Case Reports: Mimics of Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a rare, necrotizing arteritis of the medium or small arteries that lacks the production of anti-neutrophil cytoplasmic antibodies (ANCA).¹ PAN has a variety of clinical presentations and a spectrum of severity. Virtually any organ may be involved, and the disease can present with isolated or multisystem involvement. Greater than 90% of all patients experience constitutional symptoms at the time of diagnosis.² Due to the variable presentation of the disease, the differential diagnosis for PAN is broad and includes infectious diseases, other systemic vasculitides, and vasculopathies, such as segmental arterial mediolysis (SAM) and vascular Ehlers-Danlos (vEDS).^3,4

Case Presentations

Figure 1. Sagittal section from CTA of the abdomen and pelvis taken on hospital day 12 highlighting SMA involvement in vED. The circle highlights the SMA diffuse irregularity and beading of the arterial wall. Arrowheads show hyperenhancement of the distal small bowel related to intestinal ischemia from distal SMA occlusions. The arrow points to hemoperitoneum. The patient also had dilation of the proximal small bowel with cutoff at the right lower quadrant anastomosis consistent with high-grade small bowel obstruction. (Click to enlarge.)

Case 1

A 38-year-old female with a past medical history of post-traumatic splenec­tomy, Bernard-Soulier syndrome, uterine rupture and small bowel obstruction presented to the emergency department with epigastric pain, nausea and vomiting. Initial laboratory tests revealed an elevated white blood cell count of 29×103/μL, with a neutrophil predominance, hemoglobin of 11 g/dL and an elevated venous lactic acid of 3.1 mmol/L. Repeat studies over the next several hours noted an acute drop in blood hemoglobin to 4.8 g/dL, with worsening lactic acidosis.

An urgent computed tomography (CT) angiogram of the abdomen showed a moderate hemoperitoneum, right hemothorax and fatty infiltration of the large bowel suggestive of chronic ischemia. Left renal infarcts were noted, as well as a beaded appearance of the celiac, mesenteric and renal arteries, and an aneurysm of the left renal artery (see Figure 1). The findings were reported as concerning for polyarteritis nodosa.

A massive transfusion protocol was initiated, a right chest tube was inserted, and the patient was transferred to the intensive care unit.

Treatment with intravenous methylprednisolone was commenced for suspected vasculitis at a dose of 1 gm daily. The patient continued to require blood transfusions during this time. Inter­ventional radiology and vascular surgery teams were consulted to assist with stabilizing the bleed; however, the patient was deemed at high risk for vessel rupture due to suspected vessel fragility from active inflammation.

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests performed after the initiation of methylprednisolone were normal. Hepatitis serologies, extractable nuclear antigen (ENA) and ANCA tests were negative. Prior hospital imaging studies were reviewed. Magnetic resonance imaging (MRI) of the brain, performed two years prior when the patient presented to the emergency department with headache and dizziness, showed encephalomalacia and gliosis of the bilateral cerebellum. A CT angiogram of the head and neck was performed to evaluate the cerebral vasculature and demonstrated similar beading involving the carotid and vertebral arteries. The patient also endorsed a history of uterine rupture, which raised suspicion for a collagen vascular disease. Samples were taken for whole exome sequencing and microarray. A purpuric rash of the lower abdomen and a muscle biopsy were performed, but were negative for vasculitis.

The patient’s condition stabilized, and she was quickly tapered off steroids. Whole exome sequencing later revealed a COL3A1 heterozygous variant, c.1241G>T p.Gly414Val, suspected as pathogenic and consistent with vEDS.

Case 2

A 52-year-old male with a past medical history of hypertension, hyperlipidemia and prostate cancer (status post-prostatectomy) presented to a hospital with epigastric and left-side abdominal pain. He appeared diaphor­etic and pale and had severe abdominal tenderness on examination. His initial blood pressure was 88/46 mmHg. Laboratory studies revealed a hemoglobin of 12g/dL, which represented a 3.8g/dL decrease compared with a recent test performed three days prior to his presentation. A CT of the abdomen and pelvis revealed a large retroperitoneal hemorrhagic mass around the pancreatic tail. Massive transfusion protocol was initiated, and he was transferred to the intensive care unit. A CT angiogram of the abdomen showed an enlarging retroperitoneal hematoma with active bleeding. Multifocal narrowing of the celiac and inferior mesenteric arteries was noted, with areas of occlusion. There was focal dissection of the celiac artery and thrombotic occlusion of the proximal inferior mesenteric artery. The pattern of arterial involvement was considered consistent with vasculitis.

The patient remained hypotensive despite fluid resuscitation and vasopressor support and later became obtunded. He was intubated and shortly afterward went into cardiac arrest. Advanced cardiovascular life support was performed with return of spontaneous circulation achieved after five minutes. A mesenteric angiogram was performed by interventional radiology. Active extravasation was found from a branch of the inferior pancreaticoduodenal artery, which was successfully embolized. Ectasias and aneurysms from multiple superior mesenteric artery (SMA) branches, as well as multiple visceral aneurysms, were noted, along with similar findings in the bilateral renal and celiac arteries.

