CASE SUMMARY 14

“NECROTIZING FASCIITIS OF

THE RIGHT LEG IN A

DIABETIC PATIENT”

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INTRODUCTION

Necrotizing fasciitis is a surgical emergency characterized by a rapidly

progressive infection of the subcutaneous fascial layer of the skin with a potential fatal

outcome. Histopathological demonstration of necrosis of the superficial fascia;

polymorphonuclear infiltrate; microthrombosis of the cutaneous circulation; and edema of

the reticular dermis, subcutaneous fat and superficial fascia are typical findings.

Principles of management include emergent and wide debridement of the infected

necrotic fascial and skin layers; supportive treatment; combined with antibiotic therapy.

Accurate diagnosis followed by immediate institution of treatment significantly affects its

prognosis. The knowledge on the most common offending organisms will help in

determining the correct antimicrobials to deliver upon admission (File et al. 1995, Green

et al. 1996, Majeski et al. 1997, Low et al. 1998, Andreasen et al. 2001, Seal 2001, Speers

et al. 2001, Wong et al. 2003).

CASE REPORT (RN 910285)

Z.H. is a 50-year-old female diabetic for the past 15 years, developed swelling and

discoloration of skin over the right calf region three weeks prior to admission. The

swelling was initially small but progressed to a full-thickness skin necrosis with

accompanying fever and malaise. She sought treatment from several general practitioners

but the skin condition failed to resolve. Examination on admission revealed that she was

pale and dehydrated. Her blood pressure was 100/70 mmHg and pulse rate 100/minute. A

20 x 20 cm necrotic skin lesion which was foul-smelling with a discharging sinus was

noted over the medial aspect of mid-calf associated with inflammatory skin changes

ascending up to the mid-thigh laterally. The knee joint mobility was not affected.

Radiographs of the right lower limb revealed gas collection within the soft tissue of the

right leg and thigh. A diagnosis of type I necrotizing fasciitis of the right leg and thigh

was made and she was admitted for immediate surgical debridement and antibiotic

therapy. Her hemoglobin level was 6.0 g/dL with a white cell count of 24,000/µL

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(predominantly neutrophils). She was immediately started on intravenous Unasyn 1.5 gm

TDS and Metronidazole 500 mg TDS. After optimization (rehydration and blood

transfusion), she underwent surgical debridement - approximately 23 hours after

admission. Intra-operatively, there was about 100 cc of pus underneath the skin with

necrotic fascia extending circumferentially around the proximal third of the right leg

towards the lateral aspect of the right thigh (up to the level of the mid-thigh region).

Post-operatively, her toxic condition improved remarkably and her pus culture

grew Escherichia coli which was sensitive to Ampicillin. Antibiotics were continued and

she subsequently underwent multiple debridement procedures to remove all necrotic and

non-viable skin and fascia. Unfortunately, her wound was later infected with nosocomial

organisms including Pseudomonas aeruginosa, Klebsiella sp. and Acinetobacter sp. It

failed to improve despite numerous debridements and various types of antibiotic and she

subsequently underwent a right above-knee amputation, approximately three months after

the first surgical debridement.

DISCUSSION

The mortality rate from necrotizing fasciitis has not been decreasing over the past

decades despite advancements in medical knowledge and technology (Kaul et al. 1997,

Low et al. 1998, Wong et al. 2003). This is partly due to failure to alter the underlying

pathophysiological process responsible for tissue destruction and systemic toxicity; also

partly due to the paucity of cutaneous findings earlier in the course of the disease with

diagnoses being made later during the irreversible stage of systemic failure (Lukomski et

al. 1997, Wong et al. 2003). If left untreated, this rapidly lethal condition may reach a

mortality rate of over 70% (Trent et al. 2002).

Necrotizing fasciitis had been identified as early as the 5th century B.C., where

Hippocrates described it as a complication of erysipelas. Following that, this condition

had been given various names, including the malignant ulcer, gangrenous ulcer, putrid

ulcer, phagedena (“eating away”), phagedenic ulcer, phagedena gangrenosa, hospital

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gangrene, progressive bacterial synergistic gangrene (Meleney’s gangrene) and

synergistic necrotizing cellulitis. The term currently in use, necrotizing fasciitis was first

utilized by Wilson in 1952; and this term most accurately describes the most consistent

feature of the condition, i.e. fascial necrosis (Green et al. 1996, Andreasen et al. 2001).

