Research Article: Infective Endocarditis with Antineutrophil Cytoplasmic Antibody: Report of 13 Cases and Literature Review

Date Published: February 25, 2014

Publisher: Public Library of Science

Author(s): Chun-Mei Ying, Dong-Ting Yao, Hui-Hua Ding, Cheng-De Yang, Dermot Cox.


Chronic infections tend to induce the production of antineutrophil cytoplasmic antibody (ANCA). Infective endocarditis (IE) has been reported to exhibit positive ANCA tests and to mimic ANCA-associated vasculitis, which may lead to a misdiagnosis and inappropriate treatment. The aim of this study was to clarify whether there is any difference in the clinical features between ANCA-positive IE and ANCA-negative IE.

A retrospective study was carried out on 39 IE patients whose proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA levels were measured. After dividing the patients into ANCA-positive and ANCA-negative IE, we compared their clinical features.

we compared 13 ANCA-positive IE patients with 26 ANCA-negative IE patients. All 13 ANCA-positive IE patients were proteinase-3-ANCA positive. Compared with the ANCA-negative IE group, the prevalence of edema of the lower extremities, the serum lactate dehydrogenase (LDH) level and positive blood cultures rate were higher in ANCA-positive IE group, but there was no significant difference in other clinical features.

Therefore, if a patient presents with fever, arthralgia, skin rash and is ANCA-positive, appropriate steps should be taken to exclude infection (especially IE) before confirming the diagnosis of ANCA-associated vasculitis and embarking on long-term immunosuppressive therapy.

Partial Text

Antineutrophil cytoplasmic antibodies (ANCAs) directed against proteinase-3 (PR3) or myeloperoxidase (MPO) are important diagnostic markers for small small-vessel vasculitic syndromes (i.e. Granulomatosis with polyangiitis, microscopic polyangiitis, Eosinophilic granulomatosis and polyangiitis), which are commonly referred to as ANCA-associated vasculitis (AAV) [1]. However, several infectious diseases, particularly infective endocarditis (IE), have been reported to exhibit positive ANCA tests and to mimic AAV, which may lead to a misdiagnosis and inappropriate treatment [2]–[20]. Hence, IE is of particular importance in the differential diagnosis of AAV because the misdiagnosis of an infectious disease as AAV and the administration of immunosuppressive therapy could worsen the infection and lead to disastrous consequences.

This study was approved by the Ethics Review Board of Shanghai Jiaotong University (Shanghai, China). All patients including the guardians on the behalf of the minors participants provided written informed consent to be included in the study.

Detection of ANCA is highly specific for the diagnosis of AAV (e.g., anti-PR3 antibody for Granulomatosis with polyangiitis). However, various infections can result in a positive ANCA test (especially IE). Usually, IE associated with ANCA is rare, but 31 cases have been reported [2]–[20]: 16 for Streptococcus spp., 4 for Enterococcus spp, 4, for Bartonella spp., 2 for Staphylococcus spp., 1 for Neisseria spp., 1 for Propionibacterium spp., and 6 culture-negative species. IE with ANCA can mimic the manifestations of AAV such as skin purpura and glomerulonephritis. Eight cases of ANCA-associated IE misdiagnosed as AAV have been published, including our report [7], [10]–[13], [15]. The differentiation between ANCA-associated IE and AAV may be difficult, but important differences in clinical presentation do exist between these entities. Chirinos et al. [12] described some pertinent differentiating features which may be more indicative of IE than AAV: organ involvement limited to skin and kidneys; positive blood cultures; abnormal levels of complement; immune deposits; and other autoantibodies (e.g., rheumatoid factor, antinuclear antibodies, cryoglobulins, anticardiolipin antibodies). AAV with valvular compromise involved almost exclusively the aortic valve and lead almost invariably to the need for valve replacement in the reported cases. Moreover, although discrete large vegetations seen on echocardiography suggest IE, small discrete vegetations have been rarely reported in AAV with valvula compromise. However, in their study age, sex, constitutional symptoms, ESRte and leukocytosis were not significantly different between the study groups. Bonaci-Nikolic et al. [15] compared 66 AAV patients with 17 PR3 and/or MPO-ANCA-positive patients with protracted infections, including 7 IE patients. They found that AAV patients more frequently had pulmonary and nervous system manifestations, while patients with infections more frequently had dual ANCA (high PR3, low MPO), aCL and anti-β2-GP I. Whereas there was no difference in frequency of lethality, renal failure and skin lesions in the two study groups. Haseyama, et al [4] suggested that in patients with high PR3 titers 50 U/ml in association with IE, it is initial to treated with immunosuppression. However, there have been 8 cases of IE with positive ANCA, including 2 cases in our report treated initially with immunosuppression or simultaneously with antibiotics because of delayed or equivocal diagnosis [7], [10], [11], [13], [15]. Four of these patients eventually died [10], [15]. Chirinos et al. [12] reckoned that histological examination of compromised valves revealed myxomatoid or fibroid degeneration of the valve tissue rather than granulomatous inflammation in most cases, explaining the lack of response to immunosuppressive therapy. Damage occurring during the initial valvulitis could lead to further valve distortion despite remission of the valvulitis with immunosuppressive therapy. Therefore, it is important that without convincing evidence of AAV and ruling out IE, there is no strong evidence to support immunosuppression.