Enthesitis

 Enthesitis: Recognition, Clinical Associations, and Management

Introduction

Enthesitis refers to inflammation at the entheses - the sites where tendons, ligaments, fascia, or joint capsules insert into bone. It's a hallmark feature of spondyloarthritides but can be seen in various rheumatological and non-rheumatological conditions. This review examines the common sites of enthesitis, their clinical recognition, associated conditions, and current management approaches.

Pathophysiology

Entheses are specialized structures designed to dissipate mechanical stress. They consist of:

Fibrocartilaginous transition zones

Adjacent synovium and bursa

Surrounding adipose tissue

Associated bone marrow

The "enthesis organ" concept recognizes these structures function as an integrated unit. Inflammation may result from:

Mechanical stress triggering an inflammatory response

Immune dysregulation, particularly involving IL-23/IL-17 axis

Genetic predisposition (especially HLA-B27)

Microbial triggers (gut microbiome dysbiosis)

Common Sites of Enthesitis

Lower Extremity

Achilles tendon insertion - posterior calcaneus

Plantar fascia insertion - inferior calcaneus

Patellar tendon insertions - inferior patella and tibial tuberosity

Quadriceps tendon insertion - superior patella

Iliac crest - gluteal muscle attachments

Greater trochanter - gluteal tendons

Upper Extremity

Lateral epicondyle - common extensor tendon

Medial epicondyle - common flexor tendon

Supraspinatus insertion - greater tuberosity of humerus

Axial Skeleton

Anterior chest wall - costochondral and sternoclavicular junctions

Spinous processes - interspinous ligaments

Iliac crests - abdominal muscle attachments

Pubic symphysis

Clinical Recognition

Symptoms

Localized pain at insertion sites

Pain exacerbated by activity and tension on the affected tendon/ligament

Morning stiffness at the site

Decreased range of motion in adjacent joints

Physical Examination

Localized tenderness on palpation at insertion sites

Potential swelling or erythema

Pain with resistance testing of the involved muscle-tendon unit

Decreased flexibility

Standardized Assessment Tools

Leeds Enthesitis Index (LEI) - examines 6 sites (bilateral lateral epicondyles, medial femoral condyles, Achilles tendon insertions)

Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index - 16 sites

Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) - 13 sites

Clinical Associations

Spondyloarthritides

Ankylosing Spondylitis (AS) - predominantly axial involvement

Psoriatic Arthritis (PsA) - affects 30-50% of patients

Reactive Arthritis - following gastrointestinal or genitourinary infections

Enteropathic Arthritis - associated with IBD

Undifferentiated Spondyloarthritis

Other Rheumatological Conditions

Rheumatoid Arthritis - less common but can occur

Systemic Lupus Erythematosus - rare

SAPHO Syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis)

Non-Rheumatological Conditions

Mechanical Overuse - sports or occupation-related

Metabolic Disorders

Diabetes mellitus

Hyperuricemia/gout

Hyperlipidemia

Fibromyalgia - can mimic or coexist with enthesitis

Osteoarthritis - insertional tendinopathy with mechanical causes

Diagnostic Approach

Imaging Modalities

Ultrasound - first-line imaging tool

Findings: hypoechogenicity, thickening, erosions, enthesophytes, Doppler signal

Advantages: accessible, dynamic, no radiation

Magnetic Resonance Imaging (MRI)

Findings: bone marrow edema, soft tissue inflammation

Advantages: superior for deep entheses, detects early changes

Radiography

Limited for early detection

Useful for chronic changes: erosions, enthesophytes

Laboratory Assessment

Acute phase reactants (ESR, CRP) - often normal in isolated enthesitis

HLA-B27 testing - relevant for spondyloarthritis diagnosis

Rheumatoid factor and anti-CCP antibodies - usually negative

Consider infectious workup if reactive arthritis suspected

Management Approaches

Non-Pharmacological

Physical Therapy

Stretching and strengthening exercises

Correction of biomechanical abnormalities

Proper footwear with orthotic support

Activity Modification

Reduction of mechanical stress

Ergonomic adjustments

Load management in athletes

Local Measures

Ice/heat application

Bracing or taping when appropriate

Pharmacological

First-Line

NSAIDs - both topical and oral

COX-2 inhibitors for those with GI concerns

Local Therapy

Corticosteroid injections - ultrasound-guided when necessary

Caution: potential tendon weakening with repeated injections

Disease-Modifying Antirheumatic Drugs (DMARDs)

Conventional DMARDs (methotrexate, sulfasalazine, leflunomide)

Limited efficacy for isolated enthesitis

Biologic Therapies

TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab)

IL-17 inhibitors (secukinumab, ixekizumab)

IL-23/IL-12 inhibitors (ustekinumab)

JAK inhibitors (tofacitinib, upadacitinib)

Management Based on Underlying Condition

SpA-related enthesitis - escalate to biologics if inadequate NSAID response

Mechanical enthesitis - focus on physical therapy and biomechanical correction

Metabolic causes - address underlying disorder

Monitoring and Prognosis

Regular clinical assessment using standardized enthesitis indices

Periodic imaging in selected cases

Evaluation of impact on function and quality of life

Consider enthesitis as a predictor of disease severity in SpA

Emerging Therapies and Future Directions

Novel biologics targeting specific inflammatory pathways

Personalized therapy based on genetic and biomarker profiles

Advanced imaging for early detection and monitoring

Biomechanical interventions for prevention

Conclusion

Enthesitis represents a key clinical feature in spondyloarthritides and other rheumatic conditions. Proper recognition requires thorough clinical examination and appropriate imaging. Management should address the underlying cause while providing symptomatic relief. A multidisciplinary approach involving rheumatologists, physiatrists, orthopedists, and physical therapists offers the best outcomes for patients with enthesitis.