.
COMMENTARY
i.
DONOVANOSIS (GRANULOMA INGUINALE) STILL EXISTS '
• : ,.
,,.
PAUL L. A. NIEMEL, M.D., HERMAN JAN H. ENGELKENS, M.D., WILLEM 1. VAN DER MEIJDEN, M.D., AND ERNST STOLZ, M.D.
Donovanosis (granuloma inguinale, Gl), a chronic, mildly contagious, progressively destructive disease, is still prevalent in some of the tropical and subtropical regions of the world. Although a rarity in the temperate zone, donovanosis is still an important sexually transmitted disease in several developing countries. The disease is endemic in Southeast Asia, Papua New Guinea, Australia, Southern India, the Caribbean, South America, and parts of Africa. Elsewhere in the world (e.g., in the United States) small epidemics have been documented.' Due to current trends in migration, patients from endemic regions can easily transport donovanosis outside endemic regions.^ In these circumstances, the disease may cause considerable diagnostic problems, as was recently described by Bondeson et al.-' The causative organism, Calymmatobacterium granulomatis, a gram-negative, facultative intracellular, encapsulated bacillus'* is extremely difficult to culture or to demonstrate by laboratory techniques. This organism is not pathogenic for currently used laboratory animals. As well as sexual contact, which is assumed to be the most common mode of transmission, non-sexual transmission is also possible. The exact mode of transmission of this disease is still not fully understood. Outside the human beitig, a reservoir has not been established. The majority of patients are sexually active and from 15 to 30 years of age. More men than women are reported to be affected.
lesions on the vulva, labia, vagina, perineum, or cervix. The initial lesion may disappear spontaneously or be tindetected, especially in women. The classical lesion of donovanosis is a painless and friable beefy ulcer. In contrast with lymphogranuloma venereum, local lymphadenopathy is uncommon, unless secondary infection is present. Several clinical variants are recognized: hypertrophic, ulcerative or ulcerogranulomatous, sclerotic (Fig. 3), and necrotic. Different variants may appear simultaneously. Dissemination of lesions may occur, probably due to autoinoculation. The oral cavity and extragenital parts of the skin (Fig. 4) may be affected.-'-'' Systemic disease involving the bones, liver, and spleen may occur rarely; fatal outcomes have been reported.^ There is little chance of spontaneous healing in well-developed cases. Severe mutilation can result when secondary infection of skin lesions occurs. Spontaneous healing is extremely slow, with marked fibrosis, scar tissue constrictures, and lymphatic obstruction that may produce an elephantiasis-like picture.** Rectovaginal fistulas are another late sequela. Because of the availability of antibiotics, mutilating donovanosis is less common. Histopathologic features are characteristic large mononuclear cells containing inclusion bodies (Donovan bodies); however, histoplasmosis, rhinoscleroma and leishmaniasis may present similarly. Epithelial hyperplasia and dense dermal inflammatory infiltrate are common findings.
CLINICAL PICTURE
After an uncertain incubation period, the initial manifestation is a papule or nodule, usually located on the genitals. In men (Fig. 1) the prepuce, glans penis, or perianal region is commonly involved. Women (Fig. 2) may have From the Department of Dermatology and Venereology, University Hospital Rotterdam-Dijkzigt and Erasmus University, Rotterdam, The Netherlands, and the Department of Health, Disease Control Section, Boroko, Papua New Guinea. Address for correspondence: Herman Jan H. Engelkens, M.D., Department of Dermatology and Venereology, University Hospital Rotterdam-Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Figure 1. 244
Ulcerative lesion on the prepuce.
Donovanosis Niemel et al.
Figure 2.
Kissing ulcer in the vulva.