Figure 2. Coronal section from CTA of the abdomen and pelvis taken on hospital day
11 highlighting IMA involvement in SAM. The arrow points to proximal IMA thrombus with multifocal severe narrowing. The asterisk represents an area of large volume pneumoperitoneum resulting from perforation of the distal transverse colon. The arrowhead
corresponds to partially visualized large retroperitoneal hematoma. (Click to enlarge.)

Laboratory testing for hepatitis B and C, HIV and tuberculosis returned negative. ANCA, ANA, ENA tests were negative and no cryoglobulins were detected. A CRP was elevated at 168 mg/L and complement 3 protein was low at 69 mg/dL. The patient received intravenous methylprednisolone at 500 mg every 12 hours for three days, followed by 48 mg daily. He was successfully extubated after nine days.

A repeat staging CT angiogram of the abdomen showed a new large pneumoperitoneum with a large volume of free fluid suspicious for perforated viscus (see Figure 2). The patient was brought to the operating room where greater than 5 L of old clot were seen in the abdomen, along with signs of ischemia and perforation of the distal transverse colon and questionable perfusion to the left colon.

The colon was resected from the mid transverse to proximal rectum and an end side colostomy was formed. Histo­pathology from the resected bowel segments showed necrosis of the vessel wall in one of the branches of the mesenteric artery, along with degenerative changes in the smooth muscle. The findings were deemed consistent with SAM (see Figures 3a and 3b). There was no evidence of vasculitis in the vessels sampled away from the perforation site.

The patient was tapered off steroids following the results of the biopsy. Additional vessel imaging revealed a 1.1 cm aneurysm of the right internal carotid artery. His hospital course was complicated by acute kidney injury requiring intermittent hemodialysis, and critical illness myopathy. His condition slowly improved, and he was discharged to a rehabilitation facility after hospital day 27. He returned to the emergency department three months later with similar symptoms. A repeat CT of the abdomen showed arterial blush and venous pooling in the region of the pancreatic head. Angiography found multiple pseudoaneurysms throughout the mesenteric vasculature. Coil embolization was performed on a large pseudoaneurysm arising from the superior mesenteric artery.

SAM Introduction

Figure 3a. Sampling of arteries in viable areas of the colon resection demonstrates variable degrees of necrosis of the arterial wall. The H&E section (x10 objective) of one artery shows fibrinoid necrosis of the tunica media involving the entire circumference of the artery. There is no significant inflammatory infiltrate, arguing against a vasculitic process. (Click to enlarge.)

Although the etiology is unknown, SAM is characterized by four distinctive lesions: mediolysis, separation, arterial gaps and reparative fibrosis.^5-8 During the acute of injurious phase, mediolysis results in vacuolization and lysis of the outer arterial media where arterial gaps form, transmural loss of the external elastic lamina occurs and separation of media from the adventitia occurs.⁹ Aneurysms and dissecting hematomas form as a result, which may lead to sudden massive hemorrhage or vascular occlusion and thrombus formation. Both conditions occurred in our patient.

Acute intra-abdominal or retroperitoneal hemorrhage share the most common causes of increased mortality (20–50%) in the acute phase.¹⁰ The reparative phase is characterized by exuberant granulation tissue formation and fibrosis filling arterial gaps. This process remodels the artery and may lead to narrowing and stenosis from granulation tissue overgrowth into the adjacent intact intima. The reparative phase is responsible for the wide variety of angiographic lesions associated with SAM.¹¹

Presentation

Figure 3b: The EVG special stain (x10 objective) highlights in another artery segmental necrosis of the arterial wall, including absence of both the external and internal elastic lamina, as indicated by the yellow arrows and asterisk. (Click to enlarge.)

Patients with SAM present with symptoms according to the affected vascular bed. The condition most commonly affects the splanchnic vessels, often leading to abdominal apoplexy due to aneurysmal rupture, or symptoms related to ischemia and infarction, as in our case.^5,8,12 Less commonly, patients can present with hematuria or acute flank pain when the renal vasculature is involved.^7,13–15 Additionally, isolated cases with histopathologic features compatible with SAM have been described in the coronary arteries of neonates, children and young adults, and the cerebral arteries of adults.^{5–7,16–20}

vEDS Introduction

vEDS is a rare autosomal dominant disorder caused by heterogenous mutations in the α1 type III collagen gene COL3A1, leading to a deficit in collagen III.^21,22 Collagen III is a major extracellular matrix component of the vasculature and hollow organs. Abnormal or deficient collagen III production leads to arterial, intestinal and uterine fragility, the characteristic features of vEDS.^23,24 Different variants at the COL3A1 gene have been shown to influence the course of the disease and clinical phenotype, which contributes to the complexity of making the diagnosis.²³ vEDS has the worst prognosis of the Ehlers-Danlos syndromes due to its propensity to rupture hollow organs and arteries. In patients who are symptomatic, arterial complications tend to predominate, followed by digestive and obstetric complications, respectively.²³

Presentation

The majority (60%) of patients are diagnosed before the age of 18 and are identified because of a positive family history.²⁴ Early presenting features in children include excessive bruising, thin, translucent skin showing visible venous patterns, and congenital abnormalities, such as clubfoot and hip dislocation.²⁵ Patients may also display characteristic facial features, which include the presence of prominent eyes (owing to lack of lack of subcutaneous adipose tissue around the eyes), a thin, pinched nose, small lips, hollow cheeks and lobeless ears.

