Mucormycosis and Aspergillosis Infection Following Maxillofacial Trauma: Case Report

Abstract

An invasive fungal infection caused by saprophytic and aerobic fungi Rhizopus, Rhizomucor, and Cunninghamella genera of the family Mucoraceae is known as Mucormycosis. Typically, Mucormycosis manifests in patients with conditions like uncontrolled diabetes, renal failure, patients receiving chemotherapy, long term steroid therapy or patients who are immunocompromised such as Acquired Immuno Deficiency Syndrome. The authors report a case of mixed opportunistic fungal infection of Mucormycosis and Aspergillosis following maxillofacial trauma that was treated by both medical and surgical line of management.

Introduction

Among the fungal infections, Candidiasis, aspergillosis and mucormycosis stand as first, second and third most common opportunistic fungal infections. An invasive fungal infection caused by saprophytic and aerobic fungi Rhizopus, Rhizomucor, and Cunninghamella genera of the family Mucoraceae is known as Mucormycosis. In 1885, Paltauf was first to describe Mucormycosis [1].

Mucormycosis also known as zygomycosis is considered one the most lethal forms of rapidly progressing human fungal infections that spreads rapidly from the naso-maxillary complex region [2]. Typically, Mucormycosis manifests in patients with conditions like uncontrolled diabetes, renal failure, patients receiving chemotherapy, long term steroid therapy or patients who are immunocompromised such as Acquired Immuno Deficiency Syndrome. Mucormycosis has no definite sex or race predilection with a mortality rate of 50–80% [3].

The authors report a case of mixed opportunistic fungal infection of Mucormycosis and Aspergillosis following maxillofacial trauma that was treated by both medical and surgical line of management.

Case Report

A 75 year old patient reported to outpatient Department of Oral and Maxillofacial Surgery, Dental College, Pune with a painful non-healing wound over left infra-orbital region since 2 months. Patient gave a history of maxillofacial trauma 2 months back which was not addressed by any medical professional. Patient complained of suppurative discharge and foul odour from his mouth along with difficulty in mastication while chewing food. Patient had no history of past medical history contributing to the case like diabetes mellitus, tuberculosis, asthma or any previous hospitalisation. Patient gave no history of COVID-19 infection.

Extra-oral examination revealed an unhealed wound in left infra-orbital region as shown in Fig. 1 while Intra-oral examination revealed exposed necrotic bone involving the alveolar bone of anterior maxillary region along with anterior nasal spine and hard palate covered with a yellowish purulent slough as shown in Fig. 2. On palpation, the maxillary arch was mobile in transverse and superoinferior directions. Lymph nodes were neither palpable nor tender. The clinical evaluation was suggestive of a deep seated fungal infection of maxilla.

Fig. 1.

Depicts pre-operative view of non healing wound over left infra-orbital region

Fig. 2.

Depicts intra-oral pre-operative view

Haematological investigations revealed a normal fasting blood sugar level and haemoglobin levels and HbA1c with the normal range. Orthopantomogram (OPG) revealed moth eaten appearance of bone. Computed Tomography scan of paranasal sinus revealed mild soft tissue thickening in bilateral maxillary sinuses. Bony erosion of all walls of left maxillary sinus with herniation of left orbital fat, floor of right maxillary sinus, left zygomatic process with undisplaced fracture, hard palate and superior alveolar arch with Sinopalatal and nasopalatal fistulae formation.

Cytological smear and incisional biopsy were taken from alveolar and palatal regions. KOH mounting was suggestive of plenty of hyaline broad aseptate fungal hyphae with wide angled branching and sporulation formation suggestive of Mucorales. Calcofluor staining was suggestive of plenty of fluorescent broad aseptate fungal hyphae with wide angled branching suggestive of Mucorales.

On the basis of clinical, radiological and histopathological findings, the final diagnosis of rhinomaxillary mucormycosis was made. Systemic antifungal therapy with IV Amphotericin B was administered to patient and Subtotal Maxillectomy was done along with debridement of the complete nasal vault as shown in Figs. 3, 4 and 5. The specimen of subtotal maxillectomy of approximately 6 × 7 × 3.5 cm comprising of anterior and lateral walls of maxilla, hard palate and alveolar process was sent for histopathological evaluation. Maxilla showed 11 intact teeth. Lateral ends of maxilla and hard palate appeared blackened and necrotic. Bone was soft and friable. Central portion appeared discoloured and loosening of teeth was noted without any soft tissue attachments.

Fig. 3.

Depicts subtotal matxillectomy

Fig. 4.

Depicts subtotal matxillectomy

Fig. 5.

