Rheumatology: Crystal arthritis, osteoarthritis and soft tissue pain

• Crystal arthritis: Gout — Causes and Risk Factors | Gout — Clinical Features and Diagnosis | Treating a Gout Flare | Urate-lowering Therapy | Gout in Special Situations | Calcium Pyrophosphate Deposition (Pseudogout) | Basic Calcium Phosphate Disease
• Osteoarthritis: Osteoarthritis — Features and Diagnosis | Managing Osteoarthritis | Hand Osteoarthritis
• Pain syndromes and other arthropathies: Fibromyalgia and Chronic Widespread Pain | Joint Hypermobility | Metabolic and Endocrine Arthropathies | Other Joint Conditions to Know
• Revision: Crystal, Degenerative and Pain Conditions at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Crystal arthritis, osteoarthritis and soft tissue pain — page 3 of the Rheumatology chapter. Gout is the commonest inflammatory arthritis (about 1 in 40 UK adults) and is curable with urate-lowering therapy to a target — yet it is often undertreated. Osteoarthritis is the commonest joint disease of all, and exercise and weight loss are its main treatments. Chronic widespread pain (fibromyalgia) is common and needs a positive diagnosis, not endless tests. Septic arthritis is on the Trauma and Orthopaedics page; joint replacement and regional soft tissue problems (shoulder, elbow, foot) are there too.
Your four questions for every patient: Could this hot joint be infected — has it been aspirated? Is this crystal, degenerative or inflammatory disease — or pain without joint disease? What can the patient do themselves (exercise, weight, diet, alcohol)? For gout — is urate-lowering therapy indicated, and is the urate at target?

Gout — Causes and Risk Factors

• Gout — inflammation caused by monosodium urate crystals forming in and around joints when urate levels stay high (hyperuricaemia — above about 360 µmol/L, the saturation point).
• Most hyperuricaemia never causes gout — don't treat high urate without symptoms.
• Causes of high urate:
  • Reduced kidney excretion (about 90%) — CKD, diuretics (thiazides and loop), low-dose aspirin, ciclosporin and tacrolimus, pyrazinamide, ethambutol, dehydration, ketoacidosis, lead, hypothyroidism, genetics.
  • Increased production — high-purine diet (red meat, offal, seafood), alcohol (especially beer and spirits), sugary drinks (fructose), high cell turnover (myeloproliferative disease, psoriasis, haemolysis), tumour lysis, rare enzyme defects (Lesch–Nyhan).
• Risk factors — men (women after menopause), older age, obesity, metabolic syndrome, hypertension, diabetes, CKD, family history, organ transplant.
• Gout is linked with cardiovascular disease and CKD — assess CV risk in everyone with gout.
• Triggers of a flare — alcohol binges, large meals, dehydration, surgery or acute illness, trauma, new diuretics, starting or changing urate-lowering therapy (urate falls and crystals shift).

Gout — Clinical Features and Diagnosis

• Acute gout flare:
  • Sudden severe pain, peaking within 24 hours, often starting at night; can't bear the bedsheet touching the joint.
  • Red, hot, swollen, very tender joint; skin may be shiny and peel as it settles.
  • First MTP joint (big toe — "podagra") in over half of first attacks; also midfoot, ankle, knee, wrist, fingers, olecranon bursa.
  • Usually settles within 1–2 weeks even without treatment.
  • May have fever and raised CRP — can look like septic arthritis or cellulitis.
• Chronic gout — recurrent flares, more joints involved (polyarticular), persistent joint pain and damage, tophi (chalky white deposits of urate under the skin — ears, fingers, elbows, Achilles), kidney stones (urate), urate nephropathy.
• Diagnosis:
  • Gold standard — joint aspiration showing needle-shaped, negatively birefringent crystals (or aspirate from a tophus) — especially if the diagnosis is uncertain or infection is possible.
  • Often clinical in typical first MTP attacks with risk factors (NICE NG219).
  • Serum urate — can be normal during a flare (urate falls in acute inflammation) — repeat at least 2 weeks after the flare settles to confirm and to set a baseline.
  • Also check U&E, HbA1c, lipids, LFTs, FBC, BP (associated conditions).
  • Imaging — X-ray (erosions with overhanging edges — late), ultrasound (double contour sign), dual-energy CT (urate deposits).

