After reading this note you will be able to recognise, investigate and initiate appropriate acute and long‑term management of gout and other crystal‑induced arthropathies, while knowing which local protocols (Kenya MoH and hospital formulary) must be consulted for drug choices and dosing.
Definition
Gout is a metabolic disease characterised by deposition of monosodium urate (MSU) crystals in joints, peri‑articular tissues and sometimes kidneys, producing acute inflammatory arthritis. “Crystal arthropathies” is an umbrella term that includes gout, calcium pyrophosphate deposition disease (CPPD, pseudogout) and other rare crystal‑induced conditions (e.g., basic calcium phosphate disease).
Anatomy and physiology you need
- Synovial joint: lined by synovium, filled with synovial fluid; the fluid provides a medium where crystals can precipitate.
- Peri‑articular tissues: tendon sheaths, bursae and cartilage are also sites of crystal deposition.
- Renal handling of urate: ~70 % of uric acid is filtered at the glomerulus; ~90 % of the filtered load is re‑absorbed, and ~10 % is excreted. Impaired excretion or increased production raises serum urate → supersaturation → crystal formation.
- Innate immune receptors: MSU crystals are sensed by NLRP3 inflammasome in macrophages, leading to IL‑1β release and neutrophil recruitment; calcium pyrophosphate crystals activate similar pathways.
Causes and risk factors
| Category | Specific factors relevant in Kenya |
|---|---|
| Genetic | Family history of hyperuricaemia, HLA‑B*58:01 (allopurinol hypersensitivity) |
| Metabolic | Obesity, insulin resistance, hypertension, chronic kidney disease |
| Dietary | High purine foods (organ meat, certain fish), fructose‑rich drinks, alcohol (especially local brews) |
| Infectious / Tropical | HIV infection (immune activation, renal disease), TB (renal involvement, drug‑induced hyperuricaemia), malaria (hemolysis, dehydration), sickle cell disease (renal concentrating defect) |
| Medications | Diuretics, low‑dose aspirin, azathioprine, antiretrovirals (e.g., protease inhibitors), anti‑TB drugs (rifampicin) |
| Other | Lead exposure, rapid cell turnover (haemolysis, tumour lysis), dehydration (common in hot climates) |
Pathophysiology
- Increased serum urate → supersaturation of uric acid in synovial fluid
- Nucleation → formation of monosodium urate crystals (or calcium pyrophosphate crystals in CPPD)
- Crystal deposition in joint capsule, cartilage, tendon sheath
- Phagocytosis of crystals by synovial macrophages → activation of NLRP3 inflammasome
- IL‑1β release → cascade recruiting neutrophils and other inflammatory cells
- Acute inflammatory arthritis → pain, swelling, erythema, warmth
- Repeated attacks → tophus formation, chronic synovitis, joint damage, renal uric acid stones
(For CPPD replace “uric acid” with “calcium pyrophosphate” and note that crystal formation is promoted by cartilage degeneration and aging.)
Clinical features
| Aspect | Key questions / findings | Why it occurs |
|---|---|---|
| Onset | “How suddenly did the pain start?” – typical gout attacks begin within minutes to a few hours. | Deposition of monosodium urate (MSU) crystals triggers an intense neutrophil‑mediated inflammatory response. |
| Pain character | Severe, throbbing, “worst pain ever”, often described as burning or stabbing. | Crystal‑induced activation of the NLRP3 inflammasome leads to high levels of IL‑1β and intense nociception. |
| Joint distribution | First metatarsophalangeal (MTP) joint (podagra) most common; also ankles, knees, elbows, wrists, fingers, and the ear helix. | Lower temperature in distal joints favors crystal precipitation; mechanical stress and reduced blood flow promote nucleation. |
| Pattern of involvement | Mono‑articular at onset; may become poly‑articular in chronic gout or with calcium pyrophosphate deposition disease (CPPD). | Initial crystal load usually limited to one joint; with time, cumulative deposition spreads. |
| Duration | Attack lasts 3‑10 days if untreated; may recur weekly to monthly. | Ongoing crystal shedding sustains inflammation until crystal burden is cleared or anti‑inflammatory therapy is given. |
| Triggers | Recent high‑purine meals, alcohol (especially beer), dehydration, recent surgery, initiation of diuretics, rapid weight loss, infection, trauma. | Purine excess raises serum urate; dehydration concentrates urate; certain drugs reduce renal urate excretion. |
| Systemic symptoms | Fever, chills, malaise, night sweats (especially in TB‑associated gout). | Cytokine surge (IL‑1, IL‑6, TNF‑α) produces systemic inflammatory response. |
