Clinical manifestations and diagnosis of fibromuscular dysplasia

INTRODUCTION — Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disorder that leads to arterial stenosis, occlusion, aneurysm, dissection, and arterial tortuosity. These findings have been observed in nearly every arterial bed [1]. The most frequently involved arteries are the renal and internal carotid arteries, followed by the vertebral, visceral, and external iliac arteries [1,2]. Disease presentation may vary widely, depending upon the arterial segment involved and the severity of disease.

The epidemiology, pathogenesis, clinical manifestations, and diagnosis of FMD in adults are reviewed here. The treatment of FMD and the general evaluation for possible renovascular hypertension and stroke are discussed separately:

●(See "Treatment of fibromuscular dysplasia of the renal arteries".)

●(See "Establishing the diagnosis of renovascular hypertension".)

●(See "Evaluation of secondary hypertension".)

●(See "Clinical diagnosis of stroke subtypes".)

●(See "Overview of the evaluation of stroke".)

EPIDEMIOLOGY — Patients with FMD have involvement of the renal arteries approximately 75 to 80 percent of the time and involvement of the extracranial cerebrovascular arteries (eg, carotid and vertebral arteries) approximately 75 percent of the time [2]. Approximately two-thirds of patients have multiple arteries involved [1,3-5].

Among adults, FMD is more common among females. In most large series, approximately 90 percent of cases are in females. There does not appear to be a female predominance among children with FMD [6,7].

In the past, it was believed that FMD was a disease of young females. However, older individuals account for a large proportion of affected patients in several cohorts. As an example, in the United States FMD Registry, the mean age at diagnosis was 52 years, with a range of 5 to 97 years [2,8,9].

There is often a delay from the first symptom or sign until the diagnosis of FMD [7,10]. In one study, for example, the average age of hypertension diagnosis in patients with focal FMD was 26 years, but the average age of diagnosis was 30 years [10]. In another study of multifocal FMD, the average age of hypertension onset was 40 years and the average age of diagnosis of FMD was 49 years [10].

Renal arteries — Among patients with renovascular hypertension, FMD accounts for 35 to 50 percent of cases in children and 5 to 10 percent of cases in adults under the age of 60 years [11-13]. It can also occur in older patients, either in isolation or in combination with atherosclerosis, but the prevalence is not well described. Approximately 65 percent of patients with renal artery FMD also have carotid or vertebral FMD, and, similarly, patients with carotid or vertebral FMD are likely to have kidney involvement [2]. (See "Definition and diagnosis of hypertension in children and adolescents".)

FMD of the renal arteries can be an incidental finding. In a synthesis of four angiographic studies, for example, 139 of 3181 asymptomatic potential kidney donors (4.4 percent) had evidence for FMD [14]. The prevalence of incidentally discovered FMD was even higher in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial [15]. Although FMD was an exclusion criterion for enrollment in this trial, and all patients presumably had atherosclerotic renal artery stenosis, review of images by the core laboratory revealed that FMD was present in 8.8 percent of the 499 females who were enrolled and 2.8 percent of the 498 males who were enrolled [15].

Other arteries — Extracranial cerebrovascular (eg, carotid and vertebral arteries) involvement is common in patients with established renal FMD. Data from the first 447 patients entered into the United States FMD Registry reveal that approximately 65 percent have extracranial cerebrovascular disease [2]. Older literature indicated that carotid artery involvement was present in only 25 to 30 percent of patients with FMD [16]. However, it was not previously standard practice to image other vascular beds when renal artery FMD was diagnosed, possibly accounting for these historical lower-prevalence estimates. Asymptomatic extracranial cerebrovascular disease is discovered more commonly now that every patient diagnosed with renal artery FMD routinely undergoes imaging of other vascular beds.

When cerebrovascular disease is present, there is often bilateral carotid involvement, coexisting vertebral artery disease, and, less commonly, disease in the external carotid, middle cerebral, anterior cerebral, basilar, and anterior communicating arteries [2,17,18]. FMD may also be associated with intracranial aneurysms [17-21].

