Overview

Are you interested in learning about rare diseases that affect the vascular system? In this article, we will tackle a disease known as fibromuscular dysplasia, FMD in short.

So, what is FMD? It is a rare disease that affects the blood vessels; it is a non-inflammatory, non-atherosclerotic illness that usually involves the kidney and carotid (neck) arteries, but it can affect other arteries.¹ It affects younger women and makes up 10-20% of renal artery stenosis cases.¹ Classically, fibromuscular dysplasia is characterised as renovascular hypertension, but can also show as strokes in young adults.¹ It occurs when the strong, flexible cells in the arteries are changed with fibrous cells that are weaker and less flexible.² Once this change occurs, the arteries become stiffer and more susceptible to damage; hence, causing high blood pressure (hypertension), stenosis, aneurysm and at times the dissection of arteries.²

There are different types of FMD and can be summarised as:

• Medial FMD¹
• Intimal FMD¹
• Peri-adventitial FMD¹

Early diagnosis and treatment can provide the patient with a better prognosis going forward.¹ So, to further elaborate on this topic, the dedicated sections will cover the information required.

Overview of FMD types

Medial FMD

This type of fibromuscular dysplasia is the most common, taking up around 85% of cases.¹ This FMD affects the middle layer of the arterial wall and leads to the typical ‘string of beads’ pattern.³ This pattern occurs from the alternation between narrowing and enlarging of the arteries that are affected and leading to a blockage or reduced blood flow.⁴ Hence, if it is affecting the brain arteries, this can lead to a stroke or mini-stroke.⁴

This type is further broken into 3 types:¹

• Medial fibroplasia (60-70% of cases)
• Perimedial fibroplasia (15% of cases)
• Medial hyperplasia (1% of cases)3

Intimal fibroplasia

This type is the 2^nd common type after the medial one and affects the inner layer of the arterial wall causing an area of smooth narrowing of the blood vessel.^1,3 

Adventitial (Periadventitial) fibroplasia

This form is the least common (< 1% of cases), and is characterised by a dense deposition of collagen in the outermost layer of the blood vessel. ¹ This causes a smooth narrowing of the blood vessels.¹

There are 4 variants for the blood vessel appearance:

• Multifocal: involves multiple narrowing (also called stenosis) with a string of bead look (mostly associated with medial fibromuscular dysplasia)¹
• Tubular: long concentric narrowing (> 1 cm)¹
• Focal: solitary narrowing (< 1 cm)¹
• Mixed type¹

Epidemiology and symptoms

FMD was first described in the kidney arteries in 1938.¹ Its precise prevalence and cause however are still unclear.¹ FMD can be found in children and some of the cases are thought to be linked to genetics and hormones; with most FMD patients being women (assigned at birth) below the age of 50.^1,2

The symptoms of FMD vary based on the type and location it takes place, but they include:

• Headaches/migraines
• Pulsatile tinnitus, which is a ringing or swishing sound in the ears that occurs with the heartbeat
• Neck pain if it affects the carotid arteries²

Symptoms can be further separated based on the location affected:

Renal

This affects the kidneys, and the most common symptom is hypertension (resistant hypertension in particular), with other symptoms including:¹

• Pain in the flank
• Infarct in the kidneys
• Blood in the urine (also known as haematuria)
• Very low levels of potassium in the blood (known as hypokalaemia)
• Abdominal bruit
• Renal artery dissection

Cranio-cervical

Diagnosis for this type is important to avoid severe complications.¹ This type can be asymptomatic and found through imaging, but in cases of symptoms showing, they include:¹

• Headache
• Ringing in the ears
• Dizziness
• Pain in the neck
• Carotid bruit
• Cervical artery dissection
• Stroke
• Bleeding on the surface of the brain (also known as subarachnoid haemorrhage)
• Horner syndrome

Mesenteric

This form affects the intestines and can present as:¹

• Tiredness
• Abdominal pain
• Epigastric bruit
• Weight loss

Subclavian

This form affects the arteries around the neck and arms, symptoms include:¹

• Weakness in the arms (upper region)
• Steal syndrome
• Numbness, or ‘pins and needles’ sensation
• Pain or cramping in the muscles (known as claudication)

Lower limb

This type affects the lower limbs (legs) and includes:¹

• Ischemic feet
• Cold legs
• Pain and cramping of the muscles in the legs

Coronary

This type affects the heart, and symptoms include:¹

• Pain in the chest
• Shortness of breath
• Acute coronary syndrome

Diagnosis and treatment of FMD types

Renal FMD

The most common characteristic that patients with renal FMD show is arterial hypertension.⁵ It is usually witnessed in young to middle-aged women of Caucasian background.⁵

