- Email: [email protected]
Anaerobic Balanoposthitis: Two Cases and Review of the Literature
Anaerobe (2000) 6, 11±14 doi:10.1006/anae.1999.0314
CLINICAL MEDICINE/PATHOGENESIS
Anaerobic Balanoposthitis: Two Cases and Review of the Literature ShahriarTavakoli-Tabasi1, Richard J. Hamill1,2,4, and Stephen B. Greenberg1,2,3* Departments of 1Medicine, 2 Microbiology and Immunology, Baylor College of Medicine, 3 Ben Tayb General Hospital and 4 Veterans Affairs Medical Center, Houston, TX 77030 (Received 25 May 1999; accepted in revised form 31 October 1999) Key Words: Anaerobe, Balanoposthitis, Balanitis, Provetella melaninogenica, Bacteroides
Anaerobic balanoposthitis is an infection of the glans penis and prepuce caused by anaerobic Gram-negative rods. It is characterized by intense inflammation and edema of the prepuce, superficial ulcers on the glans penis, foul-smelling subpreputial discharge, and bilateral inguinal lymphadenopathy. Infection tends to be locally destructive with severe tenderness of the penis and can result in considerable necrosis and tissue damage. The presence of a tight foreskin and sub-optimal hygienic practices seem to be a prerequisite for this condition to develop. Anaerobic Gram-negative rods belonging to the genus Bacteroides are the most commonly incriminated in the pathogenesis. Possible modes of transmission include contact with infected mucosal surfaces, such as during sexual intercourse, contamination by colonized saliva, or extension from the perirectal area. We report the first two cases of anaerobic balanoposthitis in HIV-positive patients and review the literature. Both patients had a previous history of sexually transmitted diseases and practiced sub-optimal hygiene. In both cases response to therapy was complete within 48±72 h. # 2000 Academic Press
Introduction Inflammation of the glans penis (balanitis) and the foreskin (posthitis) is referred to as balanoposthitis and can be caused by a variety of infectious and noninfectious processes [1]. Although the more common causes of balanoposthitis such as Candida spp. and
* Corresponding author. Stephen B. Greenberg, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Room 550E, Houston, TX, 77030, U.S.A. Tel: (713) 798-4775. Fax: (713) 790-0681. E-mail: [email protected].
1075±9964/00/010011 + 04 $35.00/0
Herpes simplex virus are well recognized, anaerobes have received little attention in the medical literature [2,3]. Anaerobic balanoposthitis is a serious condition that, in some studies, was as common as Candida balanoposthitis. It can result in local necrosis and potentially irreversible damage to the penis; yet it is readily treatable when recognized early [4]. Individuals suffering from this condition are likely to present to urology, sexually transmitted diseases, dermatology, or primary care clinics. Physicians practicing in such clinics should be aware of this condition and institute the appropriate diagnostic and therapeutic measures as soon as possible. # 2000 Academic Press
12
S. Tavakoli-Tabasi et al.
We report two cases of anaerobic balanoposthitis in this paper. Both patients were HIV-positive. We also review the available literature on this unusual infection. Case 1 A 45-year-old African-American male with AIDS and a history of syphilis and genital herpes infection presented to the medicine clinic with a chief complaint of painful penile lesions and discharge around the glans penis for 9 days. He had a CD4 count of 80 cells/ml and HIV-1 viral load of 90 000 RNA copies/mL while taking a combination of zidovudine, lamivudine, and saquinavir. He had been on suppressive doses of acyclovir for the previous 2 years. This was changed to a full dose of valacyclovir 500 mg twice a day after he called his primary care physician 9 days prior to this visit. He denied dysuria and had not noticed urethral discharge. On physical examination, the penile shaft was exquisitely tender and there was diffuse superficial ulceration on the glans, especially around the corona. A thin, purulent, grayish, non-foul smelling exudate was detected under the prepuce. No uretheral discharge was present. In the inguinal area there were multiple tender lymph nodes bilaterally, the largest of which measured less than 2 cm in diameter. Gram stains showed predominantly coccobacillary Gram-negative forms. Bacterial cultures grew three different nonfragilis Bacteroides spp. that were identified as Provetella melaninogenica. Bacteroides urealyticus, and Porphyromonas asaccharolytica (RapID ANAII biochemical identification kit, Innovation Diagnostic systems, L.P.). Viral cultures remained negative. The patient was started on oral metronidazole, 500 mg tid for 7 days, with complete resolution of the symptoms with 48 h. Case 2 A 28-year-old African American male was admitted to the urology service with a penile mass and severe penile tenderness for 1 month. He had a past medical history of gonococcal urethritis and chronic osteomyelitis of the right iliac bone secondary to a gunshot wound. There was no history of genital herpes. HIV serology was positive. On physical examination, the whole penis was exquisitely tender, swollen, and edematous. The foreskin was retracted and necrotic and formed a 262 cm irregular mass under the glans penis. Necrosis was limited to the foreskin. There were punctate superfical ulcerations on the glans and especially around the coronal sulcus. A profuse, foul smelling, brown-gray, purulent discharge was present
under the foreskin. There were multiple enlarged tender lymph nodes in the inguinal area, 2±2.5 cm in diameter, bilaterally. Due to suspicion for squamous cell carcinoma of the penis the patient underwent circumcision and debridement of the necrotic foreskin. Pathological examination showed a severe inflammatory reaction with neutrophil infiltration. There was no malignant transformation and there were no pathologic changes consistent with a viral infection. Intra-operative cultures grew Staphylococcus aureus and Prevotella melaninogenica (RapID ANA II biochemical identification kit, innovative Diagnostic systems, L.P.). Viral cultures were negative. The susceptibility pattern of the S. aureus was the same as the organism isolated from the sinus tract discharge form the iliac bone osteomyelitis for which he was already on vancomycin for 5 days. The patient was started on metronidazole 500 mg every 8 h for 7 days, with full resolution of his symptoms within 3 days. Unfortunately, the patient did not attend the HIV clinic for follow up, therefore, viral loads and CD4 counts could not be obtained.
