Type I is found in 80 % of cases where it results from synergistic mixture of anaerobic, aerobic, and facultatively anaerobic bacteria (e.g., E. coli, Pseudomonas spp., and Bacteroides spp.). Type I NF particularly affects the immunocompromised or those with underlying abdominal pathology. The common aerobic species isolated from these infections are Streptococci, Staphylococci, Enterococci, and the family of Gram-negative rods. Bacteroides species are the most common anaerobes involved [7–9].

Type II is found in about 20 % of cases, which is usually monomicrobial and due to Gram-positive organisms, and the commonest type II NF is caused most frequently by group A β-hemolytic streptococcal alone or occasionally with Staphylococcus aureus. It carries a very high mortality of 43–58 %. Historically, monomicrobial S. aureus NF is uncommon, but occurs in neonates.

The commonest Gram-negative causes of NF remain Vibrio spp., such as V. damselae and V. vulnificus, which were responsible for 0.53 cases per 100,000 in Hong Kong in the late 1990s. V. vulnificus, associated with raw oyster ingestion, is the commonest cause of seafood-related deaths in the USA, particularly affecting patients with liver disease and iron overload. Wound contamination with seawater accounts for 25 % of cases. Virulence factors and digestive enzymes contribute to the high mortality of 30–40 % despite prompt diagnosis and aggressive therapy [10].

Rarely NF can be caused by Candida, especially in immunocompromised patients. In contrast, zygomycotic necrotizing infections (Mucor and Rhizopus spp.) affect immunocompetent patients after severe trauma and are responsible for nearly 32 % of NF cases in some countries. Fungal invasion most commonly follows traumatic wounds or burns, and aspergillus or zygomycetes may be isolated [11].

NSTI is the condition where the microbial virulence overweighs the host defense system. Impaired host immunity or local tissue hypoxia as in atherosclerosis, burns, cancer or other immunocompromised states, chronic alcoholism, corticosteroid use, diabetes mellitus, hypoalbuminemia, intravenous drug abuse, malnutrition, obesity, occult diverticulitis, peripheral vascular disease, postoperative infection, and trauma predispose to NSTI. The pathogenesis of the development of NF depends on the causative organism(s). Synergistic NF is a comparatively slow process, evolving over days. Often, following complicated abdominal surgery and ischiorectal or perineal abscesses, synergistic NF develops particularly where gut flora breaches the mucosa, entering tissue planes. A slowly evolving bruise on the abdominal wall or perineal infection may reflect underlying malignancy. Gas-forming organisms and anaerobic infection may produce crepitus. Surgically, classical “dishwater fluid” due to lysis of polymorphs and serous discharge, together with macroscopic fascial necrosis, myositis, or myonecrosis, may be demonstrated. “Crescendo” pain, necessitating progressively stronger analgesia, is typical as occlusion of perforating nutrient vessels, and infarction of the nerves produces progressive skin ischemia and pain. Muscle hypoxia and swelling alter oxygen tension, increasing intracompartmental pressures, sometimes resulting in compartment syndrome [12]. Type II is initially more insidious than type I, but progresses far more rapidly. The disease may appear to have arisen spontaneously with no obvious focus. In such cases, hematogenous infection from many foci, including the throat, ascending vaginitis, primary peritonitis, or necrotizing proctitis, reaches the fascial layer. Hence, initial symptoms are ascribed to influenza, gastroenteritis, or muscle strain. This mechanism may explain the association of streptococcal infection with seemingly minor sporting injuries in athletes. The streptococcal capsule and protein M, protein F, streptolysin O, hyaluronidase, streptokinase, and pyrogenic exotoxins have their specific roles to play in the pathogenesis of streptococcal infections. Direct inoculation of GAS though wounds or associated with surgery is less common: examples include injection sites, caesarean section, plastic surgery, and even minor cosmetic procedures [13]. Hence the earliest clinical feature common to all types of NF is exquisite, agonizing pain, quite out of proportion to any external signs. The degree of pain may be lessened in diabetic neuropathy or following powerful analgesia. It is common to find patients prescribed with narcotic analgesics for “severe cellulitis” before the true diagnosis is suspected. As nerves supplying the necrotizing areas of skin die, the central areas become anesthetic, while laterally, the tissues overlying the deep spreading fascial infection remain tender. Infection in the deeper layers finally ascends, producing edema of the epidermal and dermal layers (peau d’orange) and a “woody” firmness of the tissues. Hemorrhagic bullae progress to cutaneous gangrene, with sensory and motor deficits resulting from fascial and nerve destruction [14]. Fifty percent of type II NF cases are associated with toxic shock syndrome leading to a mortality of 40–67 % with up to half of patients needing amputation [15].

