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Objective—To evaluate the eYcacy of extracorporeal shock wave treatment (ESWT) in calcaneal enthesophytosis. Methods—60 patients (43 women, 17 men) were examined who had talalgia associated with heel spur. A single blind randomised study was performed in which 30 patients underwent a regular treatment (group 1) and 30 a simulated one (shocks of 0 mJ/mm 2 energy were applied) (group 2). Variations in symptoms were evaluated by visual analogue scale (VAS). Variations in the dimension of enthesophytosis were evaluated by x ray examination. Variations in the grade of enthesitis were evaluated by sonography. Results—A significant decrease of VAS was seen in group 1. Examination by x ray showed morphological modifications (reduction of the larger diameter >1 mm) of the enthesophytosis in nine (30%) patients. Sonography did not show significant changes in the grade of enthesitis just after the end of the treatment, but a significant reduction was seen after one month. In the control group no significant decrease of VAS was seen.No modification was observed by x ray examination or sonography. Conclusion—ESWT is safe and improves the symptoms of most patients with a painful heel, it can also structurally modify enthesophytosis, and reduce inflammatory oedema. (Ann Rheum Dis 2001;60:1064‐1067) Painful heel is a common syndrome characterised by severe pain in the inferior or posterior aspect of the heel, which is aggravated by weight bearing, becoming progressively worse and often incapacitating, with evidence of a spur in about 50% of cases. 1 Until now the cause of the condition has been obscure, but numerous factors have been claimed to produce painful heel with a bony spur: functional overuse, degenerative diseases, inflammatory diseases, and metabolic diseases. 2

Ochronosis is the musculoskeletal manifestation of alcaptonuria, a rare autosomal recessive disorder with an estimated prevalence of below 1:250 000.1 Alcaptonuria is associated with deficient homogentisate 1,2-dioxygenase (HGO) activity in the liver,2 causing production of large quantities of homogentisic acid (HGA). In urine and tissues, HGA oxidises to benzoquinones, which in turn form melanin-like polymers. Tendons are sites of ochronotic pigment deposition because of their high collagen content.3 Several cases of tendon and ligament ruptures in alcaptonuria have been reported.1 4 5 To our knowledge, no studies have been carried out regarding tendon pathology in ochronosis. Ultrasonography (US) is an inexpensive, repeatable, non-invasive exam that permits accurate visualisation of tendons and ligaments. Our …

Background Shoulder pain is a common condition in rheumatologist’s practice. Ultrasound (US) gained a central role in diagnosis of painful shoulder. However, in literature there aren’t guidelines on how to report shoulder US examination and it is plausible that radiologists and rheumatologists could describe the same findings in different ways, due to different cultural background Objectives To compare US technique and reports of shoulder examination performed by radiologists and rheumatologists, to identify the main discrepancies and resolve them. Methods Five rheumatologists and 2 radiologists, experienced in US, participated. The study was divided in 2 phases, in the first one each participant performed an US of 3 patients (one shoulder each) and reported the findings, blinded to the patients diagnosis and to the other operators technique and findings. US technique of each operator was observed and reported by other 3 doctors. Subsequently, the reports along with the images were compared to identify the main discrepancies and to propose solutions in order to uniform both technical aspects and reporting of the findings. In the second phase a US exam of a fourth patient was performed in plenary, to assess feasibility and efficacy of the “common approach” as defined previously. Results The US scanning technique adopted was similar for all operators, differing only for the sequence of the scans. During the exam, rheumatologists paid more attention on US findings suggestive of inflammatory disease, while radiologists were more interested in rotator cuff pathology, in line with the ESSR recommendations for US shoulder (1). The main differences in reporting emerged in description of rotator cuff pathology. Radiologists are more imprinted in a detailed description of lesions (measurements in 2 axis and scoring of lesions according to the feedback obtained by the interaction with orthopedists), whereas rheumatologists provided a careful description of inflammatory changes to distinguish between acute and chronic disorders. Experts concluded that both approaches are important and lesions should be measured in 2 axes and grade of degeneration, concomitant disorders and the age of lesion should be reported. Another major difference emerged in the description of the “irregularities” of bone surface. Experts concluded that the irregularities should not be reported as “erosions” because such term could evocate an inflammatory joint disease (i.e rheumatoid arthritis) when it is known that the irregularities of the cortex can be found in other conditions (osteoarthritis of the shoulder). The term erosion should be used only when an inflammatory joint disease is strongly suspected. Other minor points that have been discussed and addressed will be presented in the extended work. Conclusions This study allowed to clarify some points of divergence in US reporting and represented an interesting experience of collaboration between radiologists and rheumatologists. References Klauser AS, Tagliafico A, Allen GM et al. Clinical indications for musculoskeletal ultrasound: a Delphi-based consensus paper of the European Society of Musculoskeletal Radiology Eur Radiol. 2012 May;22(5):1140-8. Epub 2012 Mar 28 Disclosure of Interest None Declared

