Marcin Milchert

Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: a study from the OMERACT Large Vessel Vasculitis Ultrasound Working Group

Objectives To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise. Methods Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise. Results Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The ‘halo’ and ‘compression’ signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the ‘halo’ sign and the ‘compression’ sign was excellent with inter-rater agreements of 91–99% and mean kappa values of 0.83–0.98 for both inter-rater and intra-rater reliabilities of all 25 experts. Conclusions The ‘halo’ and the ‘compression’ signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

Assessing Vasculitis in Giant Cell Arteritis by Ultrasound: Results of OMERACT Patient-based Reliability Exercises

Objective. To test the reliability of Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus-based ultrasound definitions for normal and vasculitic temporal and axillary arteries in patients with giant cell arteritis (GCA) and in controls. Methods. A preliminary 1-day meeting and a full 3-day meeting fulfilling OMERACT Ultrasound Group guidelines were held. Temporal and axillary arteries were examined at 2 timepoints by 12 sonographers on 4 patients with GCA and 2 controls. The aim was to test inter- and intrareader reliability for normal findings, halo sign, and compression sign. In both meetings, patients had established GCA. Pathology was more recent in the full meeting, which was preceded by 6 h of training. Scanning time was 15–20 min instead of 10–13 min. Results. In the preliminary exercise, interreader reliabilities were fair to moderate for the overall diagnosis of GCA (Light κ 0.29–0.51), and poor to fair for identifying vasculitis in the respective anatomical segments (Light κ 0.02–0.46). Intrareader reliabilities were moderate (Cohen κ 0.32–0.64). In the main exercise, interreader reliability was good to excellent (Light κ 0.76–0.86) for the overall diagnosis of GCA, and moderate to good (Light κ 0.46–0.71) for identifying vasculitis in the respective anatomical segments. Intrareader reliability was excellent for diagnosis of GCA (Cohen κ 0.91) and good (Cohen κ 0.71–0.80) for the anatomical segments. Conclusion. OMERACT-derived definitions of halo and compression signs of temporal and axillary arteries are reliable in recent-onset GCA if experienced sonographers (> 300 examinations) have 15–20 min for a standardized examination with prior training and apply > 15 MHz probes.

Polymyalgia rheumatica with normal values of both erythrocyte sedimentation rate and C-reactive protein concentration at the time of diagnosis: a four-point guidance

Raised values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentration are typical findings in patients with polymyalgia rheumatica (PMR) at the time of diagnosis. In 1979 Bird et al. proposed an ESR of 40 mm/h or higher as a diagnostic criterion, and in 1981 Jones and Hazleman considered a CRP concentration of more than 6 mg/l as an additional criterion. In a sizable proportion of PMR patients – from 7% to 22% – ESR is not raised at the time of diagnosis. However, in these patients, CRP is usually raised [1]. The normal values of both of these biomarkers at the time of diagnosis were rarely reported. Myklebust and Gran [2] found normal both ESR and CRP in 1.2% of 178 PMR patients, and only one patient amongst 177 had normal ESR and normal CRP in a prospective follow-up study conducted in two Italian secondary referral centres of rheumatology [3]. In our medical records (data unpublished), six amongst 265 PMR patients had normal values of both ESR and CRP at diagnosis. The vast majority of these patients had no constitutional manifestations. The reasons why this can be possible in an auto-inflammatory disease are only speculative. The absence of constitutional manifestations could realise a first-favouring element. PMR with low ESR is considered a more benign form of disease, with lower frequency of constitutional manifestations compared to PMR with high ESR [4]. Innate immunity may trigger fever, general malaise, fatigue, and depressive reaction. In patients with PMR, their absence can be a result of interactions between innate and adaptive immunity within a specific genetic background [5]. Some speculated that PMR might be an incomplete form of giant cell arteritis (GCA), manifested in the regions in the proximity of axillary, subclavian, and/or femoral arteritis. A biopsy-proven GCA can be present without elevation of ESR and CRP [6], and in the literature GCA with normal ESR and CRP at diagnosis is much more frequent than PMR with normal values of inflammatory markers. Accordingly, it might be hypothesised that PMR patients with normal values of both ESR and CRP have an occult GCA. In individuals aged 50 years or older, in the presence of: persistent pain involving shoulders, pelvic girdle, and/or neck plus morning stiffness lasting for more than 1 hour plus absence of other different diseases (with the exception of giant cell arteritis), the diagnosis of PMR is possible. The rapid response (seven days, on average) to low-dosed prednisone (< 20 mg per day), together with watchful observation to ensure that no alternative diagnosis appear during follow-up, can confirm the first diagnosis. However in the clinical practice we must take into account that several patients fail to achieve a complete response after one week, and – on the other hand – some diseases can mimic PMR not only in the clinical features but also in a fast response to low-dosed systemic glucocorticoids. Some of these diseases fail to maintain the first positive response in a short time (with reappearance of manifestations despite glucocorticoid therapy) but others (such as solid or haematological tumours) can do it [7]. In recent years, ultrasound (US) imaging has become an integral element of the diagnostic process in PMR. Even if there are no pathognomonic findings, subdeltoid

