Rheumatology: Inflammatory arthritis

• Rheumatoid arthritis: What Is Rheumatoid Arthritis? | Joint Features of RA | Features Outside the Joints | Diagnosis and Urgent Referral | Treating RA — Treat to Target | Long-term Care and Complications of RA | Palindromic Rheumatism and Early Arthritis
• Spondyloarthritis: The Spondyloarthritis Family | Axial Spondyloarthritis | Managing Axial Spondyloarthritis | Psoriatic Arthritis | Reactive Arthritis | Enteropathic Arthritis and Uveitis
• Revision: Inflammatory Arthritis at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Inflammatory arthritis — page 2 of the Rheumatology chapter. Rheumatoid arthritis (RA) affects about 1 in 100 adults; untreated, it destroys joints within the first 2 years — so early referral and early DMARDs ("the window of opportunity") matter most. The spondyloarthritis family (axial spondyloarthritis, psoriatic, reactive and enteropathic arthritis) affects the spine, entheses and large joints, and is often diagnosed years late. Drugs and monitoring are on the Assessment, Investigations and Drugs page.
Your four questions for every patient: Is there true synovitis — and in which pattern? Is this RA or a spondyloarthritis (or something else, such as viral arthritis, gout or SLE)? Has the patient been referred early enough to start DMARDs? Are there features outside the joints — and is cardiovascular and bone health being looked after?

What Is Rheumatoid Arthritis?

• A chronic autoimmune inflammatory arthritis — inflamed synovium (pannus) grows over cartilage and erodes bone.
• Who — women about 2–3 times more than men; peak onset 30–50 years, but any age (late-onset RA can mimic PMR).
• Risk factors — smoking (the strongest environmental factor — linked with anti-CCP positivity), family history, HLA-DR4 ("shared epitope"), female sex, periodontitis, obesity.
• Seropositive (RF and/or anti-CCP positive) RA tends to be more severe and erosive than seronegative RA.
• Course — usually persistent, sometimes relapsing–remitting; without treatment — deformity, disability, loss of work, and reduced life expectancy (mainly cardiovascular disease).

Joint Features of RA

• Symmetrical polyarthritis of small joints — MCP and PIP joints of the hands, wrists, and MTP joints of the feet; later knees, ankles, elbows, shoulders, cervical spine.
• Spares the DIP joints (think OA or psoriatic arthritis if the DIPs are involved) and the thoracic and lumbar spine.
• Morning stiffness over 1 hour, fatigue, pain, swelling; positive MCP or MTP squeeze test.
• Late hand deformities (now less common with modern treatment):
  • Ulnar deviation of the fingers and volar subluxation at the MCPs.
  • Swan neck deformity — PIP hyperextension, DIP flexion.
  • Boutonnière deformity — PIP flexion, DIP hyperextension.
  • Z-thumb, wrist subluxation, extensor tendon rupture (can't extend the ring and little fingers — caput ulnae).
  • Carpal tunnel syndrome (wrist synovitis).
• Feet — MTP subluxation, "walking on pebbles" (prominent metatarsal heads), hallux valgus, claw toes.
• Knees — effusion, Baker's cyst (rupture mimics DVT).
• Cervical spine — atlanto-axial subluxation (C1–C2 instability) — neck pain, occipital headache, risk of cord compression (especially during intubation — check flexion–extension X-rays before general anaesthesia in long-standing RA).

Features Outside the Joints

Diagnosis and Urgent Referral

• Refer urgently to rheumatology (NICE NG100) — adults with suspected persistent synovitis of unknown cause, even with normal blood tests. Refer urgently if small joints of the hands or feet are affected, more than one joint is affected, or there has been a delay of 3 months or longer since symptoms began.
• Don't wait for blood tests, and don't let a negative RF or normal CRP delay referral.
• Tests:
  • RF first — if negative, check anti-CCP (NICE); anti-CCP is the more specific test.
  • CRP and ESR, FBC, U&E, LFTs (baseline before DMARDs).
  • X-ray hands and feet (baseline erosions); ultrasound of joints if doubt about synovitis.
  • Consider urate, ANA, viral serology (parvovirus, hepatitis B and C), TFTs depending on the picture.
• ACR/EULAR 2010 classification criteria — points for the number and size of joints involved, serology (RF, anti-CCP), acute phase reactants and duration (6 weeks or more); a score of 6 or more out of 10 classifies as RA (used for research — clinical diagnosis relies on the whole picture).
• Differential diagnosis — viral arthritis (settles within weeks), psoriatic arthritis, SLE and other CTDs, polyarticular gout or CPPD, PMR (older people), haemochromatosis, hypothyroidism, sarcoidosis, hepatitis C, nodal osteoarthritis.

