Gout and Pseudogout Flares in the Hospital: A Practical Guide for the Hospitalist

Dr Neeraj Manikath , claude.ai

Abstract

Crystal-induced arthropathies, particularly gout and pseudogout, represent common yet frequently mismanaged causes of acute arthritis in hospitalized patients. These painful inflammatory conditions often arise in the context of physiologic stress, dehydration, and metabolic derangements that characterize acute illness. This review provides a comprehensive, evidence-based approach to the diagnosis and management of acute crystal arthropathy flares in the inpatient setting, with emphasis on practical clinical pearls that enable rapid recognition and treatment without specialist consultation. Understanding the nuances of diagnosis, appropriate therapeutic selection, and critical pitfalls can significantly improve patient outcomes, mobility, and satisfaction during hospitalization.

Introduction

Acute gout and pseudogout flares are among the most painful conditions encountered in hospital medicine, yet they remain surprisingly underrecognized and undertreated. The incidence of gout has increased substantially over recent decades, affecting approximately 4% of adults in the United States, with even higher prevalence among hospitalized patients due to multiple precipitating factors inherent to acute illness.¹ Pseudogout, caused by calcium pyrophosphate deposition disease (CPPD), affects approximately 5% of individuals aged 60-70 years and up to 50% of those over 90 years.²

The hospital environment creates a perfect storm for crystal arthropathy: dehydration, renal impairment, diuretic use, dietary changes, metabolic acidosis, and the stress of acute illness all promote crystal precipitation and inflammatory flares.³ Recognition and prompt treatment of these conditions not only alleviates suffering but also facilitates early mobilization, reduces length of stay, and prevents the cascade of complications associated with immobility in older adults.

Pathophysiology: Understanding the "Why Now?"

Pearl #1: The timing of gout flares during hospitalization is not random. Understanding the mechanisms helps anticipate which patients are at risk.

Gout results from monosodium urate crystal deposition in joints and soft tissues when serum uric acid levels exceed the saturation point (approximately 6.8 mg/dL). However, hyperuricemia alone is insufficient—crystal formation requires precipitating factors. In hospitalized patients, these include sudden fluctuations in serum urate levels (paradoxically, both increases and rapid decreases can trigger flares), dehydration concentrating synovial fluid, acidosis reducing urate solubility, and the inflammatory milieu of acute illness activating the NLRP3 inflammasome.⁴

Pseudogout occurs when calcium pyrophosphate dihydrate (CPPD) crystals are released from cartilage into the joint space. Unlike gout, pseudogout is strongly associated with acute medical illnesses, particularly sepsis, myocardial infarction, stroke, and major surgery.⁵ The mechanism involves crystal shedding triggered by inflammatory cytokines and metabolic stress.

Hack: Suspect crystal arthropathy in any hospitalized patient with acute monoarticular or oligoarticular arthritis, especially if they have predisposing conditions: chronic kidney disease, heart failure, diabetes, hypertension, or recent diuretic use.

Clinical Diagnosis: Trust Your Examination

The Classic Presentations

Gout classically affects the first metatarsophalangeal joint (MTP)—podagra—in approximately 50% of initial attacks and eventually in 90% of patients over their disease course.⁶ However, hospitalized patients frequently present with atypical distributions: knees, ankles, wrists, and even polyarticular involvement are common. The affected joint demonstrates the hallmarks of acute inflammation: exquisite tenderness, erythema, warmth, and swelling. Patients often cannot tolerate even the weight of bed sheets touching the affected area.

Pearl #2: The clinical diagnosis of gout in a patient with classic podagra and prior confirmed gout is sufficient to initiate treatment. Arthrocentesis, while gold standard, is not always necessary.

Pseudogout most commonly affects the knee (50% of cases), followed by the wrist, shoulder, ankle, and elbow.⁷ The presentation can be identical to gout, though pseudogout may present with more systemic symptoms including fever and elevated inflammatory markers, potentially mimicking septic arthritis more closely than gout does.

