Ecthyma gangrenosum (dermatitis gangrenosa infantum, disseminated cutaneous gangrene, pemphigus gangrenosus, rupia escharotica; Septicemia due to Pseudomonas)

Are You Confident of the Diagnosis?

This chapter will review ecthyma gangrenosum caused by Pseudomonas aeruginosa. There are many other infectious causes of ecthyma, which are reviewed in a separate chapter.

Two forms of ecthyma gangrenosum have been proposed. The first is ecthyma gangrenosum occurring secondary to pseudomonal sepsis. The skin lesions are caused by direct hematogenous spread to the skin. Typically more than one lesion is present. This has been referred to as bacteremic ecthyma gangrenosum. Blood cultures are almost always positive for the Pseudomonas bacteria. It has been estimated that ecthyma gangrenosum occurs in 1-5% of patients with pseudomonal sepsis.

The second form is thought to be caused by direct inoculation into the skin, without associated bacteremia. These cases are typically solitary, less severe, and easier to treat. Most patients will give a history of trauma to the area. This has been referred to as nonbacteremic ecthyma gangrenosum. This form has a much better overall prognosis.

Characteristic findings on physical examination

Individual lesions of ecthyma gangrenosum from Pseudomonas aeruginosa, independent of the two forms will present with similar skin manifestations (Figure 1, Figure 2). Red, hemorrhagic papules, vesicles, or vesiculopustules will rapidly develop and over hours will form a painless ulcer that is firm or indurated to palpation. Hemorrhagic bullae may also precede the ulcer formation. The ulcer becomes coated with a characteristic black eschar.

Figure 1.

Figure 2.

Varying amounts of surrounding erythema will be present and can appear identical to cellulitis. The area will be slightly warm to the touch, but not as painful as seen in those patients with cellulitis. Individuals with pancytopenia may have less inflammation surrounding the eschar. No draining purulence is seen.

The vast majority, upwards to 90%, occur on the extremities and perineal/buttocks areas. Patients are most often febrile. Hypotension and tachycardia can be seen in sepsis. Dehydration often is associated and can cause prerenal azotemia.

Expected results of diagnostic studies

Laboratory testing will show an increased erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) level. Often neutropenia and a slight anemia is present. The presence of neutropenia and leukopenia are a poor prognostic sign. Skin biopsy will show a necrotizing vasculitis, necrosis of the epidermis, or complete ulceration. Multiple bacteria may be seen in the vessel lumen and within the dermis. Tissue gram stain may be used to better accentuate the gram negative rods

Diagnosis confirmation

The clinical differential diagnosis of ecthyma gangrenosum includes:

Ecthyma caused by other bacteria or fungal agents. Multiple etiologic agents have been implicated with Stalphylococcus aureus and Streptococcus pyogenes being the two most common.

Cutaneous anthrax can present with a nonpainful black eschar that occurs at the site of inoculation. The area starts as a small papule that vesiculates and then develops necrosis, thus forming the black eschar.

Rickettsial infections can present with a small black solitary eschar at the site of the tick bite, termed tache noire. Typically these are much milder in nature than ecthyma gangrenosum. Patients will have fever and constitutional symptoms and a maculopapular rash that includes the solitary area of tache noire.

Herpes simplex virus and cowpox viral infections have also been known to present with black eschars. The history for herpes simplex is typically one of recurrent vesiculopustules that rupture and then develop an eschar. They are very tender and can be associated with adenopathy.

Cowpox is a rather uncommon viral infection and along with the other orthopoxviruses (smallpox, monkeypox) can from dark black eschars after going through a vesicular stage that lasts anywhere from 10-14 days. The eschar is typically a late finding. Fever, adenopathy and constitutional symptoms are present.

Who is at Risk for Developing this Disease?

Any immunosuppressed individual is at risk for development of ecthyma gangrenosum. Poorly controlled diabetes mellitus, leukemias (especially with neutropenia), organ transplant and bone marrow transplant patients, and any one taking immunosuppressive medications (such as long-term prednisone, azathioprine, etc) are more prone to infection. Malnourished individuals, premature infants and severely low birth weight babies are also at higher risk. It is highly unusual in healthy immunocompetent patients.

No racial or sexual predilection has been noted; however, it has been reported to occur more commonly in children. For some reason most cases have been reported from Southeast Asia. Patients that have undergone multiple bladder catheterizations, surgical and urological procedures may have a slightly increased risk.

What is the Cause of the Disease?

Etiology

The ubiquitous gram-negative facultative anaerobic bacteria P aeruginosa is the causative bacteria. The bacteria are found routinely in soil and water sources. The bacteria grows and multiples rapidly in warm water and is capable of producing a variety of pigments; the most well known being pyocyanin, which is a blue-green pigment. The bacteria is typically grown in the laboratory on blood agar, MacConkey agar or Pseudomonas isolation agar. It is lactose negative on MacConkey’s agar plate.

The bacterium moves by action of a single motile polar flagellum, and is approximately 3 micrometers in length. It causes opportunistic infections, as patients with intact skin and immune systems rarely develop Pseudomonal infections.

Pathophysiology

Small cutaneous blood vessels (venules and capillaries) become congested with bacteria. The bacteria activate the complement cascade and an inflammatory nidus is formed. Subsequent vasculitis and necrosis at the local site occurs. This can happen not only in the skin but in other organ systems as well.

Portals of entry can be a cut or burn. The external ear canal will be colonized in a small percentage of patients; those that are immunosuppressed may be at higher risk for dissemination of the pseudomonal bacteria from small defects in the epidermis of the ear canal. These defects can be caused by cotton tip applicators that are used for cleaning the ear canal. Pseudomonas can also be isolated from the intestinal tract of healthy individuals. Studies have shown a rate of 5-30% of intestinal tracts colonized with Pseudomonas.

Systemic Implications and Complications

This is a life-threatening infection that is often associated with septic shock. Prompt recognition and therapy is required to achieve an optimal outcome.

Individuals diagnosed with ecthyma gangrenosum, with no known underlying comorbidities, should have a complete physical examination, including laboratory testing, to determine if they have an underlying undiagnosed immunosuppressed state.

Complete blood count differential and platelet count, blood smear, glucose level and other laboratory tests(HIV, Hepatitis B,C, chest X-ray, Immunoglobulin levels, antinuclear antibody, etc) dependent on the history and physical examination. As an example, if the history and physical examination suggests a nutritional deficiency, zinc, copper, albumin and protein levels should be drawn.

Treatment Options

Treatment options are summarized in Table I.