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Ecthyma gangrenosum (EG) is a rare skin lesion usually found in neutropenic, immunocompromised patients with underlying hematological malignancies and patients after bone marrow transplantation [1, 2]. Mostly, EG appears secondary to Pseudomonas aeruginosa (PA) bacteremia [3, 4]. There are a few case reports of otherwise healthy individuals and patients without proven bacteremia where the skin lesions are considered to be primary [5]. Other pathogens, like Staphylococcus aureus, Klebsiella species, Escherichia coli, Neisseria meningitidis, Stenotrophomonas maltophilia, Aspergillus, Candida, Fusarium, and Rhizopus may also be causal agents [1]. Through a few stages, EG usually evolves from a macula or papula which progresses into a hemorrhagic bulla and a black necrotic eschar [1, 2, 5, 6].

Herein, we present two patients with hematologic malignancies and EG, with and without PA bacteremia. Alongside these cases, we presented a brief literature review on the essential issues associated with this condition.

Case Reports

Case 1

A 50-year-old female was admitted for the treatment of acute myeloblastic leukemia M2 French-American-British (FAB) classification, transformed from myelodysplastic syndrome. Bone marrow aplasia was induced after standard induction treatment with continuous intravenous cytarabine (7 days) and daunorubicin (3 days). On day 12 after the beginning of chemotherapy, the patient developed febrile neutropenia; the fever was 38.7[degrees] C, white blood cell count (WBC) was 2.0 x [10.sup.9]/L, and neutrophil granulocytes were 0.44 x [10.sup.9]/L. On day 14, hemorrhagic bullae appeared on her right hemiabdomen, right leg and vulva and in the course of a few days, they progressed into necrotic ulcers. Swabs were taken and sent for microbiological testing. In the meantime, empiric antibiotic treatment was initiated (ceftazidime and amikacin). When blood cultures, leg and abdominal ulcer swab results returned positive for PA, the treatment was continued according to the antibiogram. The patient was persistently febrile during the prolonged period of neutropenia (from day 14 to day 42). She was clinically at her worst on day 20, when she was hypotensive (blood pressure was 85/50 mmHg) but responded well to volume challenge. Ulcer swabs were repeated and came back positive for PA. Intermittently, two separate strains of PA were present, alongside the development of antibiotic resistance, which resulted in frequent changes of medications (Table 1). Additional ulcer treatment included surgical debridement and daily topical use of ethacridine lactate. After 118 days of hospitalization, the patient was discharged with an ulcer on her right foot measuring around 20 cm x 8 cm still positive for PA (Figure 1). Four months later, she was readmitted for further ulcer treatment. Another necrosectomy was performed, and the patient received seven doses (one every other day) of autovaccine. However, the swab remained positive for PA, and the ulcer was still open. The underlying disease was treated with 500 mg hydroxyurea a day. In the following year, she was hospitalized several times due to high fever. The blood cultures were negative. The patient received parenteral antibiotic treatment together with a topical ulcer treatment. Due to the inability to continue high dose chemotherapy, the patient died as a result of infection and underlying disease progression.

EG   - ecthyma gangrenosum
PA   - Pseudomonas aeruginosa
WBC  - white blood cell

Case 2

A 38-year-old male was admitted for autologous bone marrow transplantation. Two years earlier, he was diagnosed with nodular sclerosing Hodgkin's lymphoma, stage IV Bb. In the course of time, he received multiple lines of chemotherapy including doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), bleomycin, etoposide, doxorubicin, cyclo-phosphamide, vincristine, procarbazine, prednisone (BEACOPP) and dexamethasone, cisplatin, cytarabine (DHAP). Bone marrow transplantation was performed following the conditioning regimen, which included carmustine, etoposide, cytarabine, and melphalan (BCNU).

On day 3, the patient experienced a burning sensation and itching in the scrotal region, accompanied by an erythematous macular rash. He was afebrile with leukopenia (WBC 1.9 x [10.sup.9]/L). The patient was already on empirical antimicrobial prophylaxis, as part of the transplantation protocol (ciprofloxacin, acyclovir, and fluconazole). Due to the appearance of skin changes on day 3, the prophylactic treatment was switched to cefepime. The skin swab taken on day 3 cultivated a normal bacterial flora. After dermatological consultations, the erythematous macula was treated with topical corticosteroids and 3% solution of boric acid. Despite treatment, from day 5 to day 25, the lesion progressed into an ulcer typical for EG. Deterioration of the local finding was accompanied by a fever of 38[degrees] C starting from day 15. At that time, the patient presented with leukopenia (lowest WBC on day 16 was 0.4 x [10.sup.9]/L). He started receiving meropenem, vancomycin, and metronidazole, while blood cultures and swab results were pending. Blood cultures came back negative, but the swab from the scrotal ulcer taken on day 25 was positive for PA sensitive to piperacillin/tazobactam and cefepime. Piperacillin/tazobactam was initiated on day 25 and continued for 12 days along with topical use of 3% solution of boric acid and silver sulfadiazine. The patient had a complete ulcer resolution. After that, the patient's stay was uneventful, and he was discharged.


There are two possible pathogenic mechanisms involved in the development of EG; it either develops secondary to PA bacteremia, or it is a primary, localized skin infection without bacteremia [2]. Pseudomonas secretes enzymes such as elastase, exotoxin A, and protease, which lead to the development of necrotizing vasculitis, hemorrhage, and ulceration [1, 5]. In our cases, both mechanisms were augmented.

