Granuloma inguinal (Donovanosis) de la encía y regiones submandibulares

Granuloma inguinale (Donovanosis) of the oral cavity is uncommon, however it represents the most frequent extragenital manifestation of this infectious disease produced by the gram negative bacterium, Calymmatobacterium granulomatis. A case of gingival donovanosis in a 19 year-old homosexual man is described. The gingival lesions appeared as a painless microgranulomatous ulceration combined with spongy masses. The patient also had lesions in the submandibular region and anal areas. The diagnosis was established by gingival biopsy. In this tissue, hematoxylin and eosin (H&E) stained sections showed a marked granulomatous histiocytic reaction mixed with many neutrophils and few plasma cells. Donovan bodies were identified using the Warthin-Starry stain. Reference is made to the clinical differential diagnosis as well as to the histologic picture. The sexual behavior of the patient, suggest that the gingival involvement probably represented one of the multiple primary sites of C. granulomatis infection.However, autoinnoculation can not be discarded. Donovanosis should be considered in the differential diagnosis of granulomatous lesions affecting the oral mucosa, particularly when they occur in sexually promiscuous patients.


Granuloma inguinale (Donovanosis) of the gingiva and submandibular regions
Delgado WA, Gotuzzo E, Meneses LV, Lama JR. Granuloma inguinale (Donovanosis) of the submandibular region and gingiva. Rev Estomatol Herediana 2005; 15(1): Donovanosis is a sexually transmitted infection produce by the gram negative bacterium Calymmatobacterium granulomatis. The disease was first described by Mc Leod in India under the name of "serpiginous ulcers" (1). Donovanosis is better known as granuloma inguinale, since this infection predominantly affects the anogenital areas. In 1905, Donovan (2) described the presence of what are now called "Donovan bodies" in the exudate from an oral granulomatous lesion of a patient who also had a genital lesion.
The primary lesion starts as a small papule or indurated nodule, usually occurring after an incubation period of one to four weeks; however, longer periods of incubation have been reported (3). Lesions are characteristically painless. In men the anatomical sites more commonly involved are the prepuce, coronal sulcus and penile shaft. Rectal lesions have been reported in homosexual men (4). In women, labial, vaginal and cervical lesions may occur (4).
A case of donovanosis involving the mandibular gingiva, submandibular region and perianal skin in a 19-year old homosexual man is described.

Case report
A 19 year old man with bilateral submandibular granulomatous masses was admitted to the Tropical Medicine Institute Alexander von Humboldt of the Peruvian University Cayetano Heredia. Eighteen months before he had developed subcutaneous nodules in both submandibular regions which had been increasing slowly in size and had become ulcerated. Later the nodules developed chronic exuberant granulomatous masses. At this time, the lesions were drainage and dicloxacillin was prescribed for treatment. Biopsy of the lesions were not performed. He continued receiving many short courses of different types of antibiotics without benefit.
Upon examination the patient appeared severely ill and extremely debilitated.He had chronic diarrhea and marked anasarca. Abdominal examination revealed ascitis. The liver, spleen and lymph nodes could not be palpated. The scrotum presented marked edema. The patient stated he was a crossdressing homosexual sex worker since the age of 14. He has had multiple sex partners and rarely used condoms. He always lived in Lima and denied travel to the peruvian jungle or highlands. There was no history of tuberculosis.

Skin findings
At the anal region a painless ulcerated mass of irregular form, approximately 3 cm. in diameter was found. Symmetrical large granulomatous exuberant masses were present in the submandibular region bilaterally. The surface were ulcerated with serosanguinous discharge. The borders of the masses were sharply demarcated from the adjacent skin. The lesions were friable (Fig.1, 2). No cervical lymphadenopathy was detected.

Oral findings
Both vestibular and lingual aspects of the mandibular gingiva appeared spongy and hyperplastic. In some areas, the texture of the surface was microgranulomatous showing areas of ulceration and bleeding (Fig. 3). The mucosa adjacent to the root remnant of the first right lower molar bled easily (Fig. 4). The gingival lesions were painless and the patient was not aware of them. The rest of the oral mucosa including the tongue and tonsils were normal. Apart from the molar remmant the rest of the teeth were in good condition. A panoramic radiograph did not show bone alterations.

Gingival biopsy
The hematoxilin and esosin (H&E) sections obtained from two vestibular gingival biopsies showed accumulations of large histiocytes with pale cytoplasm located immediately below the epithelium which occupied the entire lamina propria (Fig. 5). Together with this cells many neutrophils and few plasma cells and lymphocytes were present (Fig. 6). Ulcerated areas were observed. Inside the cytoplasm of the histiocytes slightly basophilic small bodies could be detected at higher power. Sections stained with PAS and acid fast stains were negative, but the Warthin-Starry stain disclosed many black rod-shaped bodies inside the histiocytes (Fig.7). This finding together with the history of the patient established the diagnosis of donovanosis.

Smears
Once the histopathologic diagnosis was established, smears from the submandibular lesions were taken which were stained with Warthin-Starry stain. This study was also positive for Donovan bodies. (Fig.8).

Other biopsies
Specimens obtained from the skin of the submandibular and anal regions demonstrated similar histopathologic features to the gingival tissues. The Warthin-Starry stain was also positive for Donovan bodies.

