American Journal of Clinical Dermatology

https://doi.org/10.1007/s40257-021-00659-8

REVIEW ARTICLE

Cellulitis: A Review of Current Practice Guidelines and Differentiation

from Pseudocellulitis
Michelle A. Boettler1 · Benjamin H. Kaffenberger2 · Catherine G. Chung2,3

Accepted: 14 November 2021

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021

Abstract
Cellulitis, an infection involving the deep dermis and subcutaneous tissue, is the most common reason for skin-related hos-
pitalization and is seen by clinicians across various disciplines in the inpatient, outpatient, and emergency room settings,
but it can present as a diagnostic and therapeutic challenge. Cellulitis is a clinical diagnosis based on the history of present
illness and physical examination and lacks a gold standard for diagnosis. Clinical presentation with acute onset of redness,
warmth, swelling, and tenderness and pain is typical. However, cellulitis can be difficult to diagnose due to a number of
infectious and non-infectious clinical mimickers such as venous stasis dermatitis, contact dermatitis, eczema, lymphedema,
and erythema migrans. Microbiological diagnosis is often unobtainable due to poor sensitivity of culture specimens. The
majority of non-purulent, uncomplicated cases of cellulitis are caused by β-hemolytic streptococci or methicillin-sensitive
Staphylococcus aureus, and appropriate targeted coverage of this pathogen with oral antibiotics such as penicillin, amoxicil-
lin, and cephalexin is sufficient. Even with rising rates of community-acquired methicillin-resistant Staphylococcus aureus,
coverage for non-purulent cellulitis is generally not recommended.

Key Points
Cellulitis is a common dermatologic condition that
presents across multiple disciplines in the inpatient,
outpatient, and emergency room settings, with a large
impact on healthcare costs in the US.
Currently, cellulitis is a clinical diagnosis with no gold
standard for diagnosis. Differentiation from pseudocel-
lulitis and other clinical mimickers may be difficult, and
early consultation with a dermatologist may decrease
misdiagnosis and improve outcomes.
Empiric treatment of cellulitis should be informed by
clinical severity, risk factors, and likely etiological
organisms.
* Catherine G. Chung
Catherine.chung@osumc.edu
1
The Ohio State University College of Medicine, Columbus,
OH, USA
2
Division of Dermatology, Department of Internal Medicine,
The Ohio State University Wexner Medical Center,
Columbus, OH, USA
3
Department of Pathology, The Ohio State University Wexner
Medical Center, Columbus, OH, USA
1 Introduction
Cellulitis is an infection involving the deep dermis and sub-
cutaneous tissue. While this is a common condition, it can
present a diagnostic and therapeutic challenge. Over 14 mil-
lion patients in the US are treated for cellulitis annually,
accounting for over 1% of all US hospitalizations and a cost
of over $7 billion [1–3]. Additionally, it is estimated the
misdiagnosis of cellulitis results in $195–$515 million in
avoidable health care spending annually in the US [4]. In
this review, practice guidelines on cellulitis directed towards
the practicing dermatologist will be discussed, including the
clinical spectrum, differential diagnoses, diagnostic proce-
dures, and treatment options.
2 Epidemiology
In one observational retrospective cohort study utilizing
administrative claims data, the incidence of skin and soft
tissue infection (SSTI) was 45.73 episodes per person-years
(PY) in the ambulatory setting and 2.19 episodes per PY
in the inpatient setting [5]. Cellulitis accounts for 10.1%
of infectious disease hospitalizations, with an age-adjusted
rate of 156.2 hospitalizations per 100,000 persons and a
52.2% rate increase from 1998 to 2006 [6]. In one study,

Vol.:(0123456789)
 M. A. Boettler et al.

the total number and incidence of ambulatory SSTIs sig- Systemic symptoms and signs, such as fevers, chills,
nificantly increased from 1997 to 2005, with abscess/cellu- fatigue, and leukocytosis, indicate a more severe infection.
litis accounting for 95% of this increase; annual visits more Depending on the clinical setting and inclusion criteria, the
than doubled from 4.6 million to 9.6 million and visit rates percentage of patients with fever ranges from 22.5 to 71%
increased from 17.3 to 32.5 visits per 1000 population [7]. [10–12, 23, 24]. The most common site of infection is the
The mean age in hospitalized patients ranges from 56 lower extremities; however, any area of skin or soft tissue
to 66.5 years [4, 8–11], with no sex predilection in some can be affected, but is rarely bilateral [12, 19, 25]. Orbital,
studies [4, 8, 11] but with sex predilection in some studies buccal, and perianal cellulitis are variants of cellulitis dif-
with small sample sizes [9, 10, 12]. Risk factors associated ferentiated by anatomic location. Cellulitis can be compli-
with cellulitis include previous history of cellulitis, pres- cated by the development of sepsis, lymphedema, recurrent
ence of Staphylococcus aureus and/or β-hemolytic strep- cellulitis, or abscess formation [26–28].
tococci (BHS) in the toe webs, tinea pedis, obesity, older
age, lymphedema/chronic leg edema, venous insufficiency,
prior saphenectomy, psoriasis, and presence of a wound [9, 4 Evaluation
13–16]. Risk factors may vary by geographic location, as,
among Japanese patients with different patient backgrounds Cellulitis is a clinical diagnosis based on the history of
such as lower body mass index (BMI), hypoalbuminemia, present illness and physical examination and lacks a gold
lymphedema, hypertension, and hyperlipidemia were sig- standard for diagnosis. The severity of symptoms, history of
nificantly associated with cellulitis hospitalizations, whereas recurrent infections, risk factors for specific microorganisms,
classic risk factors of chronic venous insufficiency, periph- and presence or absence of purulence direct antimicrobial
eral circulatory disturbance, and deep vein thrombosis were selection, route of administration, and whether outpatient
not [17, 18]. versus inpatient treatment is warranted.
Sex differences do exist and vary among different coun-
tries [18]. When comparing sex differences between Japa-
nese hospitalized cellulitis patients, males tend to be young,
obese with diabetes, and have skin barrier dysfunction,
whereas females tend to be cancer-bearing with low body-
weight [18]. Of hospitalized Spanish patients with cellulitis,
females are significantly more likely to be older, have prior
cellulitis history, have edema/lymphedema, and location
of cellulitis other than in the lower extremities; males are
significantly more likely to have positive pus cultures [19].