Necrotizing fasciitis can be divided either by the site of infection, by duration and

extent of the infection or by its microbiological isolates. Although the extremities are the

most common site of involvement in necrotizing fasciitis, this infection can occur

anywhere, including the trunk, head and neck region, retroperitoneal area (often fatally),

scrotal region (Fornier’s gangrene) and the perineum (Green et al. 1996, Trent et al. 2002,

Wong et al. 2003). Jarrett et al. (1997) divided necrotizing fasciitis into 3 types –

fulminant, acute and subacute necrotizing fasciitis. The fulminant type is usually rapid in

progression (within several hours) with patients typically in shock at presentation. Acute

cases normally have large areas of involvement with symptoms being present for days

before admission; while in the subacute type, the affected skin is typically localized with

symptoms occurring for weeks to months before medical attention is sought. Many

authors have divided necrotizing fasciitis according to organisms cultured from their

patients (Bisno et al. 1996, Elliott et al. 2000, Trent et al. 2002). This classification is

helpful in deciding the group of antibiotics to deliver to these patients as well as in

predicting their response to therapy; however it does not help in the initial management of

these patients as isolation and identification would require some amount of time, which

these patients usually do not have. Type I infection, polymicrobial in nature, typically

affects immunocompromized hosts, such as those with diabetes mellitus, chronic liver

disease or malignancy. Type II infection affects healthy individuals and is typically

caused by Streptococcus pyogenes with or without Staphylococcus aureus (Table 1).

Z.H. presented with a subacute, type I infection which subsequently became acute

on presentation to the emergency department. The subacute nature of the initial

presentation had caused many general practitioners to miss the diagnosis. Another

possibility is that the initial presentation may be a subcutaneous abscess that had

remained quiescent with antibiotics given by the previous doctors who attended the

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patient; only to flare-up as a full-blown necrotizing fasciitis probably secondary to

uncontrolled diabetes mellitus.

Table 1 : Organisms isolated for both types of necrotizing fasciitis (Trent et al. 2002).

Apparently, clinical presentations of necrotizing fasciitis tend to overlap with

some other cutaneous infections, namely cellulitis and abscesses. A study by Wong et al.

(2003) noted that almost 60% of cases of necrotizing fasciitis were diagnosed as cellulitis

on admission to the ward (n = 89). Furthermore, signs like presence of crepitus in the skin

and evidence of subcutaneous gas formation on radiographs of the affected limb, both of

which are late signs, were only noted in 13 and 17 percent of patients, respectively. The

majority of patients in this study presented with a triad of exquisite pain on the affected

area (98%), swelling (92%) and fever (80%); all of which were non-specific. One useful

clinical feature noted by the study was tenderness beyond the apparent margins of

infection, erythema and warmth of the skin; which was the most common physical sign

noted in their patients (98%). Another useful sign to differentiate necrotizing from non-

necrotizing skin infection is pain out of proportion to its clinical cutaneous presentation

(Low et al. 1998). Bisno et al. (1996) and Wong et al. (2003) suggested that necrotizing

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fasciitis should be considered in a patient who has not responded to intravenous

antibiotics within 24 to 48 hours.

Once the diagnosis of necrotizing fasciitis has been accomplished, urgent and

thorough debridement of the infected fascia should be carried out alongside

commencement of empirical antibiotic therapy. Surgical debridement also allows excision

of thrombotic tissue expected to become necrotic. Furthermore, antibiotics will not

penetrate into infected tissue in the presence of widespread microthromboses, therefore

surgical debridement is mandatory (Seal 2001, Wong et al. 2003). Intraoperatively, all

infected fascia and necrotic tissue should be removed, and the extent of infection should

be inspected and explored thoroughly (Figure 1). One intraoperative sign which is

pathognomonic for necrotizing fasciitis is the ability to use a haemostat to split the skin

from the underlying fascial layer with ease (Chakrabarti et al. 2002, Trent et al. 2002).

