A previously healthy, 16-year-old Guatemalan girl presents to the emergency department (ED) with a 1-month history of dyspnea on exertion.
A previously healthy, 16-year-old Guatemalan girl presents to the emergency department (ED) with a 1-month history of dyspnea on exertion. These episodes are associated with an intermittent cough, occasional fever, dizziness, and a 17-pound weight loss. She had an episode of syncope 3 months prior to presentation, and occasional hemoptysis that resolved 2 weeks ago. She denies chills, orthopnea, shortness of breath at rest, vision changes, chest pain, or palpitations. She returned home from a small town in Guatemala 1 month ago, after living there for 1 year.
In the ED, the patient has a temperature of 97.7°F; heart rate of 96 beats per minute; respiratory rate of 16 respirations per minute; and blood pressure of 99/71 mm Hg. She is thin for her age, yet she appears comfortable while sitting up in bed. Her lung examination is unremarkable, and a grade II/VI systolic ejection murmur is best appreciated at the left upper sternal border without radiation. There are no signs of jugular venous distention, hepatosplenomegaly, lymphadenopathy, or peripheral edema noted. Central and peripheral pulses are normal, and her neurological and skin exams are both unremarkable.
The patient’s white blood cell count is 9450 cells/µL, with 62.5% neutrophils, 22% lymphocytes, 6.2% monocytes, 8.6% eosinophils, and 0.5% basophils. Her hemoglobin is 11.4 g/dL and platelets are 292,000/µL. Erythrocyte sedimentation rate is 20 mm/hr. C-reactive protein is 1.3 mg/dL. Her chemistry panel is normal, including transaminases and lactate dehydrogenase. Chest x-ray in the ED shows scattered multiple calcified pulmonary nodules in the bilateral perihilar spaces, a prominent cardiac silhouette, and small bilateral pleural effusions (Figure 1). Given the concern for a progressive systemic process, she is admitted for further evaluation and management.
The differential diagnosis for these multiple, nonspecific symptoms in a previously healthy teenager is quite broad (Table). Given her travel history, hemoptysis, fevers, cough, and weight loss, she is initially evaluated for primary tuberculosis. Other etiologies include histoplasmosis and coccidiomycosis, given the extent of her pulmonary involvement. Rheumatologic causes, such as eosinophilic granulomatosis with polyangiitis (EGPA) and sarcoidosis, are entertained because of the degree of eosinophilia and location of perihilar nodules. Given the significant history of weight loss, hemoptysis, and scattered lesions on chest x-ray, oncologic processes also should be considered. Further testing helps to determine her diagnosis.
The patient’s infectious and rheumatologic workups are both completely negative, and she is removed from isolation. To further evaluate lung lesions on chest x-ray, a computed tomography (CT) scan of her chest and abdomen is obtained. Diffuse and bilateral ground-glass opacities are seen, and the previously seen calcified pulmonary nodules are characterized as granulomatous in appearance with hilar and mediastinal lymph nodes (Figure 2). Her heart is moderately to severely enlarged, right worse than left. Hepatic congestion is noted with enlargement of the cardiac and pulmonary arteries. No intra-abdominal pathology is found. A transthoracic echocardiogram study is obtained demonstrating severe left atrial enlargement with a mean pressure gradient of 30 mmHg across an abnormal mitral valve, further described as a hammock mitral valve with fusion of leaflets and without defined chordae. Right atrial and ventricular dilatation is also noted. Systolic and diastolic functions are normal. Repeat labs show an increasing eosinophil count to 19.7%, raising suspicion for EGPA.
Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis characterized by necrotizing vasculitis with extravascular granulomas in patients with asthma and eosinophilia. Cardiac involvement can occur in 15% to 60% of patients with EGPA and occurs more frequently in anti-neutrophil cytoplasmic antibody (ANCA)-negative EGPA. The cardiac involvement can vary widely in patients, but can include a valvulopathy-as in this patient. She also has radiographic signs of lung granulomas and an increasing eosinophil count. Differential eosinophil counts greater than 10% are a supporting laboratory finding in EGPA.1 However, the patient lacks some of the more common symptoms and findings in EGPA including asthma, sinusitis, rhinitis, peripheral neuropathy, or dermatologic findings.