Treating RA — Treat to Target

• Start a conventional DMARD as soon as possible — ideally within 3 months of the start of persistent symptoms (NICE NG100):
  • First-line monotherapy — oral methotrexate, leflunomide or sulfasalazine (methotrexate is the usual choice).
  • Hydroxychloroquine — mild or palindromic disease.
  • Bridging steroids — short-term (oral, IM or intra-articular) while the DMARD starts to work.
  • Escalate dose, then add other DMARDs (combination therapy — e.g. methotrexate with sulfasalazine and hydroxychloroquine) if the target isn't reached.
• Treat to target — measure disease activity with the DAS28 (28 joints — tender and swollen counts, ESR or CRP and patient global score):
  • Remission — DAS28 under 2.6; low disease activity — under 3.2; moderate — 3.2–5.1; high — over 5.1.
  • Review monthly (adjusting treatment) until the target (remission or low disease activity) is reached.
• Advanced therapies (biologics or JAK inhibitors) — for disease that remains moderate or severe despite at least two conventional DMARDs (NICE TAs):
  • Anti-TNF, abatacept, tocilizumab or sarilumab, JAK inhibitors — usually with methotrexate.
  • Rituximab — usually after anti-TNF failure, or first choice in some (e.g. previous lymphoma).
  • Continue only with an adequate response at 6 months (DAS28 fall of 1.2 or more); switch class if failing.
• Tapering — if in sustained remission, consider cautiously reducing drugs (step down) — but don't stop all DMARDs.
• Flares — check adherence and infection; short course of steroids; review the DMARD plan; a rapid-access advice line.
• Multidisciplinary care — specialist nurse, physiotherapy (exercise), occupational therapy (hand function, splints, aids), podiatry (insoles, footwear), psychological support; surgery (joint replacement, tendon repair, synovectomy, fusion) for damaged joints.

Long-term Care and Complications of RA

• Annual review (NICE NG100) — disease activity and damage, function, extra-articular disease, cardiovascular risk, osteoporosis risk, mood, work, complications, need for surgery or other services.
• Cardiovascular risk — RA roughly doubles CV risk; use QRISK3 (includes RA); statins, BP control, stop smoking, exercise; control inflammation (the best CV treatment).
• Osteoporosis — FRAX includes RA; bone protection with steroids.
• Infection — higher risk from disease and drugs; vaccinations (influenza, pneumococcal, COVID-19, Shingrix as eligible).
• Lymphoma — slightly increased risk (higher with active, long-standing disease and Felty's).
• Interstitial lung disease — breathlessness or crackles — HRCT and PFTs; antifibrotics (nintedanib) for progressive fibrosis.
• Peri-operative — cervical spine imaging before anaesthesia in long-standing disease; pause biologics around major surgery (timing by drug); usually continue methotrexate (BSR); steroid cover.
• Pregnancy — RA often improves in pregnancy and flares after delivery; plan drugs before conception (see page 1 and page 6).
• Work — many people stop work within years of diagnosis — early support, occupational health, flexible working.

Palindromic Rheumatism and Early Arthritis

• Palindromic rheumatism — recurrent attacks of pain, swelling and redness in one or a few joints (or periarticular tissue) lasting hours to a few days, completely settling between attacks; about a third later develop RA (higher if anti-CCP positive); hydroxychloroquine reduces attacks and progression.
• Undifferentiated inflammatory arthritis — synovitis not yet meeting criteria for a specific disease; monitor closely; treat according to features (DMARD if persistent, especially with anti-CCP).
• Clinically suspect arthralgia — joint pain with features suggesting early RA (anti-CCP positive) but no swelling yet; watch; trials of early abatacept and methotrexate are exploring prevention.
• Late-onset RA — older people; more large-joint and shoulder involvement; can look like PMR (check for synovitis in the hands; RF and anti-CCP).
• RS3PE syndrome (remitting seronegative symmetrical synovitis with pitting oedema) — older people; sudden swelling of both hands and wrists with pitting oedema; very steroid-responsive; can be linked with cancer.

