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OBJECTIVE: Classification criteria for calcium pyrophosphate deposition disease (CPPD) will facilitate clinical research on this common crystalline arthritis. We report on the first two phases of a four-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member Steering Committee. Item generation (Phase I) included a scoping literature review of five literature databases and contributions from a 35-member Combined Expert Committee and two Patient Research Partners. Item reduction and refinement (Phase II) involved a Combined Expert Committee meeting, discussions among Clinical, Imaging, and Laboratory Advisory Groups, and an item rating exercise to assess the influence of individual items toward classification. The Steering Committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The Advisory Groups eliminated items they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the Steering Committee recommended focusing on imaging of the knee, wrist, and one additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Tophaceous pseudogout is a rare variant of the calcium pyrophosphate dihydrate (CPPD) disorder, with predilection for the TMJ. It is characterized by calcific deposits composed of rhomboid- or rectangular-shaped crystals that exhibit birefringence when examined under polarized light. We hereby present a case of a 65-year-old man with left pre-auricular tenderness and malocclusion. CT imaging was notable for a left TMJ mineralized mass with erosion of the condylar head. Treatment involved excision of the mass with eminectomy, condylectomy, and a stock total TMJ reconstruction. In this report, important considerations for diagnosis, biopsy, and surgical treatment with emphasis on reconstruction for tophaceous pseudogout of the TMJ have been highlighted by the authors.

The history of colchicine dates to ancient Egyptians when it was used for alleviation of swelling and pain. Although its popularity varied throughout the years, colchicine has been a mainstay for the treatment of several diseases, mainly rheumatic and cardiac ones. The mechanism of action of the drug involves several intracellular and extracellular targets, although interaction with tubulin is the most described. Based on several clinical trials and meta-analyses, colchicine is safely recommended as a monotherapy or as an add-on for the treatment and prevention of recurrent pericarditis, post-pericardiotomy syndrome, gout, pseudogout, familial Mediterranean fever (FMF), and Behçet’s disease (BD). Notably, drug safety has been noted during pregnancy and lactation. Besides its major indications, colchicine has shown efficacy and safety in the treatment of various conditions. Because the indications for using colchicine in the prevention of certain conditions such as acute coronary syndrome, stroke, and hepatic cirrhosis and treatment of others such as pneumonia and psoriasis are still debatable, further research works are needed.

Background Calcium pyrophosphate dihydrate (CPPD) disease, also known as pyrophosphate arthropathy or pseudogout, is defined as CPPD deposition within the articular cartilage. It was first described in 1962. The representative locations where CPPD disease occurs include the most common knee joint, followed by the wrist joint. Joint swelling and pain are the most common clinical presentations, and the typical differential diagnosis is degenerative arthritis. Microscopically, the specimen demonstrates numerous positively birefringent rhomboid shaped crystals when examined under polarized light. Case Report We present a 70-year-old female with right painful sciatica accompanied by coexisting affected limb soreness and clumsiness. Her final diagnosis was unusual lumbar extradural tumoral pseudogout that was worth noticing. Tumoral CPPD deposition was excised after laminectomy. Subsequently, her symptoms were abated postoperatively without a need for more analgesics. Her neurological function was properly recovered. Conclusion This is a rare report to proffer pseudogout in an unfamiliar lumbar extradural location, which is an unexpected diagnosis. Making a precise tentative diagnosis for the ongoing disease entity might be difficult for the clinicians because the clinical manifestations of this pathology are similar to those of other common degenerative lumbar spinal diseases.

Calcium Pyrophosphate Crystal Deposition (CPPD) disease is characterized by the deposition of calcium pyrophosphate crystals in the cartilage. In most cases, it can manifest as a subclinical condition named chondrocalcinosis, often revealed by joint x-ray examination. In other cases, deposition can cause flares of arthritis, known as acute CPP crystal arthritis. In the last few years, many pathogenic pathways have been discovered. Interleukin-1 (IL-1) plays a key role in the pathogenesis of CPPD disease, both as a mediator of inflammatory response to crystals and as a promoter of damage to articular cartilage. In this review, we investigated the role of IL-1R inhibitor, such as Anakinra, as an alternative to the various therapeutic strategies for CPPD disease, especially among patients resistant to traditional treatment with NSAIDs, corticosteroids and colchicine.