Discussion Infection of the penis and prepuce (balanoposthitis) is a common condition in patients presenting to male genitourinary clinics [5]. In uncircumcised males, the preputial area provides a warm and moist environment that can support the growth of many organisms including anaerobic and aerobic bacteria, and Candida spp. Balanitis and balanoposthitis can be caused by a variety of infectious and non-infectious conditions [1]. Our two cases of anaerobic balanoposthitis illustrate the spectrum of this infection from mild, as in the first case, to severe as in the second case. Anaerobic balanoposthitis has been recognized for more than 100 years. Bataille and Berdal (1889±1891) were the first to describe a contagious form of balanoposthitis and they demonstrated its contiguousness experimentally [6]. Scherber and Muller isolated a spirillum and a vibrio from erosive cases of balanitis and recognized that gangrene and tissue necrosis could complicate the condition [7]. They named this disease the fourth venereal disease. Corbus and Harris in 1909 reported three cases of erosive and gangrenous balanitis [8]. They recognized that both the locally destructive nature of this entity and the microorganisms that were frequently isolated from the lesions were similar to the findings in noma. They isolated two organism from these cases, a spirochete and a ``vibrio''. Only the ``vibrio'' was present in the deep layers of the foreskin. Cultures of the preputial area from healthy men showed that the spirochete was sometimes present but the ``vibrio''
Anaerobic Balanoposthitis could not be found. ``Vibrio'' grew under anaerobic conditions only. Therefore, these investigators concluded that the erosive forms of balanoposthitis were caused by an anaerobic ``vibrio''. Cree et al. conducted a prospective study of 104 patients who presented with balanoposthitis [4]. In 98 cases an infectious etiology was identified. Anaerobic balanoposthitis was diagnosed clinically in 31 patients using the following criteria: (1) edema of the prepuce; (2) tender inguinal lymphadenopathy; (3) superficial ulceration of the glans penis especially around coronal sulcus; and (4) foul-smelling, purulent subpreputial discharge. Cultures of the subpreputial discharge confirmed the clinical diagnosis of anaerobic balanoposthitis in 29 cases and all cases responded to treatment with metronidazole. The most common anaerobic isolates were ``Bacteroides melaninogenicus'' (19), unidentified Bacteroides spp. (18), Bacteroides fragilis (9), and Fusobacterium spp. (4). There were 21 polymicrobial and eight monomicrobial cultures. In 15 of the polymicrobial cultures, organisms other than anaerobes were isolated in small numbers and were usually the components of normal skin flora, such as lactobacilli and Staphylococcus epidermidis. In six patients, however, other potential pathogens such as Trichomonas vaginalis, Candida albicans, Staphylococcus aureus, and HSV were isolated concomitantly with anaerobes. All eight monomicrobial cultures belonged to the Bacteroides spp. (currently reclassified as, Bacteroides, Prevotella, and Porphyromonas). Other common causes of balanoposthitis in this study were Candida spp., non-specific bacterial infections, and HSV. In a study of 150 men attending a genitourinary clinic, Masfari et al. were able to identify 79 cases of balanitis, posthitis, or balanoposthitis, and 19 cases of balanoposthitis with concomitant non-specific urethritis [9]. Non-specific urethritis was defined on the basis of the presence of more than 10 WBC per high power field in a urethral swab and a negative culture for Neisseria gonorrhea and Trichomonas vaginalis. Anaerobic bacteria were identified in 68% of the cases in the balanoposthitis/balanitis group and 84% of cases in balanoposthitis and urethritis group. Among 28 patients from the same population who did not have any genitourinary complaints, anaerobes were isolated in 6% of subjects and only in low numbers. The most common anaerobic isolates were ``Bacteroides asaccharolyticus'', ``Bacteroides urealyticus'', and ``Bacteroides melaninogenicus''. The presence of ulcerative and necrotic lesions was significantly predictive of isolation of anaerobes. Other anaerobic bacteria included anaerobic cocci and clostridia. Although anaerobic cocci were isolated from 30 cases, in 24 of these anaerobic Gram-negative rods belonging to the genus Bacteroides were also present in the cultures.
