Spotlight

Pitfalls in Diagnosing
Necrotizing Fasciitis
Source and Credits
• This presentation is based on the July/August 2014
AHRQ WebM&M Spotlight Case
– See the full article at http://webmm.ahrq.gov
– CME credit is available
• Commentary by: Terence Goh, MBBS, Department
of Plastic Surgery, Singapore General Hospital and
Lee Gan Goh, MBBS, Division of Medicine, National
University Health System, Singapore
– Editor, AHRQ WebM&M: Robert Wachter, MD
– Spotlight Editor: Bradley A. Sharpe, MD
– Managing Editor: Erin Hartman, MS

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Objectives

At the conclusion of this educational activity,

participants should be able to:
• State the epidemiology of necrotizing fasciitis
• Appreciate the high mortality associated with
necrotizing fasciitis
• Explain the pathophysiology of necrotizing fasciitis
• Describe the main challenges in the diagnosis of
necrotizing fasciitis
• List steps which can be taken to avoid errors in the
diagnosis of necrotizing fasciitis

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Case: Diagnosing Necrotizing Fasciitis
A 49-year-old previously healthy man presented to the
emergency department (ED) after falling at work 3 days before.
He had presented to a different ED one day prior with diffuse
pain on his left side (the side of impact) and was given non-
steroidal anti-inflammatory medications and sent home. He
presented to this new ED with persistent and worsening left
arm, chest, abdomen, and thigh pain. On physical examination,
he was afebrile but tachycardic. He had diffuse, tender
ecchymoses involving his left shoulder, upper chest, lateral
abdomen, and thigh. Although ED physicians felt he had simple
bruising from the fall, they noted that he was in severe pain
requiring intravenous opiates and that he was unable to
independently ambulate.

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Case: Diagnosing Necrotizing Fasciitis (2)
Because of these symptoms, blood tests were obtained
and results showed a white blood cell count of 2.8 x 10 9/L
(normal range: 3.5–10.5 x 109/L) and acute renal
insufficiency with a creatinine of 1.4 mg/dL (normal range:
0.6–1.2 mg/dL). A CT scan of the abdomen and pelvis
showed ʺinduration in the left quadriceps muscle and fluid
layering in the abdominal wall.ʺ He was seen by the
trauma surgical service, who felt the findings were due to
diffuse bruising. The patient was admitted to an internal
medicine service. Due to ED crowding, he remained in the
ED overnight, receiving only intravenous fluids and
intravenous opiates for his pain.

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Case: Diagnosing Necrotizing Fasciitis (3)
Overnight, his pain worsened and he had persistent
tachycardia. Early morning lab results showed a white
blood cell count of 1.6 x 109/L, a creatinine of 1.6 mg/dL, a
creatine kinase of 2650 U/L (normal range 55-170 U/L)
(evidence of muscle breakdown), and a lactate of 6.2
mg/dL (normal range 0.5−2.2 mmol/L) (evidence of tissue
hypoxia). He was seen by the internal medicine team mid-
morning and diagnosed with rhabdomyolysis from trauma
and acute renal failure. He continued to receive
intravenous fluids. His pain had become so severe that he
was switched to dilaudid, administered through a patient-
controlled analgesia (PCA) pump.

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Case: Diagnosing Necrotizing Fasciitis (4)
Later that day, the patient had progressive respiratory distress
and developed septic shock. He was re-evaluated by the
surgical service and felt to have probable necrotizing fasciitis
with pyomyositis. He was urgently taken to the operating
room, where he required debridement of 7300 cm/sq (an area
roughly 2 feet by 4 feet) of skin and soft tissue from his left
arm and axilla, anterior chest wall, abdominal wall, thigh, and
leg. After surgery, he was progressively hypotensive despite
multiple vasopressors. He developed multi-organ dysfunction
and ultimately, after discussions with his family, care was
withdrawn and he died peacefully. He underwent autopsy,
which showed necrotizing fasciitis with pyomyositis secondary
to methicillin-resistant Staphylococcus aureus (MRSA).

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Skin and Soft Tissue Infections

• Skin and soft tissue infections (SSTIs) are

incredibly common in both pediatric and adult
medicine
• SSTIs involve suppurative bacterial or fungal
invasion of the epidermis, dermis, or
subcutaneous tissues
• SSTIs can range in severity from benign to
very serious (as in this case)

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Background

• An expert panel has classified skin infections

into 4 classes to help guide treatment:
1) Afebrile and healthy, other than cellulitis
2) Febrile and ill appearing, no unstable
comorbidities
3) Toxic appearance, or at least one unstable
comorbidity, or a limb-threatening infection
4) Sepsis syndrome or life-threatening infection
(e.g., necrotizing fasciitis)

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Background (2)

• This unfortunate case provides an opportunity

to focus on necrotizing fasciitis (NF)
• NF is the most severe SSTI and the
diagnosis is often missed or delayed
• Delay in diagnosis can have devastating
consequences, as with this patient

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History and Features
• Hippocrates first alluded to a clinical condition of
ʺnecrotizing erysipilasʺ in the 5th century BC as a
complication of erysipelas
• Since then, numerous terms have been applied
to this condition—phagedena gangrenosum,
hospital gangrene, Meleney gangrene, and
Fournier gangrene
• Dominant feature is inflammation and necrosis of
subcutaneous fat and deep fascia, with sparing
of muscle, leading to severe systemic toxicity

