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. 2018 Feb 20;12:1179546818759678. doi: 10.1177/1179546818759678

On the Diagnosis of Mycotic Aortic Aneurysms

Karl Sörelius 1,, Pietro G di Summa 2
PMCID: PMC5824903  PMID: 29497343

Abstract

Objective:

There is striking paucity in consensus on the terminology, definition, and diagnostic criteria of mycotic aortic aneurysms. This literature study aims to elucidate this scientific omission, discuss its consequences, and present a proposition for reporting items on this disease.

Methods:

A systematic literature review on PubMed and Medline using mycotic and infected aortic aneurysms between 1850 and 2017 was performed. Articles were assessed according to a protocol regarding terminology, definition, and diagnostic criteria. Case series with less than 5 patients were excluded.

Results:

A total of 49 articles were included. The most prevalent term was mycotic aortic aneurysm but there was no widely accepted definition. Most modern publications used a diagnostic workup based on a combination on clinical presentation, laboratory results, imaging findings, and intraoperative findings. How these protean variables should be balanced was unclear. A proposition of reporting items was framed and consisted of definition of disease used, basis of diagnostic workup, exclusion criteria, patient characteristics, laboratory and imaging findings, aneurysm anatomy, details on treatment, pre/postoperative antibiotic treatment, and details on follow-up.

Conclusions:

This article emphasizes the need to standardize definition, terminology, and diagnostic criteria for mycotic aortic aneurysms and proposes reporting items enhancing comparability between studies.

Keywords: Mycotic, aneurysm, infected, aorta, diagnosis, revised, terminology, criteria, reporting standards

Introduction

A mycotic aortic aneurysm (MAA), synonymously known as infected aortic aneurysm, is an aortic aneurysm due to infection. Mycotic aortic aneurysm most commonly develops through microbial inoculation of the diseased aortic endothelium during bacteremia.1,2 Once the microorganism has infected the aortic wall, a fast degradation of the intimal and medial layers may occur, with development of an aneurysm.36 The causative infective agents are predominantly bacteria but rare cases of fungus have been reported.79 The term “mycotic aneurysm” is thus a misnomer for infection, and imprecise, while implicating a fungal genesis, which is extremely rare. The term mycotic originates from 1885, when Sir William Osler, in his Gulstonian lectures, described a patient with valve vegetations and 4 aortic aneurysms with morphological fungal resemblance.10 The term has since stuck, probably because of common usage. Osler was, however, not the first to describe the relationship between infective endocarditis and aneurysm development; Koch in 1851, Tufnell in 1853, and Oggle in 1866 were before him, but not for aneurysms involving the aorta.1113 Many have argued that a more correct term would be infected aortic aneurysm.1416 Throughout the past 130 years, the disease MAA has gone through significant changes; in the days of Osler, most of the aneurysms due to infections were secondary to syphilitic aortitis engaging the adventitia, with aneurysm formation at necrotic focal points due to obliterative endarteritis,5,17 or infective endocarditis with septic embolization to the aorta,5,14 whereas after the 1940s and the introduction of antibiotics, bacteremia in an aged atherosclerotic aorta is the dominant pathogenetic pathway.18,19

A plethora of terms such as “mycotic aneurysm”, “primary mycotic aneurysm”, “suppurative arteritis”, “cryptogenic mycotic aneurysm”, “SAP (septic aortic pseudoaneurysm)”, and “infected aneurysm” have been used14,2024 but none with broad acceptance. It is also not uncommon in the literature to mix different infectious conditions involving the aorta, such as graft infection and aorto-enteric fistula together with aortic aneurysms due to infection.2527

There are several problems when studying MAAs such as (a) ill-defined disease, (b) variable terminology indicating fungal genesis, (c) variable or absent diagnostic criteria in the literature, and (d) mixed patient populations with different aortic infections with different natural courses, with various demands on management.

The disease is rare, with an estimated incidence of 0.6% of all aortic aneurysms in Western countries28,29 and up to 13% in Taiwan.23 Hence, most existing studies are underpowered and nonattainable for statistical inference. These problems, (a) to (d), make comparisons between studies unnecessarily challenging and sometimes impossible.