13
There was no statistically significant association between the presence of balanitis/balanoposthitis and isolation of anaerobic cocci. Chakraborty et al. studied 113 cases of balanoposthitis in India [10]. They found an infectious etiology in 92 (81.4%) of cases. The commonest infectious agents were HSV (22 cases), Hemophilus ducreyi (16 cases), and Candida (11 cases), followed by ``fusospirochetes'' and Chlamydia trachomatis (nine cases each). Fusospirochetes were isolated more frequently in the patients who practiced orogenital sex or used saliva as a lubricant during coitus. There is not a clear description of anaerobic cultures in the methods section, neither is there a clear distinction established between Fusobacterium spp. and spirochetes. In 1992, Abdullah et al. reported 86 cases of balanitis/balanoposthitis [11]. They found an infectious etiology in 47 cases. These included Candida (26), group B, beta-hemolytic streptococci (11), human papilloma virus (4), HSV (3), staphylococci, group A streptococci (1), and anaerobic streptococci (1). This group did not find any cases of balanoposthitis caused by anaerobic Gram-negative rods. Whether anaerobic cultures were performed in every case was not clear, however. In addition, the clinical characteristics and the severity of symptoms were not reported. Anaerobic Gram-positive cocci are a major part of normal urethral flora in men but the Gram-negative Bacteroides, Prevotella and Porphyromonas are generally not found [12]. On the other hand, B. urealyticus has been isolated as a normal urethral inhabitant in men and, in the studies of non-gonococcal urethritis, anaerobic Gram-negative rods including P. melaninogenica and Fusobacterium were present in eight out 30 asymptomatic subjects [13,14]. In addition Masfari et al. isolated low numbers of anaerobic Gram-negative rods from five out of the 28 healthy controls in their study [9]. These were P. asaccharolytica, P. melaninogenica, P. bivia, and P. disiens. Since Gram-negative anaerobic rods are the dominant flora of the GI tract and are commonly isolated from perirectal infections, it is conceivable that contamination of the urethra can occur as a result of direct extension from the peri-rectal area [15]. Once present under the prepuce, these bacteria may then proliferate and act as opportunistic pathogens whenever the milieu is suitable, such as in the presence of a tight foreskin and sub-optimal hygiene. Therefore, although the isolation of anaerobic Gram-negative rods, per se, may not be diagnostic, in the presence of appropriate clinical findings, as defined by Cree et al. recovery of these bacteria, in high numbers, is highly predictive of anaerobic balanoposthitis [4]. On the other hand, Gram-negative anaerobic rods are common inhabitants of the female vagina, as well as oral cavity [16,17]. Infection of male genitalia can
14
S. Tavakoli-Tabasi et al.
therefore be acquired through vaginal, rectal or oral sexual practices. This would support Bataille and Berdal's notion that the disease is contagious, as well as Scherber and MuÈller's notion that it is a sexually transmitted disease [6,7]. The organisms belonging to the genus Bacteroides including Prevotella, Porphyromonas, Bacteroides, and Fusobacterium are frequently implicated in locally destructive and ulcerative lesions such as cancrum oris and Vincent's angina [18]. In at least two of the studies mentioned above, there was a clear association between the presence of ulcerative and necrotic lesions and isolation of these organisms in high numbers [4,9]. The patient in case 2 had severe necrosis of the foreskin forming a mass of tissue with an unusual amount of edema extending to the base of the penis. This degree of necrosis had not been reported with other pathogens such as HSV or Candida. Presence of a tight foreskin and phimosis seems to be a prerequisite for this condition to develop. Hygienic practices were poor in most case reports and in both of our patients. Chakraborty and Data showed an association between low socioeconomic status and development of infectious balanoposthitis in general, and contamination with saliva and isolation of Fusarium spp. in particular [11]. Anaerobic Gram-negative rods produce various toxins, proteases, elastase, and other virulence factors [19,20]. Porphyromonas asaccharolytica, Prevotella intermedia, and P. melaninogenica have been shown to cleave lgA1. In addition, P. asaccharolytica and P. intermedia can cleave lgG [21]. The implication of these pathogenic properties and the interactions they may cause with the host remain to be studied. There are case reports of severe balanoposthitis in neutropenic patients caused by aerobic Gram-negative rods and Candida balanitis is associated with diabetes, but we could not find an association between anaerobic balanoposthitis and any systemic diseases [22,23]. We report the first two cases of anaerobic balanoposthitis in HIV-positive patients. Although in the first case HSV was not completely ruled out, the immediate response to therapy and isolation of Bacteroides supports the diagnosis of anaerobic balanoposthitis. Whether HIV-1 infection or AIDS predisposes patients to develop anaerobic balanoposthitis is not clear. Treatment of anaerobic balanoposthitis requires appropriate antibiotics and results in rapid resolution of the symptoms. In both cases presented here, response to therapy was complete within 48±72 h. In summary, anaerobic balanoposthitis is probably an under-recognized condition that occurs in uncircumcised males who present with subpreputial purulent discharge, penile tenderness, superficial
ulceration of the glans penis, and tender inguinal lymphadenpathy. Gram stains and anaerobic cultures should be performed in such cases and a prompt response to metronidazole is characteristic.
