Introduction
Vascular disorders of the hand can be acute or chronic. Trauma to blood vessels and its consequences have been described in other chapters of this book. This chapter will focus on chronic problems, including systemic diseases with expression in the hand and vascular lesions affecting the function of the hand. Systemic diseases with expression in the hand can be vasospastic or occlusive. There is considerable overlap between these two categories, with major clinical findings of hand ischemia, but there are also differences.
Noninvasive measures such as magnetic resonance angiography and high-resolution Doppler ultrasonography (US) have upgraded our diagnostic capabilities in recent years. Still, many vascular conditions remain devastating and have limited treatment options.
Table 31.1 summarizes the three major categories of vascular diseases affecting the hand. Vasospastic or vasoocclusive disease is clinically manifested with hand ischemia, which is discussed in more detail below.
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Essential knowledge
Anatomy and pathophysiology
The main arteries to the hand form the superficial palmar arch, which is a branch of the ulnar artery (complete in 81% of hands), and the deep palmar arch, which is a branch of the radial artery (complete in 95% of hands). However, there are variations on the continuity of these vessels. Dominance of radial and ulnar arteries varies, and 50% of hands have persistent median arteries. The main venous drainage is on the dorsal side of the hand and continues to the basilic and cephalic veins of the forearm.
Macrocirculation regulates blood flow to meet the metabolic requirements of the tissue. When this is compromised, pain, cold intolerance, and tissue loss may occur. Microcirculation consists of nutritional and thermoregulatory blood flow. Normally, about 85% of the circulation passes through the thermoregulatory beds. These are the areas in the fingertips where there are arteriovenous (AV) connections along the distal phalanx. Nutritional blood flow is responsible for the remaining circulation (approximately 15%). In response to stress, the increase in sympathetic tone closes the AV shunts, decreasing the thermoregulatory flow; thus the remaining blood flow is diverted to the capillary nutrient beds and nutritional blood flow is preserved in the presence of decreased overall blood flow.
Etiology
Chronic ischemia is a status of insufficient blood supply (a combination of nutritional and thermoregulatory failure), mainly resulting from occlusion, vasospasm, or a combination of the two. Vasospasm is the result of increased sympathetic tone in response to stress. Occlusion can be caused by thickening of the adventitia, which can narrow the vessel lumen and slow down the blood flow. Common causes of chronic hand ischemia are presented in Table 31.2 .
| Occlusive Arterial Diseases | Cutaneous Small-Vessel Diseases * |
|---|---|
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* These diseases are not discussed in this chapter, as they are mainly treated by other specialists.
Patient history
A history of finger pain, change in color, temperature, ulcerations, or weakness of the hand should be recorded, including timing, triggering factors (stress, cold, and work are common factors), and relief modalities (such as warming, rest, or specific drugs). Additional health problems or chronic diseases are common. , These must be reviewed and will affect management decisions.
Clinical presentation
The upper extremity should be examined for ischemic signs, which include ulcerations, skin atrophy, mass, and deformity. The latter may be related to vascular or other tumors or to an AV malformation (AVM). Palpation can help localize areas of tenderness and document the characteristics of a mass.
In the presence of vasospasm, the color and warmth of the digits may change during the examination, and differences between each hand should be noted. A handheld Doppler should be available to evaluate flow in these vessels. The examiner should regularly perform an Allen test at the wrist and digital levels.
For the assessment of hand vascularity, it is important to evaluate both microcirculation and macrocirculation. Two essential tests are capillary refill and the Allen test. Capillary refill time is the time taken for color to return to an external capillary bed after pressure has been applied to cause blanching. It is commonly used to assess finger perfusion after replantation or tissue transfers and is considered normal in the finger pulp up to 3 seconds. This test can also been used for diagnosis of vascular disorders. The Allen test ( Fig. 31.1 ) is useful in multiple clinical scenarios such as evaluation of blood supply after trauma or to confirm a specific diagnosis such as ulnar artery insufficiency after ulnar artery thrombosis (hypothenar hammer syndrome).
Imaging
Plain radiographs may hint at vascular disorders by demonstrating advanced stages of atherosclerotic disease with calcified vessels. Other often-used tools are Doppler US, magnetic resonance arteriography (MRA), and computed tomography angiography (CTA). These noninvasive methods aid in the assessment of a mass such as an aneurysm or vascular malformation but have limited value in the evaluation of digital arteries. Angiography remains the main diagnostic tool for identifying digital pathology.
