Rhino-orbito-cerebral mucormycosis is the most common form of the disease prevailing in the expanding immunocompromised population.

The management of such infections is a challenging process marked by rapid tissue necrosis as a result of vascular invasion and even patient’s death if the fungal patterns are not identified early.

Our patient is a 35-year-old male with poorly controlled diabetes who was hospitalized for decompensated diabetes. Clinical evaluation finds left periorbital edema associated with fever. Despite the antibiotic therapy, his symptoms progressed as he developed periorbital tissue necrosis, confusion, and deterioration of the general status

Complete blood count result was significant for leukocytosis of 13×109 per liter.

An orbital multislice computed tomography (CT) demonstrated left maxillary and ethmoidal sinusitis with parietal defect, diffuse fat stranding, and soft tissue thickening. The infection spread to the medial orbit and the orbital apex through the nasolacrimal duct (Figure 1).

An orbital magnetic resonance imaging (MRI) 1.5 Tesla confirmed the previously described soft tissue and sinus lesions on T1-weighted images (Figure 2A and Figure 2B) and contributed to a better assessment of the extra-ocular muscles and the infectious collection itself especially on T2-weighted fat-saturated axial images (Figure 2C, Figure 2D, Figure 2E) showing a partitioned ill-defined destructive collection of the left maxillary and ethmoid sinuses extending to the orbital apex and orbital gyri resulting in fronto-temporal collections with diffusion restriction (Figure 3A and Figure 3B) encasement of the optic nerve on CISS (Figure 3C), and peripheral enhancement of these collections on post-contrast fat-saturated T1-weighted images (Figure 4A and Figure 4B).

Magnetic resonance angiography (Figure 4C) confirmed the thrombosis of both left cavernous sinus and internal carotid artery responsible of striatocapsular and parietal infarcts seen on the previous sequences.

The patient continued to deteriorate despite aggressive therapy.

A specimen of the biopsy of the necrotic eyelid was sent to the Mycology Laboratory in a sterile tube. Direct examination of a fragment in physiologic water showed multiple hyalin large irregular and non-septate hyphae. This was highly suspicious of a mold. The other fragment was put into culture in three media: sabouraud, sabouraud with chloramphenicol, and sabouraud with chloramphenicol and cycloheximide. The three media were incubated in 27°C and 37°C in two series. Colonies rapidly grew on cultures 72 hours later in all tubes. Microscopic features were characteristics of Mucorales, first white then turning black with cottony texture (Figure 5A).

Cellophane flag method was performed in lactophenol blue solution. It showed sporangiophores arising from root-like rhizoids with numerous spores. This was compatible with the microscopic aspect of Rhizopus sp. (Figure 5B). Parenteral Amphotericin B was then initiated.

Mucormycosis is an acute and rapidly progressive fungal disease first described in 1943 by Gregory [1]. The main responsible for human infection are Rhizopus, Mucor, and Absidia.

This opportunistic infection mainly affects immunosuppressed patients, more particularly poorly balanced diabetics [2] about 70% of rhinocerebral mucormycosis cases [3].

Acidosis is the main promoting factor of fungal outbreaks as it increases the level of free iron necessary for their growth. Moreover, studies revealed that Glucose-regulated protein 78 (GRP78) was a putative endothelial cell receptor for rhizopus and other Mucorales necessary for endocytosis and subsequent endothelial cell damage. Interestingly, GRP78 expression involved both iron and glucose [4].

Five clinical forms of mucormycosis are recognized: rhino-orbito-cerebral, gastrointestinal, pulmonary, cutaneous, and disseminated [5].

The rhino-cerebral form is the most common and deadly form. The infection originates in the nasal cavity and then spreads to the paranasal sinuses and medial orbit, to the orbital apex through nasolacrimal duct reaching the brain with spread to the cavernous sinus and internal carotid artery which may result in hemorrhage or thrombosis.