FMD of the visceral arteries is less common and typically involves the celiac, superior mesenteric, inferior mesenteric, hepatic, and splenic arteries. In the lower extremities, FMD occurs most frequently in the external iliac arteries, although it also has been described in the femoral, popliteal, and tibioperoneal arteries [16,22]. Now that radial artery access is being performed more frequently for patients undergoing percutaneous coronary intervention, FMD is being identified more frequently in the brachial, radial, and ulnar arteries [23].

CLASSIFICATION (BY ANGIOGRAPHY) — In the past, FMD was classified according to the arterial layer affected (intima, media, or adventitia) [24,25]. However, pathological specimens are rarely obtained (due to the fact that, if a lesion requires treatment, percutaneous endovascular therapy is the preferred method rather than surgery). Thus, because FMD is virtually always diagnosed radiographically and histology is not typically available, pathological classification has been replaced by an angiographic classification (table 1) [5].

FMD is most commonly classified by angiographic appearance (table 1). There are two angiographic subtypes of FMD:

●Multifocal FMD (more common) (image 1) has the angiographic appearance of a "string of beads." Multifocal FMD corresponds pathologically to medial fibroplasia, the most common histologic type, and to perimedial fibroplasia, which is less common.

●Focal FMD (less common) (image 2) has the angiographic appearance of a "circumferential or tubular stenosis" and corresponds pathologically to intimal fibroplasia. Medial hyperplasia and periarterial hyperplasia are histologic types that may also have a focal appearance.

It has been shown that these two different angiographic subtypes of FMD (multifocal and focal) have different phenotypic presentations and natural history [10]. This has led some investigators to question whether FMD is, in fact, a single disease [26].

FMD is not classified histologically because pathological specimens are rarely obtained [1]. In the past, fibrous lesions were classified according to the arterial layer affected (intima, media, or adventitia) (table 1):

●Medial fibroplasia represents the most common dysplastic lesion, accounting for more than 80 percent of fibromuscular lesions [24,25]. Angiographically, medial fibroplasia is characterized by the classic "string of beads" appearance (image 1 and image 3). This appearance is due to alternating fibromuscular webs followed by poststenotic dilatation. In areas of dilatation, the internal elastic lamina is absent, which is possibly the primary defect. Total occlusion is uncommon in the absence of dissection.

●Intimal fibroplasia (which accounts for approximately 10 percent of FMD) is caused by circumferential or eccentric deposition of collagen in the intima (image 2). The internal elastic lamina may be intact, fragmented, or duplicated, the latter especially in the childhood form. There is no inflammatory or lipid component.

●In perimedial fibroplasia, which occurs predominately in children, large parts of the media (in particular, the outer zone) are replaced by collagen, with irregular thickening of the media. Total occlusion may occur with development of collateral vasculature. "Beading" is present in this type, but the "beads" are less numerous and are smaller than in medial fibroplasia. Aneurysm formation is uncommon.

●Medial hyperplasia, a rare manifestation, is caused by smooth muscle cell hyperplasia without fibrosis.

●Periarterial hyperplasia, also a rare manifestation, is caused by expansion of the fibrous adventitia; collagen extends into the periarterial fat, with accompanying inflammation.

PATHOGENESIS — The etiology of FMD remains unknown. Although a variety of factors have been implicated, most investigators now believe that genetics play an important role in the development of FMD [1,27], with some studies reporting an autosomal mode of inheritance with variable penetrance [28,29]. Another study found an association between FMD and a single nucleotide variant in the phosphatase and actin regulator 1 gene (PHACTR1) [30]. This variant, rs9349379, is also a risk locus for coronary artery disease, migraine headache, cervical artery dissection [31], and spontaneous coronary artery dissection (SCAD) [32]. Using whole-exome sequencing, targeted sequencing, and genome sequences in patients with FMD or SCAD, genetic variants in prostaglandin I2 receptor gene (PTGIR) that impair its cellular function were identified that may play a role in the pathogenesis. A limitation of this study is that the prevalence of the identified PTGIR loss-of-function variants is low and affects a small fraction of patients with FMD and SCAD [33]. FMD exhibits a plasma proteogenomic and lipid signature that includes potential causative factors, such as CD2-associated protein. This is promising for the development of a blood test for the diagnosis of FMD [34].

