Fibromuscular dysplasia differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohsen Basiri M.D.

Overview

Fibromuscular dysplasia must be differentiated from other diseases that present clinical features of multisystem involvement, hypertension, aneurysm, and dissection, such as atherosclerotic vascular disease, vasculitis, and Ehlers-Danlos Type IV.

There is a significant delay in diagnosis from the first onset of clinical symptoms/signs of 4.4 years in men and 4.1 years in women. There are several possible reasons for such a delay, including the possibility that FMD is not considered in the differential diagnosis of a patient’s symptoms because of under-recognition of this disorder, as well as the mistaken belief that FMD is predominately a rare disease of young patients, and the fact that many of the signs and symptoms of FMD are nonspecific, such as dizziness, tinnitus, and headaches.

Differentiating X from other Diseases

Fibromuscular dysplasia must be differentiated from atherosclerotic vascular disease. Patients with atherosclerosis often have multiple atherosclerotic risk factors, whereas most individuals with FMD are younger and have fewer risk factors.

In general, Atherosclerosis occurs proximally and usually involves the proximal segment of the arteries, whereas FMD involves the mid or distal portion of the blood vessel. The "string of beads" appearance is remarkable for FMD; and atherosclerotic disease and FMD can be differentiated radiographically.

• Ehlers-Danlos Type IV may be associated with medial fibroplasia. This differential diagnosis should be considered in patients who have multiple aneurysms in addition to the routine angiographic characteristics of FMD.

• Multisystem involvement is observed in both vasculitis and FMD. Those with FMD generally will not have associated anemia, thrombocytopenia, or abnormalities of acute phase reactants.

Large vessel vasculitis may occur in the absence of changes in acute phase reactants in up to 40% of cases. If histologic proof of FMD or inflammation is not available, distinguishing these entities may at times be difficult because the angiographic appearance can be similar, especially if the intimal fibroplasia is of the multivessel type.

• Segmental arterial mediolysis is a poorly understood condition characterized by spontaneous dissections, occlusion, or aneurysm formation, which may be difficult to differentiate from FMD. Similar to FMD, segmental arterial mediolysis is a noninflammatory, nonatherosclerotic arterial disease. A definitive diagnosis of segmental arterial mediolysis requires tissue examination. This lesion of segmental arterial mediolysis is characterized by the vacuolar degeneration of smooth muscle cells.

• Differential diagnosis of FMD Involving the coronary arteries, are cocaine vasculitis, coronary vasospasm, and atherosclerotic plaque.

• Moyamoya disease (MMD) is a unique disease by bilateral stenosis of the arteries of the circle of Willis and arterial collateral vessels and formation of an abnormal vascular network in the vicinity of the arterial occlusion. The most presentations of this disease are ischemic cerebrovascular events, and hemorrhagic stroke.

Preferred Table

Diseases	Clinical manifestations								Para-clinical findings						Gold standard	Additional findings
	Symptoms				Physical examination
									Lab Findings			Imaging
	Headache	Chest pain	Cerebrovascular accident	Systemic symptoms	Hypertension	Heart attack	motor or/and sensory deficit	Arterial occlusion or/and rupture	Metabolic disturbances (Hyperlipidemia/Hyperglycemia)	Inflammatory biomarkers	Specific Lab Data	Angiography	CTA/MRA	Duplex ultrasound
Fibromuscular dysplasia	+	+/-	+/-	-	+/-	+/-	+/-	+/-	-	-		+	+	+	Angiography
Atherosclerotic Vascular Disease	+/-	+	+	-	+/-	+	+/-	+/-	+	-		+/-	+/-	+/-	Angiography	Generally older than 60 yrs of age
Takayasu Arteritis	+	+/-	+/-	+	+/-	+/-	+/-	+/-	-	+		+	+	+		Female, younger than 40 yrs of age, hypertension, absent or decreased pulses, bruits, murmur of aortic regurgitation
Moyamoya disease	+	-	+		-		+	+	-			+	+	+	Angiography	Children with MMD often exhibit abnormalities on EEG. The most characteristic is the "rebuild-up" phenomenon following hyperventilation.
Ehlers-Danlos Type IV	+/-	+/-	+/-	-	-	+/-	+/-	+/-	-	-		-	-	-	Sequence and deletion/duplication testing of the COL3A1 gene/Analysis of type III procollagen from fibroblasts culture	Younger than 40 yrs of age, small body habitus, characteristic facial appearance, translucent skin, easy bruising, hypermobile joints
Segmental arterial mediolysis	+	-	+		+/-	-	-	+/-	-	-		+	+	+	Histology	A rare conditions in the elderly
Cocaine vasculitis	+/-	+/-	+/-	+	+	+/-	-	-	-	+		-	-	-	Urine toxicology/MPO-ANCA/PR3-ANCA	Men with fewer cardiovascular risk factors