Prospective double-blind study on the value of musculoskeletal ultrasound by dermatologists as a screening instrument for psoriatic arthritis

Abstract

Objectives

This study evaluated musculoskeletal ultrasound (MSUS) use by dermatologists previously trained on a novel handheld, chip-based ultrasound device (HHUD) to screen for early PsA.

Methods

Twelve dermatologists were recruited to screen psoriasis patients for PsA using the novel HHUD in one major hospital in Bonn (Germany) and six private practices in surrounding regions. Patient screening was based on medical history, clinical examination, and the GEPARD questionnaire paired with an MSUS examination of up to three painful joints. All screened patients were then referred to rheumatologists, who determined the final diagnosis. The screening effect of MSUS was assessed according to its sensitivity and specificity before and after its application.

Results

Between 1 October 2020 and 26 May 2021, a total of 140 psoriasis patients with arthralgia participated in this study. PsA was diagnosed in 19 (13.6%) cases. Before applying MSUS, dermatologists’ screening sensitivity and specificity were recorded as 88.2% and 54.4%, respectively, while after applying MSUS the sensitivity and specificity changed to 70.6% and 90.4%, respectively. MSUS led to a change of PsA suspicion in 46 cases, with PsA no longer being suspected in 45 of them.

Conclusion

This study was able to demonstrate that PsA screening using MSUS by previously trained dermatologists can lead to more precise PsA detection and potentially decreased rheumatologist referral rates.

Introduction

PsA is a seronegative, immune-mediated, chronic-progressive inflammatory joint disease. Symptoms include dactylitis, enthesitis, peripheral and axial joint inflammation, and skin and nail psoriasis [1]. Prevalence is ∼2–4% of adults in the Western population [2], and PsA occurs in 20–30% of people with psoriasis [3]. The diagnosis is set according to clinical examination, musculoskeletal ultrasound (MSUS) [4, 5], and Classification Criteria for the Diagnosis of Psoriatic Arthritis (CASPAR) [6–9]. Within 2 years, around 47% of patients acquire radiographic joint erosions, which may result in irreversible damage [10]. As a result, early diagnosis is critical.

In recent years, MSUS has been increasingly used to diagnose PsA due to its high sensitivity and specificity in diagnosis of arthritis and enthesitis. MSUS can detect preclinical manifestations, and several recent publications have highlighted its use as a screening modality [11–14]. Dermatologists play a key role in diagnosis and treatment of psoriasis. Patients with arthralgia and psoriasis are typically examined by their dermatologists first and then referred to Rheumatology, if PsA is suspected. This needs a close interdisciplinary cooperation between Rheumatology and Dermatology, especially in cases of early diagnosis [15, 16]. Due to overburdening of the rheumatological schedule, high referral rates frequently with unspecific symptoms may result in a slowed interdisciplinary diagnostic pathway. An improved PsA suspicion could accelerate this process.

Yet, dermatologists base their suspicion of PsA mostly on medical history, clinical examination and questionnaires, as they do not have the experience or expertise in MSUS to underpin their suspicion. Clinical examination can deliver objective findings, pointing in the correct direction to the diagnostic path. These findings have a high degree of inter-examiner reliability due to the different symptom expression. Backhaus et al. have demonstrated that clinical examination is less sensitive than MSUS or magnetic resonance imaging for detecting arthritis in finger joints [17].

Validated questionnaires are available to screen for PsA. The most common questionnaire in Germany is the German Psoriasis Arthritis Diagnostic Questionnaire (GEPARD), which implies a high sensitivity [18, 19]. The specificity, however, according to clinical experience is rather low. As a result, rheumatologists face a substantial number of referrals from dermatologists, but most referred patients are not diagnosed with PsA.

Given the low specificity of available screening tools, it is uncertain whether MSUS performed by dermatologists after completing a structured MSUS training can influence the accuracy of early PsA diagnosis if a relatively small and inexpensive handheld ultrasound device (HHUD) that can be easily transported to the patients’ bedside is used. To answer this question, we designed and evaluated an MSUS curriculum for dermatologists [20]. The aim of this study was to investigate if trained dermatologists’ MSUS impacts the sensitivity and specificity of early PsA diagnosis by comparing dermatologists’ pre- and post-ultrasound PsA suspicion with the final diagnosis confirmed by rheumatologists.