The Spondyloarthritis Family

• Spondyloarthritis (SpA) — a group of related diseases with shared features, linked with HLA-B27:
  • Axial spondyloarthritis (including ankylosing spondylitis).
  • Psoriatic arthritis.
  • Reactive arthritis.
  • Enteropathic arthritis (with IBD).
• Shared features:
  • Inflammatory back pain and sacroiliitis.
  • Asymmetrical oligoarthritis, mostly of large lower-limb joints.
  • Enthesitis — Achilles tendon, plantar fascia, around the pelvis.
  • Dactylitis ("sausage digit").
  • Acute anterior uveitis.
  • Psoriasis, IBD, family history.
  • Seronegative — RF and anti-CCP negative.
• HLA-B27 — present in about 90% of ankylosing spondylitis, but also in about 8% of the general population — supports, but doesn't make, the diagnosis.

Axial Spondyloarthritis

• Inflammation of the spine and sacroiliac joints; includes ankylosing spondylitis (radiographic — sacroiliitis on X-ray) and non-radiographic axial SpA (inflammation on MRI only).
• Who — onset usually under 45 (often teens to 30s); men and women (more women have non-radiographic disease); average diagnostic delay is many years.
• Inflammatory back pain:
  • Gradual onset, lasting over 3 months.
  • Morning stiffness over 30 minutes; wakes in the second half of the night.
  • Better with exercise, not with rest.
  • Alternating buttock pain (sacroiliac joints).
  • Good response to NSAIDs (within 48 hours).
• Refer to rheumatology (NICE NG65) — low back pain for 3 months or more starting before age 45, with features such as inflammatory back pain pattern, extra-articular features (uveitis, psoriasis, IBD), family history, HLA-B27, buttock pain, enthesitis, dactylitis, raised CRP.
• Signs — reduced lumbar flexion (Schober's test — under 5 cm increase), reduced chest expansion, loss of lumbar lordosis, later question mark posture (thoracic kyphosis), increased occiput-to-wall distance.
• Investigations — CRP (raised in about half), HLA-B27; X-ray sacroiliac joints (sacroiliitis — late); MRI sacroiliac joints and spine (STIR — bone marrow oedema) for early disease.
• Late X-ray changes — syndesmophytes, squaring of vertebrae, "bamboo spine" (fusion).
• Extra-spinal features ("the As"):
  • Anterior uveitis (about 30%) — painful red eye, photophobia — same-day ophthalmology.
  • Aortic regurgitation, AV block.
  • Apical lung fibrosis, restricted chest expansion.
  • Achilles enthesitis and plantar fasciitis.
  • Amyloidosis (rare now).
  • IBD and psoriasis; osteoporosis and vertebral fractures.

Managing Axial Spondyloarthritis

• Exercise and physiotherapy — the foundation — daily stretching and strengthening, posture, hydrotherapy, group exercise programmes; stop smoking.
• NSAIDs — first-line drug treatment (full dose; try at least two different NSAIDs over 2–4 weeks each before calling them a failure); give with a PPI.
• Conventional DMARDs (methotrexate, sulfasalazine) don't help axial disease — sulfasalazine may help peripheral arthritis.
• Steroids — local injections for enthesitis or peripheral joints; systemic steroids are not very helpful for spinal disease.
• Biologics (NICE TAs) — if active disease (e.g. BASDAI 4 or more and spinal pain score 4 or more) despite NSAIDs:
  • Anti-TNF (adalimumab, etanercept, certolizumab, golimumab, infliximab) — also helpful for uveitis (monoclonal antibodies, not etanercept) and IBD.
  • IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab) — good if psoriasis; avoid with IBD.
  • JAK inhibitors (tofacitinib, upadacitinib) — with MHRA cautions.
• Monitor — BASDAI (disease activity), BASFI (function), CRP, posture and spinal mobility.
• Spinal fracture risk — a fused spine breaks easily, even with minor trauma — new neck or back pain after a fall needs CT (fractures are often unstable and missed on X-ray).
• Surgery — hip replacement for hip disease; spinal osteotomy for severe deformity (rare).

