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DR10.3 | Non-Syphilitic Genital Ulcer Differential Diagnosis — SDL Guide

Learning Objectives

• Describe the clinical features of chancroid and herpes genitalis and distinguish them from syphilis.
• Use the painful-versus-painless framework to triage genital ulcer disease.
• Explain the etiopathogenesis of the principal non-syphilitic genital ulcers.
• Select and interpret the appropriate diagnostic test (Gram stain, Tzanck smear, PCR) for each cause.
• Outline the principles of treatment, including the NACO syndromic kits for genital ulcer disease.

INSTRUCTIONS

Not every genital ulcer is syphilis. Chancroid and herpes genitalis are common, and they differ from syphilis in a feature you can assess in seconds — pain. This module teaches you to use the painful-versus-painless framework to triage a genital ulcer, to recognise the principal non-syphilitic causes, and to confirm them with the right bedside test, so that you treat correctly even before serology returns.

References

• Neena Khanna, Illustrated Synopsis of Dermatology and Sexually Transmitted Diseases, Ch. on Genital Ulcer Disease (textbook)
• IADVL Textbook of Dermatology, Ch. on Chancroid, Herpes Genitalis, and Genital Ulcer Disease (textbook)
• NACO National Guidelines on Prevention, Management and Control of RTI/STI, Ministry of Health & Family Welfare, Government of India (textbook)

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Version 2.0 | NMC CBME 2024

The Genital Ulcer — A Clinical Framework for Rapid Triage

Rapid Clinical Triage of Genital Ulcers

The most useful first move with any genital ulcer is to apply a simple clinical framework built around a single, high-yield question: is the ulcer painful or painless? This one feature carries enormous discriminating power. The painful ulcers are chancroid (a painful, soft, ragged ulcer) and herpes genitalis (painful grouped vesicles that rupture into shallow ulcers). The painless ulcers are the primary chancre of syphilis (painless and indurated), and — at least early — lymphogranuloma venereum (a transient, often-unnoticed ulcer) and donovanosis (a painless, beefy-red, friable ulcer). Layered onto pain are a few other rapidly assessable features: the morphology of the ulcer (indurated and clean-based in syphilis; soft and ragged with a dirty base in chancroid; grouped vesicles in herpes; beefy-red and friable in donovanosis), the lymph nodes (non-tender and bilateral in syphilis; tender and suppurative in chancroid; tender in primary herpes; the matted "groove sign" of LGV; pseudobuboes in donovanosis), and systemic symptoms (prominent in primary herpes, usually absent in the others).

Used together, these features let you reach a working diagnosis at the bedside and decide which confirmatory test to send and which empirical treatment to start. The framework does not replace testing, but it organises the differential so that testing is targeted rather than scattershot — and so that, where testing is unavailable, syndromic treatment can begin immediately.

• Ask first: painful or painless? Painful → chancroid, herpes; painless → syphilis, LGV (early), donovanosis.
• Layer on morphology, lymph node character, and systemic symptoms.
• The framework targets testing and enables immediate syndromic treatment.

Pathogens and Pathogenesis of Non-Syphilitic Genital Ulcers

Pathogenesis of Non-Syphilitic Genital Ulcers

Each non-syphilitic ulcer's clinical behaviour follows directly from its causative organism and how that organism damages tissue. Chancroid is caused by Haemophilus ducreyi, a Gram-negative coccobacillus that produces a cytotoxin; the cytotoxin-mediated tissue necrosis explains the painful, soft, ragged ulcer with its dirty, undermined base, and the organism's tendency to spread to regional nodes explains the tender, suppurative inguinal bubo. Herpes genitalis is caused chiefly by herpes simplex virus type 2 (with HSV-1 increasingly implicated); the virus replicates lytically in genital epithelium to produce the grouped vesicles and painful ulcers, then travels up sensory nerves to establish latency in the dorsal root ganglia — and it is reactivation from this latent reservoir, triggered by fever, stress, or immunosuppression, that causes the characteristic recurrences. Lymphogranuloma venereum (LGV) is caused by the L1–L3 serovars of Chlamydia trachomatis, which are uniquely lymphotropic; this lymphatic tropism is why LGV's hallmark is not the (transient) ulcer but the dramatic inguinal lymphadenitis and later fibrosis. Donovanosis (granuloma inguinale) is caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis), an intracellular organism that provokes a chronic granulomatous response, producing the slowly progressive, beefy-red, friable, painless ulcer.

Understanding these mechanisms is not academic: the cytotoxin explains why chancroid hurts, dorsal-root-ganglion latency explains why herpes recurs, lymphotropism explains LGV's nodal disease, and the intracellular Donovan bodies that the granulomatous response harbours are exactly what you will look for on the diagnostic smear.

• Chancroid = H. ducreyi (cytotoxin → painful ragged ulcer + suppurative bubo).
• Herpes = HSV-2 (lytic epithelial replication + dorsal-root-ganglion latency → recurrence).
• LGV = C. trachomatis L1–L3 (lymphotropic → nodal disease); donovanosis = K. granulomatis (granulomatous → beefy-red friable ulcer).

Clinical Features of Chancroid and Herpes Genitalis

Clinical Differentiation of Chancroid and Herpes Genitalis

The two principal non-syphilitic ulcers have distinct clinical signatures that, with the painful-versus-painless framework, allow confident bedside differentiation. Chancroid (incubation roughly 3–10 days) presents as one or more painful ulcers that are characteristically soft (non-indurated, in deliberate contrast to the firm syphilitic chancre), with ragged, undermined edges and a dirty grey, often purulent base; about half of patients develop a tender, fluctuant, usually unilateral inguinal bubo that may rupture. Herpes genitalis presents as grouped vesicles on an erythematous base that quickly rupture to leave clusters of shallow, painful ulcers. The first (primary) episode is the most severe, often with bilateral tender inguinal lymphadenopathy and systemic symptoms (fever, malaise, myalgia); subsequent recurrences are milder, more localised, and frequently heralded by a tingling prodrome, reflecting reactivation from latency. The recurrent, grouped, vesicular nature is the giveaway.

The supporting differentials round out the picture. LGV classically gives a small, painless, transient ulcer that is often missed, followed by tender, matted inguinal lymphadenopathy with the "groove sign" (nodes above and below the inguinal ligament), and, if untreated, chronic fibrosis and genital elephantiasis. Donovanosis gives a slowly enlarging, painless, beefy-red, friable ulcer that bleeds easily on contact, characteristically without true lymphadenopathy (subcutaneous granulomas called pseudobuboes may mimic nodes).

Genital Ulcer Disease: Key Clinical Differences

• Chancroid: painful, soft, ragged, undermined ulcer + tender suppurative unilateral bubo.
• Herpes: painful grouped vesicles → shallow ulcers; primary episode systemic; recurrences with prodrome.
• LGV: transient painless ulcer + groove-sign lymphadenopathy; donovanosis: painless beefy-red friable ulcer, no true nodes.