# CIM Case: Tophaceous Gout ## Clinical Scenario **Patient:** 74-year-old male farmer **Presentation:** 3-year history of progressive, painful swelling in the anterior compartment of right leg, enlarging masses over both elbows and dorsum of feet **Relevant history:** Longstanding gout (30 years), poorly controlled, multiple previous acute flares requiring colchicine, not on regular urate-lowering therapy, CKD stage 3 (eGFR 45), hypertension on thiazide diuretic **Examination findings:** - Large irregular subcutaneous mass anterior right leg (8 x 5 cm), firm, non-tender, chalky material visible through thin overlying skin - Multiple smaller tophi over olecranon bursa bilateral - Tophi dorsum of feet bilateral, overlying 1st MTP joints - Chronic deformity 1st MTP joints bilateral (hallux valgus appearance) - Limited ROM 1st MTP, subtalar joints bilateral - Skin over some tophi thin, whitish material visible - No acute inflammation currently - No fever, systemically well --- ## Investigations Provided ### Laboratory Results | Test | Result | Normal Range | Interpretation | |------|--------|--------------|----------------| | Haemoglobin | 135 g/L | 130-170 | Normal | | WCC | 8.5 × 10⁹/L | 4-11 | Normal | | ESR | 25 mm/hr | 0-20 | Mildly elevated | | CRP | 12 mg/L | <5 | Mildly elevated | | Uric acid | 0.62 mmol/L | 0.20-0.42 | **Elevated** | | Creatinine | 155 μmol/L | 60-110 | **Elevated** (CKD3) | | eGFR | 45 mL/min | >90 | **Reduced** | | Glucose | 6.2 mmol/L | 3.0-6.0 | Mildly elevated | | Urinary uric acid | 4.8 mmol/24hr | 1.5-4.5 | Elevated (under-excretor) | ### Imaging **Image 1: Plain Radiographs - Feet AP and Lateral** **Radiological features:** - Punched-out erosions 1st MTP joints bilateral (overhanging edges) - Soft tissue swelling with calcification over 1st MTP - Joint space narrowing 1st MTP bilateral - Preserved joint space elsewhere initially - Periarticular osteopenia minimal - No acute fracture **Image 2: Plain Radiograph - Right Leg** **Radiological features:** - Large soft tissue mass anterior leg - Dense calcified deposits within mass - No underlying bone erosion - Soft tissues otherwise normal **Image 3: Dual-Energy CT (DECT) if available** **DECT findings (if performed):** - Monosodium urate deposits colour-coded green - Extensive urate deposition around 1st MTP joints - Urate deposits within anterior leg mass - Additional deposits at elbow, Achilles insertion ## Questions & Model Answers **Diagnosis: Tophaceous Gout** This patient has advanced, chronic tophaceous gout with polyarticular involvement and extra-articular tophi. **Definition of Tophi:** | Feature | Description | |---------|-------------| | **Composition** | Monosodium urate (MSU) crystal deposits | | **Structure** | Granulomatous tissue surrounding crystals | | **Appearance** | Firm, irregular nodules; may be white/chalky | | **Location** | Subcutaneous, periarticular, intra-articular, bursal | **Common Sites for Tophi:** | Site | Frequency | |------|-----------| | 1st MTP joint | Very common | | Olecranon bursa | Very common | | Finger PIPs | Common | | Ear helix | Classic (but less common) | | Achilles tendon | Common | | Extensor tendons (hand/foot) | Common | | Patella | Occasional | | Spine | Rare but reported | **Clinical Progression of Gout:** | Stage | Features | |-------|----------| | **Asymptomatic hyperuricaemia** | Elevated uric acid, no symptoms | | **Acute gouty arthritis** | Acute monoarthritis, self-limiting | | **Intercritical gout** | Asymptomatic periods between attacks | | **Chronic tophaceous gout** | **This patient** - tophi, chronic arthropathy | **Risk Factors for Tophaceous Gout:** | Factor | This Patient | |--------|--------------| | Long duration of gout | Yes (30 years) | | Poor uric acid control | Yes (no regular ULT) | | Renal impairment | Yes (CKD3) | | Diuretic use | Yes (thiazide) | | High purine intake | Possible (farmer, diet) | | Alcohol | Unknown | **Differential Diagnosis:** | Condition | Distinguishing Features | |-----------|------------------------| | Rheumatoid nodule | RA history, different location | | Soft tissue tumour | No gout history, imaging | | Chronic infection | Fever, elevated inflammatory markers | | Tumoral calcinosis | Different crystal (calcium