Version May 2024
INTRODUCTION — Tendinopathy is a clinical syndrome characterized by persistent, localized tendon pain and loss of function. Most commonly, it is the result of repeated mechanical loading (this is termed "overuse"). On occasion, a small load or increase in load can result in a tendon becoming symptomatic for the first time. Tendinopathy is distinct from tendon rupture. Tendinopathy refers to a tendon with abnormal tissue that is structurally intact.
This topic will review the clinically relevant aspects of the pathophysiology of tendinopathy in general. The diagnosis and management of tendinopathy generally and in specific tendons is discussed separately. (See "Overview of the management of overuse (persistent) tendinopathy" and "Achilles tendinopathy and tendon rupture" and "Rotator cuff tendinopathy" and "Elbow tendinopathy (tennis and golf elbow)".)
PATHOLOGY AND TERMINOLOGY — Our knowledge of the pathophysiology of overuse tendinopathy stems mainly from surgical biopsies taken from subjects with chronic tendon pain who have failed conservative treatment and undergone open or arthroscopic tendon debridement.
Historically, overuse tendinopathy was commonly referred to as tendinitis. The suffix "itis" implied that inflammation was central to the pathological process. During the 1990s, surgical biopsies from ruptured and symptomatic tendons (ie, in patients who had failed conservative treatment) became available. Numerous histopathology and gene array studies performed on these tissue specimens have revealed that the pathophysiology underlying most cases is a failed healing response within the tendon tissue [1-18]. Histopathology of a wide variety of tendons consistently reveals few inflammatory cells. This is true of the Achilles, posterior tibial, patellar, gluteal [19], adductor [20], extensor carpi radialis brevis and longus, flexor carpi ulnaris, flexor digitorum [21], and rotator cuff tendons [3,8,14,22,23]. Subsequently, the prevailing view became that tendinopathy was essentially a degenerative condition caused by repeated mechanical loading (overuse), not an inflammatory condition. The term "tendinitis" fell out of favor, and the terms "tendinopathy" and "tendinosis" became more commonly used.
Nevertheless, tissue analyses revealed the presence of iron-containing macrophages in affected tissues, suggesting prior episodes of vascular disruption and the resulting activation of the innate immune response during the development of tendinopathy [15,17]. Furthermore, the widespread presence of neovessels and chemicals such as substance P in longstanding tendinopathy suggests elements of the inflammatory response are indeed present in chronic tendinopathy.
A 2018 systematic review concluded that "prior to 2012, the majority of published reviews did not discuss monocytes, macrophages, or lymphocytes in tendinopathy; rather, they focused on the lack of neutrophils" [24]. This neutrophil-focused definition of inflammation may have contributed to suggestions that the pathophysiology is entirely noninflammatory [25].
A typical inflammatory response does occur in tendons following vascular disruption, whether from microscopic, partial, or complete rupture of the tendon [26-28]. Increased COX-2 or IL-6 expression indicates that there may be a mild low-grade inflammation even in longstanding cases [29]. Indeed, tendon cells from patients with tendinopathy produce more PGE2 than do tendon cells from those with healthy tendons [30].
The role of inflammation in acute paratendinitis (eg, De Quervain tenosynovitis) may be more prominent [13]. However, in the chronic stage, De Quervain tenosynovitis is also characterized by minimal inflammation and widespread degenerative and fibrotic changes affecting the sheath and the tendon itself.
In addition to minimal inflammation, overuse tendinopathy is characterized by changes in tendon structure that mainly reflect scarring and a healing response [31,32]. Changes can occur in different regions of a tendon, such as at the enthesis (portion of tendon that inserts onto bone) [33]. The attached figure presents examples of normal tendon appearance and some common changes observed in pathologic tissue (picture 1). These features include areas of tendon fibroblast proliferation, presence of smaller and less organized collagen fibers, and neovascularization/angiogenesis. This pathology may be summarized as "angiofibroblastic hyperplasia" [18].
