Donovanosis lesions usually start as a painless papule or subcutaneous nodule. The lesions develop the classic “beefy-red” appearance due to their high vascularity. The initial lesion takes on an ulcerative morphology after minor trauma. There is usually no regional lymphadenopathy. Developing subcutaneous granulomas known as pseudobuboes is possible. The lesions are progressive in an outward direction from the center. The borders of the lesions are sometimes described as “snake-like” in appearance. Self-inoculation is possible and may create mirror-image lesions in the same general location, usually across skin folds.[2] Patients often delayed seeking health care for many reasons, and therefore, they usually present with a more progressed lesion.[6] There are 4 types of lesions. Classic ulcerogranulomatous lesions are the most common with beefy-red, non-tender ulcers that bleed easily. The second type is hypertrophic or verrucous with irregular raise edges and dry texture. The third type is necrotic, offensive-smelling, deep ulceration that causes tissue destruction. The last type is sclerotic or cicatricial with fibrous and scar tissue. The genitals are affected in 90% of cases and the inguinal region in 10% of cases. The most common sites where men are affected are the prepuce, coronal sulcus, frenum, glans, and anus. The most common sites where women are affected are the labia minora, fourchette, cervix, and upper genital tract. Pregnant patients experience quicker progression of donovanosis lesions and respond slower to treatment compared to the general population. Extragenital lesions occur on the lips, gums, cheek, palate, pharynx, larynx, and chest 6% of the time.[3]

Diagnosis can be made by an experienced physician in endemic areas but may be difficult in other areas of the world. In nonendemic areas, the diagnosis will require a high index of suspicion. The diagnosis is confirmed by identifying Donovan bodies in a tissue smear. PCR testing is possible but is not widely available. It is seen in the research setting and often used during eradication programs. There are serologic tests that can be used for population studies, but they are not accurate enough to diagnose an individual.[3][2]

The CDC recommends that treatment should last until all lesions are healed. First-line treatment is azithromycin 1 g followed by 500 mg daily. Relapses can occur 6 to 18 months after seemingly successful treatment. Some alternative treatment regimens are doxycycline 100 mg twice per day, ciprofloxacin 750 mg twice per day, erythromycin 500 mg 4 times per day, and sulfamethoxazole/trimethoprim twice per day. Patients that are slow to respond can also be given gentamicin 500 mg every 8 hours. Erythromycin is the medication of choice in pregnancy. There is no change in the recommendations for HIV positive patients. The 2016 European Guidelines for donovanosis treatment state that antibiotics should continue for a minimum of three weeks and until symptom resolution. They also recommend azithromycin as a first-line treatment that can be given as 1 g initially then 500 mg daily or 1 g weekly. Children should be given azithromycin 20 mg/kg for a disease treatment course or prophylaxis for 3 days if exposed during birth. The first study to demonstrate the effectiveness of azithromycin was performed by Bowden et al. between June 1994 and March 1995 in Australia. Seven patients received 1 g azithromycin weekly for 4 weeks, and 4 patients received 500 mg azithromycin daily for 7 days. After 6 weeks, 3 patients from the first regimen and 1 patient from the second were healed, and all other participants in the study were significantly improved. Azithromycin was shown to be effective against donovanosis and has the added benefit of short, intermittent dosing, which may facilitate treating endemic populations. Medication alone may be the only treatment required. Surgery may be needed for extensive tissue destruction. Patients require consistent monitoring for disease resolution and possible recurrence.[3][1]

The differential diagnosis for genital ulcers is broad and includes primary syphilis, secondary syphilis (condylomata lata), chancroid, lymphogranuloma venereum, genital herpes, neoplasm, amoebiasis, and several others. The possibility of a coinfection should always be considered since the risk factors for several of these diseases are similar. Lesions that have a more destructive appearance should be evaluated for carcinoma in addition to other causes. Also, pseudo-elephantiasis, which is a possible complication of donovanosis, can mimic lymphogranuloma venereum. Additionally, women with cervical lesions should also undergo testing for carcinoma and tuberculosis. If the diagnosis of donovanosis is confirmed, the patient should undergo HIV testing due to being at increased risk of transmission with donovanosis lesions. Any patient found to have a sexually transmitted disease should be considered for HIV testing.[3]

The prognosis for uncomplicated donovanosis is positive with appropriate treatment. There is the possibility of relapse, which can occur even after symptoms appear to have resolved. Lack of improvement should prompt further investigation and testing for co-infection or alternative diagnoses. If left untreated, there can be significant scarring and tissue destruction. Malignant transformation is also possible.[3]