3 Clinical Presentation

Cellulitis typically presents with acute onset of redness

(rubor), warmth (calor), swelling (tumor), and tenderness
and pain (dolor) (Fig. 1). The spreading borders are often
poorly demarcated yet smooth. Erysipelas is a subtype of
cellulitis that is more superficial and with a sharply demar-
cated, often raised border [20]. Erysipeloid, a clinical variant
caused by Erysipelothrix rhusiopathiae, is most often local-
ized to the back of one hand and/or fingers with erythema
and well-defined, raised borders [21]. Streptococcal celluli-
tis may present as blistering distal dactylitis, involving only
the fat pad of the distal finger or, more rarely, the toe [22].
Clinical manifestations range from mild (e.g. localized ery-
thema) to severe, with cutaneous abscesses, purulence, and
life-threatening spread, including bacteremia. Lymphangitis,
tender regional lymph nodes, bullae, petechiae, and ecchy-
moses may develop. Peau d’orange or ‘orange peel’ skin may Fig. 1  Acute bacterial cellulitis presenting with characteristic bright
appear secondary to edema causing perifollicular dimpling. red erythema and edema of the lower leg
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis
Superficial swabs, biopsy, and blood or needle aspirate
cultures have low yield and are not routinely recommended
for non-purulent cellulitis by the 2014 Infectious Diseases
Society of America guidelines; however, in patients with
malignancy on chemotherapy, neutropenia, severe cell-medi-
ated immunodeficiency (SCID), immersion injuries, and ani-
mal bites, blood cultures are recommended and cultures and
microscopic examination of needle aspirates, tissue biopsy,
or swabs should be considered [29]. Skin swabs and super-
ficial wound cultures are often polymicrobial that cannot
distinguish naturally occurring transient bacteria and colo-
nizers from pathogenic microorganisms, which can compli-
cate the overall picture. Immunocompromised patients are
more likely to have positive blood culture results and have a
wider differential diagnosis with higher risk for atypical bac-
terial, viral, fungal, and parasitic agents [29, 30]. Of those
patients in the emergency department (ED) or inpatient set-
ting, the percentage of patients with a positive blood cul-
ture ranges from 1 to 11% [23, 26, 31–34]. A 2020 scoping
review examining pretest probability of bacteremia in adult
non-neutropenic inpatients with cellulitis demonstrated the
risk is low (< 10%) and low–moderate (10% to < 20%) in
patients with severe comorbidities such as liver cirrhosis and
diabetes mellitus [26, 33, 35, 36]. The percentages are likely
lower in the ambulatory setting.
Laboratory evaluation is often unnecessary in cases of
uncomplicated cellulitis or patients without comorbidi-
ties. Findings tend to be non-specific: in patients hospi-
talized or presenting to the ED with cellulitis, leukocytosis
ranges from 34 to 51% [11, 23, 37, 38], while elevated
inflammatory markers, such as erythrocyte sedimentation
rate (ESR) and C-reactive protein (CRP), range from 59
to 97% [11, 23, 38]. Although these laboratory tests are
not specific to cellulitis, some may be helpful to indicate
disease severity. In one study comparing cellulitis patients
with and without sepsis, higher leukocyte and neutrophil
counts, serum creatinine, and CRP were seen in patients
with cellulitis who developed sepsis [26]. Anti-DNase-
B (ADB) and anti-streptolysin-O (ASO) antibodies can
be used to detect recent BHS infection [39]. Of patients
with diffuse, non-culturable cellulitis, 73% had at least
one positive titer, with 50% mounting both antibodies,
29% mounting ADB, and 21% mounting ASO [39]. ASO
and ADB antibodies are however non-specific and can be
elevated in rheumatic fever, glomerulonephritis, pharyngi-
tis, tonsillitis, and scarlet fever; thus, they may be helpful
in supporting the diagnosis but should be interpreted with
caution [39].
Data are available supporting the involvement of spe-
cialists, with multiple studies showing benefits with der-
matology and infectious disease consultations [40–43].
Having specialists available may lead to a discussion of
alternative etiologies, deeper microbial analysis, and/
or more targeted antimicrobial therapies. Additionally,
administrative data have demonstrated that hospitals that
lack access to dermatology consultations have higher rates
of cellulitis and lower rates of alternative skin disease
diagnosis-related groups per bed size [44]. While special-
ists may not be available in every hospital setting, there is
moderate agreement among dermatologists in differentiat-
ing and diagnosing cellulitis and pseudocellulitis, accord-
ing to a recent study [45].
5 Imaging
Imaging studies are often unnecessary in the work-up of
cellulitis. However, given that clinical and laboratory evalu-
ation can be non-specific and lack sensitivity, in the appro-
priate setting radiographic imaging can provide diagnostic
clues, evaluate disease extension, and aid in treatment plan-
ning. Imaging is also helpful in the setting of rapid progres-
sion or severe systemic manifestations to detect underlying
deep tissue involvement. Computed tomography (CT) and
magnetic resonance imaging (MRI) have high spatial and
contrast resolution, providing detailed anatomic information
[46]. Although CT provides higher sensitivity for the detec-
tion of soft-tissue gas, MRI is the mainstay imaging tool
for the diagnosis of soft-tissue infections [46]. Non-specific
soft-tissue swelling can be seen on radiograph [46]. Deep
venous ultrasonography (U/S) can be useful to exclude non-
infectious causes of soft-tissue swelling such as DVT [46,
47]. However, in the ED setting, the use of U/S for clinical
cellulitis changed physician management in approximately
half of all cases [47]. U/S imaging of cellulitis is non-spe-
cific, demonstrating subcutaneous edema [46].
6 Microbiology
Cellulitis is often separated into purulent and non-purulent
cellulitis. Microbiological diagnosis is often unobtainable
due to poor sensitivity of culture specimens. The clinical
isolation rate of a pathogen is < 20% in non-purulent cellu-
litis, and the relative frequencies of pathogens are therefore
difficult to establish [29]. A systematic review of bacteremia
in the setting of cellulitis demonstrated BHS as the most
common pathogen (57%), followed by Gram-negative bacte-
ria (28%) and Staphylococcus aureus (14%) [20, 25, 39, 48].
In one study, patients diagnosed with BHS by serology or
culture had a 97% response to B-lactam antibiotic treatment,
while those who did not have BHS by serology or culture
had a 91% response, supporting BHS as the most common
etiology of cellulitis even in the absence of pathogen isola-
tion despite the emergence and uptick in methicillin-resistant
 M. A. Boettler et al.