Psoriatic Arthritis

• Inflammatory arthritis in people with psoriasis (about 1 in 5 people with psoriasis) — arthritis appears before the skin disease in about 15% (ask about family history; look at the scalp, ears, umbilicus, natal cleft and nails).
• Patterns (Moll and Wright):
  • Asymmetrical oligoarthritis — common.
  • Symmetrical polyarthritis — RA-like.
  • DIP joint predominant — often with nail disease.
  • Axial — spondylitis, sacroiliitis (often asymmetrical).
  • Arthritis mutilans — severe destruction, "telescoping" fingers (rare).
• Clues — nail changes (pitting, onycholysis, hyperkeratosis — strongly linked with DIP arthritis), dactylitis, enthesitis, uveitis; RF negative.
• X-ray — pencil-in-cup deformity, erosions with new bone formation (periostitis), asymmetric sacroiliitis.
• Screening — people with psoriasis should be asked about joint symptoms annually (e.g. the PEST questionnaire) (NICE CG153).
• CASPAR criteria — inflammatory joint, spine or entheseal disease plus points for current or past psoriasis (or family history), nail dystrophy, negative RF, dactylitis and new bone formation on X-ray.
• Treatment (NICE, BSR and GRAPPA):
  • NSAIDs and local steroid injections for mild disease.
  • Conventional DMARDs — methotrexate (also helps skin), leflunomide, sulfasalazine.
  • Biologics — anti-TNF, IL-17 inhibitors (good for skin), IL-12/23 and IL-23 inhibitors (peripheral and skin disease, not axial), apremilast (PDE4 inhibitor — diarrhoea, weight loss, low mood), JAK inhibitors.
  • Work with dermatology for skin disease; manage cardiovascular risk (psoriasis is linked with obesity, diabetes, fatty liver and CVD).
• Avoid stopping steroids suddenly in psoriasis (pustular flare); hydroxychloroquine may worsen psoriasis.

Reactive Arthritis

• Sterile inflammatory arthritis developing 1–4 weeks after an infection elsewhere:
  • Sexually acquired — Chlamydia trachomatis (commonest in the UK).
  • Gut infections — Campylobacter, Salmonella, Shigella, Yersinia, (C. difficile rarely).
• Features:
  • Asymmetrical oligoarthritis of the lower limbs (knees, ankles), enthesitis (heel pain), dactylitis, low back pain.
  • The classic triad (previously "Reiter's syndrome") — urethritis, conjunctivitis and arthritis ("can't see, can't pee, can't climb a tree") — present in only a minority.
  • Anterior uveitis; skin — keratoderma blennorrhagicum (pustular rash on soles and palms), circinate balanitis; painless mouth ulcers.
• Investigations — joint aspiration (exclude septic arthritis and gout), CRP, sexual health screen (chlamydia and gonorrhoea NAAT, HIV, syphilis), stool culture if diarrhoea, HLA-B27.
• Treatment:
  • NSAIDs, intra-articular steroids (after infection excluded), rest then physio.
  • Treat chlamydia (doxycycline) and partners — antibiotics don't shorten the arthritis itself but treat the infection.
  • Sulfasalazine or methotrexate if persistent (over about 6 months).
• Prognosis — most settle within 6–12 months; some recur or become chronic (especially HLA-B27 positive).
• HIV — can present with reactive or psoriatic arthritis; test.

Enteropathic Arthritis and Uveitis

• Arthritis with inflammatory bowel disease (Crohn's and ulcerative colitis) — up to about a fifth of people with IBD:
  • Type 1 (peripheral, pauciarticular) — fewer than 5 large joints, flares with active bowel disease, self-limiting.
  • Type 2 (polyarticular) — 5 or more small joints, runs independently of bowel activity, more persistent.
  • Axial — sacroiliitis and spondylitis, independent of bowel activity.
• Treatment — treat the bowel disease; sulfasalazine (peripheral); anti-TNF monoclonal antibodies (infliximab, adalimumab) help both gut and joints; use NSAIDs cautiously (can trigger IBD flares) — short courses only; avoid IL-17 inhibitors (worsen IBD).
• Other IBD-linked features — erythema nodosum, pyoderma gangrenosum, uveitis, episcleritis, primary sclerosing cholangitis.
• Whipple's disease — rare: arthritis (often years before), diarrhoea, weight loss, neurological signs; Tropheryma whipplei; small bowel biopsy (PAS-positive macrophages); antibiotics. Coeliac disease — can cause arthralgia.
• Acute anterior uveitis — linked with HLA-B27 and all forms of SpA:
  • Painful red eye (redness around the iris — ciliary flush), photophobia, blurred vision, small or irregular pupil; usually one eye at a time.
  • Same-day ophthalmology — steroid and dilating drops; recurrent uveitis may need anti-TNF (adalimumab).

Inflammatory Arthritis at a Glance

Spot the Diagnosis

Exam-style Scenarios

1. A 42-year-old woman has 10 weeks of painful, swollen hands and wrists with 2 hours of morning stiffness. Both hands show MCP and PIP swelling. CRP 28. RF negative; anti-CCP strongly positive.
Answer: Early rheumatoid arthritis.

• Urgent rheumatology referral (persistent synovitis, small joints, multiple joints); X-ray hands and feet; baseline bloods and screening (hepatitis B and C, HIV, chest X-ray).
• Start methotrexate (weekly, with weekly folic acid) as soon as possible, with bridging steroids; monitoring bloods.
• Treat to target — monthly DAS28 until remission; stop smoking; education, physio and OT.