Given the predominance in females of childbearing age, hormonal influences are thought to also be important in the pathogenesis of FMD, yet there are no definitive studies. It is also possible that mechanical factors such as stretching of smooth muscle cells and trauma to the blood vessel wall may initiate the changes seen in FMD, but this theory has never been proven.

CLINICAL MANIFESTATIONS — Disease manifestations may result from the following mechanisms [4,5]:

●Ischemia related to stenosis

●Dissection and occlusion of major arteries (renal infarction, stroke, myocardial infarction)

●Rupture of aneurysms

●Embolization of intravascular thrombi from dissection or aneurysms

Thus, disease presentation may vary widely, depending upon the arterial segment involved, the length and degree of stenosis, and the angiographic type of FMD.

Common presenting symptoms and signs — The clinical presentation of FMD varies somewhat in males as compared with females [35]. In general, manifestations of renal FMD (eg, hypertension, flank pain) are more likely to occur in males, as are arterial dissections and aneurysms. By contrast, manifestations of cerebrovascular FMD (eg, headache, pulsatile tinnitus, neck pain, carotid bruit) are more likely to occur in females.

The most common presenting symptoms in 615 individuals from the United States FMD Registry are as follows [35]:

●Headache – 57 percent (58 percent of females and 47 percent of males)

●Pulsatile tinnitus – 33 percent (36 percent of females and 9 percent of males)

●Neck pain – 27 percent (29 percent of females and 13 percent of males)

●Flank or abdominal pain – 17 percent (14 percent of females and 44 percent of males)

The most common presenting signs of FMD are as follows [35]:

●Hypertension – 67 percent (66 percent of females and 74 percent of males)

●Cervical bruit – 25 percent (27 percent of females and 4 percent of males)

●Abdominal bruit – 11 percent (12 percent of females and no males)

●Transient ischemic attack – 10 percent (10 percent of females and 4 percent of males)

●Stroke – 8 percent (8 percent of females and 4 percent of males)

Headache, pulsatile tinnitus, and neck pain are typically symptoms of extracranial cerebrovascular FMD (table 2) [36], usually caused by stenosis, aneurysm rupture, dissection, or cerebral thromboembolism [20,21,37-39]. Other manifestations suggestive of brain ischemia may occur, including amaurosis fugax, Horner syndrome, and, as noted above, transient ischemic attack or stroke [17,18]. Brain ischemia is almost always related to a dissection of the carotid or vertebral artery.

Hypertension is the most common manifestation of renal artery FMD (table 3). A decrease in kidney perfusion activates the renin-angiotensin-aldosterone system, which has direct effects on sodium excretion, sympathetic nerve activity, intrarenal prostaglandin concentrations, and nitric oxide production. These ultimately lead to renovascular hypertension. Flank pain and abdominal pain can result from ischemia, aneurysm rupture, or dissection of renal and mesenteric arteries, respectively.

Chronic mesenteric ischemia or intestinal angina may occur when two of the splanchnic arteries are occluded and the third is severely stenotic. Occasionally, mesenteric ischemia may occur with superior mesenteric artery stenosis alone, although extensive collaterals in the mesenteric circulation generally prevent ischemia when only one splanchnic vessel is occluded. Patients may present with the classic triad of postprandial abdominal pain, weight loss, and an epigastric bruit. In rare cases, the stenosis progresses to total occlusion, resulting in acute intestinal ischemia [40].

Less common manifestations — Patients with lower-extremity FMD may present with intermittent claudication, critical limb ischemia, or microembolism that manifests as painful, cyanotic toes [22]. Rarely, iliac dissection, occlusion, or aneurysm rupture may occur [41]. In the upper extremities, FMD may present with weakness, paresthesias, upper-extremity claudication, or critical limb ischemia [23]. Physical examination may reveal diminished pulses, a bruit, and cyanosis.

FMD may also be asymptomatic or, in its extreme form, may present as a multisystem disease mimicking necrotizing vasculitis [16].

Aneurysm and dissection — Patients with FMD have a high prevalence of aneurysm and/or dissection prior to or at the time of FMD diagnosis [1,7,37]. In 921 patients from the United States registry for FMD, aneurysm occurred in 200 patients (22 percent) and dissection in 237 (26 percent). Overall, 384 patients (42 percent) had an aneurysm and/or dissection among this cohort (figure 1). In our center, among 146 patients who had repeated carotid duplex ultrasound exams and among all patients who had cross-sectional imaging from the head to the pelvis, the prevalence of both aneurysm and dissection was 36 percent [42].