Staphylococcus aureus (MRSA) infections [39]. Staphylo- Table 1  Risk factors and associated pathogens in cellulitis
coccus aureus is the most common isolate of acute puru-
Risk factor Pathogen
lent SSTI [49]. There is an increasing concern over anti-
biotic resistance and rising rates of community-associated Animal and human bites
MRSA. However, in a randomized clinical trial comparing Human bite [51] Peptostreptococcus
anti-methicillin-sensitive Staphylococcus aureus (MSSA) Fusobacterium
and anti-MRSA antibiotics in the outpatient treatment of Veillonella
Clostridium
cellulitis without abscess, the addition of trimethoprim-sul- α-hemolytic Streptococci
famethoxazole to cephalexin did not improve outcomes [50]. β-hemolytic Streptococci
The most common pathogen of cellulitis is bacteria; how- Staphylococcus aureus
ever, immunosuppression creates a unique environment for Staphylococcus epidermidis
Corynebacterium sp.
opportunistic infection with fungi and atypical bacteria such Eikenella corrodens
as Mycobacterium species (Fig. 2). Bacteroidesfragilis
Pathogens related to specific risk factors are charted Prevotella
in Table 1. Inoculation via animal or human bite, aquatic Porphyromonas
exposure, immunosuppression, and chronic liver and kidney Cat bite [51] Pasteurella multocida
Bacteroides fragilis
disease can increase the likelihood of an atypical pathogen, Prevotella
necessitating a different treatment choice. Porphyromonas
Peptostreptococcus
Fusobacterium sp.
Veillonella pawula
7 Histopathology Dog bite [51] Pasteurella multocida
Staphylococcus sp.
Currently, tissue biopsy is considered low yield and is not Streptococcus sp.
recommended unless the patient is immunocompromised Corynebacterium sp.
(e.g. history of transplant, in the setting of systemic ster- Bacteroides fragilis
Prevotella
oids or other immunosuppressive treatment, or in individu- Porphyromonas
als with HIV/AIDS), febrile with neutropenia, or at risk of Peptostreptococcus
specific pathogens (water or animal bites exposure) [1, 29]. Fusobacterium sp.
If there is no improvement with antibiotic initiation and/or Veillonella pawula
Capnocytophaga canimorsus
there is suspicion of non-infectious pseudocellulitis, punch
Marine water exposure [52] Vibrio spp.
biopsy should be obtained for histopathologic analysis. His- Aeromonas spp.
topathology of cellulitis includes dermal edema, lymphatic Shewanella spp.
and/or vascular dilation, and prominent diffuse neutrophilic Erysipelothrix rhusiopathiae
Mycobacterium marinum
Streptococcus iniae
Clostridium
Pseudomonas
Plesiomonas
Immunosuppression Mycobacterium hemophilum [53,
54]
Cryptococcus neoformans [53]
Mycobacterium tuberculosis [54]
Vibrio cholerae [55]
Helicobacter [56, 57]
Fusarium [58]
Chryseobacterium meningosepti-
cum [59]
Cedecea sp. [60]
Serratia marcescens [61]
Stenotrophomonas maltophilia
[62]
Streptococcus pneumoniae [63]
Escherichia coli [64, 65]
Campylobacter fetus [66]
Shewanella putrefaciens [67]
Fig. 2  Cryoptococcal cellulitis in a patient with chronic liver disease Hemophilus influenzae [68]
presenting with well-circumscribed bright red erythema and edema of
the upper extremity
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis
Table 1  (continued)
Risk factor Pathogen
Chronic liver disease [61] Vibrio cholerae [55]
Group A Streptococci
Staphylococcus aureus
Escherichia coli
Klebsiella spp.
Pseudomonas aeruginosa
Aeromonas spp.
Chronic kidney disease Cedecea sp. [60]
Helicobacter cinaedi [57]
Escherichia coli [65]
infiltration that involves the dermis and may extend to the
soft tissues. In cases where cellulitis is accompanied by
tissue necrosis, secondary necrotizing vasculitis may also
be present. Identification of microorganisms ranges from
numerous (especially in the setting of necrosis) to scant.
Lymphocytes, histiocytes, and granulation tissue may
develop in established, more chronic cases [69–72].
8 Differential Diagnosis
Cellulitis can be difficult to diagnose due to a number of
infectious and non-infectious clinical mimickers (Table 2)
that may present with the characteristic warmth, erythema,
edema, pain, fever, and/or leukocytosis seen in cellulitis. In
fact, 30 [43, 73] to 74% [74] of cellulitis cases are eventually
diagnosed as a pseudocellulitis. Of the causes of pseudocel-
lulitis, venous stasis dermatitis, contact dermatitis, eczema,
lymphedema, and erythema migrans are among the top con-
tributors to misdiagnosis [43, 73, 74]. A thorough history
and clinical examination and specialist consultation with
dermatology when available can help differentiate cellulitis
from pseudocellulitis [44].
Venous stasis dermatitis is caused by venous hyperten-
sion resulting from retrograde flow, which subsequently
creates an inflammatory process and further tissue changes
[75]. Stasis dermatitis presents as poorly demarcated ery-
thematous plaques of the lower legs bilaterally, classically
involving the medial malleolus, whereas cellulitis of the
lower extremities is typically unilateral and infrequently, if
ever, bilateral. Duplex ultrasound can be utilized to demon-
strate venous reflux.
Contact dermatitis is due to an irritant or allergen causing
a delayed type IV hypersensitivity reaction (Fig. 3), with
pruritus as the classic symptom, differentiating it from cel-
lulitis. The use of medical adhesives over a wound can cause
a hypersensitivity reaction that must be distinguished from
cellulitis [76]. Investigating triggers of contact dermatitis
such as the use of topical antibiotics, hair dye, cosmetic
products, fragrances, rubber, latex, plants, acrylates, and
metals such as nickel is important to determine an etiology
[77].
Lymphedema is a chronic progressive localized form
of tissue swelling due to excessive retention of lymphatic
fluid in the interstitial compartment caused by impaired
lymphatic drainage [28]. Lymphedema often causes over-
lying cutaneous changes (Fig. 4) and is commonly compli-
cated by secondary skin infections, with one study demon-
strating 29% of patients with lymphedema were admitted
for intravenous antibiotics over the course of 12 months
[78]. Information on family history, history of penetrating
trauma, infection, cancer, heart failure, hypothyroidism,
hypoalbuminemia, sepsis, venous or lymphatic obstruc-
tion, inguinal/axillary radiation, lymphadenectomy, and
travel to areas endemic for filariasis should be elicited
[28]. Lymphoscintigraphy is the standard imaging tool to
confirm the diagnosis of lymphedema [28]. Acute inflam-
matory edema is characterized by bilateral, erythematous,
and edematous plaques involving areas of dependence and
sparing areas of pressure, most commonly the thighs and
abdomen of critically ill patients with acute fluid overload
[79]. This type of pseudocellulitis can mimic cellulitis
clinically and histopathologically, given the presence of
neutrophils [79].
Erythema migrans, or primary Lyme disease, is an ery-
thematous macule or papule that expands centrifugally to
form a patch of erythema that may develop a targetoid, ‘bull-
seye’ appearance caused by Ixodes tick transmitting Borrelia
burgdorferi. The expanding nature of erythema can clini-
cally mimic cellulitis, but pertinent history regarding travel
or residence in an endemic, history of recent tick bite within
2 weeks, late spring/summer, and locations atypical for bac-
terial cellulitis such as the axilla, popliteal fossa, groin, and
waist can provide clues to Lyme disease [80].
DVT, necrotizing soft tissue infection (NSTI), septic
arthritis, and gout are less common causes of pseudocel-
lulitis but can cause significant morbidity and mortality if
misdiagnosed and are therefore essential to differentiate.
DVT is caused by a blood clot obstruction of the venous
system, which can migrate to the pulmonary system or
brain, causing pulmonary embolism or stroke, respec-
tively. DVT often presents similarly to cellulitis, with uni-
lateral limb swelling, erythema, and pain. In a systematic
review and meta-analysis on the risk of DVT in patients
with cellulitis and erysipelas, 3.1% of 1054 patients with
cellulitis or erysipelas had any type of DVT via compres-
sion ultrasound [81]. The overall prevalence of DVT in
patients with cellulitis or erysipelas appears to be low;
however, if there is concern for DVT, patients should be
sent to an urgent care center or ED for further evaluation.
Symptoms of gout and septic arthritis can cause a rapid
onset of pain, erythema, swelling, and warmth over an over-
lying joint. Patients with underlying joint pain require joint
 M. A. Boettler et al.

Table 2  Differential diagnosis of cellulitis

Characteristics Evaluation

Infectious
Necrotizing soft tissue infection Rapidly progressive erythema or purpura, pain out of proportion, fever, Evaluation by general surgery
systemic toxicity, swelling, hemorrhagic or bluish bullae, skin necrosis or if clinically suspicious
extensive ecchymosis, gas, or crepitus
Cutaneous abscess Nodule with fluctuance and drainage in addition to features of cellulitis
Herpes simplex Grouped vesicles on an erythematous base. Most often appear in the trigemi- Polymerase chain reaction
nal or sacral ganglia distribution but may occur at other body locations is the most sensitive and
preferred diagnostic test
if clinical presentation is
unclear [89, 90]
Herpes zoster Painful dermatomal erythematous patch or plaque with grouped vesicles Polymerase chain reaction
without crossing the midline unless disseminated is the most sensitive and
preferred diagnostic test
if clinical presentation is
unclear [90]
Erythema migrans Well-demarcated circular erythematous macule, patch, or plaque that History of a tick bite or recent
expands and may develop central clearing, forming a targetoid bullseye travel to an endemic area
appearance
Septic arthritis Painful, swollen, warm, erythematous skin overlying a joint. It can be Joint aspiration for diagnosis
accompanied by fever and leukocytosis
Non-infectious inflammatory
Sweet syndrome Abrupt painful, edematous, erythematous papules, plaques, or nodules that Both major criteria and two
coalesce. Fever and leukocytosis frequently accompany the cutaneous of four minor criteria are
lesions required for diagnosis [91]
Contact dermatitis Acute presentation of erythema or vesicles. Scaling and fissures are seen
chronically. Well-demarcated geometric or non-organic pattern and distri-
bution. Pruritus is the most common symptom
Erythema nodosum Erythematous, tender, immobile nodules and plaques most commonly on the
bilateral shins [92]
Gout Painful, swollen, warm, erythematous skin overlying a joint. It can be History of gout. Joint aspira-
accompanied by fever and leukocytosis. Subcutaneous gout nodules (tophi) tion for diagnosis
appear as white or yellow
Acute bursitis Painful, swollen, warm, erythematous skin overlying a bursa. Often due to
trauma or infection
Pyoderma gangrenosum Papule, pustule, vesicle, or nodule that rapidly expands and forms an erosion
or ulcer. Pathergy often seen
Familial mediterranean fever Erysipelas-like reaction with a tender, erythematous, raised lesion over the Recurrent nature and positive
lower extremities during an attack family history
Vascular
Stasis dermatitis Bilateral, chronic history that improves with leg elevation, compression
therapy, and topical corticosteroids. Often hyperpigmentation, varicose
veins, ulcerations
Deep vein thrombosis Unilateral swelling, erythema, warmth, or tenderness. Risk factors include Ultrasound is a sensitive and
prolonged immobilization, prior history of deep vein thrombosis, active relatively cheap tool for
malignancy, recent surgery, and pregnancy diagnosis [93]
Erythromelalgia Bilateral, warm, erythematous extremities with burning paresthesia that is
out of proportion to clinical examination and improves with cooling
Lymphatics
Lymphedema Feeling of heaviness and discomfort commonly accompanies swelling. Pit- Lymphoscintigraphy is the
ting is variable in patients with lymphedema and can be absent if chronic. standard imaging tool to
Cutaneous and subcutaneous thickening if severe confirm the diagnosis [28]
Acute inflammatory edema Bilateral, erythematous, edematous plaques most frequently on the abdomen
and thighs. Often in critically ill, fluid overloaded patients with high body
mass index
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis

Table 2  (continued)
Characteristics Evaluation

Neoplasm
Carcinoma erysipeloides
Miscellaneous
Fixed drug eruption
Hypersensitivity reaction
Cutaneous metastasis presenting as a fixed erythematous, well-demarcated Most often associated with
patch or plaque often overlying a primary cancer breast carcinoma, which
presents on the chest [94]
Usually non-tender eruption soon after drug ingestion. Most often on the
face, lips, trunk, genitalia, hands, and feet [95]
Pruritic reaction with variable presentation depending on the type of hyper-
sensitivity

hemodynamic collapse, and organ failure, with delays in sur-

Fig. 3  Allergic contact dermatitis to neomycin
Fig. 4  Chronic lymphedema: bilateral lower extremity edema with
overlying skin changes, including thickening, hyperpigmentation, and
scale
gical debridement, antibiotic use, and resuscitation impact-
ing morbidity and mortality. The absence of fever or early
cutaneous manifestations, non-specific radiographic tests,
recent history of non-penetrating trauma, surgery, or child-
birth, and chronic underlying diseases can complicate diagno-
sis [82]. Classic clinical findings of NSTI include soft tissue
edema (75%), erythema (72%), severe pain (72%), tenderness
(68%), fever (60%), and skin blebs, bullae, or necrosis (38%)
[83]. While certain ‘hard’ clinical signs are associated with
necrotizing fasciitis, such as hemodynamic instability, crepi-
tance, skin necrosis, bullae, and gas on x-ray, a majority of
patients unfortunately present with none of these [84]. The
Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC)
is a clinical tool to screen for necrotizing fasciitis based on
CRP, total white blood cell count, hemoglobin, sodium, cre-
atinine, and glucose [85]. An LRINEC score of six or greater
confers a higher risk of necrotizing fasciitis [85]. The LRINEC
score is most specific for severe disease [86]. Newer scoring
systems such as the SIARI score (Site other than the lower
limb, Immunosuppression, Age ≤ 60 years, Renal impairment
[creatinine > 141 µmol/L], and Inflammatory markers [CRP >
150, white blood cell count > 25]) developed in New Zealand
showed greater diagnostic ability compared with the LRINEC
score [87] (Table 3). A modified LRINEC score has also been
created with alteration of laboratory parameters (including
fibrinogen levels and erythrocyte counts) and the addition of
clinical symptoms, leading to higher positive predictive value
without losing specificity [88].
If clinical suspicion of necrotizing fasciitis is high,
immediate surgical evaluation and antibiotic treatment are
required.

fluid analysis via arthrocentesis for diagnosis and treatment 9 Treatment

to prevent joint destruction and permanent damage.
NSTI, such as necrotizing cellulitis and necrotizing A systematic review and meta-analysis showed a high
fasciitis, is a severe, life-threatening infection character- overall treatment failure rate of nearly 20%, likely due to
ized by widespread tissue destruction, systemic toxicity, a significant proportion of cellulitis misdiagnoses [96]. As

Table 3  The laboratory risk indicator for necrotizing fasciitis [85]
Parameter Range
Hb (g/dL) > 13.5
11–13.5
< 11
White blood cells (­ 109/L) < 15
15–25
> 25
Sodium (mmol/L) < 135
Creatinine (μmol/L) > 141
Glucose > 10
C-reactive protein > 150
Score ≤ 5 = < 50% risk (low); 6–7 = intermediate risk; ≥ 8 = > 75%
risk (high)
mentioned previously, the causative microbe in cellulitis is
often not recovered, and treatment is most often initiated
empirically. The majority of non-purulent, uncomplicated
cases of cellulitis are caused by BHS or MSSA and appropri-
ate targeted coverage of this pathogen is sufficient. Patients
can often be managed with oral antibiotics. Suitable options
include penicillin, amoxicillin, and cephalexin. Cephalexin,
dicloxacillin, and amoxicillin-clavulanate cover for MSSA
in addition to BHS. Patients with a penicillin allergy can
be treated with clindamycin or trimethoprim-sulfamethox-
azole, which demonstrate near equivalent cure rates [97].
The recommended duration of treatment is 5 days unless
infection has not improved during this time span, and treat-
ment should be extended [29, 98]. Even with rising rates
of community-acquired MRSA, β-lactam and non-β-lactam
antibiotic clinical failure rates for uncomplicated cellulitis
do not differ [99]. Coverage of MRSA for non-purulent cel-
lulitis is generally not recommended unless patients have
failed initial antibiotic treatment, markedly impaired host
defenses, systemic inflammatory response syndrome and
hypotension, cellulitis associated with penetrating trauma,
evidence of MRSA infection elsewhere, nasal colonization
with MRSA, community-associated MRSA-prevalent set-
ting, or injection drug use [29, 100, 101]. Oral antibiotics
with MRSA coverage such as trimethoprim-sulfamethoxa-
zole, clindamycin, doxycycline, and linezolid may be chosen
by providers. The rates of MRSA vary considerably depend-
ing on geographic location, hospitalization, and residence,
and should be taken into consideration [102]. Systemic signs
of infection (e.g. fever, tachycardia, leukocytosis) warrant
systemic antibiotics [29]. However, the benefit of the intra-
venous versus oral route of antibiotic administration for
cellulitis of similar severity has not been proven to be sig-
nificant [98, 103]. Various randomized control trials have
shown no evidence of difference in clinical response rates,
mean days until no advancement of the area of cellulitis,
M. A. Boettler et al.
rates of relapse or recurrence, or patients’ pain scores and
satisfaction between intravenous versus oral routes of anti-
Score
biotic administration [103]. In the hospital setting, the use of
0 antimicrobials with broad aerobic gram-negative, anti-pseu-
1 domonal, or broad anaerobic activity are frequently used
2 without a corresponding decrease in clinical failure [104]. A
0 multicenter clinical trial on the use of single, renally admin-
1 istered, long-acting intravenous dalbavancin for stable ED
2 patients with advanced SSTI showed a significant reduction
2 in the hospitalization rate [105]. In severely compromised
2 patients with malignancy on chemotherapy, neutropenia,
1 SCID, immersion injuries, and animal bites, broad spectrum
4 coverage such as vancomycin plus piperacillin/tazobactam
or imipenem/meropenem may be considered [29]. Purulent
cellulitis should be managed with incision and drainage,
with the addition of antibiotics for those who are immuno-
compromised and display systemic signs of infection, signs
of deeper infection, or antibiotic failure [29].
Antibiotic options and standard dosing based on the
route of administration are shown in Table 4. Poor out-
comes are significantly associated with age, previous epi-
sodes of cellulitis, prior wounds and skin lesions, venous
insufficiency, lymphedema, immunosuppression, and
involvement of the lower limbs [8].
A number of patients are susceptible to recurrent cel-
lulitis infections. A previous episode of cellulitis has a
recurrence rate ranging from 8 to 20% annually, especially
if occurring on the legs [29]. In a prospective case-control
study, 49% of hospitalized cellulitis patients had a positive
history of at least one cellulitis episode before entering
the study [106]. Obesity (BMI ≥ 30) and previous ipsilat-
eral surgical procedure of the site of cellulitis were sig-
nificantly more common in these patients [106]. Episodes
of cellulitis cause post-inflammatory lymphatic damage,
leading to a vicious cycle since lymphedema predisposes
to cellulitis [107]. A Cochrane systematic review of inter-
ventions for recurrent cellulitis demonstrated antibiotic
prophylaxis, compared with no treatment or placebo,
decreased the risk of cellulitis recurrence after treatment
by 69%, and reduced the incidence rate of cellulitis by
56% [108]. However, the protective effects of antibiotic
prophylaxis did not persist after treatment cessation [108].
Proposed regimens include oral penicillin 250 mg twice
daily, oral penicillin 2–4 g daily depending on body weight
(1 g twice daily if < 90 kg; 1 g + 2 g daily if 90–120 kg;
2 g twice daily if > 120 kg), intramuscular penicillin 1.2
million units every 15 days, and oral erythromycin 250
mg twice daily [108]. It has been suggested that those who
experience three to four episodes of cellulitis per year may
benefit from prophylactic antibiotics, whereas the system-
atic review demonstrated the effects are most relevant for
people after just two episodes of leg cellulitis occurring
within a period of up to 3 years [29, 108]. Adverse effects
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis

Table 4  Antimicrobial treatment options for cellulitis by route Treatment for long-term success of cellulitis includes
targeting risk factors. It is estimated 10–30% of people
Antibiotic Standard dosing
who have one episode of cellulitis will experience repeated
Oral attacks across different time intervals [108]. Diabetes mel-
Penicillin 500 mg PO qid litus, history of previous episodes of cellulitis, edema of
­Amoxicillina 500 mg PO tid the lower extremities, peripheral vascular disease, obesity,
Amoxicillin-clavulanatea 875–125 mg PO bid immunosuppression, alcoholism, and dermatomycosis are
Dicloxacillin 500 mg PO qid among the most common underlying conditions associated
­Cephalexina 500 mg PO qid with cellulitis [12, 108]. The treatment or management of
­Clindamycinb 300 mg PO tid underlying predisposing conditions may prevent recurrence.
Alternatives Various methods to reduce limb lymphedema and edema,
Trimethoprim- 1–2 double-strength tablets PO venous insufficiency, local skin care and hygiene maintain
sulfamethoxazolea,b q12h the integrity of skin and decrease the likelihood of creation
­Doxycyclineb 100 mg PO qid of a nidus for infection. Combined decongestive therapy is
­Minocyclineb 200 mg PO once, then 100 mg a multimodal approach to lymphedema that includes com-
PO q12h
pression therapy, manual lymphatic drainage, exercise, and
Flucloxacillin 500 mg PO qid
skincare and is regarded as the standard of treatment [28].
­Delafloxacinb 450 mg PO bid
The acquisition of acute pneumatic compression devices for
­Linezolidb 600 mg PO bid
lymphedema is associated with significant reductions in epi-
­Tedizolidb 200 mg PO bid
sodes of cellulitis and patient care costs [109]. Weight loss
Intravenous
for obese patients is strongly recommended and leg elevation
­Penicillina 2–4 million units IV, q4h–q6h
in early-stage disease can reduce fluid accumulation [28].
­Cefazolina 1–2 g IV q8h
Diuretics do not play a role in lymphedema and surgical
Nafcillin 1–2 g IV q4–6h
intervention is considered when conservative management
Ceftriaxone 1–2 g IV q24h
fails [28]. Lymphaticovenular anastomosis is a potential
­Clindamycinb 600–900 mg IV q12h
surgical intervention for lymphedema that has shown a sta-
Alternatives
tistically significant reduction in the rate of cellulitis [110].
­Vancomycina,b 15–20 mg/kg IV q8–12h
Interdigital toe space examination and treatment for fis-
­Daptomycina,b 4–6 mg/kg IV q24h
suring, scaling, or maceration in lower extremity cellulitis
­Ceftarolinea,b 600 mg IV q12h
may eradicate pathogen colonization and reduce the inci-
­Linezolidb 600 mg IV bid
dence of recurrent infections [29]. In a randomized control
­Tedizolidb 200 mg IV bid
trial of participants with chronic leg edema and recurrent
­Dalbavancina,b 1500 mg IV single dose
cellulitis, compression therapy caused a lower incidence of
­Ciprofloxacina 400 mg IV q12h
recurrent cellulitis than conservative treatment and the trial
Flucloxacillin 2 g IV q6h
was stopped for efficacy [111]. Antibiotic prophylaxis fail-
Oxacillin 1–2 g IV q4h
ure with penicillin is associated with a BMI ≥ 33, three or
This is a standard guide of possible treatment regimens and is not more previous episodes of cellulitis, and presence of edema,
meant to be all-inclusive. Clinicians should refer to their institution’s which a large proportion of patients who benefit from com-
antimicrobial stewardship guidelines and other resources for prescrib- pression therapy have [111, 112]. However, compression
ing
therapy should not be used during an active infection.
PO orally, bid twice daily, TID three times daily, QID four times
daily, IV intravenous, qxh every x hours, MRSA methicillin-resistant
Staphylococcus aureus
a
May need adjustment for renal function 10 Patient Education
b
Provides MRSA coverage
Patients should be counseled on cellulitis and the pre-
scribed antibiotics. Completion of the full course of anti-
are rare and most commonly consist of gastrointestinal biotics should be encouraged despite improvement before
symptoms, mainly nausea and diarrhea; rash, with no the course ends; improvement should be seen within
cases of severe cutaneous adverse reactions reported; and 24–48 h of initiating antibiotics. Providers may find util-
thrush [108]. Importantly, antimicrobial resistance was not ity to mark the margins of the infection to indicate to
assessed. patients whether it is improving or worsening. Patients

