Recognize the signs of enthesitis
The enthesis is the insertion of tendons and ligaments into the surface of the bone, which enables movement and stability.4
Some broaden the definition to include the structures that comprise the entheseal organ.5,6
Recognize the signs of enthesitis
Enthesitis
Inflammation of the entheses. 30% to 70% of patients with psoriatic arthritis (PsA) are reported to have this condition.4,7,8
Distinguishing enthesitis from synovitis
Synovitis
Inflammation of the synovial membrane. It occurs in ~90% of patients with rheumatoid arthritis (RA).4,9
Enthesitis and synovitis can occur separately or concomitantly in PsA; however, enthesitis is a characterizing condition of PsA but not of RA.4,9
Sites where enthesitis most commonly occurs7
Achilles tendon insertion and plantar fascia insertion
Lateral epicondyle and medial epicondyle
Superior border of patella, interior role A patella, and tibial tubercle
Unseen and underestimated
Enthesitis is a hallmark of early PsA. As a distinctive clinical aspect, it helps differentiate PsA from other forms of arthritis.1-3,10
Some studies have suggested that enthesitis may be one of the first symptoms of PsA.1-3
As many as
OF
patients with PsA
present with enthesitis7*
In a multicenter study using power Doppler ultrasound, the presence of enthesitis in patients with PsA was found to be as high as 71%.8
*Defined as at least 1 tender entheseal site out of 18 as measured by the SPARCC enthesitis index.
PsA=psoriatic arthritis; SPARCC=Spondyloarthritis Research Consortium of Canada.
Enthesitis frequently goes undiagnosed
This is due to a variety of complicating factors:
• Absence of external swelling4
• Deep entheseal insertions are difficult to assess with physical examination4
• Entheseal sites are numerous, and enthesitis may be present in sites not usually assessed4
• Can mimic other conditions, such as:
• Mechanical stress injury5
• Tendinitis4
• Synovitis4
involvement
Enthesitis often presents without swelling; however, there are other disease features associated with the presence of enthesitis.
Dactylitis, tenosynovitis, and pain have been independently associated with enthesitis.7
• In fact, one study observed enthesitis at the collateral ligament insertions in 75% of dactylitic digits11
In PsA, enthesitis is linked to nail involvement.12,13
• The fascia of the nail root is an extension of the extensor tendon enthesis13
Patients with PsA who have nail dystrophy may also have enthesitis.14
Enthesitis adds to the burden patients with PsA already face
Patients with PsA experience15-17:
• Functional disabilities
• Increased pain
• Decreased ability to work
Enthesitis magnifies the disease burden of PsA, which underscores the importance of understanding, investigating, and uncovering this condition.7,18
Compared to patients with PsA alone, those with enthesitis have:
tender/swollen joints7
less likely to achieve minimal disease activity (MDA)18*
higher mean HAQ scores18†
higher self-reported pain (VAS)18‡
higher self-reported fatigue (VAS)18§
more likely to miss work18
more likely to have any overall work impairment18
greater chance of radiographic peripheral damage7
greater chance of radiographic axial joint damage with severe enthesitis (higher MASEI scores)7
*Modified MDA (enthesitis) achieved by 41/277 (15%) of patients with PsA with enthesitis vs 193/789 (24%) of those without enthesitis.18
†Mean HAQ (0-3): 0.8 with enthesitis vs 0.6 without enthesitis.18
‡Mean VAS pain (0-100): 44.3 with enthesitis vs 35.1 without enthesitis.18
§Mean VAS fatigue (0-100): 46.7 with enthesitis vs 38.2 without enthesitis.18
HAQ=Health Assessment Questionnaire; MASEI=MAdrid Sonography Enthesitis Index; PsA=psoriatic arthritis; VAS=visual analog scale.
The fuel that feeds enthesitis
PsA is not a mild condition. Erosions can be present even in early stages and the condition frequently progresses to permanent joint damage over time. As an early symptom of PsA, and a complicating factor of the disease, the similar origins of PsA and enthesitis should be recognized.1,3
Many cytokines are activated in the inflammatory process, including IL-17A, IL-22, IL-23, and TNF. IL-17A appears to play a common role in both PsA and enthesitis.4
IL=interleukin; PsA=psoriatic arthritis; TNF=tumor necrosis factor.
Though the process is not completely understood, it is likely that biomechanical stress triggers entheseal inflammation.4,19,20
Inflammation is triggered
Patients with PsA and SpA are thought to have a lower threshold for setting off entheseal inflammation, which allows enthesitis to develop.4
• This resembles an excessive reaction to low-level mechanical strain.4
T-cells respond
Once the entheseal inflammation is triggered, PGE2 forces the blood vessels to widen, while IL-23 activates Th17 cells and other inflammatory cytokines.4,21
IL-17A IL-17A
TNF
IL-22stem cells
Cascade of more inflammation and pain
IL-17A and TNF prompt neutrophil migration and activation.4
• In the enthesis, neutrophils augment the inflammatory response and aggravate pain responses4
• A similar process can be seen in psoriatic plaques, linking IL-17A activation with the effector phase of inflammation4,21
The damage continues
IL-17A and IL-22 trigger the activation and proliferation of mesenchymal stem cells, which in turn signal osteoclasts and osteoblasts, leading to bone erosion and pathological bone formation.4,21
IL=interleukin; PGE2=prostaglandin E2; PsA=psoriatic arthritis; SpA=spondyloarthritis; TNF=tumor necrosis factor.
