Abstract

Ecthyma gangrenosum (EG) is a well-recognized but rare skin infection most commonly occurring in the setting of immunocompromised individuals with bacteremia. Currently, there are very few reports of EG caused by methicillin-resistant Staphylococcus aureus (MRSA) and even fewer cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). We present only the second case of bacteremic EG associated with MSSA bacteremia and aim to review the literature as well as examine common findings amongst patients with EG associated with Staphylococcus aureus.

1. Introduction

Ecthyma gangrenosum (EG) is a well-recognized but rare skin infection most commonly occurring in the setting of immunocompromised individuals. Pseudomonas aeruginosa is the most frequent organism identified in EG. In rare cases, it may be caused by other bacteria, viruses, and even fungi. ¹ Currently, there are very few reports of EG caused by methicillin-resistant Staphylococcus aureus (MRSA), and even fewer cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). ² We present only the second case of bacteremic EG associated with MSSA bacteremia and aim to review the literature as well as examine common findings amongst patients with EG associated with Staphylococcus aureus.

2. Case Report

A 71-year-old male with a past medical history of stage IV small cell lung cancer with metastasis to the brain on chemotherapy presented to the emergency department with complaints of fever, diarrhea, and painful skin lesions on upper and lower lips as well as neck and right elbow. Carboplatin, etoposide, and atezolizumab were started approximately one week prior. His temperature on arrival at the hospital was 100.4^oF, with labs revealing a white blood cell count of 0.6 × 10⁹/L, an absolute neutrophil count of 0.2 x 10⁹/L, and a platelet count of 30,000 x 10⁹/L.

A physical exam revealed four tender papules and plaques with surrounding induration and erythema around a necrotic center on the patient's upper and lower lips as well as on his right posterior elbow, left proximal palmar hand, and at the base of the second phalange on his left dorsal hand (Figure 1). Blood cultures were positive for methicillin-sensitive staphylococcus aureus (MSSA) in 2/2 sets. The patient was initially started on IV vancomycin and cefepime for suspected febrile neutropenia and bacteremia. Given the bacteremia and associated neutropenia, the patient's skin findings were suspected to be EG secondary to methicillin-sensitive Staphylococcus aureus bacteremia. Throughout the patient's hospital course, the patient's neutropenia and skin lesion began to improve, and thus, a skin biopsy was forgone. The patient was ultimately de-escalated to IV cefazolin and discharged home.

Given this patient's neutropenia, typical skin lesions, and MSSA bacteremia, MSSA bacteremia EG was the most likely diagnosis. However, other EG-associated pathogens were also considered in the differential diagnosis. Noninfectious causes such as autoimmune vasculitis, pyoderma gangrenosum, septic emboli, calciphylaxis, and disseminated intravascular coagulation were also considered.

3. Discussion

EG is a rare cutaneous infection most commonly associated with P. aeruginosa. Although P. aeruginosa has been identified in up to 75% of EG cases, other organisms have been reported, such as MRSA, streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, fungi, and viruses. ¹ Our patient presented with MSSA-associated EG, an organism not often thought of when a patient presents with EG. We completed a PubMed review between 1966 and 2022, using keywords of ecthyma gangrenosum, Staphylococcus aureus, methicillin-sensitive, and methicillin-resistant (Table 1). [2-12] We found only eleven cases of Staphylococcus aureus-associated EG, with only four reported cases of MSSA. The median age of patients was 40 years old, and 45% of these cases were seen in women (5 cases).

EG lesions begin as painless, round erythematous macules and patches that evolve to become tender with a central gangrenous ulcer and gray-black eschar surrounded by erythema. Skin findings can progress rapidly from vesiculobullous to hemorrhagic lesions. ¹⁰ While EG can occur anywhere on the body, the most common locations are the gluteal/perineal area (57%), followed by the extremities (30%), the trunk (6%), and the face (6%). ¹ Staphylococcus aureus-associated EG presents in similar locations, with 7 cases affecting the lower extremities, 5 affecting the trunk, 3 affecting upper extremities, 3 affecting the head/face, and 2 affecting the gluteal/perineal area.