To date, medical diagnosis of gout and pseudogout has been performed by observing the crystals in the joint fluid of patients under a polarized microscope. Conventional diagnostic methods using a polarized microscope have disadvantages, such as time-consuming analysis, a high false negative rate, and difficulty in distinguishing gout with monosodium urate (MSU) crystals and pseudogout with calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluids. In this study, a chromogenic assay for the diagnosis of gout and pseudogout, without the requirement of a polarized microscope and trained experts, was proposed using Fv antibodies with specific binding activities to MSU and CPPD crystals. The IgG V

OBJECTIVE Identifying pseudogout in large data sets is difficult due to its episodic nature and a lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. The objective of this study was to evaluate a novel machine learning approach for classifying pseudogout using electronic health record (EHR) data. METHODS We created an EHR data mart of patients with ≥1 relevant billing code or ≥2 natural language processing (NLP) mentions of pseudogout or chondrocalcinosis, 1991-2017. We selected 900 subjects for gold standard chart review for definite pseudogout (synovitis + synovial fluid CPP crystals), probable pseudogout (synovitis + chondrocalcinosis), or not pseudogout. We applied a topic modeling approach to identify definite/probable pseudogout. A combined algorithm included topic modeling plus manually reviewed CPP crystal results. We compared algorithm performance and cohorts identified by billing codes, the presence of CPP crystals, topic modeling, and a combined algorithm. RESULTS Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had a sensitivity of 65% and a positive predictive value (PPV) of 22% for pseudogout. The presence of CPP crystals had a sensitivity of 29% and a PPV of 92%. Without using CPP crystal results, topic modeling had a sensitivity of 29% and a PPV of 79%. The combined algorithm yielded a sensitivity of 42% and a PPV of 81%. The combined algorithm identified 50% more patients than the presence of CPP crystals; the latter captured a portion of definite pseudogout and missed probable pseudogout. CONCLUSION For pseudogout, an episodic disease with no specific billing code, combining NLP, machine learning methods, and synovial fluid laboratory results yielded an algorithm that significantly boosted the PPV compared to billing codes.

ZusammenfassungDer aktuelle Fall beschreibt den Fall eines 84 jährigen Patienten mit zunächst unklaren Rückenschmerzen und hohen Entzündungsparameter. Nach Ausschluss infektiöser Ursache konnte im Verlauf eine CPPD (Calcium pyrophosphat deposition disease) Erkrankung mit Wirbelsäulenbefall diagnostiziert werden. Neue radiologische Segmentierungsverfahren erlaubten zudem die Detektion von CPPD Kristallen in peripheren Gelenken. Nach Gabe von Prednisolon und Kineret konnte die Beschwerdesymptomatik erfolgreich behandelt werden.

Crowned dens syndrome (CDS) is a rare form of pseudogout which causes acute neck pain due to calcium pyrophosphate dehydrate deposition surrounding the odontoid process, commonly causing neck pain with rigidity. While invasive procedures such as surgery are known to present a risk of acute pseudogout, reports of occurrence after endoscopic procedures are scarce. We report the case of a 75-year-old man who presented with sudden neck pain after endoscopic submucosal dissection (ESD) for gastric cancer. He could nod but could not rotate his head. Computed tomography showed calcifications surrounding the odontoid process consistent with CDS. Prolonged dietary restrictions and proton pump inhibitor use following the ESD procedure may have caused hypomagnesemia, a precipitating factor for CDS. We prescribed colchicine 1 mg/day and symptoms resolved completely in 3 days. This is the first report of CDS after ESD. CDS should be included in the differential diagnosis of neck pain after endoscopic procedures.

Pseudogout, also known as calcium pyrophosphate deposition disease, is an inflammatory arthropathy that primarily occurs in the peripheral joints, such as the knee or elbow. Spinal pseudogout is uncommon, and neck pain is its most common clinical manifestation. However, cervical myeloradiculopathy as an initial presentation of pseudogout attack of the ligamentum flavum has rarely been reported in the literature. We report a case of a 65-year-old woman who presented with neck pain, bilateral finger numbness, and left-sided upper extremity weakness. Magnetic resonance images showed an epidural mass at the C4-5 level, compressing the spinal cord. Following laminectomy with removal of the calcified mass, the profound neurologic deficits gradually recovered. A pathological examination confirmed the diagnosis of cervical pseudogout.

