Tendinopathy of the Main Body of the Achilles Tendon 7

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intrinsic factors. Excessive motion of the hindfoot in the frontal plane, especially a lateral heel strike with excessive compensatory pronation, is thought to cause a “whipping action” on the Achilles tendon, and predispose it to tendinopathy. Also, forefoot varus is frequent in patients with Achilles tendinopathy. Changes in training pattern, poor technique, previous injuries, footwear, and environmental factors such as training on hard, slippery, or slanting surfaces are extrinsic factors that may predispose the athlete to Achilles tendinopathy.

Excessive loading of tendons during vigorous physical training is regarded as the main patho- logical stimulus for tendinopathy.

Tendons respond to repetitive overload beyond physiologi- cal threshold by either infl ammation of their sheath, histological changes of their body, or a combination of both.

It remains unclear whether different stresses induce different responses.

Active repair of fatigue damage must occur, or tendons would weaken and eventually rupture.

The repair mechanism is probably mediated by resident tenocytes, which continually monitor the extracellular matrix. Failure to adapt to recurrent excessive loads results in the release of cytokines leading to further modulation of cell activity.

Tendon damage may even occur from stresses within physiological limits, as frequent cumula- tive microtrauma may not allow enough time for repair.

Microtrauma can also result from nonuniform stress within tendons, producing abnormal load concentrations and frictional forces between the fi brils, with localized fi ber damage.

Introduction

In the past three decades, the incidence of Achilles tendinopathy has risen as a result of greater par- ticipation in recreational and competitive sport- ing activities.

A 10-fold increase in Achilles tendon injuries has been reported in runners compared to age-matched controls. The incidence of Achilles tendinopathy in top-level runners has been estimated at around 7–9%. Achilles tendi- nopathy is also common among athletes partici- pating in racquet sports, track and fi eld, volleyball, and soccer. However, Achilles tendinopathy does not exclusively affect athletes. In a recent study, 31% of 58 Achilles tendinopathy patients did not participate in vigorous physical activity.

Etiology and Pathophysiology

Tendon injuries can be acute or chronic and are caused by intrinsic or extrinsic factors, either alone or in combination. In acute trauma, extrin- sic factors predominate. Overuse injuries gener- ally have a multifactorial origin.

In chronic tendon disorders, interaction between intrinsic and extrinsic factors is common.

There is sparse scientifi c knowledge about the etiology and patho- physiology of chronic painful tendon conditions, and most hypotheses put forward have not been substantiated by sound scientifi c research.

Tendon vascularity, gastrocnemius-soleus dys- function, age, gender, body weight and height, pes cavus, and lateral ankle instability are common

Tendinopathy of the Main Body of the Achilles Tendon

Adam Ajis, Nicola Maffulli, Hakan Alfredson, and Louis C. Almekinders

The etiology of tendinopathy remains unclear, and many factors have been implicated.

Free radical damage occurring on reperfusion after ischemia, hypoxia, hyperthermia, and impaired tenocyte apoptosis have been linked with tendi- nopathy.

In animal studies, local administration of cytokines and infl ammatory agents such as prostaglandins has resulted in tendinopathy.

Fluoroquinolones have also been implicated in the pathogenesis of tendinopathy. Ciprofl oxacin causes enhanced interleukin-1 β mediated MMP3 release, inhibits tenocyte proliferation, and reduces collagen and matrix synthesis.

Degenerative tendinopathy is the most common histological fi nding in spontaneous tendon rup- tures. Tendon degeneration may lead to reduced tensile strength and a predisposition to rupture.

Indeed, ruptured Achilles tendons have more advanced intratendinous changes than tendino- pathic tendons.

In Achilles tendinopathy, changes in the expression of genes regulating cell-cell and cell-matrix interactions have been reported, with down-regulation of matrix metalloproteinase 3 (MMP 3) mRNA.

Signifi - cantly higher levels of type I and type III collagen mRNAs have been reported in tendinopathic samples compared to normal samples.

In tendi- nopathic Achilles tendons, up-regulation of MMP 2 and VEGF has been reported, while MMP 3 was down-regulated compared to control samples.

Imbalance in MMP activity in response to repeated injury or mechanical strain may result in tendinopathy.

