Calcium Pyrophosphate Deposition (CPPD) Disease Treatment & Management

Updated: Apr 07, 2023
  • Author: Constantine K Saadeh, MD; Chief Editor: Herbert S Diamond, MD  more...
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Approach Considerations

Disease-modifying agents are not available for treatment of calcium pyrophosphate deposition (CPPD) disease, so therapy focuses on reducing inflammation and alleviating clinical manifestations. Evidence-based treatment guidelines are lacking, and several of the commonly used treatments are extrapolated from use in gout. [3, 42]

Asymptomatic (lanthanic) CPPD should not be treated. However, if CPPD is a possible manifestation of other syndromes, such as hyperparathyroidism or hemochromatosis, treatment of the underlying condition is important to prevent further end-organ damage, although it cannot reverse the joint disease.

Acute CPP crystal arthritis (pseudogout) may be treated with joint aspiration and intra-articular corticosteroid injection; systemic corticosteroids; nonsteroidal anti-inflammatory drugs (NSAIDs); or, occasionally, high-dose colchicine. Sodium hyaluronate, which is injected intra-articularly to increase joint mobility and improve function when conventional drugs have failed, is approved for treatment of osteoarthritis and has been shown to be effective in CPPD disease as well (note that osteoarthritis can result from CPPD). [43, 44, 45]

Treatment for osteoarthritis with CPPD is similar to that for typical osteoarthritis. Patients with chronic CPP inflammatory crystal arthritis (pseudo–rheumatoid arthritis) can be treated with small doses of corticosteroids, such as prednisone 5 mg daily.

Hydroxychloroquine can be used as adjuvant therapy to prevent flareups. It reduces the release of cytokines such as interleukin-1 (IL-1) and IL-6 and tumor necrosis factor alpha by macrophages. In an animal model of CPPD, it inhibited the activity of matrix metalloprotease. [46]  A double-blind prospective 6-month trial found hydroxychloroquine to be beneficial for chronic CPPD-related arthropathy. [43, 44, 45]

Methotrexate has proved effective in small numbers of patients with severe disease, especially those with joint destruction. However, this treatment has been described only in patients with the pseudo-rheumatoid presentation. [47]  Methotrexate does help reduce joint pain and swelling, and it decreases serum levels of inflammatory biomarkers. In one study of 10 patients with acute inflammation resistant to conventional therapies, methotrexate seemed to be partially effective. [43, 44, 45]

Studies have indicated that activation of IL-1 by the inflammasome complex plays a pivotal role in pseudogout attacks, which suggested the IL-1 receptor antagonist anakinra (Kineret) as a potential alternative for treating patients with CPPD. [48, 49, 50] A systematic review found 74 cases of anakinra use in CPPD, in patients with refractory disease (85.1%) or contraindications to standard treatments. Clinical response to anakinra was observed in 80.6% of patients with acute CPPD disease and in 42.9% of those with chronic CPPD disease. Short-term treatment was well tolerated; adverse events were reported in 4.1% of cases. [51]

Finally, a theoretical possibility for pharmacologic treatment of CPPD is the use of anticrystal agents to prevent deposition of calcium pyrophosphate dihydrate. Such agents include probenecid, phosphocitrate, and polyphosphate. The mechanism of action appears to be through inhibition of transforming growth factor beta 1 (TGF-beta 1), which is an important stimulant of nucleoside triphosphate pyrophosphohydrolase (NTPPPH), an enyzme required for pyrophosphate synthesis. [43, 44, 45]

Radiosynovectomy is a minimally invasive technique that involves the intra-articular injection of small radioactive particles to remove inflamed synovium. Patients with CPPD secondary to hemophilia have responded well to radiosynovectomy, particularly those with a history of repeated joint bleeding. This procedure is considered to be safe, cost-effective, and efficient, with low radiation exposure. [45]

Patients with pseudoneuropathic arthropathy that is refractory to medical management may benefit from surgical replacement of the damaged joint with a bioprosthesis. [43, 44, 45]  

Theoretically, surgically removing calcifications from an affected joint could be beneficial. However, this is currently considered an experimental procedure.


Pharmacotherapy for Pseudogout

The use of NSAIDs can be considered, generally in higher doses during the acute attack and in lesser doses for prevention. Be aware of toxicity, which is common in elderly patients, including gastrointestinal and renal toxicities. Cyclooxygenase-2 (COX-2) ̶ selective NSAIDs (eg, celecoxib) may be as effective as traditional NSAIDs but with less toxicity, although this has not been rigorously tested.

Injection of corticosteroids—such as 40-80 mg (depending on the size of the joint) of methylprednisolone or triamcinolone—into the affected joint has the advantage of avoiding the adverse effects of systemic NSAIDs. Short courses of systemic corticosteroids may be used for polyarticular attacks of pseudogout.  

Oral colchicine, or even intravenous (IV) colchicine, can be considered for the treatment of acute pseudogout. Colchicine should be a treatment of last resort because of its poor therapeutic ratio.

Preventing acute attacks of pseudogout is difficult. Small doses of colchicine (0.6 mg once or twice daily) or NSAIDs have been tried, with variable success.

Anakinra has demonstrated efficacy in patients with recurrent acute CPP arthritis who have intolerance of, or inadequate response to, standard treatments. [51] There is also evidence supporting use of the anti–IL-6 receptor antibody tocilizumab in such cases. [51, 52, 53]