FOOT & ANKLE INTERNATIONAL

Copyright 2006 by the American Orthopaedic Foot & Ankle Society, Inc.

Necrotizing Soft-Tissue Infection of a Limb: Clinical Presentation and Factors

Related to Mortality

Metin Ozalay, M.D.1 ; Gurkan Ozkoc, M.D.1 ; Sercan Akpinar, M.D.1 ; Murat Ali Hersekli, M.D.1 ; Reha N. Tandogan, M.D.2
Adana, Turkey

ABSTRACT
Background: Necrotizing fasciitis is a rare and often fatal soft-
tissue infection. Prompt diagnosis and immediate aggressive
surgical debridement of all compromised tissues are critical to
reducing morbidity and mortality in these rapidly progressive
infections. The purpose of this study was to analyze the clin-
ical presentation and evaluate factors that determine mortality
associated with this uncommon surgical emergency. Methods:
The study retrospectively investigated the medical records of
22 patients who were diagnosed and treated for necrotizing
fasciitis of the lower extremity, 14 of whom had involvement
of the foot (nine patients) or foot and ankle (five patients) at
our hospital. The data collected for each of the 22 patients
were age, sex, underlying systemic factors, location of infec-
tion, duration of symptoms, portal of entry of infection, initial
diagnosis on admission, physical, radiographic and laboratory
findings, microbiological cultures, the type of therapy used
(debridement or amputation), treatment outcome, and number
of days in the hospital. Results: A total of 23 extremities of
22 consecutive patients with necrotizing fasciitis who under-
went surgical debridement or amputation were retrospectively
reviewed. Radical surgical debridement was done in 16 extrem-
ities initially, and this treatment was repeated a mean of two
times (range one to four debridements) to completely remove
all the necrotic tissue. Nine patients (41%) required below-knee
or above-knee amputation. There were three deaths, one related
directly to sepsis and organ failure, one due to gastrointestinal
hemorrhage, and one caused by pulmonary embolism. There
were no significant differences between patients who had the
1
Baskent University School of Medicine, Department of Orthopaedics and Trauma-
tology, Adana Medical Center, Adana, Turkey
2
Baskent University School of Medicine, Department of Orthopaedics and Trauma-
tology, Ankara Medical Center, Ankara, Turkey
Corresponding Author:
Metin Ozalay, M.D.
Baskent University Hospital
Dadaloglu mah. 39.sok, No. 6
Yuregir, 01250
Adana
Turkey
E-mail: mozalay@baskent-adn.edu.tr
For information on prices and availability of reprints, call 410-494-4994 X226
598
amputations and those who did not with respect to mortality
rate or age (p = 0.538 and p = 0.493, respectively). Those who
died were significantly older than the survivors (p = 0.038).
Conclusions: The diagnosis of necrotizing fasciitis should be
considered for any individual who has unexplained limb pain,
especially if that person has diabetes mellitus or chronic liver
disease. There was no difference in mortality rates between
patients with or without amputation. The primary treatment
is early and aggressive debridement of involved skin, subcuta-
neous fat, and fascia.
Key Words: Amputation; Diabetic Foot Ulcers; Limb
Threatening
INTRODUCTION
Necrotizing fasciitis (NF) is a rare and often fatal soft-
tissue infection that involves the superficial and deep fascial
layers of the extremities, abdomen, or perineum. This condi-
tion is the most aggressive form of soft-tissue infection. In
some patients, there are definite clinical signs (hypotension,
crepitus, skin necrosis, bullae, gas on radiographs), but these
are not always present. Necrotizing fasciitis is caused by
a mixture of aerobic and anaerobic organisms. The infection
leads to necrosis of subcutaneous tissue, usually including the
fascia. Prompt diagnosis is imperative because most necro-
tizing infections spread rapidly and can result in multiple
organ failure, adult respiratory distress syndrome, or death.
The treatment for this disease is complete surgical debride-
ment of all involved tissues, but additional debridement or
amputation may be necessary.5,7,15,17,19 The purpose of this
study was to analyze the clinical presentation and eval-
uate factors that determine mortality associated with this
uncommon surgical emergency.
MATERIALS AND METHODS
The medical records of all patients (22) who were treated
for NF of a lower limb at our institution from 1998 through