Diagnosis of polymyalgia rheumatica usually means a favourable outcome for your patient

Polymyalgia rheumatica (PMR) is a unique disease of elderly people, traditionally diagnosed based on a clinical picture. A typical case is a combination of severe musculoskeletal symptoms and systemic inflammatory response with spectacular response to corticosteroids treatment. The severity of symptoms may be surprising in older patients where immunosenescence is normally expected. However, PMR may be diagnosed in haste if there is a temptation to use this diagnosis as a shortcut to achieve rapid therapeutic success. Overdiagnosis of PMR may cause more problems compared to underdiagnosis. The 2012 PMR criteria proposed by European League against Rheumatism/American College of Rheumatology aim to minimize the role of clinical intuition and build on more objective features. However, questions arise if this is possible in PMR. This has been discussed in this review.

Arteriosclerosis or Vasculitis? Color Duplex Sonography in Giant Cell Arteritis

To the Editor: We followed with great interest the report by Czihal, et al 1 presenting new possibilities of objective, noninvasive diagnostic procedures that remain insufficient in giant cell arteritis (GCA). We would like to share our clinical experiences with arteritic changes in patients with GCA. Sonographic presentations of vasculitis may be mistaken for arteriosclerosis, especially in elderly patients who typically have GCA. That was the case in a patient with mild systemic manifestations and insidious disease onset. A 64-year-old woman presented with carotidynia — a rare manifestation of GCA. Color duplex sonography (CDS) revealed hypoechoic, homogenous, circumferential but not symmetrical bilateral wall thickening involving carotid and internal carotid arteries up to 15 mm from the carotid … Address correspondence to Dr. Milchert; E-mail: marcmilc{at}hotmail.com

High prevalence of anti-beta-2 glycoprotein-I and anti-prothrombin antibodies in adult-onset Still’s disease. Comment on “Portal vein thrombosis in adult-onset Still’s disease: a case report and literature review”

We have followed with great interest case report by Morita et al [1]. In our group of eight patients diagnosed with Adult-onset Still’s disease (AOSD) according to Yamaguchi criteria, we reviewed presence of antiphospholipid antibodies. They were detected in six of eight patients: the most common were anti-prothrombin (anti-PT) followed by anti-beta2 glycoprotein-I antibodies (anti-b2GPI) (Table 1). D-dimer level was elevated in all patients; however, no related thrombosis was diagnosed. Only one patient presented with deep vein thrombosis at the time of AOSD relapse, and one woman had a history of miscarriage, however, not fulfilling current antiphospholipid syndrome classification criteria. Our first reflection was how difficult differential diagnosis of liver disease in AOSD is, as raised serum aminotransferase (AT) level may be associated with high

Chronic Urticaria and Mild Arthritis Associated with Autoimmune Thyroid Disease: Successful Treatment with L-Thyroxine

Sir, Some cases of chronic urticaria, regarded so far as idiopathic, are in fact of autoimmune origin (1). Autoimmune thyroid disease (ATD) is characterized by the presence of anti-thyroid antibodies. Association of chronic urticaria and ATD is well known. Most studies have found a 15–30% prevalence of anti-thyroid antibodies in patients with chronic urticaria (2, 3). There have been some reports of successful treatment with L-thyroxine of either arthritis (4, 5) or autoimmune urticaria (1, 3) associated with ATD, as well as in euthyroid patients (3–5).