Methods

This is a prospective double-blind single-centre study that included psoriasis patients suffering with arthralgia between 1 October 2020 and 26 May 2021. Patients underwent a PsA-screening by one of 12 dermatologists, who had been previously trained in MSUS and equipped with an innovative HHUD (Butterfly IQ 6+, Butterfly Network, Inc., Burlington, MA, USA). The screening consisted of medical history (date of psoriasis diagnosis, Psoriasis Activity and Severity Index (PASI), current psoriasis medication, arthralgia and duration of arthralgia), clinical examination (swollen and tender joint count), the GEPARD questionnaire, and MSUS of up to three painful joints. Two suspected diagnoses—one before and one after the MSUS exam—were given, corresponding to a conventional and MSUS-based screening suspicion. All screened patients were then referred to rheumatologists, who determined the final diagnosis. Both screening methods were compared regarding their screening sensitivity and specificity.

Population

The study was focused on adult psoriasis patients who presented to dermatologists with arthralgia in daily practice. Inclusion criteria were age over 18 years, psoriasis diagnosis set by a dermatologist, arthralgia of at least one joint, no PsA diagnosis in the history, and signed informed consent to take part in the study. Exclusion criteria were solely non-fulfillment of any of the inclusion criteria. Laboratory parameters (CRP, RF, CCP antibodies) were extracted from the routine laboratory examination. The ethics committee of University Hospital Bonn approved the study (no. 337/19).

Musculoskeletal ultrasound training

The MSUS training was held between 31 March and 30 September 2020. Only the most sensitive and specific ultrasound planes to detect joint effusion and synovial hyperperfusion were taught. The performance rating of all participants was verified in an Objective Structured Clinical Examination. Using the standard German grading system ranging from 1 (‘excellent’) to 6 (‘insufficient’), the average grade was 2 (‘good’) with a mean of 21.86 points (87.4%) out of 25 points [20].

Dermatological assessment process

Two distinct approaches were employed to test for PsA in psoriasis patients with arthralgia. One was conventional screening, consisting of medical history, clinical examination and the GEPARD questionnaire. A diagnosis of whether a patient is suspected of suffering from PsA was given. A paper clinical report form (CRF) for dermatological clinical assessment was used to document the initial suspicion and all collected findings. The second was an MSUS exam of up to three painful joints was conducted by the dermatologists. The HHUD used by the dermatologists was the Butterfly IQ system version 6+, an innovative chip-based ultrasound probe, generating 6–10 MHz in the MSUS preset. A tablet computer (2020 Apple iPad 9, 10.2-inch display size; Apple Inc., Cupertino, CA, USA) was connected by wire to the HHUD and used as a monitor. The scanning focused on finding joint effusion and synovial hyperperfusion. In cases where at least one of these pathologies was present, the examined joint was considered suspicious and noted accordingly on the CRF. The examined joint was considered unsuspicious if no pathology was found. Finally, a second preliminary diagnosis based on the MSUS findings was given. The only possible suspected diagnoses for pre- and post-ultrasound were presence or absence of PsA. In addition, a PASI [21] value and the current psoriasis medication were recorded for each patient. The CRFs of all patients were sent to the Department of Rheumatology and Clinical Immunology at the University Hospital Bonn for appointment scheduling, independent of the preliminary diagnosis.

Rheumatological assessment process

The two rheumatologists (P.K. and V.S.S.) involved in the following examination process were blinded to the preliminary suspicion determined by the dermatologists. Within 48 h of receiving the CRF, appointments were scheduled. Prior to their consultation, each patient arriving at the rheumatology facility was requested to complete the following questionnaires:

• Patient Health Questionnaire-9 (PHQ-9) to assess the degree of depressive conditions among the included population [22].

• Numerical Rating Scale (NRS) 1–10 quantifying joint, skin and general pain complaints with higher numbers indicating stronger complaints.

Then, each patient was examined by a rheumatologist. The examination consisted of the medical history, clinical examination of all painful joints, and MSUS of up to six painful joints, including those previously examined by the dermatologist. The ultrasound was performed by two experienced musculoskeletal ultrasonographers (DEGUM/EFSUMB level II and III; P.K., 13 years of expertise, and V.S.S., 14 years of expertise) using a GE Logiq S8 XDclear (GE Healthcare, Milwaukee, WI, USA) ultrasound machine manufactured in 2018 with a linear probe of 9–15 MHz range and a hockey stick probe of 8–18 MHz range. The ultrasound planes applied were the standard MSUS planes for each joint defined by the German Society for Ultrasound in Medicine (DEGUM) MSUS section [23].

