Infective Endocarditis Caused by Streptococcus sanguinis Resulting in Stroke, Ruptured Infected Pseudoaneurysm of Superior Mesenteric Artery, and Rapidly Progressive Glomerulonephritis

Abstract

A 71-year-old-man was admitted to our hospital with a cerebral embolism and diagnosed with infective endocarditis (IE) caused by Streptococcus sanguinis. Mitral valve replacement was performed. About one month later, he experienced sudden abdominal pain and shock due to a ruptured infected mesenteric artery pseudoaneurysm. Forty-four days after abdominal surgery, he presented with rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies. He was treated with plasma exchange and prednisolone, and his renal function gradually improved. Since postoperative complications often occur within a few years after surgery for IE, careful follow-up is important, even after antimicrobial therapy and valve surgery.

Introduction

Infective endocarditis (IE) is a fatal disease that causes various clinical symptoms and complications, including bacteremia, vascular embolization, and cardiac injury, due to the formation of vegetations containing bacterial colonies in the cardiac valves, endothelium, and intima of large vessels (1). Even today, the early diagnosis of IE is challenging (2). Most cases of IE present with a fever. However, while a fever is one of the modified Duke's diagnostic criteria, it is difficult to make an accurate diagnosis in cases where a patient is afebrile due to being treated with antibacterial or anti-inflammatory drugs by the time of consultation (3).

Symptomatic neurological complications are observed in 12-40% of IE patients (4), of which cerebral stroke is the most common (5). Superior and inferior mesenteric artery aneurysms caused by infection are rare (6). Septic emboli within the arterial lumen gradually weaken the arterial wall, with enlargement of the artery occurring, until finally an aneurysm is formed (7). Acute renal failure occurs in about one-third of IE patients (1). The most common cause is septic emboli. Glomerulonephritis associated with IE is mainly due to vasculitis and less frequently to immune complex (8).

We herein report a case of IE caused by Streptococcus sanguinis. Cerebral infarction was the initial symptom and was followed by a ruptured infected pseudoaneurysm and anti-glomerular basement membrane antibody-related rapidly progressive glomerulonephritis after the diagnosis of IE and cardiac surgery.

Case Report

A 71-year-old man was admitted to our hospital after experiencing left-hand paralysis for the past month. He had a history of hypertension and cerebral infarction at 53 years old. He took loxoprofen regularly for chronic back pain. Head magnetic resonance imaging (MRI) revealed new cerebral infarctions in the parietal region on both sides (Fig. 1). His blood pressure was 132/82 mmHg, and no heart murmur was heard. His body temperature was 36.4°C, and his pulse was regular. An electrocardiogram showed regular sinus rhythm. Blood tests showed an increased inflammatory response. His renal function was normal (Table).

Figure 1.

Head MRI findings on admission. Cerebral infarctions are seen in the left (A) and right (B) parietal lobes (arrow). MRI: magnetic resonance imaging

Table.

Laboratory Data on Admission.

