Dermatologic Therapy, Vol.

24, 2011, 229239

Printed in the United States All rights reserved

2011 Wiley Periodicals, Inc.

DERMATOLOGIC THERAPY
ISSN 1396-0296

Cellulitis: diagnosis
and management
dth_1398

229..239

Elizabeth Bailey* & Daniela Kroshinsky

*Columbia University College of Physicians and Surgeons, New York, New
York and Department of Dermatology, Massachusetts General Hospital,
Boston, Massachusetts

ABSTRACT: Cellulitis is an acute infection of the dermal and subcutaneous layers of the skin, often
occurring after a local skin trauma. It is a common diagnosis in both inpatient and outpatient dermatology, as well as in the primary care setting. Cellulitis classically presents with erythema, swelling,
warmth, and tenderness over the affected area. There are many other dermatologic diseases, which can
present with similar findings, highlighting the need to consider a broad differential diagnosis. Some of
the most common mimics of cellulitis include venous stasis dermatitis, contact dermatitis, deep vein
thrombosis, and panniculitis. History, local characteristics of the affected area, systemic signs, laboratory tests, and, in some cases, skin biopsy can be helpful in confirming the correct diagnosis. Most
patients can be treated as an outpatient with oral antibiotics, with dicloxacillin or cephalexin being the
oral therapy of choice when methicillin-resistant Staphylococcus aureus is not a concern.
KEYWORDS: cellulitis, diagnosis, erysipelas, hospitalized patient, treatment

Introduction
Cellulitis is an acute infection of the dermis and
subcutaneous tissue, often complicating acute or
chronic trauma to the skin. It is a common cause
of outpatient medical visits and inpatient hospital
admissions, accounting for 10% of infectious
disease-related US hospitalizations from 1998 to
2006 (1). In 2005 alone, 14.2 million ambulatory
visits in the United States were attributed to skin
and soft tissue infections (2). A significant portion
of cases misdiagnosed as cellulitis may actually
represent other dermatologic or systemic conditions (3). Unfortunately, dermatologists are often
not consulted to aid in the diagnosis of these
patients until there is a failed response to standard
therapy. Not surprisingly, the determination of the
true underlying diagnosis can lead to significant
changes in clinical care. Given its high prevalence
Address correspondence and reprint requests to: Daniela
Kroshinsky, MD, Department of Dermatology, Massachusetts
General Hospital, 1653 W. Congress Pkwy, Boston, MA 60612,
or email: dkroshinsky@gmail.com.

and lack of a gold standard for diagnosis, familiarity with the presentation of cellulitis, knowledge of
common cellulitis mimickers, and understanding
of current therapeutic options are of great use to
the practicing dermatologist.

Presentation
Cellulitis typically presents with rubor, dolor,
calor, and tumor or erythema, pain, warmth,
and edema (see FIG. 1). Typically, the borders of
cellulitis are smooth and ill-defined. In severe
cases, vesicles, bullae, pustules, and necrosis may
be present (4). It may also present with ascending
lymphangitis and regional lymphadenopathy. A
report of pruritus or burning, as opposed to pain,
is less consistent with cellulitis and should prompt
consideration of other diagnoses. In addition,
pain out of proportion to the physical findings
raises the concern for deeper infections such as
necrotizing fasciitis (5). The timeline of progression
at the potential site of infection is an important
clue to the underlying etiology, as a chronic, slow

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Bailey & Kroshinsky

Table 1. Differential diagnosis for cellulitis

Diagnosis

Distinctive clinical features

Stasis dermatitis

FIG. 1. Classic cellulitis demonstrating unilateral lower

extremity edema and poorly demarcated erythema in the
setting of tinea pedis and onychomycosis.

