JURNAL 2

Arch Orthop Trauma Surg (2010) 130:1515–1522

DOI 10.1007/s00402-010-1101-8

123

TRAUMA SURGERY

Necrotizing fasciitis of the extremities: 34 cases at a single centre

over the past 5 years

Henning Ryssel · Günter Germann · Oliver Kloeters ·

Christian Andreas Radu · Matthias Reichenberger ·

Emre Gazyakan

Received: 3 November 2009 / Published online: 25 May 2010

© Springer-Verlag 2010

Abstract

Background Worldwide the incidence of necrotizing fasciitis

(NF) is on the rise. This rapidly progressive infection

is a true infectious disease emergency due to its high morbidity

and mortality. The mainstay of therapy is prompt

surgical debridement, intravenous antibiotics, and supportive

care with Xuid and electrolyte management. Because of

its high mortality rate, patients are increasingly referred to

burn centres for specialized wound and critical care issues.

Methods A retrospective chart review was performed of

34 consecutive patients over a 5-year period with NF of the

upper and/or lower extremities that required surgical

debridement and reconstruction.

Results The overall survival rate was 96%, with an average

length of hospital stay of 64.0 § 5.5 days. The time

until the Wrst operation was 1.3 days. The average age of

the patients was 56.7 § 10.6 years. The patients averaged

1.6 relevant comorbidities. One patient who had Wve

comorbidities died. The aVected total body surface (TBS)

averaged 8.2 § 2.1%.

Conclusion Early recognition and treatment remain the

most important factors inXuencing survival in NF. Yet,

early diagnosis of the condition is diYcult due to its similarities

with other soft-tissue disorders. Repeated surgical

debridement and incisional drainage continues to be essential

for the survival. However, these infections continue to

be a source of high morbidity, mortality and signiWcant

healthcare resource consumption. These challenging

patients are best served with prompt diagnosis, immediate

radical surgical debridement and aggressive critical care

management. Referral to a major burn centre may help to

provide optimal surgical intervention, wound care and critical

care management.

Keywords Necrotizing fasciitis · Extremities ·

Soft-tissue-infections · Critical care issues · ICU · Burn

center

Introduction

Necrotizing fasciitis (NF) is a severe form of soft-tissue

infection that primarily involves the fascial system. It may

result from any insult to the skin or from haematogenous

spread. It can occur in almost any area of the body at the

site of a skin biopsy, laceration, insect bite, needle puncture,

surgical wound, skin abscess chronic venous ulcer and

areas aVected by herpes zoster [1]. This rapidly spreading

infection can involve a whole limb within a very short time,

for which reason early surgical debridement and antibiotic

treatment are essential to avoid a fatal outcome [2]. The

two most common pitfalls in the management of NF are the

failure of an early diagnosis and inadequate surgical

debridement. NF places signiWcant demands upon hospital

and medical resources. In the US, the annual age-adjusted

incidence was 4.3 invasive infections per 100.000 (medline-

based retrospective multicenter-analysis from 1990 to

1998) [1]. An Australian study reported that the mean

length of hospital stay for survivors of NF was 36 days and

that the average cost per patient during their hospital stay

averaged 64.517 Australian dollars [2]. The average length

of stay in the Intensive Care Unit (ICU) was 11 days for

H. Ryssel (&) · G. Germann · O. Kloeters · C. A. Radu ·

M. Reichenberger · E. Gazyakan

Department of Hand-, Plastic- and Reconstructive Surgery,

Burn Center, BG Trauma Center Ludwigshafen,

Plastic- and Hand-Surgery, University of Heidelberg,

Ludwig-Guttmann-Str. 13, 67071 Ludwigshafen, Germany

e-mail: hryssel@bgu-ludwigshafen.de

1516 Arch Orthop Trauma Surg (2010) 130:1515–1522

123

63% of the patients admitted to the ICU. These results are

conWrmed by Liu et al. [3] who reported an average length

of hospital stay of 34 days.

Causative agents

Necrotizing fasciitis is usually categorized as Type I and II.