Treating a Gout Flare

• Treat early — the sooner treatment starts, the better it works; patients should keep a "pill in the pocket".
• First-line options (NICE NG219) — choose by comorbidities and patient preference:
  • NSAID (e.g. naproxen) with a PPI — avoid in CKD, heart failure, peptic ulcer, anticoagulants.
  • Colchicine — best started within 24 hours; low dose (500 micrograms 2–4 times a day — see BNF for maximum course dose) is as effective as high dose with fewer side effects; diarrhoea is common; reduce or avoid in CKD; interactions — clarithromycin, erythromycin, ciclosporin, verapamil, diltiazem, some statins (toxicity, myopathy).
  • Short course of oral steroid (e.g. prednisolone 30–35 mg daily for 3–5 days) — useful when NSAIDs and colchicine are unsuitable (CKD, heart failure).
• Second-line — intra-articular steroid injection (once infection excluded) or IM steroid; IL-1 inhibitors (anakinra, canakinumab — specialist) if others are unsuitable.
• Supportive — rest, raise the limb, ice packs, fluids; avoid alcohol.
• Don't stop urate-lowering therapy during a flare if already taking it.
• Review diuretics — switch from a thiazide or loop diuretic if possible (e.g. for hypertension — consider losartan or amlodipine, which lower urate slightly). Don't stop diuretics needed for heart failure.

⚠️ Safety Pearl — a hot joint in a patient with "known gout" can still be septic. If the patient is unwell, febrile, immunosuppressed, has a prosthetic joint, or the attack is atypical — aspirate.

Urate-lowering Therapy

• Offer urate-lowering therapy (ULT) to everyone with gout after discussing it, especially if (NICE NG219):
  • Recurrent flares (2 or more a year).
  • Tophi.
  • Chronic gouty arthritis or joint damage.
  • CKD stage 3–5.
  • Diuretic therapy that can't be stopped.
  • Kidney stones, or young age at onset (under 40).
• When to start — usually 2–4 weeks after a flare settles (or during a flare if flares are frequent).
• Treat to target — serum urate below 360 µmol/L; below 300 µmol/L if tophi, chronic gouty arthritis or ongoing frequent flares (dissolves crystals faster). Once at target for some years and tophi have gone, a target under 360 is enough.
• Drugs:
  • Allopurinol (xanthine oxidase inhibitor) — first-line; start low (100 mg daily, or lower in CKD) and increase monthly (by 100 mg) according to urate until at target (often 300–600 mg or more; up to 900 mg); check urate monthly while titrating.
  • Febuxostat — if allopurinol is not tolerated or not effective; caution in major cardiovascular disease (MHRA) — allopurinol is preferred in those patients.
  • Uricosurics (benzbromarone, sulfinpyrazone — specialist; probenecid), pegloticase (severe tophaceous gout — rarely used).
• Flare prophylaxis when starting ULT — colchicine 500 micrograms once or twice daily (or low-dose NSAID or steroid if unsuitable) for up to 6 months; warn that flares may increase at first.
• Allopurinol hypersensitivity syndrome — rare but life-threatening (fever, rash — SJS/TEN or DRESS, hepatitis, kidney injury); higher risk in CKD, high starting doses, and people of Han Chinese, Thai or Korean descent with HLA-B*58:01 (test before starting in these groups). Stop at the first sign of rash.
• Interaction — azathioprine and mercaptopurine with allopurinol or febuxostat → severe marrow toxicity — avoid or greatly reduce the dose (specialist).
• Lifestyle — weight loss, regular exercise, reduce alcohol (especially beer and spirits), avoid sugary drinks, keep hydrated, stop smoking; diet alone rarely lowers urate enough.
• Long-term — ULT is usually lifelong; check urate annually once at target; adherence is the main problem (education helps).

