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11 February 2024: Articles  China (mainland)

Immunoglobulin G4-Related Disease Complicating Ruptured Isolated Iliac Artery Aneurysm: A Complex Management Dilemma

Challenging differential diagnosis, Unusual or unexpected effect of treatment, Diagnostic / therapeutic accidents, Unexpected drug reaction, Rare disease, Clinical situation which can not be reproduced for ethical reasons

Yizhe Meng12ABDE, Xunhong Duan2ADE, Jianping Liu2DE*

DOI: 10.12659/AJCR.942727

Am J Case Rep 2024; 25:e942727




BACKGROUND: Managing IgG4-related disease (IgG4-RD) in the context of vascular complications, such as aneurysms, poses significant challenges, particularly when considering surgical intervention options. The risk of rupture and infection in patients on long-term glucocorticoid therapy complicates treatment decisions.

CASE REPORT: A 63-year-old woman with a history of IgG4-RD presented with a ruptured right iliac artery aneurysm. She was on long-term oral glucocorticoid therapy. Initial emergency endovascular stent graft implantation was followed by embolization for suspected arterial bleeding and subsequent Salmonella bacteremia. Repeated hospitalizations involved stent graft removal and surgical repair due to persistent infection. Over 2 years, the patient required multiple pelvic drainages and long-term antibiotic and prednisolone therapy, yet her quality of life remained compromised.

CONCLUSIONS: Our case highlights the unique challenges and considerations in the treatment of IgG4-related aneurysms. Patients with IgG4-RD who are on long-term oral glucocorticoids have an inherent risk of aneurysm rupture. We believe regular follow-ups to monitor the progression of the aorta and iliac arteries into aneurysms are essential. For patients who have developed aneurysms, it is advisable to reduce the dosage of glucocorticoids or even consider surgical treatment as soon as possible. As for the choice of surgical method, there is no consensus yet. While endovascular treatment is less invasive and quicker, it can increase the risk of rupture and bleeding. Open surgery might be a better option. More data are needed to make a definitive judgment.

Keywords: Immunoglobulin G4-Related Disease, Iliac Aneurysm, endovascular procedures, perioperative period, infections


Isolated aneurysms of the iliac arteries are extremely rare, comprising less than 2% of all aneurysmal diseases [1]. Among them, reports regarding immunoglobulin G4-related disease (IgG4-RD) as a cause of isolated iliac artery aneurysms (IAAs) are even rarer. Consequently, our knowledge of the treatment of such diseases and the management of surgical complications is quite limited.

We report a case of a 63-year-old woman with a ruptured isolated iliac artery aneurysm complicated by IgG4-RD, who underwent endovascular treatment and subsequently developed multiple complications postoperatively. Currently, there is no ideal treatment approach for such patients. We have documented this case report in the hope of stimulating further discussion and exploration in this area.

Case Report

A 63-year-old woman was admitted due to rupture of the right iliac artery aneurysm, leading to half-day of hemorrhagic shock. Physical examination showed temperature 37.4°C, pulse rate 141 beats per minute, respiratory rate 25 breaths per minute, and blood pressure 75/40 mmHg. She appeared alert but mentally compromised, displaying features of acute shock and pale complexion. An emergency abdominal aortic and iliac artery computed tomography angiography (CTA) from another hospital indicated the rupture of the right iliac artery aneurysm, measuring approximately 30 mm, accompanied by intraperitoneal hemorrhage. The patient, with a history of IgG4-RD, had been on long-term oral prednisone therapy at a dose of 15 mg once daily. In-hospital laboratory testing revealed an elevated IgG4 level of 285 mg/dL. In fact, during the subsequent 2-year follow-up, IgG4 levels fluctuated between 243 and 373 mg/dL (12 measurements). She tested negative for anti-dsDNA, anti-SSA/Ro, and anti-SSB/La antibodies, as well as p-ANCA and c-ANCA. Concurrently, she had chronic renal dysfunction, with creatinine levels ranging from 105.3 to 216.7 μmol/L in multiple follow-up visits. CT scans revealed the presence of multiple small circular low-density lesions within the renal parenchyma, predominantly on the right side (Figure 1). Unfortunately, we were unable to obtain specific organ pathology specimens from the patient.

