Pseudogout: Symptoms, Types, Causes and Treatment

Pseudogout, medically known as calcium pyrophosphate deposition disease (CPPD), is a common but often misunderstood joint condition, especially prevalent in older adults. While it shares some features with gout, pseudogout has distinct causes, symptoms, and treatment options. This article offers a comprehensive, evidence-based overview of pseudogout, including its symptoms, types, underlying causes, and the latest approaches to treatment.

Symptoms of Pseudogout

Pseudogout can present in many ways, from sudden painful joint attacks to more subtle, chronic discomfort. Recognizing its symptoms is crucial for timely diagnosis and effective management.

Symptom	Description	Frequency/Severity	Source(s)
Joint Pain	Sudden, severe pain in one or more joints	Acute, can be intense	1, 2, 8
Swelling	Joint swelling, warmth, and redness	Common during flares	2, 8, 10
Stiffness	Reduced joint mobility, especially in knees	Often present	1, 8
Systemic Signs	Fever, fatigue, headache in severe cases	Occasionally	1, 4
Neurologic	Neuropathic symptoms (rare)	Rare, can be severe	2, 4

Table 1: Key Symptoms

Common Joint Manifestations

Pseudogout typically causes acute attacks of pain, swelling, and warmth in large joints, most often the knees, but also the wrists, shoulders, ankles, and elbows. The onset is usually sudden, with joints becoming visibly swollen and tender. Movement may be restricted due to pain and stiffness. While less commonly, smaller joints can also be affected 1, 2, 8.

Systemic and Unusual Symptoms

Some patients may experience fever, chills, or even headaches during a flare, mimicking infections or other systemic illnesses 1. In rare cases, pseudogout can cause symptoms beyond the joints, including neurological complications. For example, inflammation in the neck (crowned dens syndrome) can mimic meningoencephalitis, while crystal-induced swelling in the wrist may cause neuropathic symptoms such as numbness or tingling in the hand 1, 2, 4.

Chronic and Atypical Presentations

Chronic pseudogout may present as persistent low-grade pain and stiffness, sometimes mistaken for osteoarthritis. Severe cases can involve the formation of large, tumor-like masses (tophaceous pseudogout), causing joint deformity or even bone destruction 3, 4.

Types of Pseudogout

While "pseudogout" is often used as a general term, CPPD can manifest in several distinct forms, each with unique characteristics and clinical implications.

Type	Key Features	Typical Locations	Source(s)
Acute Pseudogout	Sudden, painful joint attacks	Knees, wrists, elbows	2, 8, 10
Chronic CPPD	Ongoing, mild-moderate pain	Multiple large joints	8, 10
Tophaceous	Masses of crystal deposits	TMJ, digits, periarticular sites	3, 4
Crowned Dens	Neck pain, neurological signs	Cervical spine (dens)	1, 4

Table 2: Types of Pseudogout

Acute Pseudogout

The most recognizable form, acute pseudogout, refers to sudden attacks of severe joint pain and swelling. Flares may last days to weeks and often recur. The knee is the classic site, but other large joints can be involved 2, 8, 10.

Chronic CPPD Arthropathy

Some individuals develop a chronic form characterized by persistent, low-level inflammation and degeneration, similar to osteoarthritis. This can lead to ongoing joint pain, stiffness, and reduced mobility 8, 10.

Tophaceous Pseudogout

In rare cases, CPPD crystals accumulate to form large, tumor-like masses known as tophi. These growths may invade surrounding tissues, cause bone destruction, and sometimes mimic neoplastic conditions. The temporomandibular joint (TMJ) and digits are reported sites 3, 4.

Crowned Dens Syndrome

A unique variant, crowned dens syndrome, involves crystal deposition around the odontoid process (dens) of the cervical spine. Symptoms include severe neck pain, headache, fever, and sometimes neurological signs, mimicking serious infections 1, 4.

Causes of Pseudogout

Understanding what triggers pseudogout is key for both prevention and management. The root cause lies in the deposition of calcium pyrophosphate dihydrate (CPPD) crystals, but several risk factors and underlying mechanisms contribute to disease development.

Cause/Risk Factor	Description	Relative Risk / Association	Source(s)
Aging	Increased risk with advancing age	High	8, 10
Osteoarthritis	Joint degeneration linked to crystal buildup	Moderate to high	6, 10
Hyperparathyroidism	Hormonal imbalance raises calcium levels	Strong	6, 10
Loop Diuretics	Medication increases risk of crystalization	Mild to moderate	6
Chronic Renal Failure	Impaired kidney function	Moderate	6
Genetic/Unknown	Familial cases, idiopathic origins	Variable	3, 10
Inflammatory Response	NALP3 inflammasome activation	Key molecular mechanism	5, 10

Table 3: Causes and Risk Factors

Crystal Deposition and Joint Environment

Pseudogout is fundamentally caused by the accumulation of CPPD crystals in cartilage and joint tissues. These crystals can trigger intense inflammation when released into the joint space, leading to pain and swelling 3, 5, 8, 10.

