Fibromuscular Dysplasia: Symptoms, Types, Causes and Treatment

Fibromuscular dysplasia (FMD) is a perplexing vascular disease that, despite its obscure name, affects thousands of people—most of them women—around the world. Characterized by abnormal cell growth within artery walls, FMD can cause arteries to narrow, bulge, or tear, leading to a wide range of symptoms and complications. Over the past decade, research registries and international collaborations have expanded our understanding of this systemic, noninflammatory, and nonatherosclerotic disease, revealing its complexity and the critical need for early recognition and tailored care. This article explores FMD’s symptoms, types, causes, and treatments, weaving together the latest findings to provide a clear, patient-centered overview.

Symptoms of Fibromuscular Dysplasia

FMD often masquerades as other illnesses due to its varied and sometimes subtle symptoms. Many patients experience a delay in diagnosis for years, which can contribute to poorer outcomes. Recognizing the key symptoms is essential for early detection and better management.

Symptom	Description	Common Artery Involved	Source(s)
Hypertension	High blood pressure, often sudden	Renal	1 2 3 7 8
Headache	Frequently migraine-type	Carotid/Vertebral	1 4 5 7
Pulsatile tinnitus	Hearing heartbeat in the ear	Carotid/Vertebral	1 2 5
Dizziness/TIA/Stroke	Dizziness, mini-stroke, or stroke	Carotid/Vertebral	1 2 4 6 7

Table 1: Key Symptoms

Common Presentations

FMD’s clinical presentation is primarily determined by which arteries are affected:

• Renal artery involvement often leads to hypertension, which is the most common presenting symptom, especially in younger women without traditional risk factors for high blood pressure 1 2 3 7 8.
• Carotid and vertebral artery involvement can cause neurological symptoms such as headaches (often migraine-like), pulsatile tinnitus, dizziness, transient ischemic attacks (TIAs), or even strokes 1 2 4 5 6 7.

Symptom Details

Hypertension

Sudden or difficult-to-control hypertension is a hallmark of FMD when the renal arteries are affected. This is often the first sign that leads to further investigation, particularly in younger patients or those without classic risk factors for high blood pressure. In some cases, hypertension may be severe and resistant to standard treatments 1 2 3 7 8.

Neurological Symptoms

When FMD involves the arteries supplying the brain, patients may experience:

• Headaches: Up to 70% of patients report headaches, primarily of the migraine type 4 5.
• Pulsatile tinnitus: A rhythmic "whooshing" sound in the ear, matching the heartbeat, is particularly suggestive of FMD involving the carotid or vertebral arteries 1 2 5.
• Dizziness, TIAs, or strokes: Some patients present with symptoms of decreased blood flow to the brain, ranging from lightheadedness to full-blown strokes. Dissections (tears) of these arteries can also precipitate these events 1 2 4 6 7.

Other Manifestations

• Bruits: Physicians may detect abnormal sounds (bruits) over the neck or abdomen during physical exams, hinting at turbulent blood flow from arterial narrowing 2 7 15.
• Aneurysms and Dissections: Some patients experience aneurysms (arterial bulges) or dissections, leading to additional symptoms such as pain or sudden neurological deficits 1 4 8.

Delayed Diagnosis and Asymptomatic Cases

FMD is often underdiagnosed. Many patients experience nonspecific symptoms or are diagnosed incidentally during imaging for unrelated issues. The average delay from symptom onset to diagnosis is 4–9 years, contributing to potentially avoidable complications 2 15. As awareness increases, more cases are being detected in asymptomatic individuals 7 15.

Types of Fibromuscular Dysplasia

FMD is not a single disease but a group of arterial disorders. Understanding its types is crucial for proper diagnosis and management.