Type I is caused by more than two bacterial genera

(polymicrobial infection) such as anaerobic bacteria and

streptococci other than streptococcal serogroup A [4–11].

Type II (monomicrobial infection) is caused by group A

streptococcus (GAS) [12]. There is no consistent data on

which type is more common. In two Taiwanese studies 20–

38% of the patients had a polymicrobial and 49–68% a

monomicrobial infection [3, 13]. Monomicrobial infection

was most commonly caused by group A streptococcus

(25% of cases) although 71–75% of tissue culture isolates

yielded mixed aerobic and anaerobic bacteria [14]. A Turkish

study found that 82% of their cases had polymicrobial

infections [15–17]. Worldwide GAS was the most common

single bacterial pathogen responsible for NF [3]. Liu et al.

[3] also found out that the most common ports of entry are

the sites of prior trauma and skin lesions (44.8% of

patients).

Other bacteria commonly associated with NF include

Aeromonas and Clostridium species [18–22]. Aeromonas

as well as Vibrio have potential virulence factors causing

severe illness and even death [3, 23]. Aeromonas hydrophilia

infections are often encountered in association with

immunosuppression, burns, or trauma [24–26].

Pathogenesis

Most bacteria and fungi proliferate within viable tissue.

The Wbrous attachments between the subcutaneous tissues

and fascial planes can help to limit the spread of

infection. However, the natural lack of these Wbrous

attachments in larger areas of the body such as the trunk

or the extremities facilitates the rapid spreading of the

infection [27–31]. The primary site of this pathology is the

superWcial fascia. The factors responsible for enhanced

invasive potential are unclear. Bacterial enzymes such as

hyaluronidase degrade connective tissue to allow rapid

spreading along the tissues in streptococcal-induced NF

[32]. Uncontrolled proliferation of bacteria causes angiothrombotic

microbial invasion and liquefactive necrosis

of the superWcial fascia [32]. The infection spreads along

fascial planes, causing widespread thrombosis of perforating

nutrient vessels to the skin and progressive skin

ischaemia [32, 33]. This is the underlying event responsible

for the cutaneous manifestations of NF [33]. Initially

a horizontal phase predominates with rapid spread

through the fascia with extensive undermining of apparently

healthy-looking skin. As the disease progresses,

ischaemic skin necrosis ensues and manifests as the

decay of body tissues such as subcutaneous fat, dermis

and epidermis, followed by progressive bullae formation

and ulceration [32].

Clinical stages

The clinical presentation of NF entails progressive skin

changes. In the early stages, signs of tenderness, swelling,

erythema and warm skin may be apparent whereas speciWc

signs such as crepitus and blistering are usually rare [32–

35]. In an Indian study, the majority of patients presented

with local tenderness (91%), oedema (99%), erythema

(72%), ulceration (73%) and purulent or serous discharge

(72%) [36]. Occasionally some patients had inconsistent

presentations. Various US studies could demonstrate additional

symptoms to the common signs of swelling and redness

(in 78–100% of cases) [28, 37, 38]. The patients

demonstrated severe pain (83%), fever (86%), hypotension

with a systolic blood pressure of less than 90 mmHg

(33%), disorientation (23%) and local anaesthesia (24%)

[15–18]. Less frequent symptoms such as crepitus and

blistering were noted in

38]. Critical skin ischaemia results in formation of blisters

or bullae, which are rarely found in cellulitis or erysipelas

[32, 34]. Blistering is caused by ischaemia-induced necrolysis.

The invading organisms cause progressive thrombosis

of the nutrient skin vessels which penetrate the fascia

[32]. In the late stages, NF lesions turn black and form a

necrotic crust with fascial tissue and brown grayish secretions

underneath the crust (Fig. 1) [34]. The occurrence of

Fig. 1 Late stage necrotising fasciitis lesion with a necrotic crust

Arch Orthop Trauma Surg (2010) 130:1515–1522 1517

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tissue necrosis results in local hyposensitivity or anaesthesia

as the nerves become involved [34]. The subcutaneous

cellular tissue gets friable and is loosened from the fascia

[34]. Tissue crepitation can occur due to gas production of

anaerobic bacteria [34]. Characteristically, the skin

becomes more erythematous, painful and swollen with

indistinct borders, violaceous hues, and necrotic bullae

[34, 40]. Eventually, it becomes haemorrhagic and gangrenous

(Table 1).

Clinical diagnosis

Diagnosis of NF depends on recognition of the characteristic

rapidly progressive clinical course [41]. There could

be a history of soft tissue injury from an animal or insect

bite, blunt or penetrating trauma, minor skin infection,

postoperative infection, or even injections (e.g. subcutaneous

insulin or illicit drugs) [31, 36]. Due to clinical similarities

between cellulitis and NF, many patients are

falsely diagnosed with cellulitis, resulting in delayed

management. The only distinguishing feature is disproportional

pain in contrast to the physical Wndings [42].

The infection in cellulitis begins at the junction between

the dermis and superWcial fascia. In NF it starts at the

level of subcutaneous fat and deep fascia, while the epidermal

and dermal layers are spared in the early stages

[39]. Oedema of the epidermal and dermal layers and erythema

of skin are therefore not obvious initially [39].

However, a number of symptoms and signs that may help

to diVerentiate the two conditions have been proposed. A

Canadian study described patients with NF as more likely

to have a generalised erythematous rash and a toxic

appearance [42]. The responsible organisms produce pyogenic

exotoxins and cytolysin that are responsible for

hypotension, multi-organ failure and disseminated intravascular

coagulation [39]. Patients with NF were also

more likely to have low platelet counts at presentation

[42]. Thrombosis of skin vessels leads to necrosis and the

severe pain fades as nerves die [39, 42, 47, 48–51].

Surgical diagnosis

The gold standard for detecting necrotizing soft-tissue

infections is a tissue biopsy obtained at the time of wound

exploration and surgical debridement [31, 42, 43]. During

wound exploration, tissue integrity and depth of invasion

are also evaluated. The presence of fascial necrosis and

myonecrosis are indicative of NF as well as loss of fascial

integrity along tissue planes, frank evidence of muscle

involvement, and kind of dishwater-coloured pus (Fig. 2)

[31, 42, 47, 48–51]. A bedside procedure that aids diagnosis

is the ‘Wnger test’. A 2-cm incision down to the deep

fascia is made under local anaesthesia and the level of the

superWcial fascia is probed with a gloved Wnger. Lack of

bleeding, foul-smelling ‘dishwater’ pus, and minimal tissue

resistance to Wnger dissection indicate a positive Wnger test

and are pathognomonic for NF [32, 33]. The operative Wndings

include the presence of dusky grey subcutaneous fat

and fascia with a scanty serosanguineous discharge [33].

There is also a lack of resistance of the normally adherent

superWcial fascia to blunt dissection, accompanied by a lack

of bleeding and the presence of foul-smelling ‘dishwater’

pus [32, 42]. Surgical diagnosis also involves examination

of frozen sections for neutrophil inWltrates at wound margins

after exploration of suspect areas.

Patients and methods

A retrospective chart review was performed of 34 consecutive

patients over a 5-year period with isolated NF of the

extremities. The patients were analysed in terms of age,

total body surface (TBS) infected, comorbidities, aetiology

of NF, bacterial analysis and number of surgical treatments.

Parts of the data have been published in another language in

a peer-reviewed manuscript previously.

Table 1 Clinical stages of necrotising fasciitis

Stage 1 Stage 2 Stage 3

Tenderness Blisters and bullae Tissue necrosis

Erythema Hyposensitivity

Edema Anaesthesia

Warm skin Tissue crepitation

Fever Haemorrhagic bullae

Sever pain

Fig. 2 Intraoperative situation after debridement

1518 Arch Orthop Trauma Surg (2010) 130:1515–1522

123

Results

Demographic data

We identiWed 34 patients in the period between 2003 and

2008 with a NF of the upper or lower extremities, or both

but without involvement of the trunk. Of these patients, 18

were males and 16 females. The average age was

56.7 § 10.6 years at arrival (Table 2).