EPIDEMIOLOGY — Increased participation in recreational sporting activity, particularly among middle-aged adults, has led to an increasing incidence of overuse tendinopathies [34]. Risk factors for tendinopathy are often divided into intrinsic factors (pertaining to the properties of an individual's tendon or healing capacity) and extrinsic factors (pertaining to the load placed on the tendon; ie, the volume of exercise) (table 1). Among these many factors, advancing age (intrinsic) and increased overall volume of tendon load (extrinsic) pose the greatest risk for developing overuse tendinopathy.
Age over 35 years is associated with an increased incidence of many overuse tendinopathies, including Achilles tendinopathy in runners and rotator cuff tendinopathy in throwing athletes or manual laborers [34]. As tendons age, they lose their energy-storing capacity (in particular the Achilles tendon), which may predispose to injury [35-37]. In addition, age may reduce the tendon's capacity to repair the ongoing microtrauma that occurs during tendon loading activity [38]. Generally speaking, apophysitis (such as Osgood-Schlatter disease and calcaneal apophysitis) is more common than tendinopathy in adolescents [34]. (See "Osgood-Schlatter disease (tibial tuberosity avulsion)" and "Heel pain in the active child or skeletally immature adolescent: Overview of causes", section on 'Calcaneal apophysitis (Sever disease)'.)
Gender strongly influences the risk of developing certain tendinopathies. As an example, patellar tendinopathy is five times more common in male than female jumping athletes [39]. By contrast, lateral elbow tendinopathy appears equally distributed among males and females [40,41]. The influence of gender on tendinopathy is incompletely understood but may represent a combination of biomechanical variables (eg, hip-to-knee angles), hormonal influences (eg, estrogen levels and menopausal status), and different sporting or occupational behaviors [42].
Biomechanical abnormalities are associated with an increased risk of tendinopathy, particularly in the lower extremity. Thus, if unusual postures or movements are noted in patients with chronic tendon pain, a complete biomechanical assessment by a physiotherapist or other clinician with comparable expertise should be performed. Pes planus (flat foot) or pes cavus (high arched foot), subtalar joint stiffness, reduced ankle dorsiflexion, muscle tightness, and sacroiliac joint dysfunction have all been reported to play a role in the development of tendinopathy [43-46].
Prior tendon lesions represent a significant risk factor for developing tendinopathy. In high-risk groups, such as athletes participating in jumping sports with a high prevalence of patellar or Achilles tendinopathy, asymptomatic lesions identified on ultrasound at the start of an athletic season are associated with an increased risk of developing a symptomatic tendinopathy during the season [47,48].
Tendinopathies often develop bilaterally or at multiple locations in the same individual. Some progress has been made in exploring the role of the genetics and the heritability of overuse tendinopathies, and this research may eventually lead to the identification of high-risk individuals [49]. A single nucleotide polymorphism associated with reduced levels of GDF-5 (growth and differentiation factor 5, important for tendon development and healing) is associated with twice the risk of developing Achilles tendinopathy [50]. The presentation of symptomatic tendinopathy should lead the clinician to inquire about tendinopathy at other locations [41].
Extrinsic risk factors for overuse tendinopathy include training errors (eg, sudden increase in tendon loading activity, inadequate rest), poor environmental conditions (eg, cambered road surfaces, hard gym floors, frozen turf, extreme temperatures, poor ergonomics), inadequate equipment (eg, old or inappropriate footwear), or a premature return to sport [34,51-55]. Of these risk factors, sudden substantial increases in training load without adequate time for the body to adjust (eg, doubling of cumulative running distances from one week to the next) incur the greatest risk.
More recently, clinicians have come to appreciate the role of metabolic diseases in tendinopathy. The most common example is diabetes mellitus [56]. Diabetic patients are more likely to develop tendinopathy at a variety of sites (eg, rotator cuff, hand flexor tendons). In addition, tendinopathy in diabetics is more likely to be refractory to treatment. Other metabolic disorders that increase the risk for tendinopathy include hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Even in the absence of discrete diagnoses, a relatively small increase in waist size is a risk factor for patellar tendinopathy [57].
