Pancreaticoduodenal artery aneurysm associated with polyarteritis nodosa presenting as massive upper gastrointestinal bleeding

Abstract

The pancreaticoduodenal arteries are rare sites for true aneurysm formation, but these may develop in association with occlusion of the coeliac circulation, degenerative conditions or inflammatory vascular disorders. These have a high risk of rupture regardless of size or other factors. One identified cause is polyarteritis nodosa (PAN), which is an autoimmune necrotising vascular condition that affects small-sized and medium-sized arteries. We report a case of a 40-year-old man with massive gastrointestinal tract bleeding from a ruptured pancreaticoduodenal artery aneurysm secondary to PAN. This was managed with emergent open aneurysm ligation followed by high-dose corticosteroids and cyclophosphamide pulse therapy. Only three other cases of PAN-associated pancreaticoduodenal artery aneurysms have been reported in the literature.

Background

True aneurysms are defined as abnormal weakening and dilatation of arterial segments with involvement of all three vessel wall layers, in contrast to false aneurysms, or pseudoaneurysms, which form from localised disruption of the arterial intima and media layers, and may be contained by the arterial adventitia or the surrounding tissues.¹ True aneurysms are less commonly encountered than false aneurysms in the peripancreatic region, with the latter arising from trauma or inflammatory conditions such as acute or chronic pancreatitis with direct injury to the adjacent gastroduodenal, pancreaticoduodenal or splenic arteries. True peripancreatic aneurysms may be associated with lifestyle-related conditions such as hypertension and arteriosclerosis with splanchnic arterial occlusive disease. Other rarer causes include mycotic aneurysms and autoimmune vasculitic disorders. We report a case of a true intrapancreatic aneurysm arising from the pancreaticoduodenal artery (PDA) secondary to polyarteritis nodosa (PAN) in a 40-year-old man presenting as massive upper gastrointestinal bleeding that was definitively managed with emergent open surgery.

Case presentation

The patient is a 40-year-old man with previously diagnosed hypertension 4 years ago but was poorly compliant to maintenance medications. He had no history of tobacco use and had good baseline functional status with no health-related problems. He presented with passage of black tarry stools, mild abdominal pain and lightheadedness 2 weeks prior to consult. There was no associated fever, weight loss, anorexia or sensorimotor deficits reported. He was initially admitted at another institution, where multiple transfusions of packed red blood cells were given to address his anaemia. An esophagogastroduodenoscopy (EGD) showed a submucosal duodenal nodule with overlying ulceration, and an abdominal computed tomography (CT) scan revealed a subcentimetre nodular lesion at the descending duodenal segment. This was initially assessed to be a duodenal gastrointestinal stromal tumour.

The patient was transferred to our institution after experiencing recurrence of melena. On admission, he had with normal vital signs a non-distended non-tender abdomen with no bruits on auscultation, but digital rectal examination showed melenic stools per examining finger. The initial laboratory workup showed normochromic normocytic anaemia, while blood chemistry and bleeding parameters were within normal limits.

Investigations

A repeat EGD showed a 1.6×0.8 cm Forrest IB ulcer beyond the ampulla. Clipping was done to achieve haemostasis. The unusual postampullary location of the ulcer, combined with the previous CT finding of a nodular submucosal lesion, prompted further investigation using cross-sectional imaging. CT angiography revealed a broad-based saccular outpouching measuring 1.4×1.6 × 1.1 cm arising from the inferior pancreaticoduodenal branch of the superior mesenteric artery (SMA) at the junction of the second and third portions of the duodenum. There was also a fusiform dilatation of the coeliac trunk up to its trifurcation with an involved length of 1.5 cm and widest diameter of 1.3 cm, with dissection seen into the splenic artery. The proximal segment of the common hepatic artery had circumferential wall thickening with an abrupt cut-off around 1 cm from the coeliac trunk, with note of collateral branches arising from the SMA supplying the distal common hepatic artery (figure 1).

Figure 1.

