AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Background

Ecthyma gangrenosum (EG) is a well-recognized but uncommon cutaneous infection most often associated with a Pseudomonas aeruginosa bacteremia. EG usually occurs in patients who are critically ill and immunocompromised and is almost always a sign of pseudomonal sepsis. The characteristic lesions of EG are hemorrhagic pustules or infracted-appearing areas with surrounding erythema that evolve into necrotic ulcers surrounded by erythema. These were first described in association with Pseudomonas septicemia by Barker in 1897 and were later given the name "ecthyma gangrenosum" by Hitschmann and Kreibich.

Related Medscape CME courses include the following:

• Resistance Wars: Master Clinicians Discuss Emerging Strategies for Fighting Infection (Slides With Transcript)
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Additionally, related eMedicine articles include the following:

• Pseudomonas aeruginosa Infections
• Pseudomonas Infection

Pathophysiology

Impaired humoral or cellular immunity leads to increased susceptibility to infections with P aeruginosa or other pathogens. In addition, breakdown of mechanical defensive barriers, such as the skin and mucosa, may allow infectious organisms to disseminate. The lesions of EG result from perivascular bacterial invasion of arteries and veins in the dermis and subcutaneous tissues, producing a necrotizing vasculitis. Perivascular involvement can occur by hematogenous seeding of the skin in bacteremic patients or by direct inoculation through the skin in nonbacteremic patients. Extravasation, edema, and necrosis around the vessel interrupt the blood supply to these tissues, resulting in secondary ischemic necrosis of the epidermis and dermis, which manifests as nodular lesions that rapidly evolve through stages of central hemorrhage, ulceration, and necrosis.

Frequency

United States

EG develops in 1.3-13% patients with P aeruginosa sepsis and, to a lesser extent, in patients who are not bacteremic.

Mortality/Morbidity

A high mortality rate is reported with delayed diagnosis and therapy. Mortality rates of Pseudomonas sepsis in immunocompromised persons range from 18-96%, whereas the mortality rate of EG in nonbacteremic patients is 15.4%. Coexisting conditions in patients prone to Pseudomonas sepsis may contribute to the morbidity and mortality rates.

Sex

No sexual predilection is evident in the overall prevalence of EG; however, a slight predominance of bacteremic EG in males (male-to-female ratio, 1.3-5:1) and nonbacteremic EG in females (female-to-male ratio, 2.3:1) has been observed.

Age

EG may affect patients of any age, although it is commonly reported in infants and elderly patients due to underdeveloped and/or compromised immune systems.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

History

• EG typically occurs in patients who are immunocompromised, including patients with hematologic malignancies, immunodeficiency syndromes, severe burns, malnutrition, recent chemotherapy, immunosuppressive therapy, and diabetes mellitus. While a few case reports describe the development of EG in previously healthy children, most of these patients had unrecognized risk factors for the development of EG, including intra-abdominal or appendiceal abscesses, recent viral illness, or antibiotic treatment for underlying medical conditions such as hypogammaglobulinemia and neutropenia.
• Two reports describe toxic epidermal necrolysis followed by EG, one in a 62-year-old woman and the other in a 3-year-old boy.^{1, 2}
• Breakdown of mechanical defense barriers increases susceptibility to pseudomonal or fungal infections.
• • Pseudomonas sepsis frequently occurs after surgical procedures, especially urologic procedures.
  • Long-term indwelling urinary catheters, long-term intravenous placements, and tracheostomies have been associated with EG.
• In several reported cases, patients with EG were on prolonged antibiotic therapy targeting non-Pseudomonas organisms. This may have led to elimination of normal flora and promoted Pseudomonas overgrowth.
• Children with EG may develop diarrhea (30%) before the onset of cutaneous lesions.
• Patients often present with fever a few days prior to developing EG.

Physical

• Primary lesions: Primary cutaneous lesions of EG initially appear as painless round erythematous macules that rapidly become pustular with surrounding erythema. A hemorrhagic focus appears in the center, forming a bulla. As the hemorrhagic bulla spreads peripherally, it evolves into a gangrenous ulcer with a central black/gray eschar surrounded by an erythematous halo. The transformation of an early lesion to a necrotic ulcer may occur in as little as 12 hours.
• Distribution of lesions: The patient may have a single lesion or multiple lesions. EG may appear at any location on the body; however, it predominately affects the anogenital and axillary areas. Distribution occurs at the following frequencies: gluteal or perineal region (57%), extremities (30%), trunk (6%), and face (6%); bilateral periorbital manifestations are rare but have been reported.^{3, 4}

Causes

EG is typically and most commonly caused by P aeruginosa; however, EG-like lesions have been observed in patients with other bacterial and fungal infections.⁵ Organisms that cause ecthyma and EG-like lesions include the following:

