REPORT
GRANULOMA INGUINALE: THREE CASES DIAGNOSED IN TORONTO, CANADA PETER HACKER, M.D., E.R,C,P,C,, BENJAMIN K, EISHER, M.D,, F,R,C,P,C., JOEL DEKOVEN, M,D,, E.R,C,P,C,, AND R, MICHAEL SHIER, M,D,, E.R.C.S.C.
Abstract Granuloma inguinale (GI) is a sexually transmitted disease seldom seen in the United States and Canada, We are reporting three cases recently seen in Toronto, Ontario, two in immigrants, and one in a native born Canadian who had an intimate relationship with a foreign visitor. The basic features of the disease are discussed, IntJ Dermatol 1992; 31:696-699 Granuloma inguinale (donovanosis) is one of tbe "classic" sexually transmitted diseases. It is endemic in different parts of the world, such as Papua New Guinea,' India,^'^ and South America,"* but it is infrequently seen in Europe and North America. We are reporting three cases of the disease diagnosed in three unrelated patients seen within a period of a few weeks in Toronto, Canada. Case Reports Case 1: A 22-year-old man developed a progressive eruption on his penis in 1989, the same year in which he had immigrated to Canada from El Salvador, The eruption was only minimally symptomatic. He had married in 1988 and stated that he always used a condom during sexual intercourse. On examination, there were eight beefy-red nodules, measuring 3 to 6 mm in diameter on the foreskin of the penis (Fig, 1), Several of the lesions were ulcerated. The ulcers were shallow and had a foul odor. There was no regional lymphadenopathy. On a skin biopsy and a thin tissue smear stained with Giemsa, Donovan bodies were demonstrated (Fig, 2), The patient was treated with tetracycline, 500 mg four times daily. Significant improvement was noted in 2 weeks. At this time, there was only minimal scarring of the foreskin. The wife was examined and no sign of the disease was found. She was, however, given a 2 week course of tetracycline.
From the Divisions of Dermatology and Obstetrics and Gynecology, The Wellesley Hospital, Women's College Hospital and the University of Toronto Faculty of Medicine, Toronto, Ontario, Canada.
Figure 1. (case 1).
Multiple ulcerated red-beefy nodules on penis
Figure 2. Tissue smear from a lesion in Fig. 1. Within a histiocyte a group of bipolar "safety-pin-like", Calymmatobacteria (Donovan bodies) can be seen (Case 1). (Giemsa stain, original magnification xlOO)
Address for correspondence: Benjamin K. Fisher, M,D., The Wellesley Hospital, 160 Wellesley Street East, Suite 326 Jones Building, Toronto, ONT, Canada M4Y 1J3. 696
Granuloma Inguinale Hacker ct al.
Case 2: A 22-year-old white woman was admitted to the Obstetrical Service with a 4 month history of a painful vulvar eruption, which was gradually getting worse. The patient was in her 5th month of pregnancy and was a G5 P2 A2, Her past medical history included syphilis diagnosed 2 years previously and treated with benzathine penicillin, 2,4 million units. Her current sexual partner, the prospective father, was a visitor from Turkey, He could not be located because he had returned to his native country. The patient had not noted any obvious genital lesions in her sexual partner. On examination, there were three foul smelling erythematous, ulcerated nodules, 4 to 8 mm in diameter, one in the fourchette, two on the labia majora (Fig, 3), There were three small, mobile, nontender left inguinal nodes palpable. Her VDRL was reactive 1,4, An HIV test was negative. The first skin biopsy showed a nonspecific inflammatory reaction, A second biopsy and a semi-thin section as well as Giemsastained tissue smear showed Donovan bodies (Figs, 4 and 5), Because of her pregnancy the patient was treated with erythromycin, 500 mg four times a day. Improvement was evident in 1 week and after 4 more weeks of treatment, the vulvar area appeared normal. She was also retreated for syphilis with benzathine penicillin, 2,4 million units. The patient delivered a healthy infant 4 months later. Case 3: A 30-year-old Jamaican black woman, who had been in Canada for several years was referred to the Sexu-