(A) CT angiogram cross-sectional image showing the saccular broad-based aneurysm (white arrow) within the pancreatic head parenchyma with the superior and inferior pancreaticoduodenal artery (PDA) (white arrowheads) supplying the aneurysm. (B) CT angiogram cross-sectional image showing the aneurysmal dilation of the coeliac axis (thick white arow), circumferential thickening with abrupt cut-off of the common hepatic artery (thin white arrow), and the splenic artery dissection with intimal flap and false lumen (white arrowhead). (C) Three-dimensional reconstruction of CT angiogram showing the PDA aneurysm (thick white arrow) with superior and inferior feeding vessels entering the aneurysm and the applied duodenal clips adjacent to it. The coeliac axis aneurysm (white arrowhead), the common hepatic artery occlusion (thin white arrow) and collateral vessels into the hepatic artery arising from the superior mesenteric artery are also seen.

Treatment

A few hours after the CT angiography, the patient suddenly had multiple episodes of massive haematochezia associated with hypotension (systolic blood pressure of 70 mm Hg). Interventional angiography was not immediately available at that time; hence, the patient was brought to the operating theatre for emergent surgery. Abdominal exploration and complete mobilisation of the duodenum using the Kocher manoeuvre was done, with no intraperitoneal bleeding noted but a 1.5 cm pulsatile mass was palpable within the substance of the pancreatic head near the junction of D2 and D3. Intraoperative ultrasonography confirmed the presence of the intrapancreatic aneurysm arising from the pancreaticoduodenal arcade, and both the superior and inferior feeding vessels were identified (figure 2).

Figure 2.

(A) Intraoperative ultrasound image of the pancreaticoduodenal artery (PDA) aneurysm showing the superior feeding vessel (white arrows) within the pancreatic parenchyma. (B) Intraoperative ultrasound image of the PDA aneurysm showing the inferior feeding vessel (white arrows) within the pancreatic parenchyma.

The pancreaticoduodenal arteries could be safely ligated without compromising the hepatic arterial supply because other SMA branches provided collateral flow to the proper hepatic artery. The feeding vessels of the aneurysm were identified under ultrasound guidance within the pancreatic parenchyma along the outer rim of the pancreatic head and ligated (figure 3). Ligation of the aneurysmal feeding vessels as well as preservation of adequate hepatic arterial flow through the collateral vessels were confirmed using intraoperative Doppler studies.

Figure 3.

Intraoperative image of the surgical field, with the position of the pancreaticoduodenal artery aneurysm (white circle) and the sites of ligation of the superior and inferior feeding vessels within the pancreatic parenchyma along the rim of the pancreatic head (white arrows).

The constellation of findings on the CT angiography, with multiple aneurysms with dissection and occlusion within the splanchnic vasculature, prompted postoperative rheumatological referral and investigation for possible vasculitides. High-sensitivity C reactive protein (CRP) level was 180.1 mg/L (normal value 1–3 mg/L), hepatitis profile showed a past hepatitis B infection (with non-reactive hepatitis B surface antigen (HBsAg) and reactive anti-HBs, anti-HBc, and anti-HBe titres) and both C-antineutrophil cytoplasmic antibodies (ANCA) and P-ANCA studies were negative. The patient did not have any other stigma of vasculitis such as livedo reticularis, mucocutaneous lesions or glomerulonephritis. The involvement of medium-sized visceral arteries, the history of hypertensive disease, markedly elevated CRP levels and negative ANCA studies supported the diagnosis of PAN.

Outcome and follow-up

There was no recurrence of bleeding during the postoperative period, and diet was progressed normally. The vascular surgery service assessed the coeliac artery aneurysm to have a minimal risk of rupture owing to the small diameter, and the splenic dissection to have greater risk of occlusion if stenting was attempted. The decision was made to observe the status of the other vascular lesions, with surveillance imaging to be done once the patient had received systemic treatment for the vasculitis. The patient was started on high-dose prednisone (1 mg/kg/day) and given his first cyclophosphamide infusion (1000 mg) during admission. He was discharged well on the 10th day after operation.

The patient received cyclophosphamide infusions every 4 weeks and started slow tapering of the steroid dose after 3 months of treatment. Repeat CT angiography was done 5 months into the immunosuppressive therapy, which showed obliteration of the intrapancreatic aneurysm, with no significant change in the status of the coeliac artery aneurysm, splenic artery dissection and the common hepatic artery occlusion (figure 4). There was adequate arterial perfusion into the liver and other distributions of the coeliac axis via the collateral vessels. The plan is to continue immunosuppressive treatment up to 12 months to maximise the chance of resolution of the lesions.

