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. CRP can be markedly raised in bacterial infection, severe viral infection, inflammatory disease, malignancy, tissue injury, pancreatitis, postoperative states and major trauma. NICE acute respiratory infection evidence (NG237) shows CRP thresholds cannot replace clinical assessment: CRP >100 mg/L only moderately increases the probability of pneumonia, and CRP <20 mg/L does not exclude bacterial infection. CRP supports assessment of inflammation but does not diagnose sepsis, bacterial infection or treatment failure — interpret it with examination, observations, NEWS2, source assessment, lactate, blood tests and trajectory.

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 reduces the negative surface charge (zeta potential) that normally keeps red blood cells apart, 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 — very high ESR with mild CRP — is a prompt to consider myeloma when clinically plausible and request SPEP (serum protein electrophoresis) + serum free light chains + FBC per NICE NG12; it also occurs with anaemia, renal disease, age and pregnancy. 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 supports the diagnosis, but GCA can occur with modestly raised, discordant or rarely normal markers — the diagnosis is clinical.

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 lowers CRP), 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 — starting steroids while urgent ultrasound and/or biopsy are arranged carries minimal harm, whereas withholding steroids while awaiting tests can result in permanent blindness. Imaging is most useful before or soon after treatment begins.

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 (commonly 40–60 mg daily per the local fast-track protocol) 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). NICE TA518 (2018) recommends it only for adults with relapsing or refractory GCA who have not had tocilizumab before, stopping after 1 year of uninterrupted treatment at most. 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 should know that tocilizumab suppresses CRP and fever and can mask serious infection, so infection must be assessed clinically. GPs managing patients with GCA should be aware that tocilizumab is available via rheumatology services for selected relapsing or refractory disease and that patients who relapse on prednisolone, or who develop significant steroid side effects (diabetes, osteoporosis, cataracts, infections), should be referred for tocilizumab consideration.

Procalcitonin (PCT) is a precursor of calcitonin produced by multiple cell types in response to bacterial toxins and infection; it tends to rise less in viral infection, but it is neither perfectly sensitive nor specific — it can be raised after surgery or trauma, in renal impairment and in malignancy, and can be low early in, or with localised, bacterial infection. Trial evidence of reduced antibiotic use applies only to the specific populations and validated hospital protocols studied. NICE HTG386 (formerly DG18, 2015) did not recommend routine procalcitonin testing to guide antibiotics in suspected sepsis, so availability and local use vary; inappropriate antibiotic prescribing remains the main driver of antimicrobial resistance. Antibiotic decisions in primary care rest on clinical assessment, not a PCT or CRP threshold.

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: severe periodontal disease is associated with higher cardiovascular risk and raised CRP. 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. Dental health, sleep, exercise, smoking cessation and weight management are reasonable general advice, but they must not distract from investigating persistent unexplained inflammation.

CRP kinetics during antibiotic treatment vary considerably with source, treatment, drainage, renal function, immunosuppression and the inflammatory condition, so there is no universal percentage-fall rule. Lack of clinical improvement is what requires reassessment — 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 patient who is not improving clinically after 3–4 days of antibiotics (NICE NG250 suggests considering CRP or PCT only when there is clinical concern about treatment failure) should prompt: CT imaging to exclude an undrained collection, repeat blood cultures, review of antimicrobial sensitivities (if cultures available), and reconsideration of the diagnosis.