progression is less consistent with cellulitis. Because patients with risk factors for cellulitis may
have recurrent events, it is also important to determine whether this is the first such event (68).
Other associated symptoms that may provide clues
to an underlying bacteremia or more significant
infectious process are presence of fever or chills,
headache, cough, arthritis, or diarrhea.
During the initial history and evaluation, information that may indicate a predisposing factor for
cellulitis should be elicited. Trauma to the skin is
an important risk factor for the development of
cellulitis. Potential sources of trauma include
piercings, intravenous drug use or skin popping,
animal or human bites, and self-induced skin
trauma (8). In addition, tinea pedis or onychomycosis can create local foot inflammation and skin
breakdown that allows for the entry of bacteria
and subsequent cellulitis (7). Underlying lymphatic or vascular compromise is another important predisposing condition. Peripheral vascular
disease, previous lymph node dissection, liposuction, and radiation therapy can cause changes
in normal lymphatic flow, which can predispose
to cutaneous infections (6,9). Disruption of vascular flow after leg vein harvesting for coronary
artery bypass grafting can lead to infection as well
(10).
The clinical history should also include an
evaluation for possible sources of immunosuppression or neutropenia such as diabetes mellitus,
human immunodeficiency virus, chronic steroid
use, malignancy, the use of any immunosuppressive agents, and past history of organ transplant.
This information may provide clues to the underlying diagnosis, as well as guide therapeutic deci-

230

Bilateral involvement
Prominence over medial malleoli
Post-inflammatory
hyperpigmentation changes
Response to leg elevation,
compression, and topical steroid
use
Contact dermatitis Presence of pruritis
Nonorganic or geometric
distribution of skin reaction
Report of exposure to an irritating
agent
Thrombophlebitis Presence of risk factors for DVT
and DVT
(active cancer, history of
immobilization, positive family
history)
Elevated D-dimer test
Positive compression ultrasound
test
Panniculitis
Lesions at multiple sites
Recurrence of lesions
History of previous episodes
Erythema migrans Targetoid lesion with central
clearing (in some cases)
Occurrence in the spring or
summer
History of a tick bite (in some
cases)
Recent travel to endemic areas
(Northeast, Upper Midwest, and
Northwest United States, and
parts of Canada, Europe, and
Asia)
Cellulitis
Erythema, pain, warmth, and
edema
Unilateral (in most cases)
Smooth and ill-defined borders
History of predisposing factors
(skin trauma, tinea pedis or
onychomychosis, lymphatic or
vascular compromise,
immunosuppresion or
neutropenia)
DVT, deep vein thrombosis.

sion making. A family history of similar symptoms

should be determined, as alternative diagnoses
such as Familial Mediterranean Fever can present
with recurrent erythema and have an underlying
genetic etiology. Other information such as recent
travel, time outdoors, or contact with animals
might provide clues to other infectious sources,
such as Lyme disease. Eliciting a social history
including illicit drug use and route of use, hobbies,

Cellulitis

Table 2. Treatment recommendations for cellulitis in the adult patient (4,40,41)

Clinical presentation

Antibiotic

Dosage

Comments

Erysipelas

Penicillin A

36 MU orally in 3 divided
doses

Amoxicillin
Dicloxacillin

34.5 g orally per day

500 mg orally every 6 hours

Cephalexin

500 mg orally every 6 hours

Nafcillin or oxacillin

12 g intravenously every
4 hours
1 g intravenously every
8 hours

Duration should be 1020 days.

Initial intravenous therapy with
Penicillin G (1020 MU every
68 hours) can also be used
initially (usually first 3 days).
Duration should be 1020 days.
Oral drug of choice for MSSA
strains
For penicillin-allergic patients,
except those with immediate
hypersensitivity reaction
Parenteral drug of choice

Routine cellulitis
(low suspicion of MRSA)

Cefazolin

For patients with suspicion of

MRSA or penicillin-allergic
patients with immediate
hypersensitivity reaction

For patients with suspicion of

MRSA or penicillin-allergic
patients with immediate
hypersensitivity reaction
presenting with signs of severe
infection or in patients who did
not respond to initial therapy

Doxycycline

100 mg orally twice daily

Clindamycin

300450 mg orally three

times a day

Trimethoprim-sulfamethoxazole

One or two double-strength

tablets orally twice daily
30 mg/kg/day intravenously
in two divided doses

Vancomycin

Linezolid

For penicillin-allergic patients,

except those with immediate
hypersensitivity reaction
Should not be used in pregnant
women or children under 8
years old
If pathogen strain is
erythromycin-resistant, further
testing for clindamycinresistance should be performed
before therapy is prescribed.
Can also be administered
intravenously, 600 mg/kg
every 8 hours.

