Primer: CPPD Disease (Pseudogout)

Writing in the June 30 issue of the New England Journal of Medicine, Ann K. Rosenthal, M.D., and Lawrence M. Ryan, M.D., both of the Medical College of Wisconsin, provide an overview of calcium pyrophosphate deposition (CPPD) disease, which is arthritis caused by calcium pyrophosphate (CPP) crystals – a syndrome known as pseudogout.

The term pseudogout was once used to describe patients with acute arthritis that appeared to manifest as gout, but because synovial fluid crystals were resistant to uricase, it wasn’t defined as gout.

A diagnosis of CPPD has evolved over the years. In the very first cases, it was defined as a “dense narrow band following the contour of the epiphysis” in the articular cartilage, the authors wrote. It was once also referred to as “calcium pyrophosphate dihydrate deposition disease.”

In 2011, the European League against Rheumatism (EULAR) made recommendations designed to address the confusing nomenclature issues. EULAR recommended that (1) calcium pyrophosphate crystals be referred to as CPP crystals; (2) “acute CPP crystal arthritis” refer to the acute inflammatory arthritis (once called pseudogout); and, (3) “chronic CPP crystal arthritis” be used for other types of arthritis associated with CPP crystals. In this review article, the authors use “CPPD disease” to include all related clinical presentations. 

"Approximately 55 years after the initial description of CPPD disease, this common form of arthritis has garnered little attention in the medical community. Diagnostic challenges result in underdiagnosis, but most important, there is a paucity of specific and effective therapies for affected patients. Although no proven disease-modulating agents are available, we can improve outcomes in patients by the careful diagnosis of CPPD disease with the use of a thorough analysis of synovial fluid and the initiation of appropriate treatment strategies," the authors wrote.

Clinical presentation

Acute CPP crystal arthritis (or pseudogout) is the most widely recognized form of CPPD disease. Patients typically present with the acute onset of monoarticular or oligoarticular arthritis. The affected joint – usually the knee or wrist - is usually associated with warmth, erythema and swelling with fevers, chills, and constitutional symptoms. The involvement of joints may indicate CPPD disease.

Pathogenesis

The pathogenesis of CPPD disease is not fully understood, but the formation of CPP crystals in the pericellular matrix of cartilage is the first step in the disease process. Their presence leads to the destruction of tissue by initiating an inflammatory reaction.

Prevalence

CPPD affects 4 to 7 percent of adults in the U.S. and Europe, but it disproportionately affects people who are 60 years old and older:  approximately 44 percent of patients 84 years old or older.

Diagnosis

CPPD disease is underdiagnosed. According to an analysis of patients who were to have joint replacement, 20 percent of these patients had CPP crystals in their synovial fluid.

Management

Reducing inflammation is the primary goal. Current therapies have been borrowed from therapies prescribed for acute gouty arthritis.

For patients with monoarticular or oligoarticular large-joint involvement, repeated intraarticular injections of glucocorticoids may control symptoms. The daily use of oral colchicine at a low dose (0.6 to 1.2 mg) may be useful in reducing the frequency of acute attacks. Alternatively, NSAIDs may produce similar beneficial effects if that they do not cause bothersome side effects. Low-dose systemic glucocorticoids may be necessary to control pain and inflammation in patients in whom colchicine or NSAIDs are ineffective or are associated with unacceptable side effects. Some data support the use of hydroxychloroquine in patients with CPPD disease.

To read the complete article in NEJM, please click here.

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References:

"Calcium Pyrophosphate Deposition Disease."

 Ann K. Rosenthal, M.D., and Lawrence M. Ryan, M.D. N Engl J Med 2016; 374:2575-2584June 30, 2016 DOI: 10.1056/NEJMra1511117