The most common locations for aneurysms are the renal artery (34 percent), carotid artery (31 percent), and intracranial arteries (22 percent). Less frequently, the mesenteric arteries, vertebral arteries, and aorta are involved [19,37].

In patients who presented with dissections, the most commonly involved arteries were the carotid artery (64 percent), vertebral artery (21 percent), renal artery (11 percent), and coronary artery (10 percent). Less frequently, the aorta, mesenteric artery, and iliac arteries were involved [37].

The majority of patients (50 to 75 percent) who experience spontaneous coronary artery dissection (SCAD) have FMD identified in another arterial circulation [43-48]. It is not uncommon for SCAD to be misdiagnosed as atherosclerosis in females with few or no cardiovascular risk factors [49].

The recognition that patients with FMD have a high prevalence of arterial aneurysm and dissection has led to the recommendation that every patient diagnosed with FMD should have one-time, head-to-pelvic cross-sectional imaging [1]. Similar recommendations have been made for patients with SCAD [50]. The preferred imaging strategy is computed tomography angiography (CTA), and magnetic resonance angiography (MRA) is an alternative. If CTA is performed, we prefer CTA of the neck and head on one day followed one week later by CTA of the chest, abdomen, and pelvis [37,51,52].

When to suspect fibromuscular dysplasia — FMD should be suspected in the following settings:

●In a patient with hypertension (particularly in a woman under the age of 60 years) who has findings that would prompt an evaluation for secondary hypertension or renovascular disease, including (table 4) (see "Evaluation of secondary hypertension"):

•Severe or resistant hypertension

•Onset of hypertension before the age of 35 years

•A sudden rise in blood pressure over a previously stable baseline

•A significant increase in the serum creatinine concentration (≥0.5 to 1 mg/dL [44 to 88 micromol/L]) that occurs after the institution of therapy with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in the absence of an excessive reduction in blood pressure

•An epigastric/abdominal bruit

●The presence of a carotid bruit in a patient under the age of 60 years, especially if other common risk factors for atherosclerosis, aside from hypertension, are absent.

●Severe and persistent headache or pulsatile tinnitus that has no other obvious explanation or is accompanied by focal neurologic symptoms or signs. (See "Evaluation of headache in adults" and "Etiology and diagnosis of tinnitus".)

●Transient ischemic attack or stroke in a woman under the age of 60 years, especially if other common risk factors for atherosclerosis, aside from hypertension, are absent.

●Dissection of a peripheral (carotid, vertebral, renal) or coronary artery (ie, SCAD). (See "Spontaneous coronary artery dissection".)

●Aneurysm in a visceral, carotid, vertebral, or intracranial vessel.

●Aortic aneurysm in a patient younger than 60 years.

●Subarachnoid hemorrhage.

●Renal infarction.

DIAGNOSIS OF FIBROMUSCULAR DYSPLASIA

Confirming the diagnosis — In patients with suspected FMD, the diagnosis is confirmed by diagnostic imaging that reveals consistent findings (see 'Classification (by angiography)' above). A noninvasive imaging test is usually performed first. Invasive angiography is performed in patients if there is a high clinical suspicion of FMD, and treatment with revascularization is planned if a stenosis is found. A negative angiogram excludes a diagnosis of FMD in the vascular bed that was imaged. (See 'Choice of diagnostic imaging' below.)

Because FMD has a propensity to occur in multiple vascular beds, and because patients with FMD have a high prevalence of arterial aneurysm and dissection, every patient diagnosed with FMD should undergo one-time, head-to-pelvic, cross-sectional imaging [1,53].

As noted above, the angiographic appearance of FMD falls into the following classes (table 1) (see 'Classification (by angiography)' above):

●Multifocal FMD – Imaging may reveal a beaded appearance to the affected artery (ie, "string of beads") (image 1 and image 3). Most commonly, beads are numerous and are larger than the diameter of the vessel. Less commonly (typically in children with FMD), beads are few and are smaller than the diameter of the vessel.

●Focal FMD – Imaging may reveal a concentric, smooth, band-like focal stenosis or a tubular stenosis (image 2).

