The Nikolsky sign is a critical bedside test for distinguishing SJS/TEN from other blistering disorders — lateral pressure applied to normal-appearing skin adjacent to a blistered area causes skin detachment (positive Nikolsky sign) in SJS/TEN (and pemphigus vulgaris), but not in bullous pemphigoid or erythema multiforme. Any patient with a new widespread rash and blistering should have the Nikolsky sign tested: gently press and slide a finger on apparently normal skin — if the epidermis slides off or wrinkles, this indicates epidermal-dermal separation (positive = SJS/TEN or pemphigus). The causative drug principle in SJS/TEN: the 'suspect window' is 1–8 weeks before the rash onset for most drugs. Allopurinol is now the most common cause of SJS/TEN in the UK. The HLA-B*5801 allele (common in South/East Asian patients) dramatically increases allopurinol SJS/TEN risk — pharmacogenomic screening before allopurinol in high-risk patients is recommended by some guidelines but not yet universally implemented in the UK.

The amoxicillin-EBV rash interaction is one of the most frequently misunderstood phenomena in primary care — approximately 80–90% of patients with infectious mononucleosis (EBV) who are given amoxicillin or ampicillin develop a widespread maculopapular rash. This is NOT a penicillin allergy — it is a drug-virus interaction where EBV-infected B-cells produce a specific immune response that makes ampicillin/amoxicillin immunogenic. Patients who develop this rash can safely receive other beta-lactams in the future and should NOT have penicillin allergy recorded in their medical notes. The clinical importance: (1) if a patient with EBV-confirmed mononucleosis develops a rash after amoxicillin, do NOT label them as penicillin-allergic — perform allergy testing before labelling if uncertain; (2) the best way to avoid this rash is to not prescribe amoxicillin/ampicillin for pharyngitis without excluding EBV (monospot test or EBV serology) — prescribing amoxicillin for what appears to be bacterial pharyngitis but is actually EBV is the cause of approximately 50% of amoxicillin rash presentations in primary care.

The glass (tumbler) test for non-blanching rash is one of the most important clinical skills in primary care — meningococcal disease begins as a blanching maculopapular rash and evolves to non-blanching purpura as the disease progresses (from sepsis + DIC). Early treatment (before purpura develops) dramatically improves outcome. GPs must check for non-blanching at every febrile rash assessment: press a clear glass firmly against the rash — if the rash disappears (blanches) under pressure, it is caused by vasodilation and is not purpura. If the rash persists under glass pressure (does not blanch), it represents haemorrhage into the skin and is a purpuric or petechial rash — in a febrile patient, this is meningococcal disease until proved otherwise. The sensitivity of the glass test in the field: approximately 95% for meningococcal rash detection in febrile patients. The specificity is lower (other conditions cause non-blanching rash), but in the context of fever + rash + ill child, a non-blanching result should trigger immediate benzylpenicillin and 999.

Secondary syphilis is the classic 'great imitator' — it can mimic virtually any skin condition and is frequently missed in primary care. The clinical clue is the combination of: (1) involvement of the palms and soles (extremely few rashes involve palms and soles — secondary syphilis, hand-foot-mouth disease, and palmoplantar psoriasis are the main differentials); (2) generalised lymphadenopathy; (3) a history of potential sexual exposure (genital ulcer in the past few months — primary syphilis chancre, which may have healed unnoticed); (4) condylomata lata (flat moist wart-like lesions at mucosal junctions — perianal and vulval); (5) oral mucosal patches ('snail-track' ulcers). Secondary syphilis is contagious — the skin lesions teem with Treponema pallidum and direct contact can transmit infection. Any patient with a palms-and-soles maculopapular rash must have syphilis serology (TPHA + RPR) performed, regardless of whether syphilis seems likely.

Kawasaki disease diagnostic criteria require the presence of fever for ≥5 days PLUS at least 4 of: (1) bilateral non-purulent conjunctivitis; (2) changes in lips/oral mucosa (strawberry tongue, lip erythema/cracking); (3) changes in peripheral extremities (erythema/oedema of hands/feet acutely, periungual desquamation in convalescent phase); (4) polymorphous rash (erythematous, maculopapular, targetoid — not vesicular); (5) cervical lymphadenopathy (typically unilateral, >1.5 cm). Incomplete Kawasaki disease (fewer than 4 criteria) is increasingly recognised, particularly in infants — any child under 1 year with fever >5 days and even 2–3 features should be assessed for Kawasaki disease. Coronary artery aneurysms (the feared complication) develop in 25% of untreated children vs 3–5% with IVIG treatment — making prompt diagnosis genuinely protective. Echocardiography (coronary artery Z-scores) at diagnosis, 2 weeks, and 6 weeks is standard in all confirmed cases.