2. A 29-year-old man has 2 years of low back pain, worse in the early morning, waking him at 4 am, and improving with exercise. He had a painful red eye last year. Schober's test shows reduced flexion. CRP 18.
Answer: Axial spondyloarthritis.

• Refer to rheumatology; MRI sacroiliac joints (STIR), X-ray pelvis, HLA-B27.
• Daily exercise and physiotherapy; full-dose NSAIDs with PPI; stop smoking.
• If still active after two NSAIDs — anti-TNF (a monoclonal such as adalimumab — also reduces uveitis) or an IL-17 inhibitor; advise urgent eye review for future red eyes.

3. A 50-year-old man with plaque psoriasis has a swollen left knee, a swollen right second toe, painful heels and pitted nails. RF is negative.
Answer: Psoriatic arthritis (oligoarthritis, dactylitis, enthesitis).

• Refer to rheumatology; X-rays; check CV risk factors, liver function and alcohol (methotrexate).
• Methotrexate (helps skin and joints) ± local steroid injection to the knee; NSAIDs for symptoms.
• Biologic (anti-TNF, IL-17 or IL-23) if active despite DMARDs; liaise with dermatology.

4. A 24-year-old man has a hot swollen right knee and painful left heel 3 weeks after an episode of urethral discharge. He also has sore red eyes.
Answer: Reactive arthritis (likely post-chlamydial).

• Aspirate the knee (exclude septic arthritis, gonococcus and crystals); full sexual health screen (NAAT, HIV, syphilis).
• Treat chlamydia (doxycycline) and partners; NSAIDs; intra-articular steroid once infection excluded; eye review if uveitis suspected.
• Most settle within 6–12 months; sulfasalazine if persistent.

5. A 68-year-old woman with 25 years of RA needs a hip replacement. She has neck pain and occasional tingling in her hands.
Answer: Possible atlanto-axial subluxation — peri-operative risk.

• Flexion and extension cervical spine X-rays (± MRI if neurological symptoms) before anaesthesia; inform the anaesthetist (airway handling).
• Plan drugs around surgery — usually continue methotrexate, pause biologics according to dosing interval, steroid cover if on long-term prednisolone.
• Check for ILD, anaemia, CV risk and osteoporosis before surgery.

Key Points

• Refer suspected persistent synovitis urgently — don't wait for blood tests.
• RA — symmetrical small-joint polyarthritis sparing the DIPs; smoking is the major risk factor.
• Check RF, then anti-CCP if negative; X-ray hands and feet.
• Start a DMARD (usually methotrexate) within 3 months of persistent symptoms, with bridging steroids.
• Treat to target — monthly DAS28 until remission (under 2.6) or low activity (under 3.2).
• Biologics after two conventional DMARDs for moderate or severe disease.
• RA extra-articular — nodules, ILD, scleritis, Felty's, amyloid, vasculitis; CV risk is doubled.
• Check the cervical spine before anaesthesia in long-standing RA.
• Spondyloarthritis — seronegative, HLA-B27, enthesitis, dactylitis, uveitis, asymmetric large joints.
• Inflammatory back pain — under 45, morning stiffness, night pain, better with exercise.
• Axial SpA — exercise and NSAIDs first; conventional DMARDs don't work for the spine; then anti-TNF or IL-17.
• New pain after a fall in a fused spine — CT for fracture.
• Psoriatic arthritis — nail pitting, DIP disease, dactylitis, pencil-in-cup; screen psoriasis patients annually.
• Reactive arthritis — 1–4 weeks after chlamydia or gut infection; screen for STIs; usually settles.
• Enteropathic arthritis — avoid IL-17 inhibitors; anti-TNF antibodies treat gut and joints.
• Painful red eye with photophobia in SpA — same-day ophthalmology.

Guidelines and Further Reading

• NICE NG100: Rheumatoid arthritis in adults — management
• NICE Technology Appraisals for biologics and JAK inhibitors in RA, PsA and axial SpA
• BSR: Guideline for the management of rheumatoid arthritis
• ACR/EULAR: 2010 rheumatoid arthritis classification criteria
• NICE NG65: Spondyloarthritis in over 16s — diagnosis and management
• BSR: Guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs
• NICE CG153: Psoriasis — assessment and management (annual PsA screening)
• GRAPPA: Treatment recommendations for psoriatic arthritis
• National Axial Spondyloarthritis Society (NASS) and Versus Arthritis resources
• BNF — for current doses