Last Updated on February 20, 2025
Pseudogout refers to acute inflammation of joints caused by calcium pyrophosphate deposition in and around the joints. The term means false gout as it resembles gout in symptoms. Pseudogout can occasionally coexist with gout. It is often used synonymously with all calcium pyrophosphate deposition diseases.
Calcium pyrophosphate deposition disease refers to the deposition of CPPD crystals in the synovial and periarticular tissues of larger and weight-bearing joints. It may be asymptomatic to acute or chronic inflammatory arthritis. In acute presentation, the condition is called pseudogout. Its chronic presentation is termed pseudo-rheumatoid arthritis. The diagnosis is made by joint aspiration and crystal analysis. Pseudogout often affects the elderly. Young patients are rarely affected.
Chondrocalcinosis is a radiological finding and denotes the deposition of calcium in cartilage. It is known to occur in conditions other than calcium pyrophosphate crystal deposition disease.
However, the terms pseudogout, chondrocalcinosis, and calcium pyrophosphate crystal deposition disease may be used interchangeably. Some authors term CPPD as chronic pseudogout too.
Pseudogout mimics gout but is seen in the elderly and favors large joints as compared to gout which favors small joints. Pseudogout and gout can coexist.
Pathophysiology
Calcium Pyrophosphate Deposition Disease
Calcium pyrophosphate deposition disease crystals have been found in high concentrations in
- Hyaline cartilage
- Synovial tissue
- Capsule,
- Meniscus
- Labrum
- Ligamentum flavum
- The soft tissue of the hand
- Fibrocartilage of the temporomandibular joint (rare)
The estimated frequency of this disease is between 4% – 25% of the population by age 80 years. Prevalence increases with age and the males are slightly more affected than females.
The deposition is believed to be caused by an imbalance between the production of pyrophosphate and the levels of pyrophosphatases in diseased cartilage. Increased levels of pyrophosphate deposits occur that combine with calcium to form calcium pyrophosphate. Deposition of CPP is thought to activate the immune system causing inflammation and further soft tissue injury.
Deposition of calcium pyrophosphate is believed to cause activation of the immune system producing inflammation and further soft tissue injury.
This leads to the escape of intracellular calcium to the matrix. Calcium and inorganic pyrophosphate from calcium pyrophosphate crystals within the affected matrix.
Associated Conditions/Risk Factors
The incidence of calcium pyrophosphate deposition disease is increased in persons with
- Joint trauma
- Hemochromatosis
- Hyperparathyroidism
- SLE
- Gout
- Rheumatoid arthritis
- Osteoarthritis
- Wilson’s disease
- Hemophilia
- Long term hemodialysis
- Hypomagnesemia- decreased levels of magnesium
- Chronic kidney disease
- Calcium supplementation
Calcium pyrophosphate deposition disease presents in the following forms.
- Acute pseudogout: Occurs in 25% of patients with CPPD
- Asymptomatic chondrocalcinosis: No symptoms but chondrocalcinosis noted in x-rays
- Pseudo-osteoarthritis: Progressive articular degeneration typically involving the knees, wrists, metacarpophalangeal (MCP) joints, hips, shoulders, spine, elbows and ankles.
- Pseudo-rheumatoid arthritis: Inflammatory arthritis that mimics rheumatoid arthritis. Occurs in a small percentage.
- Pseudo-polymyalgia rheumatica: Occurs in very old people. Presents with systemic symptoms like fatigue, stiffness, and muscle weakness.
- Pseudo-neuropathic arthropathy: Severe destructive monoarthritis that resembles a neuropathic Charcot’s joint
Pseudogout
Pseudogout refers to acute joint arthropathy due to CPDD. The knee is most commonly joint in pseudogout. Other sites include the wrist, shoulder, ankle, elbow, and hands. Rarely, the temporomandibular joint and ligamentum flavum of the spinal canal is involved.
Pseudogout attack may be precipitated by
- Trauma, such as physical injury to an extremity
- Joint surgery
- Sprain
- A rapid decrease of serum calcium concentration after parathyroidectomy.