DIFFERENTIAL DIAGNOSIS AND LABORATORY INVESTIGATIONS
Figure 3. Sclerotic ulcerating lesion. Genital lesions in donovanosis must be differentiated from syphilis, chancroid, herpes progenitalis, lymphogranuloma venereum, candidiasis, anogenital cutaneous amebiasis, and traumatic ulcers. Ulcers may mimic carcinoma or neoplasms, especially in longstanding lesions of GI. Lesions located extragenitally must be differentiated from tuberculosis, histoplasmosis, filariasis, leishmaniasis, actinomycosis, or fixed drug eruption. As well as the clinical picture, laboratory confirmation by demonstration of typical Donovan bodies in direct tissue smears from tissue scrapings—using Giemsa's, Leishman's, or Wright's staining method, or in biopsy material, staining by hematoxylin and eosin, a silver staining method, or slow-Giemsa stain'—is necessary to confirm the diagnosis of donovanosis. The intra- and/or extracellular micro-organisms exhibit bipolar staining and resemble closed safety pins. Unfortunately, reliable cultural techniques and serologic tests are not yet available for routine investigations.
THERAPY
The current recommended treatment regimen consists of trimethoprim (80 mg) and sulfamethoxazoie (400 mg), two tablets twice daily for at least 2 weeks.'"'" An alternative therapy consists of oral tetracycline separate or in combination with streptomycin by intramuscular injection.'- Erythromycin, especially during pregnancy, gentamicin, and chloramphenicol are other alternatives. After treatment, prolonged follow-up is necessary to assess the effect of therapy. Relapses or reinfection may occur in some cases, after apparently successful initial treatment.
Figure 4. Extragenital extensive ulcerative disease. CONCLUSION
Although donovanosis has become a rarity in the United States and Europe, a diagnosis of donovanosis must be considered in patients originating from endemic regions. There are many reasons to explain why this dis245
International Journal of Dermatology Vol. 31, No. 4, April 1992
ease has not been eradicated; for example, neglect of the disease, ignorance in large populations about sexually transmitted diseases in general, unfamiliarity with the disease in the medical profession, limited understanding of the pathogenesis and the epidemiology, the lack of simple and reliable inexpensive serologic tests for the diagnosis, in combination with the protean manifestations of granuloma inguinale. Recently, it has been reported that GI has remained unrecognized for nearly half a century in South Africa, due to a lack of awareness. This underlines the importance of continuing surveillance for the disease.'-' The importance of genital ulcerations in the transmission of HIV infection has recently been postulated.''' The limited data which are available have demonstrated strong associations between HlV-seropositivity and infectious syphilis, genital herpes simplex infection, and chancroid. The precise interrelationship between genital ulcerative disease including donovanosis and HIV infection remains undetermined. We suspect that the easily bleeding and usually painless ulcers in donovanosis may also facilitate the transmission of HIV infection. Frequently, patients presenting with donovanosis suffer from other STD. With limited financial resources for laboratory equipment in many parts of the world, and the absence of efficient screening methods, continued outbreaks of this disease seem likely. The biology and pathogenesis of Calymmatobacterium granulomatis are not fully understood. Treatment strategies for donovanosis have currently been effective. A possible association of donovanosis with neoplasms in the genital area has not yet been fully elucidated and requires further study.'-'' Early diagnosis of donovanosis is critical to therapeutic outcome. Untreated disease is associated with mutilation and prolonged morbidity. More research is needed.
REFERENCES
2.
Hoyer H, Weismann K. Granuloma venereum. Eine seltene, importierte Geschlechtskrankheit. Hautarzt 1981; 32:374-375.
3.
Bondeson J, Bohe M, Carlsson U, et al. Perianal abscess and sinuses caused by granuloma inguinale. Gase report. Acta Ghir Scand 1989; 155:607-610.
4.
Kuherski T, Papadimitriou JM, Phillips P. Ultrastructure of Calymmatobacterium granulomatis in lesions of granuloma inguinale. J Infect Dis 1980; 142:744-749. Goovadia YM, Steinberg JL, Kharsany A. Granuloma inguinale (donovanosis) of the oral cavity. A case report. S Afr Med J 1985; 68:815-817.
5.
6.
7.
8.
9.
10.
11.
12.
13. 14.
• . ; . , :
15. 1.
Rosen T, Tschen JA, Ramsdell W, et al. Granuloma inguinale. J Am Acad Dermatol 1984; 11:433-437.