The PsA diagnosis was made by one of the two rheumatologists. Classification was done using CASPAR criteria [6–9]. Patients diagnosed with PsA were asked to fill out the EULAR Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for clinical practice [24] assessing the PsA’s impact on the patients’ health.

To evaluate the disease activity at the time of diagnosis, Disease Activity Score 28–CRP (DAS28-CRP) [25, 26] and Disease Activity in Psoriatic Arthritis (DAPSA) [27] were calculated. Fig. 1 shows the overall study protocol.

Data collection and analysis

Data were transferred and collected in a specially designed electronic case report form (eCRF) developed by the Department of Rheumatology and Clinical Immunology at the University Hospital Bonn in cooperation with the Institute of Medical Biometrics, Informatics and Epidemiology at the University Hospital Bonn. The software used for this purpose was REDCap (Version 9.5.6.; Vanderbilt University Vanderbilt, Nashville, TN, USA).

Statistical analysis was performed using SAS (Version 9.4; SAS Institute, Cary, NC, USA) and R (Version 4.1.2; R foundation for Statistical Computing, Vienna, Austria). Continuous variables were summarized as means (s.d.). Categorical data were expressed as proportions and compared (if applicable) with Fisher’s exact test. Sensitivity and specificity were determined together with their 95.0% confidence intervals. No confirmatory analysis was planned for the trial.

Results

Patient characteristics

A total of 140 patients (58.6% female) with a mean age of 49.87 years (s.d. 13.58) were enrolled. At the time of inclusion, all patients had psoriasis, for a mean of 14.69 years (s.d. 13.98), and had a mean PASI of 8.54 (s.d. 7.52). Nineteen patients (13.6%) were diagnosed with PsA as final diagnosis by one of the two blinded rheumatologists. The most frequent psoriasis form was psoriasis vulgaris (72.1%). Psoriasis medication was administered to 91.4%, while systemic glucocorticoids were not prescribed to any patients (Supplementary Table S1, available at Rheumatology online). The NRS (1–10) showed moderate severity of skin (n [s.d.] 4.49 ± 2.81) and joint (n [s.d.] 4.70 ± 2.52) complaints, as well as general pain (n [s.d.] 4.84 [2.44]). The PHQ-9 questionnaire indicated that 67.8% (95% CI: 59.4, 75.5%) of the patients could suffer from depressive states, while the overall mean result was 9.2 (s.d. 6.4) out of 27 points. Table 1 shows further population characteristics.

Dermatological screening results

After dermatological pre-ultrasound screening, in 67 (51.2%) cases suspicion of PsA was confirmed, while in 64 (48.8%) cases PsA was excluded. In nine cases, the suspected diagnosis could not be extracted properly due to contradicting CRF specification, which led to an exclusion of these cases in the final screening effect comparison (Fig. 2).

Following MSUS, the preliminary diagnosis was revised in 46 patients, with PsA no longer being suspected in 45 of them. In one initially non-suspicious case, the MSUS led to a PsA suspicion. According to the GEPARD questionnaire, 124 patients achieved 4 or more points, indicating PsA. The mean score for patients without a final PsA diagnosis was 7.6 points, while the mean score for patients with PsA was 7.4 points, yielding a sensitivity of 89.5% (95% CI: 67.0, 99.0%) and a specificity of 10.8% (95% CI: 6.0, 18.0%), respectively.

Rheumatological assessment results

The most frequent final diagnosis among our cohort was osteoarthritis in 47.1% of patients, followed by unspecific arthralgia in 30.7% of them. Additionally, two (1.4%) patients were diagnosed with rheumatoid arthritis and one (0.7%) patient presented with a shoulder impingement syndrome.

The CASPAR criteria indicated a PsA in 66 cases, while only 19 (13.6%) patients were de facto diagnosed with PsA (Fig. 3). Furthermore, the CASPAR criteria showed a sensitivity of 78.9% (95% CI: 54.0, 94.0%) and specificity of 57.8% (95% CI: 49.0, 67.0%).

