Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from Postgraduate Medical Journal (May 1977) 53, 237-242.

Necrotizing M. A. TEHRANI I. McA. LEDINGHAM F.R.C.S. M.B., Ch.B. University Department ofSurgery, Western Infirmary, Glasgow

Summary stated that 'the essentially produces a The authors' experience of fourteen patients with of the subcutaneous tissues, subsequently it is reviewed. The pathognomonic causes of a part of the overlying skin'. In feature of this condition is an extensive of Meleney's report, bacterial culture showed that the subcutaneous caused by a vicious cycle of infec- haemolytic 'was the only organism tion, local ischaemia and reduced host defence invariably present'. Other organisms which were mechanisms. The diagnosis can only be confirmed by identified were fewer in number and none of them immediate exploratory incision. appeared regularly enough to be considered as the The reported mortality of 30-40%/ reflects the 'causative organism'-hence the term 'haemolytic inadequacy of conservative in the treatment of streptococcus gangrene'. this serious condition. Mortality can be reduced by Wilson (1952) was the first to use the descriptive early recognition followed by radical excision of the term 'necrotizing fasciitis' because of the charac- necrotic and overlying skin. The preservation teristic necrotic fascia and subsequently observed and subsequent use of the excised skin has the ad- non-specificity of the pathogenic organism involved. vantage of economy in the use of donor areas and Others in later reports (Rea and Wyrick, 1970;copyright. reduction in morbidity. Hyperbaric oxygen therapy Meade and Mueller, 1968; Ledingham and Tehrani, does not halt the spread of the necrotizing process and 1975) have confirmed the validity of this statement is not a substitute for radical surgery. and have continued to use this term in preference to other descriptive names. Definition and historical background Necrotizing fasciitis is a relentlessly destructive Bacteriology bacterial infection characterized by extensive necrosis Pathogenic organisms undoubtedly play a major of the subcutaneous tissues of the abdominal wall role in initiating and spreading the necrotizing and, less frequently, the extremities. The condition is process. The type of now encountered, http://pmj.bmj.com/ fortunately uncommon but is potentially fatal and however, seem to differ from those in earlier reports. demands early recognition in order that treatment In Wilson's series of twenty-two patients (Wilson, may be effective. Although the serious nature of this 1952), haemolytic organisms were found in pure condition was recognized as long as 100 years ago culture in 58% of cases studied bacteriologically and (Jones, 1871), confusion in the literature was com- were present along with non-haemolytic bacteria in pounded by the multiplicity of descriptive termi- an additional 26% of the patients. The majority of and data. Thus the were nology inadequate bacteriological organisms (88%) pathogenic staphylococci. on October 2, 2021 by guest. Protected condition has been referred to as 'hospital gangrene' Rea and Wyrick (1970) reported forty-four patients (Jones, 1871), 'acute infective gangrene' (Fedden, with necrotizing fasciitis seen during 15 years at 1909), 'necrotizing ' (Pfanner, 1918), Parkland Memorial Hospital in Dallas. In this 'haemolytic streptococcus gangrene' (Meleney, 1924, group, haemolytic streptococci and pathogenic 1929), and 'suppurative fasciitis' (McCafferty and staphylococci together accounted for 89% of the Lyons, 1948). wound with enteric Gram-negative The first large series published in the present organisms responsible for the remaining 11%. In a century was that of Meleney who, in 1924, reported recent report, Wilson and Haltalin (1973) described twenty patients from China. Meleney described the eleven children with necrotizing fasciitis. Haemolytic condition as a rapidly developing gangrene which streptococci were found in 50%/ of cases. The other occurred more frequently in males and the extremi- organisms were staphylococci and Pseudomonas ties were affected in the large majority of cases. He aeruginosa. In the report by Ledingham and Tehrani the in initial wound Correspondence: Dr lain McA. Ledingham, University (1975) predominant organisms Department of Surgery, Western Infirmary, Glasgow culture, obtained through fresh incisions in the Gil 6NT. affected areas, were coliforms in combination most Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from 238 M. A. Tehrani and . McA. Ledingham frequently with enterococci and streptococci; in only Lyons (1948) postulated activation by streptokinase one case was the streptococcus of the a-haemolytic or staphylokinase of a serum proteolytic , variety. Other organisms included , present in the inflammatory exudate, causing pro- diphtheroids, welchii, Proteus, Staphylo- gressive collagen necrosis. coccus and Ps. aeruginosa. Since colonizing bacteria Haemolytic streptococci are capable of producing rapidly invade the affected area, bacteriological