The clinical presentation is not specific and can range from a subtle facial swelling to tissue necrosis with associated fever, headache, reduced visual acuity, and neurological deficit.

Magnetic resonance imaging has a major role in the diagnosis of rhino-cerebral mucormycosis, for early detection of orbital and intracranial complications [6].

Lesions can show variable MR signal characteristics on T1 and T2-weighted images, variable contrast enhancement, and restriction of diffusion. Contrast-enhanced T1-weighted images are helpful in delineating the orbital and intracranial spread [6],[7]. Some findings can be helpful in differentiating mucormycosis from bacterial sinusitis such as the non-enhancement of the involved mucosal tissue on contrast MRI known as the “black turbinate” sign. This phenomenon is indicative of mucosal ischemia secondary to fungal vascular damage. Magnetic resonance spectroscopy has been reported to help differentiate central nervous system (CNS) mucormycosis from bacterial cerebritis, but this modality still needs further validation [7].

Computed tomography scan shows evidence of bony destruction in sinus walls, the turbinate, orbital wall, skull base, and hard palate in 40% of rhino-orbito-cerebral mucormycosis (ROCM) cases and demonstrates almost the same findings as MRI with less sensitivity, such as soft tissue opacification of the sinuses with hyperdense material, nodular mucosal thickening [8].

Imaging discloses the most fearsome complications such as brain infarction and hemorrhage due to diffuse fungal vascular invasion which weakens the walls of blood vessels forming aneurysms and contributes to intravascular thrombi formation. This has been previously described in a study by Lowe and Hudson [9].

We can also find orbital apex syndrome defined as a damage of multiple orbital structures like motor nerves, optic nerve, third cranial nerve paralysis, and proptosis due to venous congestion secondary to cavernous thrombosis, meningitis, brain abscesses, Garcin syndrome mimicking diseases like tuberculosis or neoplasms and finally facial deformity [9].

The differential diagnosis of ROCM includes infectious diseases like tuberculosis, aspergillosis, and other fungal diseases, but also non-infectious inflammatory diseases, such as ocular Sweet’s syndrome, idiopathic orbital inflammatory syndrome, and intraorbital masses, including lymphoma, ocular leukemia, and metastases [4].

Mucormycosis management requires both surgical and medical interventions. Surgical debridement was associated with improved survival in several case series [4]. As for antifungal treatment, amphotericin B, more particularly the liposomal formulation, remains the mainstay therapeutic agent against mucormycosis, but its usage is limited due to nephrotoxicity which makes Posaconazole, a potent and wide-spectrum triazole agent, an attractive alternative for the patient, who is intolerant, or even refractory to amphotericin B [2].

Literature review reported some adjunctive therapeutic modalities like hyperbaric oxygen (HBO) to increase survival rate in diabetic patients (94%) treated with HBO [10].

In our case, the imaging findings were suggestive of an important bony destruction, ethmoido-maxillary abscess, with orbital invasion resulting in class 5 cellulitis with neurological complications manifested in optic neuritis, meningo-encephalo-vasculitis with mycotic thromboembolism.

High clinical-radiological suspicion coupled with early identification is key to the treatment of mucormycosis as it involves a combination of surgical interventions with adjunctive aggressive antifungal therapy [11].

Prognosis is known to be very poor and mortality very high in rhino-cerebral mucormycosis with intracranial extension [12].

The purpose behind this report is to foreground the importance of MRI imaging modality in making an early diagnosis and detecting complications, CT scan in detecting any bony defects as complimentary to MRI, and finally culture of specimens allows identification to the genus and species level, and eventually antifungal susceptibility testing.

The spread of mucormycosis due to late diagnosis results in an extensive encephalitis with severe vascular complications; thrombosis of the entire internal carotid artery and cavernous sinus, and clear damage of the orbit, ethmoid, and maxillary sinuses. Such impairment is worth displaying as part of raising awareness about opportunistic infection management in immune suppressed population.