Gout in Special Situations

• CKD — gout is common; colchicine and NSAIDs are limited — use steroids for flares; allopurinol is still used (start low, increase slowly to target — not limited by eGFR-based maximums if monitored); febuxostat needs no dose change in mild to moderate CKD.
• Heart failure — avoid NSAIDs; diuretics often unavoidable; colchicine or steroids for flares.
• Transplant recipients — ciclosporin and tacrolimus raise urate; colchicine interacts with ciclosporin; allopurinol interacts with azathioprine — specialist advice.
• Tumour lysis syndrome — chemotherapy for bulky leukaemias and lymphomas; high urate, potassium and phosphate, low calcium, AKI — prevent with IV fluids, allopurinol or rasburicase (high risk; avoid in G6PD deficiency) (see the Oncological Emergencies chapter).
• Women — gout before menopause is unusual — look for CKD, diuretics or a genetic cause.
• Gout in young people (under 25) or with kidney stones — consider enzyme defects or familial juvenile hyperuricaemic nephropathy.
• Hospital inpatients — flares are common after surgery, dehydration or diuretic changes; continue ULT during admission.

Calcium Pyrophosphate Deposition (Pseudogout)

• Calcium pyrophosphate (CPP) crystals deposit in cartilage; commonest in older people (most over 65).
• Forms:
  • Chondrocalcinosis — calcium in cartilage on X-ray (knee menisci, wrist triangular fibrocartilage, symphysis pubis) — often without symptoms.
  • Acute CPP crystal arthritis ("pseudogout") — sudden hot swollen joint, usually the knee or wrist; often during acute illness, after surgery or trauma; fever and confusion in older people.
  • Chronic CPP arthritis — OA-like disease in unusual joints (wrists, MCPs, shoulders, elbows) with flares.
  • Crowned dens syndrome — acute severe neck pain and stiffness with fever and high CRP in older people (CPPD around C2) — mimics meningitis or PMR; CT neck.
• Diagnosis — joint aspiration: rhomboid, weakly positively birefringent crystals; exclude infection (can coexist).
• Treatment of acute attacks — aspiration (relieves pain) and intra-articular steroid; NSAIDs or colchicine (with caution in older people); oral steroids. No treatment removes CPP crystals.
• Recurrent attacks — low-dose colchicine prophylaxis; methotrexate or hydroxychloroquine (limited evidence).
• Look for metabolic causes — especially if under 55 or with widespread chondrocalcinosis:
  • Haemochromatosis (ferritin, transferrin saturation).
  • Hyperparathyroidism (calcium, PTH).
  • Hypomagnesaemia (including Gitelman syndrome; PPIs).
  • Hypophosphatasia (low ALP).
  • Wilson's disease (rare).

Basic Calcium Phosphate Disease

• Basic calcium phosphate (hydroxyapatite) crystals — not visible on standard polarised microscopy.
• Calcific tendinopathy — calcium deposits in tendons, especially the supraspinatus (shoulder); acute calcific periarthritis causes sudden, severe pain, redness and swelling (mimics gout or infection); NSAIDs, steroid injection, ultrasound-guided barbotage.
• Milwaukee shoulder — older women; rapidly destructive shoulder arthritis with large, often blood-stained effusions and rotator cuff loss.
• Calcinosis — calcium deposits in the skin in systemic sclerosis (limited — CREST) and dermatomyositis (especially in children); may ulcerate and discharge chalky material.
• Metastatic calcification — high calcium–phosphate product (advanced CKD — calciphylaxis risk).

Osteoarthritis — Features and Diagnosis

• Osteoarthritis (OA) — the commonest joint disease; a process of joint damage and repair affecting cartilage, bone, synovium and ligaments — not simply "wear and tear".
• Risk factors — age, obesity (knees and hands), female sex, previous joint injury or surgery (meniscectomy, ACL tear), joint malalignment, occupation (kneeling, heavy lifting), genetics, muscle weakness.
• Joints affected — knees, hips, hands (DIP, PIP, thumb base), cervical and lumbar spine, first MTP; uncommon in the wrist, elbow, shoulder and ankle (think trauma, CPPD, or another cause).
• Symptoms — pain on use, eased by rest; short morning stiffness (under 30 minutes); "gelling" after inactivity; reduced function; night pain in advanced disease.
• Signs — bony swelling, crepitus, reduced and painful movement, effusion (cool), deformity (varus knee), quadriceps wasting, joint line tenderness.
• Diagnose clinically without imaging (NICE NG226) if:
  • Age 45 or over, AND
  • Activity-related joint pain, AND
  • No morning stiffness, or stiffness lasting no longer than 30 minutes.
• Consider other diagnoses if atypical — history of trauma, prolonged morning stiffness, rapid deterioration, a hot swollen joint (gout, CPPD, infection), night pain or weight loss (cancer), younger age.
• X-ray (if needed) — LOSS: Loss of joint space (asymmetric), Osteophytes, Subchondral sclerosis, Subchondral cysts. X-ray changes correlate poorly with symptoms.
• Blood tests are normal in OA.