phosphate) | | Xanthoma | Yellow, associated with hyperlipidaemia | > **Consultant Tip:** Tophaceous gout indicates prolonged hyperuricaemia and inadequate treatment. The uric acid level during chronic phase may be misleadingly normal - always correlate with clinical picture. **Investigation Strategy for Tophaceous Gout:** **1. Laboratory Investigations:** **Serum Uric Acid:** | Finding | Interpretation | |---------|----------------| | >0.42 mmol/L (7 mg/dL) | Hyperuricaemia | | May be normal during acute attack | Urate shifts into tissue | | This patient: 0.62 mmol/L | Significantly elevated | **Inflammatory Markers:** | Test | This Patient | Significance | |------|--------------|--------------| | ESR | 25 | Mildly elevated (chronic inflammation) | | CRP | 12 | Mildly elevated | **Renal Function:** | Test | This Patient | Importance | |------|--------------|------------| | Creatinine | 155 | CKD3 - affects drug choice | | eGFR | 45 | Reduced urate excretion | **Urinary Uric Acid:** | Finding | Classification | Management | |---------|----------------|------------| | <800 mg/24hr (4.8 mmol) | Under-excretor (90%) | Uricosuric may help | | >800 mg/24hr | Over-producer (10%) | Avoid uricosurics | **This Patient:** Elevated urinary urate but still elevated serum = reduced renal excretion capacity. **2. Imaging:** **Plain Radiographs:** | Feature | Gout-Specific Finding | |---------|----------------------| | Erosions | Punched-out with overhanging edges ("rat bite") | | Soft tissue | Nodular swelling ± calcification | | Joint space | Preserved until late (unlike RA) | | Bone density | Normal (unlike RA) | | Distribution | Asymmetric | **Ultrasound:** | Finding | Description | |---------|-------------| | **Double contour sign** | Urate on cartilage surface | | **Snowstorm appearance** | Urate within soft tissue | | **Tophi** | Heterogeneous hypoechoic masses | **Dual-Energy CT (DECT):** | Advantage | Detail | |-----------|--------| | **Specificity** | Colour-codes urate deposits | | **Quantification** | Can measure urate volume | | **Detection** | Even subclinical deposits | | **Use** | Diagnosis, monitoring treatment | **3. Joint Aspiration (if acute or diagnostic uncertainty):** **Synovial Fluid Findings:** | Feature | Gout Finding | |---------|--------------| | **Crystals** | Needle-shaped, negatively birefringent | | **Polarised microscopy** | Yellow when parallel to compensator | | **WCC** | 20,000-100,000 (inflammatory) | | **Culture** | Negative (rule out septic) | > **Consultant Tip:** DECT is excellent for confirming diagnosis and quantifying urate burden. Aspiration remains gold standard if diagnostic uncertainty - crystals can be seen even from chronic tophi. **Pathophysiology of Gout:** **1. Uric Acid Metabolism:** | Step | Process | |------|---------| | **Production** | End product of purine metabolism | | **Source** | Endogenous (cell turnover) + exogenous (diet) | | **Excretion** | 70% renal, 30% GI | | **Enzyme** | Xanthine oxidase converts hypoxanthine → xanthine → uric acid | **Hyperuricaemia Causes:** | Mechanism | Proportion | Examples | |-----------|------------|----------| | **Under-excretion** | 90% | CKD, thiazides, low-dose aspirin | | **Over-production** | 10% | Myeloproliferative, Lesch-Nyhan | | **Combined** | Variable | Alcohol (both mechanisms) | **This Patient:** Under-excretor (CKD3 + thiazide diuretic). **2. Crystal Formation:** | Factor | Effect | |--------|--------| | Serum urate >0.42 mmol/L | Supersaturation → crystallisation | | Local factors | pH, temperature, trauma, dehydration | | Time | Prolonged hyperuricaemia → deposition | **3. Inflammatory Response to Crystals:** | Step | Mechanism | |------|-----------| | 1 | MSU crystals phagocytosed by macrophages | | 2 | NLRP3 inflammasome activation | | 3 | IL-1β release | | 4 | Neutrophil recruitment | | 5 | Acute inflammatory response | **4. Tophi Formation:** | Process | Description | |---------|-------------| | **Crystal accumulation** | Continued deposition in tissues | | **Granulomatous response** | Giant cells, macrophages surround crystals | | **Fibrosis** | Chronic scarring | | **Result** | Firm, irregular tophi | **Why Tophaceous Disease in This Patient:** | Factor | Contribution | |--------|--------------| | **Long duration** | 30 years of gout | | **No ULT** | Never achieved target uric acid | | **CKD** | Reduced urate excretion | | **Thiazide** | Further reduces urate excretion | | **Multiple flares** | Indicates ongoing urate burden | **Target Uric Acid:** | Situation | Target | |-----------|--------| | Gout without tophi | <0.36 mmol/L (<6 mg/dL) | | Tophaceous gout | <0.30 mmol/L (<5 mg/dL) | **Lower target in tophaceous disease promotes tophi dissolution.