Ecthyma gangrenosum mimicking acute invasive fungal sinusitis in an immunocompromised patient
Ecthyma gangrenosum is a necrotizing cutaneous infection caused by gram-negative bacteria, most commonly Pseudomonas aeruginosa. It is typically associated with pseudomonal bacteremia in immunocompromised patients, particularly those with neutropenia. It is most common in children, nearly all cases of adult infection have involved patients with a hematologic malignancy or myeloid pathology.1-4 Only 6% of all cases of ecthyma gangrenosum occur in the head and neck.2,3 We report what we believe is the first case of ecthyma gangrenosum occurring in the sinonasal mucosa.
A 39-year-old white man with history of bilateral endoscopic sinus surgery for chronic rhinosinusitis and a recent diagnosis of acute lymphocytic leukemia presented to the Emergency Department with a complaint of several days of fever, confusion, right frontal headache, right-sided facial pressure, and occasional blurred vision. Although the onset of the patient's symptoms coincided with the completion of a 3-week course of inpatient chemotherapy, he was not neutropenic at presentation. He denied nasal obstruction, purulent rhinorrhea, postnasal drip, cough, and epistaxis. His social history was significant for a 15-pack-year smoking habit in the distant past.
The patient was admitted to the oncology service, where computed tomography (CT) of the head revealed a partial opacification of the right ethmoid air cells, no other intracranial pathology was noted. The CT finding prompted an otolaryngology consult to rule out invasive fungal sinusitis as a potential etiology. A dedicated maxillofacial CT was obtained, in addition to the partial opacification of the right frontal sinus and frontoethmoid recess, it detected a small polypoid mass in the contralateral maxillary sinus. No evidence of sinonasal bony erosion or air-fluid levels was present. On the basis of the patient's history and radiographic findings, a diagnosis of acute sinusitis was made. The patient was started on broad-spectrum antibiotics and antifungal agents.
On physical examination, the patient's temperature had fallen from 102.0°,,F earlier in the day to 97.8°,,F, and he was in no distress. Findings on a cranial nerve examination and gross vision assessment were normal. Scleral icterus and mild erythema of the right upper eyelid were observed. The face was not tender to palpation, and no cervical lymphadenopathy was noted. Rigid nasal endoscopy (0°,,) revealed insensate and necrotic-appearing areas on the anterior tip of the right middle turbinate and on the nasal septum (figure 1). The surrounding mucosa was sensate and well vascularized. A bedside biopsy of the middle turbinate revealed ischemic necrosis without fungal elements, and further tissue biopsies were recommended.
Figure 1. Rigid nasal endoscopy (0°,,) shows the necrotic-appearing areas on the right middle turbinate (MT) and the nasal septum (S). (IT = inferior turbinate.)
Out of concern that the patient might have acute fulminant invasive fungal sinusitis, he was urgently taken to the operating room for endoscopic debridement and possibly a total maxillectomy and orbital exenteration. During a rigid endoscopic nasal examination, a small necrotic area was identified on the right medial orbital wall, and the middle turbinate was found to be diffusely ischemic. The middle turbinate was then resected in its entirety, and the other necrotic lesions were widely excised. No gross purulence was encountered. The left nasal cavity was disease-free.
Intraoperative frozen sections of all areas in question demonstrated ischemic necrosis and numerous bacteria, but no invasive fungus. A Gram stain revealed numerous gram-negative rods, including some in an endovascular location in a coagulative necrotic background (figure 2). These findings are characteristic of ecthyma gangrenosum. The final pathology report confirmed the presence of necrotic sinonasal mucosa and marked acute suppurative inflammation (figure 3). The tissue cultures had grown pansensitive P aeruginosa and coagulase-negative staphylococci, which were adequately covered by empiric treatment at the time of the otolaryngology consult and likely explain the patient's defervescence.
Figure 2. A: Gram stain demonstrates vascular necrosis (original magnification x100). (X = blood vessel wall, + = gram-negative bacteria within the vessel wall. B: Gram-negative bacteria (*) are seen within the sinonasal mucosa (original magnification x100)
Figure 3. Specimen exhibits the acute necrotizing sinusitis in the sinonasal mucosa with mucosal ulceration, inflammatory infiltrate, and coagulative necrosis (H&,E, original magnification x25)
Findings on further fever workup studies were unremarkable with the exception of one blood culture that was weakly positive for coagulase-negative staphylococci. The patient was subsequently placed on culture-directed antibiotic therapy consisting of high-dose intravenous levofloxacin and vancomycin. Over the next 48 hours, the fever curve normalized, the symptoms of acute sinusitis subsided, and the patient was discharged home on a levofloxacin/linezolid regimen.
P aeruginosa infection is an opportunistic infection that is usually encountered in immunocompromised patients and burn patients. In addition to developing pneumonia, urinary tract infections, and line sepsis, patients with pseudomonal infections can develop cutaneous involvement. Skin signs include diffuse maculopapular lesions and painful clusters of small vesicles or pustules, as well as ecthyma gangrenosum, which is an aggressive, rapidly evolving necrotic lesion of the skin and mucous membranes.