Parenteral drug of choice for

treatment of infections caused
by MRSA

600 mg intravenously every

12 hours or 600 mg orally
twice per day

Special exposures therapies to consider in addition to therapy for standard organisms

Human bite
Oral anaerobes (bacteroides
species, peptostreptococci);
Eikenella corredens; viridans
streptococci; Staphylococcus
aureus
Cat or dog bite
Pasteurella multocida and other
pasteurella species; S. aureus,
Suillus intermedius, Neisseria
canis, Haemophilus felix,
Capnocytophaga canimorsus;
anaerobes
Limb-threatening diabetic foot
ulcer
Aerobic gram-negative bacilli
(Enterobacteriaceae,
Pseudomonas aeruginosa,
acinetobacter); anaerobes
(bacteroides, peptococcus)

Amoxicillin-clavulanate

500 mg orally every 8 hours

Alternative therapy: penicillin plus

a cephalosporin

Amoxicillin-clavulanate

500 mg orally every 8 hours

Alternative therapy: moxifloxacin

plus clindamycin

Ampicillin-sulbactam

3 g intravenously every
6 hours

Alternative therapies include:

meropenem or imipenemcilastatin; clindamycin
plus a broad-spectrum
fluoroquinolone
(ciprofloxacin or levofloxacin);
metronidazole plus a
fluoroquinolone or ceftriaxone

Note: Switch to oral treatment when afebrile and skin findings are resolving (usually 35 days).
Total treatment duration should be at least 714 days, depending on the rate of response.
Longer treatment with abscess, tissue necrosis, or underlying skin disorder.
MRSA, methicillin-resistant S. aureus; MSSA, methicillin-sensitive S. aureus.

231

Bailey & Kroshinsky

Table 3. Treatment recommendations for cellulitis in the pediatric patient (4,13,40,42)

Clinical presentation

Antibiotic

Dosage

Comments

Erysipelas

Penicillin V

2550 mg/kg/day
orally in four
divided doses
2040 mg/kg/day
orally in three
divided doses
25 mg/kg/day
orally in four
divided doses
25 mg/kg/day
orally in four
divided doses
100150 mg/kg/day
intravenously in
four divided doses
50 mg/kg/day
intravenously in
three divided doses
1020 mg/kg/day
orally in three
divided doses

Treatment duration 1020 days

Amoxicillin

Routine cellulitis
(low suspicion of MRSA)

Dicloxacillin

Cephalexin

Nafcillin or
oxacillin
Cefazolin

For patients with suspicion of

MRSA or penicillin-allergic
patients with immediate
hypersensitivity reaction

For patients with suspicion of

MRSA or penicillin-allergic
patients with immediate
hypersensitivity reaction
presenting with signs of severe
infection or in
patients who did not
respond to initial therapy

Clindamycin

Trimethoprim812 mg/kg/day
sulfamethoxazole
orally in two
divided doses
Vancomycin
40 mg/kg/day
intravenously
in four divided
doses
Linezolid
10 mg/kg
intravenously
or orally every
12 hours

Can induce rash (<4% of children)

and diarrhea (10% of children);
treatment duration 1020 days
Oral drug of choice for MSSA
strains
For penicillin-allergic patients,
except those with immediate
hypersensitivity reaction
Parenteral drug of choice

For penicillin-allergic patients,

except those with immediate
hypersensitivity reaction
If pathogen strain is
erythromycin-resistant, further
testing for clindamycin
resistance should be performed
before therapy is prescribed; can
also be given intravenously,
2540 mg/kg/day in three
divided doses
Can also be given intravenously,
812 mg/kg/day in four divided
doses
Parenteral drug of choice for
treatment of infections caused
by MRSA

Special cases
AmoxicillinHuman bite
clavulanate
Oral anaerobes (bacteroides
species, peptostreptococci);
Eikenella corredens; viridans
streptococci; Staphylococcus
aureus
AmoxicillinCat or dog bite
clavulanate
Pasteurella multocida and other
pasteurella species; S. aureus,
Suillus intermedius, Neisseria
canis, Haemophilus felix,
Capnocytophaga canimorsus;
anaerobes
Periorbital cellulitis
Cefotaxime

25 mg/kg/day orally
every 12 hours

Alternative therapy: penicillin plus

a cephalosporin

25 mg/kg/day orally
every 12 hours

Alternative therapy: moxifloxacin

plus clindamycin

150 mg/kg/day
intravenously
every 8 hours

Vancomycin 60 mg/kg/day every 6

hours or rifampin 20 mg/kg
once daily should be added if
cerebrospinal fluid pleocytosis is
present.

MRSA, methicillin-resistant S. aureus; MSSA, methicillin-sensitive S. aureus.