** > **Consultant Tip:** Tophaceous gout is a failure of long-term uric acid control. The key is achieving target uric acid <0.30 mmol/L which will gradually dissolve tophi over months to years. **Medical Management of Tophaceous Gout:** **Goals of Treatment:** | Goal | Target | |------|--------| | **Uric acid** | <0.30 mmol/L (tophaceous disease) | | **Prevent flares** | Prophylaxis during ULT initiation | | **Dissolve tophi** | Gradual regression over 6-24 months | | **Prevent joint destruction** | Long-term urate control | | **Address modifiable factors** | Stop thiazide if possible | **Modifiable Factors:** | Factor | Action | |--------|--------| | **Thiazide diuretic** | Switch to alternative antihypertensive | | **Diet** | Reduce red meat, seafood, alcohol | | **Alcohol** | Reduce/stop (especially beer) | | **Obesity** | Weight loss if applicable | | **Hydration** | Adequate fluid intake | **Urate-Lowering Therapy Options:** **1. Allopurinol (Xanthine Oxidase Inhibitor) - First Line:** | Aspect | Details | |--------|---------| | **Mechanism** | Inhibits xanthine oxidase | | **Starting dose** | 100 mg daily (50 mg if eGFR <30) | | **Titration** | Increase by 100 mg every 2-4 weeks | | **Target dose** | 300-600 mg (max 800 mg) to achieve target | | **CKD dosing** | Lower start, slower titration, same target | | **This patient** | Start 100 mg, titrate to target | **Allopurinol Hypersensitivity Syndrome (AHS):** | Feature | Prevention | |---------|------------| | **Risk** | CKD, HLA-B*5801 (Asian populations) | | **Features** | Rash, eosinophilia, hepatitis, renal failure | | **Prevention** | Start low, go slow; check HLA-B*5801 in high-risk | | **Mortality** | 20-25% if severe | **2. Febuxostat (Alternative XOI):** | Aspect | Details | |--------|---------| | **Indication** | Allopurinol intolerance/failure | | **Dose** | 40-80 mg daily | | **Renal** | No dose adjustment needed | | **Concern** | Possible increased CV risk (CARES trial) | **3. Uricosurics (Probenecid):** | Aspect | Details | |--------|---------| | **Mechanism** | Increases renal urate excretion | | **Contraindication** | CKD, uric acid stones | | **This patient** | NOT appropriate (CKD3) | **4. Pegloticase (Recombinant Uricase):** | Aspect | Details | |--------|---------| | **Mechanism** | Converts uric acid to allantoin | | **Indication** | Refractory tophaceous gout | | **Administration** | IV infusion every 2 weeks | | **Issues** | Immunogenicity, infusion reactions | **Flare Prophylaxis During ULT Initiation:** | Agent | Regimen | |-------|---------| | **Colchicine** | 0.5 mg once or twice daily | | **Duration** | 3-6 months (or until tophi resolved) | | **Caution** | CKD - reduce dose, avoid with clarithromycin | | **Alternative** | Low-dose NSAID or prednisolone | **This Patient's Plan:** 1. Stop thiazide, switch to alternative antihypertensive (consult GP/cardiologist) 2. Start allopurinol 100 mg daily 3. Start colchicine 0.5 mg daily for prophylaxis 4. Check uric acid and creatinine at 4 weeks 5. Titrate allopurinol to achieve uric acid <0.30 mmol/L 6. Continue prophylaxis for 6 months minimum > **Consultant Tip:** "Start low, go slow" with allopurinol in CKD but still aim for target uric acid. The dose required may be higher than traditional "renal-adjusted" doses, but titration should be gradual. **Surgical Indications in Tophaceous Gout:** **Indications for Surgery:** | Indication | Description | |------------|-------------| | **Mechanical impairment** | Joint function limited by tophus size | | **Skin ulceration/infection** | Tophi eroding through skin, secondary infection | | **Nerve compression** | Carpal tunnel, ulnar nerve entrapment | | **Tendon rupture** | Tophus weakening tendon | | **Intractable pain** | Not controlled with medical therapy | | **Cosmesis** | Significant functional/aesthetic concern | **This Patient's Leg Mass:** - 8 x 5 cm mass causing discomfort - Visible chalky material (impending ulceration risk) - Consider surgical excision **Surgical Options:** **1. Tophus Debulking/Excision:** | Step | Detail | |------|--------| | **Indication** | Large, symptomatic tophus | | **Technique** | Incision, careful dissection from surrounding tissue | | **Removal** | May not achieve complete excision (adherent to deep structures) | | **Closure** | Primary if skin adequate; may need skin graft/flap | **Technical Considerations:** | Factor | Consideration | |--------|---------------| | **Skin quality** | Often thin, fragile over tophi | | **Wound healing** | May be poor (urate deposits) | | **Incomplete excision** | Acceptable if symptomatic relief achieved | | **Bleeding** | Tophi are vascular; may ooze | **2. Joint Surgery:** | Procedure | Indication | |-----------|------------| | **Arthrodesis (1st MTP)** | Severe destruction, chronic pain | | **Arthroplasty** | Destruction with mobile joint desired | | **Synovectomy** | Debridement of urate deposits | | **Tendon repair** | Extensor tendon rupture | **3. Amputation:** | Indication | Situation | |------------|-----------| | Severe infection | Septic joint, osteomyelitis not controlled | | Non-healing wound | Failed multiple attempts | | Severe vascular disease | Combination with PVD | **Pre-operative Optimisation:** | Factor | Action | |--------|--------| | Uric acid control | Start/optimise ULT if not already | | Acute flare | Not during acute attack | | Infection | Treat any secondary infection first | | Medical fitness | Assess renal, cardiac status | **Post-operative Management:** | Phase | Management | |-------|------------| | Wound care | Close monitoring for breakdown | | Flare prophylaxis | Continue colchicine through surgery | | ULT | Continue urate-lowering therapy | | Rehabilitation | Early mobilisation when wound healed | **Prognosis After Surgery:** | Outcome | Expected | |---------|----------| | Pain relief | Usually good (80%+) | | Wound healing | May be slow (20-30% complications) | | Recurrence | Possible if uric acid not controlled | | Function | Improved but depends on pre-op joint damage | > **Consultant Tip:** Surgery for tophi is palliative, not curative. Continued urate-lowering therapy is essential to prevent recurrence. Warn patients about wound healing issues. **Long-Term Complications of Tophaceous Gout:** **1. Joint Destruction (Gouty Arthropathy):** | Feature | Consequence | |---------|-------------| | Progressive erosions | Joint destruction | | Cartilage loss | Secondary OA | | Deformity | Fixed joint deformity | | Disability | Impaired function | **2. Renal Complications:** | Complication | Mechanism | |--------------|-----------| | **Urate nephropathy** | Crystal deposition in kidney | | **Uric acid stones** | 10-25% of gout patients | | **CKD progression** | Hyperuricaemia may worsen CKD | **3. Cardiovascular Disease:** | Association | Evidence | |-------------|----------| | Hypertension | Common comorbidity | | Coronary artery disease | Independent risk factor | | Heart failure | Associated with hyperuricaemia | | Stroke | Increased risk | **4. Metabolic Syndrome:** | Component | Prevalence in Gout | |-----------|-------------------| | Obesity | 50-70% | | Diabetes | 20-30% | | Hyperlipidaemia | 50-70% | | Hypertension | 50-80% | **Monitoring Protocol:** **Regular Visits:** | Timeframe | Assessment | |-----------|------------| | **First 6 months** | Monthly - titrating ULT | | **Established on ULT** | 3-6 monthly | | **Stable** | 6-12 monthly | **Laboratory Monitoring:** | Test | Frequency | Target | |------|-----------|--------| | Uric acid | Each visit during titration | <0.30 mmol/L | | Creatinine/eGFR | 3-6 monthly | Monitor CKD | | LFTs | Baseline, then if on febuxostat | Normal | | FBC | If on colchicine | Normal | **Clinical Assessment:** | Assessment | Purpose | |------------|---------| | Joint examination | Function, new erosions | | Tophus size | Measuring regression | | Flare frequency | Assess control | | Skin integrity | Check for ulceration | **Imaging Follow-up:** | Modality | Indication | |----------|------------| | X-rays | Baseline, then