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REVIEW ARTICLE

Necrotizing fasciitis: Classification, diagnosis, and management


Luca Lancerotto, MD, Ilaria Tocco, MD, Roberto Salmaso, MD, Vincenzo Vindigni, MD, PhD,
and Franco Bassetto, MD, Padova, Italy

ABSTRACT: Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical and surgical emergency. It is
characterized by subtle, rapid onset of spreading inflammation and necrosis starting from the fascia, muscles, and subcutaneous
fat, with subsequent necrosis of the overlying skin. Once suspected, immediate and extensive radical debridement of necrotic
tissues is mandatory. Appropriate antibiotics and intensive general support avoid massive systemic diffusion of the infective
process and are the key for successful treatment. However, early diagnosis is missed or delayed in 85% to 100% of cases in large
published series: because of the lack of specific clinical features in the initial stage of the disease, it is often underestimated or
confused with cellulitis or abscess. Mortality rates are still high and have shown no tendency to decrease in the last 100 years.
Unfortunately, the prevalence of the disease is such that physicians rarely become sufficiently confident with NF to be able to
proceed with rapid diagnosis and management. This review covers the literature published in MEDLINE in the period 1970 to
December 31, 2010. Particular attention is given to the clinical and laboratory elements to be considered for diagnosis. A wide
variety of diagnostic tools have been described to facilitate and hasten the diagnosis of NF, but the most important tool for early
diagnosis still remains a high index of clinical suspicion. (J Trauma. 2012;72: 560 566. Copyright 2012 by Lippincott Williams
& Wilkins)
KEY WORDS: Necrotizing fasciitis; subcutaneous tissue; fascia; soft tissue infection; skin.

N ecrotizing fasciitis (NF) is a rare infection of the soft


tissues, characterized by rapid but subtle onset of
spreading inflammation and necrosis starting from the fascia,
MATERIALS AND METHODS
This review is based on a search of the literature on NF
and related skin diseases (necrotizing and nonnecrotizing soft
involving muscles and subcutaneous fat, with subsequent tissue infections) published in MEDLINE in the period 1970
necrosis of the overlying skin. Hippocrates (500 BC) gave an to December 31, 2010, and bibliographies of retrieved arti-
early description as diffused erysipelas caused by trivial cles. Key words searched were necrotizing fasciitis (NF),
accidents, [where] flesh, sinews, and bones fell away in large cellulitis, fascia, subcutaneous tissue infection, group A
quantities, [leading to] death in many cases. NF features and Streptococcus, and necrotizing soft tissue infection. Reviews,
rapidity are such that it continues to attract peoples imagi- randomized controlled trials, observational studies, and case
nation and the attention of the mass media.1 Once suspected, reports in English or French were considered. Data were
rapid, extensive radical debridement of necrotic tissues, ap- extracted independently by three reviewers, and any disagree-
propriate antibiotics, and intensive general support avoid ment was resolved by consensus.
massive systemic diffusion of the infective process and are Epidemiology
the key for successful treatment.2,3 However, the lack of
NF is a rare disease. The US Center for Disease Control
specific clinical features and skin changes in the initial stage and Prevention estimates that 500 to 1,000 cases of NF are
of the disease easily lead to underestimation or misdiagnosis diagnosed each year in the United States (population
as cellulitis or abscess.4 6 For this reason, mortality rates 309,000,000).7 The incidence of NF in adults is reported to be
have remained almost unchanged through the centuries. Un- 0.40 cases per 100,000 population.8 It progressively increases
fortunately, the prevalence of the disease is such that physi- among patients aged 50 years and older, reaching 12 per
cians rarely become sufficiently confident with NF to be able 100,000 over the age of 80.9 A seasonal fluctuation has been
to proceed with rapid diagnosis and management. observed, with higher incidence in cold months (January to
April).9 No significant difference in incidence is observed
between men or women. Authors report periodical peaks in
the population, partially explained by increased microbial
Submitted: May 28, 2011, Accepted: August 12, 2011. virulence and resistance to antibiotics.9,10 The results of
From the Clinic of Plastic Surgery (L.L., I.T., V.V., F.B.), University of Padova,
Padova, Italy; and Department of Pathology (R.S.), University Hospital of
population-based surveillance suggest that 85% of invasive
Padova, Padova, Italy. infections occur sporadically in the community, 10% are
Address for reprints: Luca Lancerotto, MD, Clinic of Plastic Surgery, Uni- hospital acquired, 4% occur in residents of long-term care
versity of Padova, Via Giustiniani 2, 35128 Padova, Italy; email: facilities, and 1% after close contact with a case.11 The results
luca.lancerotto@unipd.it.
of population-based active surveillance in Ontario, Canada,
DOI: 10.1097/TA.0b013e318232a6b3 suggest that the rate of secondary cases of streptococcal toxic