In cases of suspected FMD, the recommended procedure will involve the usage of computed tomographic angiography (CTA) to confirm the diagnosis.⁵ Magnetic resonance angiography (MRA) can be used, however, CTA is a better option as it provides a better spatial resolution and can visualise the tiny calcifications more than MRA.⁵

While the imaging is important, it does not give enough data regarding the severity of the stenosis, hence translesional pressure gradient measurement will be required to check for the hemodynamic significance of the narrowing of the blood vessel.⁵ This procedure can also be used alongside intravascular ultrasound or optical coherence tomography.⁵

When patients present with hemodynamically significant renal FMD, which involves a translesional pressure gradient of 10% and above, then they should be treated with angioplasty without stenting. ⁵

If angioplasty fails, then surgery can be an option and is the standard approach for complex cases of FMD lesions.⁵

Additionally, patients can be prescribed high blood pressure medication to alleviate the increase and lower the risk of more complications.³

Cerebrovascular FMD

Cerebrovascular FMD can present itself in multiple ways; it can be asymptomatic, or give general symptoms that are not specific for FMD such as headaches, neck pain, dizziness, ringing in the ears or even strokes.⁵

With the risk of intracranial aneurysm and rupture of blood vessels, people who have a confirmed FMD diagnosis in any location are recommended to do a brain screen using CTA or MRA.⁵ Catheter-based angiography is the gold standard for imaging but it is reserved for complicated cases that may require an intervention like severe stenotic lesions.⁵

Treatment has multiple approaches. For example, people suffering from migraines will require lifestyle modification and avoidance of triggers or even medications for headaches.⁵ Ringing in the ears can be approached through sound or cognitive behavioural therapy.⁵ In some cases, surgical clipping or endovascular coiling can be used as a preventative aneurysm exclusion.⁵

Visceral FMD

This form of FMD is less common than the first two, where it accounts for about 14-21% of cases.⁵ The celiac axis, splenic and mesenteric arteries are the most common ones to be involved.⁵ Most cases are asymptomatic, but they can also appear as postprandial flank pain, abdominal aches, nausea and weight loss.⁵

This type is usually confirmed using CTA or MRA, with catheter based angiography being the gold standard.⁵

Treatment is based on the symptoms present, with the location and arteries involved; for example, smoking is to be avoided, with the treatment of high blood pressure and hyperlipidaemia according to the set guidelines.⁵ Additionally, treatment with antiplatelet drugs, in combination with anticoagulation therapy is also an option.⁵

Upper extremity

This FMD has been seen in 3-16% of cases with the brachial artery being the most involved one (but it can take place in other arteries like the ulnar or radial arteries). This form is usually asymptomatic and can be diagnosed through duplex ultrasound, CTA or MRA.⁵

Treatment can involve symptom treatment (conservative), angioplasty or surgery.⁵

Lower extremity (and iliac) FMD

This form may present as asymptomatic in most patients and can be seen to have femoral bruits either by physical examination or imaging.⁵

This form can be diagnosed using CTA, MRA or the gold standard catheter-based angiography. It can also be done via duplex ultrasound, however it will not visualise the arteries well. It is important to distinguish FMD from atherosclerosis according to the lesion nature and lack of plaque.⁵

The treatment will involve symptomatic care, with surgery being an option for more severe cases, however, most patients do well with symptom care and antiplatelet therapy.⁵

Coronary FMD

This type of FMD overlaps with another disease known as spontaneous coronary artery dissection (SCAD), where SCAD is an uncommon cause of acute coronary syndrome. Both of these illnesses share a genetic profile, having the PHACTR1 locus. These diseases are thought to be overlapping ones rather than a single illness, hence more research is required for this in the future. Treatment usually involves a conservative method.⁵

Summary

FMD is a non-inflammatory, non-atherosclerotic illness of unclear origin (also referred to as idiopathic). It affects the musculature of small-medium-sized arteries and is an illness that mostly affects young women, but can also affect men and women of any age. The most common arteries involved in FMD include the renal and cervical ones, however, it can be found in all arterial beds. The diagnosis of FMD is very variable, from picking it up by chance in asymptomatic people, to life-threatening lesions. It is usually caught through CTA, MRA or catheter-based angiography. Treatment depends on the symptoms at hand and can range from conservative treatment to surgery.