PRN for progression | | DECT | Quantify urate burden reduction | | Ultrasound | Monitor tophus size | **Expected Outcomes with Treatment:** | Outcome | Timeline | |---------|----------| | Flare frequency | Decreases over 6-12 months | | Tophus regression | Begins 6-12 months, complete 2+ years | | Joint improvement | Limited if established damage | | Uric acid target | Should achieve within 6 months | **Counselling Points for This Patient:** 1. Gout is a lifelong condition requiring lifelong treatment 2. Target is uric acid <0.30 mmol/L 3. Tophi will slowly dissolve over 1-2 years with treatment 4. May have more flares initially when starting ULT (expected) 5. Continue prophylaxis for 6+ months 6. Address cardiovascular risk factors 7. Avoid thiazide diuretics, reduce alcohol 8. Surgery may help large tophi but medical treatment is key **Prognosis:** | Factor | This Patient | |--------|--------------| | Tophi dissolution | Expected over 1-2 years with target uric acid | | Joint damage | May be irreversible (already present) | | Flares | Should reduce with treatment | | Renal function | May stabilise with uric acid control | | Quality of life | Should improve significantly | > **Consultant Tip:** Tophaceous gout is reversible with aggressive urate-lowering. The key is patient education and long-term adherence. Most tophi will dissolve within 2 years if target uric acid is achieved. --- ## Key Teaching Points ### Pattern Recognition **This pattern suggests Tophaceous Gout:** - Long history of recurrent gout - Subcutaneous nodules at characteristic sites (olecranon, 1st MTP, Achilles) - Chalky material visible through skin - Chronic joint deformity - Elevated serum uric acid - Characteristic X-ray findings (punched-out erosions, overhanging edges) **Comparison - Gout vs Rheumatoid Nodules:** | Feature | Gouty Tophi | RA Nodules | |---------|------------|------------| | Composition | MSU crystals | Fibrinoid necrosis | | Location | MTP, olecranon, ear | Olecranon, extensor surfaces | | X-ray | Punched-out erosions | Periarticular erosions | | Crystals | Negatively birefringent | None | | Serology | Normal RF | RF/anti-CCP positive | | Joint space | Preserved | Narrowed early | ### Critical Management Points 1. **Target uric acid <0.30 mmol/L** - lower target for tophaceous disease 2. **Start low, go slow with allopurinol** - especially in CKD 3. **Flare prophylaxis essential** - 3-6 months minimum 4. **Stop thiazide if possible** - major contributor to hyperuricaemia 5. **Surgery is palliative** - medical therapy remains cornerstone 6. **Tophi dissolve with treatment** - patient education and adherence key --- ## Common Examiner Follow-ups **Q: "What is the mechanism of colchicine and why is it used for prophylaxis?"** | Aspect | Description | |--------|-------------| | **Mechanism** | Inhibits microtubule polymerisation | | **Effect** | Impairs neutrophil chemotaxis and phagocytosis | | **Result** | Reduces inflammatory response to crystals | | **Prophylaxis** | Prevents flares during ULT initiation | | **Duration** | 3-6 months (longer for tophaceous) | | **CKD caution** | Reduce dose; avoid with clarithromycin | --- **Q: "How do you manage an acute gout flare in this patient with CKD?"** | Option | Consideration for CKD | |--------|----------------------| | **Colchicine** | Reduce dose (0.5 mg BD), avoid if eGFR <30 | | **NSAIDs** | Generally avoid in CKD | | **Prednisolone** | Safe option - 20-30 mg tapering | | **IL-1 inhibitors** | Anakinra if other options contraindicated | | **Joint aspiration** | Reduces pain, confirms diagnosis | Prednisolone is often the safest option in CKD. --- **Q: "What is the role of febuxostat vs allopurinol?"** | Aspect | Allopurinol | Febuxostat | |--------|-------------|------------| | **First-line** | Yes | No (second-line) | | **CKD** | Dose-adjusted start, titrate | No adjustment needed | | **Efficacy** | Good | May be more potent | | **CV safety** | Established | CARES trial concern | | **Cost** | Cheaper | More expensive | | **Indication** | First-line | Allopurinol intolerance/failure | --- ## Related Topics - Gout and Acute Gouty Arthritis - Crystal Arthropathies - Pseudogout (CPPD) - Chronic Kidney Disease and Orthopaedics - Metabolic Bone Disease