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shock syndrome (STSS) or NF infection is 2.9 cases per 1,000 TABLE 2. Diagnostic Criteria of Streptococcal Toxic Shock
household contacts, which is 200 times the baseline risk in the Syndrome
community; but the 95% confidence interval around this esti-
mated rate are wide (0.8 7.5 per 1,000).11 Isolation of group A Streptococcus (pyogenes) from a normally sterile site
(e.g., blood and liquor) and hypotension (90 mm Hg) and two or
NF is a predominantly adult disorder: it has been reported more of:
in 0.08 per 100,000 children per year. However, in children, it Renal impairment (creatinine 2 normal)
has a fulminant course with a high mortality rate.12 Coagulopathy (CID) or platelets 100.000/mm3
The hospital admission rate for NF is 2.73 per 10,000 Liver involvement (AST, ALT or bilirubine 2 normal)
admissions.2,13,14 An Australian study reported that the mean Adult respiratory distress syndrome
hospital length of stay for survivors of NF was 36 days, and the Generalized erythematous rash that may desquamate
average cost per patient during hospital stay was AUS$64.517 Soft tissue necrosis (NF, myositis, or gangrene)
(47.0265; US$47.0265).15 For 63% of their patients admitted to
Modified from Davies.13
the intensive care unit (ICU), the average length of stay in the
ICU was 11 days. A similar average duration of hospitalization
(34 days) was reported from Taiwan.16
Microbiology
Classification From an examination of recent case series, bacteria of the
NF is classified into two types, based on microbiology Streptococcus species seem to be the most common single
(Table 1). Type I NF is a polymicrobial infection, with at causative organism. Staphylococcus aureus stands as the second
least one anaerobic species in combination with one or more most frequently isolated aerobic bacteria, followed by Entero-
facultative anaerobic species, such as nontypable streptococci coccus species, Lactobacillus, and Corinebacterium species.
and members of Enterobacteriaceae.17 It is typically located Escherichia coli and Klebsiella were the commonest facultative
at the trunk, abdominal wall, perianal and groin areas, and in anaerobic bacteria isolated, followed by anaerobic cocci. Clos-
postoperative wounds.5 In newborns, type I NF can be a tridium species are now a rare cause of NF, despite their
life-threatening complication of omphalitis.18 Approximately historical prevalence, as a result of improved sanitation. How-
55% to 75% of all NF result from type I infection. ever, hundreds of single reports are found in the literature in
Type II NF is a monomicrobial infection, most commonly which cases of NF were caused by an extremely high variety of
caused by invasive group A Streptococci (GAS)-pyogenes, less microorganisms. Indeed, the clinical manifestations known by
frequently by other streptococci or staphylococci. the name of NF are the common angiothrombotic and necrotiz-
Type II is associated with minor cutaneous/muscular ing outcomes of a spectrum of invasive soft tissue infections, in
injuries in otherwise healthy, immunocompetent patients. which a common element is the primary involvement of fascial
Predominant isolation sites are the head/neck and extremities. structures.
GAS NF may present together or complicate with streptococ- In the last 6 years, an increasing incidence of methicillin-
cal toxic shock syndrome (STSS) in about 30% of cases resistant S. aureus soft tissue infections has been reported, so
(Table 2).13,14,19 No difference in mortality rates is observed that today methicillin-resistant S. aureus is cultured in up to
between type I and type II.20 40% of necrotic wounds.23 In general, polymicrobial infec-
Recently, authors have also described a third type because tions tend to have longer incubation periods than monomi-
of marine Vibrio species, reported as following minor injuries crobial infections, thus making them difficult to detect at an
exposed to salt water, i.e., fish stings and bites or shellfish early stage.
injuries. This third type is associated with a fulminant course, Sites of Infection
with development of multiorgan failure within 24 hours if not
The most common sites of infection are extremities,
treated.10,20,21 When affecting the scrotum/perineum, NF is
particularly the upper limb, primary site in 10% to 48% of NF
known by the name of Fourniers gangrene, from Jean Alfred
in large series. Lower extremities (28%), perineum (21%),
Fournier who first described it in 1886.22
trunk (18%), and head or neck (5%) follow.14 In newborns,
necrotizing soft tissue infections most commonly involve the
abdominal wall as the initial site, followed by the thorax,
TABLE 1. Necrotizing Fasciitis Classification back, scalp, and extremities including the thigh and groin.24
Type Species Localization Predisposing Factors
Type 1 Polimicrobial: at least one Trunk, abdomen, More than half the patients developing NF have preexist-
anaerobic facultative anaerobes and perineum ing medical conditions, 35% at least two.25 The most common
(Enterobacteriaceae, nongroup A predisposing risk factors include diabetes mellitus (30%), im-
streptococci)
mune suppression (17%), end-stage renal failure, liver cirrhosis,
Type 2 Monomicrobial: group A -hemolytic Extremities pulmonary diseases (6%), malignancy (5%), and use of injection
streptococci and/or other
streptococci staphylococci drugs.2,14,26 A recent Varicella infection has been identified as a
Type 3 Marine Vibrios Extremities risk factor for GAS NF among children.13 Blunt trauma has long
been anecdotally associated with higher risk of NF, and two
Modified from Low and McGeer.5
recent case-control studies seem to confirm this observation in