Suboptimal ergonomics play a role in the development of many upper extremity tendinopathies [51]. Excessive movement or awkward postures involving the hand, wrist, or shoulder during daily or occupational activities can strain tendons.
Certain medications increase the risk of acute and chronic tendinopathy. These include fluoroquinolones, glucocorticoids, and aromatase inhibitors. Tendon conditions have been attributed to 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (ie, statins), but debate continues as to whether these are due to the medication or the hypercholesterolemia for which they are prescribed [58,59]. (See "Fluoroquinolones", section on 'Tendinopathy' and "Statin muscle-related adverse events".)
MAJOR CLINICAL FINDINGS — A careful history and physical examination can help to confirm whether an injury involves a tendon and why the injury occurred now. Important questions to ask include:
●Has there been any recent increase in training volume or any new activities?
●Has there been any change in equipment (eg new racquet) or training programming (eg, running on a different surface, hill running)?
●Have you recently returned from time away from training or regular activities (tendons lose strength and conditioning quickly)?
●Is there any history of an inflammatory condition, such as inflammatory joint or spinal disease, psoriasis, or inflammatory bowel disease, in the patient or their family?
●Has there been any recent use of tendinopathic medications (eg, quinolone antibiotics, aromatase inhibitors)?
Tendinopathy affecting superficial tendons, such as the Achilles, may demonstrate readily observable tendon thickening. In nonsuperficial tendons, thickening may not be apparent but is often clinically significant, as in the case of the rotator cuff where thickening of both tendon and bursa can exacerbate impingement in the subacromial space. (See "Subacromial (shoulder) impingement syndrome".)
A characteristic of many tendinopathies is the delayed appearance of more severe pain, termed "latency." Latency is seen characteristically in Achilles and patellar tendinopathy but is found with other tendons. During loading of the tendon (eg, during exercise such as running), there may be a short-lived increase in pain at the tendon initially that subsides as exercise continues. However, subsequently (ie, a few hours after exercise or the next day), more severe pain, worse than baseline, develops.
Although pathology may exist within the tendon or its associated structures, it is important to note that the underlying cause of tendinopathy may lie elsewhere. A thorough assessment performed by a clinician knowledgeable about musculoskeletal evaluation often reveals changes elsewhere in the kinetic chain, including muscle weakness, abnormal movement patterns, or joint stiffness. In addition, tendinopathy, like other pain syndromes, may involve referred pain, muscle spasm or tenderness, or other regional (or even contralateral) motor abnormalities [60]. The role of associated structures generally, and the adjacent fat pad in cases of the Achilles and patellar tendon in particular, is the subject of debate [61].
DIAGNOSTIC IMAGING — Characteristic changes in tendon appearance on ultrasound or magnetic resonance imaging (MRI) studies can be used to confirm the likelihood of tendinopathy as a source of load-related tendon pain, identify macroscopic tears (which may be amenable to surgical repair), and determine the extent of involvement of associated structures (eg, presence of bony spurs or fragments, labral lesions, bursal pathology).
Greyscale or color Doppler ultrasound are particularly useful for detecting tendon pathology and may reveal tendon thickening, hypoechoic areas, and increased blood flow in the deep portions of the tendon. There is a moderate association between the extent of Doppler signal and patients' symptoms and functional limitations [62]; however, Doppler signal is of limited use for prognosis [63]. MRI reveals increased signal in abnormal tendons, corresponding to the increased water content associated with excessive proteoglycans and increased blood flow, and is more effective than ultrasound at distinguishing partial tears [64].
Improvements in ultrasound technology have enabled trained musculoskeletal ultrasonographers to better distinguish the pathological conditions underlying tendinopathy, including tendon dislocations, paratendinitis, and partial tendon tears. This may influence management. As an example, a patient with Achilles tendinopathy where the pathology is predominantly paratendinous may be able to tolerate high levels of exercise more quickly than a patient with a partial tendon tear.
