The 3-week rule for oral ulcers is one of NICE NG12's most clinically important recommendations — any ulcer in the oral cavity that has been present for more than 3 weeks without a clear benign cause (known aphthous ulcer pattern, identifiable trauma, clearly responding to topical treatment) must be referred urgently for specialist assessment to exclude oral squamous cell carcinoma. Oral cancer is the 6th most common cancer worldwide and has a poor prognosis — 5-year survival is only 50% overall, largely because most oral cancers are diagnosed at stage III or IV when symptoms have been present for months. The most common sites are the lateral tongue (40% of oral SCC), floor of mouth, soft palate, and buccal mucosa. The classic appearance of oral SCC is an indurated ulcer with raised, rolled, or everted edges, a firm base, and failure to heal — but early lesions can appear deceptively benign (erythematous patch, white patch, or shallow ulcer). The rule is simple: any ulcer not healed in 3 weeks → 2WW. Stevens-Johnson Syndrome is one of the most dangerous drug reactions in medicine — mortality of SJS is 5–10% and TEN (the severe end of the spectrum with >30% body surface area epidermal detachment) has a mortality of 25–35%. The most common causative drugs are: allopurinol (most commonly in Asian patients with HLA-B*5801 genotype — genetic testing recommended before initiation in South Asian patients), aromatic antiepileptics (carbamazepine, phenytoin, lamotrigine — especially lamotrigine without slow titration), sulfonamide antibiotics, NSAIDs (particularly meloxicam and piroxicam), and nevirapine. Any patient on a new drug who develops oral mucosal involvement + skin rash is SJS until proven otherwise. The drug must be stopped immediately, and the patient sent to hospital.

Nicorandil-induced oral ulcers deserve special emphasis because they are a perfect example of a drug-induced condition that is completely reversible once recognised, but causes significant patient suffering and inappropriate treatments until identified. Nicorandil is a potassium channel opener used for angina — it causes large, single or multiple, clean-based, very painful oral ulcers (and can also cause perianal and vulval ulcers by the same mechanism — ischaemic mucosal injury). The ulcers are distinctive: they have clean, well-demarcated edges, can be very large (several centimetres), and are exquisitely painful. They do not heal despite all standard aphthous ulcer treatments. Stopping nicorandil results in complete healing within 3–6 weeks. The diagnosis is straightforward if the drug history is taken — but nicorandil is often overlooked because it is not a commonly prescribed drug. The SLS (sodium lauryl sulfate) connection to aphthous ulcers is important to advise patients — SLS is the foaming agent in most commercial toothpastes and has been shown in multiple RCTs to worsen recurrent aphthous stomatitis by disrupting the mucosal protective barrier. Switching to an SLS-free toothpaste (Sensodyne Original is SLS-free; Biotène is specifically formulated without SLS) reduces RAS frequency and severity in approximately 50% of patients who have the SLS sensitivity. This is a simple, zero-risk lifestyle modification that GP can recommend at the consultation and which often provides dramatic improvement in recurrent aphthous patients. The anatomical location of aphthous ulcers is diagnostically useful: genuine aphthous ulcers only occur on non-keratinised mucosa (buccal, labial, floor of mouth, soft palate, ventral tongue). Ulcers on the hard palate or gingiva (both keratinised mucosa) are NOT aphthous — they are more likely to be traumatic, herpetic (hard palate is a common site for HSV recurrence), or in the case of gingival ulceration, pemphigoid or pemphigus.

The 20% prevalence of haematological deficiencies in recurrent aphthous stomatitis patients makes investigation mandatory — iron deficiency is the most common finding, present in approximately 15% of RAS patients, and correction of the deficiency resolves or substantially reduces ulcer frequency in the majority of these patients. The mechanism is that iron (and B12 and folate) are essential cofactors for epithelial cell turnover and mucosal barrier function — deficiency impairs the rapid renewal of the oral mucosal epithelium (which turns over every 7–14 days), creating fragility and susceptibility to ulceration. The clinical significance is that iron deficiency can cause RAS without causing anaemia — the ferritin may be low while the haemoglobin is still normal, so FBC alone is insufficient. A GP who prescribes ferrous sulphate for an iron-deficient patient with recurrent aphthous ulcers is both treating a systemic deficiency and likely resolving a frustrating and painful chronic oral condition — a satisfying intervention at minimal cost. The coeliac-RAS connection is well-established in the literature — recurrent oral ulcers are found in approximately 3–5% of coeliac disease patients and may be the only presenting symptom of coeliac disease in the absence of GI symptoms. The implication is that every patient presenting to a GP with recurrent aphthous stomatitis should be screened for coeliac disease with TTG IgA + total IgA — a simple blood test that costs very little and, if positive, leads to dietary treatment (gluten-free diet) that resolves both the oral ulcers and the intestinal damage. The total IgA is essential because 1 in 500 individuals has selective IgA deficiency, in which case TTG IgA will be falsely negative and TTG IgG or EMA IgG must be used instead. PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis) is an important diagnosis in children with recurrent oral ulcers — it causes precisely periodic febrile episodes (every 3–6 weeks, like clockwork) with the four components, lasting 3–6 days and resolving completely between episodes. The periodicity is the diagnostic clue — if a parent says "my child gets a fever with mouth ulcers and a sore throat every month on a predictable schedule," PFAPA should be strongly considered. Paediatric referral for confirmation and management (corticosteroid at episode onset is highly effective; tonsillectomy is curative in many cases).

