Travel-Related Streptococcal Toxic Shock Syndrome Caused by emm Type 78 Streptococcus pyogenes

Abstract

Streptococcal toxic shock syndrome is a serious health problem in developed and developing countries. We here report a case of severe protracted disease after a minor skin infection in a young traveler returning from West Malaysia which was caused by an unusual emm-type strain harboring speG and smeZ superantigen genes.

CASE REPORT

A 26-year-old Caucasian woman was seen with purpura fulminans-like acral lesions of both feet and fingers of the right hand in our travel clinic in Germany in April 2010 (Fig. 1). Symptoms had started suddenly 3 weeks before with high fever, headache, and collapse, which had led to a hospital admission in peninsular Malaysia, where the patient had spent her holiday. Initially, dengue shock syndrome with multiorgan dysfunction had been diagnosed clinically, as the patient had developed anuria, dyspnea, and an extensive maculopapular rash with vesiculation and pustulation covering both legs. Her condition had deteriorated after 4 days of supportive treatment, and she had been transferred to a hospital in Singapore. There, the clinical diagnosis of septic shock had been made. Echocardiography had shown signs of septic cardiomyopathy, and hemodialysis had been performed once. Leukocytosis of 19,970/μl had been present (83% neutrophils, 11% lymphocytes, 4% monocytes, 2% metamyelocytes), with a thrombocytopenia of 24,000/μl and a low hemoglobin concentration (11.2 g/dl) and hematocrit (31.6%). No data on inflammatory parameters could be obtained retrospectively. Dengue virus and leptospirosis serology had been negative. The patient had received meropenem, penicillin, cloxacillin, and doxycycline for 5 days, followed by amoxicillin-clavulanic acid before she had been transferred back to Germany in a clinically stable condition. On admission in our travel clinic, the patient complained about pain in the fingers and toes. The lesions were dry, and surrounding inflammation was minimal. C-reactive protein was 9.71 mg/dl, with a leukocyte count of 11,000/μl, and a platelet count of 346,000/μl. A swab taken from a dry lesion did not yield bacterial growth after 2 days of culture, and oral amoxicillin-clavulanic acid treatment was thereupon discontinued. One day after cessation of antibacterial chemotherapy, a fever of 39.2°C developed, which was accompanied by tachycardia (140/min) and a massive purulent secretion around the nail of the big toe. A Gram stain of the pus revealed Gram-positive streptococci, and beta-hemolytic colonies on sheep blood agar were observed after culture. The organism was identified as Streptococcus pyogenes by positive Lancefield group A agglutination. The isolate was forwarded to the German National Reference Center for Streptococci for molecular characterization, as the course of clinical disease appeared to be unusual. Sequencing of the emm gene revealed emm type 78, and PCR tests for all 11 known superantigens were positive for streptococcal pyogenic exotoxin G (speG gene) and streptococcal mitogenic exotoxin Z (smeZ gene). Genes for other exotoxins (speA1 to speA5, speC, speH, speI, speJ, speK, speL, speM, and ssa) were negative. The isolate was susceptible to penicillin (MIC, 0.015 mg/liter), clindamycin (MIC, 0.12 mg/liter), and clarithromycin (MIC, 0.12 mg/liter) but resistant to tetracycline (MIC, 16.0 mg/liter). The patient was treated with sultamicillin in order to resume the formerly successful aminopenicillin therapy, and clindamycin. The distal phalanx of the fourth toe had to be amputated, because the tissue was entirely necrotic. Streptococcal toxic shock syndrome (STSS) was diagnosed retrospectively, and a three-month follow-up period was uneventful.

Fig. 1.

Dried blisters and patchy hemorrhage on both legs. Inset shows close-up of severe hemorrhage and necrosis of the right foot.

The global burden of invasive Streptococcus pyogenes disease is estimated to be high, with a mortality rate of 30 to 70% in STSS (2, 3). STSS has become a serious health problem in both developed and developing countries (2). The disease is characterized by sudden onset of shock and multiorgan failure, often followed by soft tissue necrosis and disseminated coagulopathy (5). Humans are believed to be the only reservoir for S. pyogenes, and skin and soft tissue infections during travel in tropical countries are a common complaint. The portal of entry in this case was presumably an infected blister on the right heel which had occurred during travel in West Malaysia. The initiating injury may seem trivial, but soft tissue infections are more commonly associated with STSS than pharyngitis (5). According to the case definition of STSS (5), group A streptococci must be cultured from a normally sterile site (e.g., a tissue biopsy site) in order to fulfill the criteria for a definite diagnosis. In this case, the bacterial isolate was cultured from deep tissue secretions and thus the diagnosis of STSS is highly likely.

Besides the streptococcal pyogenic superantigens, the streptococcal mitogenic exotoxin Z found here has been implicated in the pathophysiology of STSS (7), and, accordingly, the smeZ gene is statistically found more often in invasive than in noninvasive strains (6). The impairment of negative regulators of virulence genes has recently been suggested to lead to STSS (2), and the superantigen genes speA1 to speA4 and speM have a positive predictive value for invasiveness (6). Also, host genetic factors, such as human leukocyte antigen class II haplotypes, have been described to play a role in the outcome of invasive group A streptococcal infections (4). In the case presented, leukocyte antigen haplotyping was not performed. The patient was an otherwise healthy young adult. The M protein is considered to be a major virulence factor, and the emm types 1, 3, 12, 28, and 89 were the five most common types responsible for invasive S. pyogenes disease, including STSS, in a recent survey in Germany (3). emm types are associated with certain superantigen profiles (1). The particular emm type found here has not been found in invasive S. pyogenes disease in Germany in the period of 2003 to 2007 (3) and, apart from the case described here, also not after 2007. These data underscore the acquisition of this unusual strain abroad.