Ecthyma Gangrenosum of Scrotum in a Patient with Neutropenic Fever: A Case Report

Background

Infections are the most common complications with high morbidity and mortality for patients with acute myeloid leukemia. These patients are at particularly high risk of infection, likely related to the intensity of their therapy resulting in profound neutropenia. Ecthyma gangrenosum is an uncommon cutaneous manifestation most often seen in patients who are immunocompromised, with an approximate incidence of 19% [1,2]. It can be a potentially fatal systemic infection with a high mortality rate, ranging from 38% to 77% [3]. Most previous reports indicated that the skin lesions are most commonly seen in axilla, buttocks, and limbs but scrotal ecthyma gangrenosum is uncommon [2,4]. We report a patient with acute myeloid leukemia who developed ecthyma gangrenosum of left scrotum associated with Pseudomonas aeruginosa bacteremia in the setting of post-chemotherapy neutropenia.

Case Report

A 68-year-old Caucasian male with a history of acute myeloid leukemia presented to Memorial Hospital West Emergency Department complaining of abdominal pain, fever, and genital ulcers. He was currently on chemotherapy with daunorubicin and cytarabine. He had a blood pressure of 81/53 mm Hg and heart rate of 75 beats per minute requiring aggressive intravenous fluid resuscitation for volume expansion. He was found to have 2 necrotic ulcers with black eschars on the left scrotum with induration (Figure 1). Laboratory analysis was significant for leukopenia (400 white blood cells/µL) with an absolute neutrophil count of 200/µL, anemia (4.3 g/dL hemoglobin) with a hematocrit of 12.6%, and thrombocytopenia (7000/µL platelets). An uncompensated metabolic acidosis (4.0 mmol/L lactic acid venous) also and increased level of blood urea nitrogen (30 mg/dL BUN) were observed. A diagnosis of ecthyma gangrenosum with P. aeruginosa septicemia was suspected, and the patient was started empirically on intravenous therapy (IV) with amikacin (1 g, once a day), metronidazole (500 mg, 3 times a day), cefepime (2 g, 3 times a day) and vancomycin (15 mg/kg, 2 times a day) after collecting blood and skin lesion samples. Aerobic blood culture and wound cultures showed growth of Gram-negative bacilli, and MacConkey Agar media plate showed a non-lactose fermenter organism. P. aeruginosa was confirmed with a matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF, Biomerieux) [5]. Thus, a diagnosis of ecthyma gangrenosum with P. aeruginosa septicemia was confirmed, the susceptibly reported as pan sensitive and the treatment was continued with cefepime (2 g, 3 times a day, IV) alone for 14 days from first negative blood culture. The patient underwent a full recovery. There was a significant improvement of the lesions, and no sign of recurrence or new lesions was observed on follow-up visits.

Discussion

An early diagnosis of ecthyma gangrenosum is based on the clinical characteristics of lesions. The first skin lesion can be expressed as an erythematous macule that subsequently becomes small indurated erythematous base with rim, progressing rapidly (12–18 hours) into a necrotic ulcer with surrounding erythema and a central black eschar [2,4]. Single or multiple lesions can be seen in any skin or cutaneous membranes of the body, as seen in our case ecthyma gangrenosum was found in the left scrotum, making it an unusual and more challenging location to diagnose. On biopsy perivascular hemorrhage vasculitis and infiltration of neutrophilic granulocytes with central necrosis and surrounding bacilli can be seen in ecthyma gangrenosum lesions, which establishes a definitive diagnosis [4]. Differential diagnosis should consider pyoderma gangrenosum, cutaneous anthrax, necrotizing fasciitis, heparin or warfarin induced necrosis, cocaine-induced skin necrosis, embolic phenomenon and necrosis secondary to the use of vasoactive drugs [6].

The presence of ecthyma gangrenosum is indicative of bacteremia caused by P. aeruginosa, an opportunistic bacterium that can be found on the skin, in the nose and throat, and is mostly implicated in hospital acquired infections with multidrug resistant and a mortality rate ranging from 16% to 90% [6–8]. In our case, blood and wound cultures revealed P. aeruginosa bacteremia that was further confirmed by flight mass spectrometry [5]. Also, other bacterial and fungal pathogens including Aeromonas, Escherichia coli, Klebsiella pneumonia, various Pseudomonas species, Candida, Aspergillus, and Zygomycetes have been reported to cause ecthyma gangrenosum with or without septicemia [7,9–11].

Ecthyma gangrenosum typically occurs in immunocompromised patients with conditions such as neutropenia, chemotherapy, hematologic malignancies, immunodeficiency syndromes, severe burns, malnutrition, immunosuppressive therapy, and diabetes mellitus [11]. This is specifically true for our patient, who had severe neutropenia, secondary to both the hematological disorder and its aggressive therapy, later developed ecthyma gangrenosum. It should be noted that there have been rare case reports of ecthyma gangrenosum occurred in previously healthy children [2,12,13]. In such cases, an immunological evaluation should be performed to rule out underlying immunodeficiencies, because 50% of these individuals may have a primary subclinical immunodeficiency or unrecognized underlying medical conditions [3,12,14]. It has been reported that severe P. aeruginosa infection can occur in previously healthy children with a mortality rate of 55% [13].

In cases of ecthyma gangrenosum, early recognition and management with empirical antibiotics is essential due to rapid disease progression. Antibiotics with spectrum for P. aeruginosa including cephalosporins, β-lactam penicillin such as piper-acillin with an aminoglycoside or fluoroquinolone are recommended [15]. Surgical excision and skin grafting are indicated if no improvement of the lesions after aggressive antibiotic treatment, because ecthyma gangrenosum manifests as necrotizing soft-tissue lesion, carrying a high mortality rate [16,17]. In our case, the patient was started on broad-spectrum antibiotics prior to the return of the blood and wound culture, and a quick curative effect was achieved. The lesions were significantly improved, becoming rapidly smaller with no tender, and follow-up visits revealed no sign of recurrence or new lesions.

Conclusions

We describe a patient with acute myeloid leukemia who developed P. aeruginosa ecthyma gangrenosum on the left scrotum after chemotherapy, and who responded well to systemic combined antibiotics. Our case illustrates the rare presentation of scrotal ecthyma gangrenosum. This case highlights the importance of early diagnosis and aggressive antimicrobial treatment if there is clinical suspicion of ecthyma gangrenosum.