Candida Arteritis in Patients Who Have Not Received Organ Transplants: Case Report and Review of the Literature
- Caroline Chapuis-Taillard1,
- Oriol Manuel1,
- Jacques Bille2,
- Thierry Calandra1,
- Samuel Rotman3, and
- Philip E. Tarr1,a
- 1Infectious Diseases Service, Department of Medicine, Department of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
- 2Institute of Microbiology, and Department of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
- 3Department of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
- Reprints or correspondence: Dr. Philip E. Tarr, Infectious Diseases Service, Kantonsspital Bruderholz, University of Basel, CH-4101 Bruderholz, Switzerland (philip.tarr{at}unibas.ch).
Abstract
Fungal arteritis is a rare entity, associated with significant morbidity and mortality, that typically involves graft arteries in solid organ transplant recipients. Here, we report the first case of Candida carotid arteritis and review 22 other cases of Candida arteritis reported since 1966 in patients who have not received transplants. Most patients had serious underlying conditions. All cases were anatomically characterized by pseudoaneurysm formation. Patients presented with fever (n=17), local pain (n=13), and an expanding pulsatile mass (n=4), with subsequent rupture and hemorrhage (n=7). Evidence of Candida colonization or infection was present in 15 patients before arteritis occurred. Treatment typically included a combined surgical and antifungal approach. The outcome was favorable in 11 patients, but follow-up was limited. A high index of suspicion, early diagnosis, and prompt antifungal and surgical treatment seem crucial to efforts to avoid life-threatening arterial rupture and hemorrhage.
The term “mycotic endarteritis” was coined by Osler [1] in 1885 to indicate infection of blood vessel walls due to septic embolization in patients with infectious endocarditis. This term is a misnomer, because the vast majority of arterial aneurysm infections are bacterial in origin [2–4], typically occurring in the context of arterial trauma due to injection drug use [5] or cardiogenic bacterial emboli.
Arterial infection associated with Candida species is an emerging problem in solid organ transplant (SOT) recipients, in whom it generally occurs as anastomotic site infection of graft vessels [5–8]. In several cases, the infection has been transmitted from the donor, most often via contaminated kidney graft infusate (reviewed in [8]). Graft loss and/or severe hemorrhage are common complications [6, 7, 9–13]. In addition to SOT recipients, 22 cases of Candida arteritis in patients who have not received SOTs have been published [2, 3, 7, 13–22]. Here, we report the first case, to our knowledge, of carotid arteritis due to Candida albicans and review the 22 published non-SOT cases, to describe the clinical and microbiological features of this entity.
Methods
We searched the PubMed database (1966–2006; all languages) using the terms “candida,” “pseudoaneurysm,” “aneurysm,” and “arteritis.” Cases were considered to be definite if yeast elements were present microscopically, if Candida was grown in culture of a surgical artery-wall specimen or vascular graft [2, 3, 6, 8–10, 14–18, 20, 23–31], or if Candida organisms were present in culture of an aneurysm vegetation [32]. Probable cases were defined as those in patients with candidemia who had radiographic evidence of a new vascular (pseudo)aneurysm, in the absence of other compatible pathogens in blood or artery-wall culture [4, 6, 33, 34].
Six possible cases were excluded from our review: 4 were in patients who had polymicrobial infection; thus, it was unclear which symptoms and signs were attributable to Candida and which were due to the other organism [19, 35–37]. Two cases were excluded because Candida organisms were cultured from the urine or other sites but not from the blood or artery wall [38, 39].
Case Report
A 75-year-old man presented in December 2002 with hoarseness and an enlarging, painful, pulsatile mass in the right side of his neck. He had end-stage diabetic and hypertensive nephropathy and had been hemodialysis dependent for the previous 5 years, with an arteriovenous prosthesis of the forearm in place. The patient had severe peripheral arterial disease, with multiple previous arterial leg bypass operations and with endoscopic insertion, in August 2002, of an intra-arterial prosthesis because of an internal iliac aneurysm. Ultrasound examination of the neck mass showed a pseudoaneurysm of the right common carotid. Surgical resection and insertion of a prosthetic graft was done. Two days later, pneumonia and empyema due to Enterobacter cloacae developed, which was treated with chest tube drainage and imipenem administered intravenously.
