Hemorrhagic Vesiculobullous Lesions of Ecthyma Gangrenosum in a Diabetic Patient with Myelofibrosis: A Rare Presentation of Septic Shock without Bacteremia

Background

Ecthyma gangrenosum is a serious and rare, but well-known cutaneous infection that is classically associated with Pseudomonas bacteremia [1]. In non-bacteremia patients, sepsis is not a common complication, and immunocompromised patients are more commonly affected. If diagnosis and therapy are delayed, the mortality rate is 18–96% [2]. Early diagnosis, with special attention to cutaneous and clinical findings, is vital for effective case management. Here, we present a case of unusual cutaneous ecthyma gangrenosum complicated by septic shock and end-organ failure despite the absence of bacteremia and neutropenia. Thus, in immunocompromised patients with suspected signs of septic shock, careful examination of any skin lesion might reveal the source of infection.

Case Report

Three days following the administration of amikacin for an E. coli-infected amputation stump of the big toe, a 52-year-old diabetes patient with myelofibrosis presented with hemorrhagic vesicular eruption, vesiculobullous lesions, and necrotic eschar-covered erosive ulcerated lesions over the upper and lower extremities, gluteal and anogenital areas, and oral and nasal mucosa. The lesions were also associated with a right eye discharge (Figures 1, 2). The patient was pale and looked unwell. Moreover, he presented with severe lower gastrointestinal bleeding. His blood pressure was 98/54 mmHg, and his temperature was 36.7°C. Blood chemistry and complete blood count (CBC) laboratory test results were as follows: CBC including platelets: 396×109 (his baseline was 600–900); white blood cells (WBC): 17×109/L (4–10); hemoglobin: 5.7 G/dL (13–17); WBC differential: 85% neutrophils and 8% lymphocytes; platelet large cell ratio: 40%; arterial blood gas analyses: pH: 7.36, pCO2: 36.9 mmHg, pO2: 31 mmHg, aO2: 33.4%; urea: 39.7 mmol/L (3.2–7.1); creatinine: 290 µmol/L (53–120); aspartate transaminase: 424 U/L (0–40); alanine transaminase: 395 U/L (30–65); direct bilirubin: 20.8 µmol/L (2–5); international normalized ratio: 3.6% (0.9–1.2); partial thromboplastin time: 45.9 seconds (26–36); prothrombin time: 46.9 seconds (9.8–13.2).

Because the patient gave a history of severe beta-lactam-induced allergic reactions, a non-dermatologist suspected that anaphylaxis was the underlying cause of his initial clinical presentation; ie, hypotension and a cutaneous rash that appeared right after systemic antibiotic ingestion.

However, after a careful examination of the nature of his cutaneous lesions by an expert dermatologist, along with the overall clinical status and the preliminary lab findings, septic shock with signs of end-stage organ failure was suspected to be the top differential diagnosis.

A bacterial culture grown from a swab of a leg cutaneous lesion underneath the scab was positive for Pseudomonas aeruginosa. Histopathological findings of an ulcerated vesicular lesion obtained from the thumb showed epidermal necrosis and sloughing, in addition to sparse neutrophilic vasculitis that extended deeply into the subcutaneous tissue, with violaceous fibrinous debris surrounding the vascular wall (Figure 3). A Gram stain preparation of the tissue revealed numerous gram-negative rods surrounding necrotic blood vessels.

Upper and lower gastrointestinal endoscopies were performed and failed to identify any necrotic, inflammatory, or pathologic causes of bleeding, which was probably related to the deterioration of his coagulation profile. Given these results, a diagnosis of ecthyma gangrenosum-induced septic shock was made.

Since this patient had a history of severe allergic reactions to beta-lactam antibiotics, and the antibacterial sensitivity results were readily available within the first 3 days, levofloxacin was initiated to treat the antibiotic-resistant Pseudomonas sp. infection. This patient was successfully managed with early initiation of proper antibiotics after consulting infectious disease specialists and was discharged from the intensive care unit 10 days after starting the antibiotics. Six weeks after being discharged from the hospital, the patient was doing well, his renal and liver functions were normal, and his coagulation profile was also normal.

Discussion

Although the patient presented to the emergency room as hypotensive, the timeline between the administration of amikacin and his presentation, as well as the types of skin lesions, did not suggest a type 1 hypersensitivity reaction. The most commonly reported allergic reactions to aminoglycosides are caused by gentamicin and tobramycin, with amikacin being the least reported cause. Allergies to aminoglycosides are infrequent compared with cephalosporins or quinolones [3].

Microscopic polyangiitis would be another differential diagnosis to consider in the context of small-medium vessel neutrophilic vasculitis and clear evidence of acute kidney injury (AKI). However, in septic-looking, hypotensive patients with signs of end-stage organ failure, disseminated intravascular coagulation (DIC)-induced hemorrhage, and clear evidence of positive bacterial culture, a diagnosis of ecthyma gangrenosum complicated by septic shock is highly suggested [4].

The patient’s clinical findings were highly suggestive of bacterial sepsis, including a systolic blood pressure of <90 mmHg, neutrophil/lymphocyte ratio of >10: 1, and relative thrombocytopenia, with a high platelet large cell ratio, while the following complications suggested septic shock: AKI, DIC, and acute respiratory distress syndrome [5]. Although the patient was afebrile, immunocompromised patients can develop sepsis with normothermia.

Although ecthyma gangrenosum is commonly associated with Pseudomonas bacteremia, it rarely presents as a primary skin infection. Our patient’s blood and urine cultures were negative, which was favorable regarding the likelihood of a response to treatment. Blood cultures may be obtained before initiating antibiotic therapy; however, immediate treatment for septic shock should ensue without delay. Ecthyma gangrenosum has a high mortality rate if diagnosis and treatment is delayed; thus, prompt treatment strategies under the care of a multi-disciplinary team involving infectious disease specialists and the intensive care unit must be implemented.

While awaiting the results, antipseudomonal penicillins in conjunction with gentamicin can be used as an empirical treatment [6]. However, when the antibacterial sensitivity results are readily available, the choice of proper antibiotics should be based on those results. Therefore, oral levofloxacin was initiated to treat the antibiotic-resistant Pseudomonas infection, based on retained susceptibility as shown by the local resistance pattern [7].

Conclusions

Early detection and a high suspicion of ecthyma gangrenosum, with special consideration for the clinical presentation of ecthyma gangrenosum, is a vital part of patient management to reduce the high mortality risk of the disease. Although bacteremia is associated with a high risk for fatalities, cutaneous ecthyma gangrenosum is also serious, as it can be complicated by septic shock and serious adverse events. The involvement of multidisciplinary teams in patient management is an essential aspect of ecthyma gangrenosum disease management.