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the case of invasive GAS disease. Interestingly, the same studies Clinical Presentation
found no significant association between blunt trauma and cel- The term necrotizing fasciitis, first coined by Wilson
lulitis.27 Bryant et al.28 suggested that, at least in case of GAS, in 1952, is perhaps the most accurate in describing the key
this may be due to the higher exposure of vimentin on the features of the infectious process.31
surface of injured muscle cells, which would act as binding The most constant initial clinical feature is pain out of
protein for the bacteria. proportion to physical findings, in which case NF should
In newborns, several underlying conditions have been definitely be considered in differential diagnosis. Wang et
identified as contributing to the development of NF, including al.32 developed a clinical staging system based on a retro-
omphalitis, mammitis, balanitis, fetal scalp monitoring, post- spective evaluation of 22 patients (Table 3). At initial assess-
operative complications, septicemia, and necrotizing entero- ment (day 0), almost all patients presented with erythema,
colitis.24 Overall, 16% of NFs in children are associated with tenderness, warm skin, and swelling (Fig. 1). Blistering
a chronic underlying illness, patients with leukemia having an occurred in 41% of patients at presentation, whereas late
increased risk above all.29 signs such as skin crepitus, necrosis, and anesthesia were
infrequently seen (0 5%). As time elapsed, more patients had
Diagnosis blistering (77% had blisters at day 4) and eventually the late
Establishing the diagnosis of necrotizing soft tissue signs of NF, skin crepitus, necrosis (Fig. 2), and anesthesia
infections is not easy. In early stages, cases of NF are easily (9 36%). It is important to emphasize that these hard signs,
confused with cellulitis or abscesses. Early diagnosis is although typical and specific, are observed in only 10% to
missed in 85% to 100% of cases in large published series14 40% of patients.4,14,33 Moreover, they can quickly progress
and it is reported as the single cause of fatal outcomes.30 A within 24 hours to 48 hours, especially when NF is substained
wide variety of diagnostic tools have been described and by Streptococcus species. The absence of respiratory symp-
tested to facilitate and hasten the diagnosis of NF, based on toms, the presence of focal pain, and a recent history of
the close relation of rapid diagnosis and clinical outcome. penetrating or blunt trauma may be helpful diagnostic
clues.13,14,19,34 Introduction of the pathogen into the subcuta-
neous space may occur via any disruption of the overlying
skin (cut, abrasion, burn, laceration, contusion, bite, injection,
TABLE 3. Necrotizing Fasciitis Signs and Symptoms or surgical incision).
NF of the upper limb has a rapid centripetal diffusion to
Early Late
shoulder, neck, and trunk, which is facilitated by the rich
Local vascularity of the elbow region and of the fascial planes of
Skin puncture or injury Hematic/gas bullae arm and forearm.3537 Involvement of the chest area is asso-
Erythema Necrosis ciated with a negative outcome and must be prevented.38,39 A
Warmness Purple/blue skin colour combination of lesions in the perineal and lower extremities
Tenderness Crepitus has rarely been documented.
Myalgia Hypoesthesia
Hypersensitive skin Sensory/motor deficit Laboratory
Systemic Laboratory findings are nonspecific: 1white blood
Pain out of proportion Fever (sometimes hypothermia) cell count (WBC), 1creatine phosphokinase, 2albumin,
Swelling Hypotension 2sodium (Na), 1prothrombin time, or activated partial
Fever Mental confusion thromboplastin time have been suggested as useful param-
Multiorgan failure eters to identify NF cases, but are not exclusive.13,34 Wall
Modified from Wang et al.32 et al.26 suggested WBC 15.4 109 and Na 135
mmol/L, the former more important than the latter, as