Type/Pattern	Description	Typical Appearance	Source(s)
Medial (Multifocal)	Most common; "string of beads"	Alternating narrowings	6 7 8 9
Intimal	Rare; smooth, focal stenosis	Single narrowing	7 8 16
Perimedial	Uncommon; ambiguous appearance	Tubular/focal	7 8 16 17
Anatomical	Renal, Carotid, Vertebral, etc.	Varies by artery	1 2 3 7 8

Table 2: Classification of FMD Types

Histological Types

Medial (Multifocal) FMD

• Most common subtype (up to 80–90% of FMD cases)
• Characterized by alternating areas of narrowing and dilation, producing the classic "string of beads" seen on angiography 6 7 8 9.
• Primarily affects the middle and distal segments of medium-sized arteries.

Intimal FMD

• Rare, accounting for a small fraction of cases.
• Presents as a smooth, focal narrowing (stenosis) rather than multiple narrowings.
• May be mistaken for atherosclerosis or other vascular diseases 7 8 16.

Perimedial FMD

• Less frequent, with features overlapping with other types.
• May appear as tubular or focal stenoses on imaging 7 8 16 17.

Angiographic Patterns

• Multifocal pattern: Multiple narrowings interspersed with small bulges ("string of beads"), almost always attributable to medial FMD.
• Focal pattern: Single, discrete narrowing, often reflecting intimal or perimedial involvement 7 8 9.

Anatomical Distribution

FMD can affect any artery, but some are more commonly involved:

• Renal arteries: Most frequent site, often leading to hypertension 1 2 3 7 8 9.
• Carotid and vertebral arteries: Often associated with neurological symptoms 1 2 4 6 7 8 10.
• Other arteries: Less commonly, FMD involves the iliac, subclavian, mesenteric, or coronary arteries 3 8 9.

Multivessel and Systemic Involvement

• Many patients have FMD in more than one vascular bed; up to 48% in some studies 8 9.
• Increasing evidence supports the view of FMD as a systemic arterial disease rather than a localized process 8 11.

Causes of Fibromuscular Dysplasia

Despite decades of research, the exact cause of FMD remains elusive. However, recent advances shed light on possible contributing factors.

Factor	Contribution	Evidence/Notes	Source(s)
Genetic	Familial clusters, GWAS	Rare familial cases; risk loci	1 4 11 12 13
Hormonal	Female predominance	90%+ of patients are women	1 2 7 8
Mechanical	Arterial stress/trauma	E.g., kidney mobility	3 8
Environmental	Smoking association	Smoking may worsen progression	8

Table 3: Proposed Causes of FMD

Genetic Susceptibility

• Familial Cases: While most patients have no known family history, about 5–10% of cases show familial clustering, suggesting a genetic component 1 4 7 12.
• Identified Genes: Genome-wide association studies (GWAS) have identified risk loci, including PHACTR1, LRP1, ATP2B1, and LIMA1, all of which are involved in vascular structure and function 13.
• Rare Syndromes: Mutations in the YY1AP1 gene cause Grange syndrome, a rare FMD-like vascular disease 12.
• Shared Genetics: FMD shares genetic risk with other cardiovascular conditions, including migraine, hypertension, and aneurysm formation 13.

Hormonal and Sex-Related Factors

• Female Predominance: Over 90% of FMD patients are women, typically presenting between ages 20 and 60, suggesting a hormonal influence, though no direct hormonal cause has been proven 1 2 7 8.
• Not Exclusively Female: Men, children, and the elderly can also develop FMD 1 7 15.

Mechanical and Environmental Factors

• Mechanical Stress: Repeated trauma or movement of arteries (e.g., renal artery due to kidney movement) may contribute to the development of FMD 3 8.
• Smoking: Smoking has been associated with increased risk and more severe disease, particularly in progression of FMD 8.

Systemic and Molecular Features

• Systemic Disease: Detailed studies show that FMD may involve changes in connective tissue and signaling pathways (e.g., TGF-β), further supporting its systemic nature 11.
• Noninflammatory/Nonatherosclerotic: FMD is distinct from atherosclerosis and vasculitis—arterial wall inflammation is absent, and fatty plaques are not seen 1 2 3 8.