The bimanual palpation technique for the floor of mouth is a clinical skill that dramatically increases the sensitivity of oral cancer detection — floor of mouth SCC often begins as a small, relatively painless, indurated lesion that is much more palpable than visible. With one finger inside the mouth on the floor and the other hand under the chin, a lesion that cannot be seen can be felt as a firm cord or thickening against the surrounding soft tissue. This technique takes 10 seconds and is taught in RCGP resources as part of the oral cancer awareness campaign. GPs should include floor of mouth palpation as a routine part of any oral examination in patients with mouth ulcers. Erythroplakia (red velvety patches of oral mucosa that cannot be wiped off) is the oral lesion with the highest malignant transformation rate — up to 50% of erythroplakic lesions will transform to SCC if untreated, compared to 5–17% for leukoplakia. Despite this, erythroplakia receives less clinical attention than leukoplakia because it is less visually dramatic. Any red non-wipeable patch in the mouth of an adult, particularly at a high-risk site (floor of mouth, lateral tongue, soft palate), warrants urgent 2WW referral even if an ulcer is not present. Tonsillar asymmetry in an adult (one tonsil visibly larger than the other) is a finding that must not be dismissed as normal variation without further assessment — unilateral tonsillar enlargement in an adult is an indication for urgent referral to exclude tonsillar lymphoma (rapidly growing, non-tender, firm) or tonsillar SCC (particularly HPV-positive oropharyngeal cancer, which is rising rapidly in the UK, predominantly affecting non-smoking men aged 40–60 years). NICE NG12 specifies 2WW referral for unexplained tonsillar asymmetry in adults.

Ludwig's angina is one of the most dangerous conditions in all of primary care — it is a rapidly spreading bilateral cellulitis of the floor of the mouth (submandibular, submental, and sublingual spaces) originating from dental infection (usually mandibular molar or premolar). The infection spreads along fascial planes to the floor of the mouth, causing a woody, brawny swelling that displaces the tongue superiorly and posteriorly. This leads to progressive airway obstruction — patients become unable to swallow saliva, hold the airway open, or breathe. Death from asphyxia can occur within hours of onset in an untreated case. The key clinical features are: floor of mouth induration (wooden feel on palpation rather than fluctuant — because the infection is diffuse through the fascial spaces rather than localised to an abscess), bilateral submandibular swelling, raised tongue, drooling, and inability to open the mouth fully. Any patient with these features must be called 999 immediately — this is not a case for GP prescription of antibiotics. The 2WW oral cancer pathway threshold of 3 weeks for non-healing ulcers is critical and must be applied without exceptions — the most common cause of delayed oral cancer diagnosis is a GP who gives an ulcer "one more week" beyond 3 weeks, then "another week," allowing the cancer to progress while the patient and GP wait for spontaneous resolution. The rule must be applied with the same inflexibility as the 2WW rule for rectal bleeding or a breast lump: any unexplained oral ulcer at 3 weeks from first presentation = 2WW, regardless of the patient's age, smoking status, or the GP's suspicion level. If the referral proves unnecessary, the specialist will discharge the patient at the outpatient appointment — no harm done.

Benzydamine hydrochloride (Difflam) mouthwash is underused in primary care — it is both an analgesic (via sodium channel blockade, similar mechanism to lidocaine) and an anti-inflammatory (via prostaglandin synthesis inhibition), making it effective for reducing the pain of aphthous ulcers during eating and drinking. It is licensed OTC, costs approximately £6, and can be recommended without prescription. For patients with major aphthous ulcers who cannot eat, Difflam mouthwash used 30 minutes before meals can make the difference between maintaining adequate oral intake and requiring hospital admission for fluid and nutritional support. The instruction is to rinse for 30–60 seconds, spit out, and then eat — the anaesthetic effect lasts approximately 30–60 minutes. Corlan pellets (hydrocortisone 2.5 mg mucoadhesive buccal tablets) are the most practical and widely used topical corticosteroid for aphthous ulcers in UK primary care — they are placed against the ulcer surface (on a dry mucosa for best adhesion) and allowed to dissolve slowly, delivering corticosteroid locally with negligible systemic absorption. They are most effective when started as soon as the prodromal tingling is felt (the 24-hour period before the ulcer appears when patients often feel a localised burning sensation) — at this stage they can abort the ulcer entirely. Patients should be instructed to start treatment at the prodromal stage rather than waiting for the ulcer to appear. Thalidomide for severe refractory RAS and HIV-associated major aphthous is a specialist intervention but is one of the most effective treatments known for this indication — complete or near-complete remission in 70–90% of patients. The strict teratogenicity requirements (thalidomide is absolutely contraindicated in pregnancy and was responsible for thousands of cases of phocomelia in the 1960s) mean it is only prescribed by specialists with a mandatory pregnancy prevention programme in all women of childbearing potential. GPs should be aware of this option for patients with truly refractory severe RAS who have failed multiple other treatments, so they can discuss specialist referral appropriately.