Pain is the main symptom of Achilles tendi- nopathy, but the underlying mechanism causing pain is not fully understood. Traditionally, pain has been thought to arise through infl ammation, or via collagen fi ber separation or disruption.

However, chronically painful Achilles tendons have no evidence of infl ammation, and many tendons with intratendinous pathology detected on MRI or ultrasound are not painful.

As ten- dinopathies are not infl ammatory conditions, pain may originate from a combination of mechanical and biochemical causes:

chemical irritants and neurotransmitters may generate pain. Microdialysis sampling revealed a twofold increase in lactate levels in tendinopathic tendons compared to controls.

High concentrations of the neurotransmitter glutamate, with no abnor-

mal elevation of the pro-infl ammatory prosta- glandin PGE

, have been found in patients with Achilles and patellar tendinopathy.

Several studies have confi rmed the occurrence of sensory neuropeptides in both animal and human tendons, and Substance P (SP) has been found in tendinopathic Achilles tendons.

Endogenous opioids provide a peripheral anti- nociceptive system, and morphine inhibits the release of SP from peripheral sensory nerve endings.

Under normal conditions, a balance probably exists between nociceptive and anti- nociceptive peptides. However, this balance may be altered in pathological conditions.

Histopathology

The pathologic label tendinosis is used to describe the disorganized impaired healing response in tendinopathy. Despite that, most clinicians still use the term tendonitis or tendinitis, thus imply- ing that the fundamental problem is infl amma- tory. We advocate the use of the term tendinopathy as a generic descriptor of the clinical conditions in and around tendons arising from overuse, and suggest that the terms tendinosis, tendonitis and tendinitis only be used after histopathological examination.

Histologically, Achilles tendinopathy is charac- terized by an absence of infl ammatory cells and a poor healing response. Other changes include: noninfl ammatory intratendinous colla- gen degeneration, fi ber disorientation and thin- ning, hypercellularity, scattered vascular ingrowth, and increased interfi brillar glycosaminogly- cans.

Frank infl ammatory lesions and granu- lation tissue are mostly associated with tendon ruptures.

Various types of so-called degeneration may be seen in tendons, but in the Achilles tendon

“mucoid” or “lipoid” degeneration is usually seen.

In mucoid degeneration, light microscopy reveals large mucoid patches and vacuoles between fi bers. In lipoid degeneration, abnormal intraten- dinous accumulation of lipid occurs, with disrup- tion of collagen fi ber structure.

Paratendinopathy may occur alone or in com-

bination with degeneration of the tendon body.

Histologically, mucoid degeneration, fi brosis, and

vascular proliferation with a slight infl ammat- ory infi ltrate have been reported.

Clinically, edema and hyperemia of the paratenon are seen.

A fi brinous exudate accumulates within the tendon sheath, and crepitus may be felt on clinical examination.

Metalloproteases in Achilles Tendinopathy

Disorganized healing is constant in chronic tendi- nopathy. Normal tendon is mostly composed of Type I collagen, while tendinopathic tendons have a greater proportion of Type III collagen, which is associated with tendon rupture.

Matrix metallo- proteases (MMPs) are involved in remodeling of the extracellular matrix (ECM) of tendons, being either up- or down-regulated in tendinopathy. A balance between MMPs and tissue inhibitors of metalloproteases (TIMPs) is probably necessary to maintain tendon homeostasis. The mechanism of activation of MMPs is poorly understood, and their precise role in tendinopathy is still unclear.

Degradation of collagen and other ECM com- pounds is initiated by matrix metalloproteases (MMPs).

These are zinc and calcium-dependent endopeptidases secreted from cells in proenzyme form.

MMPs are the major enzymes involved in remodeling of ECM because of their effi cacy at neutral pH and their broad proteolytic capability against the ECM.

The MMP family comprises 23 members,

subdivided into four main classes: collagenases, gelatinases, stromelysins, and membrane-type MMPs.

MMPs are involved in many other physi- ological remodeling processes, including wound healing, menstruation, uterine involution, bone growth and development, and angiogenesis.

They also play a role in pathological processes such as tumor invasion and metastasis,

mul- tiple sclerosis,

periodontal disease,

hyperten- sion,

and arthritis.