should inform their provider if the margin is spreading
or not improving, the pain worsens, or persistent fever
develops.
Patients should maintain appropriate hand hygiene when
attending to the site of infection and keep the area clean and
dry. As feasible, patients should elevate the site to reduce
edema [29].
11 Summary
Cellulitis is a common condition that causes significant
health care costs, can be difficult to distinguish clinically,
and lacks a gold standard for diagnosis. A thorough his-
tory and clinical examination can assist in the diagnosis,
and evaluation with laboratory and imaging investigation
is usually not necessary. The clinical isolation rate of a
pathogen is low and treatment is most often begun empiri-
cally. The most significant risk factor for the development
of cellulitis is a prior episode of cellulitis, and treatment
should also address underlying conditions and patient
education.
Declarations
Funding No sources of funding were used to assist in the preparation
of this article.
Conflicts of Interest Michelle Boettler, Benjamin Kaffenberger and
Catherine Chung state no conflicts of interest.
Ethics Approval Not applicable.
Informed Consent Not applicable.
Consent for publication Not applicable.
Data Availability Data sharing is not applicable to this article as no
datasets were generated or analyzed during the current study.
Code availability Not applicable.
Author Contributions All authors contributed to the review conception
and design. The first draft of the manuscript was written by Michelle
Boettler and all authors commented on previous versions of the manu-
script. All authors read and approved the final manuscript.
References
1. Raff AB, Kroshinsky D. Cellulitis: a review. JAMA.
2016;316(3):325–37.
2. Zhang M, Markova A, Harp J, Dusza S, Rosenbach M, Kaf-
fenberger BH. Dermatology-specific and all-cause 30-day and
calendar-year readmissions and costs for dermatologic diseases
from 2010 to 2014. J Am Acad Dermatol. 2019;81(3):740–8.
3. Peterson RA, Polgreen LA, Cavanaugh JE, Polgreen PM. Increas-
ing incidence, cost, and seasonality in patients hospitalized for
cellulitis. Open Forum Infect Dis. 2017;4(1):ofx008.
M. A. Boettler et al.
4. Weng QY, Raff AB, Cohen JM, Gunasekera N, Okhovat
JP, Vedak P, et al. Costs and consequences associated with
misdiagnosed lower extremity cellulitis. JAMA Dermatol.
2017;153(2):141–6.
5. Miller LG, Eisenberg DF, Liu H, Chang CL, Wang Y, Luthra R,
et al. Incidence of skin and soft tissue infections in ambulatory
and inpatient settings, 2005–2010. BMC Infect Dis. 2015;15:362.
6. Christensen KL, Holman RC, Steiner CA, Sejvar JJ, Stoll BJ,
Schonberger LB. Infectious disease hospitalizations in the United
States. Clin Infect Dis. 2009;49(7):1025–35.
7. Hersh AL, Chambers HF, Maselli JH, Gonzales R. National
trends in ambulatory visits and antibiotic prescribing for skin and
soft-tissue infections. Arch Intern Med. 2008;168(14):1585–91.
8. Collazos J, de la Fuente B, García A, Gómez H, Menéndez C,
Enríquez H, et al. Cellulitis in adult patients: a large, multicenter,
observational, prospective study of 606 episodes and analysis
of the factors related to the response to treatment. PLoS ONE.
2018;13(9): e0204036.
9. Björnsdóttir S, Gottfredsson M, Thórisdóttir AS, Gunnarsson
GB, Ríkardsdóttir H, Kristjánsson M, et al. Risk factors for acute
cellulitis of the lower limb: a prospective case-control study. Clin
Infect Dis. 2005;41(10):1416–22.
10. Chartier C, Grosshans E. Erysipelas. Int J Dermatol.
1990;29(7):459–67.
11. Lazzarini L, Conti E, Tositti G, de Lalla F. Erysipelas and cel-
lulitis: clinical and microbiological spectrum in an Italian tertiary
care hospital. J Infect. 2005;51(5):383–9.
12. Koutkia P, Mylonakis E, Boyce J. Cellulitis: evaluation of possi-
ble predisposing factors in hospitalized patients. Diagn Microbiol
Infect Dis. 1999;34(4):325–7.
13. Quirke M, Ayoub F, McCabe A, Boland F, Smith B, O’Sullivan
R, et al. Risk factors for nonpurulent leg cellulitis: a systematic
review and meta-analysis. Br J Dermatol. 2017;177(2):382–94.
14. McNamara DR, Tleyjeh IM, Berbari EF, Lahr BD, Martinez
JW, Mirzoyev SA, et al. Incidence of lower-extremity cellulitis:
a population-based study in Olmsted county, Minnesota. Mayo
Clin Proc. 2007;82(7):817–21.
15. Dupuy A, Benchikhi H, Roujeau JC, Bernard P, Vaillant L,
Chosidow O, et al. Risk factors for erysipelas of the leg (cel-
lulitis): case-control study. BMJ. 1999;318(7198):1591–4.
16. Wakkee M, de Vries E, van den Haak P, Nijsten T. Increased
risk of infectious disease requiring hospitalization among
patients with psoriasis: a population-based cohort. J Am Acad
Dermatol. 2011;65(6):1135–44.
17. Norimatsu Y, Ohno Y. Predictors for readmission due to cel-
lulitis among Japanese patients. J Dermatol. 2021;48(5):681–4.
18. Norimatsu Y, Ohno Y. Sex-based differences in Japanese
patients with cellulitis. J Dermatol. 2021;48(11):1797–8.
19. Collazos J, de la Fuente B, de la Fuente J, García A, Gómez
H, Rivas-Carmenado M, et al. Sex differences in hospitalized
adult patients with cellulitis: a prospective, multicenter study.
Int J Infect Dis. 2021;104:584–91.
20. Eriksson B, Jorup-Rönström C, Karkkonen K, Sjöblom AC,
Holm SE. Erysipelas: clinical and bacteriologic spectrum and
serological aspects. Clin Infect Dis. 1996;23(5):1091–8.
21. Veraldi S, Girgenti V, Dassoni F, Gianotti R. Erysipeloid: a
review. Clin Exp Dermatol. 2009;34(8):859–62.
22. Olivieri I, Scarano E, Padula A, Giasi V, Priolo F. Dactyli-
tis, a term for different digit diseases. Scand J Rheumatol.
2006;35(5):333–40.
23. Hook EW, Hooton TM, Horton CA, Coyle MB, Ramsey PG,
Turck M. Microbiologic evaluation of cutaneous cellulitis in
adults. Arch Intern Med. 1986;146(2):295–7.
24. Musher DM, Fainstein V, Young EJ. Treatment of cel-
lulitis with ceforanide. Antimicrob Agents Chemother.
1980;17(2):254–7.
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis
25. Bruun T, Oppegaard O, Kittang BR, Mylvaganam H, Lange-
land N, Skrede S. Etiology of cellulitis and clinical prediction of
streptococcal disease: a prospective study. Open Forum Infect
Dis. 2016;3(1):ofv181.
26. Collazos J, de la Fuente B, de la Fuente J, García A, Gómez H,
Menéndez C, et al. Factors associated with sepsis development
in 606 Spanish adult patients with cellulitis. BMC Infect Dis.
2020;20(1):211.
27. Picard D, Klein A, Grigioni S, Joly P. Risk factors for abscess
formation in patients with superficial cellulitis (erysipelas) of the
leg. Br J Dermatol. 2013;168(4):859–63.
28. Grada AA, Phillips TJ. Lymphedema: diagnostic workup and
