Eur J Clin Microbiol Infect Dis (2001) 20:910Ð913 DOI 10.1007/s100960100620

BRIEF REPORT

E. Merino á V. Boix á J. Portilla á S. Reus á M. Priego Fournier’s Gangrene in HIV-Infected Patients

Published online: 12 December 2001 © Springer-Verlag 2001

Fournier’s gangrene (FG) is a form of necrotizing fasci- 5 days’ duration. One year previously, oral lichen planus itis occurring around the genitals. It usually affects pa- had been diagnosed, which was being treated with ste- tients with underlying systemic conditions like chronic roids. On admission he was febrile (temperature, 38.5¡C) alcoholism (25Ð50%) or mellitus (40Ð60%) [1]. and hypotense (110/60 mmHg). Oropharyngeal candidia- Increased risk has also been reported after immunosup- sis was evident. A necrotic area was found over the scro- pressive treatment, such as chemotherapy for malignant tum with a malodorous yellow-brown discharge, erythe- disease and adrenal , or in transplant recipients. ma and swelling of the perineum. The perirectal area and It can affect patients of widely varying ages, from neo- abdominal wall were not affected. No general predispos- nates to the very old. The highest incidence has been re- ing factors could be identified. ported among patients around 50 years of age [2]. The Surgical debridement of the necrotic tissue was per- pathogens most commonly found are Escherichia coli, formed, and imipenem and gentamicin were adminis- Bacteroides spp., streptococci, staphylococci, pepto- tered for 15 days. Culture of the necrotic tissue grew streptococci and clostridia, all of which belong to the Escherichia coli and a Peptostreptococcus sp. Citrobac- normal flora of the lower gastrointestinal tract and peri- ter freundii was isolated from blood cultures. Urine cul- neum [3]. Localised cellulitis at the site of entry pro- ture was sterile. Although the patient denied any risk be- gresses to a diffuse inflammatory reaction involving haviour for HIV infection, HIV serology was positive: deep fascial spaces. An obliterating endarteritis causes his CD4+ cell count was 6/mm3 and the HIV viral load cutaneous and subcutaneous vascular thrombosis with was 1,879,000 RNA copies/ml. Triple antiretroviral necrosis of the tissue, which allows commensal flora to treatment was initiated, but 1 month later the patient de- enter previously sterile areas. Tissue destruction then re- veloped bilateral pneumococcal pneumonia and died as a sults from a combination of ischemia and the action of result of nosocomial Pseudomonas aeruginosa sepsis. different bacteria. In October 1998, a 67-year-old man was admitted to Although the importance of bacterial infections in pa- hospital with fever and pain affecting the scrotum. He tients infected with the human immunodeficiency virus had been diagnosed with HIV infection 5 years previous- (HIV) was recognised early [4], necrotising fasciitis is ly during a preoperative study for a transurethral resec- unusual in these patients and FG is exceptional. Since tion of a bladder carcinoma (stage I). His only infectious the first description of a patient with AIDS and FG ap- had been a perianal abscess that needed peared in 1991 [5], only nine other cases have been re- surgical debridement 2 years prior to presentation. The ported in the Western literature [6, 7, 8, 9, 10, 11]. Re- patient was being treated with triple antiretroviral thera- ported here are two additional cases of FG that occurred py; 2 months prior to admission his viral load had been in HIV-infected patients and a review of previously pub- undetectable and his CD4+ cell count was 386/mm3. lished cases. Seven days before consultation he developed a high tem- In June 1998, a 39-year-old man was admitted to hos- perature and discharge through a perianal fistula. Oral pital for pain, swelling of the scrotum and fever of ofloxacin treatment was started, but the patient remained febrile and developed a tender swelling of the right E. Merino (✉) á V. Boix á J. Portilla á S. Reus á M. Priego hemiscrotum. Hospital General Universitario de Alicante, A general examination showed a toxic febrile patient Unidad de Enfermedades Infecciosas (temperature, 39¡C) who had evident cyanosis and (Unit of Infectious Diseases), Maestro Alonso 109, 03010 Alicante, Spain bronzin of the scrotum with induration, crepitus and ar- e-mail: [email protected] eas of cutaneous necrosis and a perianal fistula without Tel.: +34-96-5938356, Fax: +34-96-5938979 discharge or anal abscess. FG was diagnosed and an ur- 911 sp., , =4) n Proteus mirabilis Proteus pneumoniae Streptococcus Klebsiella 11, 12 [11] 11, (bacterial pneumonia) ND sp., gram- negative Pepto-- , coli sp., sp. sp. anaerobes coccus coccus sterile sterile ND ND ND Streptococcus Strepto- Escherichia Enterococcus left axilla, right eye Pseudomonas , sp. sp., sp., penicillin metronidazole aztreonam tobramycin penicillin Proteus mirabilis Proteus coccus Escherichia coli (IV drugs in femoral veins) sp. , sp., Bacteroides coccus scrotum scrotumfistulasterile abscess scrotum, penis sterile penisrectumperineum fissure distal rectum sp. Pepto- viridans , Pseudomonas aeruginosa