In addition to the multifocal arterial beading or focal stenosis that can occur with FMD, patients with FMD may have extreme arterial tortuosity. This is most common in the carotid, vertebral, and coronary arteries (image 4), and occurs more frequently in patients with FMD than in age- and sex-matched controls [49,54]. This tortuosity is not specific for FMD, and its consequence in patients with FMD is unknown.

Histopathology (and histologic classification) is no longer part of the diagnosis. Histopathology of FMD lesions is performed only in the rare patient who requires surgical revascularization or resection of an aneurysm.

Choice of diagnostic imaging — FMD is most frequently diagnosed using noninvasive imaging tests [1,55-59], specifically computed tomography angiography (CTA), magnetic resonance angiography (MRA), or duplex ultrasonography, and less frequently by catheter-based angiography.

Choosing a noninvasive imaging technique depends upon the expertise of a given institution but is also influenced by the vascular bed that is presumed to be involved. While duplex ultrasound is an excellent technique for the carotid, vertebral, and renal arteries, it has the lowest spatial resolution of all of the cross-sectional imaging modalities, has the most operator dependence, and should be used as the first choice only in high-volume centers with extensive expertise in this technique [1]. Thus, while there are some centers who use duplex ultrasound as initial screening, for most centers, either CTA or MRA would be a better diagnostic choice. CTA is preferable due to higher spatial resolution than MRA, less dependence upon technical expertise, and a shorter scan time [1]. In addition, MRA may miss FMD if the FMD is mild.

Although noninvasive imaging techniques are usually sufficient to diagnose FMD, catheter-based angiography, which is the reference standard, can improve visualization of the arteries by eliminating background soft tissue and bone and has higher spatial resolution than any of the other imaging modalities [16].

When performed, angiography can also be used to measure the pressure gradient across the stenosis; a pressure decrease threshold (using a pressure wire) of 10 percent or more of the mean pressure should be used to decide whether a lesion is hemodynamically significant [1,5,60]. In addition, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can be helpful in determining if a dissection or intramural hematoma is present as well as help to determine if angioplasty has improved the stenosis.

Computed tomography angiography — Multirow detector CTA has excellent diagnostic accuracy for FMD of the main renal arteries, although the sensitivity decreases when FMD is only present in the smaller branch renal arteries. In one study, in which CTA reconstructions (including multiplanar reformatted images, maximum intensity projections, and axial images) were evaluated in patients with known FMD, CTA detected FMD lesions in 100 percent of 37 arteries studied [58].

Multirow detector CT scanners, which offer more rapid image acquisition, variable section thickness, three-dimensional rendering, diminished helical artifacts, and smaller contrast requirements, may gain an increased role in the diagnosis and follow-up of renal artery FMD [58,59].

Magnetic resonance angiography — MRA offers inconsistent detection of FMD and is performed if CTA is contraindicated [5,56,61]. In one series, for example, the sensitivity was only 22 percent [56]. The spatial resolution in the branch vessels is not adequate, and artifact may occur, suggesting "beading" when none is present. However, MRA can be useful for detecting aneurysms and dissections.

Duplex ultrasonography — Duplex ultrasound can detect elevated blood flow velocities in the mid and distal portions of the renal artery and internal carotid arteries, the most common locations for FMD [4,55]. Ultrasound results are most helpful if they report an increased peak systolic velocity, turbulent blood flow, and tortuosity of the mid and distal artery. Reports that assign a percent diameter stenosis of the artery are less helpful since such statements are usually inaccurate. In general, duplex ultrasonography should be used for diagnosis of FMD only in high-volume centers with expertise in this technique or if CTA and MRA cannot be performed [1].

Duplex of the extracranial cerebrovascular arteries may also be useful in patients with FMD if the ultrasonographer can image the most distal portion of the carotid and vertebral arteries up to the point where they enter the skull base (image 3).

DIFFERENTIAL DIAGNOSIS — The conditions that most commonly mimic the presentation of FMD are atherosclerotic vascular disease and vasculitis.