Schneider J, O'Shea J, Finlay-Jones LR, et al. Extragenital donovanosis: three cases from Western Australia. Genitourin Med 1986; 62:196-201. Rajam RV, Rangiah PN. Donovanosis (granuloma inguinale, granuloma venereum). WHO Monograph Series, no. 24. Geneva: World Flealth Organization, 1954. Sehgal VN, Jain MK, Sharma VK. Pseudoelephantiasis induced by donovanosis. Genitourin Med 1987; 63: 54-56. Sehgal VN, Jain MK. Tissue section Donovan bodies identification through slow-Giemsa (overnight) technique. Dermatologica 1987; 174:228-231. Lai S, Garg BR. Further evidence of the efficacy of cotrimoxazole in granuioma venereum. Br J Vener Dis 1980; 56:412-413. STD Treatment Strategies. WHO Consultation on Development of Sexually Transmitted Diseases Treatment Strategies. Geneva: World Health Organization. WHO/ VDT/89.447; September 1989. Latif AS, Mason PR, Paraiwa F. The treatment of donovanosis (granuloma inguinale). Sex Transm Dis 1988; 15:27-29. Freinkel AL. The enigma of granuloma inguinale in South Africa. S Afr Med J 1990; 77:301-303. Global Programme on AIDS and Programme of STD. Consensus statement from consultation on sexually transmitted diseases as a risk factor for HIV transmission. Geneva: World Health Organization. WHO/ GPA/INF/89.I; January 1989. Sengupta BS. Vulvar carcinoma in premenopausal Jamaican women. Int J Gynaecol Obstet 1980; 17: 526 -530.
SPTS. TURPENTINE The dose tor ordfnmry purposes is from 5to 40 drops, repeated •very hour or two in acute, and three or four dines a day ia chronic diseases. It may be eivrn OD su^ar r r in cmulalon.
DBS.
A. il. & L . E. METER, Props
THiaODAUX.
LOUISIANA
From the collection of "La Pharmacie Frangaise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 246
COMMENTARY
i.
DONOVANOSIS (GRANULOMA INGUINALE) STILL EXISTS '
• : ,.
,,.
PAUL L. A. NIEMEL, M.D., HERMAN JAN H. ENGELKENS, M.D., WILLEM 1. VAN DER MEIJDEN, M.D., AND ERNST STOLZ, M.D.
Donovanosis (granuloma inguinale, Gl), a chronic, mildly contagious, progressively destructive disease, is still prevalent in some of the tropical and subtropical regions of the world. Although a rarity in the temperate zone, donovanosis is still an important sexually transmitted disease in several developing countries. The disease is endemic in Southeast Asia, Papua New Guinea, Australia, Southern India, the Caribbean, South America, and parts of Africa. Elsewhere in the world (e.g., in the United States) small epidemics have been documented.' Due to current trends in migration, patients from endemic regions can easily transport donovanosis outside endemic regions.^ In these circumstances, the disease may cause considerable diagnostic problems, as was recently described by Bondeson et al.-' The causative organism, Calymmatobacterium granulomatis, a gram-negative, facultative intracellular, encapsulated bacillus'* is extremely difficult to culture or to demonstrate by laboratory techniques. This organism is not pathogenic for currently used laboratory animals. As well as sexual contact, which is assumed to be the most common mode of transmission, non-sexual transmission is also possible. The exact mode of transmission of this disease is still not fully understood. Outside the human beitig, a reservoir has not been established. The majority of patients are sexually active and from 15 to 30 years of age. More men than women are reported to be affected.
