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Sharon Cowley, Geraldine McCarthy Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, IrelandCorrespondence: Sharon Cowley, Mater Misericordiae University Hospital, Dublin, Ireland, Email sharoncowley111@gmail.comAbstract: Calcium Pyrophosphate Dihydrate (CPPD) crystal-related arthropathies are a common cause of acute and chronic arthritis caused by the deposition of calcium pyrophosphate crystals in joints and soft tissues, resulting in inflammation and joint damage. They present with a wide spectrum of clinical manifestations and often present challenges to diagnosis and management as they commonly affect older co-morbid patients. The challenges are compounded by a lack of a well-defined description of CPPD. However, an international expert-driven process is underway to develop CPPD classification criteria. Treatment is also problematic as unlike gout, there are no agents available that decrease the crystal burden. Treatment options have often been extrapolated from gout treatment pathways without having extensive trials or a solid evidence base. It is hoped the new CPPD classification guidelines will contribute to large multicentre studies, with well-defined patient cohorts, which will facilitate the production of high-quality evidence to guide the management of this condition. Here, we discuss the barriers and facilitators in diagnosing and treating CPPD-related arthropathy.Keywords: crystal arthropathy, calcium pyrophosphate dihydrate, CPPD

Calcium crystal deposition diseases are transient benign diseases that can cause intense pain. They can sometimes cause masses and soft tissue edema around the calcification, which should be differentiated from tumors and abscesses. We report a case of calcium crystal deposition disease with an enhanced mass on the ventral side of the vertebral bodies resembling tumors and abscesses.A female patient in her 50s visited our hospital complaining of chest pain. Computed tomography revealed a soft tissue mass with polygonal high-density lesions on the ventral side of the thoracic spine. Initially, we suspected it to be a perivertebral tumor and considered a biopsy. However, the pain rapidly improved with the administration of oral acetaminophen (Caronal, Chuo-ku/Tokyo/Japan). Hence, the patient was followed up for the time being. The mass disappeared after 3 months. In addition, polygonal high-density lesions inside the mass disappeared over time. Therefore, it was diagnosed as an inflammatory mass due to calcium crystal deposition disease.Calcium crystal deposition diseases can cause soft tissue edema and inflammatory mass around the calcium crystal deposit that can be confused with a perivertebral tumor. This report elucidates the importance of identifying calcifications within and near the masses to diagnose an inflammatory mass resulting from calcium crystal deposition.

The retro-odontoid pseudotumor is often concurrent with atlantoaxial subluxation (AAS). Therefore, the pseudotumor is relatively common in rheumatoid arthritis (RA) but rare in primary osteoarthritis (OA). This is a case report of an elderly male patient suffering from neck pain and compression myelopathy caused by the craniocervical pseudotumor with OA but without atlantoaxial instability. He had long-lasting peripheral and spinal pain treated by nonsteroidal anti-inflammatory drugs. Imaging found upper cervical spondylosis without AAS or dynamic instability but with periodontoid calcifications and ossifications, suggesting calcium pyrophosphate dihydrate (CPPD) crystal deposition. Based on a comprehensive literature search and review, CPPD disease around the atlantodental joint is a possible contributor to secondary OA development and retro-odontoid pannus formation through chronic inflammation, which can be enough severe to induce compression myelopathy in non-RA patients without AAS. The global increase in the aged population advises caution regarding more prevalent upper cervical spine disorders associated with OA and CPPD.

Abstract Background Involvement in cervical ligamentum flavum is a rare manifestation of the calcium pyrophosphate dihydrate deposition disease. Only few cases of this condition have been reported. We revealed eighteen cases of CPPD in cervical ligamentum flavum that diagnosed at a single medical center. In our case series, clinical characteristics and magnetic resonance imaging findings of patients are described. Methods We retrospectively reviewed the medical charts and imaging studies of the eighteen patients with pseudogout attack of the cervical ligamentum flavum. In addition, we discussed the differences between this disease and ossification of ligamentum flavum in image manifestations. Results There were fourteen men and four women aged between 59 and 87 years. Diabetes mellitus and hypertension were the most common comorbidities. Myelopathy and neck pain were presented in most patients. C4–5 and C5–6 were attacked most frequently, and multiple- rather than single-level involvement could be observed in our series. “Acute on chronic phenomenon” was a specific magnetic resonance image finding in patients whose symptom durations were between 2 to 5 months. Compared to ossification of ligamentum flavum, calcium pyrophosphate dihydrate crystal deposition had different image signs, including morphology, side of the involved ligament, no continuity with the lamina, acute on chronic phenomenon, and presence of retro-odontoid mass. Conclusions Nodular calcifications in cervical ligamentum flavum raise highly suspicion for calcium pyrophosphate dihydrate deposition and must be diagnosed by histological examination and polarized light microscopy. This disease is different from ossification of ligamentum flavum, and it could be recognized by specific image features.

Basic calcium phosphate (BCP)-based calcification of cartilage is a common finding during osteoarthritis (OA) and is directly linked to the severity of the disease and hypertrophic differentiation of chondrocytes. Chondrocalcinosis (CC) is associated with calcium pyrophosphate dihydrate (CPPD) deposition disease in the joint inducing OA-like symptoms. There is only little knowledge about the effect of CPPD crystals on chondrocytes and the signaling pathways involved in their generation. The aim of this study was to investigate the chondrocyte phenotype in CC cartilage and the effect of CPPD crystals on chondrocytes. Cartilage samples of patients with CC, patients with severe OA, and healthy donors were included in this study. The presence of CC was evaluated using standard X-ray pictures, as well as von Kossa staining of cartilage sections. OA severity was evaluated using the Chambers Score on cartilage sections, as well as the radiological Kellgren–Lawrence Score. Patients with radiologically detectable CC presented calcification mainly on the cartilage surface, whereas OA patients showed calcification mainly in the pericellular matrix of hypertrophic chondrocytes. OA cartilage exhibited increased levels of collagen X and matrix metalloproteinase 13 (MMP13) compared with CC and healthy cartilage. This observation was confirmed by qRT-PCR using cartilage samples. No relevant influence of CPPD crystals on hypertrophic marker genes was observed in vitro, whereas BCP crystals significantly induced hypertrophic differentiation of chondrocytes. Interestingly, we observed an increased expression of p16 and p21 in cartilage samples of CC patients compared with OA patients and healthy controls, indicating cellular senescence. To investigate whether CPPD crystals were sufficient to induce senescence, we incubated chondrocytes with BCP and CPPD crystals and quantified senescence using β-gal staining. No significant difference was observed for the staining, but an increase of p16 expression was observed after 10 days of culture. Primary chondrocytes from CC patients produced CPPD crystals in culture. This phenotype was stabilized by mitomycin C-induced senescence. Healthy and OA chondrocytes did not exhibit this phenotype. BCP and CPPD crystals seem to be associated with two different chondrocyte phenotypes. Whereas BCP deposition is associated with chondrocyte hypertrophy, CPPD deposition is associated with cellular senescence.