Genital Ulcer Disease

Genital ulcer disease (GUD) is a syndromic group of sexually transmitted infections producing a break in the skin or mucosa of the genitalia, with or without regional lymphadenopathy. For NEET PG the entire topic collapses into one decision tree: painful vs painless ulcer, the smear/dark-field finding, and the syndromic drug. Master those three axes and the questions answer themselves.

Definition & Core Concept

A genital ulcer is a loss of epidermis (and often dermis) on the penis, vulva, perineum, anus or cervix. Most are infective and sexually transmitted; the five classical causes are syphilis, chancroid, lymphogranuloma venereum (LGV), donovanosis (granuloma inguinale) and genital herpes. The diagnostic game is won by combining number of ulcers, pain, edge/base, induration, and the inguinal node (bubo).

High-yield: The single most useful discriminator in the exam is pain. Painless, clean, indurated ulcer → think syphilis or donovanosis. Painful, soft, ragged, undermined ulcer → think chancroid or herpes.

The big three "tropical" bacterial GUDs (chancroid, LGV, donovanosis) are far commoner in NEET PG than in modern Western practice, so memorise their organisms and smears cold.

Aetiology — Organism Map

Disease	Organism	Gram/Type	Classic body / pattern
Syphilis (chancre)	Treponema pallidum	Spirochaete	Dark-ground motile spirochaetes
Chancroid (soft chancre)	Haemophilus ducreyi	Gram-negative coccobacillus	"School of fish" / shoal / railroad track
LGV	Chlamydia trachomatis L1–L3	Obligate intracellular	Inclusion bodies; groove sign clinically
Donovanosis (granuloma inguinale)	Klebsiella granulomatis (formerly Calymmatobacterium)	Gram-negative	Donovan bodies (safety-pin) in macrophages
Genital herpes	HSV-2 > HSV-1	DNA virus	Tzanck: multinucleate giant cells, Cowdry A

High-yield: Match the eponymous body to the disease — Donovan bodies = donovanosis, school-of-fish = chancroid, dark-ground spirochaetes = syphilis, Tzanck giant cells = herpes. This pairing is the most repeated single MCQ in the chapter.

The Master Comparison Table

Feature	Syphilis (1°)	Chancroid	LGV	Donovanosis	Herpes
Organism	T. pallidum	H. ducreyi	C. trachomatis L1–3	K. granulomatis	HSV-2
Incubation	9–90 d (avg 21)	3–7 d	3 d–6 wk	1–4 wk (up to mo)	2–7 d
Number	Usually single	Multiple	Single, transient (often missed)	Single/multiple, coalesce	Multiple grouped vesicles → ulcers
Pain	Painless	Very painful	Painless ulcer	Painless	Painful
Base	Clean, serous	Dirty, purulent, necrotic	Variable	Beefy-red, friable, bleeds easily	Erythematous
Edge	Indurated, rolled	Soft, ragged, undermined	—	Rolled, elevated	—
Induration	Hard (hard chancre)	Soft (soft chancre)	—	Firm granulation	None
Lymph node	Bilateral, rubbery, painless, non-suppurative	Unilateral, painful, suppurative, may fistulate	Groove sign, suppurative, "stellate" buboes	Pseudobubo (subcutaneous granuloma, not true node)	Tender bilateral

High-yield: Learn the bubo behaviour. Chancroid = painful suppurating bubo that ruptures via a single sinus. LGV = matted nodes above and below the inguinal ligament split by it → groove sign (sign of Greenblatt). Donovanosis = pseudobubo (it is granulation tissue, not a lymph node). Syphilis = painless, non-suppurative, bilateral.