management. J Am Acad Dermatol. 2017;77(6):995–1006.
29. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein
EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and
management of skin and soft tissue infections: 2014 update by
the Infectious Diseases Society of America. Clin Infect Dis.
2014;59(2):e10-52.
30. Carey CF, Dall L. Diagnosis of cellulitis in the immunocompro-
mised host. Can J Infect Dis. 1990;1(4):133–5.
31. Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Dobry
AS, et al. Clinical usefulness of imaging and blood cultures in
cellulitis evaluation. JAMA Intern Med. 2018;178(7):994–6.
32. Perl B, Gottehrer NP, Raveh D, Schlesinger Y, Rudensky B, Yin-
non AM. Cost-effectiveness of blood cultures for adult patients
with cellulitis. Clin Infect Dis. 1999;29(6):1483–8.
33. Lee CY, Kunin CM, Chang C, Lee SS, Chen YS, Tsai HC. Devel-
opment of a prediction model for bacteremia in hospitalized
adults with cellulitis to aid in the efficient use of blood cultures:
a retrospective cohort study. BMC Infect Dis. 2016;16(1):581.
34. Paolo WF, Poreda AR, Grant W, Scordino D, Wojcik S. Blood
culture results do not affect treatment in complicated cellulitis. J
Emerg Med. 2013;45(2):163–7.
35. Fabre V, Sharara SL, Salinas AB, Carroll KC, Desai S, Cosgrove
SE. Does this patient need blood cultures? A scoping review of
indications for blood cultures in adult nonneutropenic inpatients.
Clin Infect Dis. 2020;71(5):1339–47.
36. van Daalen FV, Kallen MC, van den Bosch CMA, Hulscher
MEJL, Geerlings SE, Prins JM. Clinical condition and comor-
bidity as determinants for blood culture positivity in patients with
skin and soft-tissue infections. Eur J Clin Microbiol Infect Dis.
2017;36(10):1853–8.
37. Raff AB, Weng QY, Cohen JM, Gunasekera N, Okhovat JP,
Vedak P, et al. A predictive model for diagnosis of lower extrem-
ity cellulitis: a cross-sectional study. J Am Acad Dermatol.
2017;76(4):618-25.e2.
38. Krasagakis K, Valachis A, Maniatakis P, Krüger-Krasagakis
S, Samonis G, Tosca AD. Analysis of epidemiology, clini-
cal features and management of erysipelas. Int J Dermatol.
2010;49(9):1012–7.
39. Jeng A, Beheshti M, Li J, Nathan R. The role of beta-hemo-
lytic streptococci in causing diffuse, nonculturable cel-
lulitis: a prospective investigation. Medicine (Baltimore).
2010;89(4):217–26.
40. Wells A, Gupta P, Tian F, Adkins E, Kaffenberger B. The effect
of implementing teledermatology in patients presenting with
cellulitis versus pseudocellulitis in an academic emergency
department setting: a pilot study. J Clin Aesthet Dermatol.
2020;13(4):43–4.
41. Gupta P, Tolliver S, Zhang M, Schumacher E, Kaffenberger BH.
Impact of dermatology and teledermatology consultations for
patients admitted with cellulitis: a pilot study. J Am Acad Der-
matol. 2020;82(2):513–5.
42. Jain SR, Hosseini-Moghaddam SM, Dwek P, Gupta K, Elsayed S,
Thompson GW, et al. Infectious diseases specialist management
improves outcomes for outpatients diagnosed with cellulitis in
the emergency department: a double cohort study. Diagn Micro-
biol Infect Dis. 2017;87(4):371–5.
43. Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P,
Shah R, et al. Effect of dermatology consultation on outcomes
for patients with presumed cellulitis: a randomized clinical trial.
JAMA Dermatol. 2018;154(5):529–36.
44. Ly N, Goldenberg M, Korman AM, Spaccarelli N, Wang H,
Chung C, et al. A retrospective study of cellulitis outcomes in
Ohio hospitals with or without access to dermatology residency
programs. Int J Dermatol. 2021. https://​doi.​org/​10.​1111/​ijd.​
15611.
45. Korman AM, Kroshinsky D, Raff AB, Mostaghimi A, Micheletti
RG, Rosenbach M, et al. A survey-based study of diagnostic
and treatment concordance in standardized cases of cellulitis
and pseudocellulitis via teledermatology. J Am Acad Dermatol.
2020;82(5):1221–3.
46. Hayeri MR, Ziai P, Shehata ML, Teytelboym OM, Huang BK.
Soft-tissue infections and their imaging mimics: from cellulitis
to necrotizing fasciitis. Radiographics. 2016;36(6):1888–910.
47. Tayal VS, Hasan N, Norton HJ, Tomaszewski CA. The effect
of soft-tissue ultrasound on the management of cellulitis in the
emergency department. Acad Emerg Med. 2006;13(4):384–8.
48. Gunderson CG, Martinello RA. A systematic review of bactere-
mias in cellulitis and erysipelas. J Infect. 2012;64(2):148–55.
49. Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal
LK, Carey RB, et al. Methicillin-resistant S. aureus infections
among patients in the emergency department. N Engl J Med.
2006;355(7):666–74.
50. Pallin DJ, Binder WD, Allen MB, Lederman M, Parmar S, Filbin
MR, et al. Clinical trial: comparative effectiveness of cephalexin
plus trimethoprim-sulfamethoxazole versus cephalexin alone for
treatment of uncomplicated cellulitis: a randomized controlled
trial. Clin Infect Dis. 2013;56(12):1754–62.
51. Griego RD, Rosen T, Orengo IF, Wolf JE. Dog, cat, and human
bites: a review. J Am Acad Dermatol. 1995;33(6):1019–29.
52. Finkelstein R, Oren I. Soft tissue infections caused by marine
bacterial pathogens: epidemiology, diagnosis, and management.
Curr Infect Dis Rep. 2011;13(5):470–7.
53. Sayabovorn N, Chongtrakool P, Chayakulkeeree M. Cryptococ-
cal fungemia and Mycobacterium haemophilum cellulitis in a
patient receiving ruxolitinib: a case report and literature review.
BMC Infect Dis. 2021;21(1):27.
54. Franco-Paredes C, Marcos LA, Henao-Martínez AF, Rod-
ríguez-Morales AJ, Villamil-Gómez WE, Gotuzzo E, et al.
Cutaneous mycobacterial infections. Clin Microbiol Rev.
2018;32(1):e00069-e118.
55. Maraki S, Christidou A, Anastasaki M, Scoulica E. Non-O1, non-
O139 Vibrio cholerae bacteremic skin and soft tissue infections.
Infect Dis (Lond). 2016;48(3):171–6.
56. Flahou B, Haesebrouck F, Smet A, Yonezawa H, Osaki T,
Kamiya S. Gastric and enterohepatic non-Helicobacter pylori
Helicobacters. Helicobacter. 2013;18(Suppl 1):66–72.
57. Shimizu S, Shimizu H. Cutaneous manifestations of Helicobacter
cinaedi: a review. Br J Dermatol. 2016;175(1):62–8.
58. Dignani MC, Anaissie E. Human fusariosis. Clin Microbiol
Infect. 2004;10(Suppl 1):67–75.
59. Bloch KC, Nadarajah R, Jacobs R. Chryseobacterium meningo-
septicum: an emerging pathogen among immunocompromised
adults. Report of 6 cases and literature review. Medicine (Balti-
more). 1997;76(1):30–41.
60. Thompson DK, Sharkady SM. Expanding spectrum of oppor-
tunistic Cedecea infections: current clinical status and multidrug
resistance. Int J Infect Dis. 2020;100:461–9.
61. Ekpanyapong S, Reddy KR. Infections in cirrhosis. Curr Treat
Options Gastroenterol. 2019;17(2):254–70.