Managing Osteoarthritis

• Core treatments for everyone (NICE NG226):
  • Exercise — tailored strengthening and general aerobic fitness (physiotherapy, group classes such as ESCAPE-pain); combine with education.
  • Weight loss if overweight — even 5–10% weight loss helps knee pain.
  • Information and self-management — OA is not inevitably progressive; activity does not "wear out" joints.
• Drug treatment (alongside core treatment):
  • Topical NSAIDs — first choice for knee OA (and hand OA).
  • Oral NSAIDs — lowest dose, shortest time, with a PPI, considering GI, renal and CV risks.
  • Don't routinely offer paracetamol (alone), weak opioids (unless short-term and other options unsuitable), strong opioids, glucosamine, chondroitin, or hyaluronic acid injections.
  • Intra-articular steroid — short-term relief (weeks) for flares when other treatments aren't enough.
• Aids — walking aids (stick in the opposite hand to the painful hip or knee), supportive footwear, assistive devices; acupuncture is not recommended; arthroscopic washout is not recommended (unless locking).
• Refer for joint replacement when symptoms substantially affect quality of life despite non-surgical treatment — don't exclude people based on age, weight, smoking or comorbidities alone (see the Trauma and Orthopaedics page).
• Also manage — sleep, low mood, other conditions; review regularly.

Hand Osteoarthritis

• Nodal OA — Heberden's nodes (DIP joints) and Bouchard's nodes (PIP joints); middle-aged women, family history; often painful early then less painful as nodes form.
• Thumb base OA (first carpometacarpal joint) — pain on pinching and gripping (opening jars), "squaring" of the thumb base; splints, injections, surgery (trapeziectomy).
• Erosive hand OA — painful, inflammatory attacks of the interphalangeal joints; "gull-wing" central erosions on X-ray; can look like inflammatory arthritis (bloods normal).
• Treatment — hand exercises, OT (joint protection, aids), splints, topical NSAIDs, oral NSAIDs for short periods, steroid injection (thumb base); hydroxychloroquine does not help.
• Mucous cysts — small cysts over DIP joints (linked with OA) — may cause nail grooves.
• DIP involvement differential — OA, psoriatic arthritis (nail changes, dactylitis), gout.

Fibromyalgia and Chronic Widespread Pain

• Fibromyalgia — chronic widespread pain (over 3 months) with fatigue, unrefreshing sleep and cognitive difficulties ("fibro fog"), often with headaches, IBS, bladder symptoms, anxiety and low mood; a disorder of pain processing (central sensitisation). It is a type of chronic primary pain.
• Who — more common in women, middle age; often follows stress, illness or injury; common alongside RA, SLE and other diseases.
• Diagnosis — clinical (ACR 2016 criteria — widespread pain index and symptom severity score); examination is normal apart from widespread tenderness; no swelling.
• Tests to exclude mimics (keep limited) — FBC, CRP/ESR, U&E, LFTs, bone profile, TFTs, CK, vitamin D, HbA1c, coeliac serology if relevant. Don't test ANA or RF without other features (false positives cause harm).
• Management (NICE NG193 — chronic primary pain):
  • Give a clear diagnosis and explanation — the pain is real; the body is not being damaged.
  • Exercise — graded, regular activity (supervised programmes).
  • Psychological therapies — CBT or acceptance and commitment therapy (ACT); acupuncture (NICE allows a course).
  • Antidepressants can be considered (e.g. amitriptyline, duloxetine, SSRIs) — for pain, sleep and mood.
  • Avoid starting — opioids, gabapentinoids, NSAIDs, paracetamol, benzodiazepines, local anaesthetics (NICE) — they lack benefit and cause harm.
  • Sleep hygiene, pacing, return-to-work support.
• Chronic fatigue syndrome / ME overlaps — see NICE NG206.

