Case Presentation

An 8-year-old female presents to the emergency department (ED) referred by her primary care provider (PCP) for left-sided neck swelling and murmur. Per the patient’s mother, the patient has had left-sided neck swelling for 1 month. The patient also experienced subjective fevers, chills, headaches, and malaise. Over that same period, mom also noticed about 5 pounds (2 kg) of weight loss and intermittent side pain. Because of these concerns, mom took her daughter to the PCP 2 weeks before ED presentation and was diagnosed with lymphadenitis and started on oral amoxicillin-clavulanic acid and told to follow up the following week. At the following visit, there was a minimal improvement of the neck swelling, so the patient was switched to oral clindamycin. After a week of being on the clindamycin, the patient presented again to the PCP with minimal improvement of her symptoms. At this visit, the PCP also noticed a new cardiac murmur. Because the patient had failed outpatient antibiotic therapy and had this new heart murmur, the PCP referred the patient to the ED.

Initial Evaluation

On arrival to the ED, the patient had appropriate vital signs for her age other than a blood pressure of 169/96. On physical exam, the patient was noted to have a grade 2/6 systolic heart murmur without evidence of radiation. She denies any symptoms of lightheadedness, syncope, palpitations, or fatigue with exertion. Mom states that the patient never had any heart problems nor was there significant family history. The other significant findings on the physical exam were a firm, yet mobile 2-cm mass slightly superior to the left anterior cervical lymphatic chain as well as a weak left radial and brachial pulse.

Differential Diagnosis

Differential diagnosis includes, but is not limited to:

Cardiovascular

• Aneurysm
• Arterial-vascular malformation
• Atherosclerosis
• Fibromuscular dysplasia
• Giant cell arteritis
• Infectious aortitis
• Takayasu arteritis

Infectious Disease

• Abscess
• Cellulitis
• Cat scratch disease
• Ebstein Barr virus/mononucleosis (EBV)
• Human immunodeficiency virus (HIV)
• Lymphadenitis
• Mycobacterium/Tuberculosis (TB)
• Sepsis

Hematology/Oncology

• Leukemia
• Lymphoma

Immunologic/Lymphatic

• Branchial cleft cyst
• Dermoid cyst
• Fibroma
• Kawasaki
• Salivary gland cyst
• Thyroglossal duct cyst

Confirmatory Evaluation

Lab workup included:

• Blood culture
• Complete blood count
• Comprehensive metabolic profile
• Inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein [CRP])
• Ebstein Barr panel/monospot
• Streptococcal throat swab

Laboratory testing including HIV, EBV, TB, blood, urine, and throat cultures was all negative.

ESR and CRP were elevated at 72 and 11.7. Blood count was unremarkable and metabolic panel was notable for hypokalemia to 3.1.

Diagnostic imaging included:

• Chest x-ray
• Echocardiography (ECHO)
• Electrocardiogram
• Magnetic Resonance Imaging and Arteriogram (MRI/MRA)
• Ultrasound of the neck and soft tissue

Ultrasound of neck showed wall thickening of the left common carotid artery with possible involvement of the left internal carotid artery.

The ECHO was notable for a bicuspid aortic valve, as well as a mildly dilated left ventricle with mildly decreased left ventricular function.

MRI/MRA revealed large vessel vasculitis involving the left external carotid artery, left renal artery, superior mesenteric artery, and left subclavian artery.

Diagnosis

With the combination of hypertension, a dilated left ventricle, and multiple areas of vasculitis, the diagnosis of Takayasu arteritis was made. The neck mass was likely secondary to vasculitis involving the left carotid artery. Given the physical exam findings, elevated inflammatory markers, multiple cardiac findings, and hypertension, cardiology was consulted, and the patient was admitted.[1][2][3]

Management

In the ED, nifedipine was given once for hypertension, and her blood pressure responded appropriately. The patient also had a 4/5 headache that was treated with acetaminophen and ibuprofen, and it improved. Nephrology was consulted. The specialist recommended a renal ultrasound and other labs as well as starting amlodipine 5 mg daily. The patient was admitted to the hospital for further management.[4][5][6]

The patient was started on nifedipine (calcium channel blocker, anti-hypertensive) for her hypertension and then ultimately discharged on carvedilol. Furthermore, for coagulation prophylaxis, she was started on low-dose aspirin due to arteritis involving the left common carotid and vertebral artery.

Rheumatology was also consulted and recommended to start low-dose steroids and mycophenolic acid to help decrease the amount of arterial inflammation.

Nephrology was also consulted in conjunction with cardiology for blood pressure management. In addition to starting anti-hypertensive medications, she was placed on daily fluid restriction.

Discussion

Takayasu arteritis is a condition in which pathogenesis is poorly understood. It is believed that pathological infiltration of inflammatory cells in the aorta and its different luminal layers and branches are the underlying mechanisms for this disease. This inflammatory process eventually leads to dilation, occlusion, or stenosis of the affected vessel, which can all present in a variety of clinical manifestations.[7]

Takayasu arteritis is a chronic disease with many episodes of exacerbations and remissions of the inflammatory processes. Adult women are primarily affected as they represent 80% to 90% of cases. This disease onset is between 10 to 40 years old, and the diagnosis of Takayasu arteritis tends to be delayed due to the sub-acute onset of symptoms in this disease. This can sometimes lead to worsening progression of disease in this asymptomatic period.

Since the pathophysiology can affect the vessels in different ways, patients can present with a wide array of clinical symptoms. Non-specific findings such as fever, fatigue, and malaise can be the only symptoms present early in the course of this disease. Other common signs and symptoms include weak peripheral pulses, hypertension, limb claudication, gastrointestinal (GI) symptoms, and murmurs.

• Physical exam: Physical exam should include careful examination of peripheral pulses and cardiac auscultation. Blood pressure reading in all extremities can also be used as a tool to help aid in diagnosis.
• Laboratory: This condition is largely an inflammatory process so inflammatory markers such as ESR and CRP should be obtained. However, these values can still be within the normal range and not reliable in the detection of the active disease process.
• Diagnostic imaging: Imaging of the aorta is needed to determine the extent of damage to the aorta. Computerized tomography (CT) of the chest or MRI can be used to detect patency of the aortic lumen.

Histology shows infiltration of predominantly lymphocytes, histiocytes, macrophages, and plasma cells in the media of the aorta and its branches. Progressive damage and destruction of the lamina and media can lead to aneurysmal dilation or dense scarring.

The mainstay of treatment for this condition is steroids. Steroids suppress the progression of the disease and can sometimes reverse early complications. Surgery is an option for patients with aneurysms or severe stenosis. The patient can eventually be weaned off of steroids with symptom and inflammatory marker improvement.

Pearls of Wisdom

• Recognize age-appropriate vital signs.
• Do a thorough physical exam especially with patients who have failed outpatient management.
• Takayasu arteritis is often misdiagnosed and therefore not properly treated. It is important to recognize early signs of this disease and provide work-up and reassessment accordingly.