Background Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) are coming exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dose and primary diagnosis. Objectives The objective of this study was to evaluate the incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dose, BMD values, specific treatment for GIOP, etc.) in a large cohort of consecutive patients aged > 21 years, on chronic treatment with GC (≥5 mg prednisone –PN- equivalent), attending rheumatology centres located all over Italy. Methods Here the results of an interim analysis of the first 553 enrolled patients are presented. Systemic Lupus Erythematosus or other Connectivites (CON), Polymialgia Rheumatica (PMR), and Rheumatoid arthritis (RA) were the underlying diseases. Results In the table are shown the main clinical characteristics : Conclusions In real life the prevalence of clinical fractures in patients with rheumatic diseases is high even before GC treatment and the incidence of new clinical fractures while on chronic GC treatment (PN- equivalent ≥ 5 mg/day) is somewhat lower than hitherto assumed. These results emphasize the importance of the underlying disease in the risk of GIOP associated fractures. Disclosure of Interest None Declared

Background Viscosupplementation by intra-articular injections (IAI) of hyaluronic acid in the knee is widely used for symptom relief in patients with osteoarthritis of this joint. Previous studies have demonstrated that blind IAI are not always accurate in placing the needle in the knee joint space. Objectives The aim of our study was to establish by ultrasonography the rate of correct, intra-articular delivery of the drug in patients with knee joint osteoarthritis, undergoing IAI of hyaluronic acid, and to individuate the main factors that could influence the IAI outcome Methods All patients with knee osteoarthritis referred to our outpatient clinic for IAI were enrolled in the study. Demographic data of patients, Body Mass Index (BMI) and radiological grade of osteoarthritis were recorded. Injections were performed by two medical doctors, one with many years experience in IAI and the other with only a few months experience, in a random way (alternating one patient to each during the sessions). The access used for IAI was decided by the operator at the time of injection. A small air bubble was intentionally left in the syringe so that ultrasound could precisely identify the drug. Within 15 min of injection, patients were examined by ultrasound to define drug position (intra- or extra-articular). SPSS software was used for statistical analysis. Results 42 patients (42 knees) were enrolled in the study (38 females). Air bubbles were easily recognized in all patients and exact drug position was readily identified. 24 IAI were performed by the expert operator. In 12 cases, lateral midpatellar access was used, while in the other cases anterolateral access was preferred. The drug was correctly positioned in 28 cases (67%). Logistic regression analysis demonstrated that the only variable influencing IAI outcome (among age, BMI, grade of osteoarthritis, operator experience, presence of intra-articular effusion) was operator experience. Conclusions Two out of three IAI were correctly placed in the knee joint. Operator experience was the most important factor for correct intra-articular injection. BMI, effusion and the grade of osteoarthritis did not seem to influence the outcome of IAI. Correct training in IAI is therefore very important. References Jackson DW, Evans NA, Thomas BM. Accuracy of needle placement into the intra-articular space of the knee. J Bone Joint Surg Am. 2002 Sep;84-A(9):1522-7 Qvistgaard E, Kristoffersen H, Terslev L, Danneskiold-Samsoe B, Torp-Pedersen S, Bliddal H. Guidance by ultrasound of intra-articular injections in the knee and hip joints. Osteoarthritis Cartilage. 2001 Aug;9(6):512-7. Disclosure of Interest None Declared