Other than arthritis, crystal deposition may cause intervertebral disk and ligament calcification with restriction of spine mobility and rarely spinal stenosis. Pseudogout involves multiple joints in at least two-thirds of patients.
The term tophaceous pseudogout is used when an excess of calcium pyrophosphate material gives rise to external swelling. These lesions are in relatively smaller joints like the temporomandibular joint, sternoclavicular joint, etc.
Clinical Presentation
Pseudogout generally presents with acute, onset joint pain. Often the flareup is seen in a single joint. The knee is the most commonly involved joint followed by the wrist. The patient may complain of the warmth of the joint. About half of the patients have a fever.
On examination the affected joint is swollen and redness may be present. The joint would be tender to palpation.
Rarely, patients may present with palpable nodules or masses (tphaceous pseudogout). Spine stiffness and bony ankylosis resembling ankylosing spondylitis may occur in patients with spinal involvement.
Calcification of the posterior longitudinal ligament may cause symptoms of spinal cord compression.
Diagnostic Workup pf Pseudogout
Lab Tests
Routine blood counts would reveal an increase in the number of white blood cells. Neutrophils are the predominant cells. To know about associated conditions, the following tests should be done
- Serum calcium
- Serum phosphorus
- Alkaline phosphatase
- Serum magnesium
- Serum ferritin
- Transferrin saturation
Arthrocentesis
Arthrocentesis is the aspiration of the joint. Examination of synovial fluids involved would reveal an inflammatory nature and calcium pyrophosphate crystals.
These demonstrate weak positive birefringence on polarized light microscopy and are rhomboid in shape. The fluid often demonstrates elevated white blood cells, which is indicative of inflammation (2,000-50,000 cells/µL).
A white blood cell count exceeding 50,000 cells/µL suggests an infection.
Gout crystals are needle-shaped and have negative birefringence (the optical property of certain materials that splits a ray of light into two rays). Pseudogout crystals are rod or rhomboid-shaped and have no or weak positive birefringence.
Microbial staining and culture may be required to differentiate from infection in doubtful cases.
Imaging
For making a diagnosis plain X-ray films are most valuable wherein the presence of chondrocalcinosis (streaking of the soft tissues with calcium) is pathognomonic.
High-frequency ultrasonography is a sensitive method to detect the presence of crystals in the synovial fluid and soft tissue.
Routinely CT or MRI is not needed. MRI may be of help in spinal disease. However, the absence of calcinosis does not rule out
Histologic Findings
Soft tissues demonstrate the presence of crystal deposition and adjacent chondroid metaplasia. Synovial hyperplasia with inflammatory changes consisting of mononuclear cells may be seen.
In tophaceous pseudogout, giant cells often are visualized.
Differential Diagnoses
Treatment of Pseudogout
The goal of the treatment is to reduce the pain of the acute episode, reduce the frequency of occurrence, and if required treatment of degenerated joints.
Medical Therapy
As arthritis is the most common presentation of the disease, these patients are treated in the same line of osteoarthritis. These patients are managed by lifestyle modification, physiotherapy, and nonsteroidal anti-inflammatory drugs. Those patients who do not respond to medical treatment are candidates for surgical treatment.
In acute presentations following measures are taken –
- Joint aspiration – This decreases joint pressure.
- Intraarticular steroid injections.
- Nonsteroidal and-inflammatory agents
- Oral corticosteroids.
- Low doses of colchicine
If one or two joints are involved, joint aspiration and administration of an intra-articular steroid are given. However, if a greater number of joints are involved, the patient is put on NSAIDs to control the inflammation.
Those patients who have recurrent episodes of pseudogout may be put on colchicine.
Surgical Therapy
Surgical procedures are needed only in advanced joint destruction. The various options are
- Debridement [arthroscopic or open]
- Microfracture chondroplasty
- Radiofrequency chondroplasty
- Osteochondral transfers
- Osteotomies
- Joint replacement
In large tophaceous lesions, surgical excision is indicated.
