Ecthyma Gangrenosum

Shah M, Crane JS.

Continuing Education Activity

Ecthyma gangrenosum (EG) is a cutaneous infection that most commonly occurs in immunocompromised individuals with fulminant bacteremia.
EG was first described in 1897 by Canadian pathologist Dr. Lewellys Barker as a manifestation of Pseudomonas aeruginosa. Although P.
aeruginosa remains the most frequent organism identified in EG, other causative pathogens have since been described. This activity reviews the
cause and presentation of ecthyma gangrenosum and highlights the interprofessional team's role in its management.

Objectives:

Review the causes of ecthyma gangrenosum.

Describe the presentation of ecthyma gangrenosum.
Summarize the treatment options for ecthyma gangrenosum.
Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients
affected by ecthyma gangrenosum.

Earn continuing education credits (CME/CE) on this topic.

Introduction
Ecthyma gangrenosum (EG) is a cutaneous infection that most commonly occurs in immunocompromised individuals with fulminant bacteremia.
EG was first described in 1897 by Canadian pathologist Dr. Lewellys Barker as a manifestation of Pseudomonas aeruginosa.
[1] Although P. aeruginosa remains the most frequent organism identified in EG, other causative pathogens have since been described. Lesions
appear as gangrenous ulcers with erythematous borders. EG predominantly affects the axillary and anogenital areas, but the arms, legs, trunk,
and face are also sometimes involved. Perivascular invasion and resultant ischemic necrosis of the associated skin result in the classic
macroscopic appearance. Prompt recognition and empiric therapy with broad-spectrum antipseudomonal agents are of critical importance. Once
microbiology results identify the causative pathogen and sensitivities are available, antimicrobial coverage should be narrowed.[2] EG denotes a
poor prognosis, particularly in immunocompromised individuals with neutropenia.

Etiology
P. aeruginosa is the most frequent organism identified in ecthyma gangrenosum, with one study identifying P. aeruginosa in 74% of cases.[1] P.
aeruginosa is a non-lactose fermenting gram-negative aerobic, rod-shaped bacteria. The organism is found in moist environments, is often
identified in tap water samples, and can contaminate hospital equipment leading to nosocomial infections.[3][4] Other causes of EG include
methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Citrobacter freundii, Escherichia coli, Aeromonas hydrophila,
Klebsiella pneumoniae, Serratia marcescens, Xanthomonas maltophilia, Morganella morganii, Corynebacterium diphtheriae, Neisseria
gonorrhea, Yersinia pestis, fungi like the Candida species), and viruses like herpes simplex virus.[1][5][6][7]

Epidemiology
Ecthyma gangrenosum affects all age groups and genders. Immunocompromised individuals are particularly susceptible to developing this
condition, with up to 62% to 75% of affected individuals having an underlying immunodeficiency.[1][8] EG is also known to occur in otherwise
healthy immunocompetent individuals.[9] Common predisposing conditions include neutropenia, leukemia, multiple myeloma, diabetes mellitus,
malnutrition, and extensive burn wounds.[1][5][7][10][11]

Pathophysiology
Ecthyma gangrenosum is separated into bacteremic and non-bacteremic forms.[7] The bacteremic form of EG is more common than the non-
bacteremic form.[1] With bacteremia, the causative organism is spread hematogenously to the capillaries and invades the media and adventitia of
arteries and veins. Perivascular invasion ultimately leads to ischemic necrosis of the surrounding skin.[12] In the non-bacteremic form, the
lesions develop at the location of direct inoculation into the epidermis. Virulence toxins and enzymes produced by P. aeruginosa, such as
exotoxin A, elastase, and phospholipase C, cause skin and vascular destruction.[8] Multi-drug resistance of P. aeruginosa has increased
substantially in recent years, making treatment more challenging. Resistance mechanisms include decreased permeability (biofilm formation),
antibiotic efflux pumps, antibiotic inactivating mechanisms, and antibiotic target site mutations.[12][13]

