Crystal-Induced Arthropathies Beyond Gout and Pseudogout

Introduction

Crystal-induced arthropathies are caused by the precipitation of crystals in and around the joints and soft tissues. This further causes joint destruction and soft tissue masses. The most common crystal-induced arthropathies include gout and pseudogout. Antony Van Leuwenhoek was the first to recognize crystals in a diseased joint.

What Are Crystal-Induced Arthropathies?

The deposition of crystals in the joints and soft tissues results in articular and periarticular inflammation and injury. This group of disorders is known as crystal-induced arthropathies. There are two types of crystals: monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD).

The crystal arthropathies include gout, calcium pyrophosphate deposition disease, or pseudogout, basic calcium phosphate (BCP)-associated syndromes, and calcium oxalate arthritis.

The most common crystal arthropathies include gout arthropathy and pseudogout.

• The gout arthropathy occurs due to MSU deposition.

• Pseudogout occurs due to CPPD deposition.

Less common crystals include:

• Calcium phosphate hydroxyapatite in generalized peri-tendonitis, osteoarthritis, and erosive arthropathies.

• Calcium oxalate aluminum phosphate deposited in end-stage renal failure patients, short gut syndrome, and primary oxalosis.

• Cholesterol deposited in rheumatoid arthritis and osteoarthritis.

• Xanthine.

• Cysteine.

• Lysophospholipase (Charcot-Leyden).

What Are the Causes of Crystal-Induced Arthropathies?

Crystal deposition such as urate crystal in the joint causes gout leading to pain and inflammation of the joints. These urate crystals are formed among those with high uric acid levels in the blood. This situation arises when the body produces more uric acid or the kidneys cannot remove enough uric acid.

A pseudogout occurs due to the deposition of CPPD crystals in the joints. The pseudogout is called CPPD. Some individuals though have deposition of CPPD in joints, do not develop pseudogout or CPPD. The exact cause of CPPD is not known.

Other factors responsible for the development of gout include:

• A diet rich in meat, seafood, alcohol, and beverages containing fruit sugar (fructose).

• Presence of obesity.

• Presence of health issues like diabetes, hypertension, heart and kidney diseases.

• Medications like diuretics to treat high blood pressure and immunosuppressants to prevent organ rejection in the case of organ transplant recipients.

• Presence of family history of gout.

• In the case of recent surgery or injury.

• Hyperparathyroidism - Increased secretion of parathyroid hormones by parathyroid glands.

• Myeloproliferative Disorders- Blood cancers that occur due to changes in the stem cells in the bone marrow.

• Hemolysis - It is the destruction of red blood cells.

• Extreme Exercise - Work out at 70 to 85 percent of the maximum heart rate.

• Lesch-Nyhan Syndrome - It is an inherited disorder due to the deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).

• Kelley-Seegmiller Syndrome - It is an inherited disorder with the mildest form of HPRT deficiency, a hereditary disorder of purine metabolism, linked with uric acid overproduction.

It was observed that gout is not common among those with premenopause. This is due to the effect of estradiol which lowers the urate levels. This effect is called the urate-lowering effect.

Other factors responsible for the development of pseudogout (CPPD) include:

• Increased age.

• Presence of previous joint surgery or trauma.

• Presence of inherited genetic disorder.

• Increased levels of calcium or iron in the blood.

• Decreased levels of magnesium in the blood.

• Overactive or underactive thyroid.

What Are the Symptoms of Crystal-Induced Arthropathies?

The symptoms of gout can be observed usually at night. These include:

• Experience severe pain in the big toe, ankles, knees, elbows, wrists, and fingers.

• Lingering type and milder pain are observed in joints.

• Redness and inflammation are seen in joints.

• Reduced motion may be observed.

Some individuals with CPPD may not exhibit any symptoms. If symptoms are present, they include severe joint pain, swelling, and warmth.

What Is Gout?

