• Clinical science

Fibromuscular dysplasia

Abstract

Fibromuscular dysplasia (FMD), a disease that primarily affects young to middle-aged women, is characterized by the proliferation of connective tissue and muscle fibers within the arterial vessel walls. The resulting stenosis impairs perfusion of the affected organ, causing ischemia. The symptoms of fibromuscular dysplasia vary depending on the site, the histopathology of FMD, and the degree of stenosis of FMD. The renal, internal carotid, and vertebral arteries are predominantly involved. Carotid and vertebral artery involvement may present with transient ischemic attack (TIA) and/or stroke, while patients with renal FMD usually present with secondary hypertension and chronic renal insufficiency. Bruits at the costovertebral angle and the carotid region are characteristic findings of renal and carotid artery involvement respectively. In rare cases, patients may present with mesenteric ischemia and/or peripheral artery disease as a result of splanchnic or peripheral arterial involvement. The “string of beads” sign, a characteristic finding on angiography, distinguishes FMD from other causes of arterial occlusion. All patients with renal FMD should be treated with ACE inhibitors and/or ARBs, while those with carotid artery involvement should be placed on stroke prophylaxis (low-dose aspirin therapy). Balloon angioplasty without stenting is the definitive treatment.

Epidemiology

  • Age of onset: typically 30–50 years; , but can manifest at any age
  • Sex: > (8:1)
    • Among children:
  • Ethnicity: increased prevalence among the white population

References:[1][2][3][4]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

Fibromuscular dysplasia (FMD) is an idiopathic, non-inflammatory, non-atherosclerotic, developmental condition that primarily affects small and medium-sized muscular arteries.

Histopathology

The most commonly encountered histology is medial fibroplasia. (∼ 75–80%)

Pathological classification has been replaced by angiographic classification because biopsy specimens are rarely obtained today. However, angiographic appearance is closely related to the histology of FMD.

Histological classification Frequency Histopathology Pattern of arterial involvement Appearance on angiography
Medial dysplasia Medial fibroplasia 75–80%

Regions of thickened fibromuscular ridges containing collagen and an intact internal elastic lamina, interspersed with segments having thinned-out tunica media and a missing internal elastic lamina.

Multifocal Strings of beads
Perimedial fibroplasia 10–15% Collagen deposits in the outer half of the tunica media (hence perimedial)
Medial hyperplasia 1–2%

Smooth muscle hyperplasia without fibrosis (no collagen deposition)

Tubular stenosis
Intimal fibroplasia < 10% Collagen deposition in the intima without inflammation Focal
Adventitial fibroplasia < 1% Collagen deposition in periarterial fat with inflammation and expansion of the tunica adventitia

Pathophysiology

Disease localization

Approx. 26% of patients with FMD have lesions in more than one arterial system and approx. 66% have involvement of more than one artery.

  • Renal artery (renal FMD; ∼ 75–80% of cases)
  • Carotid and vertebral artery involvement (extracranial cerebrovascular FMD; ∼ 65–75% of cases and often bilateral)
  • Splanchnic blood vessels (visceral FMD; ∼ 10%):
  • Arteries of extremities (∼ 5%)

References:[1][1][5][5][5][2][3][4]

Clinical features

The symptoms of fibromuscular dysplasia are nonspecific and vary depending on the site of FMD, the degree of stenosis, and the underlying pathology (e.g., arterial dissection).

References:[1][1][5][5][5][2][3]

Diagnostics

  • Imaging
    • Imaging modalities
      • Best initial tests for renal FMD: duplex ultrasonography and/or CT angiography (see “Diagnostics” in renal artery stenosis)
        • Patients with renal FMD require periodic duplex ultrasonography every 6–12 months.
      • Best initial tests for cerebrovascular FMD: CT angiography
        • Patients with cerebrovascular FMD who have small aneurysms with a size below the threshold for surgical management should be followed up with MR angiography every 6–12 months to monitor the size of the aneurysm.
      • Gold standard: digital subtraction angiography (DSA)
    • Finding
      • Common finding: “string of beads” sign
      • Less commonly: a single, circumferential/tubular stenotic lesion
  • Laboratory tests: serum creatinine

References:[2][3]

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

References:[6][7][8]