WBC

108×102

/μL

eGFR

70.9

CEA

1.6

ng/mL

Eos

0.6

%

Na

139

mEq/L

CA19-9

<2.0

ng/mL

Neu

69.4

%

K

4.1

mEq/L

PSA

0.201

ng/mL

Lym

23.3

%

Cl

99

mEq/L

VB1

35.6

ng/mL

RBC

354×104

/μL

TP

6.8

g/dL

VB12

846

pg/mL

Hb

10.6

g/dL

Alb

3.3

μg/mL

MCV

91

fL

CRP

4.31

mg/dL

Urinalysis

MCHC

32.9

%

Fe

39

μg/dL

Dipstick

PLT

29.0×104

/μL

Ferritin

232.5

ng/mL

pH

6.5

ALP

216

U/L

ESR-1h

100

mm

Protein

1+

AST

23

IU/L

ANA

×40

Blood

2+

ALT

13

IU/L

RF

13

IU/mL

Cast

CK

24

IU/L

C3

140

mg/dL

Hyaline

2+

BUN

14.2

mg/dL

C4

24.8

mg/dL

Granular

2+

Cr

0.82

mg/dL

CH50

64

U/mL

WBC: white blood cell, Eos: eosinophil, Neu: neutrophil, Lym: lymphocyte, RBC: red blood cell, Hb: hemoglobin, MCV: mean corpuscular volume, MCHC: mean corpuscular hemoglobin concentration, PLT: platelet, ALP: alkaline phosphatase, AST: aspartate aminotransferase, ALT: alanine aminotransferase, CK: creatine phosphokinase, BUN: blood urea nitrogen, Cr: creatinine, eGFR: estimated glomerular filtration rate, Na: sodium, K: potassium, Cl: chlorine, TP: total protein, Alb: albumin, CRP: C-reactive protein, Fe: iron, ESR-1h: one hour erythrocyte sedimentation rate, ANA: anti-nuclear antibody, RF: rheumatoid factor, C3: complement component 3, C4: complement component 4, CH50: 50% hemolytic complement unit, CEA: carcinoembryonic antigen, CA19-9: carbohydrate antigen 19-9, PSA: prostate-specific antigen, VB1: vitamin B1, VB12: vitamin B12, pH: power of hydrogen

On hospital day 5, he complained of abdominal pain and underwent upper gastrointestinal endoscopy and abdominal computed tomography (CT), but there were no obvious abnormalities (Fig. 2A). The cause of the abdominal pain was unclear, but the symptoms subsequently resolved. Transesophageal echocardiography revealed a 15-mm large mobile vegetation adherent to the posterior leaf of the mitral valve (Fig. 3A, arrow) and moderate mitral regurgitation (Fig. 3B). Streptococcus sanguinis was detected in three different blood cultures. The patient was diagnosed with multiple cerebral embolisms due to subacute IE and underwent mitral valve replacement (MVR) on hospital day 18.

Figure 2.

A: Abdominal CT findings with contrast agent on hospital day 5. Nothing of note was found. B: Plain abdominal CT performed for abdominal pain and shock revealed a superior mesenteric aneurysm that had not been present on day 5. C: Resected mesenteric aneurysm. D: Resected mesenteric aneurysm split surface. CT: computed tomography

Figure 3.

A: Transesophageal echocardiographic image. A 15-mm large mobile vegetation was attached to the posterior leaf of the mitral valve. B: Transesophageal echocardiographic color Doppler image. Moderate mitral regurgitation was observed.

The postoperative course was satisfactory, but on postoperative day 36, the patient complained of severe abdominal pain and went into shock. Abdominal CT revealed a 4-cm mesenteric aneurysm that had not been observed on admission (Fig. 2B, arrow). Emergent laparotomy, hematoma removal, and aneurysmal resection were performed (Fig. 2C, D). Gram staining of the resected aneurysm did not reveal the presence of bacteria. The artery in the lesion had a disrupted internal/external elastic plate and tunica media structure, with a fresh thrombus inside and hemosiderin-phagocytic macrophages and neutrophil infiltration in the surrounding area. The pathological diagnosis was a ruptured infected pseudoaneurysm.

Blood tests on hospital day 141 showed a worsening of the renal function. Microscopic hematuria and proteinuria persisted, and the renal function progressively worsened. Anti-glomerular basement membrane (GBM) antibody positivity was pronounced, and a diagnosis of rapidly progressive glomerulonephritis (RPGN) was made. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) were both negative. A renal biopsy was not performed because the patient did not provide his consent. The patient was treated with seven rounds of plasma exchange and prednisolone. His condition gradually improved with continued prednisolone administration, and he was discharged on hospital day 394 (Fig. 4). One year after discharge, he was negative for anti-GBM antibodies.

Figure 4.

Patient time course. Solid lines represent serum creatinine levels and dashed lines represent anti-GBM antibodies. Anti-GBM-ab: anti-glomerular membrane antibody, MVR: mitral valve replacement, PSL: prednisolone, Cr: serum creatinine

Discussion

The present patient developed IE due to infection by S. sanguinis, resulting in three complications. Each complication was serious and life-threating, but given the difference in timing of their occurrence, they were treatable, and the patient survived.

