Thursday, October 19, 2006
Severe Relapsing Erysipelas Associated with Chronic Streptococcus agalactiae Vaginal Colonization
P. Del Giudice,1 N. van der Mee-Marquet,4 F. David-Rubin,2 F. Le Duff,1 K. Benchia,3 E. Counillon,1 A. S. Domelier,3 and R. Quentin4
1Unité de Maladies Infectieuses et Dermatologie, 2Laboratoire de Biologie, and 3Service de Gynécologie-Obstétrique, Hôpital Bonnet, Fréjus, and 4Laboratoire associé au Centre National de Référence pour Streptococcus agalactiae, Hôpital Trousseau, Tours, France
We report a case of severe recurrent erysipelas of the breast due to infection with Streptococcus agalactiae and demonstrate that strains isolated from the skin were closely related to strains isolated from the vagina, which is consistent with the claim that the vagina acts as a reservoir for S. agalactiae isolates that are responsible for erysipelas relapse. Hypervirulence of strains and persistence of a bacterial reservoir may explain why 5 months of prophylaxis with penicillin V (1 million U daily) was necessary to achieve permanent eradication of vaginal carriage and to prevent recurrence of erysipelas caused by S. agalactiae infection.
Received 9 May 2006; accepted 13 June 2006; electronically published 22 August 2006.
Reprints or correspondence: Dr. N. van der Mee-Marquet, Laboratoire de Bactériologie et Hygiène, Hôpital Trousseau, 37044 Tours cedex, France (firstname.lastname@example.org).
Erysipelas is an acute, superficial, dermal-hypodermal infection that usually affects the legs. It is commonly caused by streptococci —mainly from group A, but occasionally from groups C or G. The reservoir of an implicated pathogen is often unclear; the rectum and the spaces between the toes have been identified as possible reservoirs for streptococci [2, 3].
Streptococcus agalactiae, a bacterial pathogen of the group B streptococci that is frequently found in normal fecal and/or vaginal flora, is a leading cause of severe bacterial infections in newborn infants . In nonpregnant adults, S. agalactiae is responsible for various conditions such as urinary tract infections, arthritis, osteomyelitis, endophthalmy, pneumopathies, and endocarditis , especially in elderly individuals and patients with diabetes. S. agalactiae may also cause erysipelas . Severe skin and soft-tissue S. agalactiae infections, such as necrotizing cellulitis, necrotizing fasciitis, and toxic shock syndrome, are being reported with increasing frequency [6–11]. The vagina was once thought to serve as a bacterial reservoir for erysipelas-causing S. agalactiae , but this has not been supported by molecular characterization of isolated skin and vaginal strains.
We report a case of a severe relapsing erysipelas of the thorax due to S. agalactiae in a patient with a history of breast adenocarcinoma. We isolated strains from skin lesions and vaginal secretions to genetically identify them. We discuss the penicillin tolerance and virulence factors that are associated with the different strains that were identified in our patient, to highlight strain characteristics that could be associated with recurrent S. agalactiae infections.
Case report. In August 2005, a 50-year-old woman was referred to the dermatology department of Hôpital Bonnet (Fréjus, France) for extensive thoracic erysipelas. The patient's medical history included a tumorectomy of a breast adenocarcinoma, lymphadenectomy, and local radiotherapy in July 2002 and 4 reconstructive surgical interventions in November 2004, February 2005, April 2005, and July 2005. She experienced the first episode of erysipelas at the end of July 2005. The clinical outcome was favorable after 8 days of amoxicillin treatment (3 g daily).
One month later, at the end of August 2005, the patient was readmitted to the hospital for erysipelas of the breast. At admission, she had a high-grade fever (temperature, 40°C) and chills but no clinical signs of shock; she also reported severe left-side thoracic pain. Clinical examination revealed an extensive warm and painful erythema throughout the left thoracic side that was associated with a minimal lymphedema that extended to the right side (figure 1A), with no necrotic area or clinical sign of necrotizing fasciitis. Close examination revealed an oozing and crusty skin lesion of 1 × 2 cm that was caused by a scratch. Because the patient reported that the erythema had spread from this scratch, this was considered to be the portal of entry. Initial blood investigation revealed a WBC count of 12,000 cells/mm3, 80% of which were polymorphonuclear cells. Values determined by other blood tests, including hepatic tests, renal function tests, and glucose level determination, were within normal ranges. The swab specimen that was obtained from the skin lesion yielded a rich and pure culture of S. agalactiae. Antibiotic treatment was started (amoxicillin, 6 g iv daily), and the clinical outcome was favorable after 8 days of treatment. In accordance with current recommendations for the prevention of recurrent erysipelas, long-term oral prophylaxis was initiated using penicillin V (1 million U daily). The patient reported recent S. agalactiae vaginal colonization, and a vaginal swab was sent to the microbiological laboratory for culture, where extensive vaginal colonization by S. agalactiae was detected.