This article aims to elucidate the absence of definition and classification of MAAs, to discuss the consequences of lack of standardization, and to present a suggestion for reporting items to facilitate comparability between studies.

Methods

A systematic literature search was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement on PubMed and Medline between January 1, 1850 and January 1, 2017. The search terms were mycotic aortic aneurysm and infected aortic aneurysm. Reference lists were also scrutinized to identify additional papers. The ones discussing or introducing new terminology, definitions, diagnostic criteria, and classification were selected for scrutiny. Case series of at least 5 patients were read in full to analyze the diagnostic workup of the study. Case reports were not included. Graft infection and aorto-enteric fistulas were excluded. All selected studies were reviewed according to a predefined protocol regarding terminology, definition, diagnostic criteria, and classification of the disease.

Based on previous definitions, current knowledge on the disease, and present clinical needs, a proposition was framed for reporting items to account for when reporting on the disease.

Meta-analyses were not possible to perform due to the qualitative nature of the study, neither was risk of bias assessment.

Results

A total of 49 articles were included in the literature analysis, see flowchart in Figure 1. Whether the disease is increasing is unclear, but the number of publications has doubled per decade on mycotic/infected aneurysms between 1982 and 2012.30

Figure 1.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Consort flow diagram.

Terminology and definitions

Table 1 lists different terms being used throughout history with accompanying definitions, diagnostic criteria, or significations attributed to aortic aneurysms caused by infection. The terms infective vasculitis and endovascular infection have mainly been used in the context of intracranial aneurysms due to infection. Since the 1980s, the most prevalent terms have been mycotic and infected aortic aneurysms. The most common definition was not evaluable due to too much diversity.

Table 1.

Account of the plethora of terminologies, definitions, diagnostic criteria, and significance attributed to aortic aneurysms due to infection.