Comparing the final rheumatological diagnosis to the preliminary diagnoses set by the dermatologists (Fig. 4), the conventional screening achieved a sensitivity of 88.2% (95% CI: 58.1, 94.6%) and a specificity of 54.4% (95% CI: 44.8, 64.1%), while augmented by the MSUS the sensitivity decreased to 70.6% (95% CI: 38.4, 81.9%) and the specificity increased to 90.4% (95% CI: 83.9, 95.6%). The positive predictive value (PPV) before MSUS was 25.4%, while after MSUS the PPV increased to 56.5% (Supplementary Table S2, available at Rheumatology online).

The mean disease activity for the 19 PsA patients measured with DAS28-CRP reached 8.3 (s.d. 8.1) indicating high disease activity. The DAPSA score showed a mean activity score of 16.6 points (s.d. 15.7) indicating moderate disease activity. The subjective impact of disease according to PsAID12 revealed a mean score of 5.1 points (s.d. 2.4) indicating a moderate impact on patients’ life.

MSUS results

The MSUS findings in relation to dermatological and rheumatological examinations are shown in Table 2. In the interest of a better overview only joints examined at least seven times (2.2%) in general are listed in Table 2. In total, the dermatologists examined 317 joints, and 66 thereof were found suspicious. Rheumatologists examined 457 joints, including all joints examined by the dermatologists. The most frequent investigated were the finger and wrist joints; to be more specific, wrist joints, MCP2, MCP3, PIP3, PIP2, CMC and MCP4 accounted for 65.2% of total examined joints. In matched joints the scans performed by dermatologists showed no statistically significant difference regarding the detection of joint effusion and synovial hyperperfusion compared with the final MSUS results collected by rheumatologists.

Discussion

A new PsA screening strategy combining traditional screening (medical history, clinical evaluation and questionnaires) with targeted MSUS performed by dermatologists was developed to examine its value in early PsA diagnosis. Until now, dermatologists’ use of MSUS to test for this inflammatory-joint disease has not been studied. This is the first prospective, double-blind study to investigate with this novel PsA screening approach.

Many recent studies have underlined the importance of early PsA diagnosis and the key role of the dermatologists in this process [11–14]. Unspecific arthralgia occurs in about 50% of psoriasis patients [28]. Due to individual disease expression, it may be difficult to differentiate between inflammatory and non-inflammatory arthralgia. The PsAID12 questionnaire indicated that patients with diagnosis of PsA experience moderate quality of life limitations. Hence, an early PsA diagnosis is crucial to starting targeted therapy as soon as possible.

While the clinical examination has proven to be less sensitive in detection of arthritis than MSUS or magnetic resonance imaging [17], the common screening questionnaire used in Germany, the GEPARD questionnaire, presents a relatively high sensitivity of 89.5%, but the specificity in our trial is low, at 10.8%. Because of this low specificity, patients are routinely referred to rheumatologists, although only a small fraction will be diagnosed with PsA, resulting in a large number of referrals with extended waiting times, which can lead to permanent joint damage after only 6 months [29]. Within our cohort, 124 out of 140 patients were suspected of PsA based on the GEPARD questionnaire, although only 19 (13.6%) patients were de facto diagnosed with PsA. This questionnaire combined with clinical examination and medical history led to a screening sensitivity and specificity of 88.2% and 54.4%, respectively. Yet, the specificity of conventional screening was higher compared with the GEPARD questionnaire solely, which is still dissatisfying.

MSUS, however, has been shown to be a sensitive and specific tool for detecting changes in soft tissue, superficial bone and cartilage in inflammatory arthropathies. The possibility of scanning dynamically at the bedside and its non-invasive and inexpensive characteristics distinguish this imaging modality from others (e.g. radiographs, magnetic resonance and fluorescence optical imaging). Therefore, recent literature emphasized its high value in the diagnosis of PsA [30]. Nevertheless, the deployment of MSUS by dermatologists to screen for PsA has never been investigated in literature.

In order to carry out this investigation we faced two major challenges. Firstly, there was no validated MSUS training for dermatologists. Secondly, none of the dermatologists working in private practice possessed an ultrasound machine. To proceed with the present study, we developed and validated a specially designed MSUS course for dermatologists—the MUDE protocol [20]—and equipped the trained dermatologists with innovative and inexpensive portable ultrasound devices. These devices have been successfully used in several studies focused on ultrasound education, vascular and cardiac ultrasonography [20, 31–33]. Only one study investigated the performance of this new system in 32 arthritis patients [34].