Possible complications include neoplastic change, pseudo-elephantiasis, hematogenous spread, polyarthritis, osteomyelitis, vaginal bleeding, and stenosis of the urethra, vaginal, or anus. Dissemination into the abdominal cavity is a rare possible complication. Symptoms include fever, malaise, anemia, night sweats, weight loss, and sepsis. Also, many patients receiving care after having endured the disease process for a significant amount of time may have suffered emotionally. The lesions can be embarrassing and distressing to the patient. Always consider mental health disorders such as anxiety or depression and include suicide screening in these patients. [3]Murugan et al. described some cases of significant vaginal bleeding caused by donovanosis. A 33-year-old woman from Madurai presented to Rajaji Hospital after complaining of white vaginal discharged and prolonged menstrual periods. She was found to have ulcers of the cervix and vaginal vault with areas of necrosis. Donovan bodies were found in the ulcer smears. She was initially treated with streptomycin then switched to tetracycline when she could not tolerate the side effects of the first medication. She was noted to have significant improvement with decreased ulcer size and less discharge after 20 days of treatment. Two months after treatment she reported complete resolution of her symptoms and was noted to be symptom-free after 1 year. A 19-year-old woman also from Madurai presented to Rajaji Hospital with an antepartum hemorrhage at 24 weeks gestation. She was found to have a granulomatous cauliflower-like ulcerative growth in the vaginal vault. Smears of the ulcer showed Donovan Bodies. She was successfully treated with streptomycin with an almost complete resolution of her symptoms after one month.[7] Thappa et al. described a case of malignant transformation. A 25-year-old man from India presented with a lesion over the glans penis for four years duration. Donovan Bodies were seen on the tissue smear. However, he failed treatment with co-trimoxazole and azithromycin. A biopsy revealed squamous cell carcinoma.[8]

Control and Prevention

The incidence of donovanosis has been decreasing worldwide most likely due to the realized role in HIV transmission. There have been multiple programs in the United States, Australia, and Papua New Guinea that have reduced disease prevalence. One program in Papua New Guinea involved mandatory inpatient treatment and utilized security guards in the wards to ensure completion of treatment.[3] Efforts in Australia have almost eradicated the disease. In the mid-1990s, a proactive approach to disease eradication was initiated. There were 115 cases of donovanosis noted within the aboriginal population in 1995. The Tri-State HIV/STI initiative implemented a Donovanosis Project Officer in 1997 to manage surveillance, diagnosis, and treatment. The prevalence significantly decreased over the following 3 years. In 2001, the National Donovanosis Eradication Committee was established after several organizations noted disease eradication was a worthy goal and possible. Both government and nongovernment agencies were involved, and they implemented a multidisciplinary approach. The goal of eradication was changed to elimination after realizing that eradication would require a global initiative. Elimination was defined as no new cases reported to the National Notifiable Disease Surveillance System (NNDSS) for 3 years. This second initiative utilized four Project Officers. As of 2004, there were only 5 reported cases of donovanosis.[9] Donovanosis has been targeted for eradication due to the risk of HIV transmission with genital ulcer disease. O’Farrell looked at STD clinics in Durban, South Africa and found higher rates of HIV-1 positivity in men with donovanosis as the duration of the lesions presence increased. There was a 5000-fold increase in the positive HIV-1 rates in men with donovanosis versus men with gonorrhea for greater than 3 months. Men with donovanosis are considered “super-spreaders” in regards to spreading HIV if they have the disease or acquiring the disease if they have genital lesions.[6] Since the incubation period is uncertain but estimated to be around 50 days, the CDC recommends treating anyone who has sexual contact with someone diagnosed with donovanosis within 60 days. It is unclear at this time if prophylaxis is useful in this setting. The 2016 European Guidelines also recommend prophylaxis for neonates exposed during vaginal birth.[1]

The nurse practitioner, primary care provider or the emergency department physician is unlikely to encounter donovanosis in the emergency department in the United States. Physicians will need to have a high index of suspicion based on travel history, social history, and physical exam. A broad differential diagnosis list is important when genital ulcers are present and sexually transmitted infection is suspected. Consider a pelvic exam on all women to evaluate for the presence of cervical lesions. All women of childbearing age should have a pregnancy test done in the emergency department. If donovanosis is suspected, it is important to recognize the extended course of treatment that may be required. It is reasonable to initiate treatment in the emergency department while arranging for proper follow-up testing and care.

Since donovanosis is so rare in the United States, patients should be referred to an infectious disease specialist or a clinician with experience in treating this condition. Definitive diagnosis in the emergency department is unlikely and can be pursued by a qualified specialist. It is important to prepare the patient for a prolonged treatment course and stress the importance of extended follow up to evaluate for reoccurrence. All patients presenting with possible donovanosis or sexually transmitted infection should be considered for HIV testing. 

The pharmacist should educate the patient that the treatment is often for many months and if compliance is not maintained, the risk of relapse is high.