Acute vascular-related pain has a diverse array of etiologies, including peripheral arterial disease, large and small vessel vasculitides, thrombosis, and avascular necrosis (AVN). Hematologic-related pain includes complications of sickle cell disease (SCD) such as acute chest syndrome (ACS) and priapism. The pain that is encountered in these disease processes can be a combination of multiple mechanisms (nociceptive, inflammatory, neuropathic). The clinical features, diagnostic features, and treatment are discussed for each of these etiologies of vascular- and hematologic-related pain states.

Peripheral arterial disease (PAD) is a common disease that involves atherosclerosis and partial or complete occlusion of arteries of the lower extremities. It is believed that 10%-15% of the population and ˜200 million people around the globe suffer from this condition. Risk factors for PAD include smoking (strongest association) and diabetes.¹ Of all patients with PAD, only 10%-30% actually experience the symptoms of intermittent claudication. Atherosclerosis causes arterial stenosis that can eventually completely occlude the artery. When compensatory mechanisms such as vasodilation and collateral vessels, fail, ischemia will eventually occur. Severity of the ischemia depends on how extensive the occlusion is. Intermittent claudication specifically occurs when blood flow to the lower extremities is significantly diminished during physical exertion but is sufficient at rest. Critical ischemia is the terminal stage of the inadequate blood flow—diminished tissue perfusion causes pain at rest with eventual gangrene.

Current treatment options for PAD include antiplatelet therapy, some oral anticoagulants such as rivaroxaban (but not warfarin, which has failed to show treatment benefit), risk factor reduction (eg, controlling hypertension and hypercholesterolemia with ACEi/ARBs and statins), medications (eg, cilostazol, naftidrofuryl, carnitine, buflomedil, inositol), and finally revascularization.

Spinal stenosis occurs when central canal and neural foramina are narrowed by degenerative arthritis. Other possible causes that narrow these spaces include facet join arthropathy,
loss of disk height, and hypertrophy of the ligamentum flavum. The most common regions in descending order of frequency are L4-L5, L5-S1, and L3-L4.² People over the age of 60 years are more commonly affected by this condition. Direct compression of the nerve roots and ischemia results in the neurologic claudication. Possible symptoms include pain, discomfort, weakness, numbness, or paresthesias in the lower back, buttocks, and legs. Symptoms are exacerbated by standing with the spine extended (walking, standing). Severe symptoms can include bladder incontinence. The pain is relieved with lumbar flexion to 20°-40° (bending over, sitting). Treatment options include physical therapy, epidural steroid injections, and surgery.

Osteoarthritis is a degenerative joint disease that is the most frequent cause of chronic debility in elders. The hyaline cartilage between joints degenerates due to overuse. Symptoms include aching pain that worsens with use, decreased range of motion, and stiffness. Common locations in the lower extremities include the knees and hips.

Large vessel vasculitis such as giant cell arteritis and Takayasu arteritis are conditions where granulomatous inflammation of blood vessel wall occurs especially in the aorta and aortic branches.

Giant cell arteritis occurs in the older population, more commonly with women, with a mean age of diagnosis of age 72. Granulomatous inflammation most often presents in the extracranial arteries of the head, coming off from the second to fifth order aortic branches.

There is a higher incidence in people of northern European descent.³ All layers of the arterial wall can be affected by the granulomatous infiltrates of multinucleated giant cells and histiocytes. The adventitia of the blood vessels is a critical site in GCA.⁴

Takayasu arteritis is a rare disease that occurs predominantly in women. Aortic wall dilatation and aortic aneurysm occurs in TA when the smooth muscle is replaced by fibrous tissue due to granulomatous polyarteritis in large elastic arteries. In TA, a major component of the infiltrates is CD8 T cells that cause cytolytic tissue injury.

The initial manifestations of TA include malaise, night sweats, fever loss of appetite, abdominal pain, and weight loss. Vasoocclusive disease and ischemic changes of the vertebral and carotid arteries can lead to symptoms such as headache and stroke ophthalmologic symptoms.⁶ Blood pressure changes, pulselessness, and arm claudication can occur with occlusions of the subclavian and brachiocephalic arteries. Aortitis of the aorta can lead to arrhythmia, congestive heart failure, ischemic heart disease, and aortic dilatation.

The diagnosis of TA with symptoms of vasoocclusion and systemic inflammation is done by vascular imaging of conventional angiography. Long-term immunosuppressive treatment with glucocorticoids is the treatment of choice of doses of 40-60 mg of prednisone and is needed for progressive or relapsing disease.⁷ Antiplatelet agents such as aspirin are also recommended to complement treatment with glucocorticoids. TA is considered a devastating disease. Surgical management such as bypass grafts in addition to immunosuppressive treatment with glucocorticoids can lead to better prognosis.

Polyarteritis nodosa is inflammation in the small- to medium-sized arteries and spares large-sized arteries. Polyarteritis nodosa affects the arteries of the kidney in over 70% of the cases, with the GI tract being in involved in about 50% of the cases. Laboratory tests are nonspecific.

Nerve conduction abnormalities may be confirmed with nerve conduction velocities and electromyography. Full-thickness skin biopsy confirms the diagnosis. Along with treatment with glucocorticoids, a simultaneous treatment of plasma exchange over 6 weeks has been done followed by antiviral therapy.³

Buerger disease (thromboangiitis obliterans [TAO]) affects the upper and lower extremities as a segmental, inflammatory disease of the small- and medium-sized arteries. It often presents with a systemic inflammatory response.⁸

Presentation of TAO can occur as pain or claudication of extremities followed by ischemic rest pain and is associated with ulcerations in fingers and toes. Smoking cessation is strictly advised. TAO is nonatherosclerotic where the media and intima are involved. In TAO, all three layers of the arterial wall are infiltration of round cells. There are no specific laboratory tests for TAO. Small collateral arteries around occlusion in arteriography may be seen described as “cockscrewing” or “pig-tailing” around occlusions. Management involves cessation of smoking. For symptoms, treatment with vasodilators such as calcium channel blockers and prostaglandin analogs have been used.⁹

Avascular necrosis is also known as ischemic bone necrosis, aseptic necrosis, or osteonecrosis. It involves compromise of subchondral blood supply that can lead to death of bone cells. Weight-bearing joints can collapse when the epiphysis of long bones in these joints get affected. The hip is the most common joint involved and is often associated with glucocorticoid use.¹⁰