Fig. 12.1
Hematoxylin- and eosin-stained sinus mucosal tissue at 40x magnification taken from a patient with rhino-orbital-cerebral mucormycosis (ROCM) demonstrating multiple irregularly sized nonseptate hyphae branching at 90° and wider angles (arrows)
Orbital, sinus, and brain imaging using computed tomography (CT) or magnetic resonance imaging (MRI) is imperative. CT often shows sinus opacification (Fig. 12.2) with secondary orbital extension, often into the orbital apex, and sometimes intracranial extension. Bony destruction is common. MRI shows a similar pattern with involved tissue displaying hypo- or isointensity on T1-weighted images, hypointensity to variable intensity on T2-weighted images, and enhancement with contrast (Fig. 12.3a, b) [9, 10]. The MRI appearance relates to the presence of calcium concretions, air, and ferromagnetic elements like manganese, iron, and magnesium [11].
Fig. 12.2
CT scan without contrast in the coronal plane through the central orbits in a patient with left-sided ROCM status post-endoscopic ethmoidectomy demonstrating mucosal thickening suggestive of residual disease (arrow)
Fig. 12.3
Coronal plane MRI through the mid-orbit without (a, T2 weighted) and with (b, T1 weighted) contrast taken from the same patient demonstrated in Fig. 12.2 with left-sided ROCM pre-endoscopic ethmoidectomy. (a): There is left-sided ethmoid and maxillary sinus mucosal thickening (closed arrows) with associated inferior and middle turbinate enlargement (open arrows). (b): Contrast-enhanced scan demonstrates enhancing thickened mucosa (open arrows) directly adjacent to hypointense ischemic mucosa (closed arrows) which is consistent with fungal vascular invasion
Laboratory evaluation often shows an elevated white blood cell count, and blood cultures are rarely positive. Cerebral spinal fluid analysis is typically nonspecific.
Urgent treatment is imperative given the risk of significant morbidity and mortality and involves a multidisciplinary approach, including ophthalmology, otorhinolaryngology, neurosurgery, and infectious disease [12, 13]. Urgent reversal of immunosuppression is key, and this can often be accomplished quickly in patients with ketoacidosis. Infectious disease consultation directs medical and antifungal therapy, and both otorhinolaryngology and ophthalmology work to surgically eradicate infected tissue. Wide local excision of infected tissue should be performed promptly with establishment of sinus drainage. Infected tissue bleeds very little due to ischemia from angioinvasion by fungi and should be excised until bleeding occurs. Many patients require repeated surgical debridement. Surgery frequently includes sinus and orbital exenteration. Orbital exenteration can be lifesaving even with intracranial involvement as this procedure decreases the total fungal load. Early cases can sometimes be successfully treated by surgical debridement alone without loss of the eye [14]. Local intraorbital irrigation of amphotericin B has also been reported to allow local infection control without orbital exenteration [15]. Furthermore, local surgical packing soaked with amphotericin B (1 mg/mL) can also improve outcomes by increasing the concentration of drug available to the infected tissues [16].
Medical management should be initiated urgently and includes intravenous amphotericin B (AmB) as a primary agent. AmB is a polyene antifungal agent that is fungistatic. The therapeutic dosage is 1–1.5 mg/kg/day [17]. Treatment is maintained for weeks to months. Nephrotoxicity is a major treatment limiting side effect. Liposomal amphotericin B has fewer renal side effects and is better tolerated at higher dosages. Occasionally the dosage may increasable beyond the traditional limits to provide fungicidal activity and increased efficacy. Locally administered AmB can and may also improve outcomes as mentioned previously. Newer adjunctive therapies include oral posaconazole, a triazole antifungal agent, and the echinocandins, a new class of antifungal drugs [18] that inhibits the synthesis of glucan in the fungal cell wall [19–21]. Rhizopus oryzae expresses the target enzyme of echinocandins, 1,3-beta-glucan synthase [12]. Both of these newer agents have been used in combination with liposomal AmB as the backbone therapy [12, 21]. Posaconazole has also been used in combination with liposomal AmB in refractory cases [22]. Both daily irrigation and packing of the surgical site can be helpful in the postoperative management of these patients. Daily intraorbital infusion of AmB may also be advantageous and can be readily achieved using a surgically placed catheter [23]. Kohn and Hepler successfully managed eight patients with limited debridement, intravenous AmB, and daily irrigation of the orbital tissues and involved paranasal sinuses with AmB (1 mg/cc). All eight patients avoided exenteration and retained good vision [14].
Hyperbaric oxygen therapy is another efficacious but adjunctive treatment modality. The exact mechanism of action is not well understood and is most likely multifactorial [24]. Hyperbaric oxygen treatment helps to counteract the tissue acidosis and ischemia caused by fungal angioinvasion by increasing the local oxygen tension. Additionally, the increased oxygen tension improves the action of macrophages and neutrophils and augments the effectiveness of AmB [24–27].
The mortality rate of ROCM ranges from 50 to 90% [9]. Patient prognosis depends upon a multitude of factors, but the most important is the successful reversal of the underlying immunosuppression that precipitated the infection. Therefore, patients with diabetes in ketoacidosis have the best prognosis given that controlling their blood sugar and correcting the metabolic acidosis resolve their immunosuppression. With intracranial extension, the mortality rate approaches 90% [27, 28]. Early diagnosis and prompt treatment improve the chances for survival. Even patients with cavernous sinus invasion can survive with aggressive surgical treatment including sino-orbital as well as cavernous sinus exenteration.
Aspergillosis
Aspergillosis is caused by fungi in the order Eurotiales and genus Aspergillus [2], a group of ubiquitous filamentous fungi found in decaying vegetation and soil with typically low manifest intrinsic virulence. Similar to mucormycosis, the fungus usually invades the orbit after the inhalation of spores and the spread of infection through an adjacent paranasal sinus. Sino-orbital aspergillosis can be invasive or noninvasive and can affect both immunocompromised and immunocompetent hosts. The three species most commonly involved in orbital infections are Aspergillus flavus , Aspergillus fumigatus , and Aspergillus niger .
Noninvasive variants include localized sinus aspergillomas and allergic fungal sinusitis. Aspergillomas are found in immunocompetent patients with nonatopic disease. These fungus balls are usually caused by Aspergillus fumigatus. Allergic fungal sinusitis occurs in immunocompetent young adults with a history of asthma, atopic disease, polyps, chronic sinusitis, and aspirin sensitivity. Symptoms include nasal congestion, pain, and rhinorrhea. Serum IgE is often increased. CT and MRI reveal expanded and opacified sinuses that can mimic a neoplastic process. On MRI, the opacities are usually isointense or hypointense on T1 with a more marked decrease in signal intensity on T2. Orbital involvement occurs in up to 17% of patients and is more often caused by Bipolaris species than by Aspergillus species. Treatment includes surgical debridement, aeration of the sinuses, and both topical and systemic corticosteroids. Systemic antifungals are not required.
Invasive sino-orbital aspergillosis generally occurs in immunocompromised patients. The lungs are the most common site of infection, but the paranasal sinuses, orbit, and brain may also be involved. Risk factors include an underlying hematologic malignancy such as leukemia or lymphoma, organ transplantation, diabetes, and acquired immunodeficiency syndrome (AIDS). Before modern therapies for HIV were available, sino-orbital aspergillosis was a major fatal complication of AIDS.
Presenting signs include the abrupt onset of proptosis, orbital pain, and visual loss. Inflammatory signs may be minimal. Imaging studies are helpful in establishing a diagnosis. On CT, soft tissue masses are heterogeneous due to the presence of iron, manganese, or calcium (Fig. 12.4). Bony erosion can occur due to the pressure effect from the mass and the presence of inflammatory mediators. MR imaging reveals sino-orbital contrast-enhancing masses that appear hypointense on both T1- and T2-weighted images with surrounding mucosal inflammation (Fig. 12.5a–c). In contradistinction, bacterial infections and neoplasms are more often hyperintense on T2-weighted imaging.
