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Revisiting Inflammatory Tendinopathy

Victor Klausner D.O. Family Practice/Sports Medicine/Occupational Medicine

Objectives

Learn how development of chronic tendinopathy incorporates elements

of both inflammatory and mechanical mechanisms.

Understand pathophysiology and prevalence of the most common

rheumatological syndromes that occur in diabetic patients.

List medications that can cause inflammatory Tendonopathy.

List treatment strategies (pharmaceutical, nutritional, rehabilitation…)

that can be used to treat Inflammatory tendinopathy.

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Tendinopathy: Definition and Statistics Strains- Acute overload/inability of structure to manage load intensity.

Tendinopathy- Chronic overload combined with physiologic changes associated

with chronic edema and inflammation.

• Tendon Injuries estimated at 30-50% of all sports injuries.

• Achilles Tendinopathy estimated at 60% of tendon disorders (30% of runners).

• Occupational tendon injuries frequently affect upper extremity.

Tendon Functions Normal Tendon

Linear Organized Collagen Fiber Alignment (type I)

Minimal Vascularity

Spindle Shaped Tenocytes

Tendinopathy

Disorganized Collagen Fibers (Type III)

Neovascularization & Neuronal ingrowth

↑ Cellularity - Round Tenocytes/Myofibroblasts

Inflammatory Components Extracellular Matrix

Xu, Y et al “The Basic Science of Tendinopathy”

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Applying Science to Tendon Injuries Continuum Model of Tendinopathy (Cook and Perdum)

• Three Current Theories of Pathoetiology

Mechanical Model - collagen disruption/tearing model

Inflammatory Model

Tendon cell response model (Repair and Homeostasis of tendon Matrix)

• Classification

Reactive (Acute)

Degenerative (Chronic)

Reactive on Degenerative (Acute on Chronic)

Tendon Disrepair (Atrophy/Rupture)

Pathophysiology: Mechanical

• Cumulative damage or acute overload (tension, compression, friction) exceeding physiologic

capacity of tendon to heal, resulting in injury, inflammation and poor repair (first 4 weeks).

• Normal collagen fibers can't tear in vivo without severe alterations in non-collagenous matrix.

• Collagen tearing does not occur as a result of acute loading but as a result of fiber kinking

and disorganization of collagenous fibers as a result of chronic physiologic changes.

• Treatments have included Physical exercise, injecting blood products/sclerosing agents and

modalities (ultrasound shock wave therapy) with mixed results.

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Pathophysiology: Tendon Cell Response

• Tenocyte responsible to maintain extracellular matrix in response to load/environment.

• Changes in tendon load will be sensed and result in cascade of response

Cell activation, proteoglycan expression and change in collagen type (type III)

Explains tendon adaptation to compressive loads, direct blows, or chronic overload

• Understimulation of the tendon cell due to lack of loading may play a role in

degenerative tendinopathy Degenerative tendons have mechanically silent regions

unresponsive to load (limited reversibility of degenerative tendinopathy).

• Adaptation: Proliferation of type 3 collagen fibers, disorganization of collagen fibers,

increase in vascularity, increase sensory nerves, edema extracellular matrix, breakdown

of tissue and cell death.

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Pathophysiology: Inflammatory • Inflammatory changes are frequently observed in pathologic tendinopathy and are typically

associated with autoimmune conditions such as RA with Ig and leukocyte mediated inflamm.

• Inflammatory Tendinopathy associated metabolic diseases such as diabetes, gout, obesity,

hypercholesterolemia have a different inflammatory mechanism with less leukocyte infil.

• Inflammatory mediators cause a cascade of inflammation in the extracellular matrix.

Metaloproteinases (MMP) – Maintains Homeostasis of Proteoglycans. Repetative tendon

loading causes ↑proteoglycan level, leading to edema and swelling.