References 1. Edwards S. (1996) Balanitis and balanoposthitis: a review. Genitourin Med 72: 155±159 2. Vohra S. and Badlani G. (1992) Balanitis and balanoposthitis. Urol Clin North Am 19: 143±147 3. Mandell G.L., Bennett J.E. and Dolin R. (1995) Principles and Practice of Infectious Diseases. 4th Edn, Churchill Livingstone Inc., U.S.A. 4. Cree G.E., Willis A.T., Phillips K.D. and Brazier J.S. (1982) Anaerobic balanoposthitis. BMJ 284: 859±860 5. Birley H.D.L., Walker M.M., Luzzi G.A. et al. (1993) Clinical features and management of recurrent balanitis; association with atopy and genital washing. Genitourin Med 69: 400±403 6. Berdal H. and Bataille A. (1891) La balano-posthite eÂrosive circineÂe. MeÂd Mod ii: 340±342; 380±384; 400±403; 413±418 7. MuÈller R. and Scherber G. (1904) Zur aÈtiologie und klinik der balanitis erosiva circinata und balanitis gangraenosa. Arch Dermat u Syph xxvi: 77±109 8. Corbus B.C. and Harris F.G. (1909) Erosive and gangrenous balanitis. The fourth venereal disease. JAMA 52: 1474±1477 9. Masfari A.N., Kinghorn G.R. and Duerden B.I. (1978) Anaerobes in genitourinary infection in men. Br J Vener Dis 59: 255±259 10. Chakraborty A.K. and Datta A.K. (1979) Balanoposthitis in male. Indian J Dermatol 24: 17±27 11. Abdullah A.N., Drake S.M., Wade A.A.H. and Walzman M. (1992) Balanitis (balanoposthitis) in patients attending a department of genitourinary medicine. Int J STD AIDS 3: 128±129 12. Duerden B.I. (1993) Black-pigmented Gram-negative anaerobes in genito-urinary tract and pelvic infections. FEMS Immunol Med Microbiol 6: 223±227 13. Bennett K.W., Eley A., Woolley P.D. and Duerden B.I. (1989) Isolation of Bacteroides ureolyticus from the genital tract of men with and without non-gonococcal urethritis. Eur J Clin Microbiol Infect Dis 9: 125±126 14. Fontaine E.A., Taylor-Robinson D., Hanna N.F. and Coufalik E.D. (1982) Anaerobes in men with urethritis. Br J Vener Dis 58: 321±326 15. Meislin H.W., Lerner S.A., Graves M.H., McGehee M.D., Kocka F.E., Morello J.A. and Rosen P. (1977) Cutaneous abscesses: anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 87: 145±149 16. Hentges D.J. (1993) The anaerobic microflora of the human body. Clin Infect Dis 16: S175±180 17. Hillier S.L., Krohn M.A., Rabe L.K., Klebanoff S.J. and Eschenbach D.A. (1993) The normal vaginal flora, H2O2producing lactobacilli, and bacterial vaginosis in pregnant women. Clin Infect Dis 16: S273±281 18. Enwonwu C.O. (1995) Noma: a neglected scourge of children in sub-Saharna Africa. Bull WHO 73: 541±545 19. Beighton D., Homer K.A. and de Graaf J. (1997) Endopeptidase activities of selected Porphyromonas spp., Prevotella spp. and Fusobacterium spp. of oral and non-oral origin. Arch Oral Biol 42: 827±834 20. Langworth B.L. (1977) Fusobacterium necrophorum: its characteristics and role as an animal pathogen. Bacteriol Rev 41: 373±390 21. Killian M. (1981) Degradation of immunoglobulins A1, A2, and G by suspected principal periodontal pathogens. Infect Immun 34: 757±765 22. Manian F.A. and Akford R.H. (1987) Nosocomial infectious balanoposthitis in neutropenic patients. South Med J 80: 909±911 23. Waugh M.A., Evans E.G.V., Nayyar K.C. and Fong R. (1978) Clotrimazole in the treatment of candidal balanitis in men. Br J Vener Dis 54: 184±186
CLINICAL MEDICINE/PATHOGENESIS
Anaerobic Balanoposthitis: Two Cases and Review of the Literature ShahriarTavakoli-Tabasi1, Richard J. Hamill1,2,4, and Stephen B. Greenberg1,2,3* Departments of 1Medicine, 2 Microbiology and Immunology, Baylor College of Medicine, 3 Ben Tayb General Hospital and 4 Veterans Affairs Medical Center, Houston, TX 77030 (Received 25 May 1999; accepted in revised form 31 October 1999) Key Words: Anaerobe, Balanoposthitis, Balanitis, Provetella melaninogenica, Bacteroides
Anaerobic balanoposthitis is an infection of the glans penis and prepuce caused by anaerobic Gram-negative rods. It is characterized by intense inflammation and edema of the prepuce, superficial ulcers on the glans penis, foul-smelling subpreputial discharge, and bilateral inguinal lymphadenopathy. Infection tends to be locally destructive with severe tenderness of the penis and can result in considerable necrosis and tissue damage. The presence of a tight foreskin and sub-optimal hygienic practices seem to be a prerequisite for this condition to develop. Anaerobic Gram-negative rods belonging to the genus Bacteroides are the most commonly incriminated in the pathogenesis. Possible modes of transmission include contact with infected mucosal surfaces, such as during sexual intercourse, contamination by colonized saliva, or extension from the perirectal area. We report the first two cases of anaerobic balanoposthitis in HIV-positive patients and review the literature. Both patients had a previous history of sexually transmitted diseases and practiced sub-optimal hygiene. In both cases response to therapy was complete within 48±72 h. # 2000 Academic Press