Doppler ultrasonography.
Doppler US provides dynamic assessment of blood flow through arteries and veins and enables measurement of flow volume, velocity, and a vessel’s diameter, including the thickness of its wall. This tool is highly based on the examiner’s experience. The constriction or decrease in blood flow can be observed through Doppler US in almost all chronic vascular disorders. In conjunction with a cold provocative test, it offers details on changes in blood flow in vascular disorders such as Raynaud phenomenon.
Magnetic resonance arteriography.
Magnetic resonance imaging is frequently performed with MRA to distinguish between vascular malformations and vascular and perivascular tumors. In most cases, classical sequences are performed, including gadolinium-based contrast, which can characterize soft tissue masses and evaluate perivascular lesions. , MRA does not offer detailed information on the digits to aid in treatment decisions.
Computer tomography angiography.
Computer tomography angiography (CTA) demonstrates the radial and ulnar arteries well, but the digital artery evaluation can be challenging. , Dynamic CTA is useful to evaluate vascular malformations. Enhanced anatomic pictures are possible with volume and cinematic rendering techniques. Deep-learning reconstruction algorithms using super-high-resolution computed tomography modes may improve visualization of the distal part of digital arteries.
In general, MRA and CTA do not provide adequate detail of the digits to aid in treatment decisions. Both tools are better for high-flow conditions, such as AVM, and can be good for screening or evaluation of a mass, such as an aneurysm. An angiogram is the definitive test to assess circulation and evaluate for occlusion. This can be performed with intraarterial vasodilators to evaluate the vasospastic component, and it allows for visualization of the palmar arch as well as the common and proper digital vessels.
Raynaud disease and raynaud phenomenon
The terminologies are sometimes confusing. Overall , Raynaud disease (also called primary Raynaud phenomenon ) should be distinguished from Raynaud phenomenon (secondary vasospasm associated with other disease, also called secondary Raynaud phenomenon ) ( Tables 31.2 and 31.3 ).
| Primary RP (Raynaud Disease) | Secondary RP (with Underlying Diseases) | |
|---|---|---|
| Frequency | Relatively often | Rare, a high incidence with underlying diseases |
| Sex | Female majority | Male and female |
| Onset | Early, usually before 40 years of age | Any age, usually after 30 years |
| Symmetry of symptoms | Symmetric | Variable, depending on main disease |
| Migraine | Yes | No |
| Hypertension | No | Often yes |
| Gangrene and necrosis | Rare | Possible |
| Relief of symptoms | Often | Rare |
| Systemic or vascular disease | None | Yes |
| Antinuclear antibodies | None | Possible |
| Capillaroscopy | Negative | Positive |
| Prognosis | Good | Depending on main disease |
| Family history | Positive or negative | Often positive |
In Raynaud disease, the typical symptoms do not have a known cause. The findings of Raynaud phenomenon, on the other hand, have very remarkable causes (diseases). In both conditions, the findings in the hand can all be called Raynaud phenomenon (RP). Management of the two is similar, except that, in secondary RP, the causes may need to be addressed by a surgeon or other specialist. In this section, we use RP to indicate the treatment for both clinical situations. In secondary RP, it is the underlying collagen diseases that often lead to digital ulceration. The underlying collagen diseases may have a greater effect on clinical presentations because of their effects on endothelial damage.
Clinical presentation
Raynaud disease (primary RP) is characterized by hypersensitivity to cold temperatures and episodic digital color changes with reversible tissue injury. These changes can even occur during an office visit and range from a pale color seen with vasospasm to a purplish color that can occur with rewarming or reperfusion. The color change may be caused by digital artery vasoconstriction resulting from cold temperatures, blunt trauma, or emotional stress and may not result from underlying vascular pathology.
In Raynaud disease, color changes may be triphasic (pallor, followed by cyanosis and, after warming, by erythema because of reactive hyperemia), biphasic (cyanosis, erythema), or uniphasic (pallor or cyanosis only) ( Figs. 31.2 and 31.3 ).
RP (secondary vasospasm) can present similar findings as described above, but it is associated with other diseases instead of vasospasm induced by cold or stress. Most often, the associated disease is scleroderma or systemic sclerosis (SSc). RP can also be seen in patients with mixed connective tissue disease, rheumatoid arthritis, and systemic lupus erythematosus. It is a progressive condition characterized by digital ischemic ulcerations and abnormal angiography findings. More than 90% of patients with SSc develop RP and can also have other hand-specific disease manifestations, including digital ulcerations, tightened skin, calcinosis, and joint contractures. As pathological changes progress, patients with SSc are at high risk for developing digital ulcers that progress to osteomyelitis and distal gangrene.