| Past history | Prior similar attacks, kidney stones, chronic kidney disease, hypertension, metabolic syndrome, use of allopurinol or febuxostat, HIV/TB treatment, sickle‑cell crises, malaria prophylaxis. | Co‑morbidities impair urate excretion or increase production; some infections and drugs alter urate metabolism. |
| Medication history | Loop/thiazide diuretics, low‑dose aspirin, pyrazinamide, azathioprine, protease inhibitors, antiretrovirals. | These agents decrease renal clearance of uric acid or increase its production. |
| Family history | Relatives with gout, hyperuricemia, renal disease. | Genetic variants (e.g., SLC2A9, ABCG2) affect urate transport. |
| Examination – joint | Swollen, erythematous, warm, exquisitely tender joint; overlying skin may be shiny; limited active range of motion; tophi (chalky subcutaneous nodules) over ears, olecranon, Achilles, fingers. | Acute crystal‑induced synovitis produces effusion and hyperemia; chronic deposition forms aggregates of urate crystals (tophi). |
| Examination – systemic | No other joint involvement (unless poly‑gout); check for signs of infection (lymphadenopathy, hepatosplenomegaly) or other rheumatologic disease (rash, nail changes). | Helps exclude septic arthritis, rheumatoid arthritis, systemic lupus. |
| Examination – renal | Flank tenderness, palpable kidneys, evidence of nephrolithiasis on imaging. | Urate stones may cause renal colic or chronic kidney disease. |
Differential diagnosis
| Condition | Points toward it | Distinguishing feature |
|---|---|---|
| Septic arthritis | Fever, recent skin breach, rapid joint destruction, immunosuppression (HIV, TB). | Synovial fluid: high neutrophils, positive Gram stain/culture; lack of MSU crystals. |
| Pseudogout (CPPD) | Knee or wrist predominance, older age, chondrocalcinosis on X‑ray. | Calcium pyrophosphate crystals (rhomboid, positively birefringent) on microscopy. |
| Acute rheumatoid flare | Symmetrical polyarthritis, morning stiffness >1 h, rheumatoid nodules. | Positive rheumatoid factor/anti‑CCP; erosive changes on X‑ray; no MSU crystals. |
| Reactive arthritis | Recent GI or GU infection, sacroiliac tenderness, conjunctivitis, urethritis. | Asymmetric oligoarthritis, HLA‑B27 positivity; sterile synovial fluid. |
| Osteoarthritis flare | Degenerative changes, pain worsens with use, minimal inflammation. | Radiographic osteophytes, joint space narrowing; no crystals. |
| Sickle‑cell vaso‑occlusive crisis | Known sickle‑cell disease, pain in long bones, fever, anemia. | Hemoglobin electrophoresis; no joint effusion with crystals. |
| Malaria‑related arthropathy | Recent malaria episode, fever spikes, joint pain. | Positive malaria smear; joint pain resolves with antimalarial therapy; no crystals. |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Synovial fluid analysis (microscopy, polarized light) | Presence and type of crystals; rule out infection. | MSU crystals: needle‑shaped, negatively birefringent. CPPD crystals: rhomboid, positively birefringent. Gram stain/culture negative → non‑septic. |
| Serum uric acid | Baseline urate level; supports diagnosis. | > 7 mg/dL (men) or > 6 mg/dL (women) suggests hyperuricemia but normal level does not exclude acute gout. |
| Complete blood count | Inflammation, anemia, leukocytosis. | Elevated white cells may be seen in gout or infection; neutrophil predominance supports crystal arthritis. |
| ESR / CRP | Degree of systemic inflammation. | Markedly raised in acute gout; helps monitor response. |
| Renal function (creatinine, eGFR) | Urate excretion capacity; drug dosing safety. | Impaired function → higher risk of urate accumulation, need dose adjustment of urate‑lowering agents. |
| Urinalysis (uric acid crystals, pH) | Excretion pattern, risk of uric acid stones. | Low urine pH, high uric acid crystals → stone risk. |
| Plain radiograph of affected joint | Chronic changes, tophi, chondrocalcinosis. | Soft‑tissue swelling, punched‑out erosions with overhanging edges in gout; linear calcifications in CPPD. |
| Ultrasound of joint | Detects double‑contour sign, tophi, effusion. | Double‑contour sign = urate crystal coating cartilage; aggregates = tophi. |
| Dual‑energy CT (if available) | Quantifies urate deposition. | Color‑coded urate deposits confirm gout, differentiate from calcium. |
Diagnosis and severity
Diagnostic criteria (clinical + crystal confirmation)
- Definite gout – Identification of MSU crystals in synovial fluid or tophus.
