Introduction
Crystal arthritis caused by calcium pyrophosphate (CPP) crystals.
Aetiology
Common risk factors:
- Hyperparathyroidism (strongest association)
- Age
- Gout/hyperuricemia
- Osteoarthritis (OA)
- Rheumatoid arthritis (RA) (inverse association)
- Diuretics
- Hemochromatosis
Other risk factors:
- Osteoporosis
- Hypomagnesemia, hypophosphatemia
- Chronic kidney disease
- Calcium supplementation
Deposition of calcium pyrophosphate is believed to cause activation of the immune system producing inflammation and further soft tissue injury.
Pathophysiology
Formation of CPP crystals in the pericellular matrix of cartilage is the essential first step in the disease process. CPP crystals rarely form in noncartilaginous tissues. Thus, the cells and highly specialized extra-cellular matrix of cartilage are clearly conducive to CPPD. For example, chondrocytes constitutively generate pericellular exosome-sized vesicles, termed “articular cartilage vesicles,” which serve as important sites of crystal formation in cartilage. Chondrocytes also produce high levels of extracellular inorganic pyrophosphate, which is critical to the formation of CPP crystals.
Clinical features
Acute CPP crystal arthritis “pseudogout” (25% cases):
Represent a dose-related auto-inflammatory response to CPPD crystals shed from cartilaginous tissues into the synovial cavity. Acute calcium pyrophosphate arthritis is generally self-limited, and the inflammation usually resolves within days to weeks of treatment.
- Typically present with the acute onset of monoarticular or oligoarticular arthritis
- Warmth, erythema, and swelling in and around the affected joint (due to vigorous inflammatory response to CPP crystals); indistinguishable from acute gouty arthritis or septic arthritis
- Involved joints: Knee > wrist; acute podagra in the first MTP joint is rare.
- Systemic symptoms: Fevers, chills, and constitutional symptoms
Chronic CPP crystal arthritis (50% cases): Chronic degenerative polyarticular arthritis
Chronic CPP inflammatory arthritis may present overlapping manifestations with rheumatoid arthritis, such as morning stiffness, localized edema, and decreased range of motion. Some patients also present tenosynovitis with carpal or cubital tunnel syndrome. Multiple joints are commonly involved, and the episodes of inflammation may present in a nonsynchronous, waxing, and waning clinical course lasting several months
- CPPD resembling osteoarthritis (common): Distinguishable from typical osteoarthritis by flares of inflammatory signs and symptoms and by unusually severe articular damage
- Joints such as the glenohumeral joint, the wrist, and the metacarpophalangeal joints, which are not often affected by typical osteoarthritis, should lead one to suspect the presence of CPPD disease
- CPPD resembling rheumatoid arthritis (rare): Persistent inflammatory arthritis affecting large and small joints. Flares often involve joints sequentially, and involvement is less symmetric than that seen with rheumatoid arthritis
Other clinical forms:
CPP crystals are commonly seen in spinal tissues, including inter-vertebral disks and spinal ligaments
- Crowned dens syndrome: Deposition of CPP crystals around the C2 vertebra and manifests as acute severe neck pain, fever, and high levels of inflammatory markers. This syndrome is often confused with meningitis or sepsis.
- Severely destructive arthritis similar to neurotrophic (Char-cot’s) arthropathy.
- Tumoral deposits of CPP crystals in soft tissues (rare): Can cause considerable tissue damage and may be mistaken for cancers
- Chondrocalcinosis is present without clinical arthritis: Presymptomatic phase of clinical arthritis, similar to that of hyperuricemia in gout
Diagnosis
CPPD disease is underdiagnosed. 20% unselected patients examined at the time of total joint replacement for osteoarthritis of the knee have CPP crystals in their synovial fluid.
Arthrocentesis (synovial fluid analysis):
definitive diagnosis made by identifying CPPD crystals, by compensated polarized light microscopy, in the SF of affected joints
- Rectangular/rhomboid shaped, positively birefringent crysals
Radiography:
Characteristic intra-articular radiological calcification seen
- Chondrocalcinosis (CHARACTERISTIC): Calcification in hyaline and/or fibrocartilage
Differential diagnosis:
- Gout: In contrast to the brief attacks of acute gouty arthritis that typically last for several days to 1 week, acute attacks of CPPD disease may last for weeks to months.
- Osteoarthritis
- Rheumatoid arthritis
Management
Strategies that are currently employed in ameliorating CPPD-related joint disease are broadly limited to the following; those directed against correcting underlying metabolic abnormalities and treating associated conditions, general treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids (either by local intra-articular injection or systemic therapy), and finally, low-dose oral colchicine
Acute CPP arthritis:
Acute CPP crystal arthritis is managed with strategies that are aimed at reducing inflammation and that are borrowed from therapies used for acute gouty arthritis
Chronic CPP arthritis:
All strategies are aimed at reducing inflammation. Unlike the case with gout, in which long-term therapies reduce the urate burden, no current disease-modulating treatments are available for CPPD disease.
Summary: