CRP (C-reactive protein) is a pentameric protein synthesised by the liver in response to IL-6 signalling from inflamed tissues — it rises within 6 hours of an inflammatory stimulus, peaks at 48 hours, and has a short half-life of approximately 19 hours, making it an excellent acute-phase marker that closely reflects current inflammation. ESR (erythrocyte sedimentation rate) rises more slowly (peaks at 3-5 days) and falls more slowly — it reflects fibrinogen and immunoglobulin levels more than CRP and is influenced by RBC characteristics (anaemia falsely elevates ESR; polycythaemia falsely lowers it). The practical clinical distinction: CRP is more useful for monitoring acute responses (infection, acute inflammatory flares); ESR is more useful for monitoring chronic conditions (RA, myeloma, temporal arteritis long-term). Both are non-specific — they indicate that inflammation is present but do not identify its cause. The clinical value is in the magnitude: CRP above 100 mg/L strongly suggests bacterial infection or severe tissue necrosis; CRP 10-100 mg/L is consistent with viral infection, autoimmune disease, or malignancy; CRP below 10 mg/L makes significant bacterial infection unlikely.

The CRP-ESR discordance pattern is clinically useful — multiple myeloma classically produces a very elevated ESR with a disproportionately mild CRP elevation. The pathophysiology: the monoclonal immunoglobulin (paraprotein) produced by myeloma plasma cells increases the negative surface charge of red blood cells, causing them to rouleaux (stack like coins), which increases the sedimentation rate dramatically. However, paraprotein does not stimulate IL-6 in the same way as a bacterial infection, so CRP remains relatively low. This pattern — ESR above 100 with mild CRP — is a strong prompt to request SPEP (serum protein electrophoresis) + serum free light chains + FBC to exclude myeloma. Conversely, GCA produces a very high CRP (often above 50-100 mg/L) AND a very high ESR — both markers are markedly elevated, reflecting the extensive granulomatous inflammation of the arterial wall. The dual elevation of both markers is a feature of GCA that supports the diagnosis.

Persistently mildly elevated CRP (between 5-20 mg/L) in the absence of acute illness is one of the most frequently encountered and least acted-upon findings in primary care — it is almost always attributable to lifestyle and metabolic factors (obesity, smoking, physical inactivity, insulin resistance) rather than undiagnosed occult disease. The clinical significance: chronic low-grade inflammation is associated with increased risk of cardiovascular disease, T2DM, Alzheimer's dementia, and depression. However, the finding of a mildly elevated CRP in an asymptomatic obese middle-aged patient should prompt: lifestyle modification counselling (weight loss is the most effective intervention for reducing CRP — a 5% weight reduction reduces CRP by approximately 30-40%), smoking cessation, and treatment of metabolic syndrome components — not a cascade of investigations for occult malignancy. The investigation threshold should be guided by: age, symptoms, rate of change (a CRP that has risen from 8 to 22 over 6 months warrants more investigation than a stable CRP of 12 over 3 years), and the clinical context.

The jaw claudication symptom in GCA is the most specific feature of the condition — it occurs in approximately 40-50% of GCA patients and results from ischaemia of the masseter and temporalis muscles during chewing (supplied by branches of the external carotid artery that are involved in GCA). When present, jaw claudication has a positive likelihood ratio of approximately 4.2 for GCA — making it the single most discriminating symptom. Patients describe it as jaw tiredness or aching that comes on after chewing for a few bites and resolves with rest (analogous to intermittent claudication in the legs). This is distinct from jaw pain at rest or dental pain. The immediate risk of GCA that must be prevented is anterior ischaemic optic neuropathy (AION) — caused by vasculitis obliterating the posterior ciliary arteries supplying the optic nerve head. Vision loss from AION is sudden, painless, and permanent. Prednisolone must be started immediately when GCA is clinically suspected — giving steroids for 2-3 weeks before a biopsy confirms the diagnosis carries minimal harm, whereas withholding steroids while awaiting biopsy can result in permanent blindness.

