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143: Articular Chondrocalcinosis

Matthew Brown

Key Points

  • Disease summary:

    • The diagnostic for calcium pyrophosphate dihydrate (CPPD) crystal deposition is given after the identification of CPPD crystals in synovial fluid (SF) or in tissue sections.

    • The terminology of CPPD-related diseases is still not uniform; the following definitions are the most commonly used:

      • Pseudogout—acute clinical syndrome of synovitis associated with CPPD deposition

      • Pyrophosphate arthropathy—structural abnormality of cartilage and bone associated with articular CPPD deposition

      • Chondrocalcinosis (CC)—radiographic observation of calcification of fibro and/or hyaline articular cartilage

    • CPPD deposition is the main cause of radiographic articular calcification of the knee, that is, CC. The deposition of other calcium salts, such as hydroxyapatite, can also be the cause of articular calcification.

  • Hereditary basis:

    • CPPD deposition disease (CPDD) can occur as a familial monogenic disorder showing an autosomal dominant pattern of inheritance.

  • Differential diagnosis:

    • Certain metabolic diseases predispose to CPDD deposition such as hemochromatosis, Gitelman syndrome, and hyperparathyroidism. It is possible to screen these disorders by laboratory hematologic testing and evaluate elevated serum calcium, decreased serum phosphate, elevated parathyroid hormone or parathormone, elevated alkaline phosphatase, and increased serum ferritin. However, it is important to refer that these disorders have strong genetic component themselves. In Table 143-1, it is possible to see how to perform a genetic differential diagnosis.

Table 143-1Genetic Differential Diagnosis
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Table 143-1 Genetic Differential Diagnosis
Syndrome Gene Symbol Associated Findings

Hemochromatosis

HFE, TFR2, HJ, HAM, SLC40A1

Group of phenotypically and genetically heterogeneous disorders characterized by iron overload. CPPD-CC has a well-known association with hemochromatosis affecting about 67% of the patients.

Gitelman syndrome

SLC12A3

Variant of Barter syndrome in which patients present hypokalemic alkalosis in conjunction with hypocalciuria and hypomagnesemia. CPPD-CC has been widely associated with this syndrome affecting a large majority of these patients.

Hypophosphatasia

ALPL

Heterogeneous biochemical and clinical features which include low levels of serum alkaline phosphatase, high levels of serum pyridoxal-5-prime-phosphate, early loss of teeth (odontohypophosphatasia), bowed legs, calcification of paraspinous ligaments, joint pains, and peri- and intra-articular calcifications of joints of the hands, feet, and knees and calcification of the anterior spinous ligament in the lumbar area.

Hyperparathyroidism

MEN1, HPRT2, HRPT3

This is the most common familial form of primary hyperparathyroidism. Primary chief cell hyperplasia is the main characteristic of this disorder. Many patients show hypercalcemia and radiologic changes characteristic of chondrocalcinosis.

Familial hypocalciuric hypercalcemia, type I

CASR

This was the first disorder described where renal tubular defect in calcium reabsorption is independent of parathormone. A ratio of renal calcium clearance to creatinine clearance below 0.01 suggests FHH1. The only complications attributable to the hypercalcemia are pancreatitis and chondrocalcinosis. Both the kidneys and the parathyroid glands seem insensitive to chronic hypercalcemia in this disease.

Gene names: HFE, hemochromatosis; TFR2, transferrin receptor-2; HJV, hemojuvelin; HAMP, hepcidin antimicrobial peptide; SLC40A1, solute carrier family 40 member 1; ALPL, alkaline phosphatase; MEN1, menin; HRPT2...

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