Most commonly, lesions develop in the anogenital and axillary regions, but any other body part, like the trunk and the extremities can be affected [1, 2, 4, 6]. Predisposition can be explained by the bacteria's affinity for moist and warm environments [1]. Unexpectedly, the worst lesion in the cases we presented was localized on the foot and foreleg. The rest followed a familiar pattern.

The treatment of EG is complicated for several reasons; development of multi-drug-resistant strains, presence of a severe underlying disease and usually intensive chemotherapy which further debilitates the host's weakened immune system [1, 4, 6]. These factors create a kind of vicious cycle.

There are no standard guidelines for the treatment. Authors agree, and it is our opinion as well, that early diagnosis, regular sampling of tissue specimens, prompt initiation of combined antibiotic therapy, knowledge of local Pseudomonas' resistance profile, as well as individual approach to each patient are of great importance [1, 2, 5, 6].

In our first case, we tried additional therapy with autovaccination. These vaccines, which consist of inactivated microorganisms, can be used in the treatment of chronic or recurrent infections [7, 8]. Their utilization in humans is seldom, and they are proven to boost cytokine levels, but not a specific immune response towards a particular microorganism [7]. There were no clinical benefits of this treatment in our patient, since the infection persisted with the same intensity and the swab of the ulcer remained positive.

Our cases differed in courses and outcomes. As shown in previous studies, patients with Pseudomonas bacteremia have a higher mortality rate in comparison to patients without it [3, 4]. However, in our cases, the underlying diseases had a significant impact on the patients' outcome.


Early diagnosis and prompt combined antibiotic treatment are essential in the treatment of ecthyma gangrenosum. On the other hand, the underlying disease has a great impact on the outcome as well.


[1.] Clebak KT, Malone MA. Skin infections. Prim Care. 2018;45(3):433-54.

[2.] Ferguson L, Chong H, Singh M. Ecthyma gangrenosum without bacteraemia: evidence in favour of a broader definition. Clin Exp Dermatol. 2017;42(3):324-7.

[3.] Todd N, Boucher JE, Bassal M, Dumont T, Fleming N. Ecthyma gangrenosum: vulvar ulcers, pseudomonas, and pancytopenia: a case report of an 18-month-old female toddler. J Pediatr Adolesc Gynecol. 2018;31(6):625-8.

[4.] Serra R, Grande R, Butrico L, Rossi A, Settimio UF, Caroleo B, et al. Chronic wound infections: the role of Pseudomonas aeruginosa and Staphylococcus aureus. Expert Rev Anti Infect Ther. 2015;13(5):605-13.

[5.] Li AW, Yin ES, Stahl M, Kim TK, Panse G, Zeidan AM, et al. The skin as a window to the blood: cutaneous manifestations of myeloid malignancies. Blood Rev. 2017;31(6):370-88.

[6.] Grunwald MR, McDonnell MH, Induru R, Gerber JM. Cutaneous manifestations in leukemia patients. Semin Oncol. 2016;43(3):359-65.

[7.] Bassetti M, Castaldo N, Cattelan A, Mussini C, Righi E, Tascini C, et al. Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience. Int J Antimicrob Agents. 2019; 53(4):408-15.

[8.] Pasnik J. Vaccines nonspecific - immunostimulation in patients with recurrent respiratory infections. Otolaryngol Pol. 2016;70(6):31-9.

Mirjana TOMIC (1), Ivanka PERCIC (1,2), Danijela AGIC (1,2,) Nada VLAISAVLJEVIC (1), Borivoj SEKULIC (1,2) and Ivana UROSEVIC (1,2)

Clinical Center of Vojvodina, Clinic of Hematology, Novi Sad (1) University of Novi Sad, Faculty of Medicine Novi Sad (2)

Corresponding Author: Dr Mirjana Tomic, Klinicki centar Vojvodine, Klinika za hematologiju, 21000 Novi Sad, Hajduk Veljkova 1-7, E-mail:,

Rad je primljen 4. V 2019.

Recenziran 23. V 2019.

Prihvacen za stampu 28. V 2019.

Table 1. Choice of antibiotics and the length of therapy
Tabela 1. Spisak tipova antibiotika i duzine primene

Antibiotic/Antibiotik        Days of application/Dan primene

Ceftazidime/Ceftazidim       12 - 18, 44 - 51
Amikacin/Amikacin            12 - 18, 26 - 28, 31 - 35, 40 - 44
/Piperacilin/Tazobactam      20 - 21, 29 - 41
Vancomycin/Vancomycin        21 - 27, 29 - 40
Meropenem/Meropenem          21 - 26
Ciprofloxacin/Ciprofloxacin  19 - 20
/Imipenem/Cilastatin         28 - 30, 73 - 90
Cephalexin/Cephalexin        70-73
Gentamicin/Gentamicin        113 - 118

Antibiotic/Antibiotik        Days in total/Ukupno dana

Ceftazidime/Ceftazidim                  15
Amikacin/Amikacin                       20
/Piperacilin/Tazobactam                 15
Vancomycin/Vancomycin                   19
Meropenem/Meropenem                      6
Ciprofloxacin/Ciprofloxacin              2
/Imipenem/Cilastatin                    11
Cephalexin/Cephalexin                    4
Gentamicin/Gentamicin                    6
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Author:Tomic, Mirjana; Percic, Ivanka; Agic, Danijela; Vlaisavljevic, Nada; Sekulic, Borivoj; Urosevic, Iva
Publication:Medicinski Pregled
Date:Mar 1, 2019

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