haemolysin, leucocidine, fibrinolysin, erythrogenic cultures, both aerobic and anaerobic must be taken and the enzyme hyaluronidase. The filtrate of from several sites at an early stage in the course ofthe pathogenic staphylococci has haemolytic, necrotic . and coagulating properties (Kellaway, Burnet and Williams, 1930). Other organisms such as Pseudo- monas are known to produce collagenase with a Irrespective of the species of organism involved, primary effect on subcutaneous tissues and fascia the initial bacterial growth takes place in the sub- (Meade and Mueller, 1968). cutaneous tissues, i.e. the subcutaneous fat, super- Another important factor which should be con- ficial fascia and the superficial layer of the deep sidered in the pathogenesis of a major infection of fascia, most commonly of the abdominal wall and this sort is reduction in the host defence mechanisms lower extremities. The initiating injury responsible (HDM). Primarily, local reduction in tissue resis- for introduction of the infection may follow minor tance is achieved by the action of bacterial trauma (abrasions, cuts, , bites, minor added to the effect of bacterial kinases. This action is ) or surgical incision. At times, no obvious further enhanced by the general reduction in HDM is found. occurring in the postoperative period, or by pre- In the series reported by Rea and Wyrick (1970), existing systemic such as , arterio- minor trauma was responsible for 80% of the cases sclerosis, agamma- or hypogammaglobulinaemia, and in eight patients, no history of specific injury rheumatoid arthritis, malnutrition and gastro- could be obtained. In the present series of fourteen intestinal haemorrhage (Table 1). fasciitis following patients, necrotizing developed copyright. ischio-rectal in six, abdominal surgery in five, TABLE 1. Factors involved in the pathogenesis of necro- and fractured pelvis, diabetic peripheral vascular tizing fasciitis. HDM - host defence mechanisms disease and repeated supra-pubic aspiration of urine Infection each in one patient. Similarly in eleven children, (non-specific bacteria) reported by Wilson and Haltalin (1973), the condition Postoperative occurred in and traumatic Diabetic following surgery five, Collagenase Arteriosclerosis laceration, varicella, osteomyelitis, ofbuttock Bacterial toxins Agamma/Hypo- and aspiration, each in one patient. In Proteolytic Reduced HDM globulinaemia >. Rh. arthritis the final of this series no predisposing con- http://pmj.bmj.com/ patient Malnutrition dition was present. Gastrointestinal After the initial bacterial insult, the infection Necrosis of the haemorrhage spreads rapidly along the fascial plane causing superficial fascia massive necrosis. The presence of ischaemic tissue further facilitates spread of the necrotizing process. Ischaemia The skin remains intact initially but later develops Rapid spread along patchy necrosis and becomes gangrenous as a result avascular fascial plane of thrombotic occlusion of both venules and arte- + gross undermining on October 2, 2021 by guest. Protected rioles supplying the skin. Damage to cutaneous nerves causes numbness and subsequent anaesthesia Secondary gangrene of skin of the part. Untreated, the affected skin becomes extensively necrotic. At an early stage, histological Abele et al. (1960) reported a case of progressive examination of full thickness skin biopsies reveals no fatal cutaneous gangrene associated with hypo- abnormality. The subcutaneous fat and superficial gammaglobulinaemia. In Buchanan's patient fascia show a continuing non-specific inflammatory (Buchanan and Haserick, 1970) there was elevation reaction, with fibrinoid arteriolitis and of of serum complement level and a slight increase in the vessels. Organisms may or may not be demon- IgA, but its significance was unknown. In six strated in specially stained preparations. patients in the present series, hypoalbuminaemia and The factors responsible for this alarming spread hypergammaglobulinaemia were found. Clearly are unknown. An anaphylactic reaction similar to more detailed studies are required to detect the the Schwartzmann or Arthus phenomenon was possibility of specific immunological defects contri- suggested by Meleney (1933). McCafferty and buting to the spread of necrotizing process. Diabetes Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from Necrotizing fasciitis 239 is an important predisposing condition which reduces the host-defence mechanisms. In Cros- thwait's series (Crosthwait, Crosthwait and Jordan, 1964), 50%/ of the occurred in diabetic patients and in Meade and Mueller's report (1968), neither of the two diabetic patients who developed necrotizing fasciitis, survived. Six cases recently described by Roberts and Hester (1972) as syner- gistic bacterial gangrene, had most of the features of necrotizing fasciitis and all had diabetes and keto- acidosis. Infection, local ischaemia and reduced host defence mechanisms combine to form a vicious cycle which is responsible for the initiation and spread of the lesion (Fig. 1). (a) Infection

/~:~t4 Ischaemia ·iFr:lI,

(b)~a~ copyright.