The activity of MMPs is inhibited by tissue inhibitors of metalloproteases (TIMPs).

The balance between the activities of MMPs and TIMPs regulates tendon remodeling. An imbalance in MMPs and TIMPs is associated with collagen dis- turbances.

Cytokines such as interleukin-1 (IL-

1) and tumor necrosis factor α (TNFα) enhance the production of MMPs,

whereas transform- ing growth factor β (TGFβ) and IL-6 enhance the production of TIMP-1.

MMPs can be up- or down-regulated, locally and systemically, in tendinopathy and complete tendon tears. A balance exists between expression of MMPs and TIMPs to maintain tendon homeo- stasis. More research is required to determine the mechanism of action and regulation of MMPs in tendinopathy to promote the development of spe- cifi c therapeutic strategies in these patients.

Clinical Presentation

Pain is the cardinal symptom of Achilles tendi- nopathy. Generally pain occurs at the beginning and end of a training session, with a period of diminished discomfort in between. As the patho- logical process progresses, pain may occur during exercise, and, in severe cases, it may interfere with activities of daily living. In the acute phase, the tendon is diffusely swollen and edematous, and on palpation tenderness is usually greatest 2 to 6 cm proximal to the tendon insertion. Sometimes, fi brin precipitated from the fi brinogen-rich fl uid around the tendon can cause palpable crepita- tion.

In chronic cases, exercise-induced pain is still the cardinal symptom, but crepitation and effusion diminish.

A tender, nodular swelling is usually present in chronic cases, and is believed to signify tendinosis.

The diagnosis of Achilles tendinopathy is mainly based on a careful history and detailed clinical examination. Diagnostic imaging may be required to verify a clinical suspicion or to exclude other musculoskeletal disorders, such as os trigo- num syndrome, tenosynovitis or dislocation of the peroneal tendons, tenosynovitis of the plantar fl exors, an accessory soleus muscle, tumors of the Achilles tendon (xanthomas), and neuroma of the sural nerve.

Imaging

Ultrasonography is commonly employed in

Europe to examine tendon disorders. It is readily

available, quick, safe, and inexpensive. However,

ultrasound is very operator dependent, has some- what limited soft tissue contrast, and is not as sensitive as MRI.

However, the recent addition of power Doppler US imaging has made the use of US much more pertinent to the functional imaging of Achilles tendinopathy,

as it gives physiologically functional imaging that is not available with MRI.

In acute cases, ultrasound reveals fl uid accu- mulation around the tendon. In chronic cases, peritendinous adhesions may be shown by thick- ening of the hypoechoic paratenon with poorly defi ned borders. A simple grading system has been devised for tendinopathy. Grade 1 represents a normal tendon; grade 2 an enlarged tendon; and grade 3 a tendon containing a hypoechoic area.

Hypoechoic areas can be nodular, diffuse, or mul- tifocal, and they correlate well with macroscopic fi ndings at surgery.

MRI provides information on the internal mor- phology of the tendon and the surrounding struc- tures. It is useful to evaluate chronic tendinopathy and to differentiate between tendinopathy of the main body of the tendon and paratendinopathy.

Excellent correlation between MRI and pathologi- cal fi ndings at surgery has been reported.

A recent longitudinal ultrasound study showed that mild-to-moderate changes were observed frequently in both involved and uninvolved Achil- les tendons, but the occurrence of these changes was not clearly related to patients’ symptoms.

Given the high sensitivity of these imaging modalities, an abnormality should be interpreted with caution and correlated to the patient’s symptoms before formulating management recommendations.

Management

In the early phase of Achilles tendinopathy, various forms of conservative management are normally used.

Seeking medical attention at an early stage may improve outcome, as treat- ment becomes more complicated and less predict- able when the condition becomes chronic.

Surgical management is recommended for patients who do not adequately respond to a conservative program over 3 to 6 months.

Conservative Management

Conservative management is recommended as the initial strategy,

with identifi cation and cor- rection of possible etiological factors, at times using a symptom-related approach. There are few scientifi c prospective studies, and only in the last few years studies have compared different types of conservative management regimens in the chronic painful Achilles tendon using a random- ized controlled design.

