A case of Libman–sacks endocarditis and the challenges of differentiating it from infective endocarditis

Abstract

Libman–Sacks endocarditis is a form of cardiac complication affecting patients with systemic lupus erythematosus, especially those with secondary antiphospholipid syndrome. In this case report, we present a case of Libman–Sacks endocarditis and discuss key features that differentiate it from infective endocarditis.

Introduction

Benjamin Sacks and Emanuel Libman first described a non-bacterial verrucous valvular lesion that was found in four patients with systemic lupus erythematous (SLE) in 1924. The lesion – rightfully named Libman–Sacks endocarditis (LSE) – is a form of sterile non-bacterial thrombotic endocarditis and a cardiac manifestation of SLE. Other cardiac manifestations of lupus include pericarditis, premature atherosclerosis and coronary vasculitis causing coronary artery disease and myocardial dysfunction. ¹

Case presentation

A 37-year-old lady with underlying SLE presented to the rheumatology clinic with worsening facial puffiness, reduced effort tolerance and bilateral lower limb swelling for 3 weeks. Her SLE which was predominantly haematological, mucocutaneous and renal was well-controlled with immunosuppressants prior to presentation. On examination, she had facial puffiness with swelling of bilateral lower limbs up to the sacrum and ascites. Breath sounds were reduced over bilateral basal regions of the lungs and a soft S1 with pansystolic murmur was heard on cardiovascular examination.

Blood investigations showed acute kidney injury with proteinuria and microscopic haematuria; abnormal blood counts in-keeping with haemolytic anaemia and severe hypoalbuminemia (Table 1). Erythrocyte sedimentation rate (ESR) was raised to 115 mm/hour, both complements 3 and 4 were reduced; however, C-reactive protein (CRP) was within reference range. An erect chest radiograph showed bilateral pleural effusion and cardiomegaly. Antiphospholipid antibody later returned a positive result.

Table 1.

Investigations during hospital admission.

Laboratory test	On admission	Reference range
White cell count, x 109/L	3.89	4.0–11.0
Haemoglobin, g/dL	8.7	12–15
Haematocrit, %	29	36–46
Mean cell haemoglobin,	27	27–32
Mean cell volume	94.6	83–101
Platelet, x 109/L	97	150–400
Erythrocyte sedimentation rate, mmhr	115	—
Urea, umol/L	31.0	1.7–8.3
Sodium, mmol/L	127	135–150
Potassium, mmol/L	4.7	3.5–5.0
Creatinine, umol.L	305	44–88
Total protein, g/L	54	g/l
Albuming, g/L	23	35–55
Total bilirubin, umol/L	38	<20
Alkaline phosphatase, IU/L	48	44–147
Alanine aminotransferase, IU/L	25	29–35
Aspartate aminotransferase, IU/L	27	29–35
Calcium, mmol/L	2.09	2.1–2.6
Phosphate, mmol/L	2.66	0.8–1.45
Magnesium, mmol/L	0.97	0.65–1.20
C-reactive protein, mg/dL	<0.50	<1.0
Urine protein	++	—
Urine bilirubin	Negative	—
Urine ketone	Negative	—
Urine urobilinogen	Normal	—
Urine leucocyte	Negative	—
Urine nitrate	Negative	—
Urine blood	+++	—
Complement 3	0.36	—
Complement 4	<0.08	—
Lupus anticoagulant	Positive	—
Anti-cardiolipin antibody	Positive	—
Beta2 glycoprotein	Negative	—
Anti-DsDNA	Positive	—
Prothrombin time	14.3	11.6–14.1 Seconds
APTT	106.3	31.4–43.3 Seconds
INR	1.1	Ratio

In view of clinically a heart murmur heard and cardiomegaly, an echocardiogram was performed which illustrated thickened tips of the mitral valve and severe mitral regurgitation (Figure 1). Left ventricular systolic function was preserved with an ejection fraction of 55% and minimal pericardial effusion was seen. She was subsequently admitted for SLE flare and was pulsed with intravenous methylprednisolone for 3 days.

Figure 1.

Transthoracic echocardiography at the (A) parasternal long axis view showing increased diameter of left atrium, (B) mitral regurgitation on colour-flow imaging, (C) nodular irregularities (grey arrows) at the anterior and posterior mitral leaflets, (D) pulmonary venous flow reversal, (E) dilated left atrium on apical 4-chamber view and (F) bright and thickened mitral leaflets with minimal pericardial effusion, suggestive of mitral regurgitation secondary to Libman–Sacks endocarditis with serositis.

Within the first week of admission, the patient’s renal function deteriorated, requiring haemodialysis via a femoral catheter which was later complicated by catheter-related septicaemia. Peripheral blood and catheter site pus cultures grew methicillin-sensitive Staphylococcus aureus for which vancomycin was started empirically prior to obtaining the final culture result. In view of persistent pyrexia despite antimicrobial therapy, an echocardiogram was repeated which showed severe mitral regurgitation and preserved ejection fraction as seen in the first echocardiogram persisted. She was suspected of an acute infective endocarditis (IE); however, retrospective review of her first echocardiogram video revealed that the lesions reported as thickened mitral valves were indeed endocardial mass similarly seen in the second echocardiogram. There were bright, multiple nodular irregularities on the tips of both anterior and posterior mitral valve leaflets.

Despite maximum medical therapy, the patient continued to deteriorate and succumbed to severe sepsis in her third week of hospital stay.