Treatment
The patient was hydrated and provided an adequate diet. He was treated with supplements of folic acid and vitamin B12. Doxycycline 100mg twice a day was administered for eighty days. The skin lesions disappeared slowly leaving fibrous scars in the perianal and submandibular regions (Fig. 9). The oral lesions healed without scarring (Fig. 10).

Discussion
Donovanosis is a mildly contagious, chronic, slowly progressive infection produced by the microorganism Calymmatobacterium granulomatis. Lesions are usually localized to anorectal and inguinal skin. It also affects the genitalia and oral mucosa. Occasionally, other parts of the body can be involved. Clinically, it is characterized by the development of a velvety or beefy, red, granulomatous painless ulceration that expands slowly. Definitive diagnosis is established by detection of Donovan bodies in smears and biopsies taken from affected areas. Donovan bodies are disclosed inside the cytoplasm of histiocytes using special stains. The smears can be stained with Giemsa, Leishman, Wright or Warthin-Starry techniques. In tissue sections, Giemsa stain and particularly silver stains such as Warthin-Starry demostrate the microorganism. Warthin-Starry stain clearly shows Donovan bodies as dark rod-shaped bodies measuring 0.5 -0.7 um x 1-1.5 um (3).
Granuloma inguinale is seldom systemic.Only 25% or less of cases affect the inguinal region. Therefore, the term "granuloma donovani" was pro posed by Lal and Nicholas (1). Those interested in all aspects of this infection refer to the comprehensive reviews published by Hart (3) and Sowmini (13).
Extragenital lesions are defined as those lesions located outside the inguinal or anogenital areas (3). They are estimated to occur in about 6% of cases (14)(15)(16)(17). They may represent a primary infection, may occur by autoinoculation or by hematogenous spread.. In children, lesions have been attributed to direct contact with their diseased parent (18,19). The oral mucosa represents the most commonly affected extragenital zone (14,17). In a large Indian study, 50 (5.8%) of 858 patients with donovanosis had oral involvement.In 12 of these patients, the disease produced lesions of the skin of the neck or jaw (2).
In our patient the major lesions were located in the skin of the submandibular regions and in the mandibular gingiva. The patient never sought consultation nor complained of the anal and gingival lesions. The submandibular involvement appeared as large symmetrical painless, granulomatous masses which resembled the characteristic donovanosis lesions affecting the perineum (20,21).
In the present case , the lesions in the oral cavity were confined to the mandibular gingiva and appeared as painless microgranulomatous ulcerations combined with spongy areas. The affected gums bled easily during mastication and on gentle contact. Given the oral clinical presentation, conditions considered in the differential diagnosis included paracoccidiodomycosis, histoplasmosis, and primary oral tuberculosis.
The definitive diagnosis was established by histopathologic study of biopsies obtained from the gingival lesions. Hematoxilyn-eosin stained sections showed a marked granulomatous histiocytic reaction with numerous neutrophils and limited numbers of plasma cells and lymphocytes. Donovan bodies were identified inside the histiocytes using Wharthin-Starry stain. The spongy appearance of the gingiva corresponded histologically to superficial accumulation of large histiocytes coupled with epithelial atrophy.
When using the Warthin-Starry stain, it is very important to remember that Klebsiella rhinoscleromatis can also be stained with this technique. The shape and size of both microorganisms are similar when they are disclosed with Warthin-Starry stain (22). Recently, C. granulomatis has been proposed to be reclassified as Klebsiella granulomatis due to the fact that this microorganism shows a high level of identity with Klebsiella species pathogenic to humans (23).
In order to differentiate donovanosis from rhinoscleroma, it is necessary to consider that rhinoescleroma affects the nose but also the upper and lower respiratory tracts . Involvement of oral mucosa is rare, and when this occurs lesions are located in the soft and hard palate,upper lip and maxillary gingiva. Histologically consists of closely aggregated foamy macrophages of xanthomatous appearance, some of them multinuclear (Mikulicz´s cells), a dense plasmacytic infiltrate and Russell bodies within the plasma cells (22,24). Neutrophils if present are not numerous as they are in donovanosis.
A remarkable aspect of this case, is the absense of lesions in the rest of the oral cavity in spite of the extensive mandibular gingival involvement and the duration of the infection. Also, no systemic lesions were detected. Although, the lesions of donovanosis persisted for several months, treatment with Doxycycline was effective and apart from the skin scars, no sequellae remained in the affected gums.
Since the patient also had involvement of the anus, it is difficult to prove that the lesions of the gingivae or of the submandibular regions represented primary or secondary manifestations of donovanosis. The sexual behavior of the patient suggests that the three anatomic affected areas represented multiple primary sites of C. granulomatis infection. However, the posibility that the submandibular and oral lesions were the result of autoinnoculation can not be discarded.
The present report is a good example of the extragenital manifestations of donovanosis. Since the oral cavity is reported to be the most commonly affected extragenital site and the lesions are typically chronic and asymptomatic, it is necessary to consider donovanosis in the differential diagnosis of granulomatous lesions affecting the oral mucosa. This is particularly important when epidemiological data related to endemic infections is absent in the history of sexually active patients. The biopsy of oral lesions and the use of specific stains are fundamental to establishing the correct diagnosis.