Enthesitis detection by ultrasound: where are we now? M.-A. D’Agostino Rheumatology Department, APHP, Hôpital ABSTRACT and the Group for Research and As- Ambroise Paré, INSERM U1173, Labex Over the last 25 years, ultrasound has sessment of Psoriasis and Psoriatic Ar- Inflamex, Université Versailles St-Quentin been used to evaluate involvement at thritis (GRAPPA) have recommended en Yvelines, Boulogne-Billancourt, France. the entheses in spondyloarthritis (SpA) enthesitis as one of the outcome do- Maria-Antonietta D’Agostino, MD, PhD and psoriatic arthritis (PsA). Several mains for assessing disease activity and Please address correspondence to: studies have been reported indicating response in both axial and peripheral Prof. Maria-Antonietta D’Agostino, its value in detecting active inflamma- SpA and PsA (7, 8). The introduction Service de Rhumatologie tion at entheseal sites using both gray Université Versailles St-Quentin of new pharmacological therapies with en Yvelines, scale and Doppler findings. This review improved trial designs incorporating Hôpital Ambroise Paré, APHP, explores the recent literature and ap- entheseal outcomes, magnetic reso- 9 Avenue Charles de Gaulle, praises the current knowledge and the nance imaging (MRI) and ultrasound, 92100 Boulogne-Billancourt, France. unmet needs of enthesitis detection by as well as increased use of these sensi- E-mail: ultrasound in the management of both tive modalities in research and clinical [email protected] SpA and PsA. practice, also have contributed to rec- Received and accepted on September 10, ognition of a pivotal role of enthesitis in 2018. Introduction both diagnosis and management of SpA Clin Exp Rheumatol 2018; 36 (Suppl. 114): Enthesitis is usually defined as an in- (axial and peripheral) and PsA. S127-S130. flammation of the insertion of tendons, In this context, European League Against © Copyright CLINICAL AND ligaments and capsules into the bone, Rheumatism (EULAR) and GRAPPA EXPERIMENTAL RHEUMATOLOGY 2018. and it is considered a pathological hall- in their management recommendations mark of the spondyloarthritis (SpA) for PsA, have clearly highlighted the Key words: enthesitis, ultrasonography, group of conditions, including psoriatic importance of specific recommenda- ultrasound, power Doppler, arthritis (PsA) (1-3). Recent knowl- tions for predominant entheseal disease. OMERACT, scoring system, edge regarding the function, anatomy Somewhat different in their recommen- spondyloarthritis, psoriatic arthritis and pathophysiology of the enthesis dations, ultrasound evaluation is an ac- (4, 5) has improved our understanding cepted method for detecting enthesitis in of the involvement of this anatomical both sets (8-10). structure in the course of such diseases, The clinical assessment of enthesitis by and has confirmed initial observations physical examination may be challeng- concerning the relevance of enthesitis ing as the tenderness at the entheseal to the pathogenesis and clinical mani- site, is a non-specific finding: presence festations of SpA and PsA. Enthesitis of such tenderness does not always de- is characterised by pain and stiffness at note inflammation, nor does its absence tendon insertions, such as the Achilles exclude enthesitis. tendon, the plantar fascia or the com- Considering the value and importance mon extensor tendon insertion at the of imaging to detect this characteristic epicondyle of the elbow. Clinical as- lesion, the objective of this review is to sessment of enthesitis has been based summarise current knowledge and the traditionally by recognition of tender- unmet needs concerning the use of ul- ness elicited by the palpation of the en- trasound for the detection of enthesitis theseal site. Whereas the prevalence of in diagnosis and management of SpA clinically-detected enthesitis (i.e. pain and PsA. at specific sites) appears to be between 30% and 50% in patients with PsA and Ultrasound of enthesitis where SpA (6), the overall burden of enthesi- we are now? tis might be higher using more sensitive The comprehensive description of ul- tools such as imaging techniques. trasound involvement of entheses in Enthesitis is sometimes the primary SpA patients was made for the first time clinical manifestation of active SpA by Lehtinen and colleagues in 1994 (11, disease. The Assessment of Spondy- 12) and then by Balint and colleagues Competing interests: none declared. loarthritis International Society (ASAS) in 2002 (13). Both authors described, Clinical and Experimental Rheumatology 2018 S-127 Enthesitis detection by ultrasound: where are we now? / M.