Comorbidities

The highest prevalence of comorbidities was for 19 patients

(56%) with diabetes mellitus. 14 patients (40%) presented

with hypertension and 18 patients (52%) with overweight.

Further comorbidities were coronary disorders in 10 (28%)

and renal insuYciency in 5 (16%) patients.

Aetiology of NF

In 5 patients (15%) there was no anamnestic trauma.

Patients who noticed a lesion mostly described it as erythema.

Causative traumas have been 9£ endoprosthetic

operations, 2£ vein-stripping, 2£ liposuction, 1£ insectbite

and 15£ minimal trauma (Fig. 3).

Surgical therapy

The mean time until the Wrst operation was 1.3 § 0.4 days.

On average 3.3 operations per patient were performed. In

14 patients the Wrst operation was performed in the primary

treating hospital. All other patients underwent primary radical

necrectomy at our hospital. For complete reconstruction

34 split-thickness-skin-graWngs, 4 wound revisions, 2 kneearthrodeses,

4 local Xaps, 6 free Xaps, 2 forearm-amputations,

2 upper arm-amputations and 4 thigh-amputations

were necessary (Table 3). We successfully used vacuumassisted

closure therapy before deWnite reconstruction in all

cases; the mean time for VAC-therapy before deWnite closure

was 8.3 § 0.5 days.

Microbiology and histology

In all 34 patients an initial swab was taken. Nine patients

(26%) showed -haemolytic streptococcus Group A, three

patients (9%) -haemolytic streptococcus Group B, three

patients (9%) Pseudomonas aeruginosa and sixteen

patients (47%) had polymicrobial infections (Table 4).

Three patients had negative swab diagnostic. From all

patients material for histological examinations was taken.

In three patients the histology was characterized by an

unspeciWc granulomatous reaction; the other patients

showed typical signs of NF.

Wound therapy

In the primary period after radical necrectomy the wounds

were treated with local antiseptic agents. The most commonly

used agent in our patients was polyhexanide (80%).

Other antiseptics like mafenid acetate, povidone-iodine and

acetic acid were used alternatively. The choice of the

Table 2 Demographic data

Patients 34

Age at arrival (Mean § SD) 56.7 § 10.6 years

TBS (Mean § SD) 8.2 § 2.1%

Male/female 11/8

Fig. 3 Aetiology of NF

Table 3 Surgical therapy

Type of surgery Number

Splitt-thickness-skin-grafs 34

Knee-arthrodeses 2

Local Xaps 6

Free Xaps 6

Forearm-amputation 2

Upper arm-amputation 2

Thigh-amputations 4

Secondary sutures 3

Table 4 Microbiology

Germ Patients %

-Haemolytic Streptococcus A 9 26

-Haemolytic Streptococcus B 3 9

Pseudomonas aeruginosa 3 9

Polymicrobial infection 16 47

Arch Orthop Trauma Surg (2010) 130:1515–1522 1519

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antiseptic agent depended on the swab results. The one

patient who died was positive for streptococcal septic shock

toxine on the basis of a -haemolytic Streptococcus A

infection and suVered four comorbidities. Antibiotic therapy

was done by a triple therapy consisting of a third-generation

cephalosporine with clindamycin and metronidazol. As we

have no option of hyperbaric oxygen therapy at our center,

patients could not be treated with this adjunctive method.

Clindamycin was included in the triple therapy as it facilitates

phagocytosis of GAS by inhibiting M-protein synthesis

and is supposed to reduce endotoxine-production [50].

Management options

Prompt diagnosis, adequate support to maintain vital functions,

as well as thorough and frequent surgical debridement

are the mainstay for achieving a successful outcome.

