Antineutrophil Cytoplasmic Antibody-associated Vasculitis With Alveolar Hemorrhage and Ruptured Renal Aneurysm: a Case Report and Literature Review

Background: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing damage of small -vessel vasculitis and the main violation of the kidney or lung. Manifestation of alveolar hemorrhage and renal aneurysm is extremely rare in Granulomatosis with polyangiitis (GPA). Case presentation: A 50-year-old Chinese man was admitted due to repeated cough, expectoration, fever and shortness of breath. A chest computed tomography (CT) scan showed bilateral inltrates in the lower lobe of the lung. GPA was considered based on the pulmonary capillaritis, alveolar hemorrhage, renal insuciency and cANCA -PR3 positivity. Immunosuppressive therapy combined with plasma exchange (PE) was performed. The patient suffered from a rupture of renal aneurysm. Though selective renal arterial embolization was performed, the patient had a poor outcome. Conclusions: GPA could be life-threatening, especially large vessel vasculitis involved. The possibility of aneurysmal rupture should be carefully considered and checked frequently in the condition of immunosuppressive therapy. prognosis of

His general condition and in ammatory reaction improved (Fig. 1D). Patients were satis ed with the current treatment. A lung biopsy was performed with the presence of pulmonary capillaritis with extravasation of erythrocytes, brosis proliferation and neutrophils in ltration (Fig. 2). On day 10 after admission, the patient had a sharp pain of sudden onset in his left abdominal side. His hemoglobin dropped from 99g/L to 55g/L developed in the subsequent hours, but there were no sign of hemorrhage. A chest CT scan showed increasing bilateral in ltrates in the lower lobe of the lung. ( Fig. 1E). Abdominal CT scan showed left kidney and left retroperitoneal hematoma. (Fig. 1.F) Selective arterial angiography showed multiple aneurysms in renal arteries( Fig. 1.G). A decrease in hemoglobin and a large hematoma of left kidney and left retroperitoneal were considered the possibility of the ruptured renal aneurysm. Selective renal arterial embolization was performed.

Disscussion And Conclusions
AAV is characterized by small-vessel vasculitis, particularly involving the glomerular and pulmonary capillaries that lead to rapidly progressive glomerulonephritis (RPGN) and pulmonary hemorrhage (more than 50%) [6].In this case, white lung with consolidations, alveolar hemorrhage, mild normocytic anemia, and cANCA -PR3 positivity were considered as the diagnosis of GPA. In detail, the patient suffered from multiple organ damage; in particular ARF caused by severe lung involvement and rapidly progressive AKI with a rare involvement of renal aneurysm di cult to treat.
Although the lung is the most commonly affected organ in GPA, alveolar hemorrhage and ARF is a rarely clinical manifestation that carries an extremely high mortality with incidence of only 5-10% in these patients [7][8][9][10][11]. High risk factors including infections, environment or genetic predisposition may trigger an in ammatory response that involves the release of ANCA [12]. ANCA-activated neutrophils secrete proin ammatory cytokines and release reactive oxygen species to amplify vasculitis and disrupt the vascular wall, then migrate into lung compartments through alveolar-capillary membrane, and nally reach alveolar spaces mediated by CXC chemokines [13][14]. Also, severe damage of the alveolar-capillary barrier can cause diffuse intraalveolar hemorrhage from small vessels, an important predictor of ARF in patients with AAV [15][16]. In this case, the patient's respiratory failure was developed progressively due to pulmonary hemorrhage despite the use of noninvasive mechanical ventilation. Immunosuppressive therapy combined with PE was performed according to European vasculitis study group recommendations [17]. The patient's condition was dramatically improved attributed to the supportive therapies for complications affecting vital organs.
Arterial aneurysm formation and rupture is a rare complication of GPA. To the best of our knowledge, Only cases with su cient clinical data for analysis were identi ed by a review of the literature. Finally, 6 case reports were included in the present study with renal aneurysm involved( Table 1). All the patients were male with the age of onset ranged from 24 to 50.Three patients had positive ANCA. Moreover, Three patients had a ruptured renal aneurysms, of which one died. In addition, most of these patients were treated with immunosuppressive agents such as steroids and cyclophosphamide. The prognosis of surviving patients was good. It is di cult to prove the relationship between GPA and renal aneurysm involved due to no pathological evidence found in our patient. We suggest that the incidence of both PR3-AAV and renal aneurysm by chance through their pathologies is very remote. It is more reasonable to consider that the pathology of PR3-AAV is related to the development of renal aneurysm. Aneurysms of the medium-sized arteries are frequently encountered in PAN, whereas their occurrence in smaller arteries is unclear. Damage of the internal and external elastic lamina may contribute to the development of aneurysmal dilation [18]. In addition, the vessel wall is disrupted by in ammation reaction, thrombosis and arterial narrowing resulting in aneurysm formation. Immunosuppressive therapies could lead to thinning of the adventitia that we needed to consider the risk of aneurysmal rupture [19].
In the present case, the patient developed both alveolar hemorrhage and renal aneurysm, a rare manifestation of GPA. PE is recommended in the presence of alveolar hemorrhage and severe renal disease, which is able to remove the ANCAs effectively and yield a good response for prognosis [20].Corticosteroids and cyclophosphamide are reportedly effective for the treatment with arterial aneurysms in GPA. Unfortunately, the patient's condition deteriorated progressively with ARF and AKI. Aneurysmal rupture may result in life-threatening bleeding for poor outcome. ANCA might play a role in ANCA associated large vessel disease in rare cases [21]. Large vessels involvement should be paid attention as an important factor in the development of AAV. Therefore, CT scan be considered to screen for the presence of arterial aneurysm to treat the patient as safely as possible. There are valuable experiences or lessons learned from the case when we encounter rare manifestations of rare diseases in the process of clinical diagnosis.
In conclusion, GPA could be life-threatening, especially large vessel vasculitis involved, which should not be ignored by clinicians. The possibility of aneurysmal rupture should be carefully considered and the condition of the aneurysm should be checked frequently when administering immunosuppressive therapies for GPA with aneurysm.  A lung biopsy showed pulmonary capillaritis with extravasation of erythrocytes, brosis proliferation and neutrophils in ltration Clinical course of this patient