Andreasen et al. (2001) advocated the use of the ‘finger test’; which can be performed

under local anesthesia. A 2-cm incision is made in the skin down to the deep fascia. Lack

of bleeding is an ominous sign of a necrotizing process. A gentle, probing maneuver with

the index finger is performed at the level of the deep fascia. If the tissues dissect with

minimal resistance, the finger test is positive (a similar test can be done using a probe,

known as the ‘probe test’). At the same time, tissue biopsies can be sent for frozen section

analysis. The characteristic histologic findings include obliterative vasculitis of the

subcutaneous vessels, acute inflammation, and subcutaneous tissue necrosis. Majeski et

al. (1997) noted a 100% sensitivity and specificity of bedside frozen section biopsies in

diagnosing necrotizing fasciitis in his patients (n = 43); however this approach is

impractical for most hospitals given the rare incidence of this condition (Low et al. 1998).

Other operative findings include the presence of foul-smelling ‘dishwater pus’, grayish

necrotic fascia, and lack of bleeding in the fascial layer during dissection (Andreasen et

al. 2001, Trent et al. 2002, Wong et al. 2003).

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Figure 1 : Characteristic pus drained from the subcutaneous layer in necrotizing fasciitis.

Some surgeons remove skin sparingly while extensively debriding the infected

fascia underneath it. Andreasen et al. (2001) examined the normal-appearing skin and

tissue microscopically and found out that they had extensive early vascular thrombosis

and vasculitis, which suggested a high potential for full-thickness skin loss. They

recommended that skin which is easily-elevated off its deep fascia should all be removed

during the primary debridement procedure. Wong et al. (2003) stated that skin should be

excised until healthy-looking, bleeding tissue is encountered at the margins of the wound.

This would reduce the number of subsequent debridements to remove necrotic skin which

initially appeared to be healthy during the primary procedure.

Antibiotics should be instituted as soon as the diagnosis is established. The

treating surgeon or physician should have a sound knowledge on the most common

offending organism in different types of patients. Patients who are immunocompromized,

such as those with diabetes mellitus, chronic liver disease or malignancy, will usually be

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infected with type I organisms (Table 1). Previously healthy individuals are usually

affected by Streptococcus pyogenes with or without Staphylococcus aureus (type II

organisms). Therefore, it has been recommended that the initial antibiotics given to these

patients should cover the aforementioned groups of bacteria. Recent suggestions have

include the usage of penicillin; an aminoglycoside or a third generation cephalosporin;

and clindamycin or metronidazole to cover all the potential organisms until culture results

are conclusive to allow appropriate adjustment of the regime (File et al. 1995, Bisno et al.

1996, Andreasen et al. 2001, Seal 2001, Chakrabarti et al. 2002, Trent et al. 2002).

Penicillin was noted to be less effective when there are a large number of

organisms present in the body or in the infected area (Stevens et al. 1993, Bisno et al.

1996). This so-called ‘inoculum effect’ happens when the large inoculum reaches the

stationary growth phase more quickly than with small or moderate amount of organisms;

thus ‘dampening’ the efficacy of penicillin. Stevens et al. (1993) also noted that during its

stationary growth, certain penicillin-binding proteins are not expressed by streptococci

and this effect causes failure of penicillin to act against this organism. Clindamycin, on

the other hand, acts by inhibition of protein synthesis - an effect which is independent of

the size of the inoculum or the stage of bacterial growth (Stevens et al. 1993). Other

modes of action of this antimicrobial are suppression of synthesis of bacterial toxins,

enhancement of phagocytosis, suppression of cell-wall synthesis and suppression of

production of tumor necrosis factor alpha (TNF-α) by the monocytes.

Subsequent debridement procedures, preferably done within 24 to 48 hours, are

essential to maximally eradicate all infected and non-viable tissue; while at the same time

allowing proper dressing of the frequently-extensive wound (Green et al. 1996,

Andreasen et al. 2001, Speers et al. 2001, Wong et al. 2003). Supportive therapy (fluid

resuscitation, electrolyte correction and cardiac monitoring) should be instituted together

with the above-mentioned measures. Hyperalimentation is crucial as patients are normally

in a catabolic state and suffers losses from the large, weeping wound (Andreasen et al.

