Donovanosis: Case series of a rare entity in the background of declining incidence worldwide

Abstract

Donovanosis is a rare bacterial sexually transmitted disease caused by Klebsiella granulomatis and has an indolent course. Clinically it manifests as an ulcer with exuberant granulation tissue most commonly in the genital and rarely in extragenital sites. Nowadays, case reports of Donovanosis are infrequent and are considered an ignored sexually transmitted infection in the current antibiotic era. Here, we are reporting three interesting case series of Donovanosis because of its rarity and clinical interest.

Introduction

Donovanosis is nowadays considered to be a rare bacterial sexually transmitted infection (STI), caused by a Gram-negative fastidious organism called Klebsiella granulomatis, which was formerly called Calymmatobacterium granulomatis. On review of the literature, worldwide there were only a few case reports in the last few decades. Donovanosis is endemic in tropical countries such as Papua New Guinea, India, South Africa, Brazil, and Australia. In India, the Eastern coastal regions of Odisha, Andhra Pradesh, and Tamil Nadu were endemic. There were no clear data regarding the incidence in India, but there was a gross decline in recent years. This could be attributed to donovanosis being considered a neglected or ignored STI and the wide usage of broad-spectrum antibiotics. Here, we are reporting three exotic cases of donovanosis in the current antibiotic era.

Case Reports

Case 1

A 45-year-old married male, a manual laborer, presented to our outpatient department with complaints of painless and ulcerative lesions over the genitals for the past 4 months. Initially, the lesion was small to start as a papule and gradually increased in size to attain the present size. There was no history of lesions elsewhere in the body. There was a history of frequent bleeding from the lesion after minor trauma. He is oriented heterosexually and had unprotected penovaginal intercourse with a commercial sex worker 6 months ago. His spouse was healthy with no history of similar illness.

On examination, there were multiple, regular, and well-defined nontender ulcers of varying sizes with exuberant granulation tissue and elevated margin seen over the foreskin [Figure 1a]. There was no urethral discharge on milking. There was bilateral painless and firm inguinal lymphadenopathy. Other areas including the anal and perianal region and systemic examination were normal. Genital examination of his spouse did not reveal any abnormality. Clinically, a diagnosis of donovanosis was entertained and investigations proceeded. Darkfield microscopy from the exudate was performed and negative for Treponema pallidum. Gram staining and Tzanck smear were negative. A crush smear was done on the edge of the ulcer and stained with Giemsa. It revealed pinkish and ovoid bodies containing dark blue nuclei with bipolar condensation lying within the macrophages suggestive of Donovan bodies [Figure 1b]. Serology for HIV 1 and 2, herpes simplex virus (HSV), and venereal disease research laboratory turned out to be nonreactive. A diagnosis of donovanosis without any coinfection was confirmed and he was started on capsules Doxycycline 100 mg twice daily for 21 days. Unfortunately, he did not come for a follow-up.

Figure 1.

(a) Multiple, regular, and well-defined nontender ulcers of varying sizes with exuberant granulation tissue and elevated margin over the foreskin. (b) Pinkish and ovoid bodies containing dark blue nuclei with bipolar condensation lying within the macrophages suggestive of Donovan bodies (Black arrows)

Case 2

A 22-year-old unmarried male, who is a mason by occupation, was examined for a chronic nonhealing ulcerative lesion over the left side of the groin. Initially, 3 months back, he developed a small erythematous papule over the left inguinal region which gradually increased in size. Thereafter, it ruptured and presented as an ulceroproliferative lesion. It often bleeds on manipulation. He had a history of unprotected intercourse with multiple unknown females and the last sexual act was being 2 months back.

On examination, there was a single, tender, elliptical ulceroproliferative lesion of size 1 cm × 5 cm with beefy red granulation on the floor seen over the left inguinal region [Figure 2a]. Inguinal nodes were free and mobile, felt underneath the lesion. There were no similar lesions in the genitals and perianal region. As the patient was promiscuous, clinically a diagnosis of Donovanosis was considered but an inguinal ulceroproliferative growth in the absence of a genital lesion made us keep that as a second differential diagnosis. To rule out Mycobacterium tuberculosis as an etiological agent, additional investigations were carried out apart from routine. Darkfield microscopy was negative for treponemal spirochetes. Grams staining, smear for acid-fast bacilli, and Tzanck smear were done and turned out negative. Gene Xpert was done from the exudates and M. tuberculosis was not detected. Chest X-ray was taken and normal. A crush smear was taken from the edge and stained with Giemsa. After a meticulous search, we demonstrated classical Donovan bodies inside a large monocyte [Figure 2b]. Biopsy revealed pseudoepitheliomatous hyperplasia and infiltrations of plasma cells, lymphocytes, and histiocytes in the superficial dermis [Figure 3a and b]. Surprisingly, there were Donovan bodies seen in the H and E tissue sections [Figure 4]. Serologies for HIV 1 and 2, rapid plasma reagin (RPR), and HSV status were nonreactive. Thus, donovanosis was confirmed and the patient was started on capsules doxycycline 100 mg BD for 21 days. There is complete healing of the lesion at the end of 3^rd week [Figure 5]. Partner tracing could not be done as there were multiple unknown partners.

Figure 2.

