The incidence of juvenile idiopathic arthritis (JIA) ranges from 1.6 to 23 cases per 100,000 children annually, with systemic JIA accounting for 5% to 15% of its subtypes.1 Extra-articular manifestations of JIA include rashes, fever, hepatosplenomegaly, and cardiovascular involvement. Among these, valvular involvement represents a rare yet potentially life-threatening complication, which predominantly occurs in the systemic subtype.2,3 In this report, we describe the case of a 9-year-old girl with systemic JIA who developed both aortic and mitral valve lesions. Notably, the patient demonstrated clinical improvement after aortic valve replacement and mitral valve repair, combined with perioperative immunosuppressive therapy.
Case Report
A 9-year-old girl was admitted to our hospital with a 4-month history of joint pain and 4-day onset of dyspnea. Two months before admission, the number of painful joints increased, with intermittent pain involving both ankles, knees, and hips; the pain was exacerbated during stair climbing. Magnetic resonance imaging of both hips performed at a local hospital indicated possible hip arthritis (Figure 1A).
Blood tests revealed a significantly elevated C-reactive protein (CRP) level and erythrocyte sedimentation rate. She received symptomatic treatment and was discharged. Two weeks before admission, she developed anorexia, which progressively worsened.
One week prior, her symptoms deteriorated, with new onset of chest tightness. Three days before admission, she developed dyspnea and facial edema. She was initially diagnosed with aortic valve prolapse and mitral regurgitation at a local hospital and then transferred to our institution.Figure 1Preoperative Assessment in Patients With Juvenile Idiopathic Arthritis(A) Hip MRI scan revealed synovial thickening, joint effusion, and ligament edema in the right hip.
(B) CT scan revealed bone destruction of the right hip, consistent with changes seen in JIA. Echocardiography showed aortic valve thickening (C) and severe aortic regurgitation (D). AO = aorta; CT = computed tomography; LA = left atrium; MRI = magnetic resonance imaging; RV = right ventricle.
After admission, the patient presented with pallor, dyspnea, tachycardia, a widened pulse pressure, a systolic murmur at the cardiac apex, and recurrent fever. Her white blood cell count continued to rise, reaching 47 × 109/L, with neutrophils increasing to 39.37 × 109/L, the CRP level elevated to 62 mg/L, the B-type natriuretic peptide level was >35,000 pg/mL, the cardiac troponin T level increased to 1,156 pg/mL, and the creatinine level elevated to 232.28 μmol/L. Blood gas analysis showed that the Lac level increased to 3.6 mmol/L.
Tests for rheumatoid factor, antinuclear antibodies, and HLA-B27 and blood metagenomic next-generation sequencing yielded negative results. Computed tomography examination in our hospital showed bone destruction of the right hip joint, which confirmed hip arthritis (Figure 1B). She was administered cardiotonic agents, diuretic agents, antibiotics, and immunosuppressive therapy.
A multidisciplinary consultation involving specialists from pediatric cardiology, rheumatology, hematology, and congenital heart surgery was conducted. Based on clinical manifestations—including bilateral hip arthritis, fever lasting more than 2 weeks, and a history of erythematous papular rashes on the neck, back, buttocks, and feet that resolved within 1 week—combined with laboratory findings of leukocytosis, elevated erythrocyte sedimentation rate and CRP level, acute liver and kidney injury, and microcytic anemia, she was diagnosed with JIA. Subsequently, she received treatment with methylprednisolone and tocilizumab (administered every 2 weeks), after which her white blood cell and neutrophil counts normalized.
Echocardiography at our institution revealed severe aortic regurgitation with aortic valve thickening (Figure 1C). It also showed left ventricular dilation, with a left atrial diameter of 42 mm, a left ventricular end-diastolic diameter of 52 mm, a left ventricular end-systolic diameter of 39 mm, and a left ventricular ejection fraction of 49%. Cardiac surgery was performed promptly after stabilization of inflammatory markers.
The results of transesophageal echocardiography conducted during the operation were consistent with the findings of preoperative transthoracic echocardiography (Video 1, Video 2, Video 3, Video 4). Intraoperatively, the ascending aortic wall appeared pale and edematous, with mild thickening and curling of the aortic valve leaflets; the aortic annulus was normal (Figure 2). A perforation was found in the noncoronary cusp.
The lesion extended inferiorly to the aortomitral curtain and the middle segment of the anterior mitral leaflet, forming a dissection-like lesion in the anterior leaflet. The mitral annulus was dilated, whereas the leaflets exhibited structural integrity. Given the risk of bioprosthetic valve degeneration, mechanical aortic valve replacement (ON-X ACE, 21 mm; On-X Life Technologies, Inc.) and mitral valve repair (posteromedial commissuroplasty) were performed.
