Lower Extremity Tendinopathy in the Setting of Systemic Disease
ANDREW J. ROSENBAUM
JASON P. TARTAGLIONE
MOSTAFA ABOUSAYED
MAXWELL C. ALLEY
JOSHUA S. DINES
Primary disorders of tendons are common musculoskeletal problems that represent diagnostic and treatment challenges for orthopedic surgeons, resulting in chronic and long-lasting morbidities. Recent studies have elucidated that tissue degeneration is the main pathophysiologic process responsible for tendon injuries and disorders, not inflammation.1,2,3,4,5,6 Besides overuse, any process, intrinsic or extrinsic, that alters tendon morphology or disrupts the stepwise progression of tendon healing (inflammatory, proliferative, and maturation and remodeling phases), has the potential to cause tendon injury. This includes systemic diseases such as diabetes mellitus (DM), hypercholesterolemia, gout, rheumatoid arthritis, and genetic disorders that alter collagen form and function (i.e., Ehlers-Danlos syndrome, Marfan syndrome, and ochronosis).
 FIGURE 22-1. The biologic responses of tendon fibroblasts to repetitive mechanical loading conditions are shown. Depending on mechanical loading positions, the cellular mechanobiologic responses may lead to tendon physiologic remodeling or pathologic changes such as tendinopathy. ECM, extracellular matrix; MMP, matrix metalloproteinase; PG, prostaglandins; LT, leukotriene; IL, interleukin. (Reproduced from Wang JH, Iosifidis MI, Fu FH. Biomechanical basis for tendinopathy. Clin Orthop Relat Res. 2006;443:320-332.) |
Newer theories concerning the pathogenesis of tendinopathies suggest that both inflammatory and degenerative processes play roles in this complex disease entity7 (Fig. 22-1). The most common tendons affected by tendinopathy in the foot and ankle include the Achilles, posterior tibial, peroneal,
and flexor hallucis longus (FHL). It has been estimated that 11% of runners are afflicted by Achilles tendinopathy.8 However, not all tendinopathies are associated with sporting activities, as it has been shown that approximately one-third of patients with Achilles tendinopathy do not participate in vigorous activities.9 This is exemplified by the fact that the majority of people with radiographic evidence of tendinosis are asymptomatic.7 Tendinopathies of the foot and ankle cause chronic pain and deformity and affect patients’ overall quality of lives. Treatment options depend on the specific tendon involved, duration of symptoms, previous treatments, and patient factors including age, activity level, and medical comorbidities. Both nonsurgical and operative interventions can be used on a case-by-case basis. Unfortunately, there is a paucity in the literature of quality randomized controlled studies to help guide treatment.
and flexor hallucis longus (FHL). It has been estimated that 11% of runners are afflicted by Achilles tendinopathy.8 However, not all tendinopathies are associated with sporting activities, as it has been shown that approximately one-third of patients with Achilles tendinopathy do not participate in vigorous activities.9 This is exemplified by the fact that the majority of people with radiographic evidence of tendinosis are asymptomatic.7 Tendinopathies of the foot and ankle cause chronic pain and deformity and affect patients’ overall quality of lives. Treatment options depend on the specific tendon involved, duration of symptoms, previous treatments, and patient factors including age, activity level, and medical comorbidities. Both nonsurgical and operative interventions can be used on a case-by-case basis. Unfortunately, there is a paucity in the literature of quality randomized controlled studies to help guide treatment.
In this chapter, we review the pathophysiology of tendinopathy and the risk factors predisposing patients to tendinopathy, particularly in the setting of systemic disorders, and review the evaluation and treatment of common foot and ankle tendinopathies.
