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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 amputations and those who did not with respect to mortality
rate or age (p = 0.538 and p = 0.493, respectively). Those who
Background: Necrotizing fasciitis is a rare and often fatal soft- died were significantly older than the survivors (p = 0.038).
tissue infection. Prompt diagnosis and immediate aggressive Conclusions: The diagnosis of necrotizing fasciitis should be
surgical debridement of all compromised tissues are critical to considered for any individual who has unexplained limb pain,
reducing morbidity and mortality in these rapidly progressive especially if that person has diabetes mellitus or chronic liver
infections. The purpose of this study was to analyze the clin- disease. There was no difference in mortality rates between
ical presentation and evaluate factors that determine mortality patients with or without amputation. The primary treatment
associated with this uncommon surgical emergency. Methods: is early and aggressive debridement of involved skin, subcuta-
The study retrospectively investigated the medical records of neous fat, and fascia.
22 patients who were diagnosed and treated for necrotizing
fasciitis of the lower extremity, 14 of whom had involvement Key Words: Amputation; Diabetic Foot Ulcers; Limb
of the foot (nine patients) or foot and ankle (five patients) at Threatening
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 Necrotizing fasciitis (NF) is a rare and often fatal soft-
(debridement or amputation), treatment outcome, and number tissue infection that involves the superficial and deep fascial
of days in the hospital. Results: A total of 23 extremities of layers of the extremities, abdomen, or perineum. This condi-
22 consecutive patients with necrotizing fasciitis who under- tion is the most aggressive form of soft-tissue infection. In
went surgical debridement or amputation were retrospectively some patients, there are definite clinical signs (hypotension,
reviewed. Radical surgical debridement was done in 16 extrem- crepitus, skin necrosis, bullae, gas on radiographs), but these
ities initially, and this treatment was repeated a mean of two are not always present. Necrotizing fasciitis is caused by
times (range one to four debridements) to completely remove a mixture of aerobic and anaerobic organisms. The infection
all the necrotic tissue. Nine patients (41%) required below-knee
leads to necrosis of subcutaneous tissue, usually including the
or above-knee amputation. There were three deaths, one related
directly to sepsis and organ failure, one due to gastrointestinal
fascia. Prompt diagnosis is imperative because most necro-
hemorrhage, and one caused by pulmonary embolism. There tizing infections spread rapidly and can result in multiple
were no significant differences between patients who had the organ failure, adult respiratory distress syndrome, or death.
The treatment for this disease is complete surgical debride-
Baskent University School of Medicine, Department of Orthopaedics and Trauma- ment of all involved tissues, but additional debridement or
tology, Adana Medical Center, Adana, Turkey
amputation may be necessary.5,7,15,17,19 The purpose of this
Baskent University School of Medicine, Department of Orthopaedics and Trauma-
tology, Ankara Medical Center, Ankara, Turkey study was to analyze the clinical presentation and eval-
uate factors that determine mortality associated with this
Corresponding Author:
Metin Ozalay, M.D.
uncommon surgical emergency.
Baskent University Hospital
Dadaloglu mah. 39.sok, No. 6
E-mail: mozalay@baskent-adn.edu.tr The medical records of all patients (22) who were treated
For information on prices and availability of reprints, call 410-494-4994 X226 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 NECROTIZING SOFT-TISSUE INFECTION 599

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

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

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
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
7 M 72 L Fever, DM Lower Thigh, calf Wound Cellulites Pain, erythema, gas
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
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,
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,
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.
602 OZALAY ET AL. Foot & Ankle International/Vol. 27, No. 8/August 2006

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
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
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
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,
12 MRSA 86 18 8900 0 Below-knee exitus (PE- 30
13 Klebsiella spp. 90 96 11000 0 Below-knee exitus (GIS 15
14 MRSA 88 16 6470 0 Below-knee survived 26
15 Staphylococcus 76 18 6520 1 survived 30
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
19 MRSA 110 96 22000 2 Exitus (Multiple 35
organ failure)
20 -hemolytic Group A 139 96 11800 2 survived 35
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


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

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604 OZALAY ET AL. Foot & Ankle International/Vol. 27, No. 8/August 2006

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

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Foot & Ankle International/Vol. 27, No. 8/August 2006 NECROTIZING SOFT-TISSUE INFECTION 605

and all survived. The other patient died from multiple organ 9. Meleney, FL: Hemolytic streptococcus gangrene. Arch. Surg.
failure. 9:317 364, 1924.
10. Morales, AF; Castrellon, PG; Mckinster, CD; et al: Necro-
tizing fasciitis. Report of 39 pediatric cases. Arch. Dermatol.
138:833 899, 2002.
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