- Probable gout – Typical podagra or mono‑articular attack plus hyperuricemia and response to colchicine/NSAID, with no alternative diagnosis.
Severity grading (based on attack frequency, joint involvement, and systemic impact)
| Grade | Features | Management implication |
|---|---|---|
| Mild | ≤1 attack/year, mono‑articular, no tophi, normal renal function. | Acute therapy alone; consider lifestyle modification, start urate‑lowering if serum urate persistently > 6 mg/dL. |
| Moderate | 2–4 attacks/year, poly‑articular or recurrent mono‑articular, early tophi, mild renal impairment. | Acute therapy plus early initiation of urate‑lowering (xanthine oxidase inhibitor or uricosuric); monitor renal function and urate levels. |
| Severe | >4 attacks/year, extensive tophi, chronic joint damage, renal stones or CKD stage 3+, contraindications to NSAIDs/colchicine. | Aggressive urate‑lowering (combine xanthine oxidase inhibitor with uricosuric if needed), consider IL‑1 blockade for refractory inflammation; close monitoring for drug toxicity and renal status. |
Key points for confirming diagnosis
- Presence of MSU crystals is gold‑standard.
- Hyperuricemia supports but does not replace crystal proof.
- Exclusion of infection is mandatory before initiating immunosuppressive agents.
Severity assessment guides
- Frequency of attacks dictates urgency of urate‑lowering therapy.
- Renal function determines choice of uricosuric vs. xanthine oxidase inhibitor.
- Presence of tophi or joint damage prompts imaging and possibly surgical referral.
The clinical approach integrates a focused history, targeted examination, crystal confirmation, and assessment of comorbidities to stratify severity and tailor both acute and long‑term management.
Management
| Phase | Goal | Key interventions | Monitoring / safety |
|---|---|---|---|
| Immediate stabilisation | Relieve acute pain, protect joint, prevent renal injury | • NSAID (e.g., ibuprofen, naproxen) or colchicine (if NSAID contraindicated) <br>• Adequate hydration (IV saline if oral intake poor) <br>• Elevate and immobilise affected joint | Renal function, gastrointestinal tolerance, complete blood count for colchicine toxicity |
| Definitive (long‑term) treatment | Lower serum urate, prevent recurrences, treat tophi | • Xanthine oxidase inhibitor (allopurinol, febuxostat) – start low, titrate to target urate <br>• Uricosuric agents (probenecid, lesinurad) if under‑excretion and no renal stones <br>• Continue low‑dose colchicine or intermittent NSAID for prophylaxis during urate‑lowering initiation (first 3–6 months) | Serum urate (target < 0.36 mmol/L), liver enzymes, renal function, drug interactions (e.g., allopurinol + azathioprine) |
| Lifestyle & risk‑factor modification | Reduce endogenous urate production | • Limit purine‑rich foods (organ meats, certain seafood) <br>• Reduce fructose‑sweetened drinks <br>• Encourage weight loss, regular exercise <br>• Review diuretics, low‑dose aspirin, and antiretrovirals that raise urate; switch if possible | Weight, blood pressure, medication review |
| Contra‑indications / safety | Avoid harm | • NSAID avoided in advanced CKD, active peptic ulcer, uncontrolled hypertension <br>• Colchicine avoided in severe hepatic or renal failure, concurrent strong CYP3A4 inhibitors <br>• Allopurinol avoided in known hypersensitivity; start after HLA‑B*58:01 testing in high‑risk ethnic groups (e.g., some Asian populations) | Watch for rash, eosinophilia, liver injury; stop drug promptly if severe reaction |
Complications and prognosis
- Tophi – subcutaneous urate deposits; can cause joint deformity, ulceration, nerve compression.
- Nephrolithiasis & chronic kidney disease – uric acid stones and interstitial nephropathy; monitor renal function and urine pH.
- Acute kidney injury during an attack (dehydration, NSAID nephrotoxicity).
- Cardiovascular risk – hyperuricaemia is an independent risk factor; aggressive control improves long‑term outcomes.
