Case Discussion <Case Presentation:> An 80-year-old man came to the emergency department (ER) with a two-day history of generalized malaise, fever and drowsiness. He had cut his right leg by the wheel of his bicycle five days ago and the leg began to develop local erythema and swelling two days later. His medical history is significant for poor control diabetes, hypertension and coronary artery disease and had social history for alcohol abuse for more than 50 years. He also took some black pills in recent years for gouty arthritis. He was admitted because of increasing pain and swelling of right leg and scrotum. His physical examination revealed an oral temperature of 38.8°C, pulse of 120 beats/min, respirations of 33/min, and blood pressure of 100/60 mm Hg. Extensive tender erythema, small blisters are noted at the inferior aspect of leg with air crepitus and gangrenous change of his perineum ( Figure 1 ). Blood cultures are obtained along with complete blood count with differential, chemistries,prothrombin（PT）, and arterial blood gas as shown in Table 1. Intravenous clindamycin and ceftriaxone was given and inotropic agents for hypotension. Six hours later, the patient's leg was observed to be dusky and rapidly progressed. A creatinine kinase (CK) elevated to 6983 U/L with CK-MB 5 U/L. Acute respiratory distress developed and intubation was performed. He was immediately taken to the operating room (OR) where an incision was made in the scrotum and leg. The pathological findings were shown in Figure 2 . All cultures of blood and necrotic tissues yielded Group A streptococci. The patient's condition continued to worsen despite maximal medical therapy and he died on the next day. Table 1. Blood biochemistry obtained on admission Hemogram RBC (M/uL) Hb (g/dL) Platelet (K/uL) WBC (K/uL) seg (%) lym (%) band (%)   4.78 14.8 97 15.32 89 6 5 Biochemistry Sugar (mg/dL) GPT (U/L) BUN (mg/dL) Creatinine (mg/dL) Na (U/L) K (U/L) PT (sec)   76 78 76 1.8 137 5.5 16.8 Blood gas pH PCO2 PO2 HCO3  BE     O2 mask 60% 7.13 28 158 9 -10     <Case Analysis> Necrotizing fasciitis (NF) is a severe soft-tissue infection caused by toxin-producing virulent bacteria, which is characterized by widespread fascial necrosis. It is often associated with severe systemic toxicity and is usually rapidly fatal unless promptly recognized and aggressively treated. The histology of NF revealed microbial invasion of the subepithelial soft tissues (including fascia), resulting in perivascular leukocytic infiltrate, vascular thrombosis, tissue edema, and necrosis. The perineal region is a common site of infection followed by foot ulcerations and traumatic wounds. Mortality (30-70%) can be influenced by predisposing patient characteristics (such as diabetes, liver cirrhosis, steroid use and other immunocompromised conditions) as well as the site and pathogen of infection, with perineal sources carrying the highest mortality rate in most studies. Necrotizing fasciitis present a unique and demanding diagnostic challenge to clinicians. Soft tissue infections often begin as a result of a trauma and may no longer apparent once the infection has set in. The most common signs of NF are nonspecific local pain, edema out of proportion to erythema, development of blistering, crepitus, and radiological evidence of soft tissue gas. Diagnosis of NF must be considered in cases of cellulitis with crepitus, local cutaneous anesthesia, or when progression is rapid or associated with necrosis. Radiological studies, including plain radiographs, CT, ultrasonography, and MRI have been used to aid in diagnosing NF. With evidence of NF, immediate surgical evaluation is crucial. Necrotizing fasciitis of scrotal gangrene (Fournier's gangrene) could occur with fever and scrotal edema which progresses quickly to gangrene and shock, often accompanied with anaerobic streptococci. Other common pathogens causing NF including Staphylococcus aureus, Clostridium perfringens (classic gas gangrene), gram-negative bacilli (Aeromonas hydrophilia, Vibrio vulnificus), group A streptococci. The identification of the causative pathogen is performed by Gram's stain and culture of debrided tissues. Most NF is polymicrobial and aggressive surgical debridement of lesions involved should be initiated. Patient survival is highly dependent on resuscitation from shock, early and repeated surgical debridements, broad-spectrum antibiotic coverage (third-generation cephalosporin and anaerobic coverage), and