The prevalence of RP varies depending on the regional climate, ranging from 21% of women in colder climates to 5% of women in warmer ones. , The age of symptom onset in primary RP is usually 15 to 25 years, and later presentation should be examined for related pathology. , The most common provoking factors are exposure to cold and emotional stress. , In contrast to patients with secondary RP, those with primary RP experience more numbness, less pain, and, rarely, cyanosis of the fingers. In more severe cases, the toes, ears, nose, tongue, or nipples may be involved.
Box 31.1 summarizes the main clinical features and key treatments of RP (suitable for both Raynaud disease and secondary RP).
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Characteristic color changes of fingers as a result of vasospasm.
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Can be primary (not a result of any disease) or secondary (syndrome).
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In primary Raynaud phenomenon, the cause of vasospasm is usually stress or cold exposure.
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In secondary disease, inflammation or obliteration of the vessels takes place concurrent with advancement of the primary diseases.
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Initial treatment is prevention of cold exposure, behavioral therapy, and pharmacotherapy.
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In the treatment of secondary Raynaud phenomenon, cooperation with the rheumatologist is crucial to treat the primary disease.
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With the ischemic symptoms, botulinum toxin injections can reduce Raynaud-associated pain in many patients.
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In cases with persistent symptoms, surgery is indicated. Periarterial sympathectomy or artery bypass can improve ischemic pain with healing of ulcerations.
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Advanced stages of disease with necrosis and gangrene usually require amputation.
Diagnosis
The main differential diagnosis of primary RP is idiopathic vasomotor disorders or other vascular disorders (which are discussed further in this chapter) and is made by exclusion. The diagnosis of primary RP is suggested by vasospastic attacks precipitated by cold or emotional stress; symmetric attacks involving both hands; the absence of tissue necrosis, ulceration, or gangrene; no history or physical findings suggesting secondary cause; normal nailfold capillaries; normal erythrocyte sedimentation rate; and negative serologic findings, particularly antinuclear antibodies. Compared to primary RP, secondary RP is easier to diagnose because there is an underlying systemic disease causing the clinical symptoms and findings. One may make the diagnosis directly according to clinical findings if the underlying systemic disease is already diagnosed (has usually existed for a long time).
The refill in nailfold capillaries should be routinely assessed, and within 3 seconds is considered normal. If possible, nailfold video capillaroscopy can be used. Cold provocative testing (or cold stimulation testing) assesses the ability to respond to cold temperature. If it takes 20 minutes or more for one’s finger temperature to return to room temperature (normally around 26°C) after the ice water bath, RP is likely. This test is affected by room temperature. If clinical presentation is typical, this test may not be necessary. However, characterizing the temperature changes and recovery speed in the cold provocative test can be used for assessment of medical or surgical treatment effectiveness.
Treatment
The initial management is nonoperative with lifestyle modifications to avoid stimulators of vasospasm. This includes avoiding exposure to cold and sudden changes in temperature, stress, nicotine, trauma, and medications that induce vasoconstriction. If these measures fail to improve symptoms, common medications are calcium-channel blockers (nifedipine and amlodipine) and phosphodiesterase-5 (PDE-5) inhibitors, which include sildenafil, antidepressants, and prostacyclin analogues. Use of a peripheral nerve block may also help.
Lifestyle modifications.
Lifestyle modifications and behavioral management include avoidance of cold exposure, increasing exercise, and stress management. Other measures include smoking cessation and avoidance of caffeinated beverages, vibratory exposure, and vasoconstrictive drugs such as most decongestants, beta-adrenergic antihypertensive medication, amphetamines, and cocaine. However, several behavioral interventions have been tested for their effects on RP symptoms with little evidence of success, and the outcomes are limited by patient compliance. , ,
Medications.
In more severe cases, calcium-channel blockers (nifedipine and amlodipine) are the first line of treatment to reduce the number and severity of attacks. The dosage for nifedipine retard ranges from 10 to 20 mg two or three times a day, and the adverse effects usually subside after several weeks of administration. The use of calcium-channel blockers was found to be effective compared with placebo, with a more substantial effect when treating primary RP. The addition of alpha blockers, phosphodiesterase type 5 inhibitors, prostanoids, or angiotensin receptor blockers or switching to another calcium-channel blocker are other options, although limited evidence supports their use. , There is some evidence of PDE-5 inhibitors effectively treating RP and the digital ulcerations seen with SSc.