2001, Trent et al. 2002). Frequently, patients would require an intensive-care support

through the acute stage of the illness.

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This patient’s wound seemed to be responding to antibiotics and debridement in

the initial stage; furthermore the primary pathogen involved, E. coli, was sensitive to

Unasyn instituted on admission. Her knee joint was not involved during the initial

presentation. In fact, she was planned for wound closure when the wound was

unfortunately secondarily infected. Another factor which had adversely affected her

outcome is her diabetes mellitus.

Other modalities of treatment are merely supportive rather than curative, and

shouldn’t in any way delay the institution of the main treatment strategies mentioned

earlier. Hyperbaric oxygen therapy is postulated to act via increasing the partial oxygen

pressure within tissues which in turn results in increased leukocyte killing abilities;

increased killing of anaerobic bacteria; reduced ischemic environment; stimulation of

fibroblast growth; enhanced antibiotic action; stimulation of angiogenesis; and enhanced

granulation tissue formation (Green et al. 1996, Trent et al. 2002). However, there have

been conflicting reports on the efficacy of this treatment; furthermore, this modality of

treatment is expensive and not readily available in all hospitals. Intravenous

immunoglobulin (IVIg) administration has been shown to have a profound

immunomodulatory effects on necrotizing fasciitis by neutralization of the activity of

streptococcal superantigens (streptococcal pyrogenic exotoxins, spe); inhibiting T-cell

proliferation and cytokines production (in particular the tumor necrosis factor, TNF)

induced by these toxins (Norrby-Teglund et al. 1996, Seal 2001, Trent et al. 2002). Kaul

et al. (1997) noted an improved outcome in patients with necrotizing fasciitis treated with

IVIg.

There are multiple factors which can influence the outcome in necrotizing

fasciitis. The natural course of the condition (without any treatment) has a high mortality

rate – reaching 70% (Trent et al. 2002). Even with early diagnosis and immediate

institution of treatment, this rate is within the vicinity of 20% (Wong et al. 2003, n = 89).

Diabetes mellitus is noted to be present in 70% of patients with necrotizing fasciitis in a

study by Wong et al. (2003). This ailment plus other immunocompromized states (e.g.

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peripheral vascular disease, chronic liver disease and malignancy) has been shown to

increase the mortality rate in necrotizing fasciitis. Wong et al. (2003) noted that presence

of two or more associated co-morbidities and increased age of patients significantly raised

the mortality rate in their patients (p < 0.05). However, the only independent predictor of

mortality in their patients (after adjusting for age, gender and diabetic status) was noted to

be a delay in surgery of more than 24 hours from admission. Thus, survival of patients

with necrotizing fasciitis is adversely affected by a delay in surgery of more than 24 hours

from admission (Wong et al. 2003). Elliott et al. (2000) found out that mortality in their

patients (n = 198) was affected by the presence of bacteremia, delayed or inadequate

surgery, and degree of organ system dysfunction on admission.

The role of non-steroidals (NSAIDS) in modifying the course of this condition is

worth noted. NSAIDS are said to attenuate the manifestations of necrotizing fasciitis by

masking the signs and symptoms of infection; reduce the phagocytic function of

leukocytes; and dampen the body’s humoral response to infection (Bisno et al. 1996).

However, Kaul et al. (1997) found out that the usage of NSAIDS in patients with

necrotizing fasciitis did not increase the occurrence of this condition nor did it increase

the severity of the infection.

CONCLUSION

With the absence of confirmatory clinical signs, not until during the late stage of

the disease, necrotizing fasciitis remains a potentially fatal condition. A high index of

suspicion with a good clinical knowledge on its initial manifestation would help in early

diagnosis of this devastating cutaneous infection. Emergent and thorough surgical

debridement combined with early institution of broad-spectrum antimicrobial therapy

which covers all the potential bacteria is the cornerstone in the management of this

condition.

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