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Foot & Ankle International/Vol. 27, No. 8/August 2006
2003 were retrospectively reviewed. The average age of the
14 men and eight women was 60 (range 44 to 77) years. One
patient (Case 15) had bilateral lower extremity involvement.
The presence of grayish necrotic fascia, demonstration of
a lack of resistance of normally adherent muscular fascia to
blunt dissection, and presence of foul-smelling dishwater
pus were the operative findings used to diagnose NF. In all
patients, tissue specimens were histopathologically examined
to confirm the diagnosis.
For each patient, we recorded age, sex, underlying
systemic factors, location of infection, duration of symptoms,
portal of entry of infection, initial diagnosis on admission,
and physical, radiographic and laboratory findings (white
blood cell count, erythrocyte sedimentation rate, C-reactive
protein level) at the time of admission. The results from
microbiological cultures of tissue samples obtained at the
time of first operative debridement or amputation also were
analyzed. The type of therapy used (debridement or amputa-
tion), treatment outcome, and number of days in the hospital
were noted as well.
The data were statistically analyzed with the Students
t -test and the non-parametric Mann-Whitney U test. All
calculations were done using the software SPSS for Windows
version 10.0 (SPSS Inc., Chicago, IL, USA).
RESULTS
The comorbid conditions that predisposed the patients
to NF were diabetes mellitus (20 patients), chronic renal
failure (three patients), cancer (two patients), and chronic
liver disease (one patient). At the time of admission, 13
patients were febrile, eight were hypotensive, and one had
multiple organ failure. The areas of the body involved were
the foot (nine patients) (Figure 1), calf (three patients), thigh
(four patients), thigh-calf (two patients), and foot-calf (five
patients). Seven (32%) of the patients developed NF with
no identifiable antecedent trauma based on patient history or
visible injury to the involved area. One patient (Case 16) had
a history of periarticular steroid injection. In this patient, MRI
demonstrated multiple abscesses between the muscle bellies
(Figure 2). Two patients (Cases 3,6) had had their extremities
punctured by tree thorns. The local signs and symptoms of
NF in the 22 patients were pain and erythema (all patients),
edema (nine patients), hemorrhagic bullae (eight patients),
and local warmth (one patient). The initial diagnoses at
admission were NF (11 patients), cellulitis (nine patients),
thrombophlebitis (one patient), and deep vein thrombosis
(one patient). Radiographic studies were obtained in all
patients, and the results showed soft-tissue swelling in all 22
patients and localized gas production in 11 patients (Table 1).
The laboratory findings revealed white blood cell counts in
the range of 5,200-32,200 cells/L (mean, 15,490 cells/L),
erythrocyte sedimentation rates ranging from 39 150 mm/h
(mean, 103 mm/h), and serum C-reactive protein >10 mg/L
in all patients (Table 2).
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NECROTIZING SOFT-TISSUE INFECTION 599
Fig. 1: Case 2. Necrotizing fasciitis of the foot.
All the patients required surgical intervention and empir-
ical antibiotic therapy for NF (sefazolin and amikacin and
clindamycin were used initially). Antibiotics were changed
once the results of wound or blood cultures were known.
Surgical debridement under general anesthesia was done in
16. Radical debridement was repeated a mean of two times
(range one to four debridements) to completely excise the
necrotic tissue. Nine of the infections (41%) required below-
knee or above-knee amputation. Four of the below-knee
amputations (Cases 12,13,14,17) were necessary initially
because the infection had spread rapidly from the distal part
of the limb, with extensive skin necrosis. One patient (Case
11) underwent below-knee open amputation followed by
secondary closure 5 days later. Two patients (Cases 5,6) had
below-knee amputation initially, but subsequent septicemia
and profound shock necessitated above-knee amputation as
well. In the other two patients with amputation (Cases 1, 2),
below-knee amputation was needed after debridement proved
insufficient. Culture results for the tissue specimens obtained
at the time of first operative debridement (or amputation if
that was the first procedure performed) were analyzed. A
single organism was identified in 13 patients (59%), multiple
organisms in seven patients (32%), and no organism was
identified in two (9%). The organisms found most frequently
were methicillin-resistant Staphylococcus aureus and Strep-
tococcus pyogenes (a group A -hemolytic Streptococcus)
(Table 2).
Three (14%) of the 22 patients died. One had refused
amputation and died from sepsis and multiple organ failure.
Another patient died from pulmonary embolism 25 days
after amputation. The third patient died from gastrointestinal
hemorrhage. The mean age of the survivors was 58.5 (range
44 to 72) years and the mean age of the deceased was 70.6
(range 66 to 77 years) years, and this difference in age was
significant (p = 0.038). The differences between the patients
who had amputation and those who did not with respect to
mortality rate and age were not significant (p = 0.538 and
 600

Table 1: The details of the 22 cases who had necrotizing soft tissue infection of a limb
OZALAY ET AL.