According to published data, a mean of three debridements

was suYcient to treat and control the NF [1]. In contrast to

NF of the trunk in the demonstrated cases amputation is

always an ultima ratio to safe life over limb. SigniWcant

morbidity and mortality due to toxaemia, dehydration, and

severe biochemical disturbances were reported to occur,

whenever treatment was delayed [44]. A US study indicated

that aggressive surgical debridement at the onset was

associated with a mortality rate of 4.2%, versus 38% after

delayed treatment [45]. In another US study, 17 of 29

patients who underwent early operation (within 24 h of

admission) had 6% mortality, while after delayed surgery

the mortality went up to 25% [46]. These Wndings are consistent

with a Singaporean study stating that surgery

delayed by more than 24 h signiWcantly increases mortality

[3]. Although surgical debridement or incisional drainage is

essential for survival in patients with NF, the use of appropriate

antibiotics is equally important [42]. Since the condition

is usually polymicrobial, the initial regimen should

include agents eVective against aerobic Gram-positive

cocci, Gram-negative rods, and anaerobes. The mainstay

antibiotic regimen consists of a combination of penicillin

and clindamycin [42, 49]. Clindamycin is often used

because of a 68% failure rate attributed to single use of cell

wall-inhibiting antibiotics [50]. In these deep infections,

adding protein synthesis inhibitor has a more favourable

outcome [50]. Clindamycin also facilitates phagocytosis of

GAS by inhibiting M-protein synthesis.

Hyperbaric oxygen (HBO) therapy involves placing the

patient in an environment of increased ambient pressure

while breathing 100% oxygen and results in enhanced oxygenation

of arterial blood and tissues [42, 52]. This signiWcantly

increases tissue oxygen tension, resulting in

bacteriostasis of clostridia and halting the production of

their -toxin [52]. Infected tissue is known to be hypoxic

through a combination of poor perfusion and oedema,

whereas HBO improves neutrophil function by raising tissue

oxygen tension. Hypoxia reduces the eVectiveness of

several antibiotics such as vancomycin and ciproXoxacin,

but potentiates the action of aminoglycosides as microorganisms

expel these drugs via an oxygen-dependent pump

[52].

Once the infection is controlled, HBO-induced Wbroblast

proliferation and angiogenesis appear to assist wound closure

[12, 52]. In a US review HBO-treated patients

achieved wound closure 28 days after Wrst debridement

compared with 48 days in those not receiving HBO therapy

[38]. A study from the US involving 42 patients showed

that HBO adjunctive to comprehensive, aggressive debridements

reduced mortality compared with controls not receiving

HBO (12% vs. 34%) and morbidity (amputations being

reduced 50% vs. 0%) [53–57]. However, such Wndings are

not reported consistently. Intravenous immunoglobulin

(IVIG) has been shown to reduce mortality in NF associated

with the toxic shock syndrome, possibly by neutralising

superantigen activity of -haemolytic streptococci on

cytokine release by T-cells and by reducing plasma levels

of tumor necrosis factor and interleukin-6 [49, 56].

Sequelae

Due to diYculties in diagnosing NF, the condition is associated

with high rates of morbidity and mortality. An Australian

study reported that out of 14 patients, 93% were

admitted to the ICU, 79% required mechanical ventilation,

and 71% received inotropic support [12]. In a US study of

46 patients with NF, 61% were admitted to the ICU [58].

Urgent limb amputation is performed in patients with irreversible

necrotic changes following sepsis and failed multiple

debridements [59].

Despite eVorts to treat the rapid infective process, many

patients still die through complications of sepsis (pneumonia,

heart failure and metabolic disturbance) [61]. The mortality

rate of NF ranges from 20 to 75% [15, 61]. In a US

study 33% of 12 patients died of multi-organ failure [60–

65]. Admission with erased white cell counts, hyperkalaemia,

high partial thromboplastin times and aspartate aminotransferase

levels, low arterial pH and bicarbonate

concentrations all predicted mortality [62, 63]. In our own

study mortality for isolated NF of the extremities was 4%.

Discussion

The incidence of NF has been increasing worldwide over

the past decades. Due to diYculties in diagnosis and management

of this condition, it is a growing concern for health

care providers. Early recognition of NF is diYcult, even for

experienced clinicians. Yet, certain clinical settings should

1520 Arch Orthop Trauma Surg (2010) 130:1515–1522

123

raise suspicions. Patients with diabetes mellitus, compromised

immunity or a history of intravenous drug abuse are

particularly at risk and associated with increased mortality.