Histopathology
Excisional biopsy or punch biopsy with Gram stain, culture, and histopathologic examination can be performed in equivocal cases. In cases of
pseudomonal EG, Gram stain shows many gram-negative, rod-shaped bacteria.[14] Wound cultures are frequently positive for P. aeruginosa but
may reveal a different causative organism. Microscopic examination reveals an ulcerated zone of necrotic epidermis and dermis with neutrophilic
predominance.[14][15] The epidermis adjacent to the necrotic region reveals reactive hyperkeratosis. The underlying subcutaneous tissue may
also be involved.[8]

History and Physical

When acquiring a history on presentation, it is important to note the temporal evolution of the lesions, the location of the lesions, any underlying
immunosuppressive condition, and other associated symptoms such as cough, fever, or dysuria. In individuals with the bacteremic form of
EG, the source of infection is important to ascertain. For example, productive cough or dysuria may reveal a respiratory or urinary source,
respectively. In the non-bacteremic form, it is important to note any trauma that may have introduced the infection via direct inoculation.

The lesions of ecthyma gangrenosum begin as painless, round erythematous macules and patches that develop into central pustules with
surrounding erythema. A hemorrhagic vesicle appears at the center of the lesion and evolves into a gangrenous ulcer with a black eschar.[1]
[8] Early lesions may progress to necrotic ulcers in as little as 12 hours.[8] The lesions can be localized and solitary, or widespread.[1]

EG can appear anywhere in the body but most commonly affects the anogenital and axillary areas. The gluteal/perineal area is most common
(57%), followed by the extremities (30%), the trunk (6%), and the face (6%).[8] Rare cases of periorbital involvement have also been reported.
[8] The entire body should be examined for lesions, and any fluctuance or large areas of necrosis should be noted.

Evaluation
Initial evaluation includes blood cultures, wound cultures, urinalysis, chest radiograph, complete blood count, comprehensive metabolic panel,
C-reactive protein, and HIV testing. Procalcitonin and lactate levels are important in those with EG in the setting of sepsis. Evaluation of the
lesions with a Wood's lamp may expedite the diagnosis, as P. aeruginosa will appear with green fluorescence.[8][16] Excisional or punch biopsy
can be performed in equivocal cases.

Treatment / Management
In individuals with suspected ecthyma gangrenosum, prompt treatment with broad-spectrum antibiotics should be initiated after obtaining blood
and wound cultures.

Initial empiric therapy includes antipseudomonal beta-lactams (piperacillin/tazobactam), cephalosporins (cefepime), fluoroquinolones
(levofloxacin), and carbapenems (imipenem). Combination therapy is recommended in high-risk individuals, such as those with neutropenia and
septic shock.[12] Once the causative organism and antimicrobial susceptibilities are identified, antimicrobial coverage should be narrowed.[2] In
rare cases with a fungal or viral etiology, anti-fungal and anti-viral agents should be started.

Surgical excision of necrotic lesions or abscesses is often necessary. Incision and drainage of abscesses are important for source control of the
infection. For necrotic skin lesions, aggressive debridement and grafting may be necessary for lesions larger than 10 cm.[8]

Treatment in the hospital intensive care setting is appropriate for patients with sepsis or neutropenia due to the high case fatality rate. For those
with non-bacteremic EG, treatment in the outpatient setting may be appropriate. In this setting, oral antipseudomonal agents, such as
ciprofloxacin, can be considered.

