Histoplasma Infection of Aortofemoral Bypass Graft

Histoplasma Infection of Aortofemoral Bypass Graft

CASE REPORT/FOCUSED REVIEW Histoplasma Infection of Aortofemoral Bypass Graft Authors Nishit Patel, MD and Michael S. Bronze, MD Editor Fred Lopez, ...

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CASE REPORT/FOCUSED REVIEW

Histoplasma Infection of Aortofemoral Bypass Graft

Authors Nishit Patel, MD and Michael S. Bronze, MD Editor Fred Lopez, MD Abstract: Histoplasma infection of vascular grafts is extremely rare. To our knowledge, there are only 4 cases reported with Histoplasma capsulatum infection of the aortic graft. All had previous disseminated histoplasmosis and atherosclerotic peripheral vascular disease. They were treated surgically with explantation of the infected graft and reimplantation of new graft in extra-anatomic uninfected site. The authors present a new case of H capsulatum infection of aortofemoral bypass graft, but unlike the other cases, this case was managed without surgical intervention. Key Indexing Terms: Histoplasma; Aortofemoral bypass graft; Vascular graft infection. [Am J Med Sci 2014;347(5):421–424.]

V

ascular graft infections by fungal organisms are rare, and to our knowledge, only 4 case reports of Histoplasma infections appear in literature to date. We report a new case of aortofemoral bypass prosthetic graft infection caused by Histoplasma capsulatum.

CASE PRESENTATION A 68-year-old white man with medical history of coronary artery disease status post bare metal stent placement in right coronary artery in January 2011, peripheral artery disease status post aortafemoral bypass surgery in 2000, hypertension, and hyperlipidemia presented to our facility with retrosternal chest pain relieved by sublingual nitroglycerin. Additionally, he reported an unintentional weight loss of 40 pounds in the last 6 months, night sweats, dry cough, and generalized fatigue. He was born and raised in Missouri and moved to Oklahoma at the age of 16 years. He used to do construction work and farming. He smoked 1 pack per day for 48 years and drank alcohol occasionally. On presentation, his vital signs were unremarkable and he was afebrile. Physical examination demonstrated splenomegaly and pulsatile mass over right femoral region. No abdominal or femoral bruit was appreciated. Based on history and risk factors, he was evaluated for an acute coronary syndrome; however, this From the Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Submitted January 28, 2013; accepted in revised form April 20, 2013. The authors have no financial or other conflicts of interest to disclose. Correspondence: Nishit Patel, MD, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190 (E-mail: [email protected]).

The American Journal of the Medical Sciences



was ruled out by electrocardiogram and cardiac enzymes. Additionally, a myocardial perfusion scan demonstrated no evidence of any ischemia and a left ventricular ejection fraction of 70%. Chest radiograph was unrevealing (Figure 1). Laboratory studies revealed a white blood cell count of 1,500 cells per cubic millimeter (reference range, 4,000–11,000/mm3), hemoglobin of 11.7 g/dL (reference range, 12–16 g/dL), and platelet counts of 119,000/mm3 (reference range, 140,000–440,000/mm3). Electrolytes and creatinine were within normal limits. Erythrocyte sedimentation rate was 37 mm/hr (reference range, 12–19 mm/hr). Peripheral blood smear revealed decreased numbers of platelets and rare small platelet clump, normocytic normochromic appearance of the red blood cells, and diminished number of both neutrophils and lymphocytes. No immature white cells were noted. Bone marrow biopsy showed hypocellular marrow and few granulomas. Staining for acid-fast bacteria and fungi was negative. Positron emission tomography or computed tomography (CT) scan was essentially negative except for splenomegaly and mild diffuse splenic uptake. Additional tests that were unrevealing included antinuclear antibody, VDRL, hepatitis profile, HIV panel, fungal serology, and urine and serum Histoplasma

FIGURE 1. Chest x-ray.

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FIGURE 2. First tagged white blood cell scan shows no evidence of infection in right femoral pseudoaneurysm.

antigen. Duplex ultrasonography of the pulsatile right groin mass revealed 2.5 3 4.4 3 6.6-cm hematoma along with a common femoral artery pseudoaneurysm extending into hematoma without any obliteration of flow. Vascular medicine recommended that the pseudoaneurysm should be treated conservatively with sand bag compression and aggressive control of hypertension. He was discharged home with follow-up, with vascular medicine. Twenty-five days after discharge, the laboratory reported that his admission blood culture was growing H capsulatum.