232

Cellulitis

Table 4. Treatment recommendations for cellulitis in the immunocompromised patient (4)

Underlying condition and
likely pathogen
Neutropenia (initial
infection)
Gram-positive bacteria
Gram-negative bacteria
Neutropenia (subsequent
infection)
Antibiotic-resistant
bacteria
Fungi

Cellular immune deficiency

Bacteria
Nocardia species
Atypical mycobacteria
Fungi
Cryptococcus species

Histoplasma species
Viruses
Varicella-zoster virus

Herpes simplex virus

Cytomegalovirus

Therapy

Duration of therapy

Additional treatment

Monotherapy or antibiotic
combination
Pathogen specific

714 days

G-CSF/GM-CSF;
Granulocyte therapya
No

Pathogen specific

714 days

Amphotericin B,
voricanazole, or
caspofungin

Clinical and radiologic

resolution

Trimethoprim-sulfamethoxazole
or sulfadiazine
Antibiotic combination
including a macrolide

312 months

No

36 weeks

No

Amphotericin B plus
5-fluorocytosine or
fluconazole
Amphotericin B or
itraconazole

812 weeks

No

Acyclovir
Famciclovir
Valacyclovir
Acyclovir
Famciclovir
Valacyclovir
Ganciclovir

710 days

No

7 days

No

21 days

No

710 days

G-CSF/GM-CSFb;
Granulocyte therapya
Catheter removal; G-CSF/
GM-CSFb; Granulocyte
therapya

Use if gram-negative bacillary infection is unresponsive to appropriate antimicrobial therapy or if patient has an invasive fungal
infection.
b
Use if progressive infection, pneumonia, and invasive fungal infection.
G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-monocyte colony-stimulating factor.

and occupational exposures can similarly broaden

the differential diagnosis.

Physical examination
The physical exam of a patient with possible cellulitis should begin with an evaluation of general
appearance and vital signs. Patients with cellulitis
may have fever, tachycardia because of pain, or
hypotension. The presence of fever alone does not
guarantee a diagnosis of cellulitis, and attention to
any particular patterns, such as a diurnal nature,
can be helpful as, in conjunction with a salmonpink macular exanthema, this could indicate an
underlying etiology of Stills disease (11). Patients

with more significant soft tissue infections such as

necrotizing fasciitis may present with similar
initial systemic signs but will quickly deteriorate
to more severe systemic signs of sepsis, including
metabolic acidosis, hyperthermia, and later hypothermia (5). With cellulitis and erysipelas, there
may also be ascending lymphangitis and regional
lymphadenopathy, although lymphadenopathy
may also indicate an inflammatory or neoplastic
cause.
Some special types of cellulitis with distinguishing anatomic features include erysipelas, perianal
cellulitis, preseptal cellulitis, and orbital cellulitis.
Erysipelas is a superficial cellulitis of the skin with
marked lymphatic involvement that typically
occurs on the face, hands, or scalp, more commonly

233

Bailey & Kroshinsky

seen in young children and older adults (4). It typically presents as a small area of erythema that
gradually enlarges. Like cellulitis, erysipelas is
warm and painful, but in distinction, it is also shiny
and well-demarcated. Perianal cellulitis presents
with tender, perianal erythema, possibly with
accompanying fissures, purulence, or functional
disturbances. This type of cellulitis occurs mainly in
young children and can cause severe discomfort
(12). It is usually caused by group A streptococci or
staphylococci. Preseptal or periorbital cellulitis
affects the tissue anterior to the orbital septum, a
fibrous layer extending from the skull periosteum to
the eyelids. This layer prevents the deeper spread of
infection to the orbit. Preseptal cellulitis typically
presents with warmth, erythema, and swelling in
the periorbital region, and usually occurs in children. It can occur secondary to facial skin trauma
such as from an insect bite or from hematogenous
entry of bacteria from a portal of entry in the
nasopharynx. In children under 18 months of age,
preseptal cellulitis can follow a viral upper respiratory infection (13). Orbital cellulitis is an infection
beyond this septum, which may occur because of
trauma or the tracking of infection from the sinuses.
Because of the deeper penetration of infection,
orbital cellulitis can lead to severe consequences
including vision loss and cavernous sinus thrombosis. With orbital cellulitis, patients can exhibit
proptosis, conjunctival edema, ophthalmoplegia,
and/or decreased visual acuity, in addition to the
findings seen with preseptal cellulitis (14).