sepsis) 1 month later ( nated ) (HD), cured 3 months later gentamicin gentamicin metronidazole + gentamicin + clindamycin + metronidazole + metronidazole + coccus strepto- Peptostrepto-- Peptostrepto- Staphylo- streptococcus coli Patient 1 [PR] Patient 2 [PR] Patient 3 [5] Patient 4 [6] Patient 5 [7] Patient 6 [8] Patient 7 [9] Patient 8 [10] Patient 9, 10, Citrobacter Citrobacter freundiiStreptococcus Escherichia Streptococcus aeruginosa 6 386 120 6 475 178 ND ND <200 3 Epidemiology, clinical features, etiology, treatment and outcome of Fournier’s gangrene in 12 HIV-infected patients gangrene in 12 HIV-infected treatment and outcome of Fournier’s clinical features, etiology, Epidemiology, Surgical yesSurgical reconstruction Outcome cured, died yes cured no died (dissemi- cured no renal failure cured yes cured yes cured, died cured ( yes yes yes Antibiotics imipenem + imipenem + cefotaxime + penicillin + penicillin + cefotaxime + gentamicin + ND broad spectrum cultures tissue Table 1 Characteristic Patient [reference no.] Age (years)CDC stage 39CD4/mm A3 58 A2 33 C3 29 C3 49 A2 intravenous PR, present report; ND, no data; HD, hemodialysis; IV, 47 A3 48 ND ND 21 ND 34Ð41 Necrotic Entry portal NDBlood cultures perianal ischiorectal hyfrecation elective perianal proctitis perianal fistula Viral load Viral (copies/ml) Onset (days) 1,879,000Localisation 5 scrotum 0 right hemi- 6 right hemi- ND left hemi- ND scrotum/ ND scrotum/ 7 ND anal sphincter, scrotum, ND 3 scrotum/penis, ND 2 ND 3 ND 3 ND 912 gent radical debridement of the subcutaneous necrotic was the most commonly isolated organism, followed by area was performed; debridement of deep fascia or mus- Peptostreptococcus spp., Escherichia coli, Clostridium cle was not required. Imipenem and gentamicin were ad- spp., Proteus spp., Pseudomonas aeruginosa and coagu- ministered. Blood cultures were negative. Cultures of the lase-negative staphylococci. necrotic tissue grew Streptococcus viridans, a Pepto- All patients underwent urgent surgical debridement streptococcus sp. and a Bacteroides sp. Reconstructive and received parenteral broad-spectrum antimicrobial surgery with a skin graft was performed 10 days follow- agents in double or triple combinations to cover gram- ing debridement, and a fistulotomy was performed 4 negative aerobes, streptococcal species and anaerobic or- weeks later. At 2-year follow-up the patient remained ganisms. Rapid improvement was observed in nine pa- well. tients. Although only one patient died during the first ad- A computerised search of the Medline database was mission, two other patients died in the following months. conducted to reveal all cases of FG in HIV-infected pa- Patient 3 developed acute renal failure, fever and dis- tients reported in the English-language literature from seminated intravascular coagulation and died 16 days 1980 to 2000. The key words used were “immunodefi- following admission; necropsy revealed a disseminated ciency virus infection”, “AIDS”, “Fournier’s gangrene” Candida infection. Patient 5 needed short-term hemodi- and “gangrene of scrotum”. A total of 10 cases were alysis for acute renal failure, resulting in complete recov- found, and all of the cited publications could be located ery in a few weeks. Patient 8 had a slow-healing wound, and analysed [5, 6, 7, 8, 9, 10, 11] (Table 1). Those pub- but he refused a second surgical treatment and died 3 lications were examined for case details and references months later of bacterial pneumonia. Seven patients to other published cases. Only cases reported from West- needed multiple debridements. Reconstructive surgery ern countries were analysed. was necessary in eight patients. The nine surviving pa- All 12 patients (10 published previously and 2 report- tients were asymptomatic at the end of follow-up. ed here) were male. The mean age was 40.8 years Although FG is not common, it is by no means a rari- (range, 29Ð58 years), and risk factors for HIV infection ty, with more than 400 cases being reported in the litera- were as follows: homosexual intercourse (n=8), intrave- ture [12]. In HIV-infected patients, however, only 12 nous drug use (n=1), heterosexual intercourse (n=1) and cases have been communicated from Western countries. not reported (n=2). The CD4+ lymphocyte count was Although the incidence of perianal or genital infections available for 10 patients; all were below 500/mm3 and is high among homosexual HIV-infected males, the inci- eight were below 200/mm3. Only four of the patients dence of FG remains very low. In a retrospective analy- were receiving antiretroviral therapy. The clinical stage sis of a cohort of more than 1,300 HIV-infected patients of HIV infection was reported for seven patients; five followed for 10 years, Consten et al. [11] reported an in- were in stage C, and two in stage A. FG led to the diag- cidence of perineal sepsis of 3.7% (50 cases) with only nosis of HIV infection in three patients. four cases of FG (incidence, 0.3%). According to those Three of the 12 patients had some other underlying data, HIV infection would not appear to be a significant disorders, in