Di erential Diagnosis
A thorough history, physical, and basic laboratory studies help differentiate between EG and other causes of skin necrosis. Neutropenia and
malignancy in a patient with typical skin lesions should raise suspicion for EG. Other conditions with similar macroscopic features include
autoimmune vasculitides, vasopressor-induced necrosis, calciphylaxis, warfarin-induced necrosis, and disseminated intravascular coagulation
(DIC), pyoderma gangrenosum, necrolytic migratory erythema, and livedoid vasculopathy.[1][17][18]

In individuals with underlying malignancy and pancytopenia, fibrinogen levels and fibrin split products (d-dimer) can help differentiate DIC
from EG. In individuals in the intensive care unit on vasopressors, the distribution of lesions can help differentiate between vasopressor-induced
necrosis and EG. Vasopressor-induced necrosis affects the distal extremities, while EG affects the anogenital and axillary areas.[19] Tissue
samples are critical when the diagnosis is not clear based on less invasive methods.[20]

Prognosis
The development of EG lesions in individuals with sepsis is associated with a poor prognosis and is fatal in 20% to 77% of patients.[15][21] In
individuals with non-bacteremic EG, the mortality rate is significantly lower at 8%.[15] The underlying immunosuppressive state (e.g.,
malignancy, renal failure, or other) is often the main determinant of clinical outcome.[22] The presence of neutropenia at the time of diagnosis is
the most important prognostic factor of mortality.[21]

Complications
EG is a life-threatening infection often complicated by septic shock. Prompt clinician recognition and appropriate antimicrobial therapy are
necessary to achieve optimal outcomes.

Deterrence and Patient Education

Patients need to understand that if they are immunocompromised, that underlying condition requires optimal management. These patients are
typically managed in the hospital setting.

Pearls and Other Issues

P. aeruginosa is the most common causative organism of ecthyma gangrenosum.
Lesions appear as gangrenous ulcers with erythematous borders located predominantly in the axillary and anogenital areas.
Nearly all individuals with typical skin lesions are immunocompromised, with malignancy being the most common underlying disease
state.
Neutropenia at the time of diagnosis is the most important prognostic factor.
Prompt treatment with intravenous antipseudomonal agents is indicated.
Incision and drainage may be performed for abscesses.

Enhancing Healthcare Team Outcomes

Management of ecthyma gangrenosum requires an interprofessional team approach, including providers from infectious disease, surgery,
dermatology, hematology, and critical care. The providers involved in treatment depend on the overall clinical picture and whether they are being
treated in the intensive care unit.

A dermatologist can help in the initial diagnostic workup to determine the cause (Wood's lamp evaluation, punch biopsy) and extent of the
lesions. Infectious disease specialists are helpful to determine the selection and length of antibiotic therapy. Surgeons may be needed for incision
and drainage of multiple abscesses, surgical debridement of necrotic lesions, or grafting of large-area defects. In patients with
neutropenia, granulocyte colony-stimulating factor (G-CSF) may be given at the discretion of a hematologist.

For individuals with fulminant sepsis, management in the critical care setting by an intensivist is appropriate due to the high fatality rate of
bacteremic EG. Individuals with sepsis are extremely tenuous, and careful monitoring from the nursing staff with frequent vital sign
measurements is critical and reporting to the team untoward changes. Prompt administration of effective antimicrobial therapy is known to
improve survival in sepsis.[23] [Level 1] Ideally, an infectious disease specialist pharmacist should assist with antibiotic selection and assist the
team with dose management. In addition to helping to target the causative organism. Early goal-directed therapy focusing on blood pressure and
oxygen saturation has also been shown to improve outcomes and reduce mortality in sepsis.[24] [Level 1]

Continuing Education / Review Questions

Access free multiple choice questions on this topic.
Earn continuing education credits (CME/CE) on this topic.
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References
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Publication Details

Author Information

Authors

Muneeb Shah1; Jonathan S. Crane2.

A liations
1 Penn State Health
2 Sampson Regional Med Ctr / Campbell Univ

Publication History

Last Update: January 24, 2021.

Copyright
Copyright © 2021, StatPearls Publishing LLC.
This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use,
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provided to the Creative Commons license, and any changes made are indicated.

Publisher

StatPearls Publishing, Treasure Island (FL)

NLM Citation
Shah M, Crane JS. Ecthyma Gangrenosum. [Updated 2021 Jan 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-.