Discussion

LSE commonly affects the mitral and aortic valves, although any cardiac valve may be involved. ² It often leads to valvular thickening, stenosis or regurgitation and its occurrence increases with the presence of antiphospholipid syndrome (APLS). ³ Diagnosis is made by transthoracic or transoesophageal echocardiogram which shows the presence of vegetations on valvular leaflets. This case discussed on several features and challenges in differentiating LSE from IE as the patient developed bacteraemia during the course of illness.

Infective endocarditis should be ruled out prior to making a diagnosis of LSE. In this case, her first echocardiogram did show thickened mitral valve leaflets; however, due to the lack of symptoms and blood parameters suggestive of infection such as fever, leucocytosis and raised CRP, the possible diagnosis of IE was not entertained until the patient developed bacteraemia later on during her admission. The thickened mitral valve also did not receive its due attention as it was initially not seen by a cardiologist until she was referred to one after the second echocardiogram to exclude IE after she developed bacteraemia.

The initial finding of severe mitral regurgitation (MR) in the first echocardiogram prior to bacteraemia was consistent with a chronic process due to the presence of dilated left ventricle, left atrium and right atrium suggestive of raised pulmonary pressure. She was also not in pulmonary oedema during the presentation, hence suggesting a more chronic MR rather than an acute one. She would have been hemodynamically unstable with features of acute pulmonary oedema should she have developed an acute MR secondary to IE. The repeated echocardiogram after she developed bacteraemia revealed similar findings on the mitral valve leaflets and therefore the likelihood of a vegetation due to IE was even less likely.

In addition, the symptoms during presentation were more specific towards nephrotic syndrome secondary to lupus nephritis and none of the presenting features were evident of IE except for the presence of a murmur. Initial blood parameters were also more suggestive of active lupus rather than IE with the presence of raised ESR and normal CRP. The prolonged APTT and positive lupus anticoagulant with anti-cardiolipin antibody which confirmed the diagnosis of antiphospholipid syndrome (APLS) further support the diagnosis of LSE.

A useful tool for diagnosing IE includes the modified Duke’s criteria which requires two major criteria; one major with three minor criteria or five minor criteria. In this case, the patient had possible vegetations on the mitral valve leaflets thus fulfilling one major criterion. However, a second major criterion was not met as she only had a single positive blood culture. The patient also did not meet any of the minor criteria where no clinical stigmata of IE were found on examination and other septic features such as fever, leucocytosis and raised CRP were not evident on presentation. Moreover, the nodular irregularities were demonstrable prior to the onset of sepsis and positive blood culture, the chronology of which makes CRBSI a more likely source of infection rather than IE.

The mainstay treatment for LSE is anticoagulation with warfarin and low molecular weight heparin bridging in light of the prothrombotic state in SLE. In patients with co-existing APS who have had thrombotic events, anticoagulation is continued indefinitely. ⁴ Indications for surgical intervention such as valve replacement are the same as for IE which includes heart failure, severe valvular dysfunction or large (>10 mm) mobile vegetation. ⁵

A case report published by Michael Thomas comparing IE to LSE reported a case of SLE who was treated for both conditions in view of leucocytosis and raised CRP in the presence of a mitral valve vegetation. ⁶ In our patient, as no septic biomarkers were raised prior to the onset of CRBSI, the valvular pathology is likely non-bacterial endocarditis.

Table 2 highlights and summarizes the key features in comparison of LSE and IE in terms of their clinical presentation, diagnostic approaches and management.

Table 2.

Comparison of Libman–Sacks endocarditis and infective endocarditis.

Libman-sacks endocarditis	—	Infective endocarditis
Other signs of active SLE such as joint pain, hair loss, alopecia, oral ulcers, photosensitive rash. Features of antiphospholipid syndrome such as previous miscarriages or other thrombotic events May have fever in the event of active SLE Libman–Sacks endocarditis are usually asymptomatic; however, valvular dysfunction such as mitral regurgitation is possible and may lead to clinical features of heart failure	Clinical presentation	Fever Lassitude Acute onset Signs of acute heart failure such as acute pulmonary oedema. Signs of immunological phenomenon and septic embolisation such as Roth’s spots, Osler’s nodes and Janeway’s lesions. May have risk factors such as predisposing cardiac lesion or intravenous drug users
A diagnosis of exclusion Diagnosis is supported by the presence of positive antiphospholipid antibodies in a patient with SLE. Presence of valve masses/thickening on echocardiogram Negative blood culture to proof the likelihood of a sterile vegetation	Diagnostic approach	Using modified duke criteria as mentioned above Positive blood cultures from at least two separate cultures. Raised infective parameters such as leucocytosis, C-reactive protein and procalcitonin levels. Evidence of vegetation in echocardiographic studies in the background of clinical and blood parameters suggestive of infection
Lifelong anticoagulation with warfarin and low molecular weight heparin as bridging therapy. Possible need for surgical intervention such as valve replacement in the event of acute heart failure, severe valvular dysfunction or large vegetation	Management	Antimicrobial therapy remained the single most important treatment in patient with proven infective endocarditis Surgical interventions are indicated in the presence of heart failure secondary to valvular dysfunction or perforation, uncontrolled endocardial infection or prevention of systemic embolisation especially to the brain

Conclusion

This case highlights the challenges in differentiating LSE from IE especially when a confounding source of infection is present. It is prudent to exclude infective pathologies prior to diagnosing LSE as targeted antimicrobials are crucial in the management of the former. Early expert opinion from a cardiologist should be sought when suspicious lesion is found on echocardiogram so that appropriate management and intervention can be done in the early stages.