Postoperative pathological examination demonstrated focal endothelial loss on the surface of the aortic wall tissue, irregular proliferation of interstitial collagen fibers, with areas of hyaline degeneration and myxoid changes (Figure 3). Degenerative changes were observed in the aortic valve, with no evidence of Behçet's disease involvement.Figure 2Intraoperative Findings of JIA-Related Valvular MorphologyThe aortic wall was pale and edematous (A), with no significant dilation of the annulus or sinus. Both right coronary cusp (B, white arrow) and left coronary cusp (C, white arrow) appeared thickened and curled.
A perforation was found in the noncoronary cusp (D).Figure 3Histopathological Findings of the Excised ValvePathology examination (H&E staining) revealed hyaline and myxoid degeneration in the aortic valve tissue (A). Focal endothelial loss was observed on the surface of the aortic wall tissue (B), as well as irregular proliferation of collagen fibers in the interstitium, with areas of hyaline degeneration and myxoid changes. H&E = hematoxylin and eosin.
The patient's cardiac function recovered favorably after surgery. She continued regular treatment with methylprednisolone and tocilizumab, with no reports of significant discomfort. Follow-up echocardiography at 1 year postoperatively demonstrated normal function of the aortic valve prosthesis, with a left atrial diameter of 27 mm, a left ventricular end-diastolic diameter of 36 mm, a left ventricular end-systolic diameter of 20 mm, and a left ventricular ejection fraction of 63%.
Only trace mitral regurgitation was detected. The patient had no cardiac signs and symptoms during follow-up.
Discussion
In this case, serological tests for antibodies associated with systemic lupus erythematosus, vasculitis, and ankylosing spondylitis yielded negative results. Despite the negative laboratory findings, systemic JIA was deemed the most likely diagnosis, given the patient's clinical manifestations of arthritis, fever, and prior episodes of rash.4 In addition, immunosuppressive treatments such as methylprednisolone and tocilizumab had been shown to be effective. In systemic JIA, vigilance is warranted for secondary infective endocarditis as a cause of aortic regurgitation; however, no evidence of infective endocarditis was identified in this patient after comprehensive screening.
Cardiac involvement in JIA is not frequent, estimated at 4.7%.5 The cardiac lesion found in this case was aortic valve thickening, with mitral regurgitation secondary to annular dilation. Despite the paucity of recent reports on valvular involvement in JIA, the aortic valve is the most frequently affected valve in previously documented cohorts.2,6 Huppertz et al7 reported aortic regurgitation in 4 of 40 patients who were HLA-B27-positive, including 1 case with severe regurgitation and ascending aortic dilation, suggesting that aortic regurgitation is associated with aortic root dilation, cusp edge curling, and fibrotic changes of cusps. Involvement of both mitral and aortic valves has also been reported.8,9 Sircar et al1 reported mild mitral regurgitation in 5 cases.
Alkady et al2 even observed mitral valve thickening in 24.3% and aortic valve thickening in 5.4% of patients, with no significant regurgitation being noted.
Progressive valvular disease can deteriorate prognosis and thus warrants early detection and intervention. In seropositive JIA, aortic regurgitation and impaired diastolic function can occur even in patients with only mild peripheral arthritis and short disease duration. Therefore, regular echocardiographic screening is recommended for these patients.
Measurements of left ventricular diastolic dimensions and shortening fraction may help predict disease progression and inform decisions regarding surgical timing.7 Cardiac involvement in patients with seronegative JIA may manifest as pericarditis or myocarditis.6 Regular follow-up with echocardiographic assessment is also recommended to detect potential valvular involvement.
In some cases, aortic regurgitation may regress after medical treatment.5 However, cardiac surgery should also be considered in cases of severe progressive aortic regurgitation.3,10 The Ross procedure may not be a suitable option because of the reported high risk of autograft valve failure in immune-mediated cardiac diseases. Our case report provides successful evidence of mechanical valve replacement, which supports the possibility of prompt surgical intervention once inflammation is adequately controlled.
Conclusions
JIA can lead to severe aortic valve involvement. Prompt cardiac surgery may be effective and safe to prevent progression, after monitoring by echocardiography.Visual SummaryMechanism of Juvenile Idiopathic Arthritis–Related Cardiac Manifestations
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.Take-Home Messages•Cardiac involvement in juvenile idiopathic arthritis is rare but clinically significant.•Routine echocardiographic screening and timely surgery after immunosuppressive therapy can lead to favorable outcomes.