Histologic analysis of the endarterectomy material showed an ulcerated, calcified atheromatous plaque involving the arterial intima and media. The plaque was surrounded by fibromuscular tissue displaying chronic inflammation, including lymphocytes, macrophages, and giant cells. Pseudohyphae were seen, and C. albicans grew after 5 days in culture of the resected arterial specimens. Culture results were negative for bacteria. Serum candidal antimannan antibodies were positive (41.2 ng/mL; normal, <5 ng/mL). Five sets of blood cultures did not reveal any growth. Fluconazole treatment (200 mg once daily by mouth) was initiated with a plan for long-term treatment because of the prosthetic graft. Two months after the operation, the patient had a cardiopulmonary arrest in the setting of severe hyperkalemia, with no fever or other symptoms suggesting persistent fungal infection. The patient died. Permission to perform an autopsy was not granted.
Results
Since the first description of a case of femoral artery-wall infection due to Candida species, by Anderson in 1974 [20], 39 cases of Candida arteritis have been described in the literature. Of these cases, 17 occurring in SOT recipients have recently been reviewed [8]. In addition to the case described in the above section, 19 definite and 3 probable cases [4, 33, 34] occurring outside of the SOT setting are the subject of this review. The mean age of patients was 46 years (range, 1 month–80 years), and 17 patients were male. Clinical presentations included fever (n=17), local pain (n=15), an expanding pulsatile mass (n=5), and major hemorrhage (n=7). Candida arteritis occurred in 3 patients admitted to the intensive care unit, of whom 2 received mechanical ventilation.
The arteries involved were the thoracic aorta or its branches (n=5), intracranial arteries (n=3), the abdominal aorta (n=8), the iliac artery (n=2), the femoral artery (n=3), and 1 case each in the pulmonary, brachial, popliteal, and tibioperoneal arteries. In 2 cases, 2 different arteries were involved (the abdominal aorta and brachial artery in one case and the popliteal and tibioperoneal arteries in the other). Native arteries were infected in 19 cases, whereas a prosthetic arterial graft was infected in 2 cases [15, 29], a vein graft was infected in 1 case [14], and an aortic homograft was infected in 1 case [34].
Potentially contributory conditions included advanced cancer (n=5), diabetes mellitus (n=4), major surgery (n=4), injection drug use (n=3), end-stage renal disease/hemodialysis (n=2), advanced HIV infection (n=2), and long-term corticosteroid treatment (n=2). An underlying vascular disease was documented in only 4 patients, including the patient described in the present article [5, 17, 25].
Candidemia was recorded in 11 of 22 cases for which blood cultures were performed. Seven patients had endocarditis documented (4 native valve and 3 prosthetic valve). Seven patients had candiduria; in each case, it is unclear whether this represented the source or a consequence of candidemia. One patient had concomitant Candida arthritis. An infected intravenous catheter was diagnosed in 2 cases.
Fifteen of 23 patients had a documented Candida infection or colonization before the diagnosis of Candida arteritis: 9 patients had candidemia, 4 patients had mucocutaneous or respiratory Candida infection or colonization, 1 patient had candiduria, and 1 patient had a proven Candida spondylodiskitis 4 months before the diagnosis of fungal aortitis.
Candida arteritis was diagnosed by direct, microscopic examination (n=11) or via growth in culture from surgical artery-wall specimens (n=21). The cultured Candida species included C. albicans (n=14), C. tropicalis (n=1), C. parapsilosis (n=1), and Candida not further specified (n=5). Pathologic examination of resected surgical tissue showed an inflammatory infiltrate in the 11 patients with histologic results reported, and direct tissue examination revealed yeast elements in all of these cases.