Author (year of publication) Terminology Definition (D), diagnostic criteria (DC), signification, or understanding of the disease
Oggle (1866)13 Proposing relationship between aneurysms and endocarditis
Osler (1885)10 Mycotic aneurysm Aneurysm associated with infective endocarditis
Eppinger (1887)31 Embolomycotic Infectious and embolic etiology of aneurysm
Wiesel (1906)32 Not all aneurysms due to infection are related to endocarditis, but to infection in general
Lewis (1909)33 Embolomycotic aneurysm D: Causes of aneurysm due to infection were not solely endocarditis but also trauma and other infection
Stengel (1923)3 Mycotic (bacterial) aneurysms Mycotic aneurysms may arise without endocarditis, and cultures are difficult to determine
Crane (193720 Primary multiocular mycotic aneurysm of the aorta D: Lesion developed in the aortic wall without associated intravascular focus, no intra/extravascular inflammation or endocarditis
Barker (195434 Mycotic aneurysm Recommending prompt surgery
Parkhurst (1955)5 Mycotic (bacterial) aneurysm of the aorta Preexisting disease of the aorta favors establishment of infection
Sommerville (1959)1 Infected arteriosclerotic aortic aneurysm Preexisting aneurysms may be secondarily infected
Blum (1962)21 Cryptogenic mycotic aneurysm Bacteria invading the endothelium at the site of atherosclerotic disease
Sower (1962)35 Suppurative arteritis
Bennett (1967)4 Bacterial infection of aortic aneurysm
Jarrett (1975)14 Infected aortic aneurysm Objecting the term mycotic since indicating a fungal genesis
Patel (1977)22 Mycotic aneurysm Switch of terminology. D: New classification; consider preexisting arterial status and source of infection, excluding infected preexisting aneurysms, intracranial aneurysms and infected prostheses
Wilson (1978)36 Spontaneous arterial infections D: Classification and subgroups: mycotic aneurysms, infected aneurysms, microbial arteritis, traumatic infected pseudoaneurysm
Davies (1978)37 Cryptic mycotic abdominal aneurysm DC: Combination of fever, pulsatile mass and aortography
Johansen (1983)38 Mycotic aortic aneurysm Recognizing a substantial part of patients suffer from immune suppression
Oz (1989)39 Bacterial aortitis Emphasizes that aortas of normal diameter may be infected
Chan (1989)40 Mycotic aneurysm of the aorta Naturally occurring aortic aneurysms that result from or are secondarily infected by bacteria arising in a distant site of infection
Reddy (1991)18 Infected aortoiliac aneurysm D: Retaining the Wilson classification, and adding a subgroup of aortic infection due to contiguous spread from adjacent organ
Fichelle (1993)a,41 Infected aortic aneurysm D: Subclassification: postembolic aneurysms, infective aortitis, infected atherosclerotic aneurysms. Including aortic fistulas
Sessa (1997)a,16 Infected aneurysm D: A lesion of the arterial wall due to bacterial contamination
Nair (2000)42 HIV-related aneurysms Description of multiple aneurysms in young patients with advanced HIV infection
Müller (2001)43 Mycotic aneurysm DC: Positive culture (aneurysm wall/content/surrounding tissue) and signs of infection. If negative culture, aneurysm is mycotic only if (1) intraoperatively typical aspects, (2) clinical signs of infection, and (3) treated with antibiotics before surgery
Ihaya (2001)44 Infectious aortic aneurysm
Oderich (2001)45 Infected aortic aneurysm and primary aortic infection DC: Combination of operative findings, clinical infection, and positive aneurysm culture
Luo (2003)23 Septic aortic pseudoaneurysm D: Aortic pseudoaneurysm caused by infection with or without bacteremia, excluding fusiform aneurysms
Jones (2004)a,25 Mycotic aortic aneurysm and infected false aneurysm No definition. Including aorta-bronchial, aorto-esophageal and aorto-cutaneous fistulas, which had previous thoracic aortic grafts
Kyriakides (2004)a,46 Mycotic aortic aneurysm/primarily infected aortic aneurysm Unclear definition, however excluding prosthetic graft infections, arterial infection secondary to trauma and aneurysms with positive routine culture
Hsu (2004)47 Primary infected aortic aneurysm DC: Combination of clinical signs of infection, imaging findings on CT or MR, aortic aneurysm >3 cm, and positive culture
Kuniyoshi (2005)a,48 Mycotic aortic aneurysm DC: Aneurysm morphology or intraoperative findings
Chen (2005)a,49 Mycotic aortic aneurysm DC: Positive culture from the aneurysm wall or pus surrounding the aneurysm if negative culture from the aneurysm
Tiesenhausen (2007)50 Mycotic aortic pseudoaneurysm DC: Clinical picture of infection, positive blood culture, aortic imaging
Razavi (2008)a,51 Mycotic aneurysm Unclear definition and diagnostic criteria
Hsu (2008)52 Infected aortic aneurysm DC: Combination of clinical signs of infection, imaging findings on CT or MR, aortic aneurysm >3 cm, and positive culture
Clough (2009)a,53 Mycotic aortic aneurysm D: All aneurysms of infective etiology
Sörelius (2009)24 Mycotic aortic aneurysm DC: Combination of clinical signs of infection, hematologic tests and culture, and imaging. Positive culture not requisite.
Dubois (2010)54 Mycotic aortic aneurysm DC: Combination of clinical signs, imaging, intraoperative findings, positive aneurysm culture. Recent infection was also taken into account if negative culture
Kan (2010)55 Mycotic aortic aneurysm DC: Combination of clinical course with infectious signs, positive blood or tissue culture and aortic imaging
Hsu (2011)56 Infected aortic aneurysm DC: Combination of clinical signs of infection, imaging findings on CT or MR, aortic aneurysm >3 cm, and positive culture
Kan (2011)57 Infected aortic aneurysm Author switching terminology, but retaining diagnostic criteria: combining clinical course with infectious signs, positive blood or tissue culture, and aortic imaging
Yu (2011)58 Mycotic aortic aneurysm DC: Combination of clinical signs of infection, characteristic imaging, and intraoperative inflammation or purulence
Bisdas (2011)15 Infected aneurysm Supporting the Wilson classification, and arguing for a change of terminology
Sedivy (2012)59 Infected aortic aneurysm Definition according to Wilson, diagnostic criteria unclear but excluding graft infections and fistulas, and positive culture is not a requisite
Uchida (2012)60 Mycotic aortic aneurysm DC: Combination of clinical, imaging and pathological evidence
Lin (2014)8 Primary infected aortic aneurysm DC: Combination of clinical signs of infection, imaging findings on CT or MR, aortic aneurysm >3 cm, and positive culture
Sörelius (2014)61 Mycotic aortic aneurysm DC: Combination of clinical signs of infection, hematologic tests and culture, and imaging. Positive culture not requisite
Sörelius (2016)29 Mycotic aortic aneurysm DC: Combination of clinical signs of infection, hematologic tests and culture, and imaging. Positive culture not requisite

