Granuloma inguinale

Granuloma inguinale, also known as donovanosis, is a sexually transmitted infection caused by Klebsiella granulomatis.

Granuloma inguinale is one of several causes of genital ulcers. It is a sexually transmitted infection (STI), which is caused by the bacterium Klebsiella granulomatis. The condition is most commonly found in tropical regions.

Granuloma inguinale can be treated with antibiotics, but without treatment, it causes a chronic and progressive infection. Complications include lymphoedema, which may be severe enough to cause elephantiasis (gross enlargement of a body limb due to lymph obstruction) and there is an increased risk of malignancy (squamous cell carcinoma).

Genital ulcers

The major causes of genital ulcers include:

• Syphilis: characterised by a single painless ulcer (chancre)
• Herpes simplex virus (HSV): multiple painful vesicles that ulcerate
• Granuloma inguinale: one or more nodules that eventually ulcerate. Usually painless
• Lymphogranuloma venereum (LGV): one or more painless papules that develop into shallow ulcers
• Chancroid: multiple deep painful ulcers with a purulent base.

Granuloma inguinale is most commonly seen in tropical regions of the world.

Granuloma inguinale is uncommon in the UK and usually acquired when travelling abroad in tropical and subtropical regions. The highest incidence is in Papua New Guinea. 

It typically presents in patients 20-40 years old who have acquired the infection through sexual contact.

Granuloma inguinale is caused the bacterium Klebsiella granulomatis.

Granuloma inguinale is an STI, which is transmitted through sexual contact with an infected individual. Generally, there needs to be repeated contact for transmission due to the low pathogenicity of the bacterium. Untreated, it is a chronic and progressive infection.

The incubation period (time between infection to presentation) is highly variable and can be up to one year.

The condition is also known as donovanosis due to the traditional histopathological findings. Macrophages from tissue smear samples contain intracellular inclusions that are known as Donovan bodies. They are essentially gram-negative intracytoplasmic cysts containing the causative organism, K. granulomatis, an intracellular pathogen. Rupture of these cystic structures leads to the release of the bacteria. Untreated, the infection can cause local invasion, chronic tissue damage, and scarring.

Granuloma inguinale is characterised by one or more nodules that transform into painless ulcers.

Papule & nodule

Patients usually develop a painless papule(s) or nodule(s) that has a ‘beefy red’ appearance due to the high vascularity. Lesions typically occur on the genital region (~90%) or inguinal region (~10%). In men the most common sites are the foreskin (prepuce), coronal sulcus, frenulum, and glans penis. In women they occur on the labia minora, fourchette (thin fold of skin at back of vulva), and cervix. 

Ulcer

The papule(s) or nodule(s) develop an ulcerated appearance. They typically ulcerate from the middle and have friable, raised and rolled margin. There may be adjacent lesions from autoinoculation of surrounding skin. 

Lesion types

Based on the appearance there are different types of lesion:

• Classic (ulcerovegetative): ulcerogranulomatous lesions (beefy red nodule(s) that ulcerate and bleed(s) easily). In the absence of ulceration, may be considered a nodular type. 
• Hypertrophic (verrucous): dry texture with irregular raised edges.
• Necrotic: deep ulcer with offensive smell. Can cause tissue destruction.
• Sclerotic (cicatricial): causes a fibrotic reaction with chronic scarring. Can cause lymphoedema. 

Lymphadenopathy

Lymphadenopathy is less common compared to other genital ulcer conditions.

In conditions such as LGV and chancroid, patients can develop painful unilateral lymphadenopathy that become matted together or suppurative (i.e. develop exudate/PUS). These are known as ‘buboe’. The nodular lesions in granuloma inguinale can appear similar on clinical examination. They are referred to as ‘pseudo-buboe’.

Other findings

• Lymphoedema
• Extra-genital sites (autoinoculation, direct extension or rarely haematogenous spread)

Diagnosis can be made on clinical examination by experienced clinicians in endemic regions.

In endemic regions, the diagnosis of granuloma inguinale may be made on clinical examination alone based on the classic appearance. However, in the UK and other countries where the condition is uncommon, it takes a high degree of suspicion based on travel history and tissue smear.

It is difficult to culture K. granumolatis in the laboratory. Therefore, diagnosis is made by identification of Donovan bodies from a tissue swab taken from the base of an ulcerated lesion. Polymerase chain reaction (PCR) of a tissue sample is possible but not widely available. 

Other investigations

Patients with suspected granuloma inguinale require referral and assessment at a genitourinary medicine (GUM) clinic. This enables a full sexual health screen including testing for other STIs such as chlamydia, gonorrhoea, syphilis and HIV. 

The treatment of granuloma inguinale is a minimum three week course of azithromycin.

Patients with granuloma inguinale should be treated with a three week course of azithromycin. Patients may need a longer course as treatment should be continued until all lesions are healed.

Standard regimen

• Azithromycin 1 gram weekly, or 500 mg daily for three weeks.

Gentamicin can be added in patients slow to respond. Relapse can occur up to 18 months following treatment.

Alternative regimen

• Doxycycline 100 mg twice daily for three weeks
• Ciprofloxacin 750 mg twice daily for three weeks
• Erythromycin 500 mg four times a day for three weeks

Sexual health advice

Contact tracing of previous sexual partners is usually required for partners within the last 60 days. Sexual contacts need to be notified, screened and treated as necessary. Sexual contact should be avoided whilst there is active infection but this should always be discussed with a specialist in sexual health medicine.

Granuloma inguinale can cause chronic scarring with lymphoedema.

• Lymphoedema
• Malignant change (squamous cell carcinoma)
• Haematogenous spread
• Polyarthritis
• Osteomyelitis
• Stenosis (e.g. anus, vagina)
• Mental health (e.g. anxiety/depression)