Acute calcific periarthritis (ACP) is a painful monoarticular disease commonly involving the shoulder joint, characterized by deposits of calcium hydroxyapatite crystals around joints. Clinical mimics include septic arthritis, gout, and pseudogout. It is a rare disease of hand and only few cases have been reported. We describe the imaging findings of ACP of metacarpophalangeal joint secondary to ruptured calcific dorsal bursitis, in a 30-year-old woman who presented with complaints of local pain and swelling of the left fourth finger. Accurate diagnosis of this condition is essential to avoid unnecessary investigations, procedures, and patient anxiety.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy that can involve the temporomandibular joint. It is known to accelerate the osteoarthritic process, often initially presenting with advanced level of disease. The management of CPPD in the rheumatology and orthopedic literature is one of early diagnosis and medical management of acute attacks. The cases of three patients who presented with initial complaints of joint pain and limited mouth opening are presented. Preoperative imaging identified calcifications in two of these patients. Definitive diagnosis was achieved through arthroscopic-assisted biopsy. Rheumatology referrals revealed chondrocalcinosis of the knee in one patient. All patients had improved mouth opening and pain.

This report presents a case of extensive tophaceous pseudogout involving the temporomandibular joint (TMJ), causing erosion into the middle cranial fossa. Pseudogout is a benign metabolic arthropathy caused by calcium pyrophosphate dihydrate crystal deposition within joints and peri-articular tissue. Pseudogout more frequently occurs in large joints such as the knee, wrist, symphysis pubis, and shoulder. Tophaceous pseudogout involving the TMJ is rare, with only seven cases involving erosion into the middle cranial fossa reported previously. Despite skull base erosion being a rare consequence of this erosive disease, this case highlights the importance of appropriate investigation and multidisciplinary team management.

Calcium pyrophosphate deposition disease is characterized by the deposition of pyrophosphate crystals in various joint structures. Calcium pyrophosphate deposition disease can be linked to underlying metabolic disorders such as hemochromatosis, hyperparathyroidism, hypophosphatemia, hypomagnesaemia, and hypothyroidism, all of which increase the risk of calcium pyrophosphate deposition. We present the case of a 55-year-old male who underwent diagnostic examination for the onset of recurrent joint pain in the right knee.

Background Data: Calcium pyrophosphate dihydrate (CPPD) deposition disease is a metabolic disorder caused by the deposition of CPPD crystals in the articular or periarticular structures that leads to inflammation of the joints. Spine affection is rare. Purpose: To present a rare case of lumbar facet joint cyst caused by calcium pyrophosphate arthropathy. Study Design: A case report with a brief review of the literature. Patient and Methods: Seventy-three-year-old man, who underwent PLIF L5/S1 ten years ago, presented with right L4 nerve root compression symptoms that have started two months ago. Clinical examination revealed no motor function disturbance but hypoesthesia in the L4 dermatome. He has no history of crystal deposition disorder. The patient underwent decompression and fusion at this level. Results: The symptoms were completely resolved postoperatively and after one-year follow-up. Histopathological examination of the cyst revealed fibrous granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate. Conclusion: Calcium pyrophosphate arthropathy, although rare, should be incorporated into the differential diagnosis of cystic lesions of the facet joints. (2020ESJ221)

The development of microcrystalline arthritides is most frequently associated with the formation of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals. Their identification is of crucial importance in recognizing these diseases. Objective: to determine the possibilities of histological techniques in identifying MSU and CPP crystals and to evaluate the effectiveness of the techniques. Subjects and methods. Twenty-four tissue blocks (fragments of the affected areas of the elbow joint, the interphalangeal joint of the index finger, and hip joint) from 7 patients were examined. Paraffin sections were stained with a 0.5% alcohol solution of eosin, as well as with hematoxylin and eosin. Tissue specimens were examined and digitized using an AxioScope.A1 stereo microscope with Zenblue software (Carl Zeiss MicroImaging GmbH, Germany). Results and discussion. When staining the tissue sections with hematoxylin and eosin, microcrystals were not visualized; the major portions of MSU crystals was dissolved during fixation and staining, whereas CPP crystals were masked with hematoxylin as focal basophilic aggregates. The staining technique with an alcohol solution of eosin and short formalin fixation (within 12 hours) made it possible to avoid dissolution of MSU crystals and to visualize both MSU and CPP crystals, and to determine their shape and color. Conclusion. Light microscopy of the tissue sections stained with an alcohol solution of eosin along with short formalin fixation is a reliable method to differentiate MSU and CPP crystals. In patients undergoing endoprosthetic replacement, the significance of this technique for the pathomorphological study of surgical material consists in assessing inflammatory activity and in eliminating a disease, such as microcrystalline arthropathy.

Calcium pyrophosphate dihydrate deposition (CPPD) disease, also known as pseudogout, in which crystals are deposited in the joints and/or soft tissues, leads to a variety of articular and periarticular disorders. Herein we report a 67-year-old female patient with neck pain who was diagnosed as CPPD disease of both the atlantoaxial joint and right C4-C5 facet joint with radiological findings. The combined use of computed tomography and magnetic resonance imaging can be helpful in establishing a diagnosis and providing the correct treatment.

