Nonatherosclerotic limb ischemia: Prompt evaluation and diagnosis

Diagnosing persistent sciatic artery

Diagnostic angiography is the gold standard imaging test,^15,19 although CTA is starting to replace it.^16,18

Treating persistent sciatic artery

Persistent sciatic artery that is asymptomatic and is found incidentally does not require repair; however, it should be followed with duplex ultrasonography to look for evidence of aneurysm degeneration. Degeneration requires repair in most cases.^15,16,18,19 When the persistent sciatic artery is the only blood supply to the distal extremity, open aneurysm excision and bypass is the treatment of choice.^15,16,19 If collateral flow is adequate, endovascular coil embolization is an option.¹⁵ Endovascular stent graft placement has also been described.^16,19

PHLEGMASIA CERULEA DOLENS

Phlegmasia cerulea dolens is a rare syndrome caused by extensive acute thrombosis of the ileofemoral vein.^20–23 It is defined as total or near-total occlusion of the venous outflow of an extremity, causing massive swelling and congestion that impedes arterial inflow.^20,22

Phlegmasia cerulea dolens is associated with four cardinal signs: edema, violaceous discoloration, pain, and severe venous outflow obstruction (Figure 4).²² Patients present with sudden onset of lower extremity pain, swelling, cyanosis, and arterial ischemia with or without loss of distal pulses.^20,22

This syndrome can progress to gangrene and massive fluid sequestration leading to shock and death.^21–23 From 25% to 40% of patients die, and of those who survive, 20% to 50% require amputation of the limb.^20,23

Risk factors include malignancy, immobility, heart failure, heparin-induced thrombocytopenia, antiphospholipid syndrome, pregnancy, venous catheterization (eg, to insert an inferior vena cava filter), and surgery.^20–22

Diagnosing phlegmasia cerulea dolens

The diagnosis is made on clinical suspicion with evidence of iliofemoral deep vein thrombosis. Most experts suggest venous duplex ultrasonography to identify the deep vein thrombosis,²³ although CT or MR venography can be used to better delineate the proximal extent of the thrombus.^20,23

Treating phlegmasia cerulea dolens

Initial management is aggressive fluid resuscitation, elevation of the affected limb, strict bed rest, and anticoagulation with intravenous heparin.^20,23 Interventions are aimed at urgently restoring venous outflow to prevent progression to venous gangrene and limb loss.

Although conservative therapy can succeed by itself,²³ if the condition does not improve or has already progressed to an advanced stage, the two mainstays of treatment are open venous thrombectomy and endovascular treatment.^21–23 Endovascular treatment includes catheter-directed thrombolytic therapy (with or without percutaneous mechanical or pharmacomechanical thrombectomy) and stenting.^20,23 The success rate for endovascular therapy can be as high as 90% with near-complete resolution of thrombosis.²⁰ A disadvantage is that, compared with open surgical thrombectomy, more time is needed to achieve venous outflow.^20,22

If endovascular therapy is ineffective, if lytic therapy is contraindicated, or if the disease has progressed to gangrene, open surgical thrombectomy with possible fasciotomy is the preferred option.^20,21,23 Open surgery has the advantage of restoring venous outflow faster, but disadvantages include the inability to open the smaller veins of the extremity, blood loss, and risks associated with general anesthesia.^20–22

BUERGER DISEASE

Buerger disease (thromboangiitis obliterans) is a nonatherosclerotic segmental inflammatory disease involving the small and medium-sized vessels of the arms and legs.^24–27 It is differentiated from other vasculitides by its marked male predominance, its close association with smoking, the rarity of systemic signs and symptoms, and the absence of elevated inflammatory markers.²⁶

The rate of major amputation is reported to be 11% at 5 years and 23% at 20 years.²⁴

The classic patient is a young male smoker with symptoms of arterial disease before age 45.^24,26 Patients can present with migratory thrombophlebitis or signs of arterial insufficiency in the upper or lower extremities. Two or more limbs are commonly involved. Arterial insufficiency can range from claudication and exertional discomfort of the extremity to ischemic pain at rest leading to ulceration of the distal fingers and toes. Physical findings are similar to those seen in peripheral vascular disease and arterial insufficiency, with decreased arterial brachial index, cool extremities, and wounds.

