Fibromuscular dysplasia presenting with a deep vein thrombosis

Abstract

A 41-year-old male patient presented with isolated right lower limb swelling. An ultrasound scan showed right external iliac and femoral vein deep vein thrombosis due to extrinsic compression by an aneurysm of the right common iliac artery. Investigations including imaging and a tissue biopsy of right and left femoral arteries confirmed a rare clinical presentation of fibromuscular dysplasia involving iliac, coeliac, renal and pulmonary vessels. The common iliac artery aneurysm was successfully treated with endovascular repair. Six months later, he developed coronary artery involvement with spontaneous dissection of left anterior descending artery diagnosed on coronary angiogram which was managed conservatively. At 6-year follow-up, he remains clinically asymptomatic and continues with regular surveillance imaging. Iliac arterial fibromuscular dysplasia is uncommon and clinical presentation with a complication such as a deep vein thrombosis is atypical.

Background

Fibromuscular dysplasia (FMD) is a rare non-inflammatory and non-atherosclerotic vascular disorder of unknown aetiology most often reported to affect renal and internal carotid arteries. However, it can potentially affect any arterial bed. This condition leads to vascular manifestations of stenosis, beading, aneurysms and dissections. It more commonly affects women, a male to female ratio of 9:1, and is most commonly detected between 20 and 60 years of age.¹ Clinical presentation varies according to arterial bed affected that can range from refractory hypertension secondary to renal stenosis to vascular complications, including dissection and aneurysm. Here we describe a rare case of FMD affecting multiple arterial beds presenting with a paradoxical deep vein thrombosis.

Case presentation

A 41-year-old male patient presented to hospital with gradual onset of right medial thigh swelling and pain. On examination, he had a swollen and erythematous right thigh. He was systemically well with no fever, arthralgia or myalgia. He was mildly hypertensive with a blood pressure of 144/99 mm Hg. His medical history was unremarkable with a previous surgical history of a knee reconstruction and Achilles tendon repair only. He was not on any regular medications. Family history was significant for his mother having had a 20-year history of renal artery stenosis.

Investigations

Doppler ultrasound demonstrated a right deep vein thrombosis in the common femoral vein extending into the external and common iliac veins. Proximally a right common iliac artery aneurysm measuring 63 mm (transversely)×55 mm (anterioposterior diameter)×130 mm (longitudinal) causing venous compression was also identified. A contrast-enhanced CT angiography of the abdomen and pelvis revealed multiple aneurysms involving his right common iliac artery, right external iliac artery and left common iliac artery (figure 1). Additionally, there was right external iliac vein thrombus, coeliac axis dissection (figure 2) and right renal artery dilation (figure 3). He also had a left subsegmental pulmonary embolus. Routine laboratory tests were normal except mildly elevated inflammatory markers of erythrocyte sedimentation rate (ESR) 21 mm Hg (normal 1–15) and C reactive protein (CRP) 12 mg/mL (normal <5). Thrombophilia screen including antiphospholipid antibodies was negative. Vasculitis screen including antinuclear antibodies, extractable nuclear antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), complement factors (C3, C4), anti-dsDNA and immunoglobulin levels was normal.

Figure 1.

CT angiogram demonstrating the 57 mm diameter right common iliac artery aneurysm.

Figure 2.

Sagittal CT angiogram showing the dissecting aneurysm of the coeliac axis.

Figure 3.

Flush aortogram demonstrating the renal arteries. Note: right sided aneurysms and left sided beading typical of fibromuscular dysplasia (arrowed).

Differential diagnosis

Due to the involvement of multiple vascular beds, vasculitis or connective tissue disease was considered although negative autoantibodies and clinical picture were not consistent. The working diagnosis was therefore a collagen synthesis disorder such as Ehlers-Danlos syndrome, Marfan’s syndrome, segmental arterial mediolysis (SAM) or FMD. Physical examination did not support Ehlers-Danlos syndrome or Marfan’s syndrome and given the multiple vascular beds and family history of renal artery stenosis the most likely clinical diagnosis was felt to be FMD.

Treatment

The patient underwent endovascular repair of his right common iliac artery aneurysm with an endoluminal stent graft inserted via bilateral common femoral artery cut downs to enable arterial biopsy. Intraoperatively friable vessels were noted. Histopathology revealed an abnormal muscular arterial wall with mild fibroplasia of the intima layer with thinning of the medial layer and extensive fibrosis with abundant collagen deposition separating smooth muscle cells (figure 4). These features were consistent with FMD of a medial subtype.

Figure 4.

Histological images of the right femoral artery: (A) (Verhoeff-van Gieson stain, x200) Media (M) with markedly depleted and distorted elastic fibres (black) in a pale collagenous background containing severely reduced number of myocytes. The intima (I) is thin and bound by interrupted elastic lamina (arrows) and focally continuous with the altered media. There is no well-defined external elastic lamina separating media from adventitia (A). (B) (Masson’s trichrome stain, x200) The media is extensively replaced by collagen (blue) with widely separating residual myocytes (red). Intima is widened by spindly myointimal cells and merges with the media at points of interrupted internal elastica (arrows). There is an absence of foamy histiocytes or other inflammatory cells in the intima typically seen in atheroma or vasculitis.