Differential diagnosis
A significant number of conditions clinically mimic
cellulitis. Because cellulitis and cellulitis mimickers
or pseudo-cellulitides are common in clinical
practice, it is useful to be familiar with the most
common pseudo-cellulitides. Here, the present
authors highlight several of the most common diseases which might present as cellulitis in clinical
practice: venous stasis dermatitis, contact dermatitis, deep venous thrombosis, panniculitis, and
erythema migrans (Table 1). Each of these conditions requires fairly different management and
therapy, highlighting the importance of a rapid and
accurate diagnosis.
Stasis dermatitis
Stasis dermatitis results from venous insufficiency
and is the most common diagnosis mistaken for
cellulitis (see FIG. 2). Chronic venous insufficiency

234

FIG. 2. Stasis dermatitis demonstrating bilateral lower

extremity edema and erythema.

occurs when blood refluxes through incompetent

valves in the superficial or deep venous plexuses,
leading to increased venous pressures in the legs.
Passage of fluid and plasma proteins into the tissue
can lead to edema, and extravasation of erythrocytes can lead to purpura and hemosiderin deposition (15). As a result, patients often present with
unilateral or bilateral erythema and edema of the
legs, mimicking cellulitis. Likely indicators that a
patient is not in fact suffering from cellulitis are
the bilateral involvement (particularly without a
history of bilateral skin trauma), prominence over
the medial malleoli, absence of fever, absence of
leukocytosis, and response to leg elevation, compression, and topical steroid use. Patients may
also have post-inflammatory hyperpigmentation of
these regions, suggesting chronicity to this process.
They may also report lower-extremity heaviness,
aching, cramping, itching, and restlessness, whereas cellulitic patients report fever and pain (16).
If a definitive diagnosis is sought, skin biopsy
will demonstrate a lobular proliferation of thickened blood vessels with extravasated red blood
cells, hemosiderin-laden macrophages, and
dermal fibrosis (17). More fibrosis is often present
with chronic disease. Once a diagnosis has been
made, further evaluation of the extent of venous
disease should be performed, including classification using the Clinical, Etiologic, Anatomical, and
Pathophysiological system (16). Treatment should
begin with leg elevation and compression stockings or practitioner-placed Ace-wraps. Compression can improve venous dynamics and are
effective in healing venous ulcers, and this should
be the first step before more invasive surgical
options are considered to improve venous flow

Cellulitis

FIG. 4. Allergic contact dermatitis from tobramycin eye

drops.

FIG. 3. Severe irritant contact dermatitis with focal areas of

vesiculation.

(16). The active inflammation seen in acute stasis

dermatitis can be additionally improved with a
course of mid-potency topical steroids.
Contact dermatitis
Another common mimicker of cellulitis is contact
dermatitis both allergic and irritant. Irritant
contact dermatitis is more common, typically
quoted as representing 80% of contact dermatitis
cases (18). Irritant contact dermatitis typically
produces well-demarcated, erythematous, and
often pruritic or painful skin lesions (see FIG. 3).
Allergic contact dermatitis produces erythematous, swollen, weeping, or vesiculating lesions that
often extend beyond the site of contact and are
usually pruritic but can more rarely be painful
depending on the degree of edema that results
(see FIG. 4). Environmental risk factors for contact
dermatitis include frequent contact with water,
soap, or solvents, lack of protective clothing,
contact with plants or fragrances, and frequent
washing of skin and clothing. Endogenous risk
factors include fair skin, underlying skin diseases,
and exposure of more sensitive areas such as the
dorsum of hands and feet (19). Common culprits
include detergents, solvents, disinfectants, metals,
dyes, and poison ivy or oak (19). Report of exposure to an irritating agent and presence of pruritus
can help to distinguish contact dermatitis from
cellulitis (20). In addition, there can be a characteristic nonorganic or geometric distribution of
the skin reaction based on the distribution of the
substance exposure to the skin (20). Patients with
contact dermatitis do not typically have accompanying fever, leukocytosis, or significant pain.