The early prednisolone prescription for GCA-suspected patients before ophthalmology or rheumatology review is medico-legally important and clinically correct — a GP who delays starting prednisolone in a patient with jaw claudication, temporal tenderness, and ESR of 85 mm/hr 'waiting for a rheumatology appointment' and who then develops ischaemic optic neuropathy with permanent blindness has caused avoidable harm. The correct action: start prednisolone 60 mg OD at the consultation where GCA is first suspected, refer urgently, and document the clinical reasoning. The diagnosis of GCA is clinical — biopsy confirms it but a negative biopsy does not exclude it (approximately 20-30% of biopsy specimens are false-negative due to skip lesions). Temporal artery ultrasound (halo sign — dark inflammatory halo around the arterial lumen) has equivalent sensitivity to biopsy in experienced hands and is increasingly used as a non-invasive diagnostic test in specialist centres.

The tocilizumab (IL-6 inhibitor) approval for GCA (NICE TA518, 2018) represents a major advance in GCA management — the GiACTA trial showed that tocilizumab plus a tapered prednisolone course achieved 56% sustained remission at 52 weeks compared to 14% with prednisolone alone, while also significantly reducing the cumulative steroid dose (and therefore steroid-related side effects). The NICE approval is for adults with active GCA (newly diagnosed or relapsing). Tocilizumab is given as 162 mg SC weekly or every 2 weeks as an add-on to prednisolone. The mechanism: GCA involves IL-6-driven Th17 cell activation and granulomatous arteritis; tocilizumab blocks the IL-6 receptor, interrupting this pathway. GPs managing patients with GCA should be aware that tocilizumab is now available via rheumatology services and that patients who relapse on prednisolone, or who develop significant steroid side effects (diabetes, osteoporosis, cataracts, infections), should be referred for tocilizumab consideration.

The procalcitonin (PCT) test is increasingly available in UK primary care settings and urgent treatment centres, and GPs should be aware of its utility — PCT is a precursor of calcitonin produced by multiple cell types in response to bacterial toxins and infection. In viral infections (including influenza, RSV, COVID-19), PCT remains very low (below 0.1 ng/ml) even when the patient is systemically unwell, because viral replication does not trigger the same cytokine cascade as bacterial infection. This makes PCT a highly specific marker for distinguishing bacterial from viral infection. Multiple RCTs have shown that PCT-guided antibiotic prescribing in lower respiratory tract infections reduces antibiotic prescriptions by approximately 40% without increasing adverse outcomes. The NHS antimicrobial stewardship programme is increasingly promoting PCT use in urgent care settings to reduce inappropriate antibiotic prescribing, which is the primary driver of antimicrobial resistance. A patient with CRP of 35 mg/L, fever, and cough — but PCT below 0.1 ng/ml — is very unlikely to have bacterial infection and does not need antibiotics.

Periodontal disease as a source of systemic inflammation and cardiovascular risk is one of the most underemphasised connections in primary care — the evidence base is now substantial: patients with severe periodontal disease have approximately 25-30% higher risk of cardiovascular disease and significantly elevated CRP compared to patients with healthy periodontium. The mechanism: Porphyromonas gingivalis and other oral pathogens translocate into the bloodstream through inflamed periodontal tissue, triggering systemic IL-6 and CRP production, promoting endothelial dysfunction, and contributing to atherosclerotic plaque formation. In patients with chronically mildly elevated CRP (5-20 mg/L) and no other identified cause, asking about dental health and recommending periodontal assessment by a dentist is a clinically appropriate and evidence-based intervention. Some studies suggest that periodontal treatment (scaling and root planing) reduces CRP by approximately 0.5-1.0 mg/L in patients with poor dental health.

The CRP monitoring decision rule during antibiotic treatment is a practical bedside tool: in bacterial infections treated with appropriate antibiotics, CRP should fall by more than 50% within 72 hours and normalise within 5-7 days. Failure to achieve this response is a red flag requiring clinical reassessment — the three most common causes of failure to respond are: (1) inadequate antibiotic spectrum (wrong antibiotic, resistance, or insufficient dose); (2) an undrained focus of infection (abscess — pleural, abdominal, peri-nephric, dental) that antibiotics cannot penetrate effectively; and (3) incorrect diagnosis (the elevated CRP is from a non-infectious cause such as vasculitis, malignancy, or PE rather than bacterial infection). A persistently rising CRP after 72 hours of antibiotics in a patient previously suspected of bacterial infection should prompt: CT imaging to exclude an undrained collection, repeat blood cultures, review of antimicrobial sensitivities (if cultures available), and reconsideration of the diagnosis.