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Epidemiology
• Necrotizing fasciitis is a rare disease
• The incidence of NF progressively increases
among patients aged 50 years and older
• Necrotizing fasciitis generally affects patients
with chronic illnesses
– More than half of patients have pre-existing
medical conditions and 35% have at least two
• Despite improved recognition, NF continues to
be associated with a high mortality—in the past
decade, reported to be between 15% to 45%
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Pathophysiology of NF

• Microbial invasion of the subcutaneous

tissues occurs either through:
1) External trauma
2) Direct spread from a perforated viscus
3) From a hematogenous source
• NF can affect any part of the body;
extremities and the perineum are most
commonly affected

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Pathophysiology of NF (2)

• As infection progresses, the skin becomes

more tense and red with indistinct margins
• Local pain is replaced by numbness (from
compression or infarction of nerves)
• Next, skin becomes pale, then mottled and
purple looking, and finally gangrenous
• If gas-forming bacteria are present, air under
the skin (crepitus) may be palpated

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Evolution of Physical Signs in NF
• A clinical staging of the disease has been proposed based
on cutaneous signs (see below)
• Symptoms may occur over hours to days and patients may
present with sepsis or septic shock

Stage 1 (early) Stage 2 (intermediate) Stage 3 (late)

Warm to palpation Blister or bullae formation Hemorrhagic bullae
(serous fluid)
Erythema Skin fluctuance Skin anesthesia
Tenderness to palpitation Skin induration Crepitus
(extending beyond apparent
areas of skin involvement)
Swelling Skin necrosis with dusky discoloration
progressing to frank gangrene

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Microbiology of NF
• Historically, group A–beta-hemolytic
streptococcus has been identified as the major
cause of this infection
• More recently, researchers report NF is usually
polymicrobial (Type I NF) rather than
monomicrobial (Type II NF)
• Patient in case had NF secondary to methicillin-
resistant Staphylococcus aureus (MRSA)
– Though not particularly common, community-acquired
MRSA causing NF is an emerging clinical entity

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Early Diagnosis of NF

• Early diagnosis and adequate debridement

within 24 hours are the most important factors
impacting survival
• Patients who receive surgery in the first 24
hours have mortality rate of 4.2%−6.7%
• Delaying surgery more than 24 hours is
associated with mortality rates of 23%−75%
– Thus the relative risk of death is increased by
more than 9 times

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Challenges in Diagnosis

• Early diagnosis of necrotizing

fasciitis (NF) is notoriously
difficult and misdiagnosis is
common
– In one study, NF was initially
misdiagnosed 71.4% of the
time

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Challenges in Diagnosis (2)
• Multiple factors contribute to missed or delayed
diagnosis:
– NF is a rare disease and many practitioners may be
encountering it for the first time
– NF initially can present similarly to other common soft
tissue infections (as in this patient where it appeared
he had simple bruising after his fall)
– The cutaneous signs of NF usually lag behind
disease pathology
– Systemic signs of NF may not correlate with the
cutaneous signs and vice versa; patients with
extensive infection may not be systemically ill
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Challenges in Diagnosis (3)

• The ʺhard signsʺ (e.g., bullae, numbness,

crepitus, and skin necrosis) may be absent
– In one study, they were present in only 43% of
patients with NF
• Fever may not be present
– In one review, only 32%−56% of patients with NF
had a fever
• In addition, initial symptoms of NF can be
mild until the patient rapidly deteriorates and
develops septic shock
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Strategies to Improve Diagnosis
• Multiple specific strategies may help prevent
missing a diagnosis of NF
– Recognize pain out of proportion to the skin
manifestations is a consistent feature of NF
• In this case, the patient's severe pain requiring increasing
intravenous opiates and a PCA pump should have been a
sign that this was a more serious infection
– Recognize NF often has rapid progression of
infection with migration of the margins of erythema
and skin induration despite use of antibiotics
• This extension can progress over the course of hours

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Strategies to Improve Diagnosis (2)
• Three other cutaneous features can serve as diagnostic
clues:
1) Margins may be indistinct and poorly defined
2) Tenderness may extend beyond the apparent involved area
of skin
3) Lymphangitis (inflammation of lymphatics, seen as
streaking along skin) is rarely seen in NF
• Use of clinical pathways may also help aid in diagnoses
• Institutions should involve multidisciplinary teams (often
including surgeons, infectious disease specialists, and
wound care experts)
• Education of frontline clinicians is also crucial

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This Case

• Patient in this scenario presented with a

history of trauma
• Based on initial clinical exam and diagnostic
tests, it appeared to be a simple bruise
• Over time, the patient exhibited a cardinal
sign of NF—pain out of proportion to working
diagnosis
– The need for escalating intravenous opiates
should have raised concerns for NF and
prompted further diagnostic testing

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Take-Home Points
• Early diagnosis of necrotizing fasciitis and early
debridement is crucial to survival and reduction in
morbidity and need for amputation
• Early presenting signs of necrotizing fasciitis can be non-
specific
• Pain out of proportion to what one would expect for simple
cellulitis should ring alarm bells and prompt physicians to
expand the differential diagnosis to include NF
• There is an evolution of clinical signs of necrotizing
fasciitis—from early to late stages
• A keen sense of suspicion and constant review of a patient
are the only ways to reliably detect necrotizing fasciitis at
an early stage
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