• Gram-positive bacteria
• • Staphylococcus aureus
  • Streptococcus pyogenes
• Gram-negative bacteria
• • Aeromonas hydrophila
  • Burkholderia cepacia⁶
  • Chromobacterium violaceum⁷
  • Citrobacter freundii
  • Corynebacterium diphtheriae
  • Escherichia coli
  • Klebsiella pneumoniae
  • Morganella morganii⁸
  • Neisseria gonorrhea
  • Pseudomonas aeruginosa
  • Pseudomonas stutzeri
  • Serratia marcescens
  • Vibrio vulnificus
  • Yersinia pestis
  • Xanthomonas maltophilia
• Fungi
• • Aspergillus fumigatus
  • Candida albicans⁹
  • Curvularia species¹⁰
  • Exserohilum species
  • Fusarium solani¹¹
  • Mucor and Rhizopus species
  • Pseudallescheria boydii¹⁰
  • Scytalidium dimidiatum
• Viral - Herpes simplex virus¹²

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Cryoglobulinemia
Polyarteritis nodosa
Necrotizing fasciitis
Necrotizing vasculitis
Septicemia from other infectious agents

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Lab Studies

• Gram stain: A Gram stain of fluid from the central hemorrhagic pustule or bulla can rapidly indicate the diagnosis. If no fluid is present, the eschar should be elevated and the underlying tissue swabbed for a Gram stain.
• Blood cultures
• • Two specimens should be collected prior to initiating antibiotic therapy. The optimal time of collection is during temperature spikes.
  • Sensitivity studies should be performed on isolated organisms.
• Urine culture
• Skin biopsy
• • One 4- to 5-mm deep skin biopsy specimen should be obtained and placed in formalin fixative. Specimens should be stained with tissue Gram stain in addition to standard hematoxylin and eosin.
  • Staining with special stains (eg, periodic acid-Schiff, methamine silver, Fite stains) should be performed to rule out other organisms that may cause EG-like lesions.
• Tissue cultures
• • A second skin biopsy specimen should be placed in a sterile container for tissue culture. Specimens should be tested for bacteria, fungus, yeast, and mycobacteria. Preservative-free anesthetics and saline should be used for the procedure.
  • Sensitivity studies should be performed on isolated organisms.

Histologic Findings

Skin biopsy specimens of EG lesions show a necrotizing hemorrhagic vasculitis with few inflammatory cells but many surrounding bacilli. In sections stained with Gram stain, gram-negative rods are numerous in the media and adventitia of the necrotic vessels, but typically spare the intima.¹³ Extravasation of blood, edema, and necrosis are seen around the involved vessels.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Medical Care

EG requires prompt diagnosis and treatment with appropriately selected antibiotics for the underlying etiology. If the lesion fails to respond to antimicrobials, surgical debridement of the spreading, necrotic lesion may be required.^{14, 15} The presence of EG should alert the physician to the likelihood of pseudomonal bacteremia, and the early implementation of antimicrobial agents is necessary to reduce the high mortality associated with pseudomonal sepsis. Treatment of EG requires the use of antipseudomonal penicillins, aminoglycosides, fluoroquinolones, third-generation cephalosporins, or aztreonam. While awaiting results, an antipseudomonal penicillin (piperacillin) should be used in conjunction with an aminoglycoside (gentamicin). Further adjustment of antibiotics may be required after sensitivity results are known.

Systemic antifungal coverage should be considered if fungemia is suspected, including coverage against Aspergillus, Candida, and Mucor species with azole agents (eg, voriconazole, fluconazole) and/or amphotericin B if appropriate.

If empiric antimicrobial and antifungal therapy is used, it must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic selection should be guided by blood culture sensitivity results whenever feasible.

Consultations

• Dermatologist - For evaluation of cutaneous lesions
• Infectious disease specialist - For evaluation and treatment of infection
• Internist or pediatrician - For evaluation of possible immunocompromised states
• General surgeon - For evaluation of possible surgical excision of lesions that failed to respond to antibiotics

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Treatment of EG requires the use of antipseudomonal penicillins, aminoglycosides, fluoroquinolones, third-generation cephalosporins, or aztreonam. Initially, antipseudomonal penicillin (piperacillin) is used in conjunction with an aminoglycoside (gentamicin). Further adjustment of antibiotics may be required after sensitivity results are known.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Prognosis

• Mortality rates vary, ranging from 18-96% in bacteremic patients to 15.4% in nonbacteremic patients.
• Factors associated with a poor prognosis include the following:
• • Multiple lesions
  • Delayed diagnosis and institution of appropriate antibiotics
  • Persistent neutropenia
  • High bacteremic load
  • Repeated catheterization and instrumentation

ACKNOWLEDGMENTS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Frederick Fish, MD, and Nobuyoshi Kageyama, MD, to the development and writing of this article.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

Media file 1:  Violaceous plaques and necrotic ulcers on the abdomen of a renal transplant patient. Tissue cultures were positive for Pseudomonas aeruginosa.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Acknowledgments
• Multimedia
• References

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Article Last Updated: Jul 31, 2008