In our case, the organism was found through blood cultures; however, a skin biopsy or culture was not obtained due to the significant clinical improvement following empiric antibiotic therapy. Of the eleven reported cases of EG associated with Staphylococcus Aureus, only two cases with positive blood cultures were noted, ten cases reported culture lesions positive for Staphylococcus Aureus, and five cases reported gram-positive cocci on skin biopsy. The diagnosis of EG is made clinically based on the characteristic appearance and a high degree of clinical suspicion with blood cultures, tissue cultures, and a biopsy supporting the diagnosis. ¹³ Thus, given the risk factors found in this patient, MSSA bacteremia, and characteristic skin findings, he was diagnosed clinically with EG. However, it can not be ruled out that this patient's EG was unrelated to the MSSA bacteremia and that another non-bacteremic pathogen caused the EG.

Immunocompromised individuals are particularly susceptible to EG, with up to 62% to 75% of affected individuals having an underlying immunodeficiency. ¹³ Predisposing conditions include neutropenia, malignancy, diabetes mellitus, malnutrition, and burn wounds. ¹³ This patient fits the typical predisposing factors given his history of small cell lung malignancy, chemotherapy, and neutropenia. Predisposing factors we found common amongst Staphylococcus aureus-EG include other forms of malignancy (2 cases), history of chemotherapy (2 cases), and CKD (2 cases). Interestingly, three patients had past medical histories that would not support the clinical picture for EG, which included COPD and chronic alcohol use, with one patient having no significant past medical history. Common lab findings amongst Staphylococcus aureus-EG include neutropenia (3 cases), leukocytosis (3 cases), and leukopenia (2 cases).

EG is separated into two groups based on pathogenesis, bacteremic and non-bacteremic, with the bacteremic form being more common. In bacteremic EG, skin findings are the result of the hematogenous spread of a causative organism to the skin, subsequently leading to perivascular invasion causing ischemic necrosis of the surrounding skin. ¹³ In the non-bacteremic form, localized infections by organisms release toxins and enzymes, causing localized skin and vascular destruction. ¹³ While bacteremic EG is considered to be more common, we found only two other cases of bacteremic Staphylococcus aureus-EG, one case being MRSA associated and the other MSSA, which may seem counterintuitive given that Staphylococcus aureus is known to often spread hematogenously and is the most common cause of gram-positive bacteremia. ^{12, 14, 15} Thus, this case represents only the second MSSA bacteremia EG. While our patient was discharged home, the two other cases of bacteremic Staphylococcus aureus-EG died from sepsis and multiple organ failure. Furthermore, all of the patients with non-bacteremic Staphylococcus aureus-EG were discharged home. Thus, bacteremic-associated Staphylococcus aureus-EG may carry a higher risk of death, and our patient appears to be the only person to have survived this.

Broad-spectrum antibiotics should be initiated following cultures in patients with suspected EG with narrowing of antibiotics following identification of antimicrobial susceptibilities. ^{13, 16} This patient was successfully treated with IV vancomycin and cefepime and was later de-escalated to IV cefazolin. Of the eleven cases we found from the literature review, six were treated with vancomycin, and four were treated with cefepime. Other antibiotics we found commonly used were amikacin (3 cases), linezolid (2 cases), nafcillin (2 cases), and teicoplanin (2 cases).

4. Conclusion

While P. aeruginosa is the most common etiology of EG, although rare, other infectious pathogens should be considered in the differential, such as Staphylococcus aureus. This case is unique as it represents only the second case of EG due to MSSA bacteremia and the only case to have survived bacteremic-associated Staphylococcus aureus-EG. Thus, a history of immunosuppression, early culturing, and a high degree of clinical suspicion is necessary when considering rare etiologies of EG.

References