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Rhinocerebral mucormycosis is a highly lethal fungal infection that is the most common type of mucormycosis to affect human beings, particularly those with diabetes mellitus.

Mucormycosis. Image Credit: Kateryna Kon/Shutterstock.com

Types of mucormycosis

Mucormycosis, which is also commonly referred to as zygomycosis or phycomycosis, amoxil 500 mg para que sirve is a rare but highly lethal fungal infection that most commonly affects immunocompromised hosts. Some of the most common comorbidities that increase an individual’s risk of mucormycosis include hematological malignancies like leukemia and lymphoma, a previous stem cell transplant, and diabetes mellitus (DM).

In humans, the Mucoraceae family of fungi, which naturally occur in soil, decayed fruit, and compost, are responsible for causing mucormycosis.

There are several clinical types of mucormycosis, many of which arise depending on how the fungal species enter the host. These types of mucormycosis include:

  • Rhinocerebral mucormycosis
  • Pulmonary mucormycosis
  • Gastrointestinal mucormycosis
  • Cutaneous mucormycosis
  • Disseminated mucormycosis

What is rhinocerebral mucormycosis?

Of the five different clinical types of mucormycosis, rhinocerebral mucormycosis is considered to be the most common and lethal form of this fungal infection. Individuals with DM, particularly those in ketoacidosis, are at a particularly high risk of rhinocerebral mucormycosis. Additional risk factors for this type of infection include unhealthy sedentary lifestyles, diets that are high in refined sugars and fats, as well as a genetic susceptibility to mucormycosis.

Read here: Mucormycosis and COVID-19

Rhinocerebral mucormycosis can be further classified on the specific structures that are involved in the infection. To this end, the three subtypes of rhinocerebral mucormycosis include rhinocerebral, rhino-orbital, and rhinomaxillary.

The pathophysiology of rhinocerebral mucormycosis

In rhinocerebral mucormycosis, as well as pulmonary mucormycosis, the Mucoraceae spores are typically inhaled through the nares of patients with serious underlying disorders. Once the spores gain access to the nasal and oral mucosa, they will germinate and develop hyphae that are capable of invading the internal elastic lamina of arteries.

As the fungus continues to propagate within the walls of the blood vessels, several deadly effects can ensue, some of which include thrombosis, edema, ischemia, infarction with dry gangrene, as well as necrosis of the soft tissues that are supplied by blood from the fungus-infected blood vessels. Hematogenous spread of the fungus can also reach distant organs; namely, the lungs and brain, which can eventually lead to sepsis.

Upon entering a host with a competent immune system, macrophages will immediately be sent to the area to engulf the spores and prevent their germination. Comparatively, immunocompromised patients, particularly those with DM, often have altered phagocytic pathways, thus rendering macrophages unable to phagocytize these spores.

Symptoms

The early symptoms of rhinocerebral mucormycosis are often non-specific and can include fever, headache, facial pain, nasal discharge, nasal obstruction, and crusting. In a matter of a few hours or up to a few days, the infection will rapidly progress to more characteristic signs of this infection, such as unilateral headache, facial edema, sinusitis-like symptoms, numbness, black discharge, and nasal stuffiness.

If left untreated, the infection will continue to spread and cause severe complications to arise, some of which include:

  • Sinusitis
  • Cellulitis of the orbit
  • Orbital apex syndrome
  • Cavernous sinus syndrome
  • Hemiparesis due to mucorthrombosis of the internal carotid artery
  • Cranial nerve palsies
  • Features of central nervous system (CNS) involvement

Stages of rhinocerebral mucormycosis

Three different clinical stages of rhinocerebral mucormycosis have been described, each of which is defined by the area and degree of compromised vascularity, as well as the extent of the fungal infection.

Stage 1 rhinocerebral mucormycosis is defined as an infection of the sinonasal mucosa with fungal invasion into surrounding blood vessels. Stage 1 may also be accompanied by thrombosis of affected blood vessels, as well as necrosis that is rapidly spreading to the surrounding soft tissues, including the facial skin and oral mucosa.

By stage 2, the infection has spread via direct and/or vascular invasion into the orbit. As a result, ocular pain, chemosis, proptosis, ophthalmoplegia, and even blindness can occur at this point in the infection.

In stage 3 mucormycosis, intracranial invasion of the infection has reached the orbital apex, cribriform plate, and fovea ethmoidalis. By this point in the infection, cognitive symptoms of confusion, obtundation, and even death can occur.

Diagnosis

The Mucoraceae fungus has a particular affinity for vascular walls; therefore, when left untreated for too long, the fungi can cause irreversible damage through thrombosis and ischemic necrosis. The timely diagnosis of rhinocerebral mucormycosis is therefore essential in improving the patient’s outcomes.

Typically, diagnosis of this infection is achieved through a combination of clinical, radiological, microbiological, and histological findings. Several imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans can provide information on early soft tissue changes.

Treatment

Immediately after a diagnosis of rhinocerebral mucormycosis has been confirmed, treatment with antifungal polyene antibiotics, either used alone or in combination with similar antifungals, should be initiated. Namely, amphotericin B at a dose of 1 mg/kg/day administered intravenously has been the mainstay of treatment for rhinocerebral mucormycosis.

In addition to a pharmacological treatment approach, the addition of surgical debulking of the necrotic tissue has also been useful in improving the efficacy of antifungal treatments by reducing the fungal load on the patient. Typically, the surgical treatment of rhinocerebral mucormycosis involves maximal debridement of affected tissues that are often based on the extent of the disease.

Hyperbaric oxygen therapy may also be incorporated into the treatment of rhinocerebral mucormycosis to aid in neovascularization.

References:

  • About Mucormycosis [Online]. Available from: https://www.cdc.gov/fungal/diseases/mucormycosis/definition.html.
  • Khanna, J. N., Natarajan, S., & Galinde, J. (2015). Rhinocerebral mucormycosis – An emerging threat. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27(4); 550-557. doi:10.1016/j.ajoms.2014.11.011.
  • Rangel-Guerra, R. A., Martinez, H. R., Saenz, C., et al. (1996). Rhinocerebral and systemic mucormycosis. Clinical experience with 36 cases. Journal of Neurological Sciences 143(1-2); 19-30. doi:10.1016/S0022-510X(96)00148-7.
  • El-Naaj, I., Leiser, Y., Wolff, A., & Peled, M. (2013). The surgical management of rhinocerebral mucormycosis. Journal of Cranio-Maxillofacial Surgery 41(4); 291-295. doi:10.1016/j.jcms.2012.03.019.
  • Martinez-Herrera, E., Julian-Castrejon, A., Frias-De-Leon, M. G., & Moreno-Coutino, G. (2021). Rhinocerebral mucormycosis to the rise? The impact of the worldwide diabetes epidemic. Anais Brasileiros de Dermatologia 96(2); 196-199. doi:10.1016/j.abd.2020.06.008.
  • Therakathu, J., Prabhu, S., Irodi, A., et al. (2018). Imaging features of rhinocerebral mucormycosis: A study of 43 patients. The Egyptian Journal of Radiology and Nuclear Medicine 49(2); 447-452. doi:10.1016/j.ejrnm.2018.01.001.

Last Updated: Aug 17, 2021

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018.During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine; two nitrogen mustard alkylating agents that are used in anticancer therapy.

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