Treatment of Fibromuscular Dysplasia

Treatment of FMD is tailored to the patient’s symptoms, artery involvement, and risk of complications. Advances in minimally invasive procedures and medical therapy have improved outcomes for many.

Treatment	Use Case / Indication	Notes	Source(s)
Antihypertensive meds	Renal FMD with hypertension	First-line for BP control	1 2 3 7 15
Antiplatelet therapy	Stroke/TIA or cerebral FMD	Prevents thrombosis	4 7 15
Angioplasty (PTA)	Severe stenosis or symptoms	Especially renal FMD	3 7 14 15 16 17
Stenting/Surgery	Aneurysm, dissection, complex FMD	Covered stents, open repair	7 8 15 16
Observation	Asymptomatic, stable patients	Regular monitoring	4 7 16 17

Table 4: Treatment Approaches

Medical Therapy

• Blood Pressure Control: Essential for patients with renovascular hypertension. Medications include ACE inhibitors, ARBs, calcium channel blockers, or beta-blockers, tailored to patient needs 1 2 3 7 15.
• Antiplatelet Therapy: Aspirin or other antiplatelet agents are recommended for patients with cerebrovascular FMD to reduce the risk of thromboembolic events, especially if there is a history of TIA or stroke 4 7 15.
• Statins: Not routinely used unless the patient has concurrent atherosclerosis 7.

Endovascular and Surgical Interventions

• Percutaneous Transluminal Angioplasty (PTA): The preferred treatment for significant, symptomatic renal artery stenosis. Success rates are high, and the need for stenting is uncommon unless complications occur 3 7 14 15 16 17.
• Stenting and Surgery: Reserved for cases with aneurysm, arterial dissection, or where angioplasty is unsuccessful. Covered stents or open surgical repair may be required for complex cases 7 8 15 16.

Management of Cerebral Aneurysms and Dissections

• Unruptured Aneurysms: Monitored with imaging; intervention depends on size and risk factors 4 7 8.
• Ruptured Aneurysms: Require urgent neurosurgical clipping or endovascular coiling 7.
• Dissections: Treated conservatively with antiplatelet therapy unless there is ongoing ischemia or risk of rupture 4 7.

Monitoring and Follow-Up

• Imaging: Regular noninvasive imaging (ultrasound, CTA, MRA) is used to monitor disease progression, especially in patients with multivessel involvement or aneurysms 7 8 15 16.
• Lifestyle: Smoking cessation and management of other cardiovascular risk factors are encouraged 8 15.

Special Considerations

• Pregnancy: Women with FMD require close monitoring during pregnancy due to increased risk of hypertension and vascular complications 7.
• Asymptomatic Patients: Often managed conservatively with periodic monitoring and patient education 4 7 16 17.

Conclusion

Fibromuscular dysplasia is a complex, systemic vascular disease that can affect multiple arteries and present with a variety of symptoms. Early recognition, tailored diagnostic strategies, and individualized treatment have improved patient outcomes, but gaps in understanding remain. Ongoing research and growing awareness will continue to shape the future of FMD care.

Key Takeaways:

• FMD most commonly affects the renal, carotid, and vertebral arteries, with symptoms ranging from hypertension and headaches to stroke and aneurysm.
• Medial (multifocal) FMD is the most common type, but several patterns exist, and multivessel involvement is frequent.
• The exact cause is unknown but likely involves genetic, hormonal, mechanical, and environmental factors.
• Treatment ranges from medical management and angioplasty to surgery, depending on symptoms, artery involvement, and risk of complications.
• Regular follow-up and a multidisciplinary approach are essential, especially in patients with multivessel or systemic disease.

Being aware of FMD’s varied presentations and evolving treatment strategies is crucial for patients and healthcare professionals alike. As research advances, improved diagnostics and therapies offer hope for those affected by this enigmatic vascular disorder.