Pathophysiology and subclassifications

It has been recognized that MAAs might arise from different causes, see Table 2. 16,9 The table is a modified version of Wilson et al36 from 1978. In addition to the Wilson classification, one more group has been added, ie, HIV-related aneurysms. These aneurysms are seen in young patients with advance-stage HIV infection, median age of 30 years with multiple aneurysms throughout the arterial system, and so far they have only been reported from the province of KwaZulu-Natal in the Republic of South Africa. The precise pathogenesis is unclear but there is to date no evidence of direct viral action leading to arterial wall destruction.42 However, viral infection cannot be excluded as the pathogenetic pathway.

Table 2.

Amended classification of aortic aneurysms caused by infection according to Wilson et al,36 “Spontaneous arterial infections.”

Mycotic aneurysm Infected aneurysm Microbial arteritis TRAUMATIC INFECTED PSEUDOANEURYSM HIV-related aneurysma
Etiology Endocarditis Bacteremia Bacteremia Trauma/punction HIV
Sex F > M M M M or F M
Age 30-50 More than 50 More than 50 Less than 30 Around 30
Incidence Rare Unusual Common Common Unusual
Location Any vessel Distal aorta Aortoiliac Femoral, carotid Any vessel
Number Multiple Single Single Multiple Multiple
Bacteriology Gram-positive cocci Staphylococcus aureus, Escherichia coli Salmonella sp. Polymicrobial

The last column “HIV-related aneurysm” was added by the authors of this article.

Diagnosis

Different criteria for aneurysms due to infection have been in use (Table 1). In the past 15 years, the diagnosis MAA has been based on a various combination of the following 4 criteria: (1) clinical presentation (pain, fever, concomitant infection, elderly patient with cardiovascular disease, and/or immunosuppressive state); (2) laboratory findings (raised inflammatory parameters including C-reactive protein [CRP], leukocytosis, and positive culture); (3) radiological findings on computed tomography (CT) or magnetic resonance imaging (saccular, eccentric, or multilobular aneurysm, periaortic mass, periaortic gas, and rapid aortic expansion) (Figure 2); and (4) intraoperative findings. One of the criteria is solely not sufficient for the diagnosis. However, there is no algorithm for making the diagnosis. Whether a positive blood culture is a prerequisite for the diagnosis or not is a point of disagreement.24,5557,61 Argument for positive culture being requisite, either in blood or tissue, is that it is the only way to certify an infectious pathophysiologic mechanism. Arguments against a positive culture being requisite are that it is known that these aneurysms yield a positive blood or tissue culture in only approximately 50% to 75% of the cases, even if harvested from the aneurysm sac with evident infection intraoperatively. This could be explained by difficulties in obtaining anaerobic cultures or initial broad-spectrum antibiotic therapy.43,62,63 Also, if treated endovascularly, a tissue culture may not be obtained.24 Older studies have demonstrated that routine culture of abdominal aortic aneurysm wall during surgery of clinically noninfected patients may be positive in 14% to 37%, which adds further complexity to this issue.6466 The value of positron emission tomography (PET) and granulocyte scintigraphy has not been evaluated properly but could probably aid in diagnostics in uncertain cases.

Figure 2.

Figure 2.

A mycotic abdominal aortic aneurysm.

Most authors make clear distinction between an aneurysm due to infection and aorto-enteric fistulas and graft infections.

