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Imaging has been playing an important role in the pathogenetic and clinical characterisation of many rheumatic diseases, especially in the most recent years with the advent of many new, highly technological and promising techniques. Calcium pyrophosphate deposition disease (CPPD) benefited also from these new techniques, most of which can readily identify calcium crystals. Nowadays, imaging is used mainly to identify crystals in joints but given the complexity of CPPD, imaging should be used with an “holistic” approach in order to gain insights in the pathogenesis, spectrum of clinical manifestations and natural history of the disease. Furthermore, overlap or association of CPPD with other prevalent diseases of the elderly makes the differential diagnosis challenging. In this review, we provide a critical review of the current knowledge on the use of imaging both for the identification of crystals and for its application in clinical practice as an aid for determining the impact of the disease on patients.Key Points• CPPD is a complex disease with a wide spectrum of clinical manifestations and understanding of pathogenetic mechanisms and clinical phenotypes is essential for correct characterisation• Imaging has made important advances regarding identification of CPPD in recent years, and new, more sophisticated techniques are under investigation• Imaging has the potential to improve our knowledge on pathogenesis and clinical phenotypes of CPPD• Imaging techniques have to be tested thoroughly for reliability, discrimination and sensitivity to change before they can be implemented in clinical trials

Gout and calcium pyrophosphate deposition (CPPD) disease are the most common causes of crystal arthritis. Identifying the pathogenic crystal deposition is the cornerstone of the diagnosis, but also prognosis and monitoring of the diseases. Conventional radiography has been for decades the only imaging technique used, with its very restricted sensitivity in both diseases. Advanced techniques, namely ultrasound and dual-energy computed tomography (DECT), are being increasingly used in the diagnosis and management of gout and CPPD diseases, and their role is now well recognized in classification criteria and in recommendations for the diagnosis and management. In gout, ultrasound elementary lesions of monosodium urate deposition are well defined and have been shown to be sensitive to change and can be monitored, while direct quantification of these deposits can be performed with DECT. In CPPD disease, the definition of elementary lesions and their scoring has been well established for ultrasound, while the proof of concept that DECT can help discriminate calcium pyrophosphate crystal deposits among other calcium-containing structures has been shown. The aim of this narrative review is to provide an overview of the use of advanced imaging techniques in crystal-induced arthropathies.

The aim of this study was to evaluate the long-term efficacy and safety of single or 1–3 weekly injections of hylan G-F 20 at 1 year following the first injection for knee osteoarthritis (OA). Searches were conducted in PubMed/MEDLINE, Embase, and CENTRAL and included relevant conference proceedings (January 1, 1995–August 17, 2020). Randomized controlled trials (RCTs), non-randomized trials, and observational studies investigating 1-year efficacy and safety of 1–3 weekly injections or single hylan G-F 20 injection for knee OA were included. Primary outcomes were WOMAC pain, physical function, and stiffness. Meta-analyses of RCTs and non-randomized studies were conducted separately. Our search identified 24 eligible studies. Hylan G-F 20, in the meta-analyses of RCTs, showed statistically significant improvement in WOMAC pain (SMCC − 0.98, 95% CI − 1.50, − 0.46), physical function (SMCC − 1.05, 95% CI − 1.28, − 0.83), and stiffness (SMCC − 1.07, 95% CI −1.28, −0.86). Improvement was also seen for VAS pain, SF-36 MCS (mental component summary), and SF-36 PCS (physical component summary). Analyses of non-randomized studies showed similar efficacy estimates. There were no significant differences in efficacy based on injection schedule, nor between RCT and non-randomized studies. Rates of adverse events (AEs) were low for most types of AEs. Hylan G-F 20 (either as single or 1–3 weekly injections) showed improvement in 1-year efficacy outcomes in comparison to baseline and was generally well tolerated. While further research will inform the medical field regarding viscosupplementation treatment options for knee OA, these findings show that hylan G-F 20 at both frequencies/dosages are efficacious and generally well tolerated for long-term use.

Objective. To develop and test an algorithm with the aim of optimizing the implementation of ultrasound in the diagnostic workflow in clinical practice. Methods. Through a consensus among the Musculoskeletal Ultrasound (MSUS) Study Group of the Italian Society for Rheumatology, we identified clinical and laboratory variables to be included in 1000minds surveys to develop an algorithm driving clinical diagnostic suspicion. The algorithm would identify potential differential diagnoses where MSUS protocols targeted for specific diseases (rheumatoid arthritis, psoriatic arthritis, gout, calcium pyrophosphate deposition disease, polymyalgia rheumatica, and osteoarthritis) could be applied. The joint sites and elementary lesions for each disease were selected based on a previously performed systematic literature review (SLR) and consensus. Finally, we conducted a pilot study on patients with new-onset arthritis to assess the performance of the algorithm, comparing the algorithm-based diagnosis with the final clinical diagnosis. Results. Based on the consensus and the surveys, age, the number of involved joints, anti-citrullinated protein antibody, rheumatoid factor, C-reactive protein, and erythrocyte sedimentation rate were included in the algorithm. The pilot study included 59 patients: median (interquartile range) age 62.2 (54.1-72.6) years, 78% female. The agreement between the diagnosis selected by the algorithm and the final diagnosis by the rheumatologist was 88.1%. The elementary lesions and joint sites included in the different MSUS protocols were selected based on the best diagnostic accuracy, as shown by the SLR and defined by the working group. Conclusions. The developed algorithm was accurate in identifying the correct diagnosis. Thus, it could reliably drive the decision on the MSUS assessment to perform. The RADIAL study will further investigate the feasibility and added value of MSUS in the diagnostic workflow according to this newly developed clinical suspicion-driven algorithm.

