Introduction
Invasive fungal infections are the major cause of infection-related mortality in hematopoietic stem cells recipients. Although mucormycosis and aspergillosis are the most frequent fungal infections, coinfection in the same host occurs rarely (1). Furthermore, they can be frequently fatal in immunocompromised patients. Treatment options usually combine medical and surgical approaches, often including extended necrosectomies. Nevertheless, the prognosis of generalized fungal infections is very poor (2).
There have been several case reports describing combined aspergillosis and mucormycosis in various parts of the body, usually with a fatal outcome (3). However, one case report depicts a patient with relapsed acute myeloid leukemia with a combined Aspergillus and Mucorales infection (lungs, brain, spleen and bone) who has been a long time survivor (4). The aforementioned coinfection rarely occurs in healthy individuals. The case of a 22- year- old, otherwise healthy US Marine who sustained extensive soft tissue injuries was published (5). Additionally, Pozo-Laderas et al. (6) published a case of a 17- year- old immunocompetent male who developed this coinfection 11 days after a motorcycle accident.
The coinfection of mucormycosis and aspergillosis should be considered in immunosuppressed patients in order to establish early management that will lead to the improved prognosis of the patient (1).
Case report
A 54-year-old male patient was referred to the Department of Oral Medicine due to the dark red/brownish lesions on the left side of the palate (Figure 1) and vestibular exophytic, later ulcerative, lesion in the area of the teeth 25-27 (Figure 2). The lesion was well demarcated from the surrounding tissue, asymmetric and without hemorrhage.
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He was diagnosed in December 2017 with acute lymphoblastic leukemia (Ph negative and pre-B). He had primary refractory disease and was treated according to protocols HOVON71 (7) and HAM (high dose of cytosine arabinoside and mitoxantrone). During HAM protocol induced aplasia, the patient developed neutropenic colitis and Aspergillus niger was identified in his stool samples. At the time of the oral examination, the patient was treated with intravenous levofloxacin, acyclovir, metronidazole, collistine, meropenem and tigecycline.
Oral lesions appeared sixteen days after the start of the HAM protocol. The patient noticed a swelling of his left cheek. The abovementioned oral lesions were identified upon examination. The orthopantomograph (Figure 3) showed a radiopaque lesion within the left maxillary sinus. Teeth 23, 26 and 27 were avital and tooth 24 was vital. Increased loosening of these teeth was noticed. A severe form of periodontal disease was present. The patient had no pain in that area, except sometimes on palpation. No evident pathological periapical pathology within teeth could be noticed. A CT finding showed a non-homogenous bony structure within the maxillary alveolar ridge.
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Incisional biopsy of a vestibular lesion was taken. Histopathology showed tissue necrosis together with adipose tissue abundant with fungal hyphae and spores. Microbiological evaluation confirmed the presence of Aspergillus fumigatus and Rhizopus genus.
Intravenous posaconazole and amphotericine B were given for the following 28 days and inferior maxillectomy was performed. The maxillary defect was to be reconstructed after the completion of hematological treatment. Meanwhile, the patient was given an obturator. Due to poor general condition of the patient, further treatment of leukemia by the transplantation of alogenous stem cells was not possible. Therefore, the treatment with blinatumomab was initiated. Unfortunately, in June 2018, the patient died due to severe hemorrhagic shock and cardiopulmonary arrest.
Since the coinfection with Aspergillus and Rhizopus extremely rarely occurs in the oral cavity, it leads easily to the diagnostic and therapeutic dilemma.
Discussion
Acute invasive fungal infections in the paranasal sinuses and surrounding tissues are progressive and carry a high death rate in an immunocompromised patient (8). Gode et al. (8) described 37 patients with acute invasive fungal rhinosinusitis and reported that the palatal involvement was significantly associated with death rate.
There are only a few case reports about a concomitant aspergillosis and zygomicosis infection in the orofacial region (1, 2, 9).
Torres-Damas et al. (1) reported a case of a 78-year-old male patient with type 2 diabetes and ketoacidosis who presented with a swelling of the right side of his face, right facial paralysis, ptosis and a necrotic ulcer on the right palate due to the Aspergillus fumigatus and mucormycosis. Chermetz et al. (2) reported the case of a 17-year-old girl with combined aspergillosis and mucormycosis of the right side of her face with frontal maxillary area and upper airway involvement after the treatment of a recurrent glioma.
Maiorano et al. (9) reported a case of aspergillosis and mucormycosis in the patient with stage-IV Castleman disease who presented with a palatal ulceration that progressively involved the palatal mucosa and bone, the paranasal sinuses and the orbit.
Although invasive fungal infections are the major cause of infection-related mortality in hematopoietic stem cells recipients, in this particular patient invasive fungal infection occurred prior to the hematopoietic stem cell transplantation, during the period of post-chemotherapy aplasia.
Differential diagnosis of such cases includes malignancy and because of that, biopsy is mandatory. Due to high frequency of fungal infections in immunocompromised patients, microbiological testing and identification of a causative organism should be performed.
Treatment of these lesions includes surgical resection of the affected tissues as well as intravenous antifungals. Posaconazole or Amphotericin BS is the drug of choice. Caspofungine can be added in resistant cases. Nevertheless, the duration of the treatment is long (median 180 days) and the outcome is unpredictable, favorable in only 40-60% of the cases.
This case report highlights the importance of considering the coinfection with Aspergillus and Rhizopus genera in the orofacial area in patients with leukemia.