Because the skin disturbance can provide a vehicle

for infection, care must be taken to ensure that the
patient does not have a concomitant secondary
infection of the area.
A careful history and physical evaluation is
critical to the diagnosis of contact dermatitis, in
which a consistent relationship with a potential
instigating substance is determined. For allergic
contact dermatitis, diagnostic patch testing with
chemicals relevant to the exposure can confirm
the diagnosis and can help prevent future recurrences. Irritant contact dermatitis is generally a
diagnosis of exclusion after other probable causes
have been ruled out (21). Irritant contact dermatitis will typically lead to an inflammatory response
on patch testing that fades quickly with patch
removal (19). The mainstay of treatment is avoidance of exposure to the instigating antigen or irritant. Use of barrier creams and protective clothing
and gloves are effective measures to reduce exposure. An acute allergic reaction can be quieted
with a course of topical steroids. Widespread
reactions may require a steroid taper, typically
1 mg/kg/day of prednisone tapered over 3 weeks.
Cool water or Burrows solution soaks provide
symptomatic relief (18).
Thrombophlebitis, deep vein thrombosis (DVT)
DVTs and thrombophlebitis can also be difficult to
distinguish from cellulitis. DVTs usually present
with unilateral lower-extremity erythema, edema,
and warmth (22). There is also often tenderness
along the involved vein (20). A palpable clot is
rarely present (23). Complicating the clinical
picture, DVT can induce a systemic inflammatory
response leading to fever and leukocytosis in some
cases (23). Presence of risk factors for DVT in the
patients history should increase suspicion for this

235

Bailey & Kroshinsky

etiology. These include active cancer, a history of

extremity immobilization, and greater than two
first-degree relatives with a history of deep venous
thrombosis (24).
With high clinical suspicion, ultrasound imaging
should be used to rule out the diagnosis (25). There
are several validated diagnostic algorithms for
determining the presence of DVT, including a combination of clinical evaluation, D-dimer testing,
and compression ultrasonography. These diagnostic algorithms, when used in combination, aid in
making a more definitive diagnosis (22). One of the
well-validated approaches is to determine diagnosis based on a combination of clinical concern and
risk factors, D-dimer testing, and compression
ultrasound. In patients with a low level of clinical
concern and normal D-dimer test, DVT is ruled out
without ultrasound. Ultrasound should be performed, however, in patients with high clinical
concern and/or elevated D-dimer levels. Once
the presence of DVT is confirmed, treatment is targeted to relieving symptoms and preventing
embolization and recurrence. Patients should be
started on unfractionated or low-molecular-weight
heparin followed by an oral anticoagulant to a targeted international normalized ratio (INR)
between 2.0 and 3.0. In the case of contraindication
to anticoagulation, an inferior vena cava filter is an
alternative treatment option (26).

usually multifocal, it can initially present with a

solitary, warm, tender red plaque, accompanied by
fever, leukocytosis, and elevated erythrocyte sedimentation rate (ESR)). Over time, the manifestations usually progress to bilateral discrete nodular
subcutaneous lesions that can later appear bruiselike, subsequently turning yellow or green in appearance (termed erythema contusiformis) (27,28).
Clues indicating panniculitis are presence of lesions
at multiple sites, recurrence of the lesions, and a
history of previous episodes. Erythema nodosum is
thought to be a hypersensitivity response to a
variety of factors, likely leading to immune complex
formation in and around venules in the connective
tissue of septa of subcutaneous tissue (27). It is associated with many conditions, including sarcoidosis,
inflammatory bowel disease, and Behet syndrome,
as well as several infectious diseases, such as streptococcal infections, and medications, including
oral contraceptives (27).
The diagnosis of erythema nodosum can be confirmed by biopsy, which typically yields a septal
panniculitis with an infiltration of inflammatory
cells including multinucleated giant cells extending
to the preseptal areas of the fat lobules. Perivascular
infiltration by lymphocytes is usually evident in the
dermal layer. Initially, there is evidence of edema
and hemorrhage, which is later replaced by fibrosis
and granulation tissue with signs of more chronic
inflammation with lymphocytes, histiocytes, and
giant cells (27). In addition to skin biopsy, evaluation should include a complete blood count, ESR,
antistreptolysin O titer, urinalysis, throat culture,
intradermal tuberculin test, and chest X-ray,
which serve to evaluate for several potential
etiologies of erythema nodosum (27). Treatment
should be directed to resolving or removing the
underlying trigger. Typically, the presenting nodules will resolve spontaneously within several
weeks. Aspirin or nonsteroid anti-inflammatory
medications can be used for symptomatic relief.
With persistent lesions, potassium iodide at a
dosage of 400900 mg daily or two to ten drops of
saturated solution has been found to help resolve
lesions (27). Intralesional kenalog injections can be
utilized if there are a limited number of lesions, or
systemic prednisone can be used to control acute
flares and diminish severe discomfort.