Botulinum injections.
Botulinum toxin has demonstrated effectiveness for treatment of ischemic pain without digital ulcers or necrotic changes. Injections are made around common digital arteries with 10 units per vessel (2 mL) and up to 100 units. , Relief is dependent on the patient’s status but can last for years, and repeated injections are possible. , , The pain relief and improvement of finger color is found immediately in some patients and within several days in others. Transient intrinsic muscle weakness (2–3 months) has been observed in 9% to 27% of cases. Injections in patients with SSc and digital ulcerations showed improvement in skin temperature after 4 weeks and fewer subsequent ulcerations in comparison to a control group.
A central mechanism of action of toxin injection is the inactivation of Rho kinase in smooth muscles, inhibiting muscle contracture and vessel constriction. , An additional pathway acts through some molecular cascades to decrease vasoconstriction and pain.
Operative treatment.
Patients who do not improve with the above measures can be considered for operative treatment. This is more typical of secondary RP. Proximal sympathectomies have been generally abandoned because of limited benefit and possible adverse effects. Distal periarterial sympathectomies combined with venous grafting in cases of arterial occlusion have gained more support ( Box 31.2 ). ,
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Indicated primarily for patients with scleroderma or severe RP.
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Treatment should be coordinated with the rheumatologist or dermatologist.
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Digital ischemia etiology is multifactorial – vasospasm, fibrosis of surrounding structures, and adventitia of the artery and perivascular inflammation.
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First line of treatment – causes of vasospasm should be avoided to improve RP.
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Second line of treatment – vasodilating medication. The effects of other modalities such as Botox injections are limited.
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Indications for surgery (adventitial stripping) include worsening symptoms of RP, refractory pain, and digital ulcerations.
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With segmental occlusion, bypass grafting is indicated.
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Sympathectomy may be performed using two longitudinal distal forearm incisions over the radial and ulnar arteries, allowing dissection of 3 cm segments in each incision and a distal palmar crease incision. This allows for adventitial stripping along the superficial palmar arch and common digital arteries.
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Angiography is usually necessary for planning the procedure.
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An operative microscope is preferable for adventitial stripping.
Periarterial sympathectomy involves stripping the arterial adventitia, effectively denervating the vessels ( Box 31.2 ). This technique decreases the vasospasm and the AV shunting phenomenon, effectively increasing blood flow to the fingers. Common recommendations include stripping the distal ulnar and radial arteries, superficial palmar arch, and the proximal portions of the common digital arteries. , The radial and ulnar arteries can be exposed at the wrist through two parallel longitudinal incisions followed by stripping 2 to 4 cm in length of the adventitia. A transverse incision can be made in the distal palmar flexion crease, exposing the superficial palmar arch and digital arteries ( Fig. 31.4 ). ,
A more extensive approach includes stripping the adventitia from proper and common digital arteries and the superficial arch and ulnar artery and adding a vein bypass from the ulnar artery in the distal forearm into the superficial arch in an end-to-side fashion. This procedure reportedly led to decreased ischemic pain in 95% of patients, healing of the ulcerations in 78%, and better sensation in fingers. , The effect of the surgery can be increased and prolonged by topical administration of botulinum toxin to the exposed arteries and vein reconstructions and by injecting the contralateral hand during surgery.
Because patients with ulcers who undergo surgery often already have some degree of vessel thrombosis, early intervention may be beneficial. Most of the patients with SSc who exhibit RP and digital ulcerations will also have ulnar artery thrombosis. , In a study of 110 upper extremity angiograms, Leyden et al. reported a predominance of patients with SSc had ulnar artery thrombosis (57%) and less than 6% had radial artery thrombosis. The ulnar artery is more commonly thrombosed because it is smaller and in a tighter space in the Guyon canal. Therefore, patients with SSc may benefit from prophylactic release of the flexor carpi ulnaris (FCU) tendon and Guyon canal to prevent ulnar artery thrombosis.
Leyden et al. have performed prophylactic surgery in patients with no thrombosis but without arterial flow of the ulnar artery when the wrist is extended, as seen during Duplex assessment. The procedure required only a 4 cm incision to complete an FCU partial tenotomy, Guyon tunnel release, ulnar artery sympathectomy, and ulnar artery adventitial stripping. After this surgery, ulnar artery flow was restored and confirmed via Doppler studies, but long-term outcomes are not available. They consider prophylactic ulnar artery release at the wrist to be a low-risk procedure that may reduce the vascular complications of SSc if performed shortly after initial diagnosis.