Proinflammatory cytokines release leads to hypoxia, cell death, mucoid degeneration,

disorganized collagen fibrils, ↑neovascularization, ↑neurogenesis, impaired cell signaling.

Inflammatory Mediators Associated with Inflammatory Tendinopathy: IL-1, IL -6, TNF,

Cox-1, Cox-2, Prostaglandin E2, cytokines, c-reactive protein, platelet derived GF.

Normal Tendon

Degenerative Tendinopathy

Reactive on Degenerative Tendinopathy

Adaptation

Strengthen

Optimized Load

Reactive Tendinopathy

Excessive

Load Modified Load

Mechanically Compromised Tendon

Unloaded

Optimized

Load

Excessive Load

Individual Factors

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Clinical Presentation

• Younger (15-25 years)

• Rapid onset, generally related to load

• Load substantially exceeds tendon’s previous exposure

• Easily aggravated by exercise, slow to Heal

PAINFUL

LESS COMMON

• Older (30-60 years)

• Long History of Minimal Symptoms

• Variable Swelling And INFLAMMATION

• Tendon Unloading or Atrophy

NOT PAINFUL

COMMON

• Older Adult(30-60 years)

• Past history With Load Related EXACERBATION

• Onset After Overload

• Variable Swelling/Inflamm.

• Increased Pain After Load

PAINFUL

VERY COMMON

REACTIVE REACTIVE on DEGENERATIVE DEGENERATIVE

Inflammatory Tendinopathy: Diabetes

• Inflammatory changes caused by Advanced Glycation End Products, which cause cross

linking of collagen fibers, increased collagen density with disorganized fibrils, increased

inflammatory mediators, decreased fibroblast growth factors, and poor tendon repair.

• Inflammatory mediators cause a cascade of inflammation combined with microvascular

disease and hypoxia leading advanced tendon degeneration.

• Common rheumatologic presentations of Diabetes:

Upper Extremity – Cheiroarthropathy (hands), Duytrens Contracture (hands), Trigger

Finger, CTS (11-25%), Symp Rotator Cuff Tear. (10-15%), Adhesive Capsulitis (10-20%).

Lower Extremity – Achilles Tendinopathy, Plantar Fascitis, Foot/Ankle Tendinopathy.

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Inflammatory Tendinopathy: Gout

• Inflammatory changes caused by deposition of Uric Acid crystals in the extracellular matrix

of tendons and ligaments to cause inflammatory cascade, increased proteoglycans, collagen

disruption, neovascularization and inhibited cellular healing.

• Common Tendinopathy Presentations of Gout:

Upper Extremity – Medial and Lateral Epicondylitis (Enthesopathy), Rotator Cuff

Tendinopthy, Wrist Tendinopathy.

Lower Extremity – Achilles Tendinopathy, Prepatellar Tendinopathy, Plantar Fascitis, Foot

and Ankle Tendinopathy (Most common presentation is synovitis of Foot, ankle or knee).

Inflammatory Tendinopathy: Hypercholesterolemia and Obesity

• Inflammatory mechanism of cholesterol caused by deposition of ox-LDL in the extracellular

matrix and tenocytes of tendons and ligaments causing foam cells. Leads to inflammatory

cascade, collagen disruption, cell death and inhibited cellular healing (Familial Hyperchol).

• Obesity is associated with increased stress load on joints of lower extremity combined with

metabolic inflammation causing chronic tendinopathy. Obesity associated with insulin

resistance, inflammatory mediators (PG E2, TNF, LTB4), and specific peptides from adipose

tissue (chemerin, lipocalin 2, leptin, adiponectin) that affect MMP and alter tendon healing.

• Common Tendinopathy Presentation of hypercholesterolemia: Primarily Achilles Tendon.

• Common Tendinopathy Presentation of Obesity: Load bearing tendons of the lower extremity

(Achilles Tendinopathy, Prepatellar Tendinopathy, Plantar Fascitis, Foot/Ankle Tendinopathy).