Introduction Inflammation of the glans penis (balanitis) and the foreskin (posthitis) is referred to as balanoposthitis and can be caused by a variety of infectious and noninfectious processes [1]. Although the more common causes of balanoposthitis such as Candida spp. and
* Corresponding author. Stephen B. Greenberg, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Room 550E, Houston, TX, 77030, U.S.A. Tel: (713) 798-4775. Fax: (713) 790-0681. E-mail: [email protected].
1075±9964/00/010011 + 04 $35.00/0
Herpes simplex virus are well recognized, anaerobes have received little attention in the medical literature [2,3]. Anaerobic balanoposthitis is a serious condition that, in some studies, was as common as Candida balanoposthitis. It can result in local necrosis and potentially irreversible damage to the penis; yet it is readily treatable when recognized early [4]. Individuals suffering from this condition are likely to present to urology, sexually transmitted diseases, dermatology, or primary care clinics. Physicians practicing in such clinics should be aware of this condition and institute the appropriate diagnostic and therapeutic measures as soon as possible. # 2000 Academic Press
12
S. Tavakoli-Tabasi et al.
We report two cases of anaerobic balanoposthitis in this paper. Both patients were HIV-positive. We also review the available literature on this unusual infection. Case 1 A 45-year-old African-American male with AIDS and a history of syphilis and genital herpes infection presented to the medicine clinic with a chief complaint of painful penile lesions and discharge around the glans penis for 9 days. He had a CD4 count of 80 cells/ml and HIV-1 viral load of 90 000 RNA copies/mL while taking a combination of zidovudine, lamivudine, and saquinavir. He had been on suppressive doses of acyclovir for the previous 2 years. This was changed to a full dose of valacyclovir 500 mg twice a day after he called his primary care physician 9 days prior to this visit. He denied dysuria and had not noticed urethral discharge. On physical examination, the penile shaft was exquisitely tender and there was diffuse superficial ulceration on the glans, especially around the corona. A thin, purulent, grayish, non-foul smelling exudate was detected under the prepuce. No uretheral discharge was present. In the inguinal area there were multiple tender lymph nodes bilaterally, the largest of which measured less than 2 cm in diameter. Gram stains showed predominantly coccobacillary Gram-negative forms. Bacterial cultures grew three different nonfragilis Bacteroides spp. that were identified as Provetella melaninogenica. Bacteroides urealyticus, and Porphyromonas asaccharolytica (RapID ANAII biochemical identification kit, Innovation Diagnostic systems, L.P.). Viral cultures remained negative. The patient was started on oral metronidazole, 500 mg tid for 7 days, with complete resolution of the symptoms with 48 h. Case 2 A 28-year-old African American male was admitted to the urology service with a penile mass and severe penile tenderness for 1 month. He had a past medical history of gonococcal urethritis and chronic osteomyelitis of the right iliac bone secondary to a gunshot wound. There was no history of genital herpes. HIV serology was positive. On physical examination, the whole penis was exquisitely tender, swollen, and edematous. The foreskin was retracted and necrotic and formed a 262 cm irregular mass under the glans penis. Necrosis was limited to the foreskin. There were punctate superfical ulcerations on the glans and especially around the coronal sulcus. A profuse, foul smelling, brown-gray, purulent discharge was present
under the foreskin. There were multiple enlarged tender lymph nodes in the inguinal area, 2±2.5 cm in diameter, bilaterally. Due to suspicion for squamous cell carcinoma of the penis the patient underwent circumcision and debridement of the necrotic foreskin. Pathological examination showed a severe inflammatory reaction with neutrophil infiltration. There was no malignant transformation and there were no pathologic changes consistent with a viral infection. Intra-operative cultures grew Staphylococcus aureus and Prevotella melaninogenica (RapID ANA II biochemical identification kit, innovative Diagnostic systems, L.P.). Viral cultures were negative. The susceptibility pattern of the S. aureus was the same as the organism isolated from the sinus tract discharge form the iliac bone osteomyelitis for which he was already on vancomycin for 5 days. The patient was started on metronidazole 500 mg every 8 h for 7 days, with full resolution of his symptoms within 3 days. Unfortunately, the patient did not attend the HIV clinic for follow up, therefore, viral loads and CD4 counts could not be obtained.