Perhaps the biggest hurdle in early diagnosis and management of an NSTI is how to make the diagnosis. The commonly involved sites are the extremities (36–55 %), trunk (18–64 %), and perineum (up to 36 %). Events commonly predisposing patients to NSTIs include mild trauma, insect bites, drug reactions, illicit drug injections, perirectal abscesses, major traumas, and surgical procedures. Although patients may have an underlying risk factor, 30 % of the NSTIs do occur in healthy individuals [16]. The initial nonspecific signs such as tenderness, swelling, erythema, and pain at the affected site mimic nonsevere soft tissue infections such as cellulitis and erysipelas. The initial nonspecific signs are tenderness. Symptoms are much more than signs in initial phase, but by the time patients present, appearances are usually those of late NF, with visible bruising, bullae, and cutaneous necrosis due to progress of the necrotizing process. A thorough history should suggest the causative organisms in most cases. Goh et al. analyzed nine case series with a total of 1463 patients [17]. Diabetes mellitus was a comorbidity in 44.5 % of patients. Contact with marine life or ingestion of seafood in patients with liver disease was risk factors in some parts of Asia. The top three early presenting clinical features were swelling (80.8 %), pain (790.0 %), and erythema (70.7 %). These being nonspecific features, initial misdiagnosis was common and occurred in almost three-quarters of patients. Clinical features that helped early diagnosis were pain out of proportion to the physical findings, failure to improve despite broad-spectrum antibiotics, presence of bullae in the skin, and gas in the soft tissue on plain X-ray. Specific enquiries should be made about minor trauma; soft tissue injury penetrating lesions including insect or human bites, recent surgery, skin infection, or ulcers; injection sites; and illicit intravenous drug usage. Many cases, however, remain idiopathic [18]. Fever (>38 °C) is found in around 44 % of the cases, and tachycardia (>100 beats/min) is usually found in 59 % cases. Infected sites have erythema (80 %), induration (66 %), tenderness (54 %), fluctuance (35 %), skin necrosis (23 %), and bullae (11 %) [19].

We analyzed our patients of necrotizing fasciitis of the lower limb. The study reviewed 118 cases (78 males and 40 females) with mean age of 45 + 16.5 years (range 12–95 years) of lower limb necrotizing fasciitis admitted to the Department of Surgery, BHU in India between 1995 and 2007. Most patients (n = 97) presented with fever. Other presenting symptoms included painful swelling, bullae, erythema, ulcer, and necrosis. Comorbid conditions such as diabetes, tuberculosis, malignancy, and immunosuppressive therapy were associated in 72 (61 %) cases. Amputations were done in 24 patients. Thirty-one patients developed septic shock. Renal dialysis was done in 16 patients, and ventilatory support was needed in 12 patients. The most common organism identified was beta-hemolytic streptococci (n = 42). Eighteen patients died, a mortality of 15 %. The authors consider early diagnosis and aggressive surgical intervention to be crucial for the successful treatment of the disease [20] (Figs. 17.1 , 17.2 , and 17.3 ).

Type III may be associated with raw seafood ingestion or wound exposure to seawater justifies culture for Vibrio spp. A history of tonsillitis, close contacts with impetigo, or recent nonsteroidal anti-inflammatory drug (NSAID) usage suggests streptococcal infection. Patients present with fever and myalgia, severe pain, nausea, vomiting, and diarrhea. Diagnosis in initial phases is particularly difficult, since patients seen earlier in the infection were more easily misdiagnosed with muscle strains or viral illnesses. Other common misdiagnoses include gastroenteritis, sunburn, or an “allergic rash.” A widespread macular “toxic erythema” may be present in a minority of patients. Misdiagnosis of NF is particularly common in children as it is rare and then usually associated with recent varicella zoster. Despite severe pain and appearing quite unwell, some patients initially have only a mild erythema, cellulitis, or swelling overlying the affected area. Since lymphatic channels are obstructed early, lymphangitis and lymphadenitis are rare. Overall, an exquisitely tender area evolves into a smooth, swollen area of skin with distinct margins progressing to dusky blue/purple, “bruising” violaceous plaques and finally full-thickness necrosis with hemorrhagic bullae [21]. Later on patients present with gangrenous patches, and the patients are very toxic and may involve various organs with hypotension, tachycardia, renal shutdown, respiratory problems, etc.