Figure 4. Several Donovan bodies seen in pale histiocytes surrounded by a mixed inflammatory infiltrate with plasma cells (case 2). (hematoxylin and eosin, original magnification xlOO) ally Transmitted Diseases Clinic for assessment of a slightly painful ulcer, which had been present for 2 weeks, on the right labium majus. The patient stated that over the preceding year she had had sexual intercourse with only one partner, a man who had recently immigrated from Jamaica, The last sexual contact had occurred about 1 week before the onset of symptoms. Examination revealed three well-demarcated ulcers ranging in size from 0,6 to 2 cm in diameter on the right labium majus. All had slightly raised edges; the largest had a mildly exuberant beefy red appearance. Over the same site, there also were scattered punched-out ulcers 2 mm in diameter, with a few small erythematous papules, A discrete 1 cm tender lymph node was palpable in the right inguinal area, A speculum examination revealed a 2 cm grayish plaque on the cervix. The working clinical diagnosis was genital herpes simplex virus infection. Herpes simplex was indeed isolated from a direct swab of the lesions, Histologic examination of a punch biopsy specimen of one of the larger ulcers showed irregularly acanthotic epidermis with an infiltrate of polymorphs within the more superficial layers. The dermis was edematous and was filled with an infiltrate of both acute and chronic inflammatory cells. Special stains for organisms were negative; however, a modified Wright stain of a crush preparation taken from one of the
Figure 3. Ulcerated nodules on labia majora and in fourchette area (case 2). 697
International Journal of Dermatology Vol, 31, No. 10, October 1992
Table 1: Reported cases of Granuloma Inguinale in the United States (selected years). Summary of Notifiable Diseases, Centers for Disease Control, Atlanta, Georgia, 1991. Year
No. of Reported Cases
1950 1960 1970 1980 1990
1783 296 124 51 97
from Turkey. The third one was an immigrant in Canada for several years, who had had a sexual relationship with a recently immigrated Jamaican. We cannot comment on the incubation period from our cases, but it is worthwhile to note that condoms seem to have good protective value since the wife of our first case did not become infected during the 2 years of married life. The disease is caused by Calymmatobacterium granulomatis, an encapsulated gram-negative pleomorpbic rod-shaped bacterium. It may be extracellular or intracellular. Tbe diagnosis is made by tissue smear or biopsy. A semithin section used for electron microscopy, where possible, is excellent to show the presence of organisms. On smears or tissue sections, clumps of the organism are seen in histiocytes. These are called Donovan bodies. Clinically, the commonly involved areas are the penis, perianal region, vulva, vagina, and cervix, although extragenital involvement may also occur.'^''^-^^ The disease may be divided into three stages:'^ the exuberant stage, when nodules consisting of overgrowth of granulation tissue are seen; the ulcerative stage, where there are shallow ulcers of a foul odor; and the cicatricial stage, associated with scarring. The disease also spreads by auto-inoculation. Regional lymph nodes are usually not involved. Erythromycin or trimethoprim-sulfamethoxazole taken for 2 weeks is a safe and effective treatment.''•* Tetracycline is usually effective, but resistance has been reported.^" Recently norfloxacin, 400 mg twice a day for 7 to 10 days, has been found to be effective.^' As these three cases demonstrate, the possibility of granuloma inguinale should always be considered in tbe differential diagnosis of a genital lesion, particularly when it is ulcerated.
Figure 5. Semi-thin section showing Donovan bodies in histiocytes (case 2). larger ulcers revealed typical Donovan bodies establishing the diagnosis of granuloma inguinale. Cervical cultures for Chiamydia trachomatis, Neisseria gonorrhoeae, aerobic bacterial pathogens, Candida aibicans, and direct swabs of the lesions for Hemophilus ducreyi, darkfield microscopy, and serologic tests for lymphogranuloma venereum and syphilis were all negative, HIV serology was not tested. The patient was treated with doxycycline, 100 mg twice a day for 3 weeks. On re-examination following the treatment, no evidence of disease was found. The sexual partner could not be traced.