Pathophysiology Snapshots

• Syphilis: Spirochaete penetrates intact mucosa → endarteritis obliterans and a plasma-cell-rich infiltrate → painless indurated chancre that heals spontaneously in 3–6 weeks even untreated; the organism then disseminates (secondary/latent/tertiary).
• Chancroid: H. ducreyi requires a break in epithelium; produces a cytolethal distending toxin → necrotic, undermined, painful ulcer with abundant neutrophils.
• LGV: L-serovars are uniquely lymphotropic, invading lymphatics → thrombolymphangitis, peri-lymphangitis and abscess; chronic stage causes fibrosis, strictures and elephantiasis.
• Donovanosis: Slow intracellular infection of macrophages → progressive granulomatous, beefy-red, bleed-on-touch ulceration that extends by contiguity; minimal lymph node involvement.
• Herpes: Reactivation from sacral (S2–S4) dorsal root ganglia → recurrent grouped vesicles; cytopathic effect produces multinucleated giant cells.

Clinical Features by Disease

Syphilis (primary chancre): Solitary, painless, indurated ("button-like") ulcer with a clean serous base, appearing ~3 weeks after exposure, healing spontaneously. Painless bilateral rubbery inguinal nodes. Progresses to secondary syphilis — symmetrical copper-coloured rash including palms and soles, condylomata lata, mucous patches, "moth-eaten" alopecia.

Chancroid: Onset within a week. Begins as a tender papule → pustule → painful soft ulcer with ragged undermined edges and a dirty grey-yellow base that bleeds. Often multiple from autoinoculation ("kissing ulcers"). Painful unilateral fluctuant bubo that may rupture.

LGV: Three stages. Primary — small painless evanescent papule/ulcer (often unnoticed). Secondary — painful inguinal/femoral lymphadenitis with the groove sign; constitutional symptoms. Tertiary (anogenitorectal syndrome) — proctocolitis, perirectal abscess, fistulae, rectal strictures, and genital elephantiasis (esthiomene).

Donovanosis: Painless, slowly progressive, beefy-red, friable ulcer that bleeds on contact; rolled, elevated edges. Four clinical types: ulcerogranulomatous (commonest), hypertrophic/verrucous, necrotic, and sclerotic/cicatricial. Pseudobubo, not true adenopathy.

Genital herpes: Prodrome of tingling/burning → crops of grouped vesicles on an erythematous base that erode into shallow painful ulcers; first episode is severe with fever and bilateral tender adenopathy; recurrences are milder and localised.

Diagnosis & Investigation of Choice

Stepwise approach: History & exposure → inspect ulcer (pain, number, edge, base, induration) → palpate nodes (groove sign? suppuration? pseudobubo?) → targeted test for the suspected organism → always do serology for syphilis (VDRL/RPR) and offer HIV testing in every GUD case.

Disease	Investigation of choice / key test
Syphilis	Dark-ground microscopy (motile spirochaetes) = immediate; serology: VDRL/RPR (screening, non-treponemal) confirmed by TPHA/FTA-ABS (treponemal)
Chancroid	Clinical + Gram stain ("school of fish"); culture on chocolate agar + IsoVitaleX (low sensitivity); PCR most sensitive
LGV	NAAT/PCR for C. trachomatis (genotyping for L serovars); old: Frei test (now obsolete), complement fixation titre >1:64
Donovanosis	Tissue smear/crush prep with Giemsa or Wright stain → Donovan bodies (safety-pin bipolar inclusions in macrophages); not culturable on routine media
Herpes	Tzanck smear (multinucleate giant cells) bedside; PCR / viral culture = confirmatory; type-specific serology

High-yield: VDRL is non-treponemal (used for screening + treatment monitoring, becomes negative after cure) while TPHA/FTA-ABS are treponemal (confirmatory, remain positive for life). Biological false-positive VDRL mnemonic — "VDRL": Viral (EBV, HIV, hepatitis), Drugs/pregnancy, Rheumatic fever/Rheumatoid/SLE, Leprosy/Lupus/Lymphoma. FTA-ABS is the first to become positive in early syphilis.