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Inflammatory Tendinopathy: Medication causes

• Statin Induced Tendinopathy: Occurs in conjunction with Statin induced Myalgias. Primarily

affects Achilles tendon (shoulder and lateral elbow reported). Median onset at 10 months and

estimated at incidence of 2% of subjects studied. 30% of cases result in rupture Pathophysiology

of Tendon inflammation is unknown.

• Fluoroquinolones: Common. Primarily affects Achilles tendon (90% cases) and 50% of cases are

bilateral. Median onset at 8 days (to 6 months) and estimated at incidence of 2% of subjects

studied. 40% of cases result in rupture (elderly at ↑ risk) Pathophysiology of Tendon

inflammation is unknown. Patients prescribed both fluoroquinolones and corticosteroids had a

46-fold greater risk of Achilles tendon rupture (Khaliq and Zhanel, 2003).

• Corticosteroids: Impairs local collagen synthesis leading to atrophy and decreased strength.

Avoid injecting corticosteroids adjacent to weight bearing tendons (Achilles, Patellar, Bicep or

Tricep Tendons), especially in the presence of tendinopathy.

Treatment of Tendinopathy: Medication NSAIDS: Non-selective Cox inhibitors reduce PG’s and arachidonic acid causing beneficial

reduction in inflammation. Evidence shows short term benefit first month of treatment.

Injected Corticosteroid: Highly effective for focal chronic tendinopathy (shoulder, elbow, foot

and ankle). Reduces pain and swelling in short term, but risk of long term relapse.

Injected Hyaluronic Acid: Has shown benefit for lateral elbow and patellar tendinopathy by

reducing inflammation, improving collagen synthesis and reducing cell proliferation.

Injected Platelet Rich Plasma (PRP): Stimulates healing via collagen synthesis, cell proliferation

and chemotaxis. Animal models have been very promising but Human studies are mixed.

Experimental:

• Anti Tumor Necrosis Factor Agent (Adalimumab) – one study w/ benefit Chronic Achilles Tend.

• Substance P and Glutamate Inhibitors

• Nerve Growth Factor Inhibition

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Treatment of Tendinopathy: Diet

Hydration: Essential to maintain elasticity of aging connective tissue.

Low Glycemic Diet: Maintain peak metabolism and avoid glycosylation of connective tissue.

Healthy Fats: Improves lipid metabolism with proper maintenance of healthy lipoproteins.

Avoid Oxidized Lipids: Highly pathogenic (ox-LDL) ↑ cellular aptosis and ↓ collagen regeneration.

Balanced Protein: Leucine/Glycine/Lysine are essential components for hydroxyproline/collagen.

Natural Foods: Low glycemic diet with foods containing anti-oxidants.

Treatment of Tendinopathy: Supplements Vitamin C - Antioxidant vitamin and critical cofactor for two critical stages of collagen synthesis. Improved

tendon healing animal studies.

Vitamin D - Regulates bone metabolism and acts on tenocytes to increase collagen synthesis. Epidemiology

studies have demonstrated correlation between vitamin D deficiency and tendon injury.

Amino Acids - Leucine,Glycine and Lysine are essential components for hydroxyproline and improve

synthesis and stability of collagen fibers needed for tendon recovery.

Glucosamine and Chondroitin - Shown to preserve function of connective tissue. In vitro improvement of

collagen synthesis of tenocytes. Animal studies showed improved tendon strength with less inflammation

after recovery from tendon injury.

Curcumin (Tumeric) - Powerful anti-oxidant, anti-inflammatory (↓ MMP), improves cellular regeneration.

Animal studies showed improved strength of collagen fibers.

Bromelain - Stimulates healing via collagen synthesis, cell proliferation and chemotaxis. Animal models have

been very promising but Human studies are mixed.

Methylsulfonylmethane (MSM) and Boswellic Acid - Decrease inflammation and oxidative stress at cellular

level. Small studies have shown beneficial recovery from muscle and tendon injuries.