After discussion with cardiology, the patient is taken to the operating room for mitral valve replacement. Intraoperatively, her mitral valve anatomy is described as having poor delineation between anterior and posterior leaflets with shortened papillary muscles. Also noted is poor chordal mechanism that is unable to support the majority of the leaflet. A wedge biopsy of the calcified lung tissue is also obtained during surgery. Pathologic report demonstrated emphysematous changes, hemosiderin, and parenchymal fibrosis without granulomatous tissue. The combination of these clinical and pathologic findings leads to a diagnosis of mitral arcade.
Mitral arcade is a rare type of congenital malformation of the mitral valve that was first described in 1967 by Layman and Edwards.2 Mitral arcade valves are thought to develop as a result of an arrest in the embryologic development of the mitral valve before the lengthening of the chordae occur.3 It is characterized by: 1) an adequate mitral valve orifice; 2) short and thick chordae, with direct connection of papillary muscles to mitral leaflets; 3) decreased space between the chordae; and 4) chordae attached to the posterior papillary muscle. This anomaly causes both stenosis and insufficiency of varying degrees.4
The majority of cases are recognized before the age of 3 years, but some cases have reportedly been identified later into adulthood.4,5 The age of presentation and clinical course are likely attributed to when the arrest occurs during embryologic development and the resulting degree of stenosis and insufficiency. There is significant morbidity and mortality the earlier it presents, likely attributing to a higher degree of stenosis that can precipitously cause pulmonary edema and heart failure. In later presentations, the degree of stenosis is thought to be less and a more chronic, progressive course of pathologic heart changes occur.4,5
The patient in this case had a very severe mitral valve pressure gradient across the mitral valve of 30 mm Hg (normal, <2 mm Hg). Her mitral arcade was initially diagnosed via transthoracic echocardiogram and confirmed upon biopsy, which is how most are diagnosed.6 Mitral arcade can lead to pulmonary congestion, further leading to hemosiderin deposits, pulmonary ossification and abnormal lung parenchyma, as seen with this teenaged girl. Hemosiderosis also can present as ground-glass opacities on chest x-ray or CT scan.7
Postoperatively, the patient was started on anticoagulation. A repeat echocardiogram showed normalization of the pressure gradient across the new mechanical mitral valve. Her eosinophilia and clinical symptoms resolved, and she was discharged home on warfarin therapy.
Two months after surgery, the girl was noted to have partial dehiscence of the mitral valve ring, which is not a specific complication of mitral arcade repair. She is being closely monitored with frequent cardiology and cardiothoracic surgery follow-up.
1. Brucato A, Maestroni S, Masciocco G, Ammirati E, Bonacina E, Pedrotti P. Cardiac involvement in Churg-Strauss syndrome. (Article in Italian). G Ital Cardiol (Rome). 2015;16(9):493-500.
2. Layman TE, Edwards JE. Anomalous mitral arcade. A type of congenital mitral insufficiency. Circulation. 1967;35(2);389-395.
3. Séguéla PE, Houyel L, Acar P. Congenital malformations of the mitral valve. Arch Cardiovasc Dis. 2011;104(8-9):465-479.
4. Rajesh GN, Sajeer K, Nair A, Sajeev CG, Krishnan MN. Hammock mitral valve: a rare cause of congenital mitral regurgitation-a case report. Indian Heart J. 2014;66(3):370-371.
5. Federici D, Palmerini E, Lisi M, Centola L, Chiavarelli M, Mondillo S. Congenital mitral disease: anomalous mitral arcade in a young man. Ann Thorac Surg. 2010;89(2):629-631.
6. Hakim FA, Krishnaswamy C, Mookadam F. Mitral arcade in adults-a systematic overview. Echocardiography. 2013;30(3):354-359.
7. Woolley K, Stark P. Pulmonary parenchymal manifestations of mitral valve disease. Radiographics. 1999;19(4):965-972.
8. Mukhopadhyay S, Gal AA. Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med. 2010;134(5):667-690.
9. Gildea TR. Pulmonary disease in small-vessel vasculitis. Cleve Clin J Med. 2012;79(suppl 3):S27-S30.
10. Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital. Arch Pathol Lab Med. 2008;132(7):1079-1103.
Dr Uniat is a first-year pediatrics resident, Children’s Hospital Los Angeles Residency Program, Los Angeles, California. Dr Zipkin is assistant professor of clinical pediatrics, Division of Hospital Medicine, and assistant residency program director, Children’s Hospital Los Angeles, California. The authors have nothing to disclose in regard to financial interests in or affiliations with any organizations that may have an interest in any part of this article.