early hyperalimentation. Complications of NF include acute renal failure, adult respiratory distress syndrome, disseminated intravascular coagulation, multi-organ system dysfunction, surgical wound infections, and bacteremia and many patients receiving skin grafting later. Another disease entity of this patient is toxic shock syndrome (TSS), which was usually caused by Staphylococcus aureus and group A streptococcus. Nearly every clinical setting where infection or colonization with S. aureus and group A streptococcus can occur, such as post-surgical procedures, traumatic injuries, focal tissue infections and post-influenza pneumonia. The clinical picture associated with TSS includes high fever, a diffuse erythroderma involving the palms of the hands and soles of the feet that can desquamate over the course of 1-2 weeks, and hypotension. Multiple organ system involvement may also be present and can include vomiting, diarrhea, renal or hepatic dysfunction, thrombocytopenia, mucous membrane hyperemia, myalgias, and disorientation. The onset of symptoms is acute and symptoms may vary in intensity. Diagnosis is based on criteria include fever of >38.8°C, a diffuse macular erythrodermal rash, palmar and sole desquamation, hypotension (systolic <90 or orthostatic), multiple organ systems involvement, and negative results for other diseases such as Rocky Mountain Spot Fever, leptospirosis, and measles. A marked leukocytosis may be present and a transient lymphocytopenia may occur. The mortality rate in TSS is near 3% and is generally attributable to refractory hypotension or associated comorbidity with adult respiratory distress syndrome and/or disseminated intravascular coagulation. Treatment of toxic shock syndrome focused on correcting shock and the treatment of comorbid conditions. Choice of antibiotics should both cover S. aureus and streptococci, and if the diagnosis is unclear, a broad-spectrum third generation cephalosporin may be given. 繼續教育考題 1. (E) Necrotizing fasciitis occurs frequently in which following condition: A Diabetes B Alcoholics C Immunosuppressed patients D  Liver cirrhosis E All of above 2. (D) Which region of the body is less common of developing necrotizing fasciitis: A Extremities B Perineum C Abdominal wall D Head and neck E Post-surgical wound 3. (C) Which of the following statement is wrong: A Pain out of proportion to physical findings in a patient who appears to have a systemically toxic condition should raise the clinical suspicion of necrotizing fasciitis. B Typical skin manifestations of necrotizing fasciitis usually presented as dusky blisters and (hemorrhagic) bullaes, necrosis of the superficial fascia and fat and subcutaneous air crepitation. C Perivascular leukocytic infiltrate, vascular thrombosis, fascia and fat necrosis and tissue edema contribute to the necrosis of necrotizing fasciitis. Hypercalcemia can develop from extensive fat necrosis. D Subcutaneous nerves can be irritated or destroyed by necrotizing fasciitis and the previously tender skin could become hypersthetic or anesthetic. E Necrotizing fasciitis occasionally to have metastatic abscess formation in liver, lungs, spleen, brain, and other organs. 4. (A) Which pathogen is the least likely to causing necrotizing fasciitis of extremities: A Streptococcus pneumoniae B Staphylococcus aureus C Streptococcus pyogenes D  Clostridium perfrigens E Aeromonas and Vibrio species 5. (E) Which of the following clinical manifestations indicate necrotizing fasciitis rather than cellulites: A Hemorrhagic bullae formation B Necrosis or gangrenous changes of full thickeness of involved skin C Systemic toxic signs such as septic shock D Subcutaneous air crepitaions E All of above 6. (B) Which one of the following is the most important management to control the progression of necrotizing fasciitis: A Resuscitation from shock by using albumin to keep oncotic pressure B  Early and repeated surgical debridements and fasciotomy to decrease bacterial loads C Broaden antibiotic coverage for gram-positive and gram-negative bacteria D Hyperalimentation for nutritional support E Transfusion and steroid given 7. (E) Which statement about the outcome of necrotizing fasciitis is wrong: A Mortality rates of necrotizing fasciitis ranged from 30 to 70%. B Delays in diagnosis and treatment (particularly adequate surgical debridement and fasciotomy) correlated with poor outcome. C Old age, diabetes mellitus, peripheral vascular disease and other systemic disorders, poor nutritional status, and infection involving the trunk and perineum had worse prognosis. D Patient survival is highly dependent on resuscitation from shock, early and repeated surgical debridements, broad-spectrum antibiotic coverage (third-generation cephalosporin and anaerobic coverage), and early hyperalimentation. E Patients had necrotizing fasciitis usually had rapidly recovery of wound and seldom needed skin grafting. 