Age Systemic Underlying Upper/ Initiating First Clinical

No. Sex (yrs) Side factors Factors Lower Location Factors Diagnosis Findings Radiological
1 M 61 R DM,hemiplegia, Lower Foot Wound Cellulitis Pain, erythema, gas
chronic renal bullae
failure
2 M 69 R Fever DM, chronic Lower Foot Wound Cellulites Pain, erythema, gas
renal failure bullae
3 M 49 R DM, chronic Lower Foot Orange tree Cellulites Pain, erythema
renal failure thorn
4 M 44 L Fever, DM Lower Thigh None Cellulites Pain, erythema, gas
hypotension local warmth
5 M 67 L Fever DM Lower Foot, calf None Cellulites Pain, erythema gas
6 M 51 L DM Lower Foot Orange tree NF Pain, erythema gas
thorn
7 M 72 L Fever, DM Lower Thigh, calf Wound Cellulites Pain, erythema, gas
hypotension
8 F 70 R Fever, DM, breast Lower Thigh None NF Pain, erythema, gas

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hypotension carcinoma bullae
9 M 46 R Fever, DM Lower Thigh None NF Pain,
hypotension erythema,edema
10 M 59 R DM Lower Foot None NF Pain, erythema,
plantar bullae
11 M 56 R Fever DM Lower Foot,calf Wound NF Pain,erythema gas
12 M 69 R hypotension DM Lower Foot, calf Wound NF Pain, erythema gas
(Continued)
Foot & Ankle International/Vol. 27, No. 8/August 2006
 Table 1: (Continued)

Age Systemic Underlying Upper/ Initiating First Clinical

No. Sex (yrs) Side factors Factors Lower Location Factors Diagnosis Findings Radiological

13 M 66 L DM Lower Foot,calf Wound NF Pain, erythema gas

14 F 53 R Fever DM Lower Foot, calf Wound NF Pain, erythema
Foot & Ankle International/Vol. 27, No. 8/August 2006

15 M 63 RL Lower Left calf, None Thrombophlebitis Pain, erythema, gas

right foot edema
16 F 48 L Fever, DM Lower Calf Steroid Cellulites Pain, erythema,
hypotension injection oedema
17 F 64 R DM Lower Foot Wound NF Pain, erythema,
oedema
18 F 61 L Fever, DM, lung Lower Thigh None Deep venous Pain, bullae,
hypotension carcinoma thrombosis edema
19 F 77 R Multiple organ DM Lower Thigh, calf Wound Cellulites Pain, bullae,
failure edema
20 M 71 L Fever, DM Lower Foot Wound NF Pain, bullae,
hypotension edema

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21 F 57 R Fever DM Lower Foot Wound NF Pain, bullae,
edema
22 M 44 R Fever chronic liver Lower Calf None Cellulites Pain, erythema,
disease edema

M: Male, F: Female, R: Right, L: Left, DM: Diabetes Mellitus, NF: Necrotizing Fasciitis.
NECROTIZING SOFT-TISSUE INFECTION
601
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Table 2: The microbiological cultures, laboratory findings, debridement sessions, type of therapy used, treatment outcome,
number of days in hospital are shown in the table