Definitions
In the literature, the nomenclature used to describe tendon disorders has been confusing, and multiple terms are often used to describe the same disease process. Traditionally, the term tendonitis has been used to describe chronic pain or dysfunction of a tendon, with the implication that an inflammatory process is the primary underlying pathology. However, histologic review of surgical specimens from chronic tendinopathies of the Achilles, rotator cuff, patella, and extensor carpi radialis brevis has shown either absent or minimal inflammation.1,2,4,5,6
Throughout this chapter, the term “tendinopathy” will be used to describe a spectrum of tendon overuse disorders that include paratendinitis, tendonitis, and tendinosis. Paratendinitis is an acute inflammatory process affecting the paratenon and adjacent nontendinous tissues. In isolation, this pathologic process does not usually cause tendon rupture, is reversible, and can be treated with tenolysis in refractory cases.
Tendonitis is tendinopathy with the presence of a histologically proven inflammatory process. Studies have demonstrated that overloaded equine superficial digital flexor tendons undergo an acute phase of tendon injury that involves inflammatory cells early on in the injury process, which is followed by a degenerative process.10,11 Tendinosis describes a degenerative process that lacks inflammation. These tendons have intrasubstance degeneration, which can be appreciated clinically by nodules within the tendon.
Pathophysiology
Tendons are composed mainly of collagen fibrils, which are encased by an endotenon. Multiple collagen fibrils grouped together are surrounded by an epitenon that demarcates the actual tendon. In order to provide protection and lubrication and prevent friction, some tendons have a true enveloping synovial sheath (i.e., tibialis posterior and peroneal tendons), whereas other tendons are encased solely by a peritenon (i.e., Achilles). The extracellular matrix consists of collagen (65% to 80% of dry weight), most of which is Type I, which provides tendons with tensile strength. The mechanical behavior of tendons, which is viscoelastic in nature, is secondary to the cross-sectional area and length of the tendon. The larger a tendon’s cross-sectional area, the greater the load to failure rate.12 Tendons with longer fibers have decreased stiffness, equivalent load to failure rates, but increased elongation to failure rates.13 The rest of the extracellular matrix is made up of 1% to 2% elastin and a ground substance that consists of 60% to 80% water, proteoglycans, and glycoproteins.7 Tenoblasts and tenocytes form parallel rows between collagen fibers, making up 90% to 95% of tendons’ cellular components.7 Tendons carry their function through the musculotendinous junction, a richly innervated transitional area between the muscle and the tendon that experiences high mechanical forces, therefore making this region susceptible to injury. The enthesis, or osteotendinous junction, is an organized transition zone from tendon to bone allowing muscles to effectively transmit force to bone.
To date, the etiology and pathophysiology of tendinopathy are not well understood. As previously stated, tendinopathy was once believed to be the result of inflammation. However, through clinical practice, it has become recognized that anti-inflammatory medications do not relieve the pain associated with tendinopathy. In addition, using microdialysis, Alfredson et al.14 demonstrated a lack of the inflammatory mediator prostaglandin E2 in chronically affected Achilles tendons. However, clinical and basic science research often involves chronically affected tendons, making it possible that inflammation plays a role in the initial insult to chronically diseased tendons.
Histologically, chronic tendinopathy is characterized by degenerative changes, which include decreased cellularity and calcific, hypoxic, hyaline, mucoid, myxoid, fibrinoid, and fatty degenerations2,4,15 (Fig. 22-2). Chronic tendinopathy is also characterized by an increase in Type III collagen, which has less cross-links than Type I collagen, conferring decreased tensile strength, as well as degeneration and loss of organization of collagen fibers mainly due to increased activity of matrix metalloproteinases.16 Studies have shown that degenerative areas of tendons experience neovascularization.17,18 Interestingly, using in vivo powered Doppler ultrasonography, various studies have demonstrated that neovascularization is often associated with patients who are symptomatic and experiencing pain.17,19 Lastly, degenerative changes characterized by adhesions and increased number of fibroblasts and myofibroblasts are found in peritendinous tissues, most commonly occurring in tendons with synovial sheaths (posterior tibial and peroneal tendons).20 Grossly, chronically diseased tendons have a disorganized appearance illustrated by a yellowish or brown color, palpable thickenings
or nodules in the areas of chronic disease and degeneration that can be calcified.
or nodules in the areas of chronic disease and degeneration that can be calcified.