The MSUS rating of 241 joints scanned by both the dermatologist and rheumatologist within our study protocol showed no statistically significant difference in the detection of joint effusion and/or synovial hyperperfusion. Trained dermatologists seem to be capable of conducting MSUS with similar results to rheumatologists with extensive MSUS experience for the pathologies mentioned above. Additionally, the novel chip-based ultrasound systems used by the dermatologists in this study seem to be suitable for musculoskeletal point of care ultrasound and can be easily transported anywhere.

Our study demonstrated that MSUS performed by trained dermatologists, equipped with a HHUD, influences the sensitivity and specificity of early PsA diagnosis. This procedure changed the PsA suspicion in 46 cases, while in 45 cases PsA was no longer suspected. After conducting MSUS, the sensitivity decreased from 88.2% to 70.6% and the specificity increased from 54.4% to 90.4%, potentially leading to less and more precise referrals, respectively, from dermatologists to rheumatologists, as the PPV before MSUS was 25.4%, while after MSUS it increased to 56.5%.

Interestingly, 11 of the 23 patients suspected of having PsA after having MSUS performed by dermatologists were found to have no PsA in the final rheumatological examination. One probable cause is the order of dermatological screenings. If the examiner had a high suspicion of PsA before using MSUS, he could be more inclined to perceive marginal ultrasound data as suspicious. Another possible explanation is the characterization of suspicious joints in dermatologists' MSUS examinations, as joint effusion alone is already regarded as suspicious, yet this pathology is also frequent in other arthropathies.

Similar findings have been reported by Solmaz et al. who showed in a study with 51 psoriasis patients of which 20 were diagnosed with PsA that MSUS reduces the referral time from dermatology to rheumatology and the false-positive rate of the suspected diagnoses [35]. However, a significant difference from our investigation was that the ultrasound in their study protocol was performed by experienced rheumatologists, limiting the screening possibility. To generalize MSUS-based PsA screening, first contact physicians should use the ultrasound. In cases of PsA, the first contact physicians are often dermatologists [36], and therefore it is reasonable to empower their MSUS deployment.

Additionally, we found the CASPAR criteria, which have been extensively employed as a screening tool since 2006, to have an unusually low specificity of 57.8% in our cohort. In the present study, this classification indicated PsA in 66 cases, out of which only 19 patients have been diagnosed with this inflammatory-joint disease. The reason for this may be our study design. We applied the criteria to the whole cohort, out of which no patient was previously diagnosed with PsA. The literature on this topic revealed mostly high sensitivity and specificity, but most studies estimating these parameters included patients with already diagnosed PsA [6–9]. Therefore, further investigation is necessary to assess the accuracy of CASPAR criteria in routine clinical setting.

The limitations of this study include that the population of 140 patients was chosen due to the feasibility of this monocentric study. Due to the MUDE teaching concept for each joint, the dermatologists’ MSUS was confined to the most sensitive and specific ultrasound planes to ensure a lower complexity. Further we only used the GEPARD as screening questionnaire for PsA, and did not apply other (e.g. PURE4 [37]) screening questionnaires. The ultrasound of entheses was not applied due to heightened complexity, although enthesitis can be a sign of PsA [38]. Further research is needed to evaluate how entheseal ultrasound performed by dermatologists influences the early PsA diagnosis. The dermatologists used the same paper CRF to record the suspected diagnosis before and after the MSUS. This could affect the suspicion if the examiner first conducted both the traditional and MSUS-based screening and noted the suspected diagnoses afterwards.

Conclusion

To the best of our knowledge, this is the first study to evaluate the impact of MSUS performed by dermatologists using an innovative portable ultrasound device for early PsA diagnosis. In conclusion, we were able to demonstrate that targeted MSUS conducted by previously trained dermatologists can help rule out PsA, potentially leading to fewer referrals to rheumatologists and a more precise diagnosis of PsA. In addition, the use of HHUD is promising, especially for screening purposes. Furthermore, we discovered that the CASPAR criteria were ineffective in identifying PsA. Further investigation is needed to ensure the practical validity of our suggested screening application.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by Novartis Pharma.

Disclosure statement: The authors have declared no conflicts of interest.

References