Discussion
Initial symptoms of STSS are fever, pain and swelling of extremities, with rapid clinical deterioration leading to multiple organ failure, including acute respiratory distress syndrome, DIC and renal disturbance, with extremely high mortality [2]. While group A Streptococcus (GAS) is a major cause of STSS, cases of group B Streptococcus and GGS-induced STSS have recently increased [3,4]. Among GGS, SDSE infection is most frequent in humans [5]. While STSS due to GAS can occur in patients without underlying conditions [6], STSS due to GGS tends to occur in elderly patients and those with underlying conditions, such as diabetes mellitus, cardiovascular diseases, malignancies, cirrhosis, immunosuppressive conditions, or skin diseases [5,7,8]. In our case, the causative bacterium of STSS was not GAS, but SDSE of GGS. While GGS is a normal inhabitant of the nasopharyngeal cavity, skin and perineal area [5], it can cause erysipelas, cellulitis, necrotizing fasciitis, STSS, pneumonia, arthritis, osteomyelitis, meningitis, encephalitis, endocarditis, and sepsis, with clinical presentations similar to GAS. Both group C Streptococcus and GGS were previously not considered pathogenic bacteria. However, invasive infection caused by SDSE has been recently recognized, and thus, merits special attention [9,10].
When STSS is suspected, prompt diagnosis and early initiation of treatment with whole-body management, antibiotic administration and surgical intervention are critical [7]. The primary antibiotic for STSS treatment is penicillin, to which GGS is highly sensitive. Combination therapy with CLDM, which has anti-exotoxin effects with high tissue penetration properties, is also effective [5,11]. Reportedly, CLDM also suppresses penicillin-binding protein synthesis, resulting in enhancement of the penicillin effect in addition to suppression of exotoxin production [12]. Early debridement is important in cases with necrosis [7]. Although we did not administer immunoglobulin therapy in our case, it might also be effective for STSS treatment [5,13].
We used CHDF and PMX-DHP in addition to hemodynamic management and infection control. CHDF functions as an artificial kidney, removing various mediators of shock. In our case, we used an AN69ST membrane to absorb cytokines. The AN69ST membranes absorb high mobility group box protein 1 (HMGB-1), which is a late mediator of septic shock [14]. Previous reports have shown that absorption of HMGB-1 has beneficial clinical effects in patients with septic shock [15,16].
PMX-DHP removes intrinsic cannabinoids, which are critical mediators in the early stages of septic shock, and is effective in the treatment of severe sepsis [17]. In our case, fluid therapy and high doses of noradrenaline were ineffective for treating the shock state, and PMX-DHP and CHDF enabled the tapering of noradrenaline administration, suggesting that hypercytokinemia might contribute to hemodynamic disruption. We speculate that absorption and removal of cytokines by blood purification therapy using both PMX-DHP and CHDF resulted in hemodynamic stabilization and the positive outcome in our patient.
Since necrotic tissue has a poor blood supply, penetration of necrotic tissue by antibiotics is generally low. Therefore, early surgical resection of the necrotic tissue to prevent progression of tissue necrosis is prioritized in STSS with comorbid necrotic fasciitis [7,18,19]. Misiakos et al. reported that the mean interval between diagnosis of necrotizing fasciitis and debridement should be not more than approximately 12 hours, since a prolonged duration > 12 hours worsens mortality [20]. Bilton et al. reported that the mortality of patients with necrotic fasciitis who received early and adequate debridement was 4.2%, whereas delayed debridement increased the mortality to 38% [21]. In addition, necrotizing fasciitis causes persistent damage to surrounding tissues via exotoxin secreted by bacteria after establishment of the necrosis, which requires recurrent debridement [18-20]. Our patient underwent emergency debridement within several hours after admission. Furthermore, in our case, daily debridement of necrotic tissue reduced symptoms of infection and successfully preserved the affected leg. With progression of infection, the leg might require amputation. In particular, necrotizing fasciitis cases with comorbid diabetes mellitus have a higher risk of progression of symptoms, requiring amputation of the leg [22,23].
Here, we reported a case of STSS with necrotizing fasciitis and septic shock. Early multidisciplinary treatment resulted in a favorable outcome despite her advanced age.