With the blood culture findings, his clinical picture suggested subacute, progressive, disseminated histoplasmosis and he was readmitted for initiation of liposomal amphotericin B. However, this therapy had to be discontinued because he had chest pain and hypotension during the 1st infusion. Therefore, itraconazole 200 mg twice daily was initiated. A tagged white blood cell scan was performed to determine whether the pseudoaneurysm was also infected. This scan demonstrated no signs of infection (Figure 2). Finally, he was discharged home on

FIGURE 3. Second tagged white blood cell scan shows uptake in right femoral pseudoaneurysm. NM, nuclear medicine.

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Histoplasma Infection of Aortofemoral Bypass Graft

itraconazole 200 mg twice daily for 1 year and close follow-up with infectious diseases, vascular medicine, and general internal medicine as an outpatient. One month after hospital discharge, he was seen in infectious disease clinic and complained of right groin pain. Once again, there was concern for Histoplasma infection of pseudoaneurysm. Tagged white blood cell scan was repeated and confirmed increased accumulation of labeled white blood cells in the right femoral graft extending to the right external iliac graft along with a focus of increased uptake in the bifurcation of the aorta and right common iliac graft about the anastomotic site, most consistent with graft infections within these regions (Figure 3). Vascular surgery was consulted for explantation of the aortofemoral bypass graft with new extra-anatomic graft placement. It was deemed to be an extremely risky procedure with high risk of reinfection of the new graft. Eventually, infectious diseases, vascular medicine, and vascular surgery came to conclusion that he should be treated with lifelong itraconazole. After 18 months of itraconazole treatment, he was clinically improved and the right groin pain had resolved.

DISCUSSION Histoplasma capsulatum is a dimorphic fungus that exists as a mycelial form at ambient temperatures and yeast form at body temperature in mammals. It is endemic in certain parts of North America, including Ohio, Missouri, and Mississippi River Valley. Most infections are clinically asymptomatic or have selflimited influenza-like symptoms. In others, Histoplasma infection may cause mediastinal disease, chronic cavitary disease of the lungs, or disseminated infection. The incidence of prosthetic vascular graft infection is quite low ranging from 0.6% to 3.0%, and these infections are most often managed with antimicrobials and removal of the infected

graft.1 Fungal prosthetic graft infections comprise a small number of infections and may be more commonly observed in patients with chronic immunosuppression, diabetes, and injection drug use.2 Among these fungal infections, H capsulatum has been uncommonly implicated in endovascular, valvular, or cardiac infections.2–4 In patients with exposure history including spelunking, excavation, cleaning of chicken coops, remodeling of old buildings, and cutting of dead trees, H capsulatum should be considered as potential microbiological causes of endovascular infections. Our patient worked as a farmer, which may have placed him at risk. We believe that our patient initially had subacute disseminated histoplasmosis and underwent angiogram with right femoral artery access, which lead to pseudoaneurysm of right femoral artery, eventually leading to H capsulatum infection of pseduoaneurysm and vascular graft. The classic presentation of endovascular infection includes a painful pulsatile mass associated with systemic features of infection.1 Sometimes, the diagnosis may be delayed and patients may present with complications such as gastrointestinal bleeding due to aortoenteric or aortoesophageal fistula.1 Diagnosis of the arterial infection may occur years after the symptoms of the original Histoplasma infection occurred and despite prior antifungal therapy.2 Fungal serology, fungal blood cultures, and urinary antigen testing must be performed in patients suspected of having endovascular histoplasmosis. Radiologic imaging plays a critical role in diagnosing occult graft infection and extent of known infection. 99mtechnectium examethylpropyleneamine oxime (TC-HMPAO)–labeled leukocyte scintigraphy has been considered as the gold standard for the diagnosis of prosthesis infection; however, adding an fluorodeoxyglucose-positron emission tomography scan may reduce the number of false-positive infection.5,6 Moreover, CT scan with contrast has been reported to have 100% sensitivity but with low specificity values (75%) in demonstrating graft infection using sings such as perigraft soft tissue, fluid or

TABLE 1. Characteristics of patients with Histoplasma vascular graft infection Time between initial symptoms of histoplasmosis and Age discovery of arterial Operative/autopsy Patient Sex (yr) infection Antifungal findings 1: O’Connor et al1