Crystalline arthropathies are well-known pathologies in a native knee; however, the literature is scarce with regards to crystalline arthropathies in a total knee arthroplasty (TKA). The presentation of crystalline arthropathy in a TKA can be similar to a periprosthetic joint infection (PJI), making it difficult to distinguish between the 2 diagnoses. We present 1 case highlighting the similarity between crystalline arthropathy and PJI. A 71-year-old man with a history of bilateral TKAs presented with bilateral painful knee effusions and was initially presumed to have PJIs; however, he was later diagnosed with gout and successfully treated medically. A complete review of the literature demonstrates that crystalline arthropathies after TKA are infrequently reported and can be difficult to decipher from PJIs, and there is a lack of standardized treatment.

Calcium pyrophosphate deposition disease (CPPD) is a crystal arthropathy, and may present with various clinical manifestations such as asymptomatic CPPD, osteoarthritis with CPPD, acute CPPD crystal arthritis (formerly pseudogout), and chronic CPPD crystal inflammatory arthritis. It is known that aging, trauma and osteoarthritis are major risk factors for CPPD. Acute CPP arthritis may occur as monoarticular or oligoarticular and usually involves large peripheral joints such as the knees, wrists and ankles. CPPD is characterized by sudden onset of severe pain, swelling and periarticular erythema, and systemic symptoms such as fever, chills, and weakness may occur. On the other hand, axial CPPD has been reported rarely and most cases appear with symptoms related to a mass effect such as foramen magnum syndrome, spinal stenosis, radiculopathy, myelopathy, synovial cyst or cauda equina syndrome. In addition, there are fewer reported cases of spinal CPPD that cause neck and back pain. This clinical condition should be considered in the differential diagnosis of acute neck and back pain.

Background: A hot, swollen joint is a common clinical condition encountered in the ED and elective orthopaedic and rheumatology clinics. These patients can be difficult to manage and properly treat. Aims and Objectives: The aim of this study was to report a single centre retrospective analysis of patients presenting to our institution for a hot, swollen joint over a three-month period. Methods: The study included patients presenting with a hot, swollen joint to ED or electively to clinics. The synovial fluid was aspirated and sent for microbiological and cytological investigation. P value was set to < 0.001. 36 patients (22 M, 14 F) with a mean age of 72.8 ± 17.4 years met our criteria. 20 cases (55.6 %) involved the knee joint, the wrist in 10 cases (27.8%), the elbow in 3 cases (8.3%) and the shoulder in 3 cases (8.3%). Results: Of the 36 synovial fluid samples collected, only 7 (19.4%) reported evidence of infection. On cytological examination of the synovial fluid, 21 (58.3%) reported presence of calcium pyrophosphates crystals (Pseudogout), 4 (11.1 %) reported presence of uric acid crystals (Gout) and 11 (30.5%) reported absence of crystals. We found a significant correlation between age and the diagnosis of pseudogout and between previous antibiotic treatment and ED presentation. Our study sheds light on the high incidence of crystal-related pathologies. Conclusion: In order to improve our management of this common condition and enhance our understanding of the clinical diagnosis in certain patient population, further high-profile clinical studies are needed.

Purpose The purpose of this study is to assess the presence of crowned dens syndrome in patients with calcium pyrophosphate disease. We report 34 patients with crowned dens syndrome in one of the largest series from a single tertiary medical center in North America. Methods A retrospective chart review was conducted at the University of Kansas Medical Center from November 1, 2005-November 1, 2017. A total of 191 patients with calcium pyrophosphate disease were identified. The available cervical computed tomography scans were analyzed by a musculoskeletal radiologist for the presence of periodontoid calcifications and erosions. Results Of the 191 patients with calcium pyrophosphate disease, 57 had cervical computed tomography scans; 34 of them (34/57, 59.64%) had periodontoid calcifications. Only 12/34 patients were formally evaluated and diagnosed by rheumatologists with crowned dens syndrome. Twenty-two of 34 were either not seen by a rheumatologist or were not diagnosed with crowned dens syndrome. The median age was 78.5 years, with 73.52% over 70 years old; 24/34 (70.58%) were female; 17/34 patients (50%) were symptomatic; 28/34 (82.35%) had additional sites of chondrocalcinosis on available radiographs; 8 (28.57%) had 3 or more sites of chondrocalcinosis in typical calcium pyrophosphate disease locations. Six patients did not have any radiographs. Conclusion Crowned dens syndrome is an under-recognized entity that should be considered in elderly patients with neck pain in the setting of calcium pyrophosphate disease. Our data demonstrated a high percentage (about 60%) of patients with calcium pyrophosphate disease who had cervical computed tomography findings consistent with crowned dens syndrome. This underscores the importance of performing cervical computed tomography when evaluating patients with neck pain and calcium pyrophosphate disease.

