Septic arthritis is a rheumatological emergency — irreversible cartilage destruction begins within 24–48 hours of bacterial invasion due to proteolytic enzyme release from neutrophils and bacteria. Staphylococcus aureus (50%) is the most common organism, followed by streptococci (25%) and gonococci in sexually active young adults. The synovial fluid WBC threshold for septic arthritis is typically >50,000/mm³ (though crystal arthritis can produce similar counts). Joint aspiration MUST be performed before antibiotics to guide culture-directed therapy — but antibiotics should not be withheld for >1–2 hours if aspiration is delayed. Risk factors: prosthetic joint (most important — prosthetic joint infection has 20% mortality), IV drug use, immunosuppression, diabetes, skin disease (psoriasis creates skin barrier breaks), recent joint injection. Any prosthetic joint with pain + fever = surgical emergency.

The duration of morning stiffness is the single most diagnostically discriminating clinical feature for distinguishing inflammatory from mechanical joint disease. Morning stiffness >60 minutes strongly predicts inflammatory pathology (RA, psoriatic, reactive) — it reflects the time required for synovial gel phenomenon to resolve as the joint warms with activity. OA morning stiffness typically lasts <30 minutes. This 60-minute threshold is incorporated into the ACR/EULAR 2010 RA classification criteria. The second key distinction is the relationship of pain to activity: inflammatory arthritis characteristically worsens with inactivity and improves with movement (joints feel worse first thing in the morning and after sitting), while OA worsens with use (pain builds with sustained activity and relieves with rest). Patients often describe OA as "the more I do, the more it hurts" and inflammatory arthritis as "the more I rest, the stiffer I get."

The anti-CCP (anti-cyclic citrullinated peptide) antibody is the most specific test for RA — 75–80% sensitivity but 95–97% specificity. Positive anti-CCP in early inflammatory arthritis is highly predictive of RA development and is associated with more erosive, aggressive disease. A patient with anti-CCP positive symmetrical small joint polyarthritis and elevated CRP should be referred to rheumatology as a matter of urgency (NICE NG100: within 6 weeks). The 2022 NICE guideline change removed the distinction between "undifferentiated inflammatory arthritis" and "RA" — all patients with persistent joint swelling of unclear cause and elevated inflammatory markers should be referred to rheumatology within 6 weeks regardless of serology. Distinguishing RA from psoriatic arthritis is clinically important as they have different DMARD pathways — psoriatic arthritis often responds well to TNF inhibitors and IL-17 inhibitors, while methotrexate is the anchor DMARD for RA.

DAS28 (Disease Activity Score in 28 joints) is the validated clinical tool used by rheumatologists to monitor RA disease activity and guide DMARD dose escalation and treat-to-target decisions. It incorporates: 28-joint tender count, 28-joint swollen count, patient VAS (visual analogue scale for global health), and CRP (or ESR). DAS28 <2.6 = remission; 2.6–3.2 = low activity; 3.2–5.1 = moderate; >5.1 = high. NICE NG100 mandates treat-to-target (target DAS28 <2.6 = remission) — DMARDs are escalated every 3 months until remission is achieved. GPs who see patients on DMARDs should be familiar with DAS28 from rheumatology letters to understand disease activity status and treatment appropriateness.

The NICE NG100 urgency for RA referral (within 6 weeks of symptom onset) is based on evidence that treatment delay beyond 12 weeks significantly worsens long-term joint damage outcomes — the window of opportunity for suppressing the immune cascade before erosive joint destruction occurs is narrow. Patients with RA who start DMARDs within 3 months of symptom onset have significantly better 5-year and 10-year functional outcomes than those starting later. The GP should not wait for repeat bloods or X-ray reports before referring — clinical suspicion of inflammatory arthritis with elevated CRP is sufficient to refer urgently. The rheumatologist will arrange the further investigations. The most common cause of delayed RA diagnosis in primary care audit data is repeat GP consultations without progression to referral.

Starting DMARDs (methotrexate, hydroxychloroquine, sulfasalazine) in primary care before a rheumatological diagnosis is confirmed is inappropriate and potentially harmful. DMARDs require: tuberculosis screening (IGRA test — methotrexate reactivates latent TB), hepatitis B screening (methotrexate and biologics can reactivate HBV), DEXA scan baseline (steroid-sparing), full blood count and LFT baseline, and patient counselling about teratogenicity and monitoring requirements. These are rheumatologist-led investigations. The GP's role is to provide symptomatic bridge therapy (NSAIDs, short prednisolone course if severe) while ensuring urgent rheumatology referral is made. The risk of delaying DMARD initiation is real (joint erosion) but the risk of starting immunosuppression without proper screening is also significant.

Methotrexate pneumonitis (MTX-induced lung toxicity) is a rare but life-threatening complication — it presents as progressive dyspnoea, dry cough, and fever, typically within the first 12 months of treatment. Any patient on methotrexate who develops new respiratory symptoms must have methotrexate stopped immediately, chest X-ray performed, and urgent respiratory referral arranged. The mortality of methotrexate pneumonitis is 10–15% even with corticosteroid treatment. New dyspnoea in an RA patient on methotrexate must never be attributed to infection or heart failure without specifically considering MTX lung toxicity. The GPs' monitoring protocol (FBC + LFT every 12 weeks) is mandated by NICE and the British Society for Rheumatology — failure to monitor and resulting MTX toxicity is a documented cause of GP negligence claims.

Exercise is the most evidence-based treatment for OA — multiple systematic reviews and meta-analyses demonstrate that land-based exercise reduces OA pain (effect size 0.49 — comparable to NSAIDs) and improves function, with no ceiling effect across ages and severities. The key barrier is patient belief that exercise "wears out" the joint — this is scientifically incorrect and must be actively dispelled. Cartilage has no blood supply; it is nourished by the compressive-release pumping action of joint movement. Regular moderate exercise maintains cartilage health. Paracetamol has minimal evidence for OA pain — a 2016 Lancet meta-analysis of 74 trials found paracetamol had clinically insignificant effects on OA pain compared to placebo. Despite this, it remains recommended due to its safety profile while exercise takes effect. NSAIDs have better evidence but worse side effect profiles — use lowest effective dose for shortest duration.

The risk of septic arthritis in patients on biologic DMARDs (TNF inhibitors, JAK inhibitors) is 2–3-fold higher than the general population — these drugs suppress the innate and adaptive immune response that normally prevents haematogenous seeding. Any patient on a biologic who develops a hot, swollen, acutely painful joint should be considered to have septic arthritis until joint aspiration proves otherwise. This is clinically challenging because biologics also suppress the inflammatory features of gout and RA flares — leading to presentations where crystal arthritis or RA flare mimics septic arthritis. The answer in all cases is the same: urgent hospital assessment for joint aspiration and culture. GPs should have a low threshold to call rheumatology directly when managing joint flares in biologic-treated patients.