(a) Single, tender, elliptical ulceroproliferative lesion of size 1 cm × 5 cm with beefy red granulation on the floor seen over the left inguinal region. (b) Classical Donovan bodies inside a large monocyte (black arrow)

Figure 3.

(a and b) Biopsy revealed pseudoepitheliomatous hyperplasia (white arrow) and infiltrations of plasma cells (yellow arrow), lymphocytes, and histiocytes in the superficial dermis (×40)

Figure 4.

Donovan bodies seen in H and E tissue section (black arrow - macrophages and red arrow - Donovan bodies)

Figure 5.

Pre- and post- treatment response

Case 3

A 40-year-old male who is a manual laborer, presented with multiple ulcerative lesions over the genitals for the past 2 years. Initially, he had noticed the ulcerative lesion over the prepuce which increased gradually and similar multiple ulcerative lesions had developed in the shaft of the penis. He was heterosexually oriented and had multiple unprotected sex with commercial sex workers. He did not go for any consultations for 2 years. There were multiple ulceroproliferative lesions of varying sizes over the shaft and prepuce which bleeded on manipulation [Figure 6a]. The bilateral inguinal nodes were nontender and firm. A crush smear demonstrated Donovan bodies [Figure 6b] and a biopsy revealed high-grade, well-differentiated squamous cell carcinoma. RPR and HIV statuses were nonreactive. Systemic workup for dissemination of Granuloma inguinale was done and there was no evidence of dissemination. He was referred to surgical oncology and a total penectomy with inguinal block dissection was done. Partner tracing could not be done as there were multiple unknown partners.

Figure 6.

(a) Multiple fragile ulceroproliferative lesions of varying sizes over the shaft and prepuce. (b) Classical Donovan bodies inside monocytes

Discussion

Donovanosis was first described by McLeod in the year 1882 and he named it serpiginous ulceration of the groin. It is caused by Calymmatobacterium granulomatosis, a Gram-negative nonmotile encapsulated bacillus which is phylogenetically similar to Klebsiella species.[1] The causative organism was demonstrated by Major Charles Donovan in the year 1905 at Madras.[2] It is also described as granuloma inguinale, granuloma venereum, granuloma inguinale tropicum, and ulcerating granuloma of the pudenda.[1]

The incubation period ranges between 3 and 40 days. The genital region is affected in 90% of cases and the inguinal area in 10%. The most common sites of involvement are the coronal sulcus, subpreputial region, and anus in men and in women, the labia minora, fourchette, and perianal areas are involved. Lesions can occur inside the vagina and manifest as vaginal discharge.[3] Dissemination of the liver and bone has been rarely described. It can also spread by autoinoculation and fecal contamination.[4]

The morphological types described so far are classical or ulcerogranulomatous type, hypertrophic or verrucous type, sclerotic or cicatricial type, and necrotic or phagedenic type.[5] Clinically, it evolves as erythematous papules or nodules that erode through the skin and form well-defined painless ulcers with beefy red granulation which bleed on touch. In donovanosis, generally, there will not be any lymphadenopathy, and if present other causes of lymphadenopathy such as concomitant sexually transmitted infection (STI) and malignancy can be considered. The risk of HIV shedding is higher as the surface area is large and can alter the classical presentation of donovanosis and takes a longer time to heal.

There are no specific blood tests or culture facilities available for the confirmation of granuloma inguinale. The diagnosis is established based on classical clinical features and demonstration of Donovan bodies in tissue smear.[6] They are detected in 90%–95% of cases and are considered the gold standard for diagnosis of donovanosis.[7] A biopsy is not indicated in all cases. Although nonspecific, the histopathological examination will help in distinguishing between malignancy and donovanosis.[8]

Complications to be anticipated are pseudo elephantiasis as a result of lymphatic obstruction, mutilations, and obstruction of the vaginal orifice due to the destruction of tissues and subsequent fibrosis. The most dreadful complication is the malignant transformation of the ulcers in chronic and long-standing cases. This feature was observed in 0.25% of the patients in the Rajam and Rangaiah series.[9] Very rarely, donovanosis occurred as a superinfection in cases of squamous cell carcinoma of the genitals.[10,11]

According to the Centers for Disease Control and Prevention, 2021 guidelines, the recommended treatment is tablet azithromycin 500 mg daily or 1 g once weekly until complete resolution of the lesions. Alternative regimens are capsules Doxycycline 100 mg twice daily for 21 days or until complete healing of the lesion. Erythromycin and trimethoprim-sulfamethoxazole can also be given. Partners within 60 days before the onset of lesions should be examined and offered treatment.[12] Injection streptomycin 0.75 mg twice daily for 15 days is an old recommendation.[13] There is complete healing of the lesion in our second case after 3 weeks of treatment.

Conclusion

We have reported three classical cases of donovanosis without any coinfections over the genital and extragenital sites in the current antibiotic era that too with a dreadful and rare complication. Although the incidence of donovanosis has decreased nowadays, some sporadic cases are being reported. Hence, it cannot be neglected and should be considered a differential diagnosis in any case of genital ulcer. These cases imply that the ignored bacterial STIs still exist. As long as human beings survive, STIs also survive and they should be properly diagnosed and treated to prevent transmission and unnecessarycomplications.

Declaration of patient consent

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Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.