The initial management most commonly con- sists of a multi-oriented approach, with combined rehabilitation models. There are many different regimes, most often including a combination of rest (complete or modifi ed), medication (NSAIDs, corticosteroids), orthotics (heel lift, change of shoes, corrections of misalignments), stretching and massage, and strength training,

and the most widely used initial approach is eccentric strength training of the gastro-soleus complex.

Decreasing the intensity, frequency, and dura- tion of the activity that caused the injury, or modi- fi cation of that activity, may be the only necessary action to control symptoms in the acute phase.

Collagen repair and remodeling is stimulated by tendon loading, and complete rest of an injured tendon can be detrimental. Modifi ed rest, which allows activity in the uninjured body parts and reduces activity at the injured site, has been recommended.

Despite the absence of scientifi c evidence for an ongoing chemical infl ammation inside the tendon,

nonsteroidal anti-infl ammatory drugs (NSAIDs) are often being used as one part of the initial management.

In a random- ized double-blind placebo-controlled study of 70 patients with chronic painful Achilles tendi- nopathy, oral piroxicam gave similar results to placebo.

We do not recommend NSAIDs.

Management with corticosteroid injections is

being debated.

Most authors suggest that

corticosteroid injections should be placed outside

the tendon to avoid damage to the tendon tissue,

but there are groups that suggest intratendinous

injections.

Partial ruptures are found not infre-

quently after steroid injections

and manage-

ment with steroid injections has been shown to

predict a partial rupture in patients with chronic

Achilles tendinopathy.

Also, a relatively large number of patients operated on for chronic Achil- les tendinopathy had previously received cortico- steroid injections, indicating a poor effect of corticosteroids on the condition. Overall, periten- dinous injections with corticosteroids are still controversial, evidence for their effectiveness is missing, and there are no good scientifi c reasons to support their use.

Intratendinous injections of corticosteroids are to be avoided. We do not rec- ommend the use of corticosteroids, either intra- or peritendinously.

Modalities such as cryotherapy,

heat,

massage,

ultrasound,

electrical stimulation,

and laser therapy

are sometimes included in the management regimen. These have been reported to be effective but there are no well-planned scientifi c clinical studies confi rming their effects.

Cryotherapy has been regarded as a useful intervention in the acute phase of Achilles tendi- nopathy, as it has an analgesic effect, reduces the metabolic rate of the tendon, and decreases the extravasation of blood and protein from new cap- illaries found in tendon injuries.

However, recent evidence in upper limb tendinopathy indicates that the addition of ice did not offer any advan- tage over an exercise program consisting of eccen- tric and static stretching exercises.

Therapeutic ultrasound may reduce the swell- ing in the acute infl ammatory phase and improve tendon healing.

Ultrasound also stimulates col- lagen synthesis in tendon fi broblasts and stimu- lates cell division during periods of rapid cell proliferation.

Deep friction massage has been advocated for tendinopathy and paratendinopathy. In chronic cases, this should be accompanied by stretching to restore tissue elasticity and reduce the strain in the muscle-tendon unit with joint motion.

Augmented soft tissue mobilization (ASTM) is a noninvasive soft tissue mobilization technique successfully used in chronic tendinopathy patients.

This is thought to work through controlled appli- cation of microtrauma, which would increase fi broblast proliferation.

If there is foot malalignment, orthoses that place the hindfoot in neutral may prove benefi cial.

A heel lift of 12–15 mm is classically used as an adjunct to the management of Achilles tendon

pain.

Orthotics correction can alter the biome- chanics of the foot and ankle and relieve heel pain.

Therefore, orthotics are commonly used, espe- cially in runners, with up to 75% success.

Several drugs, such as low-dose heparin, wydase, and aprotinin, have been used in the management of peri- and intratendinous pathol- ogy.

Although widely used and promising, evidence of their long-term effectiveness is still unclear.

The importance of eccentric training as a part of the rehabilitation of tendon injuries was noticed in the early 1980s.

Eccentric strengthening of the triceps surae muscle and Achilles tendon are important to preserve function of its musculoten- dinous unit, possibly by restoring normal ankle joint mobility and decreasing the strain of the Achilles tendon with normal motion. Painful eccentric gastrocnemius training is effective for patients with chronic painful mid-portion Achilles tendinosis.