●Both atherosclerosis and FMD may cause renal artery stenosis and carotid artery disease. Patients with atherosclerosis are usually older and have typical cardiovascular risk factors such as dyslipidemia, diabetes mellitus, and a history of tobacco use, whereas individuals with FMD are usually younger and have fewer cardiovascular risk factors [16]. However, given that FMD can occur in older patients, age alone does not exclude the diagnosis. The oldest patient in the US Registry for FMD is 97 years old.

Atherosclerosis usually involves the ostial or proximal segment of the arteries, whereas FMD involves the middle or distal segment. In addition, the "string of beads" appearance is unique to FMD. Thus, atherosclerotic disease and FMD can typically be distinguished radiographically.

●Multisystem involvement is observed in both vasculitis and FMD. Unlike patients with a vasculitic process, those with FMD generally will not have associated anemia, thrombocytopenia, or abnormalities of acute phase reactants (eg, erythrocyte sedimentation rate or C-reactive protein), given that it is a noninflammatory process. An exception might be in the setting of an acute infarction.

●Other possibilities that may be initially considered before renal artery FMD is diagnosed include primary hypertension (formerly called "essential" hypertension) and any of the potential causes of secondary hypertension. When appropriate, an evaluation for secondary causes of hypertension should identify the presence of FMD. These issues are discussed elsewhere:

•(See "Evaluation of secondary hypertension".)

•(See "Overview of hypertension in adults", section on 'History'.)

•(See "Overview of hypertension in adults", section on 'Testing for secondary hypertension'.)

MONITORING DISEASE PROGRESSION — The patient who is being treated medically (eg, not eligible for or refusing intervention) should have monitoring of the blood pressure response to antihypertensive therapy and serum creatinine levels every three months initially, and, if the blood pressure stabilizes, annual exams may then be performed. The decision against revascularization may need to change if hypertension is treatment resistant or if there is progressive loss of kidney function. (See "Treatment of fibromuscular dysplasia of the renal arteries", section on 'Antihypertensive therapy'.)

Noninvasive imaging tests, such as duplex ultrasound, should be obtained every 6 to 12 months. Since radiation exposure is high, computed tomography angiography (CTA) should only be repeated if there is a strong clinical suspicion regarding the progression of the disease. If the patient has an aneurysm, they can be followed with magnetic resonance angiography (MRA) to follow the size of the aneurysm. However, assessing disease progression by angiographic criteria may be difficult, especially with multifocal FMD, where it is not possible to determine the degree of stenosis.

Some reports suggest that disease progression may be better monitored by measuring the kidney parenchyma. Compared with patients who have primary hypertension (formerly called "essential" hypertension), patients with unilateral renal FMD had significantly decreased mean cortical thickness and reduced kidney length as determined by CT [62]. In the contralateral, unaffected kidney, cortical thickness was also markedly decreased, although kidney length was preserved. Atrophic changes in the kidney parenchyma by ultrasound generally represent chronic ischemic damage and are not reversed after renal revascularization [63]. It is uncommon to lose kidney parenchyma from multifocal FMD in the absence of a renal artery dissection; however, focal FMD is often associated with a dramatic decrease in kidney size and is progressive, ultimately leading to occlusion of the vessel [5,26].

Most clinicians who care for a large number of patients with FMD believe that multifocal FMD is a nonprogressive disease. In a study evaluating the likelihood of progression, 146 patients with multifocal carotid artery FMD who had more than one carotid duplex ultrasound over a 12-year period were included. The mean follow-up was 35 months (range 5 to 153 months), and the mean number of carotid duplex ultrasounds were 4 (range 1 to 17). No patient developed FMD in a new arterial bed (ie, one that was not initially involved), and progression did not occur in the arteries that were involved at the first evaluation. Three patients experienced a dissection, and two of these patients had a previous dissection [42].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fibromuscular dysplasia".)

SUMMARY AND RECOMMENDATIONS

●Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disorder that leads to arterial stenosis, occlusion, aneurysm, dissection, and arterial tortuosity. It has been observed in nearly every arterial bed. The most frequently involved arteries are the renal (75 to 80 percent of patients), internal carotid, and vertebral arteries (approximately 75 percent of patients have carotid and/or vertebral involvement), followed by visceral and external iliac arteries. Among adults, FMD is more common among females (approximately 90 percent of cases are in females). There does not appear to be a female predominance among children with FMD. (See 'Introduction' above and 'Epidemiology' above.)