Panniculitis

Erythema migrans

Panniculitis is an inflammatory, noninfectious condition that is often mistaken for cellulitis on initial
evaluation (see FIG. 5). Erythema nodosum is the
most common type of panniculitis and, although

Depending on the geographic region where the

patient presents, erythema migrans the dermatologic manifestation of early Lyme disease can be a
common mimic of cellulitis (see FIG. 6). After being

FIG. 5. Erythema nodosum.

236

Cellulitis

FIG. 6. Erythema chronicum migrans.

bitten by a Borrelia burgdorferi-infected Ixodes

scapularis (United States) or Ixodes pacificus
(Europe) tick, a patient can develop expanding,
warm patches of erythema. These lesions can more
uncommonly develop vesicles, pustules, bullae, or
necrosis (29). They often lack the classically described central clearing and are often accompanied
by fever and other constitutional symptoms,
making the presentation difficult to distinguish
from cellulitis (30). Adding to the confusion, most
patients do not recall the tick bite event (29). Clinical suspicion should be higher for patients who
present with typical characteristics for Lyme exposure such as occurrence in the spring or summer,
history of a tick bite (in some cases), and recent
travel to endemic areas (Northeast, Upper Midwest,
and Northwest United States, as well as areas of
Canada, Europe, and Asia) (30). Presentation with
multiple lesions can indicate disseminated erythema chronicum migrans. The presence of the
lesion away from the lower extremities where cellulitis is most often seen should also raise concern
for possible erythema migrans (30). In cases of
clinical doubt, amoxicillin/clavulanate for 1421
days will cover staphylococci, streptococci, and
B. burgdorferi (31).

Laboratory testing
After eliciting a thorough history and performing a
physical exam, there is usually a fairly limited need
for further laboratory testing for routine cellulitis

cases. A complete blood count with differential may

be helpful. Patients with cellulitis usually have
normal or slightly elevated leukocyte counts. Liver
function tests and a chemistry panel are also valuable for determining therapeutic options and any
coexisting medical comorbidities. Cultures of any
bullae, pustules, or ulcers should also be performed
in any patient with presumed cellulitis, as these
cultures are relatively noninvasive and can provide
informative results if positive (32). Needle aspiration or punch biopsy for culture, however, are not
recommended, as they are rarely informative (32).
Except in cases of patients with atypical or severe
disease, such as infection in elderly patients,
patients with acute onset of illness, high-grade
fever, and significant leukocytosis, and immunocompromised patients, blood cultures are not routinely obtained (33). Blood cultures are usually
negative, except in patients with underlying
lymphedema, who are predisposed to bacteremia
(20). Further testing should be tailored to the most
likely alternative diagnoses.
Skin biopsy is not routinely performed to evaluate standard cellulitis. If performed, one would
expect to see subepidermal edema with diffuse
infiltration of neutrophils without abscesses. There
is often vascular lymphatic dilatation, and secondary panniculitis can be present (34). When there is
concern about a nonbacterial etiology of infection,
skin biopsy and tissue culture may be helpful. In this
case, histopathologic evaluation with hematoxylinand-eosin and special staining for organisms and
culture for bacteria, fungi, and mycobacteria
should be performed. In an immunocompromised
patient presenting with cellulitis, a skin biopsy
should always be performed to evaluate possible
bacterial, fungal, viral, parasitic, and mycobacterial
sources of infection (4,35). Skin biopsy is also
helpful in distinguishing true cellulitis from noninfectious possibilities when there is clinical doubt.
Imaging can help to distinguish cellulitis from
more severe infections. Plain-film radiography and
magnetic resonance imaging (MRI) can be used to
rule out accompanying osteomyelitis (36). MRI or
computed tomography can also help determine
the extent of infection and help distinguish cellulitis from pyomyositis or necrotizing fasciitis (37).
Ultrasonography and MRI are helpful for determining any accumulations of pus and guiding
aspiration (37).