Reduced host defence mechanisms FIG. 1. Factors involved in initiation and spread of necrotizing fasciitis. FIG. 2. (a) Portion of excised normal skin overlying an area affected by necrotizing fasciitis. Diagnosis (b) Undersurface of the same portion of skin showing

At an early stage the external appearance of the fascial necrosis. By kind permission of the Editorial http://pmj.bmj.com/ skin, in spite of the active underlying necrotizing Secretary and Publisher of British Journal of Surgery. process, is normal (Fig. 2a and b). Later the skin becomes red, hot, and oedematous, with no clear line Unit of the hospital. Death occurs as a result of of demarcation. Subsequently, dusky discoloration sepsis, respiratory or renal failure. Multi-organ with patchy necrosis of the skin occurs and the failure, therefore, is the terminal event leading to involved part, which is initially painful, becomes death in inadequately treated patients. numb. There is usually gross undermining of the The diagnosis should be established as rapidly as skin. Co-incident with these local features of pro- possible by making small incisions in the affected on October 2, 2021 by guest. Protected gressive infection, the general condition of the part. The finding of gross undermining of the skin patient deteriorates. Toxaemia, dehydration and associated with necrotic is mental apathy ensue. Anaemia is a frequent occur- pathognomonic of the condition and calls for urgent rence and is due to haemolysis, cutaneous hyper- appropriate therapeutic measures. aemia, loss of blood in extensive subcutaneous The from and spaces and bone marrow depression. Hypoprotein- progressive bacterial gangrene should not prove to aemia, hyponatraemia and hypocalcaemia, conse- be too difficult. Gas gangrene frequently occurs in quent to extensive , also commonly occur. association with penetrating wounds following Other systemic manifestations of severe infection . Invasion of muscles by clostridial such as disseminated intravascular coagulation, organisms, crepitus and a 'mousy'-smelling discharge respiratory failure and septic lead to major are characteristic. Incision reveals a characteristic haemodynamic disturbances. The majority of the bluish appearance of muscle which does not bleed. patients in the present series required continuous Progressive bacterial gangrene is a more slowly pro- haemodynamic monitoring in the Intensive Therapy gressive lesion affecting the total thickness of skin Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from 240 M. A. Tehrani and I. McA. Ledingham but not involving the deep fascia. The condition, management as initially outlined by Meleney (1924), essentially a postoperative surgical , and subsequently emphasized by Wilson (1952), occurs as a result of the synergistic action of a non- Crosthwait et al. (1964), Meade and Mueller (1968) haemolytic microaerophylic streptococcus with and Rea and Wyrick (1970), consists of multiple some other organism (Meleney, 1933), although linear incisions over the affected area as far as the several other synergistic combinations have been subcutaneous necrosis extends, thus exposing the known to produce the same lesion (Lyall and Stuart, entire area of necrotizing fasciitis. The extent of 1948; Webb and Berg, 1966). The lesion typically undermining is determined by passing a probe or by occurs at the site of the drainage tube or around the finger dissection. Fasciotomy and is laparotomy wound. The initial spreads carried out to the limit of the undermined skin and circumferentially and its centre becomes necrotic. subcutaneous tissue until it no longer separates from The gangrenous may reach tremendous pro- the deep fascia. Meleney (1924) immersed the area in portions. Surrounding the border of the gangrenous hot water and others used multiple drainage or area there is a tender purplish zone which in turn is frequent daily irrigation (Meade and surrounded by an area of oedematous red and Mueller, 1968). The denuded area is grafted with tender skin. There is no undermining of the skin and split-thickness skin grafts at a later date. the subcutaneous tissues and deep fascia are pri- Although in some earlier reports, this relatively marily intact. formation is variable. The impor- conservative approach to management was attended tance of an underlying systemic disease predisposing by excellent results with low mortality (Wilson, 1952), to the development of this condition should be borne more recent reports have shown a disturbingly high in mind. mortality ranging between 30 and 40% (Table 2). As emphasized by Rea and Wyrick (1970), even if Management conservative surgery is used at an early stage, many Once the diagnosis is established, the aims of treat- patients require further operations because of ment are two-fold. Firstly, general treatment and extension of the infection. The inadequacy of con- secondly, local measures to eradicate the source of servative in the source of infec-