The preliminary diagnosis for the patient included hemorrhagic shock, ruptured right-sided iliac artery aneurysm, IgG4-RD, renal dysfunction, hypertension, and diabetes. Laboratory test results revealed decreased levels of hemoglobin, red blood cell count, and hematocrit, with a white blood cell count of 6.38×109/L, a red blood cell count of 1.81×1012/L, a hemoglobin level of 53 g/L, a hematocrit of 17.9%, and a platelet count of 166×109/L. She underwent emergency iliac artery endovascular stent graft implantation due to the ruptured iliac artery aneurysm (Figure 2). Following the surgical procedure, she was transferred to the Intensive Care Unit (ICU) for close monitoring and intensive care. During the hospitalization, despite receiving multiple blood transfusions, the hemoglobin levels continued to decrease. There was suspicion of bleeding from the lumbar and intercostal arteries. Subsequently, a repeat procedure was performed, involving embolization of the right lumbar artery and intercostal artery. During intraoperative digital subtraction angiography (DSA) imaging, the stent placed within the iliac artery showed no signs of contrast agent leakage; otherwise, the right subcostal artery, as well as the right lumbar arteries at L1, L2, and L4, would be selected. No significant extravasation of the contrast agent was observed. Gelatin sponge embolization was employed. Following the procedure and subsequent blood transfusions, there was no further decline in hemoglobin levels. Therefore, it was suspected that bleeding from either the right lumbar artery or the intercostal artery at some location had been causing the progressive drop in hemoglobin. Unfortunately, the patient developed persistent fever. Bacterial culture of the blood revealed bacteria from the Salmonella genus. A multidisciplinary consultation was convened to address this issue, leading to the initiation of oral low-dose corticosteroids at 10 mg once daily in combination with intravenous cefoperazone/sulbactam for antimicrobial therapy. Following the implementation of this treatment regimen, the fever gradually subsided, and the patient’s overall condition improved, ultimately resulting in hospital discharge. The postoperative CTA findings are depicted in Figure 2.

One year later, the patient was hospitalized due to intraperitoneal bleeding with infection. Despite conservative treatment, she repeatedly experienced symptoms of fever and chills indicative of an ongoing infection. As a result, the decision was made to remove the stent graft and surgically repair the vessel. Following the procedure, the patient’s condition improved. A follow-up CTA was performed, and the results are depicted in Figure 3.

Over the course of the following 2 years, she underwent multiple pelvic drainage procedures, and the drainage fluid, as determined by bacterial culture, continued to show bacteria from the Salmonella genus. She has been on long-term low-dose oral cefdinir 0.1 g 3 times a day and azithromycin 0.25 g once daily to control the infection. Additionally, she has been taking low-dose oral prednisolone for the treatment of IgG4-RD. However, despite these measures, the outcomes have not been satisfactory, and the patient’s quality of life remains suboptimal.


The diagnosis and treatment process for this patient’s condition has been complex, with numerous therapeutic contradictions, significantly increasing the difficulty of treatment. Firstly, the rupture of the isolated iliac artery aneurysm required emergency surgery, leaving insufficient time to establish a comprehensive treatment plan. Secondly, the risk of infection was elevated due to a second surgery following postoperative bleeding. She also had a history of IgG4-RD, which may have been the underlying cause of the isolated artery aneurysm and was being treated with long-term corticosteroid therapy, potentially contributing to the subsequent stent graft infection. Lastly, despite removal of the covered stent graft after repeated infections and unsuccessful conservative treatment, she continued to experience recurrent pelvic infections, necessitating multiple pelvic drainage procedures, with unsatisfactory results. Additionally, the long-term or even life-long oral administration of azithromycin in combination with third-generation cephalosporins poses a significant challenge to the patient’s long-term prognosis.