Figure 4.

(A) Repeat CT angiogram image done 5 months after initiation of polyarteritis nodosa therapy showing the absence of the pancreaticoduodenal artery (PDA) aneurysm within the pancreatic head. (B) Three-dimensional reconstruction of repeat CT angiogram showing the absence of the PDA aneurysm.

Discussion

True aneurysms arising within the splanchnic circulation are suggested to be more common than abdominal aortic aneurysms based on autopsy prevalence reports, with up to 10% of autopsies revealing splanchnic artery aneurysms compared with 0.5% for abdominal aortic aneurysms.¹ Within the splanchnic vasculature, aneurysms are more commonly found in the splenic, hepatic and coeliac arteries, while less common vessels of origin include the superior and inferior mesenteric, gastric, colic, gastroduodenal and pancreaticoduodenal arteries.² In an article which combined gastroduodenal artery (GDA) and PDA true aneurysms into a single entity of peripancreatic arterial aneurysms, PDA aneurysms comprised less than 2% of all splanchnic aneurysms, with 99 true PDA aneurysms reported from 1946 to 2004.³

In a report by Moore et al, the mean age of presentation for both GDA and PDA true aneurysms was 58.2 years, while a male predilection (1.73:1 male–female ratio) was seen among cases of PDA aneurysms. The most common presenting symptoms were abdominal pain (52%), gastrointestinal bleeding (24%) and hypotension (22%). Only 6% presented with a palpable pulsatile mass, likely owing to the smaller size and deep retroperitoneal location of these lesions. Rupture of PDA aneurysms (62%) was seen almost twice as frequently than GDA aneurysms (35%). The most common site of PDA aneurysm rupture was into the retroperitoneal space. Rupture into the bowel lumen and within the peritoneal space were also reported. The size of the aneurysm did not seem to affect the likelihood of rupture in the same way as for abdominal aortic aneurysms, as 70% of GDA and PDA aneurysms less than 2 cm were noted to be ruptured on presentation compared with around 50% for those measuring 2 cm or greater. Ruptured PDA aneurysms were reported to have a mortality rate of 21%.³

True peripancreatic aneurysms have been reported to occur in association with various cardiovascular disorders. Aneurysms involving other arteries—mesenteric vessels, renal arteries, aorta, intracranial vessels—have been noted in 22% of patients with PDA and GDA aneurysms.³ The development of peripancreatic aneurysms has also been linked to arteriosclerosis and coeliac occlusive disease, which was seen in 33% of patients. Coeliac obstruction is theorised to increase collateral flow through the GDA and PDA which contributes to vessel enlargement and aneurysm formation.^{3 4} Mycotic aneurysms may develop as complications from an infectious aetiology such as infective endocarditis. Connective tissue disorders, which affect vessel wall integrity and cause structural injury, are also implicated in aneurysm formation. Takayasu arteritis, PAN and Kawasaki disease have all been shown to cause peripancreatic aneurysms in the literature.¹

PAN is defined as a necrotising arteritis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules, and not associated with ANCA.⁵ Peak incidence is during the fifth to sixth decades of life, but all age groups may be afflicted, including paediatric patients.⁶ Most cases of PAN are idiopathic in nature, but causative associations with viral infections have been established in some subsets of the disease. Hepatitis B-associated PAN is the most common among these, characterised by HBsAg positivity at the onset of the vasculitis. PAN has also been shown to be triggered by other viruses such as hepatitis C, HIV, cytomegalovirus and parvovirus B19.⁷

Immune-mediated transmural inflammation in PAN causes vessel stenosis, aneurysmal formation and possible rupture, resulting in varied local or systemic manifestations. Non-specific constitutional symptoms such as fever, malaise, anorexia and weight loss are common. Specific organ involvement can lead to cutaneous, musculoskeletal, neurological, gastrointestinal, renal, cardiac or ophthalmic manifestations.⁶ The gastrointestinal tract may be affected in up to 44% of cases, which may present as abdominal pain, nausea and vomiting, diarrhoea, gastrointestinal bleeding, mucosal ulcerations or frank peritonitis.