●FMD is virtually always diagnosed radiographically, and histology is not typically available. Thus, angiographic classification has replaced the historic histologic classification (table 1) (see 'Classification (by angiography)' above):

•Multifocal FMD (more common) (image 1 and image 3) has the angiographic appearance of a "string of beads." Multifocal FMD corresponds pathologically to medial fibroplasia, the most common histologic type, and to perimedial fibroplasia, which is less common.

•Focal FMD (less common) (image 2) has the angiographic appearance of a "circumferential or tubular stenosis" and corresponds pathologically to intimal fibroplasia. Medial hyperplasia and periarterial hyperplasia are histologic types that may also have a focal appearance.

●The most common presenting signs and symptoms of FMD include hypertension, headache, pulsatile tinnitus, neck pain, and cervical bruit. Other presenting signs and symptoms can include flank or abdominal pain, an abdominal bruit, transient ischemic attack, and stroke. These disease manifestations may result from ischemia related to stenosis, dissection, and occlusion of arteries, rupture of aneurysms, or embolization of intravascular thrombi. (See 'Clinical manifestations' above.)

●FMD should be suspected in the following settings (see 'When to suspect fibromuscular dysplasia' above):

•In a patient with hypertension (particularly in a woman under the age of 60 years) who has findings that would prompt an evaluation for secondary hypertension or renovascular disease (table 4).

•The presence of a carotid bruit in a patient under the age of 60 years, especially if other common risk factors for atherosclerosis, aside from hypertension, are absent.

•Severe and persistent headache or pulsatile tinnitus that has no other obvious explanation or is accompanied by focal neurologic symptoms or signs.

•Transient ischemic attack or stroke in a woman under the age of 60 years, especially if other common risk factors for atherosclerosis, aside from hypertension, are absent.

•Dissection of a peripheral or coronary artery (ie, spontaneous coronary artery dissection [SCAD]).

•Aneurysm of a visceral, carotid, vertebral, or intracranial artery.

•Aortic aneurysm in a patient under 60 years of age.

●In patients with suspected FMD, the diagnosis is confirmed by diagnostic imaging that reveals consistent findings. A noninvasive imaging test is usually performed first (ie, computed tomography angiography [CTA], magnetic resonance angiography [MRA], or, in some centers with sufficient expertise, duplex ultrasound). Catheter-based angiography is performed in patients if there is a high clinical suspicion of FMD, and treatment with revascularization is planned if a stenosis is found. A negative angiogram excludes a diagnosis of FMD in the vascular bed that was imaged. (See 'Diagnosis of fibromuscular dysplasia' above.)

Because patients with FMD have a high prevalence of arterial aneurysm and dissection, every patient diagnosed with FMD should have one-time, head-to-pelvic cross-sectional imaging. The preferred imaging strategy is CTA, with MRA as an alternative.

●The conditions that most commonly mimic the presentation of FMD are atherosclerotic vascular disease and vasculitis. Patients with atherosclerosis are usually older and have typical cardiovascular risk factors, whereas individuals with FMD are usually younger and have fewer cardiovascular risk factors. Atherosclerosis usually involves the ostial or proximal segment of the arteries, whereas FMD involves the middle or distal segment; the "string of beads" appearance is also unique to FMD. Thus, atherosclerotic disease and FMD can typically be distinguished radiographically. Unlike patients with a vasculitic process, those with FMD generally will not have associated anemia, thrombocytopenia, or abnormalities of acute phase reactants (eg, erythrocyte sedimentation rate or C-reactive protein), given that it is a noninflammatory process. (See 'Differential diagnosis' above.)

●Patients who are treated medically (rather than with revascularization) should have monitoring of the blood pressure response to antihypertensive therapy and serum creatinine levels every three months. The decision against revascularization may need to change if hypertension is treatment resistant or if there is progressive loss of kidney function. Noninvasive imaging tests, such as duplex ultrasound, should be obtained every 6 to 12 months. Since radiation exposure is high, CTA should only be repeated if there is a strong clinical suspicion regarding the progression of the disease. If the patient has an aneurysm, they can be followed with MRA to follow the size of the aneurysm. (See 'Monitoring disease progression' above.)