Calcium pyrophosphate dihydrate crystal deposition (CPPD), also known as pseudogout, can have spinal manifestations in roughly one quarter of patients. We present a rare, intradural manifestation of CPPD requiring surgical intervention, with a review of pertinent differential diagnoses on imaging. A 48-year-old male presented with urinary retention, and was found to have an intradural lesion with peripheral enhancement on gadolinium T1-weighted magnetic resonance imaging. Due to the patient’s progressive neurological deterioration, he was taken for a minimally invasive approach for resection of the lesion. Histopathological analysis revealed crystal deposits with rhomboidal birefringence consistent with CPPD. The imaging features of this lesion were atypical for any of the traditional intradural extramedullary lesions. Typically seen extradurally, recognizing CPPD as a potential culprit for intradural compression is helpful to recognize for providers.

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.

Hereditary hemochromatosis (HH) is an autosomal recessive mutation that results in iron overload. Undetected, it can cause irreversible organ damage to the pituitary and thyroid glands, heart, liver, pancreas, testis, skin, and joints. This irreversible damage can lead to gonadotropin insufficiency, hypothyroidism, heart disease, cirrhosis, hepatocellular carcinoma, diabetes, hypogonadism, bronzing of the skin, pseudogout, and arthropathy. This case study describes a patient who presented to a primary care office for a routine examination with nonspecific complaints and was found to have elevated aminotransferases. Further testing revealed a diagnosis of HH. This case study also illustrates new guidelines outlined for the diagnosis and treatment of HH from the American College of Gastroenterology in 2019.

Gout is a frequently diagnosed condition. However, it is rarely diagnosed with concomitant pseudogout or reactive arthritis (ReA) from ​​​​​Chlamydophila pneumoniae (C. pneumoniae). This case report describes an interesting case of a 67-year-old man who presented with a two-week history of malaise, chills, and shortness of breath. He also reported a one-day history of polyarthritis, which limited his ambulation. The results of polarized microscopy revealed uric acid and calcium pyrophosphate crystals. The respiratory panel was positive for C. pneumoniae and rhinovirus. Therefore, he was diagnosed with gout, pseudogout, and ReA. Appropriate management led to a full clinical recovery. This is the first report documenting the simultaneous occurrence of ReA, gout, and pseudogout in a single patient. The association between these rheumatic diseases and a summary of similar cases in the literature are also discussed.

Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets. Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets. Findings: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD. Conclusion: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individ-ual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA). (c) 2021 Elsevier Inc. All rights reserved.

Background:Ultrasound has been widely used in clinical settings for the assessment of different types of Arthritis as well as in their management. This Review study assessed the diagnostic value of Ultrasonography in comparison with major types of Arthritis namely Osteoarthritis (OA), Rheumatoid Arthritis (RA), Gouty Arthritis (GA), Pseudogout (Calcium Pyrophosphate Deposition Disease - CPPD), Psoriatic Arthritis (PA), Infectious Arthritis (IA) and Spondyloarthritis (SA).Methodology:Computerized literature search of PubMed was conducted from 1990 to present, for publications in English on diagnostic ultrasonography and major types of arthritis. A total of 206 publications were identified. Experimental and clinical studies that focused on the ultrasound features of the major types of Arthritis were accepted. A total of 52 out of the 206 publications, met our search criteria. Among these, 12 studies focused on OA, 7 on RA, 7 on GA, 5 on CPPD, 10 on PA, 4 on IA, and 7 on SA. From all the studies, some distinctive US features are reviewed for each of the major arthritis. Some of the features were unique and some overlapped.Conclusion:Ultrasound may demonstrate the ability to differentiate between the major types of Arthritis on a basic level when combined with history and physical examination. This can prove to be beneficial in the early diagnosis of the major types of arthritis, but with few limitations. This review literature shows that Ultrasound can be very helpful in bed side analysis of the major types of arthritis as well as in differentiating between them, because this modality besides being non-invasive is also very cheap.