The diagnosis of PAN is based on identification of the constellation of clinical symptoms and correlation with pertinent laboratory, imaging and histopathological findings. Biopsy of affected vessels demonstrating acute or chronic inflammation support the diagnosis of vasculitis, but the presence of typical angiographic lesions can still establish a diagnosis of PAN in the absence of histologic confirmation.⁶ The 1990 American College of Rheumatology criteria for classification of PAN requires the presence of at least 3 out of the 10 clinical and diagnostic criteria (table 1). These criteria are now considered with other factors specific to the presentation of PAN, particularly the absence of glomerulonephritis, sparing of small vessels and ANCA negativity.^{6 8}

Table 1.

The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa (PAN)*

Weight loss ≥4 kg	Livedo reticularis
Testicular pain or tenderness	Myalgias, weakness or leg tenderness
Mononeuropathy or polyneuropathy	Diastolic blood pressure >90 mm Hg
Elevated blood urea nitrogen (>40 mg/dL) or creatinine (>1.5 mg/dL)	Hepatitis B surface antigen or antibody reactivity
Arteriographic abnormality with aneurysms or occlusions of visceral arteries	Biopsy of small-sized or medium-sized arteries containing polymorphonuclear cells

*Presence of 3 or more criteria yields a sensitivity of 82.2% and specificity of 86.6% in the diagnosis of PAN.

Visceral angiography performed in patients with a clinical suspicion of PAN may reveal the typical finding of fusiform or saccular aneurysms, which may be as small as 1–5 mm in diameter but can reach up to several centimetres in size. PAN-associated aneurysms are predominantly located at the renal, hepatic and mesenteric artery branches; typically found at vessel bifurcations; and may be concurrent with stenotic lesions.^{6 9 10} These may be asymptomatic on detection via imaging, or may cause ischaemia with end-organ dysfunction, or frank rupture with abdominal signs and cardiovascular compromise. The incidence of PDA aneurysms in PAN is extremely rare, with only three documented cases found in the literature.^{7 10 11} The clinical, interventional and pathological features of the three reported cases and the present case are summarised in table 2.

Table 2.

Clinical, interventional and pathological characteristics of polyarteritis nodosa (PAN)-associated pancreaticoduodenal artery (PDA) aneurysms in the literature

Patient	Age	Sex	Presentation	Comorbidities	Involved vessels	WBC count	Renal function	Inflammatory markers	Hepatitis status	ANCA status	Ruptured (site)	Intervention	Histopathology	PAN treatment
1	78	F	Fever, anorexia, weight loss, dry gangrene of fingertips, abdominal pain, hypotension	Hypertension, tobacco use	Superior and inferior PDA, multiple micro aneurysms in SMA branches	13 000 /mm3	–	ESR 66 mm/hour	Negative	Negative	Yes (retroperitoneal)	Embolisation	None	Prednisone, cyclophosphamide
2	86	M	Abdominal pain, hypotension, respiratory failure	Hypertension, diabetes, abdominal aortic aneurysm, aortic valve replacement	Inferior PDA	–	BUN 30 mg/dL Crea 1.1 mg/dL	ESR 48 mm/hour CRP 15.3 mg/dL	Negative	Negative	Yes (retroperitoneal)	Surgical clipping	Medial fibrinoid degeneration, adventitial leucocyte infiltrate, medial disruption	Prednisone
3	57	F	Asymptomatic	Hypertension	Posterior PDA, inferior PDA, right gastroepiploic (with coeliac axis occlusion and SMA stenosis)	5440 /mm3	BUN 9 mg/dL Crea 0.61 mg/dL	ESR 30 mm/hour CRP 0.09 mg/L	–	Negative	No	Embolisation of posterior PDA, aorto-common hepatic artery-SMA bypass, RGE aneurysmorrhaphy, inferior PDA aneurysmectomy	Neutrophilic and lymphocytic adventitial and medial infiltrates, hyaline degeneration, fibrinoid necrosis	Prednisolone, methotrexate
4	40	M	Haematochezia and melena, syncope, hypotension	Hypertension	Inferior PDA, coeliac axis (with common hepatic artery occlusion)	10 000/mm3	BUN 15.2 mg/dL Crea 0.76 mg/dL	CRP 180.1 mg/L	Past hepatitis B	Negative	Yes (duodenum)	Surgical ligation	None	Prednisone, cyclophosphamide

ANCA, antineutrophil cytoplasmic antibodies; BUN, blood urea nitrogen; Crea, creatinine; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; PDA, pancreaticoduodenal artery; RGE, right gastroepiploic artery; SMA, superior mesenteric artery; WBC, white blood cell.