lesions on the vulva, labia, vagina, perineum, or cervix. The initial lesion may disappear spontaneously or be tindetected, especially in women. The classical lesion of donovanosis is a painless and friable beefy ulcer. In contrast with lymphogranuloma venereum, local lymphadenopathy is uncommon, unless secondary infection is present. Several clinical variants are recognized: hypertrophic, ulcerative or ulcerogranulomatous, sclerotic (Fig. 3), and necrotic. Different variants may appear simultaneously. Dissemination of lesions may occur, probably due to autoinoculation. The oral cavity and extragenital parts of the skin (Fig. 4) may be affected.-'-'' Systemic disease involving the bones, liver, and spleen may occur rarely; fatal outcomes have been reported.^ There is little chance of spontaneous healing in well-developed cases. Severe mutilation can result when secondary infection of skin lesions occurs. Spontaneous healing is extremely slow, with marked fibrosis, scar tissue constrictures, and lymphatic obstruction that may produce an elephantiasis-like picture.** Rectovaginal fistulas are another late sequela. Because of the availability of antibiotics, mutilating donovanosis is less common. Histopathologic features are characteristic large mononuclear cells containing inclusion bodies (Donovan bodies); however, histoplasmosis, rhinoscleroma and leishmaniasis may present similarly. Epithelial hyperplasia and dense dermal inflammatory infiltrate are common findings.
CLINICAL PICTURE
After an uncertain incubation period, the initial manifestation is a papule or nodule, usually located on the genitals. In men (Fig. 1) the prepuce, glans penis, or perianal region is commonly involved. Women (Fig. 2) may have From the Department of Dermatology and Venereology, University Hospital Rotterdam-Dijkzigt and Erasmus University, Rotterdam, The Netherlands, and the Department of Health, Disease Control Section, Boroko, Papua New Guinea. Address for correspondence: Herman Jan H. Engelkens, M.D., Department of Dermatology and Venereology, University Hospital Rotterdam-Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Figure 1. 244
Ulcerative lesion on the prepuce.
Donovanosis Niemel et al.
Figure 2.
Kissing ulcer in the vulva.
DIFFERENTIAL DIAGNOSIS AND LABORATORY INVESTIGATIONS
Figure 3. Sclerotic ulcerating lesion. Genital lesions in donovanosis must be differentiated from syphilis, chancroid, herpes progenitalis, lymphogranuloma venereum, candidiasis, anogenital cutaneous amebiasis, and traumatic ulcers. Ulcers may mimic carcinoma or neoplasms, especially in longstanding lesions of GI. Lesions located extragenitally must be differentiated from tuberculosis, histoplasmosis, filariasis, leishmaniasis, actinomycosis, or fixed drug eruption. As well as the clinical picture, laboratory confirmation by demonstration of typical Donovan bodies in direct tissue smears from tissue scrapings—using Giemsa's, Leishman's, or Wright's staining method, or in biopsy material, staining by hematoxylin and eosin, a silver staining method, or slow-Giemsa stain'—is necessary to confirm the diagnosis of donovanosis. The intra- and/or extracellular micro-organisms exhibit bipolar staining and resemble closed safety pins. Unfortunately, reliable cultural techniques and serologic tests are not yet available for routine investigations.
THERAPY
The current recommended treatment regimen consists of trimethoprim (80 mg) and sulfamethoxazoie (400 mg), two tablets twice daily for at least 2 weeks.'"'" An alternative therapy consists of oral tetracycline separate or in combination with streptomycin by intramuscular injection.'- Erythromycin, especially during pregnancy, gentamicin, and chloramphenicol are other alternatives. After treatment, prolonged follow-up is necessary to assess the effect of therapy. Relapses or reinfection may occur in some cases, after apparently successful initial treatment.
