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Mitral valve replacement due to Libman-Sacks endocarditis: lower limb cellulitis as a red herring
  1. Gerard Sexton1,
  2. Joseph McLoughlin2,
  3. Louise Burke3 and
  4. Kishore Doddakula2
  1. 1General Medicine, Mercy University Hospital, Cork, Ireland
  2. 2Cardiothoracic Surgery, Cork University Hospital Group, Cork, Ireland
  3. 3Pathology, Cork University Hospital Group, Cork, Ireland
  1. Correspondence to Gerard Sexton; gerardsexton{at}rcsi.ie

Abstract

A 56-year-old woman was admitted due to new ulceration and acute digital ischaemia on a background of chronic leg ulcers bilaterally. Vasculitis screening returned strongly positive lupus anticoagulant levels and elevated anticardiolipin antibodies; these remained elevated at repeat testing. A diagnosis of antiphospholipid syndrome was made. Transthoracic echocardiogram identified a mitral valve lesion suggestive of vegetation and mild mitral valve regurgitation. Blood cultures taken throughout her inpatient admission were negative. Mechanical mitral valve replacement was performed 3 months later, and subsequent culture of the excised tissue returned as sterile. Histological examination showed no morphological signs of infective endocarditis.

  • vasculitis
  • cardiothoracic surgery

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Background

Libman sacks endocarditis (LSE) is a form of non-bacterial thrombotic endocarditis, which occurs in association with antiphospholipid syndrome (APLS) or systemic lupus erythematosus (SLE).1 It is characterised by sterile, verrucous vegetations, which preferentially affect the mitral valve, the aortic valve representing the main alternative focus of disease.2 3 While associated with increased risk of stroke, thromboembolism, infective endocarditis and valvular dysfunction, it is most often an asymptomatic manifestation of APLS or SLE.4–6 Here, we present a case of LSE in a woman with previously undiagnosed APLS, for which she required mitral valve Replacement (MVR).

Case presentation

A 56-year-old Irish woman was admitted to a tertiary institution due to new ulceration of her left foot and a painful, purple third toe on her right foot. Previous medical history was otherwise notable for chronic leg ulcers bilaterally, hypertension, a myocardial infarction with stent placement over 10 years previously, and MRSA positive skin swab cultures in the recent past. There was no history of rest pain or claudication. Social history revealed that she lived independently with her husband, was a non-smoker and had no history of intravenous drug use.

She was feverish to 38°, with other vitals within normal limits. On examination, there was a longstanding ulcer above the right medial malleolus, and another on the dorsum of the left foot, the latter of which had grown in size in the preceding days. There were also several smaller, superficial ulcers and surrounding cellulitis. The left leg was also quite swollen, hot and painful, with similar longstanding ulcers noted on the dorsum of the foot. The third toe of the right foot also showed some signs of ischaemic change; it was purple in colour and the skin was beginning to break down. Dorsalis pedis and posterior tibial pulses were palpable and of normal character on both lower limbs. There were violaceous papules located at the proximal interphalangeal joints on both feet consistent with livedo reticularis. Physical examination on the index admission, including cardiovascular examination, was otherwise unremarkable.

Investigations

White cell count and C reactive protein were 12.9×109 /L and 100 mg/L, respectively. Skin swabs taken grew staphylococcus aureus, and flucloxacillin and benzylpenicillin were commenced. Ankle-brachial pressure indices (ABPIs) performed as an outpatient some months prior were 1.14 bilaterally. Skin biopsies were taken from the edges of the ulcers and showed ulcerated skin only. Vasculitis screening was performed and returned strongly positive lupus anticoagulant levels, positive antinuclear antibody titers, negative anti-double-stranded DNA and elevated anticardiolipin antibodies (IgG >15 g/L, IgM 66 g/L); these remained elevated at repeat testing. CT angiography of the lower limbs was carried out and identified mild atherosclerotic disease of the posterior tibial arteries only.

Transthoracic echocardiogram identified a large (2×0.4cm) mitral valve lesion suggestive of vegetation as well as preserved ejection fraction and mild mitral valve regurgitation (figure 1). The left ventricle was normal in size with normal wall thickness and systolic function. The left atrium was mildly dilated. No other structural abnormality was identified. Transoesophageal echocardiography visualised but could not further characterise this lesion, though concern was raised for a small valve leaflet perforation. Blood cultures taken at presentation and at regular intervals, thereafter, were persistently negative. MRI of brain was performed and reported as normal.

Figure 1

PLAX view of mitral valve lesion. PLAX, posterior leaflet, atrial side.

Differential diagnosis

Prior to the TTE detailed above, the primary differentials being considered were polyarteritis nodosa, dermatographism or APLS. Ultimately, the otherwise normal skin biopsies, the congruent vasculitic screen results, and the persistence of the findings on subsequent testing led to a diagnosis of APLS being made.

The differential diagnosis following the TTE included infective endocarditis, a non-bacterial thrombotic endocarditis process such as Libman-Sacks endocarditis, and valvular myxoma. It was not felt to be safe to assume that non-infective endocarditis was the underlying pathology despite the new diagnosis of APLS given the initial presentation with raised inflammatory markers. A valvular myxoma was considered possible but unlikely given the appearance on TTE.