 FIGURE 22-2. A summary of the pathologic findings associated with tendinopathy. (Reproduced from UpToDate, Wolters Kluwer Health.) |
There are currently three main theories describing the etiology of tendon degeneration that can progress to chronic tendinopathy and potential rupture: the mechanical, vascular, and neural theories.
The mechanical theory of tendinopathy describes how chronic repetitive damage to tendons over time could lead to a state of degeneration as opposed to inflammation. This theory states that repetitive loading of a tendon under physiologic loads progresses to degeneration and ultimate tendon failure. At rest, tendon collagen fibers are disorganized in a wave-like formation. As a tendon is loaded, these fibers begin to organize in a parallel manner. This occurs in the toe region of the stress-strain curve. Once the collagen fibers align and experience continued force, the tendon enters the elastic part of the stress-strain curve, which is characterized by a linear relationship between load and strain. It has been shown that normal physiologic loading of a tendon occurs between 4% and 8% strain.21,22,23,24,25,26 At the higher end of the physiologic loading, tendons experience microscopic trauma, leading to degeneration and failure with repetitive stress. This repetitive microtrauma can lead to the alteration of mechanical properties of tendons as well as a symptomatic tendon.21,27,28,29 This theory fails to account for why specific areas of tendons have a predilection for injury and does not explain why some patients are symptomatic and others are not.
The vascular theory of tendinopathy is formed on the basis that tendons are metabolic structures with metabolic demands requiring an adequate vascular supply. The theory states that in the absence of an adequate blood supply, tendons undergo degeneration. Certain tendons, including the Achilles30 and posterior tibial31 tendons, have been shown to have areas of hypovascularity. For example, the watershed area of the Achilles tendon has been shown to occur in the midportion of the tendon as compared to areas closer to the proximal musculotendinous junction and distal enthesis.32 However, using laser Doppler flowmetry, Astrom and Westlin32 demonstrated that the Achilles tendon has uniform blood supply, except at the distal insertion.
The neural theory of tendinopathy is based on multiple observations from various studies trying to connect the role of tendon degeneration and neural-mediated causes. Tendons are highly innervated structures that have nerve endings closely associated with mast cells. It is theorized that tendon overuse causes overstimulation of nerves and subsequent degranulation of mast cells with the release of neuromodulators such as substance P, a nociceptive neurotransmitter and proinflammatory mediator,33 and a calcitonin-related peptide.34 Increased levels of substance P have been found in rotator cuff tendinopathy,35 and the neurotransmitter glutamate has been found in Achilles tendinopathy.14 Lastly, Maffulli et al.36 discovered a relationship between sciatica and Achilles tendinopathy, suggesting a connection between tendinopathy and a neural-mediated cause. Further research is needed to understand the full significance and role of relationship between nerve stimulation and tendinopathy.
It is likely that the combination of early inflammation and later degeneration plays a role in the pathogenesis of chronic tendon injury and tendinopathy. No one theory completely explains the etiology of tendinopathy; rather, it is likely a combination of the mechanical, vascular, and neural theories that best explains the pathogenesis. Further studies are needed to better understand the interconnectedness of these theories.
Risk Factors
The risk factors implicated in the development of tendinopathy can be stratified into two large categories: extrinsic and intrinsic (Table 22-1). Extrinsic risk factors, such as overuse, are those most commonly implicated. However, other extrinsic factors that must be recognized include training errors, fatigue, environmental conditions, footwear, equipment, and medications/nutritional supplementation. Intrinsic risk factors are innate to a given individual, and include one’s genetic makeup, congenital disorders (e.g., alkaptonuria), limb malalignment, gender, aging, neurologic conditions, medical comorbidities (e.g., hypertension), and systemic diseases.