DISCUSSION
Granuloma inguinale and other "classic" sexually transmitted diseases, such as lymphogranuloma venereum and chancroid, have been mostly relegated to the realm of textbooks and board examinations, rather tban to current diagnostic literature. Tbere have, however, been reports of Gi during the past years from the USA; between 1973 and 1983, 13 cases in women bave been observed in an Atlanta, Georgia hospital,' and an epidemic of 20 cases was chronicled in 1984.'' Isolated case reports from developed countries include ones from Canada,^ Sweden,* Italy,' France,^" and Japan.'' In Canada, there is no national reporting system for GI. In the United States, GI is reportable in most states (Table 1).'^'" It is quite possible that under-reporting, decreased awareness, and difficulties in making the diagnosis account for the very low numbers of cases reported in recent years. Consideration should be given to designating Gl a reportable disease throughout Canada. With rising international travel and immigration, the disease may be seen with increasing frequency in any geographic location. Moreover, genital ulceration may be an important risk factor for the sexual transmission of the human immunodeficiency virus.'"• One of our patients was a recent immigrant from El Salvador. Another was a native-born Canadian, wbo has never been out of the country, but whose latest sexual partner had come
DRUG NAMES
tetracycline: Robitet, Sumycin, and others benzathine penicillin: Permapen erythromycin: Erythrocin, Robimycin, and others doxycyline: Vibramycin trimethoprim-sulfamethoxazole: Bactrim, Septra norfloxacin: Noroxin 698
Ciranulonia Inguinale Hacker et al.
REEERENCES
11,
1,
Vogel LC, Richens J, Donovanosis in Dutch South New Guinea: history, evolution of the epidemic and control, Papua New Guinea Med J 1989; 32:203-218.
12,
2,
Sehgal VN, Jain MK, Pattern of epidemics of donovanosis in the "non-endemic" region, Int | Dermatol 1988; 27:396-399,
3,
Sayal SK, Kar PK, Anand LC, A study of 255 cases of granuloma inguinale, Indian J Dermatol 1987; 32: 91-97.
4,
Pradinaud R. Epidemiology and pathogenesis of donovanosis. Med Cutan Ibero Lat Am 1986; 14:153-156, Wysoki RS, Majmudar B, Willis D. Granuloma inguinale (donovanosis) in women, J Reprod Med 1988; 33:709-713,
5,
6, 7,
8,
9, 10,
Rosen T, Tschen JA, Ramsdell W, et al, Granuloma inguinale, J Am Acad Dermatol 1984; 11:433-437, Diaz-Mitoma F, Benningen G, Slutchuk M, et al. Etiology of nonvesicular genital ulcers in Winnipeg. Sex Transm Dis 1987; 14:33-36, Bondeson J, Bohe M, Carlsson U, et al, Perianal abscess and sinuses caused by granuloma inguinale. Case report, Acta Chir Scand 1989; 155:607-610, Ena P, Fiori PI, Zanetti S. Donovanosis. Presentation of a case, G Ital Dermatol Venereol 1988; 123:167-169, Marchand C, Fayol D, Gaboriaux MC, et al. Donovanosis, a propos of a new case of granuloma inguinale in France. Ann Med Interne (Paris) 1986; 137:656-659.
13, 14,
Fujiwara S, Honda T, Shinkai, et al, A case of donovanosis in Japan, J Dermatol (Tokyo) 1987; 14:375-377. Summary of notifiable diseases. United States 1989. MMWR 1990; 38(No.54):53-59, Sexually Transmitted Diseases Surveillance 1990, Centres for Disease Control, Atlanta, Georgia, page 139, Cameron DW, Simonsen JN, D'Costa LJ, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989; ii:403-407,
15.
Freinkel AL, Granuloma inguinale of cervical lymph nodes simulating tuberculous lymphadenitis: two case reports and review of published reports, Genitourin Med 1988; 64:339-343, 16. Leiman G, Markowitz S, Margolius KA, Cytologic detection of cervical granuloma inguinale, Diagn Cytopathol 1986; 2:138-143, 17. Coovadia YM, Steinberg JL, Kharsany A, Granuloma inguinale (donovanosis) of the oral cavity, A case report, S Afr Med J 1985; 68:815-817, 18. Faro S, Lymphogranuloma venereum, chancroid and granuloma inguinale, Obstet Gynecol Clin North Am 1989; 16:517-530. 19, Ronald AR, Plummer FA, Chancroid and granuloma inguinale, Clin Lab Med 1989; 9:535-543. 20. Pariser RJ, Tetracycline-resistant granuloma inguinale. Arch Dermatol 1977; 113:988, 21, Ramanan C, Sarma PSA, Ghorpade A, et al. Treatment of donovanosis with uorfloxacin, Iut J Dermatol 199029:298.