Discussion Infection of the penis and prepuce (balanoposthitis) is a common condition in patients presenting to male genitourinary clinics [5]. In uncircumcised males, the preputial area provides a warm and moist environment that can support the growth of many organisms including anaerobic and aerobic bacteria, and Candida spp. Balanitis and balanoposthitis can be caused by a variety of infectious and non-infectious conditions [1]. Our two cases of anaerobic balanoposthitis illustrate the spectrum of this infection from mild, as in the first case, to severe as in the second case. Anaerobic balanoposthitis has been recognized for more than 100 years. Bataille and Berdal (1889±1891) were the first to describe a contagious form of balanoposthitis and they demonstrated its contiguousness experimentally [6]. Scherber and Muller isolated a spirillum and a vibrio from erosive cases of balanitis and recognized that gangrene and tissue necrosis could complicate the condition [7]. They named this disease the fourth venereal disease. Corbus and Harris in 1909 reported three cases of erosive and gangrenous balanitis [8]. They recognized that both the locally destructive nature of this entity and the microorganisms that were frequently isolated from the lesions were similar to the findings in noma. They isolated two organism from these cases, a spirochete and a ``vibrio''. Only the ``vibrio'' was present in the deep layers of the foreskin. Cultures of the preputial area from healthy men showed that the spirochete was sometimes present but the ``vibrio''
Anaerobic Balanoposthitis could not be found. ``Vibrio'' grew under anaerobic conditions only. Therefore, these investigators concluded that the erosive forms of balanoposthitis were caused by an anaerobic ``vibrio''. Cree et al. conducted a prospective study of 104 patients who presented with balanoposthitis [4]. In 98 cases an infectious etiology was identified. Anaerobic balanoposthitis was diagnosed clinically in 31 patients using the following criteria: (1) edema of the prepuce; (2) tender inguinal lymphadenopathy; (3) superficial ulceration of the glans penis especially around coronal sulcus; and (4) foul-smelling, purulent subpreputial discharge. Cultures of the subpreputial discharge confirmed the clinical diagnosis of anaerobic balanoposthitis in 29 cases and all cases responded to treatment with metronidazole. The most common anaerobic isolates were ``Bacteroides melaninogenicus'' (19), unidentified Bacteroides spp. (18), Bacteroides fragilis (9), and Fusobacterium spp. (4). There were 21 polymicrobial and eight monomicrobial cultures. In 15 of the polymicrobial cultures, organisms other than anaerobes were isolated in small numbers and were usually the components of normal skin flora, such as lactobacilli and Staphylococcus epidermidis. In six patients, however, other potential pathogens such as Trichomonas vaginalis, Candida albicans, Staphylococcus aureus, and HSV were isolated concomitantly with anaerobes. All eight monomicrobial cultures belonged to the Bacteroides spp. (currently reclassified as, Bacteroides, Prevotella, and Porphyromonas). Other common causes of balanoposthitis in this study were Candida spp., non-specific bacterial infections, and HSV. In a study of 150 men attending a genitourinary clinic, Masfari et al. were able to identify 79 cases of balanitis, posthitis, or balanoposthitis, and 19 cases of balanoposthitis with concomitant non-specific urethritis [9]. Non-specific urethritis was defined on the basis of the presence of more than 10 WBC per high power field in a urethral swab and a negative culture for Neisseria gonorrhea and Trichomonas vaginalis. Anaerobic bacteria were identified in 68% of the cases in the balanoposthitis/balanitis group and 84% of cases in balanoposthitis and urethritis group. Among 28 patients from the same population who did not have any genitourinary complaints, anaerobes were isolated in 6% of subjects and only in low numbers. The most common anaerobic isolates were ``Bacteroides asaccharolyticus'', ``Bacteroides urealyticus'', and ``Bacteroides melaninogenicus''. The presence of ulcerative and necrotic lesions was significantly predictive of isolation of anaerobes. Other anaerobic bacteria included anaerobic cocci and clostridia. Although anaerobic cocci were isolated from 30 cases, in 24 of these anaerobic Gram-negative rods belonging to the genus Bacteroides were also present in the cultures.