Diagnosing Buerger disease

• The Shionoya diagnostic criteria for Buerger disease are the following five clinical features^24,27:
• History of smoking
• Onset before age 50
• Infrapopliteal arterial occlusive disease
• Upper-limb involvement or phlebitis migrans
• Absence of atherosclerotic risk factors other than heavy smoking.

Various other major and minor criteria have been described to make the diagnosis as well.²⁴

There is no specific laboratory test to confirm the diagnosis of Buerger disease. A full panel of laboratory tests should be sent to rule out other causes of arterial insufficiency and vasculitides; these tests should include C-reactive protein, rheumatoid factor, erythrocyte sedimentation rate, antinuclear antibodies, antiphospholipid antibodies, anti-Scl-70 antibodies, anticentromere antibodies, complement level measurement, and hypercoagulability workup.

Imaging studies include arterial duplex ultrasonography with ankle-brachial indices and segmental pressures and CTA or MRA.²⁶ Angiography can show a “corkscrew” pattern of occlusive disease and collateral formation, which is highly associated with Buerger disease.²⁴

Treating Buerger disease

The only treatment shown to reduce the risk of amputation is complete abstention from tobacco and nicotine (smoking, secondhand smoke, and nicotine patches and gum).^24,26

Symptoms of claudication can be managed with aspirin, clopidogrel, vasodilators, pentoxifylline, and cilostazol.²⁶

Surgical bypass is rarely an option, as Buerger disease typically affects the distal blood vessels, thus precluding bypass, and the 5-year patency rate is only 49%.²⁶ Other treatments including arterial thrombolysis, sympathectomy, stem cell injection, spinal cord stimulators, omental grafting, and immunomodulation have been described, but there are only limited data to offer guidance in choosing the appropriate one.²⁴

TAKAYASU ARTERITIS

Takayasu arteritis is a form of vasculitis involving the aorta and its main branches (Figure 5).²⁸ Although seen around the world, it has a higher incidence in young Asian women. Patients can present with systemic symptoms such as fever, fatigue, vague pain, and cardinal signs of limb ischemia associated with Takayasu arteritis, such as weak or absent pulses, differences between the arms in pulses and blood pressures, unobtainable blood pressure measurement in one or both arms, limb fatigability, and pain.²⁸

Diagnosing Takayasu arteritis

Multiple diagnostic criteria have been proposed to define Takayasu arteritis.²⁸ CTA, MRA, and positron emission tomography have replaced invasive angiography as the diagnostic imaging tests of choice.²⁹

Treating Takayasu arteritis

Takayasu arteritis has an acute and chronic course. Interventions are typically reserved for severe cases, with indications that include uncontrollable hypertension from renal artery stenosis, severe coronary or cerebrovascular disease, severe aortic regurgitation or coarctation, stenotic or occlusive lesions resulting in critical limb ischemia, and aneurysm at risk of rupture.^28–30

THORACIC OUTLET SYNDROME

Thoracic outlet syndrome is compression of the brachial plexus, subclavian vein, or subclavian artery as it exits the thoracic outlet through an area known as the scalene triangle, which is bordered by the anterior scalene, first rib, and clavicle.³¹ Presenting symptoms depend on the structure compressed.

By far the most common presentation³² is neurogenic thoracic outlet syndrome, accounting for more than 90% of cases, followed by venous thoracic outlet syndrome. Arterial thoracic outlet syndrome is the least frequent at less than 1%, but carries the greatest morbidity with potential for limb loss.^31–33

The subclavian artery exits the thoracic outlet between the anterior and middle scalene muscles, and then travels over the first rib and underneath the clavicle.³¹ Repeated trauma from compression of the artery results in intimal injury leading to compression, stenosis, occlusion, or aneurysm formation.^31,32

Symptoms of arterial thoracic outlet syndrome can start out as effort fatigue of the upper extremity secondary to compression. These symptoms are usually vague and difficult to define,³¹ as these patients typically are young and do not have atherosclerotic risk factors that would prompt suspicion of a vascular cause.