A common and well-documented feature of spondyloarthropathies is inflammation of the peripheral enthesis1. Ultrasound (US) imaging is useful when assessing enthesitis, and many investigators have described its features2,3. A 50-year-old man with psoriasis developed morning stiffness, tenderness, and swelling of small joints in the hands asymmetrically during the last month. Clinical examination revealed tenderness and swelling of the proximal interphalangeal joints (PIP) of the second, third, and fourth fingers …

Both dual-photon absorptiometry (DPA) using 153Gd and dual-energy x-ray absorptiometry (DEXA) can be used for measurement of bone mineral content (BMC) and bone mineral density (BMD) of the total skeleton and its seven major regions. The short-term precision (coefficient of variation, CV) of DEXA for total-body BMD using the medium (20 minute) and fast (10 minute) speeds was 0.34 and 0.68% in 5 normal subjects; the corresponding CV in 5 osteoporotic females were 0.70 and 1.04%. The CV for BMD using DPA was 0.82% in 8 normal subjects and 0.70% in 12 osteoporotic patients. The CV for regional BMD using DPA was similar to fast-speed DEXA, without significant differences (p NS); precision with medium-speed DEXA was superior to DPA, and the differences were statistically significant (p less than 0.05) for head, spine, trunk, ribs, and pelvis. Total-body measurements using both DPA and DEXA were done on 99 subjects (84 females and 15 males). Significant correlations (r = 0.98; p less than 0.001) were found between DEXA and DPA measurements of both BMC and BMD. There were also significant correlations (r = 0.94-0.98; p less than 0.001) between DEXA and DPA measurements of anatomic regions (head, trunk, spine, pelvis, ribs, arms, and legs). DPA and DEXA results for BMD of total skeleton, ribs, pelvis, and legs were similar (p NS), and statistically significant differences were found in head, spine, and arm measurements (p less than 0.01, p less than 0.01, and p less than 0.05, respectively); regression equations allowed adjustment of DEXA values in patients already measured with the earlier DPA method.

Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age [interquartile range] 63 [59‐68] years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.

To determine the frequency and localization of synovitis and enthesitis in patients with active, untreated polymyalgia rheumatica (PMR) by ultrasonography (US).Polyarticular sonographic evaluation was carried out in 50 consecutive patients with PMR at disease onset. Results were compared with 50 consecutive patients with seronegative spondyloarthropathies (SpA) and 50 with seronegative and seropositive rheumatoid arthritis (RA) at disease onset.Synovitis and/or effusion was detected, in at least one joint, in 100% of patients with PMR. The most frequent alterations observed in patients with PMR were effusion in the subacromial-subdeltoid (SA-SD) bursa in 70% of patients, tenosynovitis of the long head of the biceps tendon (LHBT) in 68%, glenohumeral joint effusion in 66%, tenosynovitis of the flexor tendons in the carpal tunnel in 38%, radiocarpal effusion in 18%, wrist extensors tenosynovitis in 18%, coxofemoral joint effusion in 40%. knee effusion in 38%, and ankle effusion in 10%. Enthesitis and tendonitis of the anchoring tendons were relatively rare in all the articular sites. Comparison of the SpA and PMR patients showed that enthesitis (mostly in the elbow, knee, and heel) was significantly more frequent in SpA. There was a significant difference in glenohumeral and coxofemoral effusion between the PMR and SpA patients (66% vs 16% and 40% vs 14%, respectively). Comparison of PMR and RA patients showed no significant difference in the involvement of entheses, shoulder, hip, or wrist flexor tendons in the carpal tunnel. Synovitis of the elbow, knee, and wrist was significantly more frequent in the SpA and RA patients than in those with PMR.Synovitis was detected in at least one site in 100% of patients with PMR. SA-SD bursitis, LHBT tenosynovitis, carpal tunnel syndrome, and glenohumeral, knee and hip synovitis were the most frequent alterations in PMR. Enthesitis was relatively rare at any articular site.

