PSEUDOGOUT
CPPD DISEASE
Disease process
The term ‘pseudogout’ (pseudo = imitation) originates from descriptions of patients presenting with similar signs and symptoms of gout that did not respond to appropriate gout treatment. Recent developments in the understanding of pseudogout have led to the condition being more accurately referred to as calcium pyrophosphate deposition (CPPD) disease.
CPPD disease is not as well understood as gout but the two conditions are thought to share a similar process. The body regulates the levels of inorganic pyrophosphate but if excessive levels are present within a joint, calcium pyrophosphate crystals can form in the cartilage, triggering an inflammatory response and altering the mechanical properties of the cartilage.
A simple analogy of the crystal formation process would be to imagine sugar in a cup of boiled water. Initially the sugar will dissolve in the fluid but as more is added it will no longer dissolve and the sugar will collect at the bottom of the cup. The sugar is less likely to dissolve if the water is cold, which may explain why ‘colder’ joints such as the big toe are more susceptible to gout.
Risk factors
CPPD disease is more common in patients with previous trauma to a joint, especially surgery to the meniscus of the knee. CPPD disease is more common in older age groups, and unlikely to be present in individuals under the age of 60. There are no known dietary associations with CPPD disease, but individuals with excess iron (haemochromatosis), overactive parathyroid glands (hyperparthyroidism), low magnesium (hypomagnesemia), hypophosphatasia, or thyroid disorders may be at higher risk of CPPD disease.
Presentation
CPPD disease typically presents with the signs and symptoms of inflammation (pain, swelling, heat, redness and difficulty moving the joint) in one joint (monoarthrthritis) or 2-4 joints at the same time (oligoarthritis), with signs and symptoms lasting for weeks or months. The knee is the most commonly affected joint, followed by the wrist, but the big toe is unlikely to be affected.
Diagnosis
Definitive diagnosis of CPPD disease requires the identification of crystals in samples of fluid taken from the affected joint. Fluid is withdrawn from the affected joint via a needle (joint aspiration) and analysed with polarising light microscopy to confirm the presence of calcium pyrophosphate crystals. These samples should be analysed immediately at room temperature as formation and solubility of crystals are affected by temperature and pH. The sample should also be assessed for the presence of bacteria by performing gram stain and culture as CPPD disease and joint infection can present with similar signs/symptoms and the conditions can co-exist.
Elevated temperature (fever), C-Reactive protein and white blood cell levels may indicate infection, but in acute flare ups of CPPD disease, these levels may also be raised, especially when multiple joints are involved.
Imaging
Chondrocalcinosis (calcium deposits in the cartilage) may be visible on X-ray, but X-ray will not identify all patients with CPPD disease and chondrocalcinosis can also be caused by other conditions (e.g. knee osteoarthritis, rheumatoid arthritis). Ultrasound and CT scans have more recently been utilised to identify chondrocalcinosis, and therefore aid the diagnosis of crystal arthropathy.
Treatment
Acute flare-ups of CPPD disease should be managed with medication (e.g. non-steroidal anti-inflammatories (NSAIDs), colchicine, or corticosteroid), as prescribed by a qualified health care professional. Repeated corticosteroid injections into the knee may control symptoms, while daily use of colchicine may reduce the frequency of acute flare-ups. Other medication may be trialled for the management of long-standing CPPD disease; the potential risks and benefits of different medications should be discussed with the individual’s health care provider.
Since CPPD disease typically affects older patients, the presence of the disease in younger patients may indicate an underlying metabolic or genetic issue. The health care provider may therefore order a metabolic screen to check for the relevant risk factors, and treat accordingly. Unlike gout, disease modifying medication are not currently available for CPPD disease. advanced cases, knee joint replacement may be indicated for individuals with symptoms that are not responding appropriately to conservative treatment.
Signposting
Individuals presenting with a first episode of sudden onset (within 24 hours) heat, swelling and pain in the knee, with no history of injury, should attend Accident and Emergency immediately to exclude an infection in the joint (septic arthritis).
Patients that have had a previous episode of similar symptoms, which was diagnosed as inflammatory arthritis, may have a flare up and can contact their GP or rheumatologist immediately. However, a previous diagnosis of inflammatory arthritis does not exclude the possibility of joint infection; therefore, the patient should attend Accident and Emergency immediately if there is any doubt as a delay in diagnosis can have serious consequences.
Written by: Richard Norris
Peer reviewed by:
Dr Paul Kirwan (PhD) | @pdkirwan
References
Rosenthal AK, Ryan LM. Calcium Pyrophosphate Deposition Disease. N Engl J Med. 2016;374(26):2575-84.