Donovanosis

Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. The patient presents with painless nodular lesions that ulcerate, commonly with a “beefy-red” base. There is no associated inguinal lymphadenopathy. Diagnosis is via history, clinical findings, and tissue smear or biopsy showing Donovan bodies, which are intracellular inclusion bodies inside macrophages. Treatment is with a prolonged course of antibiotics until lesions are healed, with monitoring for recurrence.

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Overview

Definition

Donovanosis, or granuloma inguinale, is an STD characterized by chronic progressive ulcers affecting the genital region.

Epidemiology

  • Rare in the United States
  • Generally, incidence is declining worldwide, partly due to the focus on HIV prevention and the role genital ulcers play in the disease’s transmission.
  • Most occurrences are in the following areas:
    • Papua New Guinea
    • Southern Africa
    • French Guyana
    • India
    • Caribbean and Brazil
    • Aboriginal communities in Australia

Etiology

  • Caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis):
    • Gram-negative bacterium
    • Encapsulated
    • Facultative aerobe
    • Intracellular
  • Risk factors include:
    • Poor genital hygiene (uncircumcised men)
    • Unprotected sexual intercourse (especially between men)
    • Low socioeconomic status

Pathophysiology

  • After inoculation → painless papule or nodule → due to high vascularity, a classic “beefy-red” lesion develops
  • Minimal trauma leads to ulcerative formation, without lymphadenopathy.
  • Eventually, the lesion progressively grows outward, with borders developing a “snake-like” appearance.

Clinical Presentation

Signs and symptoms

  • Incubation period: average of 50 days (and up to a year) postinoculation 
  • Transmission: sexually transmitted
  • Site of lesion:
    • Majority are in the genital region.
    • Most common in men: prepuce, coronal sulcus, glans, and anus 
    • Most common in women: labia minora, cervix, and upper genital tract
    • 6% of patients may have extragenital lesions (lips, palate, pharynx, larynx).
  • Lesion:
    • Classic ulcerogranulomatous lesions:
      • Also known as ulcerative donovanosis
      • Most common presentation
      • Painless, expanding ulcer that bleeds easily
      • Described as a beefy-red lesion
    • Hypertrophic or verrucous ulcer:
      • Irregular edge
      • Dry texture
    • Necrotic, offensive-smelling ulcer: associated with tissue destruction
    • Sclerotic or cicatricial lesion: scar tissue
  • No regional lymphadenopathy

Complications

  • Healing of donovanosis ulcers can leave scars or hypertrophic lesions.
  • Neoplastic change: Squamous cell carcinoma may occur in long-standing untreated lesions.
  • Pseudo-elephantiasis
  • Polyarthritis or osteomyelitis
  • Stenosis of the urethra, vaginal, or anus

Diagnosis and Management

Diagnosis

  • Causative agent is difficult to culture.
  • High index of suspicion needed, especially in endemic areas
  • Diagnosis is made by a microscopic examination of a tissue smear (from the ulcer), tissue crush preparation, or biopsy:
    • Donovan bodies: bipolar-staining cytoplasmic inclusion bodies within macrophages, which may have a safety-pin appearance
    • Other histologic changes: 
      • Inflammation with plasma cell and neutrophil infiltration
      • Ulceration, microabscesses, and elongation of rete ridges in the epithelium
Tissue sample of Donovanosis patient

Tissue sample from an ulcer: a WBC that contained the pathognomonic finding of Donovan bodies, which were encapsulated, gram-negative rods, representing the responsible bacterium Klebsiella granulomatis

Image: “18899” by CDC/Susan Lindsley. License: Public Domain

Management

  • Management is a prolonged course of antibiotics until re-epithelization of ulcer has occurred (minimum 3 weeks).
  • Choice of antibiotics:
    • 1st line: azithromycin 
    • Alternatives:
      • Doxycycline
      • Ciprofloxacin
      • Erythromycin (if patient is pregnant)
      • Trimethoprim-sulfamethoxazole
  • There is a high chance of recurrence at 6–18 months, which requires initiating antibiotics again.
  • Surgical management is reserved for extensive tissue damage.
  • Patient education on safe sex is important to reduce incidence.
  • Patients should be screened for other STDs.

Differential Diagnosis

  • Chancroid: an STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (chancroid or “soft chancre”), which can be accompanied by painful inguinal lymphadenopathy. Patients may develop the complication of suppurative lymph nodes. Diagnosis is clinical and with tests ruling out syphilis and herpes. Azithromycin or ceftriaxone is the treatment of choice. Patients and their contacts must both be treated.
  • Herpes simplex: common STD caused by herpes simplex virus type 1 or 2. Prodromal symptoms often precede clusters of painful, fluid-filled vesicles on an erythematous base. These vesicles eventually form ulcers that can coalesce. Lymphadenopathy, dysuria, and severe neuralgia can occur. The diagnosis is generally clinical but confirmed with PCR and serologic testing. Management includes antiviral therapy.
  • Syphilis: an STD caused by Treponema pallidum. The disease has 4 clinical stages: Primary syphilis begins with a solitary, painless ulcer on the genitals (chancre). Progression to secondary syphilis manifests as a generalized maculopapular rash, which includes the palms and soles. The development of tertiary syphilis can cause severe neurologic (neurosyphilis), cardiovascular, and/or gummatous disease. The dormant period between secondary and tertiary syphilis is the latent stage.
  • Lymphogranuloma venereum (LGV): an STD caused by 3 strains of Chlamydia trachomatis. Patients may have a small, self-limited genital ulcer followed by painful inguinal and/or femoral lymphadenopathy. Diagnosis is clinical; although PCR testing can help, availability is limited. Management involves tetracyclines or erythromycin.

References

  1. O’Farrell N. (2018). Donovanosis. Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. (Eds.). Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill. 
  2. Santiago-Wickey JN, Crosby B. (2020) Granuloma Inguinale. StatPearls. StatPearls Publishing, Treasure Island, FL. https://www.ncbi.nlm.nih.gov/books/NBK513306/

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