PseudogoutZCalcium Pyrophosphate Deposition Disease
GENERAL PRINCIPLES
Etiology
Pseudogout results when calcium pyrophosphate dihydrate crystals deposited in bone and cartilage are released into synovial fluid and induce acute inflammation.
It can present in various ways that mimic other rheumatologic diseases.Classification
• Asymptomatic calcium pyrophosphate dihydrate deposition (CPPD) disease
• Osteoarthritis (OA) with CPPD, also known as “pseudo-OA,” refers to patients who have chondrocalcinosis or CPP crystals in a joint affected by OA
• Acute CPP crystal arthritis, also known as “pseudo-gout”
• Chronic CPP crystal inflammatory polyarthropathy, also known as “pseudo-RA”
î CPPD is primarily a disease of the elderly and the majority of these cases are idiopathic. Risk factors include older age, advanced OA, neuropathic joint, diabetes mellitus, joint trauma, or surgery.
î Early onset of CPPD can be due to an underlying condition such as hypophosphatasia (low alkaline phosphatase activity), hyperparathyroidism, hemochromatosis, hypomagnesemia, or familial CPPD disease due to genetic mutations.
DIAGNOSIS
Clinical Presentation
Pseudogout may present as an acute monoarthritis or oligoarthritis, mimicking gout, or as a chronic polyarthritis resembling RA or OA. Usually, the knee or wrist is affected, although any synovial joint can be involved.
Diagnostic Testing
• These can be useful if an underlying metabolic disease associated with CPPD is suspected, particularly in young patients or patients with severe arthritis. Workup should include calcium, phosphorous, PTH (hyperparathyroidism), iron, total iron-binding capacity, ferritin (hemochromatosis), alkaline phosphatase (hypophosphatasia), and magnesium (hypomagnesemia).
• Synovial fluid analysis
î Definitive diagnosis of CPPD is by identification of calcium pyrophosphate dihydrate crystals in synovial fluid or tissue biopsy.
CPP crystals are pleomorphic and weakly positively birefringent, which makes it more difficult to detect than urate crystals. Presence of crystals does not exclude coincident infection.î Leukocyte counts during an acute attack usually ranges between 15,000 and 30,000 cells/mm3 with neutrophilic predominance.
IMAGING
Calcium deposition in the cartilage or chondrocalcinosis is a finding that is supportive of (but not diagnostic for) pseudogout and its absence does not exclude it. Hook-like osteophytes can be seen, especially in MCPs, but unlike RA, CPPD does not have typical bony erosions. If pseudogout is suspected, films of the wrists, knees, and pubic symphysis may be ordered, as these are the most common sites for chondrocalcinosis.
TREATMENT
• Treatment is targeted at symptom control. Treatment of associated conditions should be considered, although its beneficial effect on CPPD arthritis is unknown.
• Acute symptomatic treatment: As in gout, the therapy of choice for most patients is a brief high-dose course of an NSAID. Oral corticosteroids, intra-articular corticosteroids, and colchicine may also relieve symptoms promptly.
• Treatment of chronic or recurrent symptoms: Different medications can be used including the following:
î NSAIDs
î Colchicine 0.6 mg PO daily or twice a day
î Methotrexate 5-20 mg PO weekly or hydroxychloroquine 200-400 mg PO daily can be considered in resistant cases