Depicts post-operative view

Bony tissue from central portion of maxilla, left and right lateral ends of maxilla showed foci of necrosis and acute to chronic inflammatory exudate along with broad based, non-septate hyphae suggestive of mucormycosis. Few narrow hyphae suggestive of Aspergillosis species were also noted. Angioinvasion along with bony invasion by fungal elements were identified. However, there was no evidence of Koch’s or malignancy. The excised specimen sent for histopathological evaluation confirmed our diagnosis of rhinomaxillary mucormycosis along with Aspergillosis as shown in Figs. 6, 7 and 8. Patient was followed up on regular basis and the healing was uneventful.

Fig. 6.

Depicts histopathological view of fungal strains of mucorales and aspergillus

Fig. 7.

Depicts histopathological view of fungal strains of mucorales and aspergillus

Fig. 8.

Depicts histopathological view of fungal strains of mucorales and aspergillus

Discussion

An individual can get infected by the Mucorales fungi through various routes such as inhalation, ingestion or traumatic inoculation in the oral and nasal pharyngeal mucosa of healthy patients. Mucormycosis may present in multiple clinical manifestations like cutaneous, gastrointestinal, pulmonary and disseminated forms. However, Mucormycosis involving the nose, paranasal sinuses, orbit and central nervous system are the most common and have been subclassified as rhinomaxillary and rhinocerebralorbital mucormycosis [4].

Infection causing necrosis of bone is less common in maxilla due to rich vascularity. In maxillary osteomyelitis, diabetes mellitus usually acts as a propagating factor. The presence of Ketone bodies favours the suitable environment for the growth of fungus [5]. Patients with uncontrolled diabetes mellitus are immunocompromised due to ill effects of an environment by elevated hyperglycaemic index which alters the immune function such as damage to the function of neutrophils, weakening of antioxidant system and humoral immunity [6]^. High glucose levels, excessive formation of ketone bodies, low pH environment, reduced oxygen and high iron levels play a role of paramount importance in germination and invasive growth of acquired fungal spores. Vascular invasion of the vegetative forms into vessels forms thrombus which leads to ischemic infarcts and subsequently causing necrosis of adjacent tissues [7]. However, our patient in this case report was neither diabetic nor immunocompromised.

Mucormycosis is characterized by presence of plenty large approximately 5–30 μm. These are thinned walled fungi that lack septa and branch at right angles [8]. These typical histological features of mucormycosis were observed in the present case.

The crucial step for a successful outcome in treating mucormycosis is an early initiation of treatment after a prompt diagnosis. The most effective method in the primary medical management for such opportunistic infections is to aggressively control any underlying predisposing factors like blood glucose control, tapering of steroids and reducing or stopping any immunosuppressive drugs. However, surgical management should involve radical resection such as partial or total maxillectomy, mandibulectomy and orbital exenteration [9].

Apart from CBC with emphasis on the neutrophil count, Monitoring Iron levels is of equal significance. An indicator of organism’s virulence are high ferritin levels and low total iron binding capacity.

Amphotericin B deoxycholate along with its lipid presentation is widely used as treatment of choice for mucormycosis due to it low nephrotoxicity [10]. This polyene agent binds to sterols and forms trans-membrane channels which forms pores and disrupts the fungal cell wall synthesis. In the present case report, amphotericin B deoxycholate was administered following the surgical removal of necrotic maxilla. Conventional AmB (1–1.5 mg/kg/d IV) can be used but the dose should be reduced if the serum creatinine levels exceeds 3.0 mg/100 mL or serum nitrogen levels exceeds 40 mg/100 mL. Liposomal AmB alters the biodistribution and increases circulation time making itself available in greater concentrations in infected and inflamed tissues. The recommended dose of liposomal AmB is 3–5 mg/kg/d prepared as a 1 mg/mL infusion and delivered at a rate of 2.5 mg/kg/h.

Surgical debridement helps to prevent the systemic spread of infection by removing the diseased tissue with focus of infection. Hyperbaric oxygen therapy may have an effect in patients who show no improvement despite optimal medical and surgical therapies.

Other therapies may include nebulized/local irrigation with AmB, topical hydrogen peroxide, leukocyte transfusions, treatment with interferon-gamma, the use of GM-CSF, G-CSF, or polyvalent immunoglobulin, and the combination of AmB with flucytosine, rifampin, or fluconazole [10].

Conclusion

The case report aims to highlight the importance of considering mucormycosis as a possible diagnosis in spontaneous necrotic soft tissue lesions of the face following maxillofacial trauma. The prognosis is poor usually but prompt diagnosis and meticulous medical and surgical management, prognosis can be improved with a hope to increase patient’s survival rate.

Declarations

Conflict of interests

Authors declare that they don’t have any conflict of interest.

Ethical Approval

The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work.

Informed Consent

The authors confirm that informed consent from the patients and their attenders was taken before their inclusion.

Consent to Participate

The authors confirm that informed consent from the patients and their attenders was taken before their inclusion.

Consent for Publication

Informed consent for publication from the participants was obtained.