Objective We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. Methods Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. Results A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. Conclusion Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Here, we report a case of pseudogout arthritis in a patient treated with MAGE-A4 directed T cell receptor T cells, for fallopian tube cancer. The patient developed CRS and ICANS 7 days after infusion of the T cells. Concurrently, the patient newly developed sudden onset of left knee arthritis. Synovial fluid analyses revealed the presence of calcium pyrophosphate dihydrate crystal. Notably, the pseudogout arthritis was resolved with tocilizumab, which was administered for the treatment of CRS and ICANS. Immunoprofiling of the synovial fluid showed that the proportion of inflammatory interleukin 17 (IL-17)-producing CD4+ T (Th17) cells and amount of IL-6 were notably increased, suggesting a potential role of Th17 cells in pseudogout arthritis after T-cell therapy. To the best of our knowledge, this is the first reported case of pseudogout arthritis after cell therapy. Clinicians, especially hematologists, oncologists and rheumatologists, should be aware that pseudogout arthritis can be associated with CRS/ICANS.

Calcium pyrophosphate dihydrate (CPPD) deposition in the joints, often referred to as pseudogout, can lead to debilitating arthritis. Rare cases of pseudogout associated with bisphosphonate therapy have been reported in the literature, although the mechanism for this remains unclear. We report a case of a 53-year-old female who developed an acute pseudogout attack following administration of zoledronic acid for treatment of osteoporosis.

Objectives Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5′-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. Methods Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. Results Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. Conclusion This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms.

The authors report a case of a rare, large, nodular pseudogout which developed from the temporomandibular joint (TMJ).An 83-year-old female was referred to the hospital with swelling on her left cheek. Imaging studies revealed a large calcified mass surrounding the left mandibular condyle, partially destroying the adjoining bone and extending to the skull base. Magnetic resonance imaging (MRI) revealed soft tissue masses with low signal intensity on T1- and T2-weighted images and were enhanced after intravenous gadolinium injection.The mass was clinically and radiologically suspected to be a neoplastic lesion, such as chondrosarcoma or fibrous dysplasia. However, histological analysis showed that the mass contained granulomatous lesions with numerous multiple nodular rod-shaped and diamond-shaped crystal deposits, which validated the diagnosis of pseudogout. X-ray diffraction (XRD) was performed to identify the tumor's deposited materials and revealed that these were calcium pyrophosphate dihydrate (CPPD) crystals. This result confirmed the histopathological diagnosis of "tophaceous pseudogout."

Gout is the most prevalent inflammatory arthritis found in men. A prompt diagnosis and early treatment of gout are crucial in preventing eventual functional impairment and reduction in comorbidities. In this work, the quantitative material information provided by a multi-contrast x-ray (MCXR) imaging acquisition is leveraged to develop a rapid, non-invasive, and low dose diagnostic method for gout detection and gout-pseudogout differentiation. This work establishes a theoretical foundation to demonstrate how a single-kV MCXR acquisition is capable of differentiating gout from pseudogout via a projection domain two-material decomposition. Experimental results from a benchtop MCXR system are presented. The imaging performance of the proposed MCXR technique is compared to dual-energy radiography to further validate the method.

Introduction: Accumulation of abnormal crystals in the body, derived from endogenous or exogenous materials can drive a wide spectrum of inflammatory disease states. It is well established that intra-articular deposition of monosodium urate (MSU) and calcium pyrophoshate (CPP) crystals contributes to joint destruction through pro-inflammatory processes.Areas covered: This review will focus on current understanding and recent novelty about the mechanisms and the clinical implications of the inflammation induced by MSU and CPP crystals.Expert opinion: Advances in molecular biology reveal that at the base of the inflammatory cascade, stimulated by MSU or CPP crystals, there are many complex cellular mechanisms mainly involving the NLRP3 inflammasome, the hallmark of autoinflammatory syndromes. The extensive studies carried out through in vitro and in vivo models along with a better clinical definition of the disease has led to an optimized use of existing drugs and the introduction of novel therapeutic strategies. In particular, the identification of IL-1 as the most important target in gout and pseudogout has made it possible to expand the pharmacological indications of anti-IL-1 biological drugs, opening new therapeutic perspectives for patients.

Crystal-associated arthropathies are common. Basic calcium phosphate can be associated with osteoarthritis. Calcium pyrophosphate dihydrate (CPPD) can be associated with chronic low-grade inflammation and with episodes of pseudogout. Tophi and smaller aggregates of monosodium urate (MSU) can lead to erosive, deforming arthropathy and recurrent attacks of gout. Incidence and prevalence of gout are increasing. Aspiration and polarizing microscopy, the gold standard, are not always performed. Ultrasound detects crystal deposition readily and can improve diagnosis and management. BCP crystals appear sonographically as small spheres that can aggregate to form a collection of such “bubbles.” They are found in basal joints of the thumb, finger joints, and joints of the midfoot. CPPD crystals are generated within hyaline cartilage and fibrocartilage and are found predominantly there, typically forming a hyperechoic layer in the center of cartilage. MSU crystals form tophi embedded in vascularized granulation tissue, deposit over hyaline cartilage, and create a sonographic double contour sign or form small hyperechoic aggregates within tissues. The inflammatory changes associated with crystal arthritis can be documented with color or power Doppler ultrasound. In contrast to other imaging modalities, ultrasound can be performed safely and relative inexpensively over time, is sensitive to change, and can therefore assess the treatment response.