The documentation of nicorandil as a cause of oral ulceration is a patient safety action — nicorandil is a drug that GPs prescribe, and once oral ulcers are identified as the cause, the drug must be clearly documented as contraindicated in the patient's allergy/adverse drug reaction record to prevent re-prescription by another GP or during hospital admissions. "Nicorandil — oral ulceration" should be added to the adverse drug reactions list. The patient should also be warned to inform all future prescribers of this reaction. Aciclovir timing in primary HSV gingivostomatitis is critical for efficacy — antiviral treatment significantly reduces the severity and duration of primary HSV stomatitis when started within 72 hours of symptom onset but has minimal benefit if started later. The most common reason for inadequate treatment is delay in diagnosis (many GPs do not recognise the clinical picture) or delay in presentation (parents bring children late because they assume the oral lesions are aphthous). Key features distinguishing primary HSV from aphthous: (1) affects both keratinised and non-keratinised mucosa (hard palate and gingiva are prominently involved in HSV); (2) fever + lymphadenopathy + malaise present; (3) acute onset without prior history; (4) age (most common in children and young adults — first exposure to HSV). The dehydration risk in primary HSV stomatitis in children is the most important immediate concern — the severe pain makes swallowing extremely difficult, and young children can become significantly dehydrated within 24 hours. Hospital admission for IV fluids should be considered early if the child is not maintaining adequate oral intake. A clinical decision rule: any febrile child who has not had adequate fluid intake for 12 hours because of oral pain = hospital assessment.

The smoking-aphthous paradox is one of medicine's more counterintuitive observations — nicotine has a well-documented suppressive effect on oral mucosal immune activity (it stimulates keratinocyte differentiation and increases the thickness of the keratinised epithelial layer, reducing ulcer susceptibility). This explains why smokers have lower rates of RAS than non-smokers (despite having dramatically higher rates of oral cancer), and why patients who stop smoking frequently experience a cluster of aphthous ulcers in the weeks following cessation. This information is clinically important for two reasons: (1) GPs should warn patients who are stopping smoking that a temporary increase in mouth ulcers is expected and should not be alarming or a reason to resume; and (2) this observation must absolutely not be used to justify continued smoking — the oral cancer risk reduction alone (smoking accounts for 80% of oral SCC cases) provides an overwhelming reason to stop. The DGL (deglycyrrhizinated liquorice) mouthwash evidence for RAS is modest but worth knowing — a small RCT by Das et al. showed that DGL mouthwash reduced pain and ulcer size in RAS. The deglycyrrhizination removes the glycyrrhizin component (responsible for mineralocorticoid-like effects — fluid retention, hypertension) while retaining the anti-inflammatory flavonoids. Available from health food shops, it is a safe and reasonable adjunct for patients seeking non-pharmaceutical options. The chlorhexidine staining effect is frequently not communicated to patients — brown discolouration of teeth and tongue from chlorhexidine is reversible but distressing, and patients who are not warned are often alarmed and stop using the mouthwash. The instruction is: use BD for acute episodes of aphthous ulceration (7–14 days), then switch to saline or bicarbonate rinse for maintenance. Professional scale and polish can remove chlorhexidine staining if it occurs.

The tracking of 2WW referral outcomes is a clinical governance requirement that is frequently neglected — when a GP makes a 2WW referral, the outcome of that referral should be recorded in the patient's notes when the specialist letter arrives. If no specialist letter arrives within 4 weeks, the GP should proactively chase the outcome — this both ensures the patient was seen and provides the GP with important information about the safety of their 2WW threshold. In a medicolegal context, being able to demonstrate that a 2WW referral was made and followed up to a documented outcome (benign, pre-malignant, malignant) is the standard of care. Tracking outcomes also calibrates the GP's clinical decision-making — knowing what proportion of their 2WW oral medicine referrals prove to be benign vs malignant helps them understand whether they are pitching their threshold appropriately. The Behçet's uveitis surveillance frequency (3-monthly initially) reflects the sight-threatening potential of Behçet's ocular disease — uveitis in Behçet's can be severe, posterior (choroiditis, retinal vasculitis), and rapidly progressive, causing blindness if untreated. Approximately 25% of Behçet's patients with ocular involvement lose useful vision in the long term despite treatment. The rheumatologist managing the systemic disease and the ophthalmologist monitoring for ocular complications must both be involved — this is a condition that requires explicit co-ordination between specialties, and the GP's role is to ensure that both referrals are active and that the patient is attending both follow-up clinics.