Studies of ultrasound and magnetic resonance imaging (MRI) for the diagnosis of tendon pathology report relatively high sensitivity and specificity for full-thickness tendon tears but limited test characteristics for other conditions [65,66]. Estimates of sensitivity and specificity for the detection of tendinopathy are likely to change as studies involving more advanced equipment are published. Available systematic reviews of diagnostic accuracy are difficult to interpret, as many compare imaging with physical examination findings rather than more definitive standards [67].
NATURAL HISTORY AND TREATMENT — The majority of patients with overuse tendinopathy present to health professionals in the chronic stage (over three months of symptoms). Once present, tendinopathies may be refractory to treatment, and some become career limiting for professional athletes. However, tendinopathy may also be transient, causing minor irritation that resolves over a period of days or weeks [68].
The recalcitrant nature of many cases of untreated tendinopathy is well documented. As an example, in one trial, patients with untreated, chronic Achilles tendinopathy experienced a gradual improvement in the average load-induced pain score from 7.9/10 to 5.9/10 over the course of four months [69]. However, beyond four months, only 24 percent of untreated patients reported significant improvement or cure. Improvement rates were slightly better among patients in another trial involving lateral elbow tendinopathy of at least six weeks duration [70]. In this study, after three months without treatment, 42 percent of patients reported significant improvement in day-time pain. Patients treated with physiotherapy emphasizing active exercise experienced significantly higher improvement rates than those treated with alternative approaches [71,72]. Treatment of chronic tendinopathy is discussed separately. (See "Overview of the management of overuse (persistent) tendinopathy".)
Debate continues about the extent to which the tissue changes underlying tendinopathy are reversible as determined by histology or imaging. Longitudinal studies have reported a reduction in ultrasound abnormalities in successfully treated tendons, including normalization of tendon thickness and reduction of hypoechoic areas [73]. However, considerable symptomatic improvement and successful return to activity is seen in some patients with persistent, macroscopically apparent pathology who follow a proper rehabilitation program. (See "Overview of the management of overuse (persistent) tendinopathy".)
Follow-up imaging is not typically recommended for patients who are treated with physical rehabilitation. Although several clinical trials suggest that ultrasound performed during rehabilitation and follow-up is useful for determining the effectiveness of treatment, these preliminary findings need further confirmation [74-76].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General issues in muscle and tendon injury diagnosis and management" and "Society guideline links: Muscle and tendon injuries of the upper extremity (excluding shoulder)" and "Society guideline links: Muscle and tendon injuries of the lower extremity (excluding Achilles)".)
SUMMARY AND RECOMMENDATIONS
●Pathology and terminology – Tendinopathy is a clinical syndrome characterized by chronic, localized tendon pain that is exacerbated by mechanical loading. Tendon overuse is a leading cause, and metabolic factors may contribute. (See 'Pathology and terminology' above.)
Overuse tendinopathy is primarily characterized by changes in tendon structure that reflect scarring and/or a failed healing response.
A classic cellular inflammatory reaction is present only minimally in most cases of chronic overuse tendinopathy, but elements of inflammation are involved in injury and healing.
●Epidemiology and risk factors – Risk factors for tendinopathy are often divided into intrinsic factors (pertaining to the properties of an individual's tendon or healing capacity) and extrinsic factors (pertaining to the load placed on the tendon) (table 1). Among many risk factors, advancing age and increased overall volume or intensity of tendon load pose the greatest risk for developing overuse tendinopathy. (See 'Epidemiology' above.)
●Clinical findings – The major clinical features associated with tendinopathy are pain with palpation of the affected part of the tendon and pain with tendon loading. (See 'Major clinical findings' above.)
●Diagnostic imaging – Overuse tendinopathy manifests characteristic findings on imaging studies using magnetic resonance imaging (MRI) or ultrasound. Findings include tendon thickening, abnormal tendon appearance, and increased blood flow. (See 'Diagnostic imaging' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Karim Khan, MD, who contributed to an earlier version of this topic review.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
