Special RepoRt Clinical and imaging assessment of peripheral enthesitis in ankylosing spondylitis Enthesitis, defined as inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis and joint capsules, is a hallmark of ankylosing spondylitis. The concept of entheseal organ prone to pathological changes in ankylosing spondylitis and other spondyloarthritis is well recognized. The relevant role of peripheral enthesitis is supported by the evidence that this feature, on clinical examination, has been included in the classification criteria of Amor (heel pain or other well-defined enthesopathic pain), European Spondiloarthropathy Study Group and Assessment in SpondyloArthritis International Society for axial and peripheral spondyloarthritis. Nevertheless, the assessment of enthesitis has been improved by imaging techniques to carefully detect morphological abnormalities and to monitor disease activity. 1 Keywords: ankylosing spondylitis n clinical assessment n enthesitis n MrI Antonio Spadaro* , n spondyloarthritis n ultrasound Fabio Massimo Perrotta1, In primary ankylosing spondylitis (AS) the fre- has proven to be a highly sensitive and nonin- Alessia Carboni1 quency of peripheral enthesitis has been found vasive tool to assess the presence of enthesitis, & Antongiulio Scarno1 to be between 25 and 58% [1], however, the real characterized by hypoechogenicity with loss 1Dipartimento di Medicina Interna e prevalence of this feature depends on the type of tendon fibrillar pattern, tendon thickening, Specialità Mediche – UOC di of assessment (i.e., clinical, imaging or histo- local calcifications, enthesophytes and bony ero- Reumatologia – “Sapienza” – Università di Roma – Azienda logical). Peripheral enthesitis can be revealed by sions. Moreover, the use of power Doppler US Policlinico Umberto I, Viale del clinical findings, such as localized pain, tender- (PD) allows the detection of abnormal vascu- Policlinico 155, 00161, Rome, Italy *Author for correspondence: ness and swelling, but there are no definite clini- larization of soft tissues, entheses, tendons and [email protected] cal criteria for the diagnosis of this manifesta- joints [7,8]. Recently, PET/CT scans have been tion, which may even be asymptomatic. Thus, considered as a new tool to assess enthesitis in the clinical assessment of enthesitis has a low spondyloarthritis (SpA) [5]. sensitivity, may often underestimate the pres- ence of enthesitis, and requires a careful diag- Clinical assessment of enthesitis nostic work-up with other joint and soft tissue Many clinical indices to assess enthesitis in AS disorders, such as fibromyalgia[2–4] . Histological and other SpA have been employed in previ- examination of the enthesis is the potential gold ous years. A scoring system was developed by standard for the evaluation of enthesitis, but is Mander et al., based on the patient’s response to rarely obtained owing to ethical and practical firm palpation over 66 entheses. The Mander constraints. Imaging techniques include con- Enthesis Index (MEl) was significantly corre- ventional radiography, bone scintigraphy, MRI, lated with visual analog scale for pain and stiff- ultrasonography (US) and, recently, PET/CT ness, but it was time consuming [9]. The modi- scans [1,5]. Conventional radiography may show fied MEI, however, considered only 17 entheses erosions and bone proliferation changes (ill in the spine and lower limbs [10]. defined and finely speculated), but only in more In 1995, the ‘Assessment in Ankylosing advanced phases [1]. Technetium-99m methylene Spondylitis’ working group selected a core set diphosphonate scintigraphy has been shown to for outcome assessment in AS, including physi- be a sensitive indicator of heel enthesitis, but cal function, pain, spinal mobility, patient global its specificity has not been determined. MRI assessment, peripheral joints/enthesis assessment, may show the swelling of the enthesis and the x-ray of the spine and acute phase reactants [11], peritendinous soft tissue, the distension of adja- but there was no specific instrument to measure cent bursae by fluid collection and edema of the enthesitis. Braun et al. used an enthesis index bone near the insertion. On the other hand, the (Berlin index) in a study on infliximab in AS, study of entheses with MRI is limited owing to composed of 12 entheses that are reported to be its reduced availability and high costs [6]. US commonly affected in the inflammatory process part of 10.2217/IJR.12.26 © 2012 Future Medicine Ltd Int. J. Clin. Rheumatol. (2012) 7(4), 391–396 ISSN 1758-4272 391 Special RepoRt Spadaro, Perrotta, Carboni & Scarno Clinical & imaging assessment of peripheral enthesitis in ankylosing spondylitis Special RepoRt in AS [12]. This index included