The tools to uncover enthesitis
Even though it frequently accompanies PsA and is often an early symptom, if you're not seeking out enthesitis, it can be easy to miss. Here's why:
• Enthesitis can mimic symptoms of other conditions such as mechanical injury and tendinitis4,5
• Most of the time there's no swelling, so it's invisible to the eye4
Fortunately, the key to diagnosing enthesitis is already in your hands.
The hands-on approach
LEI, SPARCC, and MASES
The INSPIRE (International Spondyloarthritis Interobserver Reliability Exercise) study compared methods of manual assessment of enthesitis.22
The Leeds Enthesitis Index (LEI) performed similarly to the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index with both indices demonstrating substantial to excellent agreement and performing better than the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) index.22
LEI
Leeds Enthesitis Index
The LEI is a practical and proven tool for the assessment of enthesitis in PsA.22,24
A brief training is enough to put the LEI to use.
A manual examination of 6 points can significantly improve clinical assessments of enthesitis24:
• Left and right lateral epicondyle
• Left and right medial femoral condyle
• Left and right Achilles tendon insertion
A patient's LEI results can be expected to improve with successful treatment of PsA.25
SPARCC
Spondyloarthritis Research Consortium of Canada index
The SPARCC index examines a total of 18 sites, bilaterally24
• Lateral epicondyle humerus
• Medial epicondyle humerus
• Achilles tendon
• Greater trochanter
• Insertion plantar fascia
• Supraspinatus insertion
• Quadriceps insertion patella
• Inferior pole patella
• Tibial tubercle
Agreement between the results of the LEI and the SPARCC index were strong in the INSPIRE study.22,24
MASES
Maastricht Ankylosing Spondylitis Enthesitis Score
The MASES was not found to function as well in PsA as either the LEI or the SPARCC.22
A step-by-step guide to the LEI
Lateral Epicondyle
Left and right25
Find the lateral epicondyle of the humerus at the common extensor origin.26
Medial Femoral Condyle
Left and right25
Find the medial condyle of the femur, superior to the joint line, at the origin of the medical collateral ligament.26
Achilles Tendon Insertion
Left and right25
Find the posterior prominence of the calcaneum at the insertion of the Achilles tendon.26
At each site, exert pressure at the enthesis sufficient to blanch the fingernail (approximately 4 kg/cm2) and assess the presence or absence of tenderness.26,27
Also assess the presence of soft-tissue swelling at the enthesis.26
Examination Points • • •
LEI
SPARCC
MASES
SPARCC
MASES
• Examination Points
• Examination Points
• Examination Points
Ultrasound
Seeing enthesitis with your own eyes
Doppler ultrasound scan showing enthesitis in the Achilles tendon6
Reprinted from Seminars in Arthritis and Rheumatism, 48, Gurjit S. Kaeley et al., Enthesitis: A hallmark of psoriatic arthritis, 2018, with permission from Elsevier.
An international committee used ultrasound to help identify enthesitis by its primary components28:
• Hypoechogenicity
• Increased thickness of the tendon insertion
• Enthesophytes
• Calcifications
• Erosions
• Power Doppler (PD) signal at enthesis
• Bursitis
• Global enthesitis
Ultrasound is the preferred imaging technique for visualization of enthesitis
While MRI and high-resolution CT have been used to assess enthesitis in clinical studies, ultrasound presents a lower-cost, practical alternative. Ultrasound allows for real-time evaluation and assessment of peripheral joints from multiple angles.6,29
• Conventional radiography is limited in its ability to identify early signs of inflammation and soft tissue damage5
• Ultrasound has been found to have advantages as a diagnostic tool for assessing damage29,30
Ultrasound
Advantages and disadvantages vs MRI
• More affordable and more widely available5
• Portable option offers benefit of real-time dynamic examination29
• Operator-dependent technology with poor repeatability, though studies have shown moderate to good interobserver reliability29
• Has been shown to detect entheseal involvement even in early, preclinical stages of PsA5
• More sensitive imaging modality for evaluating damage than for inflammation30
MRI
Magnetic Resonance Imaging
MRI has been a useful tool for identifying the hallmarks of enthesitis, particularly osteitis, which sometimes accompanies peripheral enthesitis.4
Fat-suppressed, fat-saturated, and water-sensitive MRI sequences demonstrate that the extracapsular inflammation of joints quite often represents enthesitis with variable degrees of soft tissue and bone marrow edema.5
Coronal and axial MR T1 fat-saturated sequence plus contrast. These images show severe osteitis with bone edema at the origin of the common extensor.30
Reprinted by permission from Copyright Clearance Center: Springer Nature, Rheumatology and Therapy, Clinical examination, ultrasound and MRI imaging of the painful elbow in psoriatic arthritis and rheumatoid arthritis: which is better, ultrasound or MR, for imaging enthesitis? Clare Groves, et al., Copyright © 2017.
MRI
Advantages and disadvantages vs ultrasound
• Better than ultrasound at imaging deeper structures29
• More sensitive imaging modality for evaluating inflammation than for damage30
• Can be expensive for patients and physicians5
• MRI does not allow contralateral examination and is hampered by the presence of metal artifacts that may interfere with imaging29
• Structures of the entheses have a low signal on conventional MRI5
• While sensitive, differentiating between different etiologies of enthesitis is not always possible31
of patients with PsA are
reported to have enthesitis
Only thorough and accurate diagnosis will reveal the true impact of enthesitis as a destructive force behind PsA.7,8
Until then, the sparks of enthesitis will smolder under the cover of PsA, adding to the substantial burden patients with PsA already experience.
Fortunately, the tools for diagnosis are numerous, ranging from the clinical (SPARCC, LEI, MASES) to imaging (ultrasound and MRI).
Now, more than ever, the tools to uncover enthesitis are in your hands.
