Donovanosis overview

# Overview
Donovanosis, a genital ulcer disease,  is a sexually transmitted disease caused by the fastidious Gram-negative bacterium Klebsiella granulomatis. Aragao & Vianna classified the agent as Calymmatobacterium granulomatis in 1913. However, sequencing analysis by Carter et al. revealed that the agent should be reclassified to Klebsiella granulomatis. Donovanosis is rare in developed countries but is endemic in tropical and developing areas, including India, Papua New Guinea, the Caribbean, central Australia, and southern Africa. Donovanosis must be differentiated from other diseases that cause genital ulcers without lymphadenopathy including: primary or secondary syphilis, chancroid, herpes simplex, amoebiasis, and squamous cell carcinoma. Sexually transmitted diseases characterized as genital ulcer diseases may present with similar manifestations and lesion characteristics. Pathogenesis of K. granulomatis is poorly characterized. The incubation period of Klebsiella granulomatis is debated and ranges from 1 to 360 days with a median time of 50 days. Donovanosis starts as a papule or subcutaneous nodule which eventually ulcerates. The ulcer progresses to create areas of granulomatous tissue. Typical lesion characteristics include: beefy red color, nontender, emitting rank odor, elevated above skin, smooth and rolled edge, serpiginous outline. Physical examination of lesions can classify donovanosis into ulcerogranulomatous, hypertrophic, necrotic, and sclerotic variants. The standard method for identifying K. granulomatis and suggesting donovanosis as the diagnosis is a smear and stain of ulcer material. Microscopy of the stain reveals Donovan bodies within monocytes that may or may not be capsulated. Antimicrobial therapy is the mainstay of treatment for donovanosis. Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed is the preferred regimen. Since there is no vaccine for donovanosis, methods of primary prevention include: abstaining from sexual activity, limiting number of sexual partners and using a male or female condom. The goal of secondary prevention is to stop the spread of disease. Therefore infected individuals should abstain from sexual intercourse until symptoms reside.

# Historical Perspective
Donovanosis was first called "serpiginous ulcer" in 1882. Charles Donovan first identified the cause of these genital lesions in 1905, which he called "Donovan bodies," since the etiologic agent was unknown. Aragao & Vianna classified the agent as Calymmatobacterium granulomatis in 1913. However, sequencing analysis by Carter et al. revealed that the agent should be reclassified to Klebsiella granulomatis.

# Pathophysiology
Klebsiella granulomatis may be transmitted through sexual contact, direct contact, or fecal contamination. K. granulomatis may also autoinoculate, resulting in multiple lesions. The pathogenesis of K. granulomatis is not well characterized. K. granulomatis replicates intracellularly within monocytes after being phagocytosed. Monocytes eventually rupture, recruiting additional monocytes and causing the formation of granulomas. On microscopic examination, pleomorphic Donovan bodies can be seen within the cytoplasm or phagosomes of monocytes.

# Causes
Klebsiella granulomatis, originally classified as Calymmatobacterium granulomatis,  is a fastidious Gram-negative pleomorphic bacteria causing donovanosis, a gential ulcer disease.

# Classification
Donovanosis may be classified by four different clinical appearances of the lesion: ulcerogranulomatous, hypertrophic or verrucous, nectrotic, or sclerotic. Ulcerogrnulomatous is the most common.

# Differential Diagnosis
Donovanosis must be differentiated from other diseases that cause genital ulcers without lymphadenopathy including: primary or secondary syphilis, chancroid, herpes simplex, amoebiasis, and squamous cell carcinoma. Sexually transmitted diseases characterized as genital ulcer diseases may present with similar manifestations and lesion characteristics.

# Epidemiology and Demographics
A true incidence of donovanosis is difficult to determine due to limited knowledge of the disease, limited diagnostic tests, infrequency of disease compared to other sexually transmitted diseases, and occurrence of the disease in areas with limited resources. Most infections occur in people who's ages range from 20 to 40 years. Sex and race are not a predilection for acquiring the disease. Donovanosis is rare in the United States and other developed countries. Donovanosis is endemic in tropical and developing areas, including India, Papua New Guinea, the Caribbean, central Australia, and southern Africa.

# Risk Factors
Risk factors for donovanosis include: multiple sex partners, unprotected sexual intercourse, travel to endemic areas, lack of circumcision in males, and poor genital hygiene.

# Natural History, Complications, and Prognosis
The incubation period of Klebsiella granulomatis is debated and ranges from 1 to 360 days with a median time of 50 days. Donovanosis starts as a papule or subcutaneous nodule which eventually ulcerates. The ulcer progresses to create areas of granulomatous tissue. Pseudoepitheliomatous hyperplasia of lesion borders often occurs. Ulcers autoinoculate creating multiple lesions. "Pseudobuboes" may also develop. Chronic ulcers leads to fibrosis and eventually Elephantiasis-like swelling. K. granulomatis may disseminate causing extragenital lesions and systemic infection. Complications include: genital damage and scarring, elephantiasis, phimosis in men, ] or fistulas of the urethra, vagina, or anus, foinfection with other sexually transmitted infections and carcinoma (in 0.25% of cases). Prognosis is poor without treatment because the disease has a high morbidity; untreated disease leads to damage of the genital tissue, scarring, and elephantiasis. Donovanosis may reoccur after 6 to 18 months after treatment.

# Diagnosis

## History and Symptoms
Patients develop the following local symptoms, typically 3 to 40 days after sexual contact: painless papules, painless ulcers of granulomatous tissue that spread and bleed easily, periadenitis, "pseudobuboes", and absent lymphadenopathy. If the disease disseminates as a result of chronic ulcers, systemic symptoms may develop including: fever, malaise, anemia, night sweats, weight loss and toxemia.

## Physical Examination
Donovanosis is commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. Patients in later stages may present with scarring, elephantiasis-like swelling of genitals or perianal area, or stenosis of the urethra, vagina, or anus. Typical lesion characteristics include: beefy red color, nontender, emitting rank odor, elevated above skin, smooth and rolled edge, serpiginous outline. Physical examination of lesions can classify donovanosis into ulcerogranulomatous, hypertrophic, necrotic, and sclerotic variants. Common locations in males include: coronal sulcus, subpreputial region, and anus. Common locations in females include: labia minora, cervix, and fourchette.

## Laboratory Findings
The standard method for identifying K. granulomatis and suggesting donovanosis as the diagnosis is a smear and stain of ulcer material. Microscopy of the stain reveals Donovan bodies within monocytes that may or may not be capsulated. If swabs are taken for other diagnostic tests, the smear for Donovan bodies should be taken first to ensure there is adequate material to detect the Donovan bodies. K. granulomatis has been isolated via culture methods but is difficult and not practical as a tool for diagnosis.

# Treatment

## Medical Therapy
Antimicrobial therapy is the mainstay of treatment for donovanosis. Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed is the preferred regimen. Alternative regimens include doxycycline, ciprofloxacin, erythromycin, and trimethoprim-sulfamethoxazole. Pregnant women should be treated with erythromycin. Sexual partners should also be evaluated and treated.

## Prevention
Since there is no vaccine for donovanosis, methods of primary prevention include: abstaining from sexual activity, limiting number of sexual partners and using a male or female condom. The goal of secondary prevention is to stop the spread of disease. Therefore infected individuals should abstain from sexual intercourse until symptoms reside.