Recurrence or progression of ulcerations, gangrene, and autoamputations are common. Surgical intervention in advanced RP may result in delay of wound healing and, in patients with scleroderma and RP, a 50% increase in the incidence of amputations 5 years after surgery.
Fat grafting has demonstrated improvement in hands pain, ulceration, and rate of RP events in 10 of 13 cases, 12 of which were previously treated with botulinum toxin. Adipose-derived stem cell induction of angiogenesis may explain this improvement. There is still limited data to support this technique.
Collagen vascular disease
Collagen vascular disease (also called connective tissue disease) has varied clinical presentations and affects multiple tissues and organs. The vascular endothelium is involved in the pathogenesis of systemic inflammatory diseases, especially in rheumatoid arthritis, psoriatic arthritis, SSc, and systemic lupus erythematosus (See Chapter 30 for these disorders). In these disorders, there are expressions of endothelial adhesion molecules, increased vascular permeability, and the extravasation of inflammatory cells into the interstitial matrix. Rheumatoid arthritis, as well as systemic lupus erythematosus and antiphospholipid syndrome, can be associated with vascular inflammation.
Clinical presentation
The peripheral vascular diseases are typically manifested by finger necrosis, flame-shaped subungual hemorrhages, and palmar rash with periungual telangiectasia. The most severe symptoms are seen with systemic sclerosis, which we discussed in the above section on RP. Hand involvement is common in these patients and represents an important tool for the early diagnosis of the disease.
Systemic sclerosis, also called scleroderma, is a systemic autoimmune inflammatory disease characterized by progressive generalized obliterative vasculopathy and widespread aberrant tissue fibrosis. The exact pathogenesis of SSc is not yet sufficiently understood. Environmental risk factors most likely promote epigenetic mechanisms in genetically primed subjects. Although the disease pathogenesis remains unclear, the disease process includes vascular hyperactivity and remodeling, fibroblast activation, and extracellular matrix synthesis, leading to skin and organ fibrosis and immune system dysfunction. Progressive fibrosis and ischemia involve skin and visceral organs.
Digital vascular disease occurs in almost all patients with SSc and can range in severity from symptoms of RP to irreversible ischemic injury causing ulceration, necrosis, or gangrene. The symptoms include pain, impaired hand function, reduced social participation, body image dissatisfaction, reliance on others, and reduced quality of life.
Buerger disease (thromboangiitis obliterans) is an inflammatory disease of medium- and small-sized vessels. The disease pathology includes creation of highly cellular inflammatory thrombi in the vessel lumen and not the vessel wall (in contrast to other inflammatory vasculitis diseases). Tobacco use and Jewish decent have been linked to this disease. The typical patient is a young man with signs of distal ischemia, no evidence of other collagen vascular disease, diabetes or a hypercoagulable state, and no remote source of emboli.
Diagnosis
Antinuclear antibodies (ANA) can be found in the blood tests of 90% to 95% of patients with collagen vascular disease. Several ANA specific to SSc include antibodies against topoisomerase I (anti-Scl-70) and RNA polymerase enzyme (anti-RNAP III). These have been included in the classification criteria of the disease. Other antinuclear antibodies are also often found, including ribonuclear proteins (anti-U11/U12 RNP, anti-U1 RNP, anti-U3 RNP) and nucleolar antigens (anti-Th/To, anti-NOR 90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl). Different ANA have been linked to distinct clinical features. Detecting a particular antibody type is important in predicting possible tissue involvement and prognosis and may have an impact on monitoring and treatment.
Nailfold video capillaroscopy ( Fig. 31.5 ) is the best-studied and most used method for distinguishing and quantifying microvascular morphological alterations in connective tissue disease, including primary versus secondary RP. The typical pattern of the nailfold microvasculature is characterized by a uniform distribution of hairpin-shaped capillaries ( Fig. 31.5 ). Tortuous and criss-crossing capillaries may be observed in the normal vasculature; however, giant capillaries, nonconvex capillary heads, disorganized or branching capillaries, avascular areas, and microhemorrhages are all considered abnormal. These abnormal patterns are typical of systemic inflammatory diseases, especially SSc ( Fig. 31.5 ).