- Infection risk – especially in HIV/TB patients on colchicine or steroids; maintain vigilance for secondary septic arthritis.
- Prognosis – With sustained urate lowering to target, attacks become rare, tophi may regress, and renal function stabilises. Poor adherence or continued risk factors lead to recurrent attacks and progressive joint damage.
High‑yield exam points
- Look‑alike conditions: Septic arthritis, calcium pyrophosphate deposition disease (CPPD), osteoarthritis flare, cellulitis.
- Commonest wrong first step: Starting urate‑lowering therapy during an acute attack (can prolong the flare).
- Bedside examiner questions:
- “What feature of the joint exam points to gout rather than septic arthritis?” (e.g., intense pain with minimal swelling, tophus, overlying erythema not disproportionate).
- “How would you differentiate gout from CPPD on synovial fluid analysis?” (needle‑shaped, negatively birefringent crystals vs rhomboid, positively birefringent).
- “Why is colchicine given at a lower dose in renal impairment?” (reduced clearance increases toxicity).
- “What lifestyle advice reduces urate production?” (limit purines, fructose, alcohol).
Clinical case
Case:
A 48‑year‑old male farmer presents with a 2‑day history of sudden, excruciating pain in the right first metatarsophalangeal (MTP) joint. The joint is hot, erythematous, swollen, and the patient cannot bear weight. He reports a similar episode 3 years ago that resolved spontaneously. Past history includes treated pulmonary TB 5 years ago and HIV infection on efavirenz‑based ART; serum creatinine is 110 µmol/L. No diuretic use.
Key findings:
- Acute monoarthritis of the great toe (podagra)
- HIV infection (risk factor for hyperuricaemia)
- Mild renal impairment (affects drug choice)
Questions
- What is the most appropriate immediate therapy?
Answer: Initiate a non‑steroidal anti‑inflammatory drug (e.g., naproxen) if renal function permits; otherwise give low‑dose colchicine.
- Which investigation will confirm the diagnosis and how is it interpreted?
Answer: Arthrocentesis with polarized light microscopy; identification of needle‑shaped, negatively birefringent monosodium urate crystals confirms gout.
- What long‑term strategy should be started after the acute attack resolves?
Answer: Begin a xanthine oxidase inhibitor (allopurinol) at a low dose, titrating to achieve serum urate < 0.36 mmol/L, with prophylactic low‑dose colchicine for the first 3 months.
Practice questions
Question 1
A 62‑year‑old woman with chronic kidney disease (eGFR 30 mL/min) presents with a painful swollen knee. Synovial fluid shows positively birefringent rhomboid crystals. What is the next best step?
A. High‑dose NSAID
B. Intra‑articular corticosteroid
C. Initiate allopurinol
D. Start colchicine
Answer: B. Intra‑articular corticosteroid – appropriate for CPPD flare in renal impairment where NSAID and colchicine are risky.
Question 2
A patient with known gout is admitted for a severe attack. Which of the following is contra‑indicated during the acute phase?
A. Low‑dose colchicine prophylaxis
B. Initiation of allopurinol
C. Adequate hydration
D. NSAID therapy
Answer: B. Initiation of allopurinol – starting urate‑lowering therapy during an acute attack can prolong the flare.
Question 3
Which clinical feature most strongly suggests septic arthritis rather than gout?
A. Presence of tophi
B. Fever > 38 °C and marked systemic toxicity
C. Rapid onset of pain in the first MTP joint
D. Negative birefringent crystals on microscopy
Answer: B. Fever > 38 °C and marked systemic toxicity – systemic signs point toward infection.
Question 4
A 55‑year‑old man with recurrent gout attacks is started on allopurinol. After 4 weeks his serum urate is 0.40 mmol/L and he develops a maculopapular rash. What is the most appropriate action?
A. Continue allopurinol, add antihistamine
B. Switch to febuxostat
C. Stop allopurinol immediately, avoid rechallenge
D. Reduce the dose of allopurinol
Answer: C. Stop allopurinol immediately, avoid rechallenge – rash may herald hypersensitivity; alternative urate‑lowering agent is needed.
Question 5
Which lifestyle modification has the greatest impact on lowering serum urate in a patient with gout?
A. Reducing intake of organ meats
B. Eliminating all dairy products
C. Drinking > 3 L of water daily
D. Avoiding all alcoholic beverages
Answer: D. Avoiding all alcoholic beverages – alcohol, especially beer, markedly raises urate production and reduces excretion.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.