Daniel J McCarty, MD: A Giant of Rheumatology.

There is no doubt that Dr Daniel J McCarty warrants inclusion among the giants of rheumatology. He has made major contributions to both clinical and scientific knowledge in our field, and his impact has been long-lasting and paradigm shifting. He is perhaps best known for his pioneering work in crystal arthritis, but as an astute clinician, he is also responsible for describing several other novel rheumatic conditions and developing innovative treatment protocols.

Identification of Common Pathogenic Pathways Involved in Hemochromatosis Arthritis and Calcium Pyrophosphate Deposition Disease: a Review.

Objectives: Arthritis is a common clinical manifestation of hereditary hemochromatosis (HH), and HH is one of a handful of conditions linked to calcium pyrophosphate deposition (CPPD) in joints. The connection between these two types of arthritis has not yet been fully elucidated. In light of new pathogenic pathways recently implicated in CPPD involving bone, we reviewed the literature on the etiology of hemochromatosis arthropathy (HHA) seeking shared pathogenic mechanisms.

Pathogenesis of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition disease is defined by the presence of calcium pyrophosphate (CPP) crystals in articular cartilage and is the fourth most common type of arthritis in adults. Despite its high prevalence, the etiology of CPPD disease remains unclear and no specific therapies currently exist. It has been known for several decades that abnormalities of cartilage pyrophosphate metabolism are common in patients with CPPD disease, and this classic work will be reviewed here.

Calcium pyrophosphate crystal size and characteristics.

Objective: To describe the characteristics of calcium pyrophosphate (CPP) crystal size and morphology under compensated polarized light microscopy (CPLM). Secondarily, to describe CPP crystals seen only with digital enhancement of CPLM images, confirmed with advanced imaging techniques.

Methods: Clinical lab-identified CPP-positive synovial fluid samples were collected from 16 joint aspirates.

Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group.

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.

The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negative rheumatoid arthritis patients.

Background: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers.

Effects of the TNFRSF11B Mutation Associated With Calcium Pyrophosphate Deposition Disease in Osteoclastogenesis in a Murine Model.

Objective: The gene TNFRSF11B encodes for osteoprotegerin (OPG) and was recently identified as the CCAL1 locus associated with familial calcium pyrophosphate deposition disease (CPDD). While the CCAL1 OPG mutation (OPG-XL) was originally believed to be a gain-of-function mutation, loss of OPG activity causes arthritis-associated osteolysis in mice, which is likely related to excess subchondral osteoclast formation and/or activity. The purpose of the present study was to further explore the effect of OPG-XL in osteoclastogenesis.

Management of calcium pyrophosphate crystal deposition disease: A systematic review.

Objective: Calcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety.

Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR-155 in rheumatoid arthritis.

Objectives: miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients.

Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition.

Calcium pyrophosphate (CPP) crystal deposition (CPPD) is prevalent and can be associated with synovitis and joint damage. The population of elderly persons predominantly affected by CPPD is growing rapidly. Since shortfalls exist in many aspects of CPPD, we conducted an anonymous survey of CPPD unmet needs, prioritized by experts from the Gout, Hyperuricemia and Crystal-Associated Disease Network.

Concurrence of rheumatoid arthritis and calcium pyrophosphate deposition disease: A case collection and review of the literature.

Objective: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly associated with aging as well as a handful of metabolic syndromes. Recent epidemiologic studies suggest a positive association of CPDD and rheumatoid arthritis (RA).

Basic calcium phosphate crystal-associated musculoskeletal syndromes: an update.

Purpose Of Review: Basic calcium phosphate (BCP) crystals are associated with two important musculoskeletal syndromes. Deposition of BCP crystals in tendons, bursae, and other soft tissues around joints causes calcific periarthritis, whereas intra-articular BCP crystals contribute to osteoarthritis and cause the highly destructive arthritis known as Milwaukee Shoulder Syndrome. The epidemiology and natural history of these syndromes are poorly understood, and because the pathogenesis remains unclear, few targeted therapies are available.

Calcium Pyrophosphate Deposition Disease and Associated Medical Comorbidities: A National Cross-Sectional Study of US Veterans.

Objective: Calcium pyrophosphate deposition disease (CPDD) is a common cause of acute and chronic arthritis, yet there are few large epidemiologic studies of CPDD. We sought to characterize CPDD in the national Veterans Affairs (VA) population.

Methods: Using data from the Department of VA Corporate Data Warehouse, patients with International Classification of Diseases, Ninth Revision, codes for CPDD seen at any VA medical center from 2010 through 2014 were matched by age and sex with control patients without CPDD.

Erosive osteoarthritis: A systematic analysis of definitions used in the literature.

Background: Erosive osteoarthritis (EOA) is a commonly invoked diagnosis representing an important variant of hand osteoarthritis (OA). There is increasing literature on the prevalence, risk factors, etiology, and management of EOA.

Methods: We systematically reviewed the literature to assess variability in the diagnostic definitions used to define EOA in these studies.

Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.

Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity.

The Role of ANK in Calcium Pyrophosphate Deposition Disease.

The protein product of the progressive ankylosis gene, known as ANK, is a 492-amino acid multi-pass transmembrane protein. This protein is critical for the regulation of pyrophosphate, and gain of function ANK mutations is associated with calcium pyrophosphate deposition disease. Much about the structure, function, and regulation of ANK remain unstudied.

Articular cartilage vesicles and calcium crystal deposition diseases.

Purpose Of Review: Articular cartilage vesicles (ACVs) are small extracellular vesicles that serve as foci of pathologic calcium crystal deposition in articular cartilage matrix. In this review, I have summarized the role of ACVs in calcium crystal formation and discuss recent findings that impact our understanding of the content, behavior, and origin of ACVs in healthy and diseased joints. The burgeoning interest in extracellular vesicles in other fields renders this a timely and relevant topic.

Validation of administrative codes for calcium pyrophosphate deposition: a Veterans Administration study.

Background: Despite high prevalence, progress in calcium pyrophosphate deposition (CPPD) has been limited by poor awareness and absence of validated approaches to study it in large data sets.

Objectives: We aimed to determine the accuracy of administrative codes for the diagnosis of CPPD as a foundational step for future studies.

Methods: We identified all patients with an International Classification of Diseases, Ninth Revision, Clinical Modification code for chondrocalcinosis (712.

Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes.

Imaging of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition disease (CPPD) is a common and clinically heterogeneous form of arthritis caused by the deposition of calcium pyrophosphate (CPP) crystals in articular tissues. The diagnosis of CPPD is supported by the presence of radiographic chondrocalcinosis; yet, conventional radiography detects only about 40 % of clinically important CPPD. Here, we critically review the recent literature on imaging in CPPD.

Nonpharmacologic and pharmacologic management of CPP crystal arthritis and BCP arthropathy and periarticular syndromes.

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies.

Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease.

Objective: Accumulation of excess extracellular inorganic pyrophosphate leads to calcium pyrophosphate dihydrate (CPPD) crystal formation in articular cartilage. CPPD crystal formation occurs near morphologically abnormal chondrocytes resembling hypertrophic chondrocytes. The ANK protein was recently implicated as an important factor in the transport of intracellular inorganic pyrophosphate across the cell membrane.