTEs). These manifestations can co‐occur; however, the prognosis and management of these patients are poorly understood. Methods In this retrospective observational study, we included patients diagnosed with AAV who presented with both DAH and VTE during the same outpatient visit or in the same inpatient treatment episode. Results Among 121 patients with proven DAH secondary to AAV managed at our institution, 14 (11.6%) were also diagnosed with VTE. Patients were predominantly men (71%) with median age at diagnosis of 67 (interquartile range 56–72) years. Five patients were diagnosed with DAH followed by VTE, four patients were diagnosed with VTE before developing DAH (T‐AAV), and five patients were diagnosed with VTE and DAH simultaneously (HT‐AAV). Inferior vena cava filters were placed in 13 patients (93%). Although most patients received systemic anticoagulation within 30 days of DAH diagnosis, anticoagulation management was individualized based on clinical presentation. One patient with preexisting interstitial lung disease died of respiratory failure after initially presenting with pulmonary embolism and later developing DAH during hospitalization. Bleeding complications, including recurrent DAH or retroperitoneal hematoma, were observed in six patients (43%). Three patients (21%) experienced progression or recurrence of VTE within 90 days. Conclusion Management of patients with DAH and VTE is challenging and should be guided by the severity of DAH, additional organ manifestations of AAV, and risk stratification of the presenting VTE.

ObjectiveAvacopan, an activated complement factor 5 receptor antagonist, has been approved as adjunct therapy for severe active antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Current evidence supports the management of AAV presenting with diffuse alveolar hemorrhage (DAH) by administering glucocorticoids combined with either rituximab or cyclophosphamide in addition to supportive care. The role of avacopan in patients with DAH as a primary severe disease manifestation of AAV has not been well established. Furthermore, concerns remain regarding timely access to avacopan, the best glucocorticoid tapering regimen, and long‐term efficacy and safety of the drug. We sought to identify clinical features and outcomes of patients presenting with DAH secondary to AAV who received avacopan in addition to glucocorticoids and rituximab or cyclophosphamide.MethodsWe performed a retrospective cohort study of all consecutive patients presenting with DAH as part of active severe granulomatosis with polyangiitis or microscopic polyangiitis. Demographic and clinical characteristics were collected at presentation and follow‐up.ResultsFifteen patients met inclusion criteria and were observed for a median time of 17 weeks (interquartile range [IQR] 6–37 weeks) after initiation of avacopan. Patients were predominantly female and White, had never smoked, and were a median age of 66 years (IQR 52–72 years) at diagnosis. The majority had newly diagnosed severe AAV with renal involvement. Three patients progressed to respiratory failure. The timing of avacopan introduction and patterns of glucocorticoid tapers varied widely in this cohort. Two serious adverse events related to infection were observed, including one opportunistic infection leading to the patient's death, although neither was directly attributed to avacopan administration.ConclusionWe describe the clinical course of patients who presented with the severe AAV disease manifestation of DAH and received avacopan as adjunct therapy. Most patients achieved remission during follow‐up, and adverse events, including infection, were observed.

Abstract Objective ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented. Methods A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015. Patients who experienced seroconversion were the subject of a case-crossover study. Clinical data and outcomes were retrieved from electronic medical records. Results ANCA-negative GPA was identified in 110 patients; 65% were female; median age was 55 (IQR 39–65) years at time of diagnosis. Disease severity was milder in ANCA-negative GPA (BVAS/WG = 2 vs 6, P < 0.001). Mucous membranous/eye manifestations were more frequent in ANCA-negative GPA. General symptoms, pulmonary and renal involvement were more frequent in ANCA-positive GPA. Patients with ANCA-positive GPA relapsed more over 60 months (21.8% vs. 9.1%, P = 0.009) compared with ANCA-negative GPA and had shorter time to event (P = 0.043). Patients with general manifestations, BMI > 30kg/m2 and necrotizing granulomatous inflammation were more likely to relapse. The 16 patients who seroconverted into ANCA-positive during follow-up had higher mean BVAS/WG at time of diagnosis (P < 0.001) and increased incidence of relapses (P = 0.004) after seroconversion. Necrotizing granulomatous inflammation on biopsy in ANCA-negative GPA patients was identified as a risk factor for subsequent seroconversion to ANCA-positivity. Conclusion Patients with ANCA-negative GPA have milder disease and a lower frequency of relapse than those with ANCA-positive GPA. ANCA appearance portended higher disease severity and an increased frequency of relapses.

INTRODUCTION: Recurrent pancreatitis with pseudocyst can present with gastric outlet obstruction. Endoscopic evaluation should be utilized in certain contexts, especially to exclude more sinister causes of this presentation. CASE DESCRIPTION/METHODS: A 43-year-old woman with a history of alcohol use disorder presented with a gastric outlet obstruction. This was felt secondary to a pancreatic pseudocyst given multiple episodes of recurrent pancreatitis, the last being 1 week prior to her current admission. On presentation, physical exam was significant for ascites and epigastric tenderness. Labs were notable for AST 214 U/L, ALT 99 U/L, alkaline phosphatase 147 U/L, lipase of 203 U/L, and negatives serum alcohol. Notably, Ca 19-9 was elevated to 154 IU/mL during admission 2 weeks prior. Computed tomography chest and abdomen revealed bilateral pleural effusions, pseudocyst, and abdominal ascites. A thoracentesis and paracentesis were performed with cytology for both peritoneal fluid and pleural fluid confirming metastatic adenocarcinoma. Given her refractory symptoms, an esophagogastroduodenoscopy (EGD) was performed which showed an obstructing tumor at the gastric outlet with biopsies revealing poorly differentiated gastric adenocarcinoma. A gastric stent was placed; however, she had continued nausea and vomiting. Repeat EGD showed gastric stent failure and subsequent endoscopic gastrojejunostomy with Axios stent was placed. The patient's functional status declined rapidly as a result of her advanced malignancy and on hospital day 8 she suffered a cardiac arrest, passing shortly after being transitioned to comfort cares. DISCUSSION: The patient's prior history of alcohol use disorder, recurrent pancreatitis, and imaging consistent with pancreatic pseudocyst made this case prone to numerous cognitive errors initially obscuring the etiology of her gastric outlet obstruction and pancreatitis. By reframing the presentation, we were able to question pancreatic pseudocyst as the sole source of the gastric outlet obstruction. Traditionally, Ca 19-9 is associated with pancreatic adenocarcinoma. It also can be elevated in the setting of other gastric malignancies and acute pancreatitis. In pancreatitis, absolute value and trends of Ca 19-9 can help differentiate between pancreatitis and malignancy. The diagnostic uncertainty around this patient's presentation with recurrent pancreatitis, pseudocyst, and gastric outlet obstruction required endoscopic evaluation to ultimately diagnose metastatic gastric adenocarcinoma.