Pseudogout and Calcium Pyrophosphate Deposition Disease

Overview of Terms

The term pseudogout, calcium pyrophosphate depostion disease are considered as synonyms. Though used synonymously these terms denote different meanings should be understood before we discuss the disease further.

Calcium Pyrophosphate Deposition Disease

Calcium pyrophosphate deposition disease is a disease due to deposition of calcium pyrophosphate crystals in the body. It can manifest in four forms namely pseudogout, tophaceous pseudogout, familial calcium pyrophosphate dihydrate deposition and osteoarthritis.

Pseudogout

In actual terms, pseudogout is a presentation of calcium pyrophosphate deposition disease. It occur is a type of arthritis [inflmmation of joints] caused by deposition of calcium pyrophosphate in and around the joints. The term literally means false gout as it resembles gout in symptoms. It can occasionally coexist with gout. It is often used synonymously with all calcium pyrophosphate deposition disease.

Chondrocalcinosis

It is another term used wrongly to denote pseudogout or calcium pyrophosphate crystal deposition disease. Chondrocalcinosis is a radiological finding and denotes deposition of calcium in cartilage. It is known to occur in conditions other than pseudogout or calcium pyrophosphate crystal deposition disease.

Pathophysiology

Calcium pyrophosphate deposition disease consists of the deposition of calcium pyrophosphate crystals into soft tissue. These  Crystals have been found in high concentrations in hyaline cartilage, synovial tissue, capsule, meniscus, labrum, ligamentum flavum, the soft tissue of the hand, and, rarely, the fibrocartilage of the temporomandibular joint.

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.

How exactly this disease develops is not clear but studies suggest chondrocyte and surrounding matrix as the responsible agents.  Some trigger which may be physical or chemical event is thought to begin chain of events that lead to the hypertrophy [increase in size] and degeneration of chondrocytes.

This leads to escape of intracellular calcium to the matrix.Calcium and inorganic pyrophosphate form calcium pyrophosphate crystals within the affected matrix.

Incidence of  incidence of calcium pyrophosphate deposition disease is increased in persons with hyperparathyroidism, hemochromatosis, hemosiderosis, hypomagnesemia, and hypophosphatemia.

Presentation

Calcium pyrophosphate deposition disease presents in following forms.

Pseudogout

Also called as calcium pyrophosphate dihydrate arthropathy cases. The disease which occurs due to deposition of calcium pyrophosphate crystals in joint may not be symptomatic in many cases.

McCarty and colleagues gave the term pseudogout because of its striking similarity to gout. He and others have since recognized that the clinical sequelae of calcium pyrophosphate dihydrate deposition include

The knee is most commonly the joint most frequently affected in calcium pyrophosphate dihydrate arthr involved joint in pseudogout. Other sites include the wrist, shoulder, ankle, elbow, and hands. Rarely, the temporaomandibular joint and ligamentum flavum of the spinal canal are involved.

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. Gout can be distinguished from pseudogout by examining the crystals under microscope. Gout crystals are of sodium urate and are needle shaped and have negative birefringence. Pseudogout crystals (calcium pyrophosphate) are rod or rhomboid shaped and have no or weak positive birefringence.

Pseudogout has an aggressive onset and flares within hours. It causes pain, swelling, heat, and redness of the involved joint.
The natural course is spontaneous resolution over a few days or, at most, weeks.

Tophaceous Pseudogout

This results due to deposition of calcium pyrophosphate material in large quantity producing a big peseudotumor which are often painful. The lesions have been reported in the temporomandibular joint, sternoclavicular joint, transverse ligament of C1, metatarsophalangeal joints, spinal facet joints, cubital tunnel, and other sites.

Familial Calcium Pyrophosphate Dihydrate Deposition

This is a familial condition that appears early, in third decade of life. It is an aggressive condition which is inherited in autosomal autosomal dominant mode of inheritance. Rate of sibling involvement is as high as 70%.

Osteoarthritis

In this condition the symptoms are identical to osteoarthritis. However, at some point of time, the presence of calcium pyrophosphate crystals can be appreciated. When the clinical picture resembles that of slowly progressive osteoarthritis, diagnosis may be more difficult. Mostly, this presentation is identified by chondrocalcinosis.

A number of patients are asymptomatic and symptomatic patients may have acute or chronic presentation.

Acute Attacks

Acute attacks of pseudogout or calcium pyrophosphate arthropathy may be precipitated by

• Trauma, such as physical injury to an extremity
• Joint surgery
• Sprain
• Rapid decrease of serum calcium concentration as after  parathyroidectomy.

In as many as 50 percent of cases, there could be high grade fever.

Lab Investigations

Routine blood counts would reveal an increase in number of white blood cells. Neutrophils are the predominant cells. Investigation should also include serum calcium, phosphorus, alkaline phosphatase, magnesium, serum ferritin, and transferritin saturation.

Imaging Studies

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.

Arthrocentesis

Arthrocentesis is aspiration of the joint. Examination of synovial fluids in the involved would reveal inflammatory nature and calcium pyrophosphate crystals.

These demonstrate weak positive birefringence on polarized light microscopy and are rhomboid in shape. The fluid most often demonstrates an 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.

Microbial staining and culture may be required to differentiate from infection in doubtful cases.

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.

Treatment

Goal of the treatment is to reduce pain of the acute episode, reduce frequency of occurrence and if required treatment of  degenerated joint.

Medical Therapy

As arthritis is 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 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

Joint aspiration and administration of an intra-articular steroid provides relief in acute settings. Non steroidal anti-inflammatory drugs may be used for preventing recurrent episodes.

Treatment with ethylene diamine tetraacetic acid (EDTA)  and pulsed ultrasonography appears promising but needs more testing.

Surgical Therapy

Surgeries described for the disease are debridement [arthroscopic or open], microfracture chondroplasty, radiofrequency chondroplasty, osteochondral transfers, osteotomy, and replacement of the joint are surgical options.

In large tophaceous lesions, surgical excision is indicated.