Joint Hypermobility

• Joint hypermobility — joints that move beyond the normal range; common and often harmless (dancers, gymnasts).
• Beighton score (out of 9) — little finger extension beyond 90° (1 each side), thumb to forearm (1 each side), elbow hyperextension over 10° (1 each side), knee hyperextension over 10° (1 each side), palms flat on the floor with knees straight (1). Hypermobility is usually 5 or more in adults (4 or more over 50).
• Hypermobility spectrum disorder and hypermobile Ehlers–Danlos syndrome (hEDS) — hypermobility with symptoms: joint pain, recurrent sprains, subluxations and dislocations, fatigue; associated POTS (postural tachycardia), gut symptoms, anxiety.
• Management — physiotherapy (strengthening, proprioception), pacing, pain management; avoid unnecessary surgery.
• Other heritable connective tissue disorders to recognise:
  • Vascular EDS (COL3A1) — thin translucent skin, easy bruising, arterial, bowel and uterine rupture — serious.
  • Marfan syndrome (FBN1) — tall, long limbs, lens dislocation (upwards), aortic root dilatation and dissection — echo and monitoring.
  • Osteogenesis imperfecta — fractures, blue sclerae, hearing loss.

Metabolic and Endocrine Arthropathies

Other Joint Conditions to Know

• Diffuse idiopathic skeletal hyperostosis (DISH) — older men, obesity, diabetes; "flowing" ossification along the front of at least 4 vertebrae (right side of the thoracic spine), stiffness; sacroiliac joints are normal (unlike ankylosing spondylitis); dysphagia from cervical osteophytes.
• Avascular necrosis (osteonecrosis) — loss of blood supply to bone — steroids, alcohol, sickle cell disease, SLE, antiphospholipid syndrome, radiotherapy, decompression sickness, bisphosphonates (jaw); hip pain with normal early X-rays — MRI; protected weight bearing, core decompression or joint replacement.
• Charcot (neuropathic) joint — painless joint destruction with lost sensation (diabetes — foot; syringomyelia — shoulder; tabes dorsalis — knee); the acute hot swollen foot needs urgent offloading (see the Vascular Surgery page).
• Pigmented villonodular synovitis (tenosynovial giant cell tumour) — young adults; recurrent blood-stained effusions in one joint (knee); MRI; synovectomy.
• Lyme arthritis — tick bite (UK — New Forest, Scottish Highlands, Lake District); erythema migrans, then large-joint arthritis (knee) weeks to months later; serology; doxycycline (see the Infectious Diseases chapter).
• Rheumatic fever — 2–4 weeks after streptococcal throat infection; flitting large-joint polyarthritis (Jones criteria — carditis, chorea, erythema marginatum, nodules) — rare in the UK now.
• Hypertrophic pulmonary osteoarthropathy — clubbing with painful wrists and ankles (periosteal new bone) — lung cancer (especially adenocarcinoma), bronchiectasis, mesothelioma.
• Paget's disease of bone — older people, bone pain, deformity, raised ALP with normal calcium (see the Bone Medicine chapter).

Crystal, Degenerative and Pain Conditions at a Glance

Spot the Diagnosis

Exam-style Scenarios

1. A 56-year-old man on bendroflumethiazide has his third attack of gout this year. His urate (2 weeks after the flare) is 520 µmol/L; eGFR 70. He has no tophi.
Answer: Recurrent gout — start urate-lowering therapy.

• Start allopurinol 100 mg daily, increasing by 100 mg every month according to urate (checked monthly) to a target below 360 µmol/L.
• Give colchicine 500 micrograms once or twice daily as flare prophylaxis for up to 6 months; provide a rescue plan for flares.
• Switch the thiazide (e.g. to losartan or amlodipine); assess CV risk, HbA1c and lipids; advise on alcohol, sugary drinks and weight.

2. An 81-year-old woman is admitted with pneumonia. On day 3 she develops a hot, swollen right knee and fever. The knee X-ray shows chondrocalcinosis.
Answer: Probable acute CPP crystal arthritis — but infection must be excluded.