the iliac crest, reproducible and correlated with disease activity the great trochanter of the femur, the medial and functional index [16]. and lateral condyle of the femur, the proxi- mal insertion of Achilles tendon and insertion Imaging assessment of enthesitis of the plantar fascia to the calcaneus. In this Historically, the radiographic features of enthesi- study, the enthesitis index showed a significant tis have played a pivotal role in defining enthesi- change after anti-TNF treatment. In 2003, tis lesions of SpA. Conventional radiography can Heuft-Dorenbosch et al. validated a new clini- show bone erosions and new bone formations cal index to assess enthesitis involvement in AS: at sites of insertion of tendons and ligaments the Mastricht Ankylosing Spondylitis Enthesitis [17]. Frequency of erosions at the insertion of Score (MASES). The MASES considers the pal- the Achilles tendon and enthesopathy in both pation of only 13 entheseal sites (e.g., first cos- the Achilles and plantar fascia insertions were tochondral joint, seventh costochondral joint, observed radiographically in 33–58% of cases [18]. posterior superior iliac spine, anterior superior Entheseal radiographic changes are the result of iliac spine, iliac crest, fifth lumbar spinous pro- chronic inflammation that led to an irreversible cess and proximal insertion of Achilles tendon). damage. Thus, radiography is not useful in iden- The MASES correlated with the MEI and with tifying bone lesions at an early stage and does not the Bath Ankylosing Spondylitis Disease Activity provide information regarding the status of soft Index, and seemed to be a good alternative to the tissues. However, it may be useful in differential MEI with much better feasibility [13]. Gladman diagnosis between the various forms of enthe- et al. assessed four entheseal sites bilaterally (rota- sopathy: a study by Gerster on heel pain showed tor cuff insertion at the shoulder, tibial tuber- how the bony erosions are present particularly osity at the knee, Achilles tendon and plantar in patients with rheumatoid arthritis (RA) and fascia insertions in the calcaneus) to determine AS, while, generally, the erosions are not present the reliability in a cohort of psoriatic arthritis in patients with osteoarthritis. Similarly, in the (PsA) patients. In this study, authors only found two patient groups enthesophytes had different good interobserver agreement for the detection characteristics: linear and regular in patients with of plantar fascitis [14]. Healy and Helliwell devel- osteoarthritis; irregular and ill-defined margins oped the Leeds Enthesitis Index in a cohort of in patients with AS or RA [19]. Several studies 28 PsA patients based on bilateral palpation of considered bone scintigraphy in the diagnosis three entheseal sites (lateral epicondyle, medial of sacroiliitis and to assess lower back pain, but femoral condyle and Achilles tendon insertion). assessment of peripheral enthesitis with this tech- They showed strong correlation with measures of nique is rarely used. Technetium-99m methylene disease activity; furthermore, the enthesis index diphosphonate scintigraphy has been shown to be showed a significant change after 6 months of a sensitive indicator of heel enthesitis in a study on therapy with disease-modifying antirheumatic 38 consecutive patients with Reiter’s syndrome, drugs. The authors reported that the MEI, Leeds but its specificity was not determined[20] . Enthesitis Index and Berlin index were able to In recent years, MRI has played a key role not distinguish between patients with active disease only in early diagnosis of axial SpA [21], but also and those without active disease as defined by the in the assessment of peripheral enthesitis. In fact, Disease Activity Score. This finding suggests that MRI has a higher sensitivity compared with other these measures relate to an assessment of inflam- radiological modalities and may show swelling mation on a more general scale and, probably, of the enthesis and the peritendinous soft tissue, represent localized inflammation at the enthe- distension of adjacent bursae by fluid collection, seal points [15]. Recently, Maksymowych et al. erosions, enthesophytes and bone edema near the validated a new enthesitis index in AS patients: insertion [22]. MRI bone edema can be detected the Spondyloartrhritis Research Consortium at the entheseal and subchondral level, but of Canada enthesitis index, which is based on diaphyseal involvement seems relatively specific palpation of eight entheseal sites (great trochan- to PsA [23]. Nevertheless, bone edema is not spe- ter, quadriceps tendon insertion on the patella, cific for SpA. In fact, McGonagleet al. reported inferior pole of patella, Achilles