Loiasis is known for two main clinical manifestations: eyeworm and Calabar swellings. Calabar swellings are non-pitting edemas, often on the upper limbs or presenting as unilateral orbital swelling. They are described as itchy or painful, limit mobility, and cause notable morbidity. Although adult Loa loa filariae (macrofilariae) are known to migrate widely through host tissues, their exact pathways and tissue preference (tropism) remain unclear. Whilst the exact mechanisms remain unclear, Calabar swellings are considered to be localized allergic reactions to worm antigens, resulting in angioedema. Leveraging advances in portable ultrasound, this project aimed to characterize Calabar swellings via ultrasound to better understand the pathophysiology behind them. This study was conducted in the Lékoumou department, Republic of Congo, as an ancillary investigation within the MorLo (Morbidity due to Loiasis) project. During a follow-up visit in September 2023, participants and interested villagers were invited to present if they had Calabar swellings. Participants completed a standardized questionnaire and were examined by a physician who also performed ultrasound imaging. Twenty-two individuals presented with visible swellings; 8 (36.4%) were classified as “not typical”, 12 (54.5%) as “typical” Calabar swellings and fourteen (63.6%) had subcutaneous nodules on the forearms or wrists, with 8 (36.4%) having both simultaneous swellings and nodules. Ultrasound videos of typical swellings showed nonspecific angioedema, whereas videos of nodules revealed subcutaneous trans-fascial, possibly fluid filled, retentions extending through fascia and crossing anatomical boundaries with mixed-echogenic content. Within these retentions, hyperechoic thread-like structures were visible, displaying autonomous movement in two videos. Their measured diameters corresponded to L. loa macrofilariae. The ultrasound findings are most consistent with trans-fascial migration of adult L. loa filaria, associated with fascial lesions and fluid retention. The classical Calabar swelling appears closely related to—but not directly over—the underlying lesions. Migration of adult L. loa filaria causes a destructive and disabling process that warrants research and public health responses to ensure appropriate care for affected individuals.

Objective To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal deposition and the distribution of affected sites, using ultrasonography (US), in patients affected by CPP deposition disease (CPPD). Patients and methods 42 consecutive patients affected by definite CPPD according to the McCarty criteria were enrolled in the study. All patients underwent an US examination of metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and knees, Achilles’ tendons and plantar fascia looking for CPP deposits. A dichotomous score for presence/absence of CPP and a semiquantitative score for extent of deposits (0–3: 0, absent; 1, 1–2 spots; 2, more than two spots covering <50% of the structure; 3, deposits covering >50% of the structure) were assigned to each site examined. A site distribution score (total number of affected sites) was then calculated as well as an extent score equal to the sum of the extent scores of all sites. Results The mean involvement in our patients was 4.7 sites (SD±1.7, range 2–8 sites). The knee was the most affected, site (41 of 42) followed by the wrist (at least one in 37 patients) the Achilles’ tendons (23 patients), plantar fascia (11 patients) and metacarpophalangeal joints (four patients). The highest mean values of the extent score were in the menisci, followed by the hyaline cartilage of the femoral condyles and the entheses. Conclusions The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.

Fibromyalgia syndrome (FMS) is a complex, heterogeneous disorder characterized by chronic widespread pain, fatigue, and cognitive disturbances. The multifactorial nature of FMS, with the involvement of central and peripheral mechanisms, hampers diagnosis and effective treatment. In recent years, positron emission tomography (PET) imaging has emerged as a valuable tool for exploring the neurobiological underpinnings of FMS. Several studies have investigated alterations in glucose metabolism, neurotransmitter systems (including opioid, dopamine, and GABAergic pathways), and neuroinflammation using various PET tracers. These findings have revealed distinct brain metabolic and molecular patterns in FMS patients compared to healthy controls, particularly in pain-related regions such as the thalamus, insula, and anterior cingulate cortex (ACC). Moreover, preliminary data suggest that PET imaging may help identify FMS subgroups with different pathophysiological profiles, potentially allowing for tailored therapeutic approaches. This review summarizes the current evidence on PET applications in FMS and discusses the potential role of molecular imaging in improving patient stratification and predicting treatment response.

ObjectivesThe Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) has developed a calcium pyrophosphate deposition (CPPD) nomenclature project. This systematic literature review constituted its first step and aimed to provide a state-of-the-art analysis of the medical literature of the last 20 years.MethodsA systematic literature search was undertaken in the PubMed, Cochrane and Embase databases between 2000 and 2022, restricted to studies on humans and in the English language. Eight reviewers independently and manually extracted labels related to CPPD concepts, according to an a priori list generated by the authors: pathogenic conditions and pathogenic crystal labels, elementary imaging condition elements and asymptomatic and symptomatic condition states. For each concept, labels were analysed to determine their frequency.ResultsAmong the 2375 articles identified, 886 articles were included, of which 394 (44.5%) were case reports and 169 (19.0%) were scoping reviews. Overall, the most common labels used to designate the pathogenic condition were ‘pseudogout’ in 365/783 (46.6%), ‘chondrocalcinosis’ in 207/783 (26.4%) and ‘calcium pyrophosphate deposition disease’ in 181/783 (23.1%) occurrences. The most common abbreviation was ‘CPPD’ in 312/390 (80.0%), but with different meanings. CPPD clinical phenotypes were often described as ‘pseudo-form’ labels.ConclusionThose results demonstrate the heterogeneity of labels used to describe CPPD condition concepts, with wide variation in condition labels in the medical literature. This work provides the rationale and basis to achieve agreement about CPPD technical nomenclature.