Outcome and follow-up

He had an uncomplicated recovery from his endovascular repair. However, 6 months postoperation, he presented with sharp, central, constant chest pain. Coronary angiogram identified spontaneous dissection of two proximal branches of the left anterior descending artery (diagonal branches 1 and 2) which were managed conservatively with a heparin infusion followed by dual antiplatelet therapy with aspirin and clopidogrel.

The patient has undergone regular follow-up with interval assessments of his vasculature by regular CT angiography (figure 5) and Doppler ultrasound scans. Clinically he remains asymptomatic. On imaging at 6 years postoperation, his graft remains patent with reduction in size of the right common iliac artery aneurysm sac to a maximum diameter of 35 mm and no evidence of endoleak. His other aneurysms remain stable.

Figure 5.

Surface volume rendered CT angiogram image post stent graft showing bifurcated stent graft in situ with excluded right common iliac artery aneurysm. DFOV, display field of view; VOI, volume of interest.

Discussion

FMD can affect almost any arterial vascular bed. Clinical presentation in the lower limbs is variable ranging from asymptomatic, intermittent claudication through to serious vascular manifestations such as limb ischaemia.² The distribution of arterial involvement involves renal arteries (60%–75%), carotid or vertebral arteries (23%–30%), multiple vascular beds (28%), other arterial beds such as iliac, popliteal, splanchnic, hepatic, subclavian, brachial, aorta, lower limb vessels uncommon with exact frequency unknown.³ In a large study of symptomatic renal or intracranial FMD patients, additional imaging identified multisite involvement in 48% of patients,⁴ although there may be racial differences with lower rates of multisite involvement seen in a study of Japanese FMD patients.⁵ Review of the literature on FMD affecting lower limb vasculature is limited to case reports and a small case series.^{2 6–9} However, this case is unusual in that our patient had simultaneous involvement of multiple arterial vascular beds with vascular manifestations of aneurysms and dissections, which caused compression on large veins resulting in deep vein thrombosis.

The exact aetiology of FMD remains unknown. Risk factors for this condition include smoking and hypertension.⁹ Genetic factors may also play a part, as evidenced by reports of increased incidence in first-degree relatives.² Classification of FMD is according to the arterial layer affected: intima, media or adventitia.³ Dysplasia of the media layer is most common, typically has a slower course of clinical progression and is characterised by the classical ‘string of beads’ appearance on angiography.³ Involvement of the intima occurs in less than 10% of cases but has an accelerated course of progression and may appear as focal, concentric stenosis on angiography which may mimic a necrotising vasculitis.⁶ Adventitial fibroplasia is the rarest type of FMD.^{7 8}

Diagnostic imaging modalities for less commonly involved vessel beds include contrast-enhanced CT angiography and catheter-based digital subtraction angiography. Other case reports of FMD involving the iliac arteries primarily used the gold-standard imaging modality of catheter-based angiography for diagnosis.^{2 7–9} A Japanese case report of FMD affecting both iliac arteries suggests that ultrasound and optical coherence tomography may be adjunctive tools to aide diagnosis and assessment of FMD.⁹

SAM is a rare vasculopathy that is difficult to differentiate from FMD.^{10 11} Some consider it to be early along the same spectrum of the pathogenesis underlying FMD.¹² Angiographic findings can be similar to FMD,¹¹ therefore, histopathology is the gold standard for diagnosis of SAM. On histopathology, it is characterised by non-inflammatory degeneration of the medial layer of muscular arteries with fibrin deposition.¹⁰ In contrast to FMD, SAM may present at any age and has no gender disposition.^{10 11} Typically, the distribution is limited to vessels in one anatomic site; the most commonly affected vessel is the coeliac artery and its branches.⁸ Complications include dissection, aneurysm and haemorrhage.^{10 11}

There are no clear treatment guidelines for iliac arterial complications related to FMD.¹³ Management options consist of conservative medical therapy or endovascular treatment or surgery. Studies have reported successful endovascular management of iliac artery involvement of FMD. Ketha et al conducted a single institution retrospective study over 30 years to review outcomes of endovascular management iliac artery FMD.² Of a total of 14 patients, six underwent endovascular treatment for claudication.² All six had angioplasty and two also had stents inserted for persistent aortoiliac pressure gradients. They reported symptom resolution in 83% and no complications over an average follow-up period of 63 months.² In a case of a young Chinese male patient presenting with hypertension, the CT angiogram demonstrated bilateral common iliac FMD complicated by an aneurysm on the right and dissection on the left, as well as right renal artery aneurysm and stenosis.¹³ He underwent successful endovascular repair with balloon angioplasty of the right renal artery and stent insertion in the left common iliac artery. There were no postoperative complications and at 8-month follow-up the patient was asymptomatic and had well-controlled blood pressure not requiring medical therapy.¹³

Here we have reported a rare case of FMD with multi-vessel involvement including iliac, coeliac, renal and coronary arteries with complications of aneurysm and dissection with successful endovascular repair of the iliac artery aneurysm.

Learning points.

• Fibromuscular dysplasia (FMD) simultaneously affecting multiple vessel beds is rare but can occur.

• CT angiogram is helpful to reveal vascular manifestations of FMD but the gold standard remains to be angiography allowing intervention if required.

• Endovascular repair has been successfully used in management of FMD complications such as dissection and aneurysms.