The 3-week rule is a NICE NG12 suspected-cancer referral criterion, not a diagnosis: for unexplained oral ulceration lasting more than 3 weeks NICE says consider a suspected cancer pathway referral, and this site's local safety policy is to refer by default. Oral cancer outcomes are worse when diagnosis is late. The most common sites are the lateral tongue, 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: unexplained ulceration lasting more than 3 weeks → suspected cancer pathway referral. Stevens-Johnson Syndrome and TEN (the severe end of the spectrum) are among the most dangerous drug reactions in medicine. The most common causative drugs are: allopurinol (risk is higher in HLA-B*5801 carriers — the allele is commoner in Han Chinese, Thai and Korean people, and the SPC advises considering genotyping before starting in these groups), aromatic antiepileptics (carbamazepine, phenytoin, lamotrigine — especially lamotrigine without slow titration), sulfonamide antibiotics, NSAIDs (particularly meloxicam and piroxicam), and nevirapine. Any patient on a new high-risk drug who develops mucosal erosions with a skin rash, skin pain or systemic illness: stop the suspected non-essential drug and arrange emergency hospital assessment — do not wait for Nikolsky testing.

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. Healing may take several weeks after withdrawal — but never stop nicorandil without considering angina control and discussing an alternative with the prescriber/cardiology, and persistent ulcers still require specialist assessment and may need biopsy. 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 may 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) may reduce RAS frequency in some patients. This is a simple, low-risk modification that GPs can recommend at the consultation. 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.

Haematinic deficiencies can cause or worsen recurrent aphthous ulcers, so test selectively when ulcers are adult-onset, severe, atypical or associated with systemic features, pallor, fatigue, neuropathy or dietary risk. 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. Confirmed iron deficiency needs investigation of its cause (particularly in men and postmenopausal women) as well as replacement; ulcer improvement depends on the cause. The coeliac-RAS connection is well-established in the literature — recurrent oral ulcers may be the only presenting symptom of coeliac disease in the absence of GI symptoms. Where clinically indicated, test with TTG IgA + total IgA while the patient is eating gluten, and do not start a gluten-free diet before diagnostic testing is complete. 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) carries a higher malignant potential than 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 dental/oral assessment (within 2 weeks) even if an ulcer is not present (NICE NG12); the dentist may refer through the suspected-cancer pathway if clinically suspicious. Tonsillar asymmetry alone in an adult is not automatically cancer, but persistent unexplained asymmetry needs assessment through an appropriate ENT pathway to exclude tonsillar lymphoma (rapidly growing, non-tender, firm) or tonsillar SCC (particularly HPV-positive oropharyngeal cancer, which is rising in the UK and often affects non-smokers). Unexplained tonsillar asymmetry in an adult is not itself an NG12 criterion, but warrants urgent ENT assessment on clinical judgement.

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. NICE NG12's criterion is unexplained oral ulceration lasting more than 3 weeks. Below 3 weeks: remove an obvious traumatic cause, document the lesion and arrange review before or at 3 weeks — refer promptly if it is indurated, enlarging, atypical, associated with lymphadenopathy or otherwise suspicious. If an unexplained lesion has already persisted beyond 3 weeks, suspected-cancer referral should not be delayed by further topical treatment trials.

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. Hydrocortisone 2.5 mg mucoadhesive buccal tablets (check current UK availability and product information) — 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) . Patients should be instructed to start treatment at the prodromal stage rather than waiting for the ulcer to appear. Systemic prednisolone, colchicine, dapsone, thalidomide and high-potency topical steroids are specialist oral-medicine/dermatology treatments, not a routine primary-care ladder. Thalidomide requires highly controlled specialist prescribing and pregnancy-prevention measures. Refer patients with truly refractory severe RAS for specialist assessment.

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. Primary HSV gingivostomatitis is usually self-limiting; antiviral treatment is most useful when started early and in severe disease, immunocompromise or inability to maintain oral intake. 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 dehydrated quickly. Any child unable to maintain adequate oral intake because of oral pain needs same-day 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 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 suspected cancer pathway referral outcomes is a clinical governance requirement that is frequently neglected — when a GP makes a suspected cancer pathway 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 suspected cancer referral threshold. In a medicolegal context, being able to demonstrate that a suspected cancer pathway 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 suspected cancer referrals to oral medicine prove to be benign vs malignant helps them understand whether they are pitching their threshold appropriately. Ophthalmology-directed uveitis surveillance in Behçet's 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. Same-day ophthalmology is required for painful red eye, photophobia or visual disturbance. 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.