High-yield: Donovan bodies are seen inside macrophages (mononuclear "Donovan" cells), have a closed-safety-pin appearance with bipolar chromatin condensation, and stain best with Giemsa/Wright/Leishman. K. granulomatis does not grow on standard culture media — diagnosis is by smear/biopsy.

Management / Drug of Choice

NEET PG tests both the specific drug and the syndromic (NACO/WHO) regimen. Learn the syndromic kit because Indian programmes manage GUD without waiting for lab confirmation.

Disease	Drug of choice
Syphilis (primary/secondary)	Benzathine penicillin G 2.4 MU IM single dose (3 weekly doses if late latent); penicillin allergy → doxycycline
Chancroid	Azithromycin 1 g PO single OR ceftriaxone 250 mg IM single; alt: ciprofloxacin/erythromycin
LGV	Doxycycline 100 mg BD × 21 days (longest course); alt: erythromycin
Donovanosis	Azithromycin 1 g weekly (or 500 mg daily) for ≥3 weeks AND until lesions fully heal; alt: doxycycline, co-trimoxazole
Herpes (first episode)	Aciclovir 400 mg TDS × 7–10 d (or valaciclovir/famciclovir); episodic or suppressive therapy for recurrences

Syndromic flow (NACO Kit approach): GUD non-herpetic → Kit 1 (grey) = azithromycin 1 g + benzathine penicillin 2.4 MU (covers syphilis + chancroid). GUD herpetic → Kit 2 (green) = aciclovir. Always treat the partner, counsel, offer HIV/HBV testing, and re-examine.

High-yield: Treat the partner in every GUD. For syphilis, watch for the Jarisch–Herxheimer reaction (fever, myalgia, worsening rash within hours of penicillin due to spirochaete lysis) — it is not an allergy; manage with antipyretics, continue penicillin. In pregnancy with penicillin allergy, desensitise and give penicillin (doxycycline is contraindicated).

Complications

• Syphilis: progression to cardiovascular (aortitis/aneurysm) and neurosyphilis (tabes dorsalis, Argyll Robertson pupil, general paresis); congenital syphilis if untreated in pregnancy (Hutchinson teeth, saddle nose, saber shins).
• Chancroid: phimosis, large suppurating buboes, secondary infection; strongly increases HIV transmission (any GUD does).
• LGV: rectal strictures, fistula-in-ano, genital elephantiasis (esthiomene), frozen pelvis.
• Donovanosis: chronic scarring, lymphoedema, pseudoelephantiasis, and rarely squamous cell carcinoma within long-standing lesions.
• Herpes: neonatal herpes (high mortality), aseptic meningitis, urinary retention (sacral radiculopathy), severe disease in HIV.

High-yield: All genital ulcers facilitate HIV acquisition and transmission by breaching the mucosal barrier — hence HIV testing is mandatory in every GUD patient. Donovanosis is the one classically linked to long-term malignant transformation (SCC).

Key Differentials & Non-infective Mimics

• Behçet disease: recurrent painful oral + genital aphthous ulcers, uveitis, positive pathergy test.
• Fixed drug eruption: recurrent well-defined ulcer at the same site after a drug (e.g. co-trimoxazole, NSAIDs).
• Aphthosis / trauma / Crohn's disease (knife-cut perianal ulcers).
• Squamous cell carcinoma / erythroplasia of Queyrat: chronic non-healing ulcer in an older patient — biopsy.
• Scabies, traumatic erosions, and herpes zoster can mimic early lesions.

Distinguishing painful clusters: Herpes gives grouped vesicles preceding ulcers and recurs; chancroid gives a solitary or few deep purulent painful ulcers with a suppurating node. Behçet has the oral-ocular triad and pathergy.