surgery eliminating copyright. infection. tion is clearly shown from the experience in the (I) General treatment consists of the administration management of the fourteen patients in the present of intravenous fluid, large doses of appropriate series with this condition referred from different systemic and, when necessary, resuscita- parts of the U.K. and treated in the University tive measures preferably in an Intensive Therapy Department of Surgery, Western Infirmary, Glasgow, Unit. The majority of the patients, particularly those between 1965 and 1975. with extensive trunk or lower limb involvement and those in whom the diagnosis has been delayed, TABLE 2. Mortality of patients with necrotizing fasciitis exhibit features of severe toxaemia and . http://pmj.bmj.com/ The importance of adequate volume replacement, Series No. of cases Mortality (%) monitored by measurement of central venous Meleney (1924) 20 20 pressure and hourly urine output and electrolyte Wilson (1952) 23 8-7 balance cannot be overstressed. Frequent daily Crosthwait et al. (1964) 19 31 -5 Rea and Wyrick (1970) 44 30 bacteriological swabs, taken from the involved areas, Wilson and Haltalin and blood cultures should be done to achieve (1973) 11 38 2 maximum therapeutic benefit from antibiotic therapy. Particular attention should be paid to In eight of the earlier patients of this series local on October 2, 2021 by guest. Protected preventing the respiratory and renal complications so treatment consisted of multiple incisions and drain- commonly encountered in patients with septic shock. age in five patients, and multiple incisions and exci- Adequate oxygenation and, at times, assisted venti- sion of necrotic fascia in three. All eight patients lation with frequent blood gas estimation are re- received hyperbaric oxygen therapy (OHP). The quired. Digitalisation may be necessary to reduce the initial response to treatment was good in five risk of cardiac complications of septic shock patients, fair in two and poor in another. The local (Ledingham, 1975). Likewise, daily coagulation lesion was completely arrested in only two patients. screening is desirable for early detection of a con- Seven patients (88%) died. Death was sudden in sumptive coagulopathy. As part of general treatment three cases with the clinical features of pulmonary in particular when the lower extremities are involved, embolism, and gradual in three with progressive a defunctioning transverse colostomy is usually toxaemia. The remaining patient was found at required to prevent contamination of the involved laparotomy to have secondary carcinomatosis. areas. In six later patients, extensive radical excision of (II) Local treatment. The principle of surgical the necrotic fascia and overlying skin was performed Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from Necrotizing fasciitis 241 as soon as the diagnosis was established. Two patients died. In one patient who received OHP for 2 days, the lesion was arrested but this patient died from bronchopneumonia. The other patient de- veloped necrotizing fasciitis 48 hr after negative diagnostic laparotomy for weight-loss and anaemia. Radical excision was performed (Fig. 3a and b). The lesion was completely arrested but this patient died later and post-mortem examination revealed car- cinoma of the head of pancreas. In all six patients the excised skin was defatted and preserved and used for later grafting. A detailed account of two of the patients in this group is reported elsewhere (Tehrani et al., 1976). The role of hyperbaric oxygen in the treatment of this condition remains to be determined. In most patients with gas gangrene treated in this centre, OHP combined with simple incision has usually been associated with rapid cessation of the primary con- dition. Encouraging results have also been reported (Grainger, MacKenzie and McLachlin, 1967) in the treatment of patients with synergistic bacterial gangrene. The authors have not gained evidence of a comparable beneficial effect in the treatment of necrotizing fasciitis. Certainly hyperbaric oxygen did not halt the spread of the necrotic in the

process copyright. majority of their patients. Present experience would suggest that the high mortality associated with necrotizing fasciitis could further be reduced by earlier recognition and radical surgical treatment. OHP should not be regarded as a substitute for (a) aggressive surgical intervention. The preservation and use of the excised overlying skin which has a normal appearance in the early stages of the disease

process, not only prevents later skin gangrene but http://pmj.bmj.com/ has the advantage of economy in the use of donor areas for subsequent grafting. There is the additional benefit of a reduction in the duration of in-patient hospital treatment.

