Herein we present a rare case of IgG4 aortitis, whose unusual presentation and imaging characteristics not only hindered accurate diagnosis and influenced treatment decisions, but also resulted in the detection of an underlying malignancy, enabling the patient to receive prompt initiation of treatment. Despite collaborative efforts from a multidisciplinary clinical team, comprehensive laboratory tests, and various imaging investigations, establishing a definitive diagnosis in this patient was unattainable without surgery. Intramural hematoma of the aorta characterizes by the accumulation of blood within the aortic wall, typically due to rupture of the vasa vasorum or intimal tear without full-thickness aortic wall disruption. Patients often present with sudden onset severe chest or back pain, similar to aortic dissection, but without the typical pulse deficits or blood pressure differentials seen in dissection, like it happened in this patient. Diagnosis relies heavily on imaging studies, particularly CT angiography, which can visualize the hematoma within the aortic wall.

IMH, the presumed diagnosis, was only ruled out at the time of surgery with direct visualization of the aorta, while histopathology of aortic specimens established the definitive diagnosis of IgG4 aortitis, and later the discovery of an undiagnosed CLL.

Aortitis is a type of vasculitis characterized by inflammation of the aorta and/or its major branches. The most common cause of aortitis in adults is typically large-vessel vasculitides (LVV), which include giant cell arteritis (GCA) and Takayasu arteritis (TAK). These conditions predominantly affect the proximal thoracic aorta, and are relatively uncommon [10, 26, 32, 36]. Due to its complex phenotypic spectrum, LVV frequently present with features and symptoms similar to other diseases of the proximal aorta, including intramural wall hematoma, making accurate diagnoses and subsequent management difficult. Less frequently, aortitis may also occur in association with other forms of vasculitis or underlying conditions, including: inflammatory and rheumatological diseases (i.e. rheumatoid arthritis, Behcet's disease, IgG4-related disease, RA, and SLE), as well as various infections (i.e. syphilis, salmonella, HIV, and tuberculosis) [12].

Typically presenting with nonspecific symptoms such as chest discomfort, fever, and weakness, LVV patients frequently evade diagnosis despite multiple encounters with healthcare providers [36]. This is even more apparent in cases of aortitis caused by IgG4, with case reports in literature highlighting the difficulties in diagnosing this uncommon and under recognized cause of aortitis [36, 39, 41].

Distinguishing chronic aortitis compared to atherosclerosis may be challenging on MRI, as there can be significant overlap between chronic inflammatory changes of aortitis and atherosclerosis. Unique aspects of MRI included comprehensive T2 mapping of aortitis along with LGE performed using different inversion times. These methodologies are complementary to 3D MRA and conventional evaluation of edema and enhancement on MRI [11]. Comprehensive characterization of vascular inflammation using these techniques needs prospective evaluation as currently use of these techniques is not well described in the literature (Fig. 6) [5, 16].

Lacking a definitive diagnostic test and no validated diagnostic criteria, aortitis is usually diagnosed histopathologically after surgery for aortic aneurysms or presumed aortic dissections [8, 12]. No other organ biopsies apart from the bone marrow biopsy were perrfomed to allow for a preoperative diagnosis of IgG4 aortitis, however the patient had a negative MRI of the temporal lobe, which has been found to be a good subrogate for GCA allowing to avoid invasive biopsies.

IgG4 related disease is an immune-mediate fibroinflammatory condition capable of affecting multiple organs. Clinical manifestations may include salivary gland involvement, lymphadenopathy, orbital inflammation, autoimmune pancreatitis, sclerosing cholangitis, retroperitoneal fibrosis, and vascular involvement [20]. The diagnosis of IgG4-RD requires clinical or radiologic evidence of organ involvement and a biopsy that demonstrates lymphoplasmacytic infiltrate with multiple IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Serum IgG4 is elevated in 2/3 of patients. It is estimated that IgG4-related aortitis occurs in approximately 8 percent of patients with IgG4-RD and accounts for 2–9 percent of all patients with noninfectious aortitis. Although some genetic associations like HLA class II genetic region, genes encoding for cytokines like TNF and their receptors, VEGF and ICAM-1 have been described, there is no particular symptomatology or radiological finding that can help distinguish IgG4 vasculitis from the rest of the large vessel vasculitis spectrum until the histopatological diagnosis is performed [30, 36, 43].

This case exemplifies the critical role of multidisciplinary collaborations when navigating complex aortic conditions such as aortitis. Our patient benefited from a comprehensive treatment team comprising cardiac surgeons, imagining specialists with expertise in aortic disease, a cardiac surgery intensive care unit (ICU) experienced in managing acute aortic diseases, and a rheumatologist, all actively involved in the diagnostic and decision making process. Even with this comprehensive support, uncertainties persisted regarding the presumed definitive diagnosis of IMH in this patient, posing further challenges in determining an appropriate treatment strategy.

Regarding treatment, IgG4-related vasculitis can often be treated medically with corticosteroids and immunosuppressive agents, leaving surgical excision for very severe cases. In contrast, intramural hematoma, when developed, can be managed medically with strict blood pressure control and close monitoring if non-expanding, absence of pain and no complication such as rupture develop, otherwise, surgical intervention is warranted (Table 1).

Given most data available on type A IMH favors surgical intervention, with IRAD reporting mortality rates of 40% with nonoperative strategies, surgical intervention was heavily favored in our patient [7, 15, 17, 29, 39]. Taking into account the patient’s characteristics, low surgical risk, and high risk IMH image findings, surgical intervention was established as the treatment of choice. Alternatively, had a diagnosis of aortitis been recognized, the patient may have been able to forego surgery and receive treatment directed at IgG4-RD. However, this approach would have left diseased and weakened aorta behind in a young patient, placing her at an increased lifelong risk of suffering a potentially lethal adverse aortic event. Irrespective of etiology, aortitis is related to significant morbidity and mortality, due to the development of complications such as aortic aneurysm, aortic rupture, aortic dissection, and/or thrombotic luminal obstruction [8, 12]. Particularly, aortitis of the ascending aorta is known to be associated with ascending aortic dissection and increased mortality [23, 41].

Another intriguing aspect of this case and rare diagnosis of IgG4-related aortitis, is its potential association with malignancy. Research indicates a potential precursor connection between IgG4-related conditions and invasive malignancies, such as prostate cancers, lymphomas, myeloproliferative neoplasm and acute myeloid leukemia [41, 42]. Interestingly, our patient was later diagnosed with concurrent chronic lymphocytic leukemia (CLL); however, determining which condition preceded the other remains uncertain. Fortunately, both conditions share the same treatment approach, offering some solace for the patient.