13
There was no statistically significant association between the presence of balanitis/balanoposthitis and isolation of anaerobic cocci. Chakraborty et al. studied 113 cases of balanoposthitis in India [10]. They found an infectious etiology in 92 (81.4%) of cases. The commonest infectious agents were HSV (22 cases), Hemophilus ducreyi (16 cases), and Candida (11 cases), followed by ``fusospirochetes'' and Chlamydia trachomatis (nine cases each). Fusospirochetes were isolated more frequently in the patients who practiced orogenital sex or used saliva as a lubricant during coitus. There is not a clear description of anaerobic cultures in the methods section, neither is there a clear distinction established between Fusobacterium spp. and spirochetes. In 1992, Abdullah et al. reported 86 cases of balanitis/balanoposthitis [11]. They found an infectious etiology in 47 cases. These included Candida (26), group B, beta-hemolytic streptococci (11), human papilloma virus (4), HSV (3), staphylococci, group A streptococci (1), and anaerobic streptococci (1). This group did not find any cases of balanoposthitis caused by anaerobic Gram-negative rods. Whether anaerobic cultures were performed in every case was not clear, however. In addition, the clinical characteristics and the severity of symptoms were not reported. Anaerobic Gram-positive cocci are a major part of normal urethral flora in men but the Gram-negative Bacteroides, Prevotella and Porphyromonas are generally not found [12]. On the other hand, B. urealyticus has been isolated as a normal urethral inhabitant in men and, in the studies of non-gonococcal urethritis, anaerobic Gram-negative rods including P. melaninogenica and Fusobacterium were present in eight out 30 asymptomatic subjects [13,14]. In addition Masfari et al. isolated low numbers of anaerobic Gram-negative rods from five out of the 28 healthy controls in their study [9]. These were P. asaccharolytica, P. melaninogenica, P. bivia, and P. disiens. Since Gram-negative anaerobic rods are the dominant flora of the GI tract and are commonly isolated from perirectal infections, it is conceivable that contamination of the urethra can occur as a result of direct extension from the peri-rectal area [15]. Once present under the prepuce, these bacteria may then proliferate and act as opportunistic pathogens whenever the milieu is suitable, such as in the presence of a tight foreskin and sub-optimal hygiene. Therefore, although the isolation of anaerobic Gram-negative rods, per se, may not be diagnostic, in the presence of appropriate clinical findings, as defined by Cree et al. recovery of these bacteria, in high numbers, is highly predictive of anaerobic balanoposthitis [4]. On the other hand, Gram-negative anaerobic rods are common inhabitants of the female vagina, as well as oral cavity [16,17]. Infection of male genitalia can
14
S. Tavakoli-Tabasi et al.
therefore be acquired through vaginal, rectal or oral sexual practices. This would support Bataille and Berdal's notion that the disease is contagious, as well as Scherber and MuÈller's notion that it is a sexually transmitted disease [6,7]. The organisms belonging to the genus Bacteroides including Prevotella, Porphyromonas, Bacteroides, and Fusobacterium are frequently implicated in locally destructive and ulcerative lesions such as cancrum oris and Vincent's angina [18]. In at least two of the studies mentioned above, there was a clear association between the presence of ulcerative and necrotic lesions and isolation of these organisms in high numbers [4,9]. The patient in case 2 had severe necrosis of the foreskin forming a mass of tissue with an unusual amount of edema extending to the base of the penis. This degree of necrosis had not been reported with other pathogens such as HSV or Candida. Presence of a tight foreskin and phimosis seems to be a prerequisite for this condition to develop. Hygienic practices were poor in most case reports and in both of our patients. Chakraborty and Data showed an association between low socioeconomic status and development of infectious balanoposthitis in general, and contamination with saliva and isolation of Fusarium spp. in particular [11]. Anaerobic Gram-negative rods produce various toxins, proteases, elastase, and other virulence factors [19,20]. Porphyromonas asaccharolytica, Prevotella intermedia, and P. melaninogenica have been shown to cleave lgA1. In addition, P. asaccharolytica and P. intermedia can cleave lgG [21]. The implication of these pathogenic properties and the interactions they may cause with the host remain to be studied. There are case reports of severe balanoposthitis in neutropenic patients caused by aerobic Gram-negative rods and Candida balanitis is associated with diabetes, but we could not find an association between anaerobic balanoposthitis and any systemic diseases [22,23]. We report the first two cases of anaerobic balanoposthitis in HIV-positive patients. Although in the first case HSV was not completely ruled out, the immediate response to therapy and isolation of Bacteroides supports the diagnosis of anaerobic balanoposthitis. Whether HIV-1 infection or AIDS predisposes patients to develop anaerobic balanoposthitis is not clear. Treatment of anaerobic balanoposthitis requires appropriate antibiotics and results in rapid resolution of the symptoms. In both cases presented here, response to therapy was complete within 48±72 h. In summary, anaerobic balanoposthitis is probably an under-recognized condition that occurs in uncircumcised males who present with subpreputial purulent discharge, penile tenderness, superficial
ulceration of the glans penis, and tender inguinal lymphadenpathy. Gram stains and anaerobic cultures should be performed in such cases and a prompt response to metronidazole is characteristic.