IAAs are rare conditions typically diagnosed through screening or other imaging studies [1,2]. Patients often remain asymptomatic unless the aneurysm becomes large, with symptoms primarily arising from compression of adjacent structures. Similar to abdominal aortic aneurysms (AAAs), IAA tends to have a propensity for fatal rupture as it enlarges [3–5]. The management of asymptomatic IAA depends on aneurysm size, the presence of concurrent AAA or other aneurysms, and coexisting conditions [6]. Symptomatic IAA patients should promptly undergo vascular assessment and repair [7,8].

Most iliac artery aneurysms are true aneurysms caused by degeneration of the arterial wall. The formation of true aneurysms is attributed to an imbalance in the generation and degeneration of vascular wall components, disrupting mechanical integrity [9]. The etiology of this imbalance is likely multifactorial, resulting from complex interactions of various factors, including inflammatory and immune elements, and potentially involving mechanical and genetic factors [10–13].

IgG4-RD is an immune-mediated condition that has been recognized in recent years and can affect multiple organs, including the pancreas, bile ducts, salivary glands, orbital region, kidneys, retroperitoneal tissues, lymph nodes, lungs, and thyroid [14–18]. Affected organs often exhibit proliferative enlargement and swelling due to fibrosis and chronic inflammation, leading to compression, obstruction, or functional impairment [14,15,19]. Increasing evidence suggests that the pathogenesis of IgG4-RD has an autoimmune basis, with significant roles played by B cells and T cells, particularly CD4+ T cells and T-follicular helper cells (Tfh) [19]. IgG4-RD is more commonly observed in middle-aged to elderly men but can also affect females and children [20]. Enlarged lymph nodes are a common feature, and asthma or allergic symptoms may be present. IgG4-RD can involve one or multiple organs, with manifestations reported in nearly every organ system [21,22]. It has been identified as one of the etiologies for non-infectious aortitis. A retrospective analysis of imaging studies in 160 IgG4-RD patients at one medical center revealed IgG4-RD as a unique and treatable cause of large-vessel vasculitis [23]. It may also involve secondary vascular changes related to perivascular swelling. The most common secondary vascular manifestation is periaortitis with relative sparing of the aortic wall [23]. Early treatment of IgG4-related aortitis can reduce the need for surgical repair, but in cases of inflammatory thoracic or abdominal aortic aneurysms, arterial graft placement, stent graft placement, or endovascular repair may be necessary [24,25]. Reports of IgG4-RD combined with IAAs are extremely rare, and there is no consensus on the diagnostic and therapeutic approach for ruptured iliac artery aneurysms.

IgG4-RD has an insidious onset and can progress to advanced stages with poor treatment outcomes, often resulting in severe organ damage. Therefore, early diagnosis and treatment are crucial. Once IgG4-RD is confirmed, it is essential to assess the extent of the disease before initiating treatment. Evaluation should include chest, abdominal, and pelvic CT scans, urine analysis, serum complement levels, and markers of allergic or hypersensitivity diseases, such as serum IgE levels and peripheral blood eosinophil counts. Recent guidelines [26] recommends that most patients requiring treatment should start with monotherapy using prednisone, typically at a dose of 0.6 mg/kg once daily. The treatment goal is to reduce inflammation and induce remission, with the aim of preserving organ function while minimizing the adverse effects of glucocorticoids and other medications. Infection is one of the most common drug-related adverse effects.