FRI0518 Ultrasound Definitions for Vasculitis in Cranial and Large Vessel Giant Cell Arteritis: Results of A Delphi Survey of The Omeract Ultrasound Large Vessel Vasculitis Group

Background In a systematic literature review (SLR), we identified halo sign, stenosis, occlusion, compression sign and a decreased vessel wall pulsation as elementary ultrasound (US) lesions in giant cell arteritis (GCA). Objectives To establish consensus-based definitions for the key elementary US lesions in GCA. Methods We invited 25 rheumatologists from 13 countries experienced in musculoskeletal and vascular US to participate in a Delphi exercise. Based on the results from the SLR and international expert consensus a questionnaire was developed including 12 statements on the definitions of normal temporal and extra-cranial large arteries, arteriosclerosis, halo sign, stenosis, occlusion, compression sign, and vessel wall pulsation. The experts were asked to express their level of agreement or disagreement with the proposed statements. A consensus was defined as agreement of ≥75% of participants. Results The response rate was 24/25 (96%) in round 1 and 24/24 (100%) in round 2. A consensus was achieved for 9/9 Delphi statements [normal temporal and extra-cranial large arteries, arteriosclerosis, halo sign, stenosis of temporal and extra-cranial large arteries, occlusion, compression sign (temporal arteries), US assessment of compression sign (temporal arteries) in round 1. In round 2, 3/3 Delphi statements (arteriosclerosis, halo sign, stenosis of temporal arteries) were redefined. The statements on vessel wall pulsation (definition and assessment) and measurement of vessel wall thickness did not reach the threshold for consensus. The halo and compression signs were deemed to be the most important US signs for GCA with 100% and 83.3% expert agreement, respectively. Conclusions This is the first international consensus on definitions for elementary US lesions in GCA. The next steps of the OMERACT project will be web- and patients based exercises testing the reliability of the new definitions. Disclosure of Interest None declared

Application of optical coherence tomography of subclavian and axillary arteries in a patient with Takayasu arterities.

Takayasu’s arteritis (TA) is large vessel vasculitis affecting the aorta and its major branches. The annual incidence of systemic vasculitis approaches 40 per million adults worldwide. TA can result in myocardial infarction (MI), and this should therefore be differentiated from arteriosclerotic lesions. Optical coherence tomography (OCT) is increasingly used to assess coronary stent implantation and vessel healing following stent implantation. So far, the use of OCT with Takayasu’s disease has been described only once, and it was used for a left anterior descending coronary artery lesion. This is the first case report of the use of OCT with a TA patient providing peripheral arteritis. A 27-year-old woman with psoriasis and celiac disease was admitted to our hospital with typical chest pain. In the first electrocardiogram, ST-elevation in a VR lead and ST-depressions in the other leads were revealed. The patient reported night sweats and muscle weakness in the arms. Physical examination revealed blood pressure at 90/60 mm Hg and 80/50 mm Hg in the right and left arm, respectively. Pulse at both radial arteries was barely palpable. Murmurs above both subclavian arteries and both carotid arteries were heard with auscultation. Echocardiography revealed mild hypokinesis at the apex and septum segments. Serum troponin I and creatine kinase isoenzyme MB activity was elevated significantly to MI. Coronary angiography showed a 90% focal stenosis in the ostium of the left main coronary artery (LMCA) (Fig. 1A). Ticagrelor and acetylsalicylic acid were administered immediately. Afterwards the lesion was predilated with balloons and then a 4.0 × 8 mm drug eluting stent with everolimus was deployed with a good final result. Contrasted computed tomography (CT) of the aorta and its main branches revealed vessel wall thickening, together with left carotid and subclavian arteries stenosis. Corticosteroid and cyclophosphamide therapy was added to the treatment. After 3 months, the patient underwent angiography to check the stent in the LMCA and also a control angiography and OCT of both subclavian and axillary arteries. These revealed persistent stenosis in both subclavian and right axillary arteries (Fig. 1B, C) and no restenosis in LMCA. OCT revealed intima–media thickness up to 0.75 mm over long distance without atheromatous plaque (Fig. 2). Due to lack of a proper drug-eluting balloon (DEB) for the patient the procedure was postponed. After a few weeks information was received that the patient had died due to massive MI whilst in her home city. Histological lesions in large vessel arteritis involve all layers of the arterial wall: intimal hyperplasia, medial degeneration, adventitial fibrosis, and mononuclear cellular infiltration lead to lack of a clear intima–media border. TA is an inflammatory disease, so anti-inflammatory drugs can reduce the lesions. Therefore, in peripheral arteries, the deployment of a DEB rather than stent implantation should be considered. When a culprit lesion involves the LMCA treatment with only a DEB is not acceptable. Our report provides essential knowledge concerning how an artery can look in large vessel arteritis as opposed to arteriosclerosis. The images can provide rare but important knowledge concerning peripheral and coronary diseases.