Native American-inspired tattoo pattern by Ed Hardy of San Francisco and Honolulu. From the collection of Norman Goldstein, M.D., The World of Tattoos, Honolulu, Hawaii. 699
GRANULOMA INGUINALE: THREE CASES DIAGNOSED IN TORONTO, CANADA PETER HACKER, M.D., E.R,C,P,C,, BENJAMIN K, EISHER, M.D,, F,R,C,P,C., JOEL DEKOVEN, M,D,, E.R,C,P,C,, AND R, MICHAEL SHIER, M,D,, E.R.C.S.C.
Abstract Granuloma inguinale (GI) is a sexually transmitted disease seldom seen in the United States and Canada, We are reporting three cases recently seen in Toronto, Ontario, two in immigrants, and one in a native born Canadian who had an intimate relationship with a foreign visitor. The basic features of the disease are discussed, IntJ Dermatol 1992; 31:696-699 Granuloma inguinale (donovanosis) is one of tbe "classic" sexually transmitted diseases. It is endemic in different parts of the world, such as Papua New Guinea,' India,^'^ and South America,"* but it is infrequently seen in Europe and North America. We are reporting three cases of the disease diagnosed in three unrelated patients seen within a period of a few weeks in Toronto, Canada. Case Reports Case 1: A 22-year-old man developed a progressive eruption on his penis in 1989, the same year in which he had immigrated to Canada from El Salvador, The eruption was only minimally symptomatic. He had married in 1988 and stated that he always used a condom during sexual intercourse. On examination, there were eight beefy-red nodules, measuring 3 to 6 mm in diameter on the foreskin of the penis (Fig, 1), Several of the lesions were ulcerated. The ulcers were shallow and had a foul odor. There was no regional lymphadenopathy. On a skin biopsy and a thin tissue smear stained with Giemsa, Donovan bodies were demonstrated (Fig, 2), The patient was treated with tetracycline, 500 mg four times daily. Significant improvement was noted in 2 weeks. At this time, there was only minimal scarring of the foreskin. The wife was examined and no sign of the disease was found. She was, however, given a 2 week course of tetracycline.
From the Divisions of Dermatology and Obstetrics and Gynecology, The Wellesley Hospital, Women's College Hospital and the University of Toronto Faculty of Medicine, Toronto, Ontario, Canada.
Figure 1. (case 1).
Multiple ulcerated red-beefy nodules on penis
Figure 2. Tissue smear from a lesion in Fig. 1. Within a histiocyte a group of bipolar "safety-pin-like", Calymmatobacteria (Donovan bodies) can be seen (Case 1). (Giemsa stain, original magnification xlOO)
Address for correspondence: Benjamin K. Fisher, M,D., The Wellesley Hospital, 160 Wellesley Street East, Suite 326 Jones Building, Toronto, ONT, Canada M4Y 1J3. 696
Granuloma Inguinale Hacker ct al.
Case 2: A 22-year-old white woman was admitted to the Obstetrical Service with a 4 month history of a painful vulvar eruption, which was gradually getting worse. The patient was in her 5th month of pregnancy and was a G5 P2 A2, Her past medical history included syphilis diagnosed 2 years previously and treated with benzathine penicillin, 2,4 million units. Her current sexual partner, the prospective father, was a visitor from Turkey, He could not be located because he had returned to his native country. The patient had not noted any obvious genital lesions in her sexual partner. On examination, there were three foul smelling erythematous, ulcerated nodules, 4 to 8 mm in diameter, one in the fourchette, two on the labia majora (Fig, 3), There were three small, mobile, nontender left inguinal nodes palpable. Her VDRL was reactive 1,4, An HIV test was negative. The first skin biopsy showed a nonspecific inflammatory reaction, A second biopsy and a semi-thin section as well as Giemsastained tissue smear showed Donovan bodies (Figs, 4 and 5), Because of her pregnancy the patient was treated with erythromycin, 500 mg four times a day. Improvement was evident in 1 week and after 4 more weeks of treatment, the vulvar area appeared normal. She was also retreated for syphilis with benzathine penicillin, 2,4 million units. The patient delivered a healthy infant 4 months later. Case 3: A 30-year-old Jamaican black woman, who had been in Canada for several years was referred to the Sexu-