Gout is the most common crystal-induced arthropathy and is estimated to affect 2-3 percent of adults. Gout occurs due to the deposition of MSU crystals in tissues. This may lead to inflammation and tissue damage. The clinical course of gout involves three stages. These include:

• Acute gout.

• Intercritical gout and recurrent gout.

• Chronic tophaceous gout.

Gout is characterized by hyperuricemia (increased levels of uric acid). In gout, the urate levels are more than 6.8 mg/dL. At this level, the urate can get precipitated into MSU crystals.

Gout is more common in males and usually affects at 65 years. Nearly 3 - 8 million people in America are estimated to be affected by gout. The factors affecting include increased alcohol consumption, use of a purine-rich diet, rates of obesity, metabolic syndrome, and making use of diuretic agents.

What Are the Clinical Manifestations of Gout?

The clinical manifestation of gout occurs as arthritis, soft tissue damage, and accumulation of MSU crystals (tophi) in soft tissues, and bone. Hyperuricemia may lead to nephrolithiasis and nephropathy.

Acute gouty arthritis exhibits red, inflamed, and swollen joints. This occurs in lower limbs, especially affecting the first metatarsophalangeal joint (podagra). It may later involve more joints leading to oligoarthropathy and rarely leading to polyarthropathy.

After the acute phase, Intercritical gout may be observed between acute flares. This occurs within seven to ten days. This phase is an asymptomatic period and lasts for months.

Individuals with chronic uncontrolled hyperuricemia and those having chronic kidney disease may develop chronic tophaceous gout. In this type of gout, solid urate crystal collections (tophi), and chronic, destructive changes may be observed in connective tissues. These crystals are yellowish-white, non-tender, and situated in the articular structures, bursae, or ears.

How to Diagnose Crystal-Induced Arthropathies?

The diagnosis of gout can be done by thorough evaluation and additional tests. These include:

• Physical examination by the healthcare provider.

• Taking family and personal history.

• Discussing symptoms and risk factors.

Other tests recommended include:

• Synovial Fluid Analysis: Synovial fluid is aspirated and subjected to microscopic examination. This reveals inflammatory conditions, and leukocytosis may be observed.

• Blood Test: A complete blood count, serum creatinine, and liver function tests are used to identify other comorbid conditions. Serum urate levels may be obtained. Serum urate levels are helpful in chronic gout.

• Urine Tests: A twenty-four-hour urine test is done while considering uricosuric agents.

• Radiography: These imaging modalities include ultrasound, dual-energy computed tomography (CT), and magnetic resonance imaging (MRI).

What Is the Treatment for Crystal-Induced Arthropathies?

After the diagnosis, secondary causes should be excluded, examined for known comorbidities linked to gout, and medications should be checked that can raise the levels of urates.

Patient education is considered very important to therapy and its success. Patients should be made aware of risk factors and triggering factors and about lifestyle modifications that can help reduce the levels of urate and subsequent health issues.

Medications help treat and prevent future attacks and complications. These include:

• Pain relievers like NSAIDs (nonsteroidal anti-inflammatory drugs) or Colchicine.

• Corticosteroid pills or injections at the site of joints to decrease pain and inflammation.

• Medications that can block uric acid production. These are Xanthine oxidase inhibitors (XOIs).

• Uricosurics are used to promote uric acid removal.

• Biological medications that can convert uric acid into soluble compounds can be used.

Treatment Options for CPPD:

Along with pain relievers, and corticosteroids, joint drainage is done to remove crystals from the joints and fluid.

Conclusion

Crystal-induced arthropathy is a cluster of joint disorders. These occur due to the accumulation of urate crystals in the joints and soft tissues. The most common arthropathies include gout and pseudogout. These can be identified and treated. The knowledge or awareness of these issues should be known. This helps in identifying the disease early. Early diagnosis helps in effective treatment. Effective treatment leads to a good quality of life for an affected individual.