When Clinical Diagnosis Suffices

The 2015 ACR/EULAR gout classification criteria include clinical features that, when present, provide high diagnostic confidence:⁸

• Pattern recognition: podagra, ankle/midfoot involvement
• Timing: symptom onset within 24 hours reaching maximal intensity
• Characteristics: erythema overlying the joint, severe tenderness
• Resolution: complete improvement within 14 days

Oyster #1: A normal serum uric acid level does NOT exclude acute gout. During acute flares, serum urate levels may decrease due to uricosuric effects of acute inflammation and increased renal clearance. Approximately 30-40% of patients with acute gout have serum urate levels below 6.8 mg/dL at presentation.⁹

When to Perform Arthrocentesis

Synovial fluid analysis remains the gold standard for definitive diagnosis, particularly important in several scenarios:

1. First episode without prior documented gout: Establishing the diagnosis prevents future diagnostic uncertainty
2. Suspected septic arthritis: Any uncertainty about infection mandates aspiration
3. Atypical presentation: Polyarticular involvement, unusual joints, or inadequate response to therapy
4. Immunocompromised patients: Higher risk of both crystal disease and infection

Technique Pearl: When aspirating for crystal analysis, use a plain tube (without heparin or other additives) and examine under polarized microscopy promptly. Gout crystals are needle-shaped and strongly negatively birefringent (yellow when parallel to the compensator axis). CPPD crystals are rhomboid-shaped and weakly positively birefringent (blue when parallel).

Hack: If immediate microscopy is unavailable, synovial fluid can be refrigerated (not frozen) for up to 48 hours without significant crystal dissolution.

Differentiating from Mimics: The Critical Distinctions

Septic Arthritis: The Cannot-Miss Diagnosis

Distinguishing crystal arthropathy from bacterial septic arthritis represents the most crucial clinical decision, as delayed antibiotic therapy for septic arthritis increases morbidity and mortality significantly.

Clinical clues favoring septic arthritis:

• Systemic toxicity: high fever (>38.5°C), rigors, hemodynamic instability
• Severe constitutional symptoms out of proportion to joint findings
• Risk factors: prosthetic joint, immunosuppression, IV drug use, recent joint injection, skin breakdown
• Extreme synovial fluid white blood cell count (>50,000/μL, though overlap exists)

Oyster #2: Crystal arthropathy and septic arthritis can coexist in the same joint. If any doubt exists, treat for septic arthritis while awaiting culture results. The presence of crystals does not exclude infection.

Pearl #3: The synovial fluid lactate level shows promise as a discriminator. Levels >10 mmol/L strongly suggest bacterial infection, while levels <5 mmol/L favor inflammatory arthritis.¹⁰ However, this test is not universally available.

Cellulitis: Periarticular vs. Intraarticular

Distinguishing between periarticular cellulitis and true joint inflammation can be challenging, particularly around the ankle and first MTP where overlying soft tissue involvement may obscure the clinical picture.

Differentiating features:

Feature	Gout/Pseudogout	Cellulitis
Pain with passive motion	Severe	Mild to moderate
Joint effusion	Present	Absent
Distribution of erythema	Concentrated over joint	Spreading, poorly demarcated
Speed of onset	Hours (usually <24h)	Days
Preceding trauma/break in skin	Rare	Common

Hack: If the patient cannot bear any passive range of motion of the joint without severe pain, suspect intraarticular pathology. Cellulitis typically allows some passive motion, even if uncomfortable.