Proposition for reporting items

To facilitate comparisons between studies on MAA the following 10 essentials would preferably be accounted for:

  1. Definition of disease and basis of diagnostic workup;

  2. Exclusion criteria;

  3. Patient characteristics (medical history: eg, cardiopulmonary disease, immunosuppressive states, or medication; data on presentation: symptoms, concurrent infection);

  4. Laboratory results (inflammatory markers: CRP, levels of leukocytes, cultures from blood/tissues, results of polymerase chain reaction for bacteria identification);

  5. Imaging findings and imaging modality (saccular or multilobular aneurysm, rapid expansion, periaortic gas formation within the aneurysm thrombus, periaortic soft tissue mass);

  6. Aneurysm anatomy (level of aorta engaged);

  7. Details on treatment (open repair; in situ bypass or extra-anatomic bypass and graft material: endovascular aortic repair; type of stent graft, hybrid procedure);

  8. Preoperative antibiotic treatment time;

  9. Postoperative treatment time (intravenous and oral);

  10. Follow-up (time, symptoms, lab results, imaging modality, outcome, bacteriology in case of infection-related complication, reoperation—why, when, how, and result thereof).

Discussion

What is unclearly said, is unclearly thought

Esaias Tegnér, 1782-1846, member of the Swedish academy and professor in Greek.

Mycotic aortic aneurysms are extremely rare, making the disease difficult to study and statistical analyses problematic. Meanwhile, its management is very demanding and carries high mortality.28,29,67 It is obvious that the terminology, definition, and diagnostic criteria of MAA are confusing. This confusion complicates comparisons between case series when this is necessary because collecting cases of MAA is a major undertaking and evidence-based treatment is lacking. An explicit definition with coherent terminology and diagnostic criteria needs to be settled. It is a fundamental process to standardize everything from definition, terminology, and methodology within science, and the discipline of vascular surgery should be of no exception. This would facilitate research, elevate the level of knowledge, make comparative analyses simpler, and enable development of treatment guidelines. Many authors prefer the term mycotic because of common usage, but if retained, it should be made explicit what the term alludes. Or, if both infected and mycotic could be used synonymously, that should be made clear as well.

It is important to distinguish MAAs from secondary aortic infections, such as graft infections, secondary aorto-enteric fistulas, and also inflammatory aneurysms, IgG4-related inflammatory aneurysms, and penetrating aortic ulcers because of differences in natural history and demand on management.2,8,28,29,68,69 A consensus document would be welcome as both the Society for Vascular Surgery (SVS) and the European Society for Vascular Surgery (ESVS) lack guidelines in treatment of MAAs. There is also a demand on evidence-based treatment guidelines because there are indications that the incidence of MAA is increasing.30,61

However, there may be many challenges defining MAAs, for example, the morphological characteristics of the aneurysm will probably matter. Most MAAs are saccular, but what is a saccular aneurysm? There is no distinct definition of saccular aneurysm either; should the diameter matter, and how should it be measured?

The same work remains for graft infections and aorto-enteric fistulas. The work by the MAGIC group is an important, encouraging step in the right direction, where a diagnostic algorithm was constructed for aortic graft infection by a multidisciplinary panel of experts.70 Until similar work is done for MAAs, this paper might stimulate the classification process, making comparisons between studies more standardized.

To date, there is not one meta-analysis on this disease, and the explanation is part the rarity of the disease, and part that the reporting is too disparate making comprehensible meta-analysis impossible. The purpose of presenting a suggestion for reporting items is to facilitate comparisons between studies in the future.

However, a consensus document to settle these issues is warranted. Such document would desirably also contain reporting standards, as the ones proposed in this article were a mere synthesis of obvious divergent reporting, or lack thereof in the literature. Until then, the diagnostic syndromic algorithms used by the teams in Taipei, Taiwan, and Uppsala, Sweden, will have to suffice, where a combination of clinical, laboratory and imaging findings compose the basis for the diagnostic workup.8,29

Conclusions

This article puts an emphasis on the need to standardize definition, terminology, and diagnostic criteria for MAAs and proposes reporting items enhancing comparability between studies.

Footnotes

Funding:The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Author Contributions: Conception and design: KS, PGdS; Analysis and interpretation: KS, PGdS; Data collection: KS; Writing the article: KS, PGdS; Critical revision of the article: KS, PGdS; Final approval of the article: KS, PGdS; Overall responsibility: KS.

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