Figure 4. Extragenital extensive ulcerative disease. CONCLUSION
Although donovanosis has become a rarity in the United States and Europe, a diagnosis of donovanosis must be considered in patients originating from endemic regions. There are many reasons to explain why this dis245
International Journal of Dermatology Vol. 31, No. 4, April 1992
ease has not been eradicated; for example, neglect of the disease, ignorance in large populations about sexually transmitted diseases in general, unfamiliarity with the disease in the medical profession, limited understanding of the pathogenesis and the epidemiology, the lack of simple and reliable inexpensive serologic tests for the diagnosis, in combination with the protean manifestations of granuloma inguinale. Recently, it has been reported that GI has remained unrecognized for nearly half a century in South Africa, due to a lack of awareness. This underlines the importance of continuing surveillance for the disease.'-' The importance of genital ulcerations in the transmission of HIV infection has recently been postulated.''' The limited data which are available have demonstrated strong associations between HlV-seropositivity and infectious syphilis, genital herpes simplex infection, and chancroid. The precise interrelationship between genital ulcerative disease including donovanosis and HIV infection remains undetermined. We suspect that the easily bleeding and usually painless ulcers in donovanosis may also facilitate the transmission of HIV infection. Frequently, patients presenting with donovanosis suffer from other STD. With limited financial resources for laboratory equipment in many parts of the world, and the absence of efficient screening methods, continued outbreaks of this disease seem likely. The biology and pathogenesis of Calymmatobacterium granulomatis are not fully understood. Treatment strategies for donovanosis have currently been effective. A possible association of donovanosis with neoplasms in the genital area has not yet been fully elucidated and requires further study.'-'' Early diagnosis of donovanosis is critical to therapeutic outcome. Untreated disease is associated with mutilation and prolonged morbidity. More research is needed.
REFERENCES
2.
Hoyer H, Weismann K. Granuloma venereum. Eine seltene, importierte Geschlechtskrankheit. Hautarzt 1981; 32:374-375.
3.
Bondeson J, Bohe M, Carlsson U, et al. Perianal abscess and sinuses caused by granuloma inguinale. Gase report. Acta Ghir Scand 1989; 155:607-610.
4.
Kuherski T, Papadimitriou JM, Phillips P. Ultrastructure of Calymmatobacterium granulomatis in lesions of granuloma inguinale. J Infect Dis 1980; 142:744-749. Goovadia YM, Steinberg JL, Kharsany A. Granuloma inguinale (donovanosis) of the oral cavity. A case report. S Afr Med J 1985; 68:815-817.
5.
6.
7.
8.
9.
10.
11.
12.
13. 14.
• . ; . , :
15. 1.
Rosen T, Tschen JA, Ramsdell W, et al. Granuloma inguinale. J Am Acad Dermatol 1984; 11:433-437.
Schneider J, O'Shea J, Finlay-Jones LR, et al. Extragenital donovanosis: three cases from Western Australia. Genitourin Med 1986; 62:196-201. Rajam RV, Rangiah PN. Donovanosis (granuloma inguinale, granuloma venereum). WHO Monograph Series, no. 24. Geneva: World Flealth Organization, 1954. Sehgal VN, Jain MK, Sharma VK. Pseudoelephantiasis induced by donovanosis. Genitourin Med 1987; 63: 54-56. Sehgal VN, Jain MK. Tissue section Donovan bodies identification through slow-Giemsa (overnight) technique. Dermatologica 1987; 174:228-231. Lai S, Garg BR. Further evidence of the efficacy of cotrimoxazole in granuioma venereum. Br J Vener Dis 1980; 56:412-413. STD Treatment Strategies. WHO Consultation on Development of Sexually Transmitted Diseases Treatment Strategies. Geneva: World Health Organization. WHO/ VDT/89.447; September 1989. Latif AS, Mason PR, Paraiwa F. The treatment of donovanosis (granuloma inguinale). Sex Transm Dis 1988; 15:27-29. Freinkel AL. The enigma of granuloma inguinale in South Africa. S Afr Med J 1990; 77:301-303. Global Programme on AIDS and Programme of STD. Consensus statement from consultation on sexually transmitted diseases as a risk factor for HIV transmission. Geneva: World Health Organization. WHO/ GPA/INF/89.I; January 1989. Sengupta BS. Vulvar carcinoma in premenopausal Jamaican women. Int J Gynaecol Obstet 1980; 17: 526 -530.
SPTS. TURPENTINE The dose tor ordfnmry purposes is from 5to 40 drops, repeated •very hour or two in acute, and three or four dines a day ia chronic diseases. It may be eivrn OD su^ar r r in cmulalon.
DBS.
A. il. & L . E. METER, Props
THiaODAUX.
LOUISIANA
From the collection of "La Pharmacie Frangaise," New Orleans, Louisiana, Mr. Ben Bavly, Curator. 246