Innate immunity is a critical partner in the regulation of inflammation and some mutations in genes implied in innate immunity pathways can cause genetic disorders characterized by seemingly unprovoked self-limited inflammatory attacks. These rare conditions are collectively named "hereditary periodic fever syndromes" (HPFS), and protean pathogenetic mechanisms combined with several clinical phenotypes characterize at least four distinct conditions: (1) familial Mediterranean fever, which is the prototype and the most widely recognized among HPFS, inherited as an autosomal recessive disorder showing recurrent dysregulated inflammatory processes, caused by an abnormal interaction between cytoskeleton and inflammasome, a key-signaling platform that releases interleukin-1β (IL-1β); (2) the group of cryopyrin-associated periodic syndrome, which upsets directly the production of IL-1β, with a dominant pattern of inheritance; (3) tumor necrosis factor receptor-associated periodic syndrome, which is an autosomal dominant disorder subverting the functions and traffic of a cell membrane protein; and (4) mevalonate kinase deficiency, which is an autosomal recessive metabolic disorder halting the biosynthesis of cholesterol. MEFV, NLRP3, TNFRSF1A, and MVK are respectively the four causing genes of these conditions, all resulting in excessive IL-1β signaling, though the encoded proteins act at different levels in cytoskeletal filament organization, apoptosis, and activation of the IL-1β-structured inflammasome. The differential diagnosis of HPFS can be challenging, as there are no universally accepted diagnostic algorithms, and near half of patients may have a specific disease without any genetic pathogenetic variant identified. Herein, we outline the most relevant aspects of HPFS at the crossroads between clinical medicine and immunology and all the most recent advances in their treatment, as the increasing use of IL-1 antagonists has achieved unexpected clinical results in a large number of patients.

In the past twenty years autopsies are performed much less frequently in the elderly than in younger patients. The clinical diagnostic error rate documented by autopsy studies ranges from 6% to 68%. We analyzed the clinical and autopsy records of 214 patients who died from 1 January 1986 to 31 December 1989 at our Institute to determine the accuracy of clinical cause of death with respect to the pathologic cause of death. The most common cause of death were bronchopneumonia (25.2%) followed by gastroenteric and lung cancer (20%), cerebrovascular accident (15.8%), myocardial infarction (8%) and pulmonary embolism (7.4%). Pulmonary embolism was correctly classified only in 25% of patients. The most accurately diagnosed condition were neoplastic diseases (88%) and cerebrovascular accident (84.8%) while bronchopneumonia were correctly diagnosed antemortem in 72.2% of the patients studied. Our data suggest that advances in diagnostic technology have not reduced the value of the autopsy and that a goal-directed autopsy remains a vital component in the assurance of good medical care.

Cryopyrin-associated periodic syndromes are categorized as a spectrum of three autoinflammatory diseases, namely familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome. All are caused by mutations in the NLRP3 gene coding for cryopyrin and result in active interleukin-1 release: their rarity and shared clinical indicators involving skin, joints, central nervous system and eyes often mean that correct diagnosis is delayed. Onset occurs early in childhood, and life-long therapy with interleukin-1 blocking agents usually leads to tangible clinical remission and inflammatory marker normalization in a large number of patients, justifying the need to facilitate early diagnosis and thus avoid irreversible negative consequences for tissues and organs.