References 1. Edwards S. (1996) Balanitis and balanoposthitis: a review. Genitourin Med 72: 155±159 2. Vohra S. and Badlani G. (1992) Balanitis and balanoposthitis. Urol Clin North Am 19: 143±147 3. Mandell G.L., Bennett J.E. and Dolin R. (1995) Principles and Practice of Infectious Diseases. 4th Edn, Churchill Livingstone Inc., U.S.A. 4. Cree G.E., Willis A.T., Phillips K.D. and Brazier J.S. (1982) Anaerobic balanoposthitis. BMJ 284: 859±860 5. Birley H.D.L., Walker M.M., Luzzi G.A. et al. (1993) Clinical features and management of recurrent balanitis; association with atopy and genital washing. Genitourin Med 69: 400±403 6. Berdal H. and Bataille A. (1891) La balano-posthite eÂrosive circineÂe. MeÂd Mod ii: 340±342; 380±384; 400±403; 413±418 7. MuÈller R. and Scherber G. (1904) Zur aÈtiologie und klinik der balanitis erosiva circinata und balanitis gangraenosa. Arch Dermat u Syph xxvi: 77±109 8. Corbus B.C. and Harris F.G. (1909) Erosive and gangrenous balanitis. The fourth venereal disease. JAMA 52: 1474±1477 9. Masfari A.N., Kinghorn G.R. and Duerden B.I. (1978) Anaerobes in genitourinary infection in men. Br J Vener Dis 59: 255±259 10. Chakraborty A.K. and Datta A.K. (1979) Balanoposthitis in male. Indian J Dermatol 24: 17±27 11. Abdullah A.N., Drake S.M., Wade A.A.H. and Walzman M. (1992) Balanitis (balanoposthitis) in patients attending a department of genitourinary medicine. Int J STD AIDS 3: 128±129 12. Duerden B.I. (1993) Black-pigmented Gram-negative anaerobes in genito-urinary tract and pelvic infections. FEMS Immunol Med Microbiol 6: 223±227 13. Bennett K.W., Eley A., Woolley P.D. and Duerden B.I. (1989) Isolation of Bacteroides ureolyticus from the genital tract of men with and without non-gonococcal urethritis. Eur J Clin Microbiol Infect Dis 9: 125±126 14. Fontaine E.A., Taylor-Robinson D., Hanna N.F. and Coufalik E.D. (1982) Anaerobes in men with urethritis. Br J Vener Dis 58: 321±326 15. Meislin H.W., Lerner S.A., Graves M.H., McGehee M.D., Kocka F.E., Morello J.A. and Rosen P. (1977) Cutaneous abscesses: anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 87: 145±149 16. Hentges D.J. (1993) The anaerobic microflora of the human body. Clin Infect Dis 16: S175±180 17. Hillier S.L., Krohn M.A., Rabe L.K., Klebanoff S.J. and Eschenbach D.A. (1993) The normal vaginal flora, H2O2producing lactobacilli, and bacterial vaginosis in pregnant women. Clin Infect Dis 16: S273±281 18. Enwonwu C.O. (1995) Noma: a neglected scourge of children in sub-Saharna Africa. Bull WHO 73: 541±545 19. Beighton D., Homer K.A. and de Graaf J. (1997) Endopeptidase activities of selected Porphyromonas spp., Prevotella spp. and Fusobacterium spp. of oral and non-oral origin. Arch Oral Biol 42: 827±834 20. Langworth B.L. (1977) Fusobacterium necrophorum: its characteristics and role as an animal pathogen. Bacteriol Rev 41: 373±390 21. Killian M. (1981) Degradation of immunoglobulins A1, A2, and G by suspected principal periodontal pathogens. Infect Immun 34: 757±765 22. Manian F.A. and Akford R.H. (1987) Nosocomial infectious balanoposthitis in neutropenic patients. South Med J 80: 909±911 23. Waugh M.A., Evans E.G.V., Nayyar K.C. and Fong R. (1978) Clotrimazole in the treatment of candidal balanitis in men. Br J Vener Dis 54: 184±186