In November 2005, during the course of long-term oral prophylaxis, the patient presented with a third episode of erysipelas with milder symptoms. The episode resolved with penicillin V treatment (2 million U daily over 8 days), and long-term oral prophylaxis was continued using penicillin V (1 million U daily).
At the beginning of January 2006, while still receiving the course of long-term oral prophylaxis, the patient experienced a fourth episode of erysipelas, with persistent vaginal S. agalactiae colonization that was revealed through culture of a vaginal swab. This episode resolved with amoxicillin treatment (3 g over 8 days). Following the most recent episode, oral penicillin V prophylaxis (1 million U daily) was continued for 1 month; it was discontinued at the end of January in the absence of clinical signs of erysipelas and with regard to the confirmed vaginal eradication of S. agalactiae.
The patient has experienced no recurrence of erysipelas since February 2006. In April 2006, a vaginal swab was sent to the microbiology laboratory, and no vaginal colonization by S. agalactiae was detected by culture.
Results. We characterized the 4 S. agalactiae strains that were isolated from the skin lesions and from the vagina at the time of the 2 relapses. All strains belonged to serotype Ia. The isolated strains were not tolerant to penicillin (MIC, 0.0325 g/L; minimum bactericidal concentration, 0.0325 g/L). Molecular characterization using SmaI macrorestriction demonstrated that (1) the strains that were isolated from the skin and the vagina had the same restriction pattern, and (2) the strains that were isolated during the different relapses also had the same restriction pattern (figure 1B).
Genetic markers of virulent S. agalactiae and Streptococcus pyogenes strain subgroups, mostly resulting from horizontal genetic transfer, have previously been described [13–18]. We searched for 20 of these markers by PCR, using the primers and procedures referenced in table 1. We identified 2 such genetic markers, which indicate that these erysipelas strains belong to a virulent S. agalactiae subgroup. The markers that were identified were a unique cluster of tRNA located at the 3 end of an rRNA operon and the prophagic DNA element F7. The erysipelas strains were sequence type (ST) 23.
Discussion. We report a patient with several relapses of erysipelas caused by a non–penicillin-tolerant strain of S. agalactiae—including 1 severe episode—and associated chronic vaginal carriage of S. agalactiae. To our knowledge, only 2 cases of recurrent S. agalactiae erysipelas have been reported. Both cases occurred after radical hysterectomy and radiation therapy [12, 19]. In 1 case, S. agalactiae was identified from cultures of vulvar vesicles, vaginal mucosa, and blood; this led the authors to suspect that S. agalactiae vaginal carriage was responsible for the recurrent erysipelas. The causal role of vaginal carriage was also suspected in a previous case of relapsing S. agalactiae bacteremia .
Our study is the first to demonstrate that S. agalactiae isolated from the skin and from the vagina during recurrent erysipelas episodes are genetically closely related. This finding strongly suggests that the chronic vaginal S. agalactiae colonization in our patient may have served as the reservoir responsible for the relapses of erysipelas.
Erysipelas of the upper body is a known complication of previous treatment for breast cancer [21–25]. Carcinologic surgery of the breast, reconstructive surgery associated with axillary lymphadenectomy, and local radiotherapy, and the resulting lymphedema are major factors that favor a relapse of erysipelas. Recommendations for the prevention of recurrent erysipelas include lymphatic drainage to reduce lymphedema, avoidance of potential sources of skin trauma, scrupulous hand hygiene, and prophylactic penicillin treatment [1, 24–26]. The reservoir of implicated pathogens is often unclear in cases of erysipelas. Eradication of streptococcal carriage is also a matter of debate [27–29]. Our results support the recommendations of long-term prophylaxis to prevent recurrent erysipelas in women with S. agalactiae vaginal carriage. More studies are needed to determine the optimal approach for recurrent erysipelas and whether eradication of S. agalactiae colonization is a key component.
The phenotypic and genotypic characterization of isolates revealed that the erysipelas-causing strains that were isolated from our patient belonged to serotype Ia, harbored 2 S. agalactiae genetic markers of virulent clones, and belonged to the phylogenetic group ST 23. These traits are known to be markers of a clone associated with severe S. agalactiae infections [13, 17, 18]. The PFGE pattern of these strains was similar to that described by Moylett et al.  in cases of neonatal sepsis/cellulitis in Texas, in 2000. This finding may suggest that some S. agalactiae strains present particular features that result in cutaneous disease. If the strains of S. agalactiae that are responsible for recurrent infections are hypervirulent strains, then the eradication of vaginal carriage may be of particular importance for patients at a high risk for cutaneous infectious disease. The hypervirulence of strains of S. agalactiae and the persistence of a bacterial reservoir may explain the fact that long-term prophylaxis, which has been empirically observed to be effective, helps to prevent recurrent erysipelas.
Financial support. Ministère de l'Éducation Nationale, de l'Enseignement Supérieur et de la Recherche (to R.Q.); Centre Hospitalier de Tours and the Institut National de Veille Sanitaire (to R.Q. and N.M-M.).
Potential conflicts of interest. All authors: no conflicts.
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