Treatment

Gentamicin was added to the initial regime of flucloxacillin and benzylpenicillin based on a provisional diagnosis of infective endocarditis due to staphylococcus aureus, with 1 Dukes Major (identified valvular vegetation) and 2 Dukes Minor (temperature >38° and vascular phenomena (potential embolism to the right third toe)) criteria. The fever and elevated inflammatory markers resolved quickly and did not recur during the inpatient stay that followed. Oral prednisolone, hydroxychloroquine and low-molecular weight heparin were commenced for the APLS. Cardiothoracic multidisciplinary team discussion concluded that mechanical MVR should be performed on the basis that the digital ischaemia could have represented an embolic event, and additionally due to signs of progressive valve calcification on TTE. Three months of antimicrobial therapy as an inpatient followed to allow resolution of the ulcers and reduce the risk of further seeding to an implanted valve. Outpatient antimicrobial therapy was not considered due to concern regarding the potential valve leaflet perforation. The delay in performing surgery was due to a combination of awaiting healing of the lower limb ulcerations and the ongoing antibiotic therapy to cover infective endocarditis in the absence of significant valve dysfunction. The vegetation was evaluated with follow-up TTE in the weeks prior to surgery, which identified no notable change. The third toe of the right foot became necrotic during this period and underwent autoamputation. The lower limb ulcers resolved gradually but completely.

A mechanical MVR via median sternotomy was performed as the definitive treatment of the vegetation. Routine aortic and bicaval cannulation was performed, and cardiopulmonary bypass was established. Inspection of the mitral valve via a medial incision of the left atrium revealed destruction of the chordae tendineae and calcification of the valve. It was concluded that in order to undertake sufficient debridement, valve replacement was indicated rather than valve repair. This was performed using a size 27 Carbomedics Standard MVR. Pacing wires and two drains (pericardial and mediastinal) were placed. Time on bypass was 32 min and the total operating time was 142 min. Blood loss was estimated at 390 mL.

Outcome and follow-up

Subsequent culture of the excised tissue grew no organisms. Histological examination of the valvular tissue included organising fibrinoid material associated with endothelial cell prominence (figure 2). Rare acute inflammatory cells were noted, although their significance was unclear. Focal calcifications were also appreciated. Diagnostic pathological features for an IE were not identified.

Figure 2

Mitral valve vegetation histology showing organising fibrinoid material associated with endothelial cell prominence.

Following surgery warfarin was commenced with a target international normalised ratio of 3–4. Therapeutic INR was achieved, and she was discharged home, with follow-up 6 weeks thereafter. She required readmission for a superficial wound infection 1 week later, but this resolved with oral flucloxacillin. She remains well at this time.

Discussion

Probably the most unusual aspect of this case was the circumstances, in which APLS was diagnosed. The majority of cases of LSE present after having been diagnosed with APLS for some years, though in this instance, the presentation with a potential thromboembolic event is consistent, where symptoms are present, LSE most often presents with symptoms of complications such as stroke, other thromboembolic events, valvular dysfunction or superimposed infective endocarditis.6 A similar case reported by Sharma et al also featured a patient who underwent MVR and was diagnosed with LSE on the basis of specimen analysis, the primary difference being that the former was in an adolescent.7 The diagnosis of APLS was initially made in this case on the basis of both biochemical and clinical findings, specifically the presence of persistently elevated anticardiolipin antibodies and vascular thrombosis in the form of digital ischaemia.8 Ultimately it remains unclear whether the digital ischaemia came about as a result of thrombosis or embolism, but the subsequent identification of findings consistent with LSE further clarifies the diagnosis of APLS. Cutaneous ulceration is also a known associated manifestation of APLS, and in this case, this would seem to have been a manifestation of longstanding undiagnosed disease—this is evident from the normal ABPIs, the lack of clinical signs of peripheral venous insufficiency and the presence of livedo reticularis, itself another clinical manifestation of APLS. This illustrates the value of vasculitis screening in those with atypical or refractory lower limb ulceration.

Mitral valve repair and replacement have both been discussed previously in the literature as management options for rheumatic heart disease, though there is a noted preponderance of replacement over repair in patients with secondary APLS.3 There is still controversy as to whether repair or replacement is superior in terms of outcomes, though in instances of significantly destroyed valve replacement becomes inevitable. In this case, replacement was necessitated as a result of significant calcification of the valve, destruction of chordae tendineae locally and concerns leading up to the surgery that the lesion was of infective origin, obviating a need for sufficient debridement of surrounding tissue to ensure no focus of infection remained.

Indeed, the primary concern in the lead up to surgery in this case was whether the lesion represented a focus of infection; the mass was detected prior to the diagnosis of APLS and. thus. infective endocarditis seemed the most logical option. Ultimately, the decision was made that the risk of not treating as a case of infective endocarditis outweighed the benefit. While the histological features of the specimens were consistent with LSE, the possibility of infective endocarditis, which had been rendered sterile by prolonged antibiotic therapy, could not be completely ruled out. Consideration was given during the patients prolonged admission to various other adjuvant treatment options, namely, intravenous rituximab to treat her underlying APLS. This was commenced following her discharge and recovery from MVR, but was felt to add little in the perioperative setting due to the risk of wound complications.

Learning points

  • Non-infective endocarditis remains part of the differential in persistently culture-negative patients with valve vegetations.

  • Systemic lupus erythematosus and antiphospholipid syndrome are both significant risk factors for non-infective endocarditis.

  • Mitral valve replacement or repair represents the definitive management options in the setting of valvular dysfunction or thromboembolic phenomena.

  • An underlying vasculitis should be considered in those with ulceration of the lower limbs in the absence of obvious underlying arterial or venous insufficiency.

Ethics statements

Patient consent for publication

References

Footnotes

  • Contributors Concept and first draft: GS. Critical revision of the manuscript for important intellectual content: GS, JM, LB, KD. Histological slide provision and interpretation: LB.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.