First-Line Treatment: Choose Wisely Based on Patient Factors

The three first-line options for acute crystal arthropathy are NSAIDs, colchicine, and corticosteroids. Selection depends on renal function, comorbidities, and contraindications rather than efficacy—all three work well when appropriately chosen.¹¹

NSAIDs: Effective but Often Contraindicated

Indomethacin (50 mg TID) has traditionally been considered the "gold standard" NSAID for gout, though evidence suggests equivalent efficacy across NSAIDs including naproxen (500 mg BID), ibuprofen (800 mg TID), and celecoxib (200 mg BID initially).¹²

Contraindications to consider:

• Estimated GFR <60 mL/min/1.73m² (relative)
• Active peptic ulcer disease
• Recent GI bleeding
• Heart failure
• Concurrent anticoagulation
• Cardiovascular disease (especially recent MI or stroke)

Pearl #4: In hospitalized patients, NSAIDs are frequently contraindicated. Don't hesitate to move to alternative therapies—they work just as well and often more safely in this population.

Colchicine: Low-Dose is as Effective as High-Dose

The AGREE trial revolutionized colchicine dosing, demonstrating that low-dose regimens provide equivalent efficacy to traditional high-dose protocols while significantly reducing gastrointestinal side effects.¹³

Correct dosing regimen:

• Initial dose: 1.2 mg immediately
• Second dose: 0.6 mg one hour later
• Maintenance: 0.6 mg twice daily (starting the next day)

Oyster #3: The old high-dose colchicine protocol (0.6 mg every hour until diarrhea or symptom relief, up to 6 mg) is obsolete and dangerous. Never use this approach.

Renal dosing considerations:

• CrCl 30-60 mL/min: Reduce maintenance to 0.6 mg once daily
• CrCl <30 mL/min: Consider avoiding or use 0.6 mg every other day with extreme caution
• Dialysis patients: Generally avoid colchicine

Drug interaction warning: Colchicine is metabolized by CYP3A4 and is a P-glycoprotein substrate. Concurrent use with strong CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir) or P-glycoprotein inhibitors (cyclosporine) can lead to fatal colchicine toxicity.¹⁴ Check the medication list carefully.

Pearl #5: Colchicine works best when started within 36 hours of symptom onset. After 48-72 hours, efficacy diminishes substantially.

Corticosteroids: The Workhorse for Hospitalized Patients

Corticosteroids represent an excellent choice for hospitalized patients, particularly those with renal impairment, multiple comorbidities, or contraindications to NSAIDs and colchicine.

Dosing regimens:

• Oral prednisone: 30-40 mg daily for 5-7 days
• Alternative: Prednisolone 30-35 mg daily
• Intravenous: Methylprednisolone 40 mg daily (if patient cannot take oral)

Hack: For short courses (≤7 days), no taper is necessary. Abrupt discontinuation after brief treatment does not cause adrenal suppression and simplifies the regimen, improving compliance and preventing prolonged steroid exposure.¹⁵

Intraarticular corticosteroid injection:

For monoarticular flares, particularly in patients with multiple contraindications to systemic therapy, intraarticular corticosteroid injection provides rapid relief with minimal systemic effects.

• Large joints (knee): Triamcinolone 40 mg or methylprednisolone 40-80 mg
• Medium joints (ankle, wrist): Triamcinolone 20-30 mg
• Small joints (MTP): Triamcinolone 10-20 mg

Critical caveat: Only perform intraarticular injection after infection has been definitively excluded. If septic arthritis remains in the differential, aspirate for analysis and culture before any steroid administration.

What NOT to Do: Common Pitfalls

Never Start Allopurinol During an Acute Flare

Oyster #4: This represents the most important "pearl" to avoid. Initiating urate-lowering therapy (allopurinol, febuxostat) during an acute gout attack paradoxically worsens and prolongs the flare by causing rapid fluctuations in serum urate levels and promoting further crystal shedding.¹⁶

Correct approach:

• Treat the acute flare completely
• Wait 2-4 weeks after complete resolution
• Initiate urate-lowering therapy with concurrent prophylaxis (low-dose colchicine 0.6 mg daily or NSAIDs)
• Continue prophylaxis for 3-6 months during urate-lowering therapy titration

Exception: If a patient is already on chronic allopurinol when admitted, continue it. Stopping established therapy can also trigger flares.

Don't Over-Rely on Uric Acid Levels

Serum uric acid has limited diagnostic utility during acute flares. It may be normal, elevated, or low depending on timing and acute phase response. Do not use serum urate levels to rule in or rule out acute gout.