The most common presentation of arterial thoracic outlet syndrome is upper extremity embolization from a partially thrombosed aneurysm or area of stenosis with ischemia.³² Symptoms can range from ischemia of the fingers due to  microembolization to acute limb ischemia due to complete thrombosis of the subclavian artery.^31,32 Arterial thoracic outlet syndrome is most commonly associated with a bony abnormality (ie, cervical rib or anomalous first rib),^31–33 and on physical examination the bony abnormality may be palpated in the supraclavicular fossa.³¹

Other physical findings include a bruit over the subclavian artery, a blood pressure difference of 20 mm Hg or more between the affected and unaffected arms, loss of brachial, radial, or ulnar pulses with arm abduction, and loss of the radial pulse with the head rotated to the affected side as the patient takes a deep breath (the Adson maneuver).³¹ While postural changes in the pulse examination hint at arterial thoracic outlet syndrome, extremity pulses may be reduced or even absent in up to 60% of normal patients.³²

Diagnosing thoracic outlet syndrome

The workup should start with noninvasive imaging with pulse volume recording and wrist and finger systolic pressures, followed by arterial duplex ultrasonography.

Chest radiography may be able to identify bony abnormalities, and MRA or CTA with the patient in two positions—ie, arms down at  the sides, and arms held above the head—can help identify arterial compression from bony or muscular structures in the thoracic outlet. Upper extremity angiography provides high-resolution imaging of the digital arteries and can help identify a subclavian artery aneurysm, which may be a subtle finding.³¹

It is important to have objective evidence of arterial or venous mechanical obstruction before deciding to remove the first rib.

Treating thoracic outlet syndrome

Treatment is determined by the severity and acuity of symptoms. If the patient presents with acute limb ischemia, prompt treatment with either open surgery or endovascular treatment is required.^31,32,34 Once the acute phase has resolved or if the patient presents with chronic disease, open surgical repair is needed to remove the compression of the artery. If an arterial abnormality is identified (aneurysm or significant stenosis), an arterial reconstruction with bypass may be required.³¹

The standard treatment for thoracic outlet syndrome is resection of the first rib (and removal of the cervical rib if present).^31,34 This can be by a transaxillary approach unless arterial reconstruction is needed, in which case a supraclavicular approach is used.^31,34 When a patient without symptoms is found to have evidence of arterial compression, most experts would recommend resection of the first rib if there is evidence of an arterial abnormality, or follow-up with duplex imaging for patients with only subtle findings.³¹

EXTERNAL ILIAC ENDOFIBROSIS

External iliac endofibrosis is a rare cause of intermittent claudication, typically in high-performance athletes, resulting from thickening of the intima in the external iliac artery causing luminal narrowing and resultant ischemia.^35–37 The estimated incidence is as high as 20% in elite competitive cyclists, and the condition has been described in other sports as well.³⁷

External iliac endofibrosis typically presents as unilateral leg pain or cramping at near-maximal exercise with an associated feeling of swelling and numbness on the affected side.^35,37 It is bilateral in up to 15% of cases.³⁵ While claudication of the thigh is the predominant presenting symptom, dissection and thrombosis of the external iliac artery have been described, presenting with acute limb ischemia in up to 4% of patients.^35,36

The condition has been attributed to factors such as physical position, psoas hypertrophy, tethering of the external iliac artery to the psoas muscle, kinking and tortuosity of the vessel, and high-flow states secondary to increased cardiac output and adaptive systolic hypertension.^36,37

Diagnosing external iliac endofibrosis

The diagnosis is difficult, as symptoms typically manifest only during maximal exercise. Delays of 12 to 41 months between the onset of symptoms and diagnosis have been reported.³⁷ Physical findings are nonspecific, and pulses and ankle-brachial indices are typically normal at rest. A careful history with a focus on location and duration of symptoms and a high index of suspicion have been shown to increase the sensitivity of diagnosis.³⁶

Noninvasive vascular imaging with arterial duplex ultrasonography with physiologic studies (the ankle-brachial index) at rest and at maximal exertion should be obtained first.^35,37 If findings on ultrasonography are positive, CTA or MRA can be used to identify a suspected stenosis.

Diagnostic angiography is still the gold standard for imaging, as real-time images of the artery with different leg positions can be obtained and pressure gradients can be measured with or without the use of a vasodilator to determine the hemodynamic significance of a lesion.^35–37

Treating external iliac endofibrosis

Treatment should initially be conservative. Recreational athletes should consider changing to a sport that does not require hip flexion, and cyclists should be advised to reduce the amount of time spent cycling and to raise the handlebars or bring the saddle position forward to minimize hip flexion.³⁷

Definitive treatment is open surgical repair. Surgical options include arterial release of the tethered artery, endofibrosectomy and vessel shortening, endofibrosectomy and patch angioplasty, and interposition bypass grafting.^35–37