Introduction Calcification of the ligamentum flavum can cause acute neck pain and compression of the spinal cord, which can induce myelopathy. However, there are very few reports of acute exacerbation of myelopathy due to a pseudogout attack of the cervical ligamentum flavum, and there are no reports of that after a cervical spinal cord injury. Here, we report the case of a patient with acute neck pain and tetraplegia caused by pseudogout attack of the cervical ligamentum flavum after cervical central spinal cord injury. Case presentation A 78-year-old man experienced mild tetraplegia after falling. He was diagnosed with cervical spinal cord injury without radiographic abnormality. Four days after the injury, he developed fever and his paralysis worsened. Magnetic resonance imaging revealed increasing of spinal stenosis at the C4-5 level. Computed tomography revealed calcification of the ligamentum flavum at the same level. C3 laminectomy and C4-5 laminoplasty were performed. A collection of turbid yellow fluid was found in the ligamentum flavum. A histopathological examination revealed evidence of calcium pyrophosphate dihydrate crystals in the fluid. Discussion With increase in the aging population in Japan, the patients with acute exacerbation of myelopathy due to pseudogout in the cervical spine following spinal cord injury without radiographic abnormality may increase in the future. Computed tomography is useful for the diagnosis of such cases.

Gout is a common metabolic disease with growing burden, caused by monosodium urate (MSU) microcrystal deposition. In situ and chemical-specific histological identification of MSU is crucial in the diagnosis and management of gout, yet it remains inaccessible for current histological methods. Methods: Stimulated Raman scattering (SRS) microscopy was utilized to image MSU based on its fingerprint Raman spectra. We first tested SRS for the diagnosis capability of gout and the differentiation power from pseudogout with rat models of acute gout arthritis, calcium pyrophosphate deposition disease (CPDD) and comorbidity. Then, human synovial fluid and surgical specimens (n=120) were were imaged with SRS to obtain the histopathology of MSU and collagen fibers. Finally, quantitative SRS analysis was performed in gout tissue of different physiological phases (n=120) to correlate with traditional histopathology including H&E and immunohistochemistry staining. Results: We demonstrated that SRS is capable of early diagnosis of gout, rapid detection of MSU in synovial fluid and fresh unprocessed surgical tissues, and accurate differentiation of gout from pseudogout in various pathophysiological conditions. Furthermore, quantitative SRS analysis revealed the optical characteristics of MSU deposition at different pathophysiological stages, which were found to matched well with corresponding immunofluorescence histochemistry features. Conclusion: Our work demonstrated the potential of SRS microscopy for rapid intraoperative diagnosis of gout and may facilitate future fundamental researches of MSU-based diseases.

Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and diagnostic tests overlap. Accurate differentiation is important as treatment plans vary significantly. We sought to systematically review all cases of total knee arthroplasty (TKA) periprosthetic crystalline arthropathy reported in the literature and summarize clinical, diagnostic, and operative findings in the context of guidelines for diagnosing PJI. The goal of this systematic review is to determine the amount of diagnostic overlap and to identify best practices for differentiating between these two diagnoses. MEDLINE and Google Scholar were searched to identify cases of crystalline arthropathy following TKA. Case reports were reviewed for patient characteristics, clinical symptoms, physical exam, laboratory results, and treatment outcomes. These findings were summarized across patients and dichotomized based on current thresholds for diagnosing PJI according to Musculoskeletal Infection Society criteria. Twenty-six articles were identified which included 42 cases of periprosthetic crystalline arthropathy (17 gout, 16 pseudogout, one both, and eight not specified). Of these cases, 25 presented over 1 year after their index arthroplasty and 15 had no prior history of crystalline arthropathy. Only six cases had a superimposed infection based on aspiration or intraoperative cultures. For cases without a culture-positive infection, several diagnostic tests overlap with PJI thresholds: 95% of patients had C-reactive protein greater than 1 mg/dL, 76% had an erythrocyte sedimentation rate greater than 30 mm/hour, 91% had a synovial white blood cell greater than 3,000 cells, and 76% had a synovial polymorphonuclear cells percent greater than 80%. Patients without co-infection were managed with non-steroidal anti-inflammatory drugs, colchicine, allopurinol, steroids, or a combination of these treatments and most had complete resolution of symptoms within 1 week. Commonly used markers of PJI fail to reliably distinguish periprosthetic crystalline arthropathy from infection. Though clinical judgement and consideration of the implications of delayed treatment for acute PJI remain paramount, in the setting of synovial crystals, surgeons may wish to consider this alternate etiology as the source of the patient's clinical symptoms.

Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to ‘trap extracellular particles’, including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack.

Crowned dens syndrome (CDS) is a relatively uncommon presentation of calcium pyrophosphate dihydrate (CPPD) deposition disease that manifests as acute attacks of neck pain with fever, neck rigidity and elevated inflammatory markers related to radiodense deposits of CPPD in ligaments around the odontoid process. We present a case of CDS.

In this case, a 78-year-old female with no previous medical history of crystalline arthropathy presented with pain, effusion, and erythema about a total knee arthroplasty (TKA) performed 13 years prior. Implementation of a novel synovial fluid alpha-defensin assay ruled out periprosthetic joint infection (PJI) despite a positive 2018 Musculoskeletal Infection Society (MSIS) minor criteria score of 8 points, a significant diagnostic differentiation which prevented secondary invasive debridement or joint irrigation intervention. Confirmatory histologic study was positive for calcium pyrophosphate crystals, indicative of acute pseudogout inflammation rather than PJI or septic arthritis manifestation. The patient was then conservatively managed medically for a pseudogout flare and had no evidence of infection with normal physical exam and laboratory study at one- and two-years post treatment, respectively. Given the predominantly clinical nature of current PJI assessment in-clinic coupled with notable risks associated with aggressive re-intervention in the setting of suspected infection, critical need exists for the maturation of sensitive, reliable empiric measures which may assist in guiding orthopaedic surgeon evaluation of patients presenting with inflammatory symptomology around a previous surgical site. In this case, we conclude that patients with a negative alpha-defensin assay alongside crystalline arthropathy on histology may be cautiously yet successfully treated non-operatively despite clinical MSIS criteria concerning for PJI.

Objective. To report a rare case of an acute attack of calcium pyrophosphate dihydrate (CPPD) deposition disease in a patient with lumbar spondylolytic spondylolisthesis, which demonstrated widespread lesion with neurological deficit. Methods. An 86-year-old woman presented with high fever and bilateral neurological deficit of the lower extremities. Results. CRP was elevated (20.9 mg/dl). Plain radiographs and computed tomography images showed bilateral L4 spondylolytic spondylolisthesis. Sagittal magnetic resonance (MR) images revealed effusion at the L3-4 interspinous space, and a gadolinium- (GD-) enhanced epidural mass was observed at the level of L4 vertebral body. Axial MR images showed an intra- or epidural lesion at L2-3. Moreover, epidural GD-enhanced masses compressed the dural sac in the shape of a cross at the L3-4 and L4-5 segments. The patient was suspected of having pyogenic arthritis of the lumbar spine in initial diagnosis. A total of 1.2 ml of fluid with a murky, pus-like synovial effusion was aspirated from the L3-4 interspinous space under the fluoroscopic image. Smear speculum of synovial fluid tested negative for bacteria and fungi; however, a number of crystals were seen. Based on the result of smear speculum, we suspected the pathology as crystal deposition disease. Based on polarized light microscopy, which revealed monocle or triclinic intracellular crystals with a positive birefringence, the patient was diagnosed with pseudogout of the lumbar spine. Nonsteroidal anti-inflammatory drugs (NSAIDs) were administered by intravenous drip injection for 3 days, and local and systemic inflammatory signs, as well as neurological deficits, dramatically improved. Conclusions. We encountered the rare case of an acute attack of pseudogout with the wide lesion in the lumbar spondylolytic spondylolisthesis. Multiple culture of the effusion provided a definitive diagnosis, which allowed for appropriate, minimally invasive treatment for 8 weeks of NSAID administration that provided the satisfactory recovery from the symptoms.

We read the comment on our article by Lopez-Gonzalez et al with great interest.1 2 The authors detail the presentation of four cases of acute arthritis in patients hospitalised with COVID-19 and underlying gout (three cases) or recurrent arthritis of unknown origin (one case). Although we await further reports, there have been anecdotes of newly diagnosed inflammatory arthritis in the context of COVID-19 infection, perhaps representing either a viral-associated arthritis or a reactive arthritis.3 4 However, as the authors note, common causes of acute inflammatory arthritis must continue to be considered in the differential diagnosis—these include crystal-associated arthritis, such as gout or pseudogout. Acute …