Figure 4. Several Donovan bodies seen in pale histiocytes surrounded by a mixed inflammatory infiltrate with plasma cells (case 2). (hematoxylin and eosin, original magnification xlOO) ally Transmitted Diseases Clinic for assessment of a slightly painful ulcer, which had been present for 2 weeks, on the right labium majus. The patient stated that over the preceding year she had had sexual intercourse with only one partner, a man who had recently immigrated from Jamaica, The last sexual contact had occurred about 1 week before the onset of symptoms. Examination revealed three well-demarcated ulcers ranging in size from 0,6 to 2 cm in diameter on the right labium majus. All had slightly raised edges; the largest had a mildly exuberant beefy red appearance. Over the same site, there also were scattered punched-out ulcers 2 mm in diameter, with a few small erythematous papules, A discrete 1 cm tender lymph node was palpable in the right inguinal area, A speculum examination revealed a 2 cm grayish plaque on the cervix. The working clinical diagnosis was genital herpes simplex virus infection. Herpes simplex was indeed isolated from a direct swab of the lesions, Histologic examination of a punch biopsy specimen of one of the larger ulcers showed irregularly acanthotic epidermis with an infiltrate of polymorphs within the more superficial layers. The dermis was edematous and was filled with an infiltrate of both acute and chronic inflammatory cells. Special stains for organisms were negative; however, a modified Wright stain of a crush preparation taken from one of the
Figure 3. Ulcerated nodules on labia majora and in fourchette area (case 2). 697
International Journal of Dermatology Vol, 31, No. 10, October 1992
Table 1: Reported cases of Granuloma Inguinale in the United States (selected years). Summary of Notifiable Diseases, Centers for Disease Control, Atlanta, Georgia, 1991. Year
No. of Reported Cases
1950 1960 1970 1980 1990
1783 296 124 51 97
from Turkey. The third one was an immigrant in Canada for several years, who had had a sexual relationship with a recently immigrated Jamaican. We cannot comment on the incubation period from our cases, but it is worthwhile to note that condoms seem to have good protective value since the wife of our first case did not become infected during the 2 years of married life. The disease is caused by Calymmatobacterium granulomatis, an encapsulated gram-negative pleomorpbic rod-shaped bacterium. It may be extracellular or intracellular. Tbe diagnosis is made by tissue smear or biopsy. A semithin section used for electron microscopy, where possible, is excellent to show the presence of organisms. On smears or tissue sections, clumps of the organism are seen in histiocytes. These are called Donovan bodies. Clinically, the commonly involved areas are the penis, perianal region, vulva, vagina, and cervix, although extragenital involvement may also occur.'^''^-^^ The disease may be divided into three stages:'^ the exuberant stage, when nodules consisting of overgrowth of granulation tissue are seen; the ulcerative stage, where there are shallow ulcers of a foul odor; and the cicatricial stage, associated with scarring. The disease also spreads by auto-inoculation. Regional lymph nodes are usually not involved. Erythromycin or trimethoprim-sulfamethoxazole taken for 2 weeks is a safe and effective treatment.''•* Tetracycline is usually effective, but resistance has been reported.^" Recently norfloxacin, 400 mg twice a day for 7 to 10 days, has been found to be effective.^' As these three cases demonstrate, the possibility of granuloma inguinale should always be considered in tbe differential diagnosis of a genital lesion, particularly when it is ulcerated.
Figure 5. Semi-thin section showing Donovan bodies in histiocytes (case 2). larger ulcers revealed typical Donovan bodies establishing the diagnosis of granuloma inguinale. Cervical cultures for Chiamydia trachomatis, Neisseria gonorrhoeae, aerobic bacterial pathogens, Candida aibicans, and direct swabs of the lesions for Hemophilus ducreyi, darkfield microscopy, and serologic tests for lymphogranuloma venereum and syphilis were all negative, HIV serology was not tested. The patient was treated with doxycycline, 100 mg twice a day for 3 weeks. On re-examination following the treatment, no evidence of disease was found. The sexual partner could not be traced.
