Primary syphilis is the most important single STI diagnosis not to miss in primary care — the incidence of syphilis in England has increased by over 700% since 2010, with approximately 8,000 diagnoses per year (2023 UKHSA data), making it one of the fastest-rising STIs. The primary chancre is pathognomonic but frequently missed because: (1) it is painless (unlike HSV which is intensely painful), so patients may not notice it; (2) it can occur on the cervix, vagina, or rectum where it is not visible; (3) it resolves spontaneously in 3-6 weeks even without treatment, leaving the patient in the latent phase; and (4) it can be confused with other genital ulcers. The GP assessment standard: any painless, hard-based, well-defined genital ulcer in a sexually active adult, in any anatomical location, is syphilis until syphilis serology proves otherwise. The test of choice is a combined TPHA (Treponema pallidum haemagglutination assay) + RPR (rapid plasma reagin) — both should be requested. Treatment via GUM clinic: partner notification is mandatory.

The Lipschutz ulcer (ulcus vulvae acutum) is an important diagnosis that prevents unnecessary STI investigation and patient distress in adolescent girls — it presents as an acute painful vulvar ulcer in a girl or young woman who has not been sexually active, and is caused by a non-sexually transmitted systemic infection, most commonly primary EBV (infectious mononucleosis) or primary CMV infection. The clinical features: acute onset, intensely painful ulcers on the labia majora or labia minora, often multiple (2-5 ulcers), shallow with grey or necrotic base, occurring within days of a viral prodrome. Investigation: EBV monospot/Paul-Bunnell + EBV IgM; CMV serology. Management: analgesia (topical lidocaine gel + oral ibuprofen), saline bathing, aciclovir NOT required (these are not herpetic ulcers). Reassurance: these are not STIs and will resolve in 2-4 weeks. This diagnosis prevents unnecessary STI investigations, HPV testing, and the psychological trauma of an incorrect STI diagnosis in a child or adolescent.

The 4th generation HIV test (combined antigen-antibody test) is the current standard for HIV diagnosis in the UK — it detects both HIV antibodies (which develop 3-8 weeks after infection) and HIV p24 antigen (which is detectable as early as 2-3 weeks after infection, before antibodies develop). This significantly reduces the window period compared to 3rd generation antibody-only tests. The HIV window period for the 4th generation test is approximately 45 days (most people seroconvert within 23-90 days). The practical implications for anogenital ulcer patients: if the HIV test is negative but there was a high-risk exposure within the last 45 days, a repeat test at 6-8 weeks after the potential exposure is required. If there was a recent high-risk exposure within 72 hours: PEP (post-exposure prophylaxis — tenofovir/emtricitabine + raltegravir) should be offered urgently via GUM clinic or A&E.

LGV (Lymphogranuloma venereum) anorectal syndrome in MSM is one of the most clinically significant STI syndromes to recognise in primary care — the anorectal presentation (proctitis) causes rectal pain, tenesmus, bloody or mucoid anal discharge, and constipation, and is frequently misdiagnosed as inflammatory bowel disease (particularly Crohn's proctitis) because the endoscopic appearance (rectal erythema, ulceration, friability) is similar. The key clinical discriminator: LGV proctitis occurs in MSM who practise receptive anal sex and may have concurrent STIs; IBD typically occurs in a different demographic and does not have concurrent STIs. Any MSM presenting with proctitis should have rectal NAAT swab for chlamydia + LGV genotyping + other STI screens before colorectal or gastroenterological investigation. Treatment: doxycycline 100 mg BD x 21 days — azithromycin (used for standard chlamydia) is NOT adequate for LGV.

The primary care HIV test offer in any patient presenting with an STI or anogenital ulcer is a NICE and BHIVA quality standard — HIV testing should be offered at every STI consultation as a routine, not a targeted, investigation. The rationale: HIV-positive individuals who are unaware of their status are the primary drivers of new HIV transmissions; HIV testing at all STI contacts maximises case detection; modern HIV treatment (ART) is highly effective and starts immediately after diagnosis. The GP should frame the HIV test as routine: 'We routinely test for HIV as part of our sexual health check — it is a simple blood test and I recommend it for everyone being assessed for any STI.' The opt-out approach (testing unless declined) significantly increases HIV testing rates compared to the opt-in approach.

The Jarisch-Herxheimer reaction after syphilis treatment is an important patient safety counselling point — approximately 30-70% of patients with primary or secondary syphilis develop the reaction within 6-12 hours of their first benzathine penicillin injection: fever (temperature typically rising to 38-40°C), rigors, headache, myalgia, and worsening of existing lesions. It is caused by the rapid release of lipoproteins from dying Treponema pallidum spirochaetes, triggering a systemic inflammatory response. The reaction is expected, transient (resolves within 12-24 hours), and does not indicate treatment failure or allergy. Patients must be warned before treatment: 'You may feel quite unwell with fever and chills tonight — this is the infection dying off and it means the treatment is working. Take paracetamol, rest, and drink fluids. Contact us if you feel very unwell.' Failing to warn the patient often leads to unnecessary re-presentation to A&E with the self-described 'allergic reaction' to penicillin.

The doxycycline 21-day course for LGV proctitis is a critical prescribing distinction from standard chlamydia treatment — Chlamydia trachomatis serotypes D-K (non-LGV) are treated with azithromycin 1g single dose or doxycycline 100 mg BD x 7 days. LGV serovars L1-L3 require doxycycline 100 mg BD x 21 days — azithromycin is not adequate for LGV. A patient treated for 'chlamydia' with azithromycin who actually has LGV will fail treatment, with ongoing proctitis and risk of rectal stricture formation from untreated LGV proctitis. The clinical lesson: any patient with chlamydia confirmed on rectal swab who has symptoms of proctitis (rectal pain, tenesmus, rectal discharge) must have LGV serogrouping requested before selecting antibiotic treatment.

The psychological impact of genital herpes diagnosis is substantial and well-documented — studies show that over 60% of patients with newly diagnosed genital herpes experience significant anxiety, shame, and relationship distress. The prognosis, however, is significantly better than most patients initially fear: approximately 30-40% of HSV-2 positive individuals never have a recognised recurrence; most who do have recurrences find they become less frequent and less severe over time; and suppressive therapy reduces recurrence by 70-80%. The GP's communication at the time of HSV diagnosis is critical for long-term psychological outcomes — stating clearly: 'Genital herpes is a very common condition — approximately 1 in 6 adults in the UK carries the virus. It is manageable, it does not define your sexual health, and there are effective treatments to reduce outbreaks.' This evidence-based reassurance, combined with written information and referral to specialist sexual health nursing, significantly reduces anxiety and stigma.

The neonatal herpes transmission risk from a mother with genital HSV is one of the most important antenatal safety discussions in primary care — neonatal HSV has a mortality of approximately 30-50% without treatment and causes devastating neurological sequelae in survivors. The highest-risk scenario: primary genital HSV infection in the third trimester (particularly at ≥36 weeks) because: (1) the mother has not yet developed protective antibodies; (2) viral shedding is maximal; and (3) the infant will not receive passive antibody protection. Management: any primary HSV infection at ≥34 weeks of pregnancy should be discussed with obstetrics — Caesarean section is offered because the risk of neonatal transmission during vaginal delivery is approximately 30-50%. Suppressive aciclovir 400 mg TDS from 36 weeks reduces viral shedding and recurrence at delivery, reducing the need for Caesarean section in women with recurrent (non-primary) HSV. All women with a history of genital HSV should inform their midwife and obstetrician at booking.