8. (E) Which complications could be occurred in patients with necrotizing fasciitis: A Overwhelming sepsis B Multiple organ system failure C Acute respiratory distress syndrome (ARDS) D Disseminated intravascular coagulation (DIC) E All of above 9. (E) Which manifestations is common of patients with toxic shock syndrome: A High fever (>38.8°C) with leukocytosis B Diffuse erythroderma involving the palms of the hands and soles of the feet and desquamation C  Hypotension (systolic <90 mmHg or orthostatic hypotension) D Multiple organ systems involvement included vomiting, diarrhea, renal or hepatic dysfunction, thrombocytopenia and disorientation. E All of above 10. (C) Which following statement about toxic shock syndrome is wrong: A Both Staphylococcus aureus and group A streptococcus could develop toxic shock syndrome B Colonization of S. aureus and group A streptococcus could participate development of toxic shock syndrome C Mortality rate of toxic shock syndrome is near necrotizing fasciitis D Treatment of toxic shock syndrome focused on correcting shock and the treatment of comorbid conditions. E Broad-spectrum antibiotic for toxic shock syndrome if the etiology is not clear   References  Weinbren MJ, Perinpanayagam RM. Streptococcal necrotising fasciitis. J Infect 1992; 25:299-302. Donaldson PMW, et al. Rapidly fatal necrotising fasciitis caused by Streptococcus pyogenes.J Clin Pathol 1993; 46:617-20. Voros D, et al. Role of early and extensive surgery in the treatment of severe necrotizing soft tissue infections. Br J Surg 1993; 80:1190-91. McHenry CR, et al. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995; 221:558-65. Stevens DL. Invasive group A streptococcal infections. Clin Infect Dis 1992; 14:2-13. Green RJ, et al. Necrotizing fasciitis. Chest 1996;110:219-29. <答案解說 > Ans: E There is no age or sex predilection for necrotizing fasciitis. The disease occurs more frequently in diabetics, alcoholics, patients with chronic renal and liver diseases, immunosuppressed patients, IV drug users, and patients with peripheral vascular disease. Occasionally, necrotizing fasciitis may also occurs in young, previously healthy individuals because of the pathogenic organism is virulent (such as group A streptococcus).  Ans: D Although it can occur in any region of the body, necrotizing fasciitis most commonly occurs in the extremities. Introduction of the pathogen into the subcutaneous space can occur via any disruption of the overlying skin, such as a cut, abrasion, burn, laceration, contusion, bite, injection, or surgical incision, blunt or penetrating trauma, postoperative complications, cutaneous infections or ulcers, intravenous drug injections, perirectal abscesses and animal or insect bites. It may even develop at the site of a trivial scratch or wound or even in seemingly intact skin. Necrotizing fasciitis of the head and neck is rare. Ans: C Erythematous, tender, swollen, hot area of cellulitis, accompanied by local pain and fever, is commonly the first sign of necrotizing fasciitis. Leukocytosis with a left shift and systemic toxic signs are usually present at the time of hospital admission. Pain out of proportion to physical findings in a patient who appears to have a systemically toxic condition should raise the clinical suspicion of necrotizing fasciitis. Dusky blue as blisters and bullae develop later accompanied with necrosis of the superficial fascia and fat caused by bacterial enzymes, including hyaluronidase and lipases. The subcutaneous nerves are then destroyed by the infectious process and the previously tender skin becomes hypersthetic or anesthetic. Hypocalcemia can develop from extensive fat necrosis. Metastatic abscess formation in liver, lungs, spleen, brain, and pericardium from necrotizing fasciitis is common.  