Special Situations & Pearls

• GUD in pregnancy: Syphilis must be treated with penicillin (desensitise if allergic) — untreated maternal syphilis causes abortion, stillbirth and congenital syphilis. Doxycycline (LGV, donovanosis) is contraindicated; use erythromycin/azithromycin. Aciclovir is safe and reduces neonatal herpes; deliver by caesarean if active genital herpes lesions are present at term.
• GUD with HIV: Ulcers are larger, multiple, atypical and slower to heal; herpes may be chronic and ulcerative; syphilis serology may behave atypically (delayed or very high titres, prozone phenomenon). Lower the threshold for biopsy and longer therapy.
• Mixed infections are common — a chancroid ulcer co-infected with syphilis is the classic "mixed chancre"; always do syphilis serology even when another cause looks obvious.
• Prozone phenomenon: A false-negative VDRL from very high antibody titres (often in secondary syphilis/HIV) — repeat after serum dilution.
• Recurrence pattern distinguishes herpes (recurrent) from the bacterial ulcers (single episode unless re-exposed).

Mnemonics & Eponyms

• Painful ulcers = "Herpes and chancroid Hurt" (H & C). Painless = syphilis, LGV, donovanosis.
• School of fish → chancroid; Donovan → donovanosis; Tzanck → herpes; Dark-ground → syphilis. (organism-test pairing).
• Groove sign = Sign of Greenblatt = LGV.
• Pseudobubo = donovanosis (it is NOT a node).
• Esthiomene (vulval elephantiasis) and anogenitorectal syndrome = late LGV.
• Frei test (obsolete intradermal test) = LGV; Ito–Reenstierna is its counterpart history.

Recently asked / exam angle

• "Painful genital ulcer with a suppurative inguinal bubo, smear shows school of fish — diagnosis/organism?" → Chancroid / H. ducreyi.
• "Groove sign is seen in?" → LGV.
• "Donovan bodies are diagnostic of?" → Donovanosis (Klebsiella granulomatis); stained best by Giemsa.
• "Drug of choice for LGV / duration?" → Doxycycline 100 mg BD × 21 days.
• "Pseudobubo is a feature of?" → Donovanosis.
• "Investigation of choice for primary syphilis ulcer?" → Dark-ground microscopy; first serological test to turn positive → FTA-ABS.
• "NACO syndromic Kit for non-herpetic GUD?" → Kit 1 = benzathine penicillin + azithromycin.
• "Beefy-red ulcer that bleeds on touch, painless?" → Donovanosis.
• Image-based: Tzanck smear giant cells → herpes; multinucleate cells, intranuclear Cowdry A inclusions.
• Match-the-following columns pairing organism ↔ disease ↔ smear are perennial.

Rapid revision

1. Painless + indurated single clean ulcer = primary syphilis (hard chancre, T. pallidum).
2. Painful + soft + ragged undermined dirty ulcer, multiple = chancroid (H. ducreyi, school of fish).
3. Groove sign + transient painless ulcer + matted buboes = LGV (C. trachomatis L1–L3); Rx doxycycline 21 days.
4. Beefy-red painless ulcer that bleeds + pseudobubo + Donovan bodies = donovanosis (K. granulomatis).
5. Grouped painful vesicles → shallow ulcers, recurrent + Tzanck giant cells = genital herpes (HSV-2).
6. Dark-ground microscopy = bedside test for syphilis; VDRL/RPR screen, TPHA/FTA-ABS confirm.
7. Benzathine penicillin 2.4 MU IM single dose = DOC for early syphilis; desensitise in pregnancy if allergic.
8. Azithromycin 1 g single dose treats chancroid; weekly azithromycin (≥3 wk + until healed) treats donovanosis.
9. Jarisch–Herxheimer reaction follows penicillin in syphilis — fever/myalgia, not allergy.
10. All GUDs increase HIV transmission — test every patient for HIV; treat the partner.
11. Donovanosis can undergo malignant change to squamous cell carcinoma; not culturable on routine media.
12. Behçet, fixed drug eruption, Crohn's, SCC are the key non-STI ulcer mimics — biopsy chronic non-healing ulcers.