Complications are overall rare in childhood, but up to 25% of patients may experience their first major event by the age of 20 and 80% by the age of 40.²⁶ The majority of complications are arterial in nature and consist of aneurysm formation, dissection or rupture of medium-sized vessels. The most frequently involved sites include the abdominal visceral arteries, iliac arteries and thoracic and abdominal aorta.²⁷ Abdominal visceral aneurysms or dissections often involve multiple visceral arteries. The next most frequent locations of arterial involvement include carotid, subclavian, ulnar, popliteal and tibial arteries.²⁸ Most patients will develop multiple vascular complications without any antecedent trauma, which may be symptomatic or discovered incidentally.³⁴

Gastrointestinal complications occur in up to 25% of patients, with spontaneous rupture of the sigmoid colon being the most common complication.^25,28 In the 30-year Mayo Clinic experience, the reported survival free from an arterial, intestinal or uterine complication was 84% at age 20, 37% at age 30 and only 4% at age 60. This highlights the risk of patients with the condition developing devastating complications over time.²⁸

Differential

The differential diagnosis for SAM and vEDS is broad because many vascu­lopathies demonstrate similar radiologic findings. The differential includes atherosclerosis, fibromuscular dysplasia (FMD), infections (e.g., mycotic aneurysm and endocarditis), small-to medium-sized vasculitides (e.g., ANCA-associated vasculitides and polyarteritis nodosa), connective tissue diseases (e.g., systemic lupus erythe­matosus and Behçet disease) and inherited defects in vessel wall struc­tured proteins (e.g., Ehlers-Danlos and Marfan’s syndrome).²⁹

Most cases can be excluded on clinical grounds, and laboratory studies are typically normal in terms of inflammatory markers and auto­immune serologies in patients with SAM. FMD can be difficult to differentiate from SAM because the conditions are both non-inflammatory, non-atherosclerotic arterial diseases with similar histologic and angiographic findings.^30–33 However, the clinical profiles differ, with FMD occurring in mainly in young to middle-aged women who may be asymptomatic or present with symptoms associated with occlusive disease and rarely rupture. The pattern of arterial involvement is also different with FMD in which the renal and internal carotid arteries are most affected. Extrarenal visceral involvement is considered less common in FMD as well, in contrast with SAM where the converse is true.^5,8,12,34

Discussion

Rare, non-atherosclerotic, non-inflammatory arteriopathies, vEDS and SAM are potentially life-threatening, as indicated in our cases. Both conditions can present with imaging findings that mimic PAN and can similarly lead to devastating complications including aneurysm formation, dissection and spontaneous vascular rupture.

Despite the potential similarities with regards to presentation, vEDS and SAM are managed differently than PAN. Given immune-mediated underpinnings, PAN typically requires treatment with systemic glucocorticoids and immunosuppres­sants, such as mycophenolate mofetil or metho­trexate. In severe, organ- or life-threatening disease, cyclophosphamide may be used.³⁵ In contrast, management of vEDS and SAM do not involve immunosuppression and are primarily preventive and supportive—including regular vascular surveillance, strict blood pressure control and lifestyle modifications (e.g., avoidance of unnecessary invasive procedures and trauma). In the setting of complications, such as hemorrhage, ischemia or rapid evolution of vascular defects, surgery, endovascular embolization or stenting may be required.^18,28

Ultimately, vEDS and SAM should be considered in the differential for patients presenting with clinical features or imaging suggestive of PAN, especially in the absence of systemic symptoms, because accurate diagnosis can have profound impacts on management.

Shane Murray, BMBS, RhMSUS, obtained his medical degree at the University of Limerick, Ireland. He completed an internal medicine residency at Mount Sinai Morningside & Mount Sinai West Hospitals, New York, and a rheumatology fellowship at Columbia University Irving Medical Center, N.Y. He joined the Department of Rheumatology at the Yale School of Medicine in 2024.

Zhe Ran Duan, MD, PhD, obtained her medical degree at Weill Cornell Medical College, New York. She completed an anatomic pathology residency at Columbia University Irving Medical Center, New York, and is currently completing a surgical pathology fellowship there.

Daniel DeMizio, MD, obtained his medical degree at Albert Einstein College of Medicine in New York. He completed his internal medicine residency at Mount Sinai Hospital in New York and his rheumatology fellowship at Columbia University Irving Medical Center, N.Y. He has served as chief of rheumatology at Richmond University Medical Center, New York, since 2023.

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