The Jarisch-Herxheimer reaction after penicillin treatment for syphilis is important to explain to patients before giving the first dose — it occurs in approximately 70–90% of secondary syphilis patients treated with penicillin, typically 2–8 hours after the first injection. It consists of: fever, rigors, myalgia, headache, and transient worsening of the skin rash. It is caused by the sudden release of bacterial antigens from dying treponemes, triggering an immune reaction. It is NOT an allergic reaction to penicillin and does NOT mean the patient is penicillin-allergic. Patients should be warned explicitly: 'In the next 12 hours after the injection, you may develop fever, chills, and muscle aches, and your rash may temporarily look worse. This is a sign the treatment is working — it means the antibiotic is killing the bacteria. It will pass within 24 hours. Take paracetamol if uncomfortable.' Mistaking the Jarisch-Herxheimer reaction for penicillin allergy and switching to an inferior antibiotic is a recognised error in syphilis management.

The penicillin allergy over-labelling problem is one of the most significant antibiotic stewardship issues in UK primary care — approximately 5–10% of the UK population is labelled as 'penicillin allergic,' but studies show that fewer than 10% of labelled patients have true IgE-mediated penicillin allergy. The most common reasons for false penicillin allergy labelling: (1) amoxicillin-EBV rash (as above); (2) maculopapular drug rash that was incorrectly attributed to penicillin (rather than the true cause — virus, another drug); (3) family history of allergy mistakenly applied to the patient; (4) vague childhood rash for which no documentation exists. The consequences of false penicillin allergy labelling: patients receive inferior second-line antibiotics for serious infections (C. difficile risk is 2–3× higher with broad-spectrum alternatives), higher cost, and reduced treatment options. NICE and NHS England have developed penicillin allergy delabelling programmes — GPs can now perform low-risk oral amoxicillin challenge (after a negative penicillin skin test or on the basis of low-risk history alone) to formally delabel patients with non-anaphylactic penicillin allergy histories.

The measles notification responsibility is a legal requirement under the Health Protection (Notification) Regulations 2010 — measles is one of the 31 notifiable diseases in England (similar lists in Scotland, Wales, Northern Ireland). GPs must notify the local Health Protection Team by telephone (not just by submitting the lab form) when they suspect measles — clinical notification is required, and laboratory confirmation is a separate process. The reason telephone notification is required (not waiting for the lab): measles is highly contagious (R0 approximately 15–18 — each case can infect 15–18 unvaccinated contacts), and rapid contact tracing and post-exposure prophylaxis (MMR within 72 hours or HNIG — human normal immunoglobulin — within 6 days for immunocompromised contacts) can prevent secondary cases. A single missed notification in a community with low vaccine coverage can allow a cluster to become an outbreak. The PHE HPT telephone number for the local area is available on the gov.uk HPT directory.

The SJS/TEN drug documentation principle is one of the most important medico-legal and safety actions after a patient survives Stevens-Johnson syndrome or TEN — the causative drug must be: (1) documented as a severe allergy in the patient's medical record immediately; (2) communicated to the patient in writing with a clear 'never take this drug or related drugs again' instruction; (3) entered as an allergy in all NHS electronic records (GP system, Summary Care Record, hospital records); and (4) the patient should be advised to carry a medical alert card or wear a MedicAlert bracelet. Re-exposure to the causative drug after SJS/TEN can cause the condition to recur with potentially fatal consequences. The cross-reactivity patterns are important: sulfonamide allergy → avoid all sulfonamide-containing drugs (dapsone, co-trimoxazole, furosemide has sulfonamide structure but clinical cross-reactivity is rare). Carbamazepine → may cross-react with other aromatic antiepileptics (phenytoin, phenobarbital, lamotrigine — but cross-reactivity is unpredictable). Always document the specific drug, not just the class, when recording SJS/TEN allergy.