Heavy-load eccentric train- ing is superior to concentric training in decreasing pain in chronic Achilles tendinopathy affecting the main body of the Achilles tendon.

Results have been obtained using an intensive heavy-load eccentric muscle training regimen.

However, this regimen gave poor results when applied to patients with insertional Achilles tendinopathy.

When painful eccentric training was compared with painful concentric exercises in patients with tendinopathy of the main body of the Achilles tendon, eccentric training was clearly superior.

Follow-up of patients who underwent eccentric training showed that most were satisfi ed and back to their previous tendon loading activity level.

Interestingly, the Achilles tendon thickness had decreased signifi cantly, and the tendon structure looked ultrasonographically more normal.

Explanations for the good clinical results

achieved with painful eccentric calf-muscle train-

ing are as yet uncertain. Relief of pain may result

from the increased tensile strength in the tendon

or possibly from stretching with “lengthening” of

the muscle-tendon unit, causing less strain during

ankle joint motion. Also, the eccentric training

regimen is painful to perform. This type of painful

loading may be associated with some kind of

alteration of the pain perception from the

tendon.

Sclerosing Injections and Neovascularization In Achilles tendons with chronic painful tendi- nopathy, but not in normal pain-free tendons, there is neovascularization outside and inside the ventral part of the tendinopathic area.

During eccentric calf-muscle contraction, the fl ow in the neovessels disappears on ankle dorsifl exion. The good clinical effects with eccentric training may be due to action on the neovessels and accompa- nying nerves. Also, local anesthetic injected in the area of neovascularization outside the tendon resulted in a pain-free tendon, indicating that this area is involved in pain generation.

The above fi ndings are the bases for a novel management modality whereby the sclerosing substance poli- docanol under ultrasound and color Doppler- guidance is injected, targeting the area with neovessels and nerves outside the tendon. Reha- bilitation after sclerosing injections includes a short period of rest (1–3 days), followed by gradual increase of tendon loading activities, but no maximum loading (jumping, fast runs, heavy strength training) for the fi rst two weeks. After this period, normal tendon loading is allowed.

Most patients with good clinical results after treat- ments with sclerosing injections had no residual neovessels. Patients with poor results showed residual neovascularisation.

The results of this new intervention are promising, but longer follow- ups of clinical status and sonographic fi ndings are needed for further evaluation.

Surgical Management

In 24% to 45.5% of patients with Achilles tendi- nopathy, conservative management is unsuccess- ful, and surgery is recommended after exhausting conservative methods of management, often tried for at least six months.

However, long- standing Achilles tendinopathy is associated with poor postoperative results, with a greater rate of reoperation before reaching an acceptable outcome.

The objective of surgery is to excise fi brotic adhesions, remove areas of failed healing and make multiple longitudinal incisions in the tendon to detect intratendinous lesions, and to restore vascularity and possibly stimulate the remaining viable cells to initiate cell matrix response and

healing.

Recent studies show that multiple longitudinal tenotomies trigger neoangiogenesis at the Achilles tendon, with increased blood fl ow.

This would result in improved nutrition and a more favorable environment for healing.

Patients are encouraged to weight-bear as soon as possible after surgery.

Most authors report excellent or good results in up to 85% of cases, although this is not always observed in routine nonspecialized clinical prac- tice.

It is diffi cult to compare the results of studies as most investigations do not report their assessment procedure.

Also, no prospective randomized studies comparing operative and conservative treatment of Achilles tendinopathy have been published; thus most of our knowledge on treatment effi cacy is based on clinical experi- ence and descriptive studies.

It is still debatable why tendinopathic tendons respond to surgery.

For example, we do not know whether surgery induces long-term revas- cularization, denervation, or both, resulting in pain reduction. It is also unclear exactly how lon- gitudinal tenotomy improves vascularization.

Conclusion

Although Achilles tendinopathy has been exten- sively studied, there is a clear lack of properly conducted scientifi c research to clarify its etiol- ogy, pathology, and optimal management. Most patients respond to conservative measures, and the symptoms can be controlled, especially if the patients accept that a decreased level of activities may be necessary.

As the biology of ten- dinopathy is being clarifi ed, more effective management regimes may come to light, improv- ing the success rate of both conservative and operative management.

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