Recently, COVID-19 has affected millions of people worldwide with a wide range of clinical signs ranging from mild to severe and life-threatening pneumonia [12]. In addition, there is an association between the incidence of secondary fungal infection and COVID-19 [3, 13]. In the last 2 years, many kinds of literature have reported a great number of mucormycosis cases, but we summarized the case reports having erosion of the maxilla or other facial bones [1, 4, 6, 7, 13,14,15,16,17,18,19,20,21,22,23] in Table 2.
Inhalation, ingestion, and open wounds are the major routes of mucormycosis infection [14]. Inhalation of fungal spores into the nasal cavity and its inoculation and germination in hypoxic conditions is the initial stage of ROCM infection. After that, extension into the paranasal sinuses, orbit, erosion of the adjacent bone, and involvement of cavernous sinus and intracranium will occur. Also, Rajasekaran et al. reported mucormycosis in diabetic patients without a history of COVID-19, followed by tooth extraction [24]. In these cases, the socket of extracted teeth plays the role of an open wound and is the primary route of this fungal infection. Unlike them, tooth extraction was not the source of infection spread, but the history of maxillary sinus involvement was noteworthy. The infection of an affected maxillary sinus distributes to the adjacent maxillary bone and nearby soft tissues resulting in maxillary bone osteomyelitis.
The most presented clinical sign and symptoms in the recently published papers summarized in Table 2 are fever, headache, sinusitis, nasal blockage, proptosis, unilateral facial pain, numbness, teeth mobility, blurred vision, and other neurologic symptoms depending on the site of involvement. In our case series, the clinical findings were facial swelling and erythema, mucosal and skin redness, swelling or ulceration in the palate, tooth mobility, tooth pain, headache, denuded bone, fistula, tenderness, and skin paresthesia (Table 1). In addition, all of them suffered from maxillary osteomyelitis with involvement of the other adjacent facial bones in the final stage.
Due to the high mortality rate (up to 70%) [10], early diagnosis and treatment of mucormycosis are essential. Besides clinical signs, imaging result has a critical role in detecting the disease and its extension. In the previous studies, CT and magnetic resonance imaging (MRI) were the modalities of choice used for disease evaluation [4, 6, 8, 9, 12, 25, 26]. We also used CBCT, a highly recommended modality for detecting slight osseous changes because of its high bony resolution.
On the other hand, some of our cases in the first step were diagnosed as paranasal sinus mucormycosis, and their treatment strategy focused on these anatomical regions. After a while, some patients referred with the chief complaint of tooth mobility. Hence, in these cases, CBCT was taken for a more accurate investigation of the trabecular and osseous changes in the maxillary and palatal bones. These changes were missed on MRI and soft tissue algorithm of CT images. The maxillary sinus floor may be the first site to be involved, and infection may blow out the maxillary bone and palate following erosion and destruction of the sinus floor. It is interesting to mention that all of these cases had become infected in the Delta peak of the Coronavirus disease, which could indicate that the chance for mucormycosis osteomyelitis may be more in this type of disease.
The most frequent CBCT findings of our cases were mucosal thickening of the paranasal sinuses, bony alterations such as ill-defined radiolucency (bone hypodensity), loss of definition of lamina dura of involved teeth, erosion, breach, or destruction of bony structures, including cortical borders of the maxilla, the zygoma, the inferior rim of the orbit, the palatal bones, the nasal floor, and maxillary sinus walls and sometimes bony sequestra. Other radiographic appearances of infected bones such as “ground glass” and “salt and pepper” were also observed in our cases. In these cases, the counterpart surgical findings were necrotic, fragile, and cheese-like texture of bone.
Similar radiographic findings could also be found in malignant and metastatic bone lesions, osteoradionecrosis, and bisphosphonate-related osteonecrosis. However, metastasis, radiation- and drug-induced osteomyelitis are more common in the mandible. In addition, the patient history is helpful to differentiate these conditions.
It is essential to know; that all clinical findings in patients with a history of COVID-19 are important and should be considered seriously. In addition, in patients with suspected sinus involvement, bone window CT or CBCT imaging is mandatory to detect any subtle osseous changes in the maxilla and adjacent bony structures in the early stages of the disease, which affects the extent of surgery and final prognosis.
Based on the anatomical extension of the mucormycosis infection, Muley et al. graded the CT findings of mucormycosis: grade (1) involvement of maxillary sinus with or without alveolar bone changes, grade (2) grade 1 plus osteolytic changes in the maxilla, nasal involvement, opacification of maxillary or ethmoid sinus, and grade (3) advanced osteolytic changes in the maxilla, nasal cavity, sinus walls and zygoma, and opacification of all paranasal sinuses [3]. Although we had all grading forms in our case series, most of the cases were in the first and third stages.
In addition, detection of hyperdense foci within opacified sinuses is noticeable as CT findings of fungal sinusitis [8], but we did not find such foci in our cases.
Ambereen et al. reported multiple air foci in the marrow spaces in the body and ramus of the mandible on contrast-enhanced CT [7] as mandibular mucormycosis findings.
Mucormycosis is diagnosed definitively through tissue biopsy, which demonstrates large size, non-septate, and thin wall hyphae in right-angle branching [24], but fungal culture is a time-consuming process and may lead to delay in initiation of treatment and thus disease progression [7]. However, the mentioned radiographic findings are non-specific, but the patient’s history, clinical signs, imaging findings, and surgical findings could be helpful in the diagnosis of mucormycosis.
Early recognition and proper treatment, including medical management and aggressive surgical procedure depending on the extension of the involvement, can improve the prognosis and reduce morbidity and mortality rates.
In conclusion, since osteomyelitis is less common in the maxilla because of its high vascularity, radiographic findings, including bony erosion and extra sinus extension, especially in patients with a history of COVID-19 and underlying disease, must be considered as mucormycosis unless otherwise proven. In addition, dentists, maxillofacial radiologists, and surgeons may be the first ones who encounter these patients, so it is essential to know the critical radiographic findings and face this kind of osteomyelitis seriously.
