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| REVIEW ARTICLE |
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| Year : 2018 | Volume
: 15
| Issue : 1 | Page : 6-10 |
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Mucormycosis of the head and neck
Santosh Kumar Swain1, Mahesh Chandra Sahu2, Manash Ranjan Baisakh3
1 Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha, “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Directorate of Medical Research, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
3 Department of Pathology, Apollo Hospital, Bhubaneswar, Odisha, India
| Date of Web Publication | 2-Apr-2018 |
Correspondence Address:
Santosh Kumar Swain
Department of Otorhinolaryngology, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar - 751 003, Odisha
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/am.am_12_18
Mucormycosis is a rare clinical entity, often affecting immunocompromised patients. It is often an emergency situation and has poor prognosis. In head-and-neck region, mucormycosis spread by angioinvasion and may present with sinonasal, rhino-orbito-cerebral, palatal, cutaneous, or disseminated involvement. Prompt diagnosis with tissue biopsy, local control of the disease by aggressive surgical debridement, and appropriate systemic antifungal treatment improve the prognosis and survival of the patients. Treatment of mucormycosis needs antifungal agents such as amphotericin B and wide surgical debridement. Early diagnosis and treatment is often needed for survival of the patients. This paper will review the etiopathogenesis, epidemiology, clinical presentations, investigations, and treatment of the dreaded fungal infections called mucormycosis in the head-and-neck region. Keywords: Amphotericin B, head and neck, mucormycosis, surgical debridement
How to cite this article:
Swain SK, Sahu MC, Baisakh MR. Mucormycosis of the head and neck. Apollo Med 2018;15:6-10 |
| Introduction | |  |
Mucormycosis is a rare and dreaded clinical entity caused by a fungus of the order Mucorales. It is a life-threatening infection which has high morbidity and mortality. It is an opportunistic fungal infection. Mucormycosis was first described by previous literature.[1] It is also known as zygomycosis, harmless to a healthy person but fatal in immunocompromised patients. Most commonly Rhizopus species are causative organisms for the mucormycosis. Diabetic ketoacidosis and neutropenia are common predisposing conditions. This life-threatening infection has a remarkable affinity for arteries. They have a tendency for spreading into vessels and lymphatics causing formation of Mucor thrombi and leads to ischemia and infarction of the affected tissue. This fungus often dissects internal elastic lamina from the media of the blood vessels, resulting extensive damage to the endothelium and leads to thrombosis. Mucormycosis is classified into different forms as per anatomic sites such as rhinomaxillary, central nervous system (CNS), cutaneous, pulmonary, disseminated, and miscellaneous. The rhino-orbito-cerebral is the most common variety of mucormycosis.[2] In clinical practice common types of mucormycosis, infections are paranasal sinuses (39%), lungs (24%), skin (19%), brain (9%), and gastrointestinal (7%) forms and other miscellaneous types are extremely rare.[3] The involvement of the head-and-neck region is often lethal and leads to intracranial invasion with high mortality. The ideal treatment needs the correction of underlying risk factors, antifungal treatment with amphotericin B, and aggressive surgery. This article will review the etiopathogenesis, epidemiology, clinical presentations, investigations, and treatment of mucormycosis specifically affecting the head-and-neck region.
| Epidemiology | | |
The mucormycosis has been reported from all parts of the world. After aspergillosis and candidiasis, the mucormycosis is the third most invasive fungal infection in the human being. Although mucormycosis has been reported from all parts of the world, this infection is more common in tropical and subtropical countries. A few studies show seasonal variations in mucormycosis. In one study from Israel, there are 16 out of 19 cases of rhino-orbito-cerebral mucormycosis occurred between August and November.[4] In another study from Japan, a similar type of seasonal variation among hematology patients showing six out of the seven cases of mucormycosis in between August and September.[5] Out of the five clinical types of mucormycosis, rhino-orbito-cerebral mucormycosis is the most common form (44%–49%), followed by cutaneous (10%–16%), pulmonary (10%–11%), disseminated form (6%–11.6%), and gastrointestinal (2%–11%) presentations.[6]
| Etiopathology | | |
The class Zygomycetes is classified into two orders: Mucorales and Entomophthorales. These two orders give rise to two different infections. Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea) cause mucormycosis which is an angioinvasive infection. Mucormycosis is caused by saprophytic fungi of many genera related to Phycomycetes (Zygomycetes) and order Mucorales.[7] The fungus has a great affinity toward to arteries and adheres to the arterial wall. It grows along the internal elastic lamina of the blood vessels causing thrombosis, ischemia, and necrosis of the surrounding tissues. Mucorales are abundantly seen in soil, decaying vegetables, animal excreta, and foodstuffs. They grow rapidly in humid environment and the sporangiospores are released into the environment and spread as airborne propagules. The incidence of mucormycosis in head-and-neck region is not related to sex or age.[8] There are three different modes of transmission such as inhalation, ingestion, and percutaneous introduction spores of mucormycosis. There is no person-to-person spread of the mucormycosis. In India, the air-borne spores are more during transition from summer to rainy season as it may be ideal for fungal growth.[9] The Mucorales hyphae are broad (5–20 μm), nonseptate, thin-walled, branched at right angles, and twisted. It can be demonstrated histologically by hematoxylin and eosin, periodic acid–Schiff reaction, or by Grocott-Gomori's methenamine silver nitrate staining. These fungi possess an enzyme called ketone reductase, which facilitates