Features and diagnosis of Calcium Pyrophosphate Dihydrate Crystal Deposition Disease

Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease

This week in clinic I saw a case of CPPD with Dr. Lai. Previously I was under the impression that CPPD caused an acute arthritis (pseudogout). However, I came to know that there is a wide spectrum of findings in CPPD disease which I will discuss here. 

Etiology of CPPD disease

• Idiopathic (most common form)
• Hereditary (AD pattern of inheritance, mutation in the ANKH gene)
• Secondary 
• Hemachromatosis.
• Hyperparathyroidism
• Hypothyroidism
• Hypomagnesemia
• Previous Joint Injury

Thus it can be important to investigate for CPPD in this medical conditions and these secondary causes should be considered during the work-up for CPPD

As per the EULAR task force, the term calcium pyrophosphate crystal deposition (CPPD) is actually an umbrella term for the many different types of clinical presentations. These can include:

1.) Asymptomatic CPPD Disease 

(CPP Crystal deposition is present radiographically but clinical asymptomatic) 

2.) Acute CPP crystal arthritis 

(Commonly referred to as "Pseudogout", this refers to the acute flare of arthritis similar to gout)

3.) Chronic CPP crystal arthritis 

(Sometimes referred to as "Pseudo-RA", this refers to a chronic inflammatory arthritis with morning stiffness, fatigue, synovial thickening, localized edema, and restricted motion; this can also be in conjunction with osteoarthritis which is the most prevalent form of symptomatic CPPD) 

4.) Severe joint degeneration 

(Finally some reports have documented a severe joint degeneration that resembles Charcot joints or Charcot foot which is commonly seen in neurological conditions such as diabetic neuropathy)

Figure 1. Although CPPD deposition disease exists on a continuum, it does not necessarily follow a typical progression. Patients may present anywhere on the continuum

Diagnosis

Diagnosis of CPPD disease is made off synovial fluid analysis AND demonstration of cartilage calcification on radiographs

Synovial Fluid Analysis

The typical synovial fluid finding in CPPD disease include positively birefringent CPP crystals on polarized light microscopy. In an acute attack, crystals within neutrophils may also be seen. 

Figure 2. Appearance of CPPD crystals compared to Monosodium Urate Crystals on polarized light microscopy

Radiographic Features

On plain films (x-rays), CPPD crystal deposition typically appear as punctate and linear radiodensities in articular cartilage. There can also be radiodensities present in ligaments, tendons synovia bursae and joint capsules. This finding is known as chonedrocalcinosis or simply as cartilage calcification. 

Figure 3. Chondrocalcinosis of the knee, with prominent calcification of the menisci. Case courtesy of Frank Gaillard, <a href="https://radiopaedia.org/?lang=us">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/35840?lang=us">rID: 35840</a>

REFERENCES

1. McCarty DJ. Calcium pyrophosphate dihydrate crystal deposition disease--1975. Arthritis Rheum 1976; 19 Suppl 3:275.
2. Rosenthal AK, Ryan LM, McCarty DJ. Calcium pyrophosphate crystal deposition disease, pseudogout, and articular chondrocalcinosis. In: Arthritis and Allied Conditions, 15th, Koopman WJ, Moreland LW (Eds), Lippincott Williams & Wilkins, Philadelphia 2005. p.2373.
3. Rosenthal AK. Pseudogout: Presentation, natural history, and associated conditions. In: Crystal-Induced Arthropathies: Gout, Pseudogout, and Apatite-Associated Syndromes, Wortmann RL, Schumacher HR Jr, Becker MA, Ryan LM (Eds), Taylor and Francis Group, New York 2006. p.99.
4. Zhang W, Doherty M, Bardin T, et al. European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis. Ann Rheum Dis 2011; 70:563.

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