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Exercise Concepts to Consider When Treating Tendinopathy

• Tendons do not like compression or fast stretch-shortening cycle.

• Healthy tendons are highly responsive to mechanical loading (↑ Load → ↑ Strength).

• Chronic/habitual loading is needed for tendon adaptation. Training program

applies a high load intensity over long duration (>12 weeks) for collagen synthesis.

• PT Protocols: Isometrics, Eccentrics (Gold Standard), HSR Heavy Slow Resistance.

PT Protocol Strengthening Protocol

• Isometric exercise : 5 sec x 5 reps with one minute rest intervals – Early Phase/Chronic

• Eccentric Exercise 3x15 Reps, unilateral, slow 3 second contraction, 2 minute rest

between sets, 5 minute rest between exercises, Twice daily – Good for Healing Reactive

• Heavy Slow Resistance Exercise: 3 times/week, 3 second concentric and eccentric

contraction - Increase in collagen production for late phase of treatment.

Incorporate the correct protocol and get

the patient to commit to long term

exercise program (at least 12 weeks).

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PT Protocol

Modalities:

• Shock Wave Ultrasound

• Massage

• Stretching

• IASTM – Graston Technique

• Dry Needling

• Theraguns

http://blogs.bmj.com/bjsm/2013/07/23/tendinopathy-rehab-progression-part-1/

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Review • Understand mechanism of injury and always consider metabolic inflammation as a

contributing factor in your differential.

• Never hurts to run labs before coming to a diagnostic conclusion.

• LABS: HgB a1c, sed rate, uric acid, lipid panel, ANA, RF.

• Always be cognizant of medication induced tendinopathy (do no harm).

• Work with physical therapist to implement treatment with proper timing.

• Dietary intake is extremely important to address with patients.

• Educate patients on nutritional supplements, modalities and home exercises.

• Help patients to be creative regarding treatment.

• Educate and motivate patients to improve health and stay active!

Case Study #1

• Mechanism: 36-year-old Russian male bumped his right foot on a dresser 3 days prior and had mild pain over the medial and dorsal foot without limp. Following day he noticed increased pain and swelling and next day the foot swelled with warmth and erythema causing severe tenderness and difficulty ambulating.

• History of similar pain and swelling over his right medial foot 3 years ago. He jumped down on his right foot causing a delayed onset of pain and swelling. She saw an orthopedic surgeon in Arizona placed his foot into a cast with suspicion of a nondisplaced fracture. He eventually had an MRI of the right foot performed in 2015 revealing tendinopathy and swelling.

• Exam: Full passive motion. Pain with resisted ankle inversion. Swelling and joint effusion noted over the anterior and medial ankle with inflammation. Tenderness, inflammation and swelling over the medial foot adjacent to the navicular tubercle at the insertion of the tibialis posterior tendon. Ambulating with antalgic gait.

• Lab Testing reveals Uric acid 8.7, sedimentation rate 2

• MRI Right Foot reveals accessory navicular with prominent bone marrow edema adjacent to the navicular tubercle with acute inflammation and moderate tendinopathy TP tendon. Soft tissue edema over medial foot.

• Diagnosis: 1) Right foot contusion. 2) Hyperuricemia/gout. 3) Right foot tibialis posterior tenosynovitis.

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Case Study #2

• Mechanism: 38-year-old hispanic female describes progressive onset of pain and stiffness over her bilateral hand and wrist while packing ice cream at work over 10 days. Over the past three days, she has noticed stiffness and pain over her bilateral shoulder performing functional activity at work. She denies numbness or weakness. She has been working as an ice cream packer for 3 months.

• Medical History: Obesity.

• Exam: Full passive motion with pain abduction and external rotation. Tenderness over the right anterior glenohumeral joint. Pain crossover test, Hawkins test, and external rotation apprehension test.

• Lab Testing Hemoglobin A1c 5.8 (mild elevation), uric acid 4.3, and sed rate 22 (mild elevation).

• Imaging: X-ray bilateral wrist and shoulder negative.

• Diagnosis: 1) Bilateral shoulder/wrist inflammatory tendinopathy. 2) Insulin resistance.

• Treatment: I discussed the diagnosis of insulin resistance and metabolic inflammatory tendinopathy with recommendation for low-carb diet and 70-pound weight loss, patient was educated on home exercise with stretching and heat, Utilize Aleve as needed for pain and inflammation.

Case Study #3

• Mechanism: 37-year-old hispanic female was lifting a mattress to tuck in sheets and as she lifted the mattress she felt a sharp pain over her right anterior shoulder. She was able to continue working for approximately four-and-a-half hours and finished her shift. That night, she noticed increased pain and stiffness. History of a work-related right shoulder injury lifting a mattress 2 years prior.

• Medical History: Insulin resistance, hypertension, and depression.

• Exam: Passive range of motion with abduction to 160 degrees, external rotation to 90 degrees, and internal rotation to 80 degrees with pain and stiffness in all planes of motion. Tenderness over anterior and posterior subacromial and glenohumeral joint. Pain with Jobe’s test, crossover test, Hawkins test, active compression test and O’Brien’s test.

• Imaging: MRI arthrogram right shoulder reveals minimal acromioclavicular arthropathy with chronic tendinopathy noted over the distal supraspinatus and infraspinatus tendon.

• Diagnosis: 1) Mild rotator cuff strain. 2) Chronic right shoulder tendinopathy 3) Insulin resistance.

• Treatment: Educated on daily stretching and functional exercise with heat, educated on a low glycemic/low inflammatory diet, Diclofenac 75 mg BID.

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Case Study #4

• Mechanism: 34-year-old morbidly obese male stepped down hard on left foot from a two foot platform. He describes aching pain with pins and needles sensations over his left heel which worsens with walking. Over course of one week pain and swelling worsened with lump over his Achilles tendon.

• Medical History: Obesity and hyperlipidemia.

• Exam: Passive range of motion full. Left heel with mild tenderness firm lump over distal Achilles tendon. Ambulating with antalgic gait.

• Imaging: X-ray left ankle is negative.

• Lab Testing: Hemoglobin A1C at 12.1(elevated) and uric acid at 9.1 (elevated).

• Diagnosis: 1) Left heel mild Achilles tendon strain. 2) Chronic Achilles tendonopathy 3) Uncontrolled diabetes and gout with obesity and hyperlipidemia.

• Treatment: Educated on daily stretching and functional exercise with heat, educated on a low glycemic /low inflammatory/low UA diet, Ibuprofen TID, initiate treatment for diabetes/gout/↑ lipid/obesity.

Case Study #5

• Mechanism: 46-year-old caucasion female was cleaning a bathroom sink and she hit her right thumb against the edge of the sink causing pain on the dorsal right thumb. Able to continue working with stiffness in her thumb. She woke up the next morning with severe pain, swelling at volar aspect of her thumb with difficulty bending her thumb and gripping.

• Medical History: Type 2 diabetes and hypercholesterolemia.

• Exam: Right thumb limited motion MCP joint with pain on flexion to 30 degrees. Tenderness and swelling over the flexor pollicis tendon retinaculum adjacent to the anterior MCP joint.

• Imaging: X-ray right thumb is negative.

• Diagnosis: 1) Mild right thumb contusion 2) Right trigger thumb/flexor tendinopathy 3) Type 2 diabetes

• Treatment: Injection right thumb flexor tendon sheath, range of motion/stretching, heat, educated on a low glycemic diet, limited use of brace at bedtime, Ibuprofen TID.

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Thank You!

email: vklausner@cohmedical.com

Phone: 702-474-4454

Victor Klausner D.O. Family Practice/Sports Medicine/Occupational Medicine

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