• Aspirate the knee — Gram stain, culture and crystals; blood cultures.
• If CPP crystals with no infection — aspiration plus intra-articular steroid; or a short oral steroid course (NSAIDs and colchicine are riskier at her age).
• Calcium and magnesium check; mobilise when settled.

3. A 67-year-old woman with a BMI of 33 has 2 years of right knee pain on walking and stairs, with 15 minutes of morning stiffness. The knee is bony and creaky with no effusion. She asks for an X-ray and "something strong for pain".
Answer: Knee osteoarthritis — clinical diagnosis.

• No X-ray needed for diagnosis (age over 45, activity-related pain, short stiffness).
• Exercise (strengthening — physio-led programme) and support for weight loss; topical NSAID; avoid strong opioids.
• Consider intra-articular steroid for a flare; refer for replacement if symptoms severely affect quality of life despite these.

4. A 42-year-old woman has 2 years of widespread aching, exhaustion, poor sleep and poor concentration. Examination shows tenderness everywhere but no joint swelling. FBC, CRP, TFTs, CK, calcium and vitamin D are normal. She has been prescribed codeine and pregabalin.
Answer: Fibromyalgia (chronic primary pain).

• Make a positive diagnosis and explain it; avoid further investigations (ANA, RF) without new features.
• Graded exercise, CBT or ACT, sleep hygiene, pacing; consider amitriptyline or duloxetine.
• Plan to taper and stop codeine and pregabalin (not recommended for chronic primary pain); screen for depression.

5. A 48-year-old man with chronic tophaceous gout has had flares despite allopurinol 300 mg for a year. His urate is 450 µmol/L. He has a kidney transplant and takes azathioprine.
Answer: Uncontrolled gout with a dangerous drug interaction.

• Allopurinol plus azathioprine risks severe marrow suppression — check FBC urgently and contact the transplant team.
• Options — switch azathioprine to mycophenolate (transplant team) and then titrate allopurinol to a target below 300 µmol/L (tophi); or specialist alternatives.
• Flares — steroids preferred (colchicine interacts with ciclosporin; NSAIDs harm the graft).

Key Points

• Gout — sudden red hot joint (often the big toe) peaking within 24 hours; crystals are needle-shaped and negatively birefringent.
• Urate may be normal during a flare — recheck at least 2 weeks later.
• Flares — NSAID (+ PPI), colchicine or short oral steroid; don't stop ULT during a flare.
• Offer ULT to all with gout — especially recurrent flares, tophi, CKD, diuretics, young onset.
• Allopurinol first — start low, increase monthly to urate under 360 (under 300 with tophi).
• Colchicine cover for up to 6 months when starting ULT.
• Allopurinol plus azathioprine — dangerous; colchicine plus clarithromycin — toxic.
• Febuxostat — caution in major cardiovascular disease.
• Pseudogout — older people, knee or wrist, during illness; rhomboid positive crystals; look for metabolic causes if young.
• Always exclude infection in a hot joint, even with known crystal disease.
• OA — clinical diagnosis over 45 with activity pain and stiffness under 30 minutes; no X-ray needed.
• OA treatment — exercise and weight loss first; topical NSAIDs; avoid paracetamol alone and strong opioids.
• Heberden's nodes at the DIPs, Bouchard's at the PIPs; thumb base OA is common.
• Fibromyalgia — positive diagnosis, exercise, CBT, antidepressants; avoid opioids and gabapentinoids.
• Hypermobility — Beighton score; watch for vascular EDS and Marfan syndrome.
• Avascular necrosis — steroids, alcohol, sickle cell; MRI if X-ray normal.

Guidelines and Further Reading

• NICE NG219: Gout — diagnosis and management
• BSR: Guideline for the management of gout
• EULAR: Recommendations for calcium pyrophosphate deposition
• MHRA Drug Safety Update: Febuxostat — increased risk of cardiovascular death
• NICE NG226: Osteoarthritis in over 16s — diagnosis and management
• ESCAPE-pain programme (exercise for knee and hip pain)
• NICE NG193: Chronic pain (primary and secondary) in over 16s
• ACR 2016: Revised fibromyalgia diagnostic criteria
• Ehlers–Danlos Society: 2017 International classification of EDS and hypermobility spectrum disorders
• BNF — for current doses