Treatment included antifungal therapy alone (n=1) or combined with surgery (n=18). Multiple antifungal regimens were used ( [table 1), including amphotericin B (n=7), amphotericin B combined with flucytosine (n=4), fluconazole alone (n=3), amphotericin B combined with both flucytosine and fluconazole (n=2), fluconazole and itraconazole (n=1), and miconazole alone (n=1). No patient underwent surgical management without antifungal treatment. Of the 7 patients with diagnoses of Candida endocarditis, 5 underwent valve replacement and antifungal therapy, and 1 was treated medically; 1 case was diagnosed postmortem.
Table 1
Clinical features of 23 reported cases of Candida arteritis in patients who have not undergone solid organ transplantation.
Overall mortality was high; 9 of 23 patients died. In 3 cases [16, 28, 32], death was believed to be not related to the Candida infection. In all patients with intracranial arteritis, the diagnosis was made postmortem.
Discussion
Here we present the first case, to our knowledge, of Candida carotid arteritis and review the literature regarding 22 additional cases of Candida arteritis that occurred outside of the SOT setting. Patients typically presented with pain at the site of the infected artery and with fever. Documented underlying vascular disease was surprisingly infrequent. The source of Candida infection usually remained obscure, even though, in the majority of patients, Candida colonization or infection was present before Candida arteritis was diagnosed. All patients except 1 had serious concomitant conditions that were similar to those associated with invasive candidiasis [16, 25]. Mortality was high; death was most commonly due to arterial rupture and massive hemorrhage, particularly when aortic or intracranial vessels were involved in the infection.
In all cases, pseudoaneurysms of the infected artery were present. Two mechanisms have been suggested to explain fungal arteritis [20, 23]. First, infection of a preexisting atherosclerotic aneurysm might occur during an episode of candidemia; this was suggested in our patient by the atherosclerotic degeneration seen histologically in the surgical carotid specimen and the absence of endocarditis. Alternatively, localized Candida infection of the artery wall (typically via septic microemboli to the vasa vasorum of the artery wall or septic embolization in an artery, or from a contiguous infectious process extending to a nearby artery) may be followed by weakness of the artery wall and secondary pseudoaneurysm formation. It is conceivable that these 2 mechanisms coexist. The relative rarity of preexisting arterial disease in published cases suggests that the second mechanism may be more important.
Only half of the patients with Candida arteritis had documented candidemia. This is consistent with the well-recorded difficulty of premortem detection of candidemia in patients who are found to have disseminated candidiasis at autopsy [40]. When Candida arteritis is diagnosed, potential complications of candidemia (including endocarditis, endophthalmitis, and spondylodiskitis) should be searched for, even when blood culture results are negative. Another major complication of Candida arteritis is massive hemorrhage, perhaps because infected aneurysms are more prone to rupture than are atherosclerotic aneurysms. The diagnosis of Candida arteritis was frequently not made before rupture, presumably because of the nonspecific symptoms. Rupture was observed particularly with aortic, pulmonary, and cerebral artery involvement.
Treatment of Candida arteritis in most cases included a combination of different antifungal agents and surgery. In the absence of controlled studies, the optimal choice and duration of antifungal therapy is unknown. Prolonged, often lifelong therapy has been used, particularly for patients with prosthetic graft infection. The optimal surgical approach is also not well established but may include excision of all infected tissue and vascular reconstruction, often using extra-anatomic bypass or, more recently, in situ vascular grafting, particularly with aortic infection.
Because Candida arteritis is an infrequent entity, a high index of suspicion, early diagnosis, and prompt antifungal and surgical treatment seem crucial to the effort to avoid arterial rupture. Major hemorrhage can be a life-threatening complication, well recorded in the SOT setting and frequently complicating the course of Candida arteritis in patients who have not undergone SOT.
Acknowledgments
We acknowledge Dr. Gilbert Greub (Institute of Microbiology, University of Lausanne, and Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, Lausanne) for critical review of the manuscript and helpful discussions.
Potential conflicts of interest. All authors: no conflicts.
- Received October 17, 2007.
- Revision received December 17, 2007.
- Accepted April 3, 2008.
- © 2008 Infectious Diseases Society of America
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