DISCUSSION
Granuloma inguinale and other "classic" sexually transmitted diseases, such as lymphogranuloma venereum and chancroid, have been mostly relegated to the realm of textbooks and board examinations, rather tban to current diagnostic literature. Tbere have, however, been reports of Gi during the past years from the USA; between 1973 and 1983, 13 cases in women bave been observed in an Atlanta, Georgia hospital,' and an epidemic of 20 cases was chronicled in 1984.'' Isolated case reports from developed countries include ones from Canada,^ Sweden,* Italy,' France,^" and Japan.'' In Canada, there is no national reporting system for GI. In the United States, GI is reportable in most states (Table 1).'^'" It is quite possible that under-reporting, decreased awareness, and difficulties in making the diagnosis account for the very low numbers of cases reported in recent years. Consideration should be given to designating Gl a reportable disease throughout Canada. With rising international travel and immigration, the disease may be seen with increasing frequency in any geographic location. Moreover, genital ulceration may be an important risk factor for the sexual transmission of the human immunodeficiency virus.'"• One of our patients was a recent immigrant from El Salvador. Another was a native-born Canadian, wbo has never been out of the country, but whose latest sexual partner had come
DRUG NAMES
tetracycline: Robitet, Sumycin, and others benzathine penicillin: Permapen erythromycin: Erythrocin, Robimycin, and others doxycyline: Vibramycin trimethoprim-sulfamethoxazole: Bactrim, Septra norfloxacin: Noroxin 698
Ciranulonia Inguinale Hacker et al.
REEERENCES
11,
1,
Vogel LC, Richens J, Donovanosis in Dutch South New Guinea: history, evolution of the epidemic and control, Papua New Guinea Med J 1989; 32:203-218.
12,
2,
Sehgal VN, Jain MK, Pattern of epidemics of donovanosis in the "non-endemic" region, Int | Dermatol 1988; 27:396-399,
3,
Sayal SK, Kar PK, Anand LC, A study of 255 cases of granuloma inguinale, Indian J Dermatol 1987; 32: 91-97.
4,
Pradinaud R. Epidemiology and pathogenesis of donovanosis. Med Cutan Ibero Lat Am 1986; 14:153-156, Wysoki RS, Majmudar B, Willis D. Granuloma inguinale (donovanosis) in women, J Reprod Med 1988; 33:709-713,
5,
6, 7,
8,
9, 10,
Rosen T, Tschen JA, Ramsdell W, et al, Granuloma inguinale, J Am Acad Dermatol 1984; 11:433-437, Diaz-Mitoma F, Benningen G, Slutchuk M, et al. Etiology of nonvesicular genital ulcers in Winnipeg. Sex Transm Dis 1987; 14:33-36, Bondeson J, Bohe M, Carlsson U, et al, Perianal abscess and sinuses caused by granuloma inguinale. Case report, Acta Chir Scand 1989; 155:607-610, Ena P, Fiori PI, Zanetti S. Donovanosis. Presentation of a case, G Ital Dermatol Venereol 1988; 123:167-169, Marchand C, Fayol D, Gaboriaux MC, et al. Donovanosis, a propos of a new case of granuloma inguinale in France. Ann Med Interne (Paris) 1986; 137:656-659.
13, 14,
Fujiwara S, Honda T, Shinkai, et al, A case of donovanosis in Japan, J Dermatol (Tokyo) 1987; 14:375-377. Summary of notifiable diseases. United States 1989. MMWR 1990; 38(No.54):53-59, Sexually Transmitted Diseases Surveillance 1990, Centres for Disease Control, Atlanta, Georgia, page 139, Cameron DW, Simonsen JN, D'Costa LJ, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989; ii:403-407,
15.
Freinkel AL, Granuloma inguinale of cervical lymph nodes simulating tuberculous lymphadenitis: two case reports and review of published reports, Genitourin Med 1988; 64:339-343, 16. Leiman G, Markowitz S, Margolius KA, Cytologic detection of cervical granuloma inguinale, Diagn Cytopathol 1986; 2:138-143, 17. Coovadia YM, Steinberg JL, Kharsany A, Granuloma inguinale (donovanosis) of the oral cavity, A case report, S Afr Med J 1985; 68:815-817, 18. Faro S, Lymphogranuloma venereum, chancroid and granuloma inguinale, Obstet Gynecol Clin North Am 1989; 16:517-530. 19, Ronald AR, Plummer FA, Chancroid and granuloma inguinale, Clin Lab Med 1989; 9:535-543. 20. Pariser RJ, Tetracycline-resistant granuloma inguinale. Arch Dermatol 1977; 113:988, 21, Ramanan C, Sarma PSA, Ghorpade A, et al. Treatment of donovanosis with uorfloxacin, Iut J Dermatol 199029:298.
Native American-inspired tattoo pattern by Ed Hardy of San Francisco and Honolulu. From the collection of Norman Goldstein, M.D., The World of Tattoos, Honolulu, Hawaii. 699