-A. D’Agostino using grey scale (GS), ultrasound ab- been primarily focused on PsA and on trasound inflammatory activity at the normalities of lower limb entheses in the capacity of ultrasound to enhance Achilles, as well as none of the usual SpA patients, revealing a high frequen- early or differential diagnosis (23). biological parameters (C-reactive pro- cy of asymptomatic findings. Enthesi- Marchesoni and colleagues (24) in a tein and erythrocyte sedimentation tis in GS is characterised by the loss of recent report, expanded on a previous rate) used to evaluate PsA disease. normal fibrillar echogenicity of tendon observation (23) concerning the incre- However, ultrasound structural dam- insertion, especially in the acute inflam- mental value of using power Doppler age was statistically significantly as- matory phase, which appears as hypo- ultrasound to differentiate polyentheso- sociated with age, body mass index, echoic, with an increase in thickness pathic forms of PsA from fibromyalgia regular physical exercise and current and/or intralesional focal changes at the (FM). Sometimes the differential di- use of biological disease-modifying tendon insertion, such as calcific depos- agnosis between the two diseases may anti-rheumatic drugs, suggesting an in- its, fibrous scars, and periosteal changes be difficult, when the only symptom creased prevalence of structural dam- (erosions or new bone formation). The is pain. This is in part due to the fact age with increased duration of disease, latter are commonly seen during chron- that FM tender points may overlap with and increased age. These results, along ic inflammation or in longstanding fo- entheseal sites, particularly when there with those from previous studies, raise cal disease. Additionally, involvement is diffuse enthesitis involvement. In ad- a question of whether inflammatory of the body of tendon, distant from the dition, some PsA patients can present findings should be more weighted than enthesis, and of the adjacent bursae with concomitant FM symptoms to- structural damage in the development may also be observed. gether with active disease. In their first of an ultrasound enthesitis score. The Thus, GS ultrasound permits depiction cross-sectional study, they observed absence of correlation between clinical of both signs of acute and chronic in- that ultrasound findings of enthesitis in and ultrasound evaluation of enthesitis, flammation of the enthesis as well as GS were more frequent in PsA than in as well as the different ultrasound defi- structural damage. In 2002 and 2003, FM, and, furthermore, that power Dop- nitions of enthesitis used, have gener- for the first time, D’Agostino and col- pler findings were exclusively present ated discordant data about the capacity leagues described the capacity of in PsA-detected enthesitis (23). In their of the technique to clearly differentiate Doppler ultrasound, in addition to GS 2018 article they suggest a possible di- between enthesis involvement in SpA changes, to detect active inflammation agnostic algorithm which included the or PsA and in other conditions (28). at entheses as abnormal vascularisa- use of power Doppler ultrasound in This discordance is related to several tion at their bony insertion. They also case of difficulty in making the diag- factors, but in particular to the absence showed the discriminative capacity of nosis (24). Ultrasound of enthesitis also in some of these studies of a clear defi- adding Doppler information in differ- appears useful to detect SpA in ASAS- nition of ultrasound-detected enthesi- ential diagnosis and monitoring of treat- negative patients, as documented by a tis, including which components were ment response (14, 15). recent longitudinal study reported by evaluated for defining its presence Since then, several studies have been Poulain and colleagues (25). (29). Although GS scale components reported supporting the capacity of ul- The incremental value of ultrasound are important for detecting pathology trasound in GS combined with Doppler to detect enthesitis was explored in a at an entheseal site, they cannot be used (in particular, power Doppler) to evalu- study of psoriasis patients with mus- as the only information to differentiate ate enthesitis in SpA and PsA (16-22). culoskeletal complaints by van der between mechanical and inflammatory In a range of studies from those focused Ven and colleagues (26). The authors involvement. on the diagnostic value of the technique reported that adding ultrasound evalu- The absence of discriminant capac- to those exploring sensitivity to change, ation to the clinical assessment of en- ity of GS findings has already been re- all have shown that ultrasound can im- thesitis in these patients from a primary ported (15, 16) and recently confirmed prove the management of the SpA dis- care setting, demonstrated that 36% of by Wervers and colleagues and Lan- eases through