Figure 1. Case 1 (A) Edematous, tender appearance of the arm, elbow, and upper half of forearm at referral; (B) same case,
exploration of right arm revealed partially liquefied, foul smelling, darklooking fascia, and necrosis of bicep.

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Figure 2. Case 2 (A) Detail of right elbow, edematous, tender, and blistered (arrows); small necrotic area visible at wrist (*).
(B) Surgical exploration and fasciotomy of right upper limb extending from neck to hand, with drainage of fluids and debride-
ment of necrotic tissues. Skin and subcutaneous tissue necrosis is visible at wrist.

laboratory parameters to distinguish NF from nonnecrotiz- the relationship between the LRINEC score and outcomes
ing soft tissue infections. More recently, Wong et al.40 remains unclear. Of the LRINEC parameters, glucose and
proposed a scoring system (laboratory risk indicator for C-reactive protein are considered predictors of mortality in
necrotizing fasciitis [LRINEC]) based on C-reactive pro- critically ill patients, in relation to sepsis hyperglycemia and
tein, WBC, hemoglobin, Na, serum creatinine, and serum end-stage acute renal failure. A recent article reports the retro-
glucose levels at admittance, which classifies patients in spective analysis of the case notes of all patients admitted to the
low-, intermediate-, and high-risk categories of NF in the ICU, Townsville Hospital, Townsville, between January 2002
early course of the disease (Table 4). A recent retrospec- and December 2005 with the admission diagnosis of NF and the
tive study on 209 patients by Su et al.41 demonstrated application of the LRINEC score to the initial blood tests. With
increased rates of both mortality and amputation in pa- a cutoff score of 6, the LRINEC score had a sensitivity of
tients with LRINEC score 6. Although helpful in under- 80%, specificity of 67%, a positive predictive value of 57%,
standing which patients are most at risk of a fatal outcome, and a negative predictive value of 86% in distinguishing
care should be taken in the use of such indexes, because patients with proven NF from those with severe soft tissue
infections.42

TABLE 4. Laboratory Risk Indicator for Necrotizing Fasciitis Imaging


(LRINEC) Score System Confirmatory radiographic studies may be helpful.
LRINEC Score Magnetic resonance imaging is suggested to be the most
adequate radiologic technique to differentiate necrotizing and
LRINEC
Variable Value Score Points nonnecrotizing soft tissue infections.43 Specific findings for
NF include hyperintense signal on T2-weighted images at the
C-reactive protein (mg/L) 150 0
deep fascia and within muscles. Soft tissue thickening is also
150 4
a characteristic finding, but it may also be noted after trauma.
WBC (cells/mm3) 15 0
Whether its use may have an impact on morbidity or mortal-
1525 1
ity has not yet been assessed. Observation of gas in subcu-
25 2
taneous tissues, often associated with the isolation of aerobic
Hemoblobin (g/dL) 13.5 0
coliforms such as Enterobacteriaceae44 on X-ray or com-
1113.5 1
puted tomography scan, is reported in 17% to 29% of
11 2
patients.14,20,33 This is a very specific but not very sensitive
Sodium (mmol/L) 135 0
finding in patients with NF. Computed tomography is more
135 2
sensitive than X-ray in identifying signs of NF because it
Creatinine (mg/dL) 1.6 0
can show inflammatory changes such as abscesses or
1.6 2
fascial thickening, which a retrospective study associated
Glucose (mg/dL) 180 0
with 80% sensitivity for diagnosis of NF.45 Ultrasound
180 1
examination is an alternative to detect superficial ab-
LRINEC Score
Points, Sum Risk Category NF Probability scesses, although it is considered neither sensitive nor
specific for diagnosis of NF.
5 Low 50%
67 Intermediate 5075% Microscopic Features
8 High 75%
Microscopic reports typically show necrosis of the
LRINEC score system by Wong et al.; for intermediate- and high-risk patients, the superficial fascia with polymorphonuclear infiltration and
model has positive predictive value of 92% and negative predictive value of 96%.40
edema of reticular dermis, subcutaneous fat, and superficial