Avoid Premature Discontinuation of Anti-Inflammatory Therapy

Flares typically improve within 24-48 hours but require a complete treatment course (typically 7-10 days) to prevent rebound inflammation. Patients often feel dramatically better after 2-3 days and may wish to stop therapy—counsel them to complete the full course.

Special Populations

Chronic Kidney Disease Patients

Preferred approach: Corticosteroids (prednisone 30-40 mg daily × 5-7 days)

Alternative: Low-dose colchicine with appropriate renal dosing adjustments, though caution is warranted

Avoid: NSAIDs in moderate-to-severe CKD

Heart Failure Patients

NSAIDs can precipitate acute decompensation through sodium retention and increased afterload. Corticosteroids are preferred, though brief courses carry minimal fluid retention risk compared to NSAIDs.

Diabetic Patients

Corticosteroids will elevate blood glucose, often substantially. This should not preclude their use—simply anticipate the need for increased insulin or other diabetes medications during the treatment course. The benefit of treating severe inflammatory arthritis outweighs temporary hyperglycemia.

Hack: Warn patients with diabetes about expected glucose elevations and adjust diabetes medications proactively rather than reactively.

Transplant Recipients and Immunosuppressed Patients

These patients present unique challenges:

• Higher baseline risk of septic arthritis—maintain low threshold for arthrocentesis
• Chronic immunosuppression may mask typical inflammatory signs
• Drug interactions with calcineurin inhibitors and colchicine can be fatal
• Corticosteroids may be preferred, though many are already on chronic steroids

Pseudogout: Specific Considerations

Management of acute pseudogout mirrors that of gout with identical first-line therapies. However, several distinctions deserve mention:

Pearl #6: Pseudogout more commonly presents with fever and systemic symptoms, increasing the imperative to exclude infection definitively.

Unlike gout, pseudogout has no disease-modifying therapy analogous to urate-lowering agents. Management focuses on acute flare treatment and addressing underlying metabolic disorders when present (hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia).¹⁷

Radiographic clues: Look for chondrocalcinosis on plain radiographs—linear or punctate calcifications within cartilage, particularly the menisci of the knee, triangular fibrocartilage of the wrist, or symphysis pubis. However, chondrocalcinosis may be absent in acute pseudogout or present without symptoms.

Beyond Acute Management: Setting Up for Success

Patient Education

Before discharge, ensure patients understand:

• This flare represents a symptom of underlying disease requiring long-term management
• Follow-up with primary care or rheumatology for consideration of urate-lowering therapy (for gout)
• Lifestyle modifications: limit alcohol, adequate hydration, weight loss if indicated
• Dietary purine restriction has modest effects but may help

Discharge Planning

For gout patients: Consider rheumatology referral or ensure primary care follow-up within 2-4 weeks to discuss initiation of urate-lowering therapy after flare resolution. Target serum urate <6 mg/dL (or <5 mg/dL for tophaceous gout).

Documentation: Clearly document the diagnosis, treatment course, and plan for long-term management. Many patients have recurrent hospitalizations for "mystery arthritis" simply because prior diagnoses were not communicated effectively.

Conclusion

Acute gout and pseudogout flares represent common, painful, yet highly treatable conditions in hospitalized patients. Rapid clinical recognition, appropriate selection of anti-inflammatory therapy based on patient-specific factors, and avoidance of common pitfalls enable hospitalists to manage these conditions independently and effectively. Understanding that clinical diagnosis often suffices, that multiple therapeutic options exist with equivalent efficacy, and that short-course corticosteroids require no taper empowers confident management. Most critically, remembering never to initiate urate-lowering therapy during acute flares prevents iatrogenic prolongation of suffering. With these principles, hospitalists can significantly improve patient comfort, facilitate early mobilization, and optimize outcomes for this frequently encountered condition.

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Author Disclosure: No conflicts of interest to declare.

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