Bacteria ESR CRP WBC Debridement Hospital

No. Isolated (mm/h) (mg/L) (cells/L) Sessions Amputation Outcome Stay
1 MRSA, pseudomonas 120 96 24000 3 Below-knee survived 27
spp.
2 Proteus spp., 125 96 22800 2 Below-knee survived 23
escherichia coli,
klebsiella spp.
3 MRSA 140 16 5200 4 survived 60
4 None 150 18 8100 1 survived 32
5 MRSA 83 96 15200 2 Below-knee, survived 34
above-knee
6 -haemolytic Group 128 13 11300 0 Below-knee, survived 30
A streptococcus above-knee
7 Pseudomonas spp., 135 96 32200 2 survived 45
enterococcus spp.
8 Staphylococcus 150 96 17600 2 survived 29
epidermidis,
candida spp.
9 MSSA 86 16 14300 1 survived 13
10 Escherichia coli 110 45 16800 3 survived 52
11 -hemolytic Group A 87 16 6500 0 Open survived 20
streptococcus below-knee,
debridement,
secondary
closure
12 MRSA 86 18 8900 0 Below-knee exitus (PE- 30
postoperatively
25.day)
13 Klebsiella spp. 90 96 11000 0 Below-knee exitus (GIS 15
haemorrhage-
7.day)
14 MRSA 88 16 6470 0 Below-knee survived 26
15 Staphylococcus 76 18 6520 1 survived 30
epidermidis
16 MSSA 81 13 19700 1 survived 28
17 Staphylococcus 105 96 24300 0 Below-knee survived 14
coagulase ()
enterococcus spp.
18 MRSA,candida 73 96 13200 3 survived 120
spp.,pseudomonas
spp.
19 MRSA 110 96 22000 2 Exitus (Multiple 35
organ failure)
20 -hemolytic Group A 139 96 11800 2 survived 35
streptococcus,
enterococcus spp.
21 None 68 96 17800 2 survived 36
22 MSSA 39 96 26500 1 survived 31

ESR: Erythrocyte Sedimentation Rate, CRP: C-Reactive Protein, WBC: White Blood Cell Count, MRSA: Methicillin-Resistant Staphylococcus aureus,
MSSA: Methicillin-Resistant Staphylococcus aureus, PE: Pulmonary Embolism, GIS: Gastrointestinal System.

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Foot & Ankle International/Vol. 27, No. 8/August 2006 NECROTIZING SOFT-TISSUE INFECTION 603

A B

Fig. 2: A and B, Magnetic resonance imaging demonstrating multiple abscesses (arrows) between muscle bellies in case 16.

Table 3: Comparisons of age, hospital stay, and mortality in the amputated group
versus the non-amputated group

Non-amputated Amputated
Mean SD MeanSD
Median (Min-Max) Median (Min-Max) P value
Age (yrs) 58.86 11.23 61.78 6.91 0.493
60 (44 77) 64(51 69)
Hospital Stay (days) 43.14 26.11 24.33 6.91 0.01
33.5 (13 120) 26(14 34)
Mortality 1/14 (7%) 2/9 (22%) 0.538

p = 0.493, respectively). The average hospital stay for the
22 patients was 35.8 (range 13 to 120) days. The patients who
had amputation had a significantly shorter mean hospital stay
than the patients who did not have an amputation (p = 0.01)
(Table 3).
DISCUSSION
In the 16th Century, Ambroise Pare described a gangrene-
like condition that resembled todays flesh-eating disease.16
In 1952, Wilson proposed the term necrotizing fasciitis to
replace terms like gangrenous erysipelas, hospital gangrene,
acute cutaneous cellulitis, streptococcal gangrene, synergistic
necrotizing cellulitis, Meleney cellulitis, and others.16 Necro-
tizing fasciitis most often affects middle-aged adults, but
there are no sex, race, or geographic predilections with this
condition. The lower extremities are affected most frequently,
followed by the trunk and head.8,10 The pathogenesis of NF
is still not fully understood, but the rapid and destructive
clinical course of this condition is believed to result from