addition to HIV infection, that could have risk factor for FG. However, in 9 of the 12 cases we ex- compromised their immunity. One patient developed amined, AIDS had developed before FG, and 9 patients perineal gangrene during week 3 of treatment with eto- had a CD4+ cell count <200/mm3. Three of the patients poside for a severe widespread Kaposi’s sarcoma. An- had at least one other known risk factor for FG, and 11 other patient was a chronic alcoholic, and the third had patients had a local focus of infection that could have been receiving steroids for a long time. Neutropenia, an- been the portal for FG. It can be hypothesised that the other identified risk factor for the development of FG, HIV-induced immunosuppression of these patients con- was recorded in only one patient. tributed to the progression from minor perianal infec- The source of infection was recognised in 11 patients: tions to FG. anorectal foci in 8 (perianal fistula in 6, recurrent procti- In assessing the relationship between HIV and FG, it tis in 1 and drainage of bilateral ischiorectal abscesses in is also possible that HIV infection may have been over- 1), urogenital in 3 (1 balanitis, 1 hyfrecation and 1 elec- looked in other cases of FG affecting patients with a tive circumcision because of phimosis and recurrent bal- good immunologic status. However, the fact that FG anitis). Fever and pain were the cardinal complaints, and mainly affected those HIV-infected patients who were at erythema and swelling of the scrotum with induration an advanced stage of the disease suggests that severe im- and crepitus of the perineal area were the usual signs. munosuppression can increase the risk of FG, but the Obvious cutaneous necrosis was evident in 11 patients. role of CD4+ cell depletion seems to be minor. Extension beyond the genitalia was observed in five pa- In 1993, Stephens et al. [2] compared the rate of mor- tients. The condition progressed for 2Ð6 days (average, tality due to FG in the preantibiotic era (series published 3.7) after the onset of clinical manifestations, a pace before 1945) with that of the postantibiotic era (cases re- which is a bit slower than in the general population. ported from 1945 to 1988) and found no differences, Blood cultures were positive (Citrobacter freundii with a death rate of around 20Ð22%. Probably any sur- and Pseudomonas aeruginosa) in two of seven patients vival benefit coming from improved treatment is masked tested. Necrotic tissue cultures showed polymicrobial in- by a trend towards increased mortality caused by the ad- fection in all 11 patients tested. Group A Streptococcus vanced age of patients and comorbidity. We found that 913 mortality rates due to FG reported within the last decade 5. Murphy M, Buckley M, Corr J, Vinayagarnoorthy S, Grainger (1986Ð1996) range from 7% to 33%, with no difference R, Mulcahy FM: Fournier’s gangrene of scrotum in a patient with AIDS. Genitourinary Medicine (1991) 67:339Ð341 being noted between HIV-positive and HIV-negative pa- 6. Nelson MR, Cartledge J, Barton SE, Gazzard BG: Fournier’s tients. Moreover, the data presented here show that FG is gangrene following hyfrecation in a male infected with the hu- uncommon in patients with HIV infection in Western man immunodeficiency virus. Genitourinary Medicine (1992) countries. In some aspects it behaves like a low-inci- 68:401Ð402 7. McKay TC, Waters WB: Fournier’s gangrene as the presenting dence opportunistic infection, similar to bacilar angio- sign of an undiagnosed human immunodeficiency virus infec- matosis or Rhodococcus equi pneumonia. tion. Journal of (1994) 152:1552Ð1554 8. Roca B, Cunat E, Simon E: HIV infection presenting with Fournier’s gangrene. Netherlands Journal of Medicine (1998) References 53:168Ð171 9. Caird J, Abbasakoor F, Quill R: Necrotising fasciitis in a HIV- positive male: an unusual indication for abdomino-perineal re- 1. Baskin LS, Carroll PR, Cattolica EV, McAninch JW: Necroti- section. Irish Journal of Medical Science (1999) 168:251Ð253 sing soft tissue infections of the perineum and genitalia. Bac- 10. Hughes-Davies LT, Murray P, Spittle M: Fournier’s gangrene: teriology, treatment and risk assessment. British Journal of a hazard of chemotherapy in AIDS. Clinical Oncology (Royal Urology (1990) 65:524Ð529 College of Radiologists) (London) (1991) 3:241 2. Stephens BJ, Lathrop JC, Rice WT, Gruenber JC: Fournier’s 11. Consten E, Slors J, Danner S, Sars P, Obertop H, Van Lanschot gangrene: historic (1764Ð1978) versus contemporary J: Severe complications of perianal sepsis in patients with hu- (1979Ð1988) differences in etiology and clinical importance. man immunodeficiency virus. British Journal of Surgery American Surgeon (1993) 59:149Ð154 (1996) 83:778Ð780 3. Smith GL, Bunker CB, Dineen MD: Fournier’s gangrene. Brit- 12. Hejase MJU, Simonin JE, Bihrle R, Coogan C: Genital Four- ish Journal of Urology (1998) 81:347Ð355 nier’s gangrene: experience with 38 patients. Urology (1996) 4. Berger BJ, Hussain F, Roistacher K: Bacterial infections in 47:734Ð739 HIV-infected patients. Infectious Disease Clinics of North America (1994):449Ð465