Fibromuscular Dysplasia

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy that causes stenosis, aneurysm, dissection and arterial tortuosity of small and medium-sized arteries. It is a systemic disease, and multiple vascular beds are often involved.

Epidemiology

• Women account for 80 to 90% of cases, with a mean age at diagnosis of 45 to 55 years.
• True prevalence is uncertain, probably 3 to 4 per 1,000 in some imaging series.
• Genetic susceptibility is supported by familial clustering and an association with the PHACTR1 locus. Smoking and hypertension may influence progression.

Vascular beds affected

• Renal arteries in 60 to 75%, with extracranial carotid and vertebral arteries in 25 to 75% (overlapping).
• Mesenteric, iliac, subclavian and coronary arteries are involved less often, and intracranial aneurysms are found in about 7 to 20%.

Angiographic classification

• Multifocal: alternating stenoses and dilatations producing the string of beads appearance, which reflects medial fibroplasia. This is the commonest pattern in adults.
• Focal: a single tubular or concentric stenosis, more often seen in younger patients and children. It can reflect intimal fibroplasia or perimedial disease.

Complications include dissection (in about 20 to 25%), aneurysm formation (about 20%), spontaneous coronary artery dissection (FMD is found in a high proportion of SCAD cases), transient ischaemic attack and stroke, and renovascular hypertension.

Associated conditions to consider: vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Marfan syndrome, Takayasu arteritis, neurofibromatosis type 1, and alpha-1 antitrypsin deficiency.

Many patients are asymptomatic and diagnosed incidentally. Presentations are based on the bed involved:

• Renal: hypertension of early onset or resistant to treatment, flank pain, renal infarction, and abdominal bruit. Renal failure from ischaemic nephropathy is uncommon.
• Cerebrovascular: headache (often migrainous), pulsatile tinnitus, neck pain, cervical bruit, Horner syndrome, TIA, stroke, and dizziness. Cervical artery dissection can be the presenting event.
• Intracranial aneurysm: subarachnoid haemorrhage with thunderclap headache.
• Mesenteric: postprandial abdominal pain, weight loss, and intestinal ischaemia, which is uncommon.
• Coronary: chest pain from spontaneous coronary artery dissection, often in younger women, with acute myocardial infarction.
• Limb: claudication, which is uncommon.

Features that point towards the diagnosis include hypertension under 35 years of age, hypertension in a woman with no family history, pulsatile tinnitus, and dissection of a cervical or coronary artery in a young or middle-aged woman with no atherosclerotic risk factors.

Differential diagnosis

• Atherosclerotic renal artery stenosis (older, ostial, proximal).
• Takayasu arteritis and giant cell arteritis (raised inflammatory markers, wall thickening).
• Connective tissue arteriopathies.
• Essential hypertension and primary aldosteronism.
• Segmental arterial mediolysis.
• Extrinsic compression and post-radiation stenosis.

Diagnosis is by imaging showing typical features after other arteriopathies are excluded. Biopsy is not used.

Imaging strategy

• Initial test in suspected renal disease: duplex ultrasound for velocity elevations and tardus parvus waveforms, though sensitivity for distal and branch disease is limited.
• CT angiography is the preferred non-invasive study, showing string of beads, focal webs, aneurysms, dissection and tortuosity. Image from the head to the pelvis, because multiple beds are involved in a high proportion of patients.
• MR angiography of the head and neck avoids radiation, though it has lower spatial resolution for distal vessels.
• Catheter angiography is reserved for equivocal results and for procedures. A translesional pressure gradient of 10 to 20 mmHg or more indicates a haemodynamically significant renal lesion.
• Intravascular ultrasound or optical coherence tomography can help in complex coronary or renal cases.

Further work-up after the diagnosis

• Screening for intracranial aneurysm with MR angiography or CT angiography of the head.
• Careful assessment for dissection, using fat-suppressed MRI of the neck.
• Plasma renin and aldosterone, creatinine, eGFR, urinalysis and electrolytes.
• ESR and CRP to exclude large vessel vasculitis.
• Genetic testing (COL3A1, TGFBR1, TGFBR2, SMAD3 and related genes) when clinical features suggest a heritable arteriopathy.
• Echocardiography when aortic root disease is suspected.

Antithrombotic and risk factor management

• Aspirin 75 to 100 mg daily for patients with cerebrovascular disease, or after any revascularisation.
• Statin therapy only when atherosclerotic risk factors coexist.
• Smoking cessation is essential.
• Avoid neck manipulation, high-impact contact sports, heavy straining and activities with abrupt neck movements.

Hypertension

• ACE inhibitors or angiotensin receptor blockers are first line, for example ramipril 2.5 mg daily titrated to 10 mg, or losartan 50 to 100 mg daily. Monitor creatinine and potassium at 1 to 2 weeks, and exercise caution in bilateral disease or a solitary kidney.
• Add amlodipine 5 to 10 mg, a thiazide-like diuretic such as chlorthalidone 12.5 to 25 mg, or a beta blocker as needed.
• Pregnancy: labetalol 100 to 400 mg twice daily or nifedipine modified release 30 to 60 mg daily. Avoid ACE inhibitors and ARBs.

Revascularisation of renal arteries

• Indications are resistant or intolerant-to-treatment hypertension, hypertension of early onset with significant stenosis, and declining renal function with renal artery stenosis.
• Percutaneous balloon angioplasty without a stent is the treatment of choice. Hypertension is cured or improved in about 60 to 80%, with lower cure rates in older patients and those with long-standing hypertension.
• Stent placement is reserved for flow-limiting dissection or recoil after angioplasty.
• Surgical reconstruction (aortorenal bypass, autotransplantation) is used for complex branch disease, aneurysm that is not suitable for endovascular care, or failed angioplasty.
• Follow-up duplex at 1, 6 and 12 months, then annually.

Cerebrovascular disease

• Dissection: antithrombotic therapy for 3 to 6 months, either aspirin 75 to 100 mg daily or anticoagulation, as for cervical artery dissection. Stenting is reserved for recurrent ischaemic events despite medical therapy.
• Symptomatic high-grade stenosis: angioplasty with or without stenting in selected cases.
• Headache: treat migraine according to standard guidance, though triptans are avoided in patients with cervical or coronary dissection.
• Intracranial aneurysms: coiling or clipping per size, location and rupture status.

Spontaneous coronary artery dissection

• Conservative management for stable patients with preserved flow, since most lesions heal. Give aspirin 75 to 100 mg daily and a beta blocker such as metoprolol 25 to 50 mg twice daily. Avoid thrombolysis.
• Percutaneous or surgical revascularisation is reserved for ongoing ischaemia, haemodynamic compromise or left main involvement.
• Cardiac rehabilitation and counselling on future pregnancy risk.

Mesenteric and other disease

• Angioplasty for symptomatic mesenteric stenosis, and repair of aneurysms larger than 2 cm or those that are enlarging.

Follow-up

• Annual blood pressure, renal function and clinical review. Repeat head-to-pelvis imaging every 1 to 3 years in the first years, then at longer intervals if stable.
• Pregnancy: planning with a specialist team, because dissection and hypertensive complications are more likely.
• Family counselling for first-degree relatives with symptoms, with screening for those with a strong history.