Cerebral infarction triggered the diagnosis of IE in this case. Symptomatic neurological complications are observed in 12-40% of IE patients (4), of which cerebral stroke is the most common (5). Even today, the early diagnosis of IE is challenging. Although our patient had no fever, heart murmur, or heart failure, we considered the possibility of IE at an early stage due to the presence of cerebral infarction in a patient with sinus rhythm.

Superior and inferior mesenteric artery aneurysms caused by infection are rare (6). The following four mechanisms of arterial infection can lead to aneurysms: dispersal of emboli from IE, infection of existing aneurysms, direct and lymphatic transmission from local infections or pyogenic foci, and direct bacterial inoculation during trauma, such as penetrating injuries or vascular procedures (7). The first mechanism accounts for 80% of infective aneurysms and involves septic embolization within the arterial lumen from bacterial endocarditis. This is followed by gradual weakening with enlargement of the artery and aneurysm formation. In the present case, a mesenteric artery aneurysm formed and ruptured after a short period, as the aneurysm was not observed on admission. The mechanism underlying the rupture was mesenteric artery embolization caused by IE, since abdominal pain had appeared before the administration of antimicrobials. Pseudoaneurysm formation following embolization caused the aneurysm to rupture.

The third complication observed in the present case was RPGN with anti-GBM antibody positivity. According to Nasr et al., the diagnostic criteria for infection-related glomerulonephritis (IRGN) are met when at least three of the following are present: infectious disease before or at the onset of glomerulonephritis, hypocomplementemia, endocapillary proliferative and exudative glomerulonephritis on optical microscopy of renal biopsy tissue, C3-dominant deposits on immunofluorescence, and hump-like subepithelial deposits on electron microscopy (9). The present case satisfied only one criterion and thus was deemed not to have IRGN; it remains unclear why RPGN developed.

Acute renal failure occurs in about one-third of IE patients (1). The most common cause is septic emboli. Glomerulonephritis associated with IE is mainly due to vasculitis and less often to immune complex (8). Chiba et al. reported a case of crescentic GN associated with IE; that case was positive for PR3-ANCA and anti-GBM antibodies (10). However, in the present case, MPO-ANCA and PR3-ANCA were both negative, and only GBM antibodies were positive.

The antigenic epitope responsible for the development of anti-GBM antibodies is the C-terminal amino acid residue and the N-terminal-most amino acid residue of the type IV collagen α3 chain in the glomerular basement membrane. In vivo, this antigenic epitope is normally hidden and thus not antigenic. However, it is hypothesized that when the basement membrane is damaged by toxic substances or infection, the epitope is exposed and becomes antigenic, leading to the production of anti-GBM antibodies (11). The development of anti-GBM antibodies may precede the onset of clinical signs and symptoms by many months (12).

The present case had undergone surgery twice and antimicrobial therapy after the diagnosis of IE, and the renal function had already deteriorated before the onset of RPGN. Although the timing of anti-GBM antibody production could not be determined, we assume the glomerular basement membrane was damaged by infection or antimicrobial agents after the onset of IE, which led to the production of anti-GBM antibodies. The course of urinalysis is consistent with this hypothesis. It is also possible that the production of anti-GBM antibodies was related to the Streptococcus infection. GN is known to occur after infection by Streptococcus, especially in children (13). In the present case, the urinalysis showed positive urinary protein and occult blood on admission, which persisted thereafter. According to some reports, nephritis is associated with anti-GBM antibody production (8,14).

In conclusion, we reported a case of IE caused by S. sanguinis that was complicated by cerebral infarction, ruptured infected mesenteric artery pseudoaneurysm, and anti-GBM antibody-type RPGN. Since postoperative complications of IE often occur within the first year after surgery (15), careful follow-up is important after antimicrobial therapy and surgery.

The authors state that they have no Conflict of Interest (COI).