In 1897, Barker first described skin lesions evolving from erythematous macules to vesicles to necrotic ulcers in the setting of septicemia secondary to Pseudomonas aeruginosa.¹ In the same year, Hitschmann and Kreibich coined the term ecthyma gangrenosum (EG) for this characteristic cutaneous manifestation of pseudomonal septicemia.² Although P. aeruginosa is the classic pathogen in EG, other infectious organisms can produce clinically identical lesions (Table 62-1).³ Regardless of the causative organism, EG has a predilection for immunocompromised hosts, particularly individuals with neutropenia and hematologic malignancies.⁴ However, EG can also occur in previously healthy children, sometimes representing the initial presentation of a primary or acquired immunodeficiency. EG is currently considered as a morphologic pattern of cutaneous necrosis that results from occlusion of blood vessels by organisms proliferating within their walls, usually but not always associated with bacteremia or fungemia. EG tends to progress rapidly and has a high mortality rate without treatment, so early recognition and prompt administration of antimicrobial therapy are essential.

Conditions that have been associated with EG in children are listed in Table 62-2. Approximately one-third of pediatric patients with EG have leukemia or aplastic anemia, and the occurrence of EG usually coincides with neutropenia related to the administration of chemotherapy or myeloablative regimens for hematologic stem cell transplantation. However, EG occasionally heralds the onset of leukemia in a previously healthy child.⁵ Additional predisposing factors for the development of EG in cancer patients and other immunocompromised hosts include occlusion or maceration of the skin, prior antibiotic therapy, treatment with systemic corticosteroids or other immunosuppressive medications, diabetes mellitus, and hypocomplementemia. Premature infants are also at higher risk of EG, particularly when exposed to a high-humidity environment.^6-8 Intravenous catheters and invasive procedures represent other important iatrogenic risk factors.⁹ Finally, bacterial contamination (e.g. with P. aeruginosa) of “moist” hospital equipment and supplies, ranging from nebulizers to antiseptic solutions to bath toys, can be a source of nosocomial infections manifesting as EG in immunocompromised patients.^10,11

Almost half of the pediatric cases of EG reported to date occurred in previously healthy children (see Table 62-2). The median age of these patients was approximately 9 months, compared with 4.5 years for children known to have an underlying medical disorder. In children without a recognized predisposing condition, EG most often presents with fever and diarrhea in the setting of acute enteritis, and an especially virulent strain of P. aeruginosa is sometimes implicated (e.g. in “Shanghai fever”).¹² In addition, EG occasionally develops in conjunction with otitis media/externa secondary to P. aeruginosa and/or a preceding viral respiratory tract infection. The majority of previously healthy patients with EG have transient neutropenia, and approximately one-third are found to have hypogammaglobulinemia, a neutrophil disorder, or another immunodeficiency syndrome.

Regardless of the underlying medical condition, EG is observed in approximately 20% to 50% of children with pseudomonal septicemia.⁸ Cutaneous lesions that may be clinically identical to pseudomonal EG can also be seen in the setting of disseminated candidiasis (10% to 15% of cases) or aspergillosis (<5% of cases), which represent the most common systemic mycoses in neutropenic patients. Of note, EG-like skin lesions occur in 70% to 90% of disseminated infections with Fusarium, the mold second most likely to cause systemic disease in immunocompromised hosts.¹³

PATHOPHYSIOLOGY

The two major routes to the development of EG are (1) a classic bacteremic (or fungemic) form, caused by hematogenous dissemination of the organism to the skin, and (2) a nonbacteremic form in which the skin lesions are located at a cutaneous site of inoculation of the organism.^10,14,15 Although blood cultures are initially negative in the latter scenario, secondary bacteremia and clinical decompensation may occur if treatment is delayed.

The most recognized pathogen of EG, P. aeruginosa, is a gram-negative bacillus that is a component of the normal intestinal flora in 10% to 15% of healthy individuals and in more than 33% of hospitalized patients.¹⁶ Cancer patients are particularly prone to colonization of the oropharynx and gastrointestinal tract with P. aeruginosa and other potentially pathogenic microorganisms.¹⁷ Although it cannot survive on intact, dry skin, P. aeruginosa colonizes moist intertriginous areas, such as the groin and axillae, in approximately 2% of the population. Based on the frequent localization of pseudomonal EG to these intertriginous areas, as well as documentation of EG in association with blood cultures that are initially negative but later positive, some authors have postulated that the source of P. aeruginosa infection manifesting with EG in immunologically impaired hosts is often the skin itself.⁸

Abnormal neutrophil function (resulting from quantitative or qualitative defects) represents the most important risk factor for both disseminated P. aeruginosa infection and opportunistic mycoses. The vascular destruction that leads to EG lesions in septicemia due to P. aeruginosa is thought to be related to dissolution of the elastic lamina by pseudomonal elastase. Not unexpectedly, other bacteria (e.g. Aeromonas maltophilia) that have been implicated in the development of EG also produce elastase and various proteases.¹⁸ Likewise, several of the opportunistic mycoses that can cause lesions resembling EG (e.g. aspergillosis, fusariosis, zygomycosis) have a propensity to invade blood vessel walls, resulting in thrombosis and tissue necrosis.

EG typically begins as a painless, erythematous macule, often with a relatively blanched or grayish center. Over a 12- to 24-hour period, the lesion becomes indurated, and a hemorrhagic vesicle or pustule develops centrally (Figure 62-1). Rupture then leads to the formation of a necrotic ulcer with a gray-black eschar and a red to violaceous border (Figure 62-2).¹⁹ One or multiple lesions may be present, either grouped or in a scattered distribution, with sizes ranging from a few millimeters to several centimeters in diameter. Erythematous nodules may be seen adjacent to or distant from necrotic lesions.