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of the prognostic importance of missed diagnoses, we think


that, in dubious cases, surgical exploration should not be
avoided or delayed.
If no surgery is performed, the presence of cutaneous
necrosis together with classical clinical presentation and
pathogen isolation is needed for definitive diagnosis.5,48
Treatment
Surgery
Surgical debridement is a mandatory life-saving step
and should be performed as soon as possible. The most
important determinants of mortality are the timing and ade-
quacy of debridement: Wong et al.14 reported a ninefold
increase in mortality if the procedure is delayed more than 24
hours after hospital admission. Bilton et al.49 found increased
mortality from 4% to 38% in incomplete versus complete
debridement, and also Voros et al.50 reported dramatically
increasing mortality with delay and inadequate surgical
intervention.
Surgical debridement must be done until brisk bleeding
occurs from adjacent overlying subcutaneous tissues and
underlying muscles, if involved.10 All necrotic tissues, in-
cluding fascia, must be removed to reduce the bacterial load,
stimuli to inflammation, and facilitate recovery. In addition,
as it exposes tissues to oxygen, surgery may prove antago-
nistic to anaerobic bacteria. The wound should be bluntly
Figure 3. Histological features of NF. (A) Almost pure neu-
probed in all directions, especially in highly suspected areas
trophil inflammation involving fascia (hematoxylin-eosin
80); (B) intense edema of papillary dermis and neutrophil such as any pockets or subcutaneous or submuscular exten-
infiltrate of reticular dermis (hematoxylin-eosin 62); (C) sion of infection. Repeated debridements may be necessary
presence of many gram-positive cocci (Grams stain200); (as dictated by the state of the wound) until the infection is
(D) extensive areas of necrosis (hematoxylin-eosin200); adequately controlled. Tissues are often edematous and
(E) angiothrombosis encountered at all levels, also with sec- highly secreting, so wounds are usually left open after de-
ondary vasculitic alterations (hematoxylineosin200); and bridement. Sterile dressings with normal saline-soaked gauze
(F) inflammation and necrosis involving adjacent muscle once or twice each day may be used to cover the wound in the
(hematoxylin-eosin50). interim. At our Institution, iodine gauze is preferred, because
it combines antiseptic action with a stronger desiccative and
fascia of tissue excised in the operating theater (Fig. 3). foreign body effect which stimulates production of healthy
Intraoperative tissue biopsy should be obtained from the granulation tissue. Some authors recommend a second surgi-
interface between live and dead tissue. The disease is char- cal exploration 24 hours to 48 hours later as mandatory to
acterized by angiothrombosis of the perforating vessels to the ensure that the infectious process has not extended. If the
skin, caused by the local hypercoagulable state. Liquefactive patient is stable, we prefer reevaluation during dressing
necrosis of the superficial fascia initially spreads horizontally, changes, the patient being brought back to the operating room
then involving muscles and the overlying skin, the extent of only in case of need. Reconstructive surgery should be
the infection being usually much greater than that indicated considered only once the patients general conditions are
by skin findings alone (Figs. 1 and 3).46,47 stable and the infection fully eradicated. Wound coverage,
when not possible by direct suture, can be achieved by either
Surgical Exploration split thickness skin grafting or tissue transfer. Negative pres-
Surgical exploration remains the most sensitive and sure therapy may be used to promote healing and wound
specific option to confirm or exclude NF. Suggestive macro- closure, and this has helped in reducing the size of larger
scopic findings at surgical exploration include detection of defects. Other forms of surgery, such as amputation, may
gray necrotic tissue, gross fascial edema (Fig. 1), thrombosed result necessary for necrotizing infections of the extremities.
vessels, watery, thin, often foul-smelling fluid described as
dishwater pus, noncontracting muscles, and a positive fin- Antibiotic Therapy
ger test result, which is characterized by the possibility of Empirical broad-spectrum antibiotic coverage should
dissecting the subcutaneous tissue off the deep fascia with be supplied as soon as NF is diagnosed. Several multidrug
minimal resistance.2,20 Surgery also represents a mandatory regimens have been described, including high-dose penicillin,
life-saving therapy for affected patients, and although a major high-dose clindamycin, and a fluoroquinolone or aminogly-
operation can be necessary in cases of confirmation, limited coside for coverage of gram-negative bacteria. Penicillin
cutaneous access is needed as an initial step. In consideration should always be included in consideration of possible GAS