Ecthyma gangrenosum has been reported in 1 to 6% of patients with P aeruginosa bacteremia, and less often in nonbacteremic patients.2,3,5 The most common sites of ecthyma gangrenosum are the gluteal and perineal areas (57% of cases) and the extremities (30%), facial involvement is rare.5 Although there have been reports of involvement of the nasal ala,2,3,6 no case of ecthyma gangrenosum affecting the sinonasal mucosa has been previously reported in the English-language literature.
Although ecthyma gangrenosum is most often associated with P aeruginosa, it has also been described in infections with Staphylococcus aureus, Aeromonas hydrophilia, and Aspergillus, Mucor, and Serratia spp. While it is not always seen in patients known to be immunocompromised, its predisposing factors are typically discovered during the workup of such patients.7 Our patient, who had a known hematologic malignancy and subsequent immunosuppression, fit the common profile.
Acute sinusitis is a serious concern in any immunocompromised patient. Multiple opportunistic bacteria, as well as fungi, have been reported as causes of sinusitis in patients with poor immune function. Patients with acute invasive fungal sinusitis usually present with fever, facial pain, nasal congestion, epistaxis, and changes in vision or mentation. Many patients have intracranial or orbital involvement at the time of their initial presentation. On gross examination, invasive fungal sinusitis is characterized by insensate sinonasal mucosa that may appear to be necrotic. Nasal culture and biopsy are essential to differentiate between mycotic sinusitis and bacterial sinusitis.
Because rapid and complete surgical debridement in combination with appropriate antimicrobial therapy is necessary in cases of invasive fungal pathology, a high degree of suspicion is needed in immunocompromised patients, and early recognition is essential. Additionally, the increased use of broad-spectrum antibiotics in patients with neutropenia has led to widespread resistance and infections with methicillin-resistant S aureus and gram-negative organisms. Debridement is essential in these cases, as well. The distinction between acute invasive fungal sinusitis and acute sinusitis of nonmycotic origin determines which type of adjuvant medical therapy should be combined with surgical treatment.8
We were consulted on this case after CT findings raised a concern about the possibility of invasive fungal sinusitis. Although there were no gross findings on the patient's face, including the nasal ala, endoscopic examination revealed areas of necrosis in the middle turbinate and septum, a finding that was confirmed by biopsy. No fungal elements were apparent on biopsy, but the clinical picture was worrisome enough that the patient was urgently brought to the operating room. Specimens from the operating room contained gram-negative rods against a background of coagulative necrosis-findings consistent with a diagnosis of ecthyma gangrenosum. The diagnosis was confirmed by tissue culture.
The lesions found in ecthyma gangrenosum evolve over time. Initially, they are typically painless, round, and erythematous macules. Change can occur rapidly, as a hemorrhagic central focus develops and forms a bulla. These evolve into ulcerated, gangrenous lesions with a central necrotic eschar as they spread outwardly. These lesions arise as the result of perivascular invasion by the causative bacterium into the surrounding dermal and subcutaneous tissues, producing a necrotic vasculitis. Although patients are often found to be bacteremic, this is not universally the case,4,6 and it was not the case in our patient. Edema and necrosis in the perivascular area interrupts the blood supply and leads to ischemic necrosis, with the lesions progressing as described earlier. The presence of multiple lesions at different stages of development is not uncommon.
It is noteworthy in our case that at no time were blood cultures positive for P aeruginosa. Although this finding is seemingly inconsistent with the pathogenic nature of the bacterial invasion of vessels, it is not uncommon, according to other case reports in the literature, only about 50% of these patients are bacteremic. This is an important consideration in light of the necessity to rapidly initiate appropriate treatment, ideally prior to the onset of bacteremia and septicemia, which are poor prognostic factors. Mortality rates vary, mortality has been reported to range from 38 to 77% in immunocompromised patients with septicemia,9 while mortality in patients with nonbacteremic ecthyma gangrenosum has been reported to be 15.4%.10
In conclusion, it is important to recognize the signs of ecthyma gangrenosum in immunocompromised patients as a possible sequela of pseudomonal infection and to consider it as part of the differential diagnosis of necrotic-appearing lesions in the head and neck in order to ensure timely treatment with appropriate antibiotics and aggressive supportive care. The early diagnosis of this entity may obviate the need for aggressive surgical debridement.
From the Department of Otorhinolaryngology-Head and Neck Surgery (Dr. Hekiert and Dr. Palmer) and the Department of Pathology and Laboratory Medicine (Dr. Montone), University of Pennsylvania School of Medicine, Philadelphia, the Department of Otolaryngology-Head &, Neck Surgery, Boston University School of Medicine (Dr. Cohen), and the Department of Otolaryngology, Mount Sinai Medical Center, New York City (Dr. Govindaraj).
Adrianna M. Hekiert, MD, ENT and Allergy Associates, LLP, 56 Union Ave., Somerville, NJ 08876. E-mail: AHekiert@entandallergy.com