References

ABELE, D.C., DOBSON, R.L., NEWSOME, J.F. & LINDBERGER, on October 2, 2021 by guest. Protected A.S. (1960) Progressive fatal cutaneous gangrene asso- ciated with hypogammaglobulinemia. A.M.A. Archives of Dermatology, 82, 565. BUCHANAN, C.S. & HASERICK, J.R. (1970) Necrotizing fasciitis due to Group A 3-hemolytic streptococci. Archives of Dermatology, 101, 664. CROSTHWAIT, R.W., JR, CROSTHWAIT, R.W. & JORDAN, G.L., JR (1964) Necrotizing fasciitis. Journal of Trauma, 4, 148. FEDDEN, W.F. (1909) Six cases of acute infective gangrene of (b) the extremities. Proceedings of the Royal Society of IMedicine, 2, 213. GRAINGER, R.W., MACKENZIE, D.A. & MCLACHLIN, A.D. FIG. 3. (a) Necrotizing fasciitis affecting the anterior (1967) Progressive bacterial synergistic gangrene: chronic abdominal wall and right loin 48 hr after a diagnostic undermining ulcer of Meleney. Canadian Journal of laparotomy. Appearance after radical excision. Surgery, 10, 439. JONES, J. (1871) Quoted in Meleney, F. L. (1948) In: Treatise (b) Appearance after application of skin graft prepared on Surgical Infection, p. 15. Oxford University Press, New from initially preserved skin. York. Postgrad Med J: first published as 10.1136/pgmj.53.619.237 on 1 May 1977. Downloaded from 242 M. A. Tehrani and I. McA. Ledingham KELLAWAY, C.H., BURNET, F.M. & WILLIAMS, F.E. (1930) MELENEY, F.L. (1933) Differential diagnosis between certain Pharmacological action of of staphylococcus. types of infectious gangrene of the skin. Surgery, Gyne- Journal of and Bacteriology, 33, 889. cology and Obstetrics, 56, 847. LEDINGHAM, I.McA. & TEHRANI, M.A. (1975) Diagnosis, PFANNER, W. (1918) Zur kenntnis und Behandlung des clinical course and treatment of acute dermal gangrene. nekrotisierenden Erysipels. Deutsche Zeitschrift fur British Journal of Surgery, 62, 364. Chirurgie, 144, 108. LEDINGHAM, I.McA. (1975) Septic shock. British Journal of REA, W.J. & WYRICK, W.J. (1970) Necrotizing fasciitis. Surgery, 62, 777. Annals of Surgery, 172, 957. LYALL, A. & STUART, R.D. (1948) Progressive postoperative ROBERTS, D.B. & HESTER, L.L. (1972) Progressive synergistic of the skin. bacterial gangrene arising from of the vulva and gangrene Observations on aetiology in two Bartholin's gland duct. American Journal of Obstetrics and cases. Glasgow Medical Journal, 29, 1. Gynecology, 114, 285. MCCAFFERTY, E.L. & LYONS, C. (1948) Suppurative fasciitis TEHRANI, M.A., WEBSTER, M.H.C., ROBINSON, D.W. & as the essential feature of haemolytic streptococcus gan- LEDINGHAM, I.McA. (1976) Necrotising fasciitis treated by grene with notes on fasciotomy and early wound closure as radical excision of the overlying skin. British Journal of treatment of choice. Surgery, St. Louis, etc., 24, 438. Plastic Surgery, 29, 74. MEADE, J.W. & MUELLER, C.B. (1968) Necrotizing infections WEBB, R. & BERG, E. (1966) Symbiotic gangrene due to of subcutaneous tissues and fascia. Annals of Surgery, 168, Pseudomonas pyocyanea and E. coli. Australian and New 274. Zealand Journal of Surgery, 36, 159. MELENEY, F.L. (1924) Hemolytic streptococcus gangrene. WILSON, B. (1952) Necrotizing fasciitis. American Surgeon, Archives of Surgery. Chicago, 9, 317. 18, 416. MELENEY, F.L. (1929) Hemolytic streptococcus gangrene: WILSON, H.D. & HALTALIN, K. (1973) Acute necrotizing importance of early diagnosis and operation. Journal ofthe fasciitis in childhood. American Journal of Diseases of American Medical Association, 92, 2009. Children, 125, 591. copyright. http://pmj.bmj.com/ on October 2, 2021 by guest. Protected