Treatment
Routine cellulitis without underlying abscess is
usually caused by streptococci (4). Staphylococcus

237

Bailey & Kroshinsky

aureus is a possible culprit in cases with underlying

abscess or a history of penetrating trauma. In cases
of erysipelas, beta-hemolytic streptococci is almost
always the cause, and the treatment of choice is
penicillin. For cellulitis, therapeutic options to
cover streptococci and methicillin-sensitive S.
aureus include dicloxacillin, cephalexin, clindamycin, or erythromycin, if resistant organisms are not
prevalent in the community. Most patients can
immediately receive oral treatment. In more illappearing patients or patients unable to tolerate
oral therapy, intravenous therapy with a penicillinase-resistant penicillin such as nafcillin, a
first-generation cephalosporin such as cefazolin,
or, for patients with penicillin allergies, clindamycin or vancomycin can be used. Methicillinresistant S. aureus (MRSA) infection should be
considered in high-risk populations. Hospitalacquired MRSA infections are associated with previous antibiotic use, day care attendance, contact
with a health-care worker or nursing home resident,
diabetes mellitus, hospitalization, and many major
hospital procedures (38). Community-acquired
MRSA infection, a rapidly growing problem, is more
common in children, intravenous drug users, men
who have sex with men, military personnel, prisoners in correctional facilities, and certain ethnic
groups including Alaska natives, native American
Indians, Canadian aboriginal peoples, and Pacific
Islanders (39). Athletes have also recently been
reported to be at increased risk for communityacquired MRSA (39).
Most community-acquired strains are susceptible to doxycycline or minocycline; however, these
agents should be avoided in pregnant women and
children under 8 years old. Clindamycin is also an
effective agent, but there is the possibility of emergence of resistance by strains inducibly resistant to
erythromycin. For this reason, erythromycin-resistant strains should be evaluated for resistance to
clindamycin before clindamycin is prescribed.
Trimethoprim-sulfamethoxazole is also a therapeutic option for less severe disease. Linezolid,
daptomycin, and vancomycin are highly effective
but should be reserved for severe infections requiring hospitalization and patients who did not
respond to initial therapy (4) (Tables 2 and 3).
In immunocompromised patients, the range of
possible pathogens is much wider. In neutropenic
patients, initial infections are usually due to gramnegative or gram-positive bacteria. Subsequent
infections are usually due to antibiotic-resistant
bacteria, yeast, or fungi (4). These patients should
be treated with an empiric, broad-spectrum antibiotic at the first sign of infection. Choice of use of

238

oral or parenteral treatment, the need for hospitalization, and the level of antimicrobial coverage that
is necessary should be made after assessing the
level of patient risk and likelihood of presence of
resistant or atypical organisms based on local patterns (35). Duration of treatment should be based
on clinical response and neutrophil count (35). For
subsequent infections in neutropenic patients,
greater than 50% are caused by fungi, whereas the
remaining are caused by antibiotic-resistant grampositive or gram-negative organisms (4). These
patients may benefit from empirical coverage of
fungal pathogens as well as coverage for resistant
bacterial organisms for initial therapy (Table 4).
For patients with cellular immune deficiency,
infection from atypical mycobacteria, nocardia,
fungi, and viruses should be considered. Atypical
mycobacterial infection is common, particularly
after skin trauma, and should be treated with
a prolonged combination therapy including a
macrolide. Nocardia typically arises from a
primary pulmonary source, and trimethoprimsulfamethoxazole is the treatment of choice.
Cryptococcosis and histoplasmosis can lead to
cutaneous infection and should be treated initially
with amphotericin B. Varicella zoster virus and
herpes simplex virus are common causes of cutaneous viral infection in immunocompromised
patients and can present initially as a patch of
warm, tender erythema mimicking cellulitis. In
the immunocompromised, intravenous acyclovir
initially should be considered (4) (Table 4).
Most patients will sufficiently clear the infection
on antibiotic therapy alone. Elevation of the area
and compression as tolerated can speed clinical
improvement by promoting drainage of edema and
reducing inflammation. In addition, any underlying condition leading to infection should be
addressed. To reduce recurrence of cellulitis, any
interdigital maceration should be treated, and any
underlying fungal infection or edema should be
treated.

Conclusions
Cellulitis is a common diagnosis in clinical practice, and it represents a significant proportion of
inpatient and outpatient medical visits in the
United States. There are several medical diagnoses
that can be difficult to distinguish from cellulitis,
including venous stasis dermatitis, contact dermatitis, DVT, and panniculitis. Local characteristics of
the affected area, systemic signs, laboratory tests,
and, in some cases, skin biopsy can be helpful in

Cellulitis

determining the correct diagnosis. Cellulitis can

usually be treated with oral antibiotics as an outpatient and typically resolves without need for
further therapy.

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