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 — a large proportion 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 a common cause 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. A glass test is not sufficiently reliable to exclude meningococcal disease — a seriously ill patient with fever, meningococcal features or a rapidly evolving rash needs immediate emergency treatment even if the rash blanches or is absent. In the context of fever + rash + ill patient, a non-blanching result should trigger 999, with IV/IM antibiotic as soon as possible unless this would delay transfer (NICE NG240).

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 should have syphilis serology through the local sexual-health pathway, 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 are the feared complication, and prompt specialist treatment reduces the risk — making prompt diagnosis genuinely protective. Consider MIS-C and other serious differentials according to the clinical context. Do not delay same-day paediatric referral while waiting for blood tests or echocardiography; echocardiographic monitoring is paediatric-specialist led.

The Jarisch-Herxheimer reaction after penicillin treatment for syphilis is important to explain to patients before giving the first dose — it is common in secondary syphilis patients treated with penicillin, typically within hours of 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 — many people in the UK are labelled as 'penicillin allergic,' but most labelled patients do not 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 (with higher C. difficile risk from broad-spectrum alternatives), higher cost, and reduced treatment options. NHS penicillin allergy delabelling programmes have been developed — drug challenge should only be undertaken within an approved specialist protocol with appropriate resuscitation facilities, not ad hoc in primary care; refer for specialist drug-allergy assessment when confirmation would materially affect future treatment.

The measles notification responsibility is a legal requirement under the Health Protection (Notification) Regulations 2010 — measles is a notifiable disease 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, 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 UKHSA 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.