In our case, the patient experienced a ruptured IAA. Considering the unstable vital signs and the presence of an adequate iliac proximal and distal neck, we ultimately opted for a faster and less invasive endovascular treatment to reduce perioperative and intraoperative risks [27]. However, it is worth noting that some reports suggest that endovascular procedures can lead to more clinical symptoms and postoperative complications when compared to open surgery, such as persistent inflammation, periaortic fibrosis, aneurysm expansion, or even recurrent aneurysm rupture [28–30]. Maheshwari et al presented a case in which IgG4-RD was identified as the etiology of an external iliac artery aneurysm. The patient underwent iliofemoral bypass with an 8-mm polyester graft and during 1-year follow-up did not experience any related complications [28].

Some studies also suggest that glucocorticoids can lead to vascular wall thinning [31,32]. This poses a risk of aneurysm rupture. Mizushima et al and Ozawa et al reported that glucocorticoids may have a preventive effect on aneurysm expansion in non-dilated aneurysms but can exacerbate it in patients who already have aneurysm expansion [33,34]. Thus, while glucocorticoids are crucial for IgG4-RD, they can also increase the risk of aneurysm rupture, necessitating surgical treatment [35]. To determine the role of glucocorticoids in luminal dilation, larger prospective studies are needed.

Additionally, glucocorticoids create favorable conditions for secondary infections, making postoperative patient management challenging. Therefore, it is difficult to determine the optimal therapeutic strategy for IgG4-related artery lesions. We recommend low-dose oral corticosteroids to improve IgG4-related inflammatory IAA and reduce the high risk of infection.

Research indicates that the incidence of aortic stent graft infection ranges from 0.4% to 3%, with associated mortality rates of 25% to 50% [36–40]. Infection of iliac artery stent grafts is a relatively rare but severe complication in vascular surgery, with high morbidity and amputation rates once it occurs. The implantation of stent grafts can lead to endothelial cell denudation during the attachment process to the vascular wall, allowing host blood cells and plasma proteins to cover their surface, creating a polysaccharide-protein aggregate biofilm consisting of infective pathogens and extracellular matrix on the stent graft surface. This biofilm provides a microenvironment conducive to microbial survival, rendering the infective bacteria resistant to host immune responses and antimicrobial treatments [41]. On the other hand, the presence of an intravascular stent graft alters hemodynamics, resulting in increased blood flow turbulence and shear forces, enhancing endothelial cell and platelet responses, making microorganisms more prone to adhere to the vessel wall, while inhibiting the adhesion and phagocytosis of neutrophils and monocytes [42].

The treatment strategy for stent graft infection is similar to that for graft infection following open aneurysm repair. Both aggressive and conservative approaches have been used in the management of stent graft infections [43]. Among them, antimicrobial therapy is a cornerstone of both surgical and conservative treatments [44]. For patients who are not suitable candidates for surgical intervention, long-term or even life-long antimicrobial therapy may be the only viable option. The optimal duration of antimicrobial therapy is currently not standardized, but intravenous antibiotic administration for more than 6 weeks followed by oral antimicrobial therapy for more than 6 months is a feasible approach [44,45]. If the patient has no surgical contraindications, complete removal of the infected graft, thorough debridement, and reconstruction of the distal arterial blood flow are recommended. For critically ill patients with surgical difficulties, patent infected stents, no sepsis or thromboembolic complications, no vascular injury or pseudo-aneurysm, and low virulence of the infecting pathogens, conservative treatment may be considered, where the infected stent graft is not removed or is partially extracted.


In summary, our case highlights the unique challenges and considerations in the treatment of IgG4-related aneurysms. In our case, for patients with IgG4-RD who are on long-term oral glucocorticoids, there is an inherent risk of aneurysm rupture. We believe regular follow-ups are essential to monitor the progression of the aorta and iliac arteries into aneurysms. For patients who have developed aneurysms, it is advisable to reduce the dosage of glucocorticoids or even consider surgical treatment as soon as possible. As for the choice of surgical method, there is no consensus yet. While endovascular treatment is less invasive and quicker, it can increase the risk of rupture and bleeding. Open surgery might be a better option. More data are needed to make a definitive judgment.


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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923