Volume 4, Issue 1

Our understanding of the pathogenesis of large vessel vasculitis (LVV) are mainly achieved by studying the arteries taken from temporal artery biopsy in giant cell arteries (GCA) or surgical or autopsy specimens in Takayasu arteritis (TAK). These artery specimens provide invaluable information about pathological changes in these conditions that GCA and TAK are similar but are distinctly different in immune cell infiltrate and distribution of inflammatory cells in anatomical locations. However, these specimens of established arteritis do not provide information of the arteritis initiation and early events which are impossible to obtain in human artery specimens. Animal models for LVV are needed but not available. Here, several approaches are proposed for experimentation to generate animal models to aid in delineating the interaction of immune reaction with arterial wall components.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of potentially life-threatening disorders characterized by necrotizing small vessel vasculitis with positive serum ANCA. To date, the pathogenesis of AAV has not been fully elucidated, but remarkable progress has been achieved in the past few decades. In this review, we summarize the mechanism of AAV. The pathogenesis of AAV involves various factors. ANCA, neutrophils, and the complement system play key roles in disease initiation and progression, forming a feedback amplification loop leading to vasculitic injury. Neutrophils activated by ANCA undergo respiratory burst and degranulation, as well as releasing neutrophils extracellular traps (NETs), thus causing damage to vascular endothelial cells. Activated neutrophils could further activate the alternative complement pathway, leading to the generation of complement 5a (C5a), which amplifies the inflammatory response by priming neutrophils for ANCA-mediated overactivation. Neutrophils stimulated with C5a and ANCA could also activate the coagulation system, generate thrombin, and subsequently cause platelet activation. These events in turn augment complement alternative pathway activation. Moreover, disturbed B-cell and T-cell immune homeostasis is also involved in disease development. In-depth investigation in pathogenesis of AAV might help to offer more effective targeted therapies.

Objective To investigate the clinical characteristics, vascular imaging features, and prognosis of Takayasu's arteritis (TA) patients with stroke in China. Methods Medical charts of 411 in-patients who fulfilled the classification criteria of modified 1990 American College of Rheumatology (ACR) criteria for TA and with complete data from 1990 to 2014 were reviewed retrospectively. The demographic data, symptoms and signs, laboratory test results, radiological features, treatment, and interventional or surgical procedures were collected and analyzed. Patients with radiological confirmed stroke were identified. Chi-square test or Fisher exact test was used to compare the differences between patients with and without stroke. Results Twenty-two patients with ischemic stroke (IS) and 4 patients with hemorrhagic stroke were identified. The incidence of stroke in TA patients was 6.3% (26/411), of which 11 patients were considered to be the initial manifestation. Stroke patients had more visual acuity loss (15.4% vs. 4.7%, P = 0.042). Systemic inflammatory symptoms and inflammatory markers were less common in patients with stroke than in those without stroke [fever P = 0.007; erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), P < 0.001]. Cranial angiography showed that common carotid artery (CCA) (73.0%, 19/26) and subclavian artery (SCA) (73.0%, 19/26) were the most involved, followed by internal carotid artery (ICA) (57.7%, 15/26) in stroke patients. The intracranial vascular involvement rate of stroke patients was 38.5% (10/26); the middle cerebral artery (MCA) was the most common artery involved. The most common site of stroke was the basal ganglia region. The occurrence of intracranial vascular involvement was much higher in patients with stroke when compared to patients without stroke (38.5% vs. 5.5%, P < 0.001). Among all patients with intracranial vascular involvement, patients without stroke received more aggressive treatment than patients with stroke (90.4% vs. 20.0%, P < 0.001). There was no significant increase in in-hospital mortality in patients with stroke compared with patients without stroke (3.8% vs. 2.3%, P = 0.629). Conclusion Stroke is the initial presentation in 50% of TA patients with stroke. The intracranial vascular involvement rate is significantly increased in stroke patients than in patients without stroke. The artery invloved in patients with stroke are cervical artery and intracranial involvement. Systemic inflammation is less in patients with stroke. Aggressive treatment for TA with glucosteroid (GC) and immunosuppressive agents combined with anti-stroke therapy is needed to improve the prognosis of TA complicated stroke.

Objectives Risk stratification and prognosis prediction are critical for appropriate management of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Herein, we aim to develop and internally validate a prediction model specifically for long-term survival of patients with AAV. Methods We thoroughly reviewed the medical charts of patients with AAV admitted to Peking Union Medical College Hospital from January 1999 to July 2019. The Least Absolute Shrinkage and Selection Operator method and the COX proportional hazard regression was used to develop the prediction model. The Harrell's concordance index (C-index), calibration curves and Brier scores were calculated to evaluate the model performance. The model was internally validated by bootstrap resampling methods. Results A total of 653 patients were included in the study, including 303 patients with microscopic polyangiitis, 245 patients with granulomatosis with polyangiitis and 105 patients with eosinophilic granulomatosis with polyangiitis, respectively. During a median follow-up of 33 months (interquartile range 15–60 months), 120 deaths occurred. Age at admission, chest and cardiovascular involvement, serum creatinine grade, hemoglobin levels at baseline and AAV sub-types were selected as predictive parameters in the final model. The optimism-corrected C-index and integrated Brier score of our prediction model were 0.728 and 0.109. The calibration plots showed fine agreement between observed and predicted probability of all-cause death. The decision curve analysis (DCA) showed that in a wide range of threshold probabilities, our prediction model had higher net benefits compared with the revised five factor score (rFFSand) and the birmingham vasculitis activity score (BVAS) system. Conclusion Our model performs well in predicting outcomes of AAV patients. Patients with moderate-to-high probability of death should be followed closely and personalized monitoring plan should be scheduled.

Relapsing polychondritis (RP) is a rare autoimmune disease in which recurrent and progressive chondritis occurs throughout the body. We report a case of a 56-year-old female subject presented as intermittent fever and cough, who was found obvious luminal stenosis and intense 18 F-fluorodeoxyglucose (FDG) uptake in her larynx and trachea via bronchoscopy and FDG positron emission tomography/computed tomography (PET/CT). The auricular cartilage biopsy demonstrated chondritis. At first she was diagnosed as RP and treated by glucocorticoid and methotrexate, leading to completely response. Fever and cough recurred after 18 months, and FDG PET/CT were performed again and targeted a newfound nasopharyngeal lesion, where the biopsy proved to be an extranodal natural killer (NK)/T-cell lymphoma, nasal type.