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etiology. Because of the emergence of penicillin-resistant The overall mortality rate in most of the published pediatric
staphylococci, third-generation cephalosporin, alone or in com- series ranges between 5% and 10%.56
bination with an aminoglycoside and metronidazole, must be Extensive tissue necrosis may result in poor, often fatal,
considered to provide adequate cover.33 Subsequent modifica- outcomes, because of the development of septic syndrome.
tions can be made according to the organisms isolated and the Untreated, the disease is almost invariably fatal. The mortality
sensitivities obtained at antibiogram. It is suggested that, in cases rate of STSS-complicated NF doubles with dramatic progression
of NF complicated by streptococcal toxic shock syndrome to multiorgan failure.9 The association of the two conditions is
(STSS), the use of protein synthesis inhibitors such as clinda- reported to have fatal outcomes in up to 70% of patients
mycin prove more effective than penicillin; they inhibit M occurring in 76 hours to 92 hours. Significant associations with
protein and exotoxin synthesis by group A Streptococcus, thus negative outcomes have been detected for a large number of
controlling the inflammatory response. Duration of antibiotic factors, like extremes of age (60 and 1), immunologic
therapy is recommended to last until the patient no longer compromise, and systemic diseases. The main factor recognized
manifests signs of systemic inflammation, which generally to influence prognosis negatively is late surgical debride-
results in a 14-day course.14,17,20,33 Antibiotic therapy is ment.10,14,33,38 Moreover, patients with infection by Clostridia
certainly of help, but not sufficient in itself to stop the spread have a fourfold increased risk of death and limb loss compared
of the infection, because the angiothrombotic character of the both with polymicrobial and other monomicrobial infections.57
disease limits access of the drug to the affected areas. Indeed, Anaya et al.58 created a clinical scoring system that categorizes
it has been shown that, when treatment is based only on patients with NSTI according to the risk of death, based on six
antimicrobial therapy and support, mortality approaches independent parameters at admission: age 50 years, heart rate
100%. Reported risk factors that should serve as a trigger for 110 bpm, temperature 36C, WBC count 40,000/mcL,
more aggressive surgical care and antimicrobial therapy are serum creatinine concentration 1,5 mg/dL, and hematocrit
truncal involvement, leukocytosis, acidosis, hypoalbumine- 50%; the accuracy of this model was 86.8%. Complications of
mia, and hypocalcemia. the illness and its treatment are common. Widjaja et al.15
reported infections in other parts of the body as the most
Other Therapies common complication, followed by pneumonia, urinary tract
infection, and heart failure.
Intravenous immunoglobulin therapy has been used
with some success in STSS.19,51 It is mostly theoretical, and
based on binding staphylococcal- and streptococcal-derived CONCLUSION
exotoxins, thereby limiting the onset of a systemic inflam- NF is a rare condition with poor prognosis unless
matory response syndrome.52 promptly treated. Characteristic clinical presentations are ob-
Postsurgery hyperbaric oxygen (HBO) therapy is a served only late while initial findings may be misleading. NF
generally accepted possibility.2,53 A recent study using an should always be considered in differential diagnosis in cases
experimental rat model receiving HBO exposure at 2.5 ATA presenting with local pain and/or inflammation, even in patients
pressure proved that subcutaneous tissue oxygen tension with no apparent predisposition. A high index of clinical suspi-
levels increased fivefold and the carbon dioxide tension levels cion is needed, together with appropriate resuscitation and sur-
twofold compared with initial levels. Results were confirmed gery to have any effect on the very high mortality.
in six NF patients in normobaric conditions and during HBO
therapy with PO2 even regularly higher in the vicinity of the DISCLOSURE
infected area than in healthy tissues.54 However, there are no The authors declare no conflict of interest.
definitive clinical data to support the benefit of adjuvant HBO
therapy for NF. A recent retrospective study of 67 cases was REFERENCES
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