What are the clinical manifestations of fibromuscular dysplasia and what diagnostic work‑up should be performed?

Symptoms and Diagnosis of Fibromuscular Dysplasia

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory vascular disease that most commonly presents as hypertension in young to middle-aged women, and diagnosis requires imaging from head to pelvis with CT angiography or MR angiography to identify its systemic nature. 1, 2

Clinical Manifestations

Renal Artery Involvement

• Hypertension is the hallmark presentation, particularly in patients aged ≤35 years with new-onset or difficult-to-control hypertension 1, 2
• Severe hypotension or azotemia provoked by ACE inhibitors or ARBs suggests hemodynamically significant renal artery stenosis 1
• FMD characteristically involves the middle and distal two-thirds of the main renal artery and may extend into branches, unlike atherosclerotic disease which affects the ostial and proximal segments 1
• Medial fibroplasia accounts for 80-85% of renal FMD cases and typically affects both renal arteries in women aged 25-50 years 1

Cerebrovascular Involvement

• Stroke or transient ischemic attack (TIA) from reduced blood flow or thromboembolism occurs in approximately 13.4% and 12% of FMD patients respectively 1, 3
• Carotid or vertebral artery dissection, which can occur spontaneously, is a recognized complication affecting 12% of patients 4, 1, 3
• Horner syndrome from carotid involvement presents as ptosis, miosis, and anhidrosis 4, 1
• Cranial nerve palsies can occur with carotid FMD 4, 1
• Subarachnoid hemorrhage from aneurysmal rupture is a potential catastrophic complication 4, 1
• Headaches and pulsatile tinnitus are common neurological symptoms 5

Other Vascular Territories

• Pain on one side of the head or neck is typical with cervical artery dissection 4
• Vertebral artery dissection may present with headache, neck pain, vertigo, nausea, visual disturbances, or syncope 4
• The iliac arteries are commonly affected and require evaluation 3
• Any arterial bed may be affected, including visceral, subclavian, brachial, and popliteal arteries 5, 6

Pathological Manifestations

• Gross pathological features include elongation, kinking and coiling of arteries, spontaneous dissection, and aneurysmal degeneration 4
• Aneurysm occurs in 21.7% of patients and dissection in 25.7%; in total, 41.7% have an aneurysm and/or dissection by the time of FMD diagnosis 7

Diagnostic Work-Up

Initial Screening

• Duplex ultrasonography is the initial screening test for renal artery FMD 1, 2, 3
• Renal artery Doppler ultrasound with bilateral assessment of renal arterial resistive index is recommended for suspected renovascular hypertension 4, 3

Cross-Sectional Imaging (Essential)

• CT angiography or MR angiography from head to pelvis should be performed at diagnosis to identify the systemic nature of the disease 1, 2, 7
• Computed tomographic angiography (CTA) is recommended in patients with normal renal function 1, 3
• Magnetic resonance angiography (MRA) is an alternative screening modality, particularly useful when avoiding radiation or contrast 1, 3
• Contrast-enhanced CTA, MRA, or catheter angiography are all useful for diagnosing cervical artery dissection 1

Definitive Diagnosis

• Catheter-based contrast angiography is the gold standard and should be performed when clinical suspicion is high and noninvasive tests are inconclusive 1, 2, 3, 5

Characteristic Imaging Findings

• The "string of beads" appearance is pathognomonic for medial fibroplasia, where the diameter of the beading is larger than the normal arterial diameter 1, 5
• Focal stenosis can occur with intimal fibroplasia, appearing as concentric or tubular narrowing similar to atherosclerotic disease 1
• Weblike lesions may obstruct flow 1
• Aneurysmal dilation can be present 1
• Arterial tortuosity is a frequent manifestation 5, 8

Laboratory Assessment

• Very elevated renin levels raise suspicion for renovascular hypertension, though not highly sensitive 4, 3
• Assessment of sodium intake (24-hour urinary sodium or sodium-to-creatinine ratio in morning urine) is important for interpreting renin levels 4, 3

Tests NOT Recommended

• Captopril renal scintigraphy, selective renal vein renin measurements, and plasma renin activity are NOT recommended as screening tests 2, 3

Surveillance and Monitoring

• Annual noninvasive imaging of the carotid arteries is reasonable initially to detect changes in disease extent or severity 1, 2, 3
• Imaging frequency may be reduced once stability has been confirmed over time 1, 3
• Regular blood pressure monitoring and renal function assessment are essential in patients with renal artery FMD 2

Critical Pitfalls to Avoid

• Failure to recognize FMD as a systemic disease requiring evaluation of multiple vascular beds beyond the initially symptomatic site 2, 3
• Assuming normal imaging in one vascular bed excludes disease elsewhere—the extracranial carotid, renal, and intracranial arteries are the most common sites of aneurysm, while dissection most often occurs in the extracranial carotid, vertebral, renal, and coronary arteries 7
• Missing the diagnosis in men, who may have more progressive disease, especially when smoking 8
• Confusing FMD with vasculitis—FMD can manifest as a systemic vascular disease mimicking polyarteritis nodosa or Takayasu's arteritis, but requires distinct treatment (corticosteroids can directly harm the vascular wall in FMD) 6