62. Falagas ME, Kastoris AC, Vouloumanou EK, Dimopoulos G.
Community-acquired Stenotrophomonas maltophilia infec-
tions: a systematic review. Eur J Clin Microbiol Infect Dis.
2009;28(7):719–30.
63. Khan T, Martin DH. Streptococcus pneumoniae soft tissue
infections in human immunodeficiency virus. Am J Med Sci.
2011;342(3):235–8.
64. Paterson DL, Gruttadauria S, Lauro A, Scott V, Marino IR. Spon-
taneous gram-negative cellulitis in a liver transplant recipient.
Infection. 2001;29(6):345–7.
65. Yoon TY, Jung SK, Chang SH. Cellulitis due to Escherichia
coli in three immunocompromised subjects. Br J Dermatol.
1998;139(5):885–8.
66. Ichiyama S, Hirai S, Minami T, Nishiyama Y, Shimizu S,
Shimokata K, et al. Campylobacter fetus subspecies fetus cel-
lulitis associated with bacteremia in debilitated hosts. Clin Infect
Dis. 1998;27(2):252–5.
67. Chen YS, Liu YC, Yen MY, Wang JH, Wann SR, Cheng DL.
Skin and soft-tissue manifestations of Shewanella putrefaciens
infection. Clin Infect Dis. 1997;25(2):225–9.
68. Crowe HM, Levitz RE. Invasive Haemophilus influenzae disease
in adults. Arch Intern Med. 1987;147(2):241–4.
69. Beckman EN, Leonard GL, Castillo LE, Genre CF, Pankey GA.
Histopathology of marine vibrio wound infections. Am J Clin
Pathol. 1981;76(6):765–72.
70. Hurwitz RM, Leaming RD, Horine RK. Necrotic celluli-
tis. A localized form of septic vasculitis. Arch Dermatol.
1984;120(1):87–92.
71. Musher DM. Cutaneous and soft-tissue manifestations of
sepsis due to Gram-negative enteric bacilli. Rev Infect Dis.
1980;2(6):854–66.
72. Kolivras A, Provost P, Thompson CT. Erysipelas-like erythema
of familial Mediterranean fever syndrome: a case report with
emphasis on histopathologic diagnostic clues. J Cutan Pathol.
2013;40(6):585–90.
73. Levell NJ, Wingfield CG, Garioch JJ. Severe lower limb cel-
lulitis is best diagnosed by dermatologists and managed with
shared care between primary and secondary care. Br J Derma-
tol. 2011;164(6):1326–8.
74. Strazzula L, Cotliar J, Fox LP, Hughey L, Shinkai K, Gee SN,
et al. Inpatient dermatology consultation aids diagnosis of cel-
lulitis among hospitalized patients: a multi-institutional analy-
sis. J Am Acad Dermatol. 2015;73(1):70–5.
75. Sundaresan S, Migden MR, Silapunt S. Stasis dermatitis:
pathophysiology, evaluation, and management. Am J Clin
Dermatol. 2017;18(3):383–90.
76. Thornton NJ, Gibson BR, Ferry AM. Contact dermatitis and
medical adhesives: a review. Cureus. 2021;13(3): e14090.
77. Johansen JD, Werfel T. Highlights in allergic contact der-
matitis 2018/2019. Curr Opin Allergy Clin Immunol.
2019;19(4):334–40.
78. Moffatt CJ, Franks PJ, Doherty DC, Williams AF, Badger C,
Jeffs E, et al. Lymphoedema: an underestimated health prob-
lem. QJM. 2003;96(10):731–8.
79. Marchionne EM, McCalmont TH, Pincus LB, LeBoit PE, Fox
LP. Acute inflammatory edema: a mimicker of cellulitis in
critically ill patients. J Am Acad Dermatol. 2019;81(4):931–6.
80. Nadelman RB, Wormser GP. Erythema migrans and early
Lyme disease. Am J Med. 1995;98(4A):15S-23S (Discussion
23S-24S).
81. Gunderson CG, Chang JJ. Risk of deep vein thrombosis in
patients with cellulitis and erysipelas: a systematic review and
meta-analysis. Thromb Res. 2013;132(3):336–40.
82. Stevens DL, Bryant AE, Goldstein EJ. Necrotizing soft tissue
infections. Infect Dis Clin N Am. 2021;35(1):135–55.
M. A. Boettler et al.
83. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Deter-
minants of mortality for necrotizing soft-tissue infections. Ann
Surg. 1995;221(5):558–63 (Discussion 63-5).
84. Wall DB, Klein SR, Black S, de Virgilio C. A simple model to
help distinguish necrotizing fasciitis from nonnecrotizing soft
tissue infection. J Am Coll Surg. 2000;191(3):227–31.
85. Bechar J, Sepehripour S, Hardwicke J, Filobbos G. Laboratory
risk indicator for necrotising fasciitis (LRINEC) score for the
assessment of early necrotising fasciitis: a systematic review
of the literature. Ann R Coll Surg Engl. 2017;99(5):341–6.
86. Stevens DL, Bryant AE. Necrotizing soft-tissue infections. N
Engl J Med. 2017;377(23):2253–65.
87. Cribb BI, Wang MTM, Kulasegaran S, Gamble GD, Mac-
Cormick AD. The SIARI Score: a novel decision support tool
outperforms LRINEC Score in necrotizing fasciitis. World J
Surg. 2019;43(10):2393–400.
88. Borschitz T, Schlicht S, Siegel E, Hanke E, von Stebut E.
Improvement of a clinical score for necrotizing fasciitis: ‘Pain
Out of Proportion’ and high CRP levels aid the diagnosis.
PLoS ONE. 2015;10(7): e0132775.
89. Ramchandani M, Kong M, Tronstein E, Selke S, Mikhaylova
A, Magaret A, et al. Herpes simplex virus type 1 shedding in
tears and nasal and oral mucosa of healthy adults. Sex Transm
Dis. 2016;43(12):756–60.
90. Schmutzhard J, Riedel HM, Wirgart BZ, Grillner L. Detec-
tion of herpes simplex virus type 1, herpes simplex virus type
2 and varicella-zoster virus in skin lesions. Comparison of
real-time PCR, nested PCR and virus isolation. J Clin Virol.
2004;29(2):120–6.
91. von den Driesch P. Sweet’s syndrome (acute febrile neutro-
philic dermatosis). J Am Acad Dermatol. 1994;31(4):535–56
(Quiz 57-60).
92. StatPearls. Treasure Island, FL; StatPearls; 2021.
93. Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ. Deep vein
thrombosis: update on diagnosis and management. Med J Aust.
2019;210(11):516–24.
94. Cox SE, Cruz PD. A spectrum of inflammatory metastasis to
skin via lymphatics: three cases of carcinoma erysipeloides. J
Am Acad Dermatol. 1994;30(2 Pt 2):304–7.
95. Korkij W, Soltani K. Fixed drug eruption. A brief review. Arch
Dermatol. 1984;120(4):520–4.
96. Obaitan I, Dwyer R, Lipworth AD, Kupper TS, Camargo
CA, Hooper DC, et al. Failure of antibiotics in cellulitis tri-
als: a systematic review and meta-analysis. Am J Emerg Med.
2016;34(8):1645–52.
97. Miller LG, Daum RS, Creech CB, Young D, Downing MD,
Eells SJ, et al. Clindamycin versus trimethoprim-sulfameth-
oxazole for uncomplicated skin infections. N Engl J Med.
2015;372(12):1093–103.
98. Williams OM, Brindle R. Antibiotic route and duration of
therapy for cellulitis: data extracted from a multi-center clini-
cal trial. Int J Antimicrob Agents. 2020;56(3): 106076.
99. Madaras-Kelly KJ, Remington RE, Oliphant CM, Sloan KL,
Bearden DT. Efficacy of oral beta-lactam versus non-beta-
lactam treatment of uncomplicated cellulitis. Am J Med.
2008;121(5):419–25.
100. Khawcharoenporn T, Tice A. Empiric outpatient therapy with
trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for
cellulitis. Am J Med. 2010;123(10):942–50.
101. Cenizal MJ, Skiest D, Luber S, Bedimo R, Davis P, Fox P,
et al. Prospective randomized trial of empiric therapy with
trimethoprim-sulfamethoxazole or doxycycline for outpatient
skin and soft tissue infections in an area of high prevalence
of methicillin-resistant Staphylococcus aureus. Antimicrob
Agents Chemother. 2007;51(7):2628–30.
Cellulitis: A Review of Current Practice Guidelines and Differentiation from Pseudocellulitis
102. Livermore DM, Pearson A. Antibiotic resistance: location,
location, location. Clin Microbiol Infect. 2007;13(Suppl
2):7–16.
103. Cross ELA, Jordan H, Godfrey R, Onakpoya IJ, Shears A,
Fidler K, et al. Route and duration of antibiotic therapy in
acute cellulitis: a systematic review and meta-analysis of
the effectiveness and harms of antibiotic treatment. J Infect.
2020;81(4):521–31.
104. Jenkins TC, Knepper BC, Sabel AL, Sarcone EE, Long JA,
Haukoos JS, et al. Decreased antibiotic utilization after imple-
mentation of a guideline for inpatient cellulitis and cutaneous
abscess. Arch Intern Med. 2011;171(12):1072–9.
105. Talan DA, Mower WR, Lovecchio FA, Rothman RE, Steele
MT, Keyloun K, et al. Pathway with single-dose long-acting
intravenous antibiotic reduces emergency department hospi-
talizations of patients with skin infections. Acad Emerg Med.
2021;28(10):1108–17.
106. Karppelin M, Siljander T, Vuopio-Varkila J, Kere J, Huhtala
H, Vuento R, et al. Factors predisposing to acute and recurrent
bacterial non-necrotizing cellulitis in hospitalized patients:
a prospective case-control study. Clin Microbiol Infect.
2010;16(6):729–34.
107. Soo JK, Bicanic TA, Heenan S, Mortimer PS. Lymphatic
abnormalities demonstrated by lymphoscintigraphy after lower
limb cellulitis. Br J Dermatol. 2008;158(6):1350–3.
108. Dalal A, Eskin-Schwartz M, Mimouni D, Ray S, Days W,
Hodak E, et al. Interventions for the prevention of recur-
rent erysipelas and cellulitis. Cochrane Database Syst Rev.
2017;6(6): CD009758.
109. Karaca-Mandic P, Hirsch AT, Rockson SG, Ridner SH. The
cutaneous, net clinical, and health economic benefits of
advanced pneumatic compression devices in patients with
lymphedema. JAMA Dermatol. 2015;151(11):1187–93.
110. Mihara M, Hara H, Furniss D, Narushima M, Iida T, Kikuchi K,
et al. Lymphaticovenular anastomosis to prevent cellulitis asso-
ciated with lymphoedema. Br J Surg. 2014;101(11):1391–6.
111. Webb E, Neeman T, Bowden FJ, Gaida J, Mumford V, Bissett B.
Compression therapy to prevent recurrent cellulitis of the leg. N
Engl J Med. 2020;383(7):630–9.
112. Thomas KS, Crook AM, Nunn AJ, Foster KA, Mason JM, Chal-
mers JR, et al. Penicillin to prevent recurrent leg cellulitis. N
Engl J Med. 2013;368(18):1695–703.