M

55

10 yr

Amphotericin B

2: Ledtke et al3

M

46

6 mo

Amphotericin B

3: Ledtke et al3

M

56

6 mo

4: Miller et al2 M

31

4 mo

5 (Our patient)

68

7 mo

Amphotericin B followed by lifelong intraconazole therapy Amphotericin B and later itraconazole maintenance therapy Itraconazole

M

Pseudoaneurysm at proximal anastomosis of previously placed aortobifemoral graft Recurrent infected pseudoaneurysm of prosthetic graft; eventual thrombosis of aortic graft Synthetic vascular graft in ascending aorta with fibrotic neointima containing fungal yeast and hyphal forms Synthetic vascular graft with fibrotic neointima and luminal thrombus containing fungal yeast and hyphal forms Treated conservatively

Therapy of arterial infection Resection of infected graft; placement of new aortic graft

Outcome Survival at 26 mo

Resection of infected Death graft with replacement of aortic graft on 2 occasions; eventual amputation Resection of infected Alive after graft and infected 10 yr bovine aortic valve with replacement of aortic graft and valve Resection of infected Alive at 7 graft; placement of mo new aortic graft

Lifelong itraconazole

Alive at 18 mo

F, female; M, male.

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gas, anastomotic pseudoaneurysm, and graft occlusion.6,7 Magnetic resonance imaging has comparable sensitivity and specificity rates to CT in diagnosing vascular prosthetic graft infections with no risk of contrast nephrotoxicity.8 The standard treatment of infected aortic prosthetic graft infection is explantation of graft and placement of new graft through extra-anatomic uninfected site.9 Currently, there are only 5 cases reported of H capsulatum infection of vascular graft including ours (Table 1). In the 4 previously reported cases, surgical excision of infected vascular graft was performed. Three of the 4 surgical patients survived after explantation of infected graft. Our patient was thought to be a high-risk surgical candidate and therefore he was managed more conservatively with lifelong itraconazole therapy. Eighteen months after his diagnosis, he is still alive with resolution of pseudoaneurysm and clearance of blood culture positivity for H capsulatum. In summary, there is no standard guidelines for the management of Histoplasma prosthetic graft infection and decisions must be made after considering input from all physicians involved such as, infectious disease physician, vascular surgeon, and radiologist and evaluating individual patient’s clinical condition and wishes. However, most of the reported endovascular infections have been successfully treated with combined surgical and medical modalities including initial treatment with amphotericin B and then followed by oral antifungal therapy for an indefinite period.

CONCLUSIONS Vascular graft infection by Histoplasma is a rare event and should be considered among patients with appropriate exposure history. Serologic testing and fungal culture may provide a clue to diagnosis and help diagnosing this uncommon

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entity earlier. 99mTC-HMPAO–labeled leukocyte scintigraphy should be considered for imaging if there is high suspicion of vascular graft infection. A multidisciplinary approach is required in management of this difficult clinical entity. REFERENCES 1. O’Connor S, et al. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg 2006;44:38–45. 2. Miller BM, et al. Histoplasma infection of abdominal aortic aneurysms. Ann Surg 1983;197:57–62. 3. Ledtke C, et al. Endovascular infections caused by Histoplasma capsulatum: a case series and review of the literature. Arch Pathol Lab Med 2012;136:640–5. 4. Matthay RA, et al. Disseminated histoplasmosis involving an aortofemoral prosthetic graft. JAMA 1976;235:1478–9. 5. Gardet E, et al. Comparison of detection of F-18 fluorodeoxyglucose positron emission tomography and 99mTc-hexamethylpropylene amine oxime labelled leukocyte scintigraphy for an aortic graft infection. Interact Cardiovasc Thorac Surg 2010;10:142–3. 6. Liberatore M, et al. Clinical usefulness of technetium-99m-HMPAOlabeled leukocyte scan in prosthetic vascular graft infection. J Nucl Med 1998;39:875–9. 7. Johnson KK, et al. Diagnosis of synthetic vascular graft infection: comparison of CT and gallium scans. AJR Am J Roentgenol 1990;154:405–9. 8. Bruggink JL, et al. Current role of imaging in diagnosing aortic graft infections. Semin Vasc Surg 2011;24:182–90. 9. Bunt TJ. Vascular graft infections: an update. Cardiovasc Surg 2001;9: 225–33.

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