Age and Joint Disease

The risk of pseudogout increases sharply with age, particularly after age 60. Degenerative joint changes, such as those seen in osteoarthritis, make joints more susceptible to crystal deposition 6, 8, 10.

Metabolic and Endocrine Abnormalities

Certain metabolic disorders, especially hyperparathyroidism (which raises blood calcium levels), are strongly associated with pseudogout. Chronic renal failure and the use of loop diuretics also contribute to risk, likely by altering mineral balance 6, 10.

Genetic and Idiopathic Cases

Some cases appear to run in families, suggesting a genetic predisposition. However, in many instances, no clear cause can be identified—these are termed idiopathic 3, 10.

Inflammatory Pathways

At the molecular level, CPPD crystals activate the NALP3 inflammasome, leading to the production of inflammatory cytokines such as IL-1β. This process is central to the pain and swelling seen in both acute and chronic pseudogout 5, 10.

Treatment of Pseudogout

Managing pseudogout focuses on relieving acute symptoms, preventing recurrences, and addressing underlying causes. While there is no cure or crystal-dissolving therapy, several effective strategies can improve quality of life.

Treatment	Mechanism/Approach	Best For	Source(s)
NSAIDs	Reduces inflammation and pain	Acute flares	1, 8, 10
Colchicine	Reduces crystal-induced inflammation	Acute & prophylaxis	7, 10
Corticosteroids	Powerful anti-inflammatory effect	Severe/refractory cases	1, 9, 10
Anakinra (IL-1 Blockade)	Targets inflammatory pathway	Resistant disease	9, 10, 11
Surgical Intervention	Removes large crystal masses	Tophaceous cases	2, 4
Address Risk Factors	Discontinue loop diuretics, treat underlying disease	Prevention/recurrence	6, 10

Table 4: Treatment Approaches

Acute Flare Management

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): First-line treatment for acute attacks, effective in reducing pain and swelling. NSAIDs should be used with caution in elderly patients or those with comorbidities 1, 8, 10.
• Colchicine: Particularly useful if started early, colchicine can both treat acute flares and prevent recurrences. Studies show significant reduction in flare frequency with ongoing low-dose use 7, 10.
• Corticosteroids: Oral or intra-articular steroids are potent options for patients who cannot tolerate NSAIDs or colchicine, and can provide dramatic symptom relief in severe or refractory cases 1, 9, 10.

Novel and Advanced Therapies

• IL-1 Blockers (Anakinra): For patients with resistant or severe pseudogout, IL-1 inhibition has emerged as an effective therapy, targeting the core inflammatory pathway triggered by CPPD crystals. Anakinra has shown good results in clinical studies, especially in hospitalized or immunocompromised patients 9, 10, 11.

Surgical and Non-Pharmacologic Interventions

• Surgical Removal: In cases where large tophi or crystal-induced masses cause nerve compression or joint destruction, surgery may be necessary. Outcomes are generally positive when the masses are completely excised 2, 4.
• Lifestyle and Risk Factor Modification: Addressing underlying conditions—such as hyperparathyroidism, chronic kidney disease, and avoiding loop diuretics when possible—may help prevent future attacks 6, 10.

Long-Term Management and Prognosis

While there are currently no medications proven to dissolve CPPD crystals, regular monitoring and timely treatment of flares can significantly improve joint function and quality of life. Collaboration with rheumatology specialists is recommended for complex or recurrent cases 2, 10.

Conclusion

Pseudogout is a prevalent yet often underrecognized joint disease, especially among older adults. Its diverse presentations—from sudden, painful flares to chronic joint degeneration—require careful diagnosis and individualized management. While there is no definitive cure, advances in understanding its causes and inflammatory mechanisms have led to more effective treatments and improved patient outcomes.

Key Points:

• Pseudogout commonly presents with sudden joint pain, swelling, and stiffness, most often affecting large joints like the knee.
• Variants include acute, chronic, tophaceous, and crowned dens syndrome, each with unique clinical features.
• The primary cause is the deposition of calcium pyrophosphate dihydrate crystals, with risk factors including aging, osteoarthritis, metabolic disorders, and certain medications.
• Treatment focuses on symptom relief using NSAIDs, colchicine, corticosteroids, and, in severe cases, IL-1 inhibitors like anakinra. Surgery is considered for large crystal masses.
• Managing underlying risk factors and comorbidities can help prevent recurrences and improve long-term joint health.

Awareness of pseudogout’s symptoms, types, causes, and treatments empowers patients and clinicians to work together for better outcomes and quality of life.