Ans: A Many pathogens could lead to necrotizing fasciitis in certain conditions. Virulent bacteria, such as Staphylococcus aureus, Clostridium perfringens, gram-negative bacilli (Aeromonas hydrophilia, Vibrio vulnificus), group A streptococci is common causes of necrotizing fasciitis. Of patients with diabetes and post-surgical wounds related necrotizing fasciitis, anaerobes and fungi could also be contributed, too. Ans: E The most common signs of necrotizing fasciitis are nonspecific local pain, edema out of proportion to erythema, development of blistering, crepitus, and radiologic evidence of soft tissue gas. Systemic toxic signs, such as septic shock, ARDS, DIC or acute organ failure indicate necrotizing fasciitis rather than cellulitis. Diagnosis of necrotizing fasciitis must be considered in patients of cellulitis with crepitus, local cutaneous anesthesia, or when progression is rapid or associated with necrosis. Radiologic studies, including plain radiographs, CT, ultrasonography, and MRI have been used to aid in diagnosing necrotizing fasciitis. Ans: B Treatment of necrotizing fasciitis is first and foremost surgical. Adequate surgery includes early debridement of all necrotic tissue and drainage of involved fascial planes via extensive fasciotomy until healthy fascia is encountered. Early and adequate surgical debridement and fasciotomy have been associated with improved survival. Postoperatively, because of the potential for rapid progression, the surgical wound must be reevaluated frequently for evidence of disease extension. In many instances, two or more major debridements, carried out in the operating room under general anesthesia, are indicated. In cases of extremity involvement, amputation is often warranted to control infection, particularly in patients with peripheral vascular disease and/or diabetes. Ans: E The mortality rates of necrotizing fasciitis is estimated from 29 to 76% in most larger studies. Delays in diagnosis and treatment (particularly adequate surgical debridement and fasciotomy) correlated with poor outcome. Other risk factors such as old age (more than 50 years), diabetes mellitus, peripheral vascular disease and other systemic disorders, poor nutritional status and infection involving the trunk and perineum had higher mortality. Patient survival is highly dependent on resuscitation from shock, early and repeated surgical debridements, broad-spectrum antibiotic coverage (third-generation cephalosporin and anaerobic coverage), and early hyperalimentation. Complications of NF include acute renal failure, adult respiratory distress syndrome, disseminated intravascular coagulation, multi-organ system dysfunction, surgical wound infections, and bacteremia and many patients receiving skin grafting later. Ans: E Complications of NF include acute renal failure, adult respiratory distress syndrome, disseminated intravascular coagulation, multi-organ system dysfunction, surgical wound infections, and bacteremia and many patients receiving skin grafting later. The proximate cause of death in patients with necrotizing fasciitis is usually either overwhelming sepsis or multiple organ system failure with or without the ARDS. Early deaths (defined as within the first 10 days after initial debridement) were due to the consequences of sepsis syndrome, whereas late deaths were attributable to multiple organ system failure. Ans: E The clinical picture associated with TSS includes high fever, a diffuse erythroderma involving the palms of the hands and soles of the feet that can desquamate over the course of 1-2 weeks, and hypotension. Multiple organ system involvement may also be present and can include vomiting, diarrhea, renal or hepatic dysfunction, thrombocytopenia, mucous membrane hyperemia, myalgias, and disorientation. The onset of symptoms is acute and symptoms may vary in intensity. Diagnosis is based on criteria include fever of >38.8°C, a diffuse macular erythrodermal rash, palmar and sole desquamation, hypotension (systolic <90 or orthostatic), multisystem involvement, and negative results for other diseases such as Rocky Mountain Spot Fever, leptospirosis, and measles. A marked leukocytosis may be present and a transient lymphocytopenia may occur.  Ans: C The mortality rate in TSS is near 3% and is generally attributable to refractory hypotension or associated comorbidity with adult respiratory distress syndrome and/or disseminated intravascular coagulation. Treatment of toxic shock syndrome focused on correcting shock and the treatment of comorbid conditions. Choice of antibiotics should both cover S. aureus and streptococci, and if the diagnosis is unclear, a broad-spectrum third generation cephalosporin may be given.