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604 OZALAY ET AL.
multibacterial symbiosis.4 Diabetes is the main predisposing
factor in adults, but other chronic conditions, such as hyper-
tension, peripheral vascular disease, renal failure, obesity,
alcoholism, and malnutrition are other important underlying
factors.14
The initiating factors for NF reported in the literature
include minor injuries, surgical and traumatic wounds, contu-
sions, and varicella.10 In newborns, omphalitis, circumcision,
and placement of electrodes for monitoring of vital signs
also have been identified as triggering factors.10 Another
known initiator of NF is minor environmental trauma, such
as an acute force or injury to the foot causing an imme-
diate wound or soft-tissue injury that breaks the cutaneous
barrier.13 Fourteen (68%) of the 22 patients with NF in our
series had identifiable antecedent trauma: periarticular steroid
injection in one, major trauma caused by tree thorns in two,
and diabetic foot ulcers in 11. One report in the literature
described NF as a complication of steroid injection in a
painful shoulder.2 As noted, one of our patients developed
NF after subcutaneous periarticular steroid injection in the
knee for joint pain. One week after this injection, we debrided
the patients calf and diagnosed NF. Many of our diabetic
patients were not aware of the fact that they had neuropathic
feet. Because these patients may not have had information
about foot care, they may have walked with bare feet and
easily could have developed foot ulcers that were initiating
factors of the NF. Currently in the United States, more than
50,000 amputations related to diabetes are performed each
year.18 This type of operation dramatically reduces patient
function and quality of life and places a heavy burden on
affected individuals, their families, and health care systems. It
is vital that we reduce amputation rates in this patient group,
and the importance of preventing any form of minor trauma
(shoewear-related or minor environmental trauma) cannot be
overemphasized. This is especially true for patients who are
already compromised with neuropathy and vascular disease
like diabetes mellitus or chronic liver failure.
The clinical manifestations of NF appear roughly 1 week
after the initiating event, with induration and edema followed
24 to 48 hours later by erythema or purple discoloration and
increasing warmth at the site.9 Systemic signs and symptoms
develop from the toxic process and septicemia. High fever
is disproportionate to the size of the cutaneous lesion.9 Pain
is an important sign in the early stages, and some patients
exhibit crepitus at the site. Forty-eight to 72 hours after
initial signs and symptoms arise, the skin becomes smooth
and lighter in color, and serous or hemorrhagic blisters
develop. Without treatment, necrosis ensues and, by the fifth
or sixth day, the lesion turns black and features a necrotic
crust. Sometimes gas production by aerobic and anaerobic
bacteria is identified on the basis of crepitation.9 Although
inconsistently frequent, this sign is highly suggestive of NF.
It was present in 11 of our patients. In our series, NF was
diagnosed at admission in 11 of the 22 patients. Cellulitis,
thrombophlebitis, and deep vein thrombosis were the initial
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Foot & Ankle International/Vol. 27, No. 8/August 2006
diagnoses in the other 11 patients. These findings suggest
that the diagnosis of NF often is overlooked, which means
that specific therapeutic measures are delayed. The literature
indicates that bacteria are isolated from the affected tissue in
approximately 62% to 76% of NF patients.7,11 The typical
polybacterial nature of NF is well documented.3 In our series,
20 patients (91%) had positive tissue cultures, but only seven
(32%) had polymicrobial isolates. Group A -hemolytic
Streptococcus was the agent most frequently incriminated
in NF, but many other bacteria may be involved.
Various aids for achieving early diagnosis of NF have
been suggested, but the key is a high level of suspicion.6
Numerous radiological methods have been used to identify
this condition. Plain radiographs can provide information in
the form of soft-tissue thickening and internal gas formation,
but these films usually do not reveal any specific abnormality
until the necrotizing process is well advanced. It seems that
anaerobic conditions or diabetes are necessary for clinically
detectable quantities of gas to be produced. The MRI findings
in cases of necrotizing soft-tissue infection include thick-
ening of the subcutaneous tissues, enhancement of this thick-
ened tissue with contrast, possible fluid collections within
the subcutis and superficial fascia, and high signal intensity
in the deep fascia on T2-weighted images.12 Arslan et al.1
demonstrated that T2-weighted images (especially those with
fat suppression) are highly sensitive for diagnosing NF, but
that the specificity of MRI for this purpose is extremely
low.1 Work by Yen et al.20 showed that ultrasonography
gives emergency physicians accurate information that can
help identify NF. In our series, MRI was performed in only
one patient (Case 16). Plain radiography revealed gas in only
11 of the 22 patients. Reliance on adjunctive tests may delay
operative treatment and the diagnosis should be apparent if
a meticulous physical examination is done within 24 to 48
hours after the first signs appear.
The mortality rate in this series of patients was 14%.
The corresponding figures in the literature range from 8%
to 100%.11 The high mortality rate for NF reflects the
severity of this infection. Research has revealed associations
between mortality and age of the affected patient, percentage
of body surface involved, presence of systemic acidosis or
hypotension, and time delay between admission to hospital
and surgical debridement.15 In our study, we found no
significant difference between the mortality rates in the
patients with and without amputation. Early and aggressive
debridement of the involved skin, subcutaneous fat, and
fascia is the most important element of treatment. Diseased
distal extremities usually can be managed with multiple
sessions of radical debridement. Antibiotics may not reach
the necrotic tissue because of thrombosis of vessels in the
affected region; therefore, both necrotic skin and fascia must
be excised. Amputation should be considered in patients who
have proximal limb involvement.15 In our series, only six
patients had diseased proximal extremities. Five of these
individuals were treated with multiple debridement sessions
Foot & Ankle International/Vol. 27, No. 8/August 2006
and all survived. The other patient died from multiple organ
failure.
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