The public should also be aware of the risks and the common

clinical symptoms associated with NF; aVected individuals

must seek medical attention immediately. One of

the most challenging aspects of NF is its similarities with

other infections such as cellulitis. The distinction is crucial,

as cellulites responds readily to antibiotic treatment alone,

whereas in patients with NF, survival also depends on early

extensive surgical drainage and debridement, or even

amputation. NF is more likely if the patient presents with a

toxic appearance and/or there is crepitus and blistering.

However, this is rare, and usually both conditions present

with the classic inXammatory features: pain, swelling, erythema,

fever and warm skin. In the early period, pain out of

proportion to the skin leions might be the only symptom for

NF. In every case of suspected invasive soft tissue infection

surgical exploration is necessary.

Worldwide as also mentioned by other studies the incidence

of NF increased over the years [1, 2]. On average our

patients had 1.9 comorbidities and needed 3.3 operations

for reconstruction. Because all patients reported in this

study only had NF of the extremities, the mortality is not

comparable to studies including aVection of the trunk. In a

former study containing patients with NF aVection of the

trunk overall mortality was 15% [42]. The patient who died

in our study, had a fulminant variant with a streptococcal

toxic shock syndrome and suVered of four comorbidities.

The vacuum-assisted wound therapy proved to be a very

helpful adjunctive therapy. For local antiseptic wound therapy

diVerent antiseptics were used, and the most frequent

were polyhexanide, octinidine, mafenid acetate and acetic

acid. Swab diagnostic mostly showed infections with:

streptococcus group A 26%, streptococcus group B 9% and

Pseudomonas aeruginosa 9%. Polymicrobial infections

were present in 47% of our study, based on our data in

Germany the ratio between Type-I and Type-II NF seems

to be similar to that in Taiwan [3, 13]. In three patients histology

was characterized by an unspeciWc granulomatous

reaction; the other 31 showed typical signs of NF. The term

NF was classically taken for mono-organism infections

with streptococci, but nowadays it has to be changed to

necrotizing soft-tissue infections caused by multiple germs,

or a polymicrobial infection.

The antibiotic therapy should include clindamycin in

order to reduce the synthesis of adhesion molecules of

streptococci which are responsible for a more aggressive

spreading and invasion of NF.

The mortality of 4% in our study is due to the isolated

aVection of the extremities included in this study. On the

other hand, early treatment is another key to reduce mortality

in NF patients. Our experience of the past years led us to

the point of view that we recommend limb salvage surgery

as long as the patient’s life is not compromised. However,

if the septical situation is not under control amputation is

the only life saving solution. Currently, there is no evidence

to support amputation in the early stages. Achieving better

function versus the risks from disease severity must be balanced

in the individual clinical setting.

From our experience we recommend clinicians a high

index of suspicion for NF, which has an aggressive clinical

course and can progress rapidly within hours. Computed

tomography and magnetic resonance imaging can help to

diagnose NF at presentation, but these imaging tools take

time to process and may delay management. The most reliable

approach is to increase clinical awareness. Complaints

of pain out of proportion to the visible Wndings or excruciating

tenderness are clinical aids to early diagnosis. Upon

admission, the general approach to soft-tissue infections is

to start empirical antibiotics, as most conditions such as

cellulitis will respond. If the infection persists despite antibiotics,

repeated physical examinations should be performed

while maintaining a low threshold for tissue biopsy

and surgery. If signiWcant changes such as blistering, shock,

or hyposensitivity occur within hours, there should be no

hesitation in proceeding to surgery. Where the progression

is less pronounced, tissue biopsy should be performed. It is

safer to treat these ambiguous cases as NF and manage

them aggressively, as to delay treatment which can be lifethreatening.

Further eVorts must be made to educate the medical

community about the symptoms of these infections, to

ensure that the best possible care can be delivered in an

appropriate and timely manner to these patients in specialized

centers. Although rare, necrotizing soft-tissue infections

appear to be on the rise and are sources of signiWcant

morbidity and mortality.

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