Management of uncomplicated cases of PAN (without significant end-organ involvement) may be initiated with high-dose corticosteroids (ie, prednisone or prednisolone), then tapered off once symptoms are in remission. Intravenous methylprednisolone pulse therapy is an option for cases with sudden progression of symptoms or immediately life-threatening complications.⁶ For patients with signs of critical end-organ damage, the Five Factor Score has been used to quantify the degree of severity and disease prognosis, and to guide appropriate treatment (table 3). Patients with at least one factor present, as in this case which presented with massive gastrointestinal bleeding, should receive adjunctive immunosuppression with cyclophosphamide to improve remission rates.¹² Intermittent monthly cyclophosphamide pulse therapy is preferred to daily dosing as remission rates are similar between both options, but the intermittent schedule has fewer side effects. A 12-cycle schedule has been shown to provide lower rates of PAN relapse versus shorter treatment schedules, while having comparable safety profiles.¹³

Table 3.

The Five Factor Score (FFS) vasculitis prognosis index*

Proteinuria>1 g/day	One point
Renal insufficiency (creatinine >1.58 mg/dL)	One point
Severe gastrointestinal involvement (bleeding, perforation, infarction, pancreatitis)	One point
Cardiomyopathy	One point
Central nervous system involvement	One point

*FFS=0: 12% 5-year mortality; FFS=1: 26% 5-year mortality; FFS≥2: 46% 5-year mortality.

PAN-associated visceral aneurysms have been shown to regress following systemic treatment with corticosteroids or cytotoxic therapies.^{7 9} However, given the tendency of PDA aneurysms for developing complications and the absence of identified risk factors for rupture, there is no established cut-off size for treatment. Active management must be considered over observation or medical therapy.^{1 3} A combination of endovascular interventions, surgical procedures directly addressing the aneurysm, and arterial bypass techniques may be employed depending on the extent of disease, the adequacy of the splanchnic circulation, the patient’s status at presentation and the availability of treatment modalities and expert providers.

Angiography with embolisation or intravascular bypass is now the preferred mode of treatment, as the endovascular route is less invasive and allows easier access to the deep-seated splanchnic arteries. This is suitable for both intact and ruptured aneurysms with low morbidity and mortality rates.⁴ Care must be taken when mapping out the visceral vasculature and identifying routes of collateral circulation, especially in cases with accompanying occlusion of the coeliac axis or other major arterial branches, as embolisation may not be appropriate if the collateral blood supply flows mainly through the artery to be embolised or if all alternative pathways are diseased and will require intervention. In such cases, coeliac revascularisation with either open arterial bypass or endovascular transluminal stenting accompanied by synchronous or sequential embolisation or aneurysm ligation or excision are all acceptable options, and treatment may be tailored to suit individual patient situations and physician preference.^{3 11} The unavailability of immediate interventional angiography with coiling at our institution, and the persistence of the massive GI bleeding and hypotension despite resuscitation and blood transfusion, necessitated an open procedure for our patient.

Patient’s perspective.

We are very grateful to our doctors (at the managing hospital). They were able to provide us with excellent care despite being at the height of the COVID-19 pandemic. The cause of the bleeding was unclear at the start, but all the necessary tests were done in a timely manner, and our doctors were able to identify and treat the cause before it became life-threatening. Right now, the treatment is still causing some side effects which are problematic at times, but I still prefer these rather than the problems I had at the start. I pray that the treatment is effective and that I can return to my normal activities soon. [translated from Filipino]

Learning points.

• Pancreaticoduodenal artery aneurysms are uncommon vascular entities which may rarely develop in association with polyarteritis nodosa.

• This subset of visceral aneurysm does not have a clear predilection for rupture based on size, warranting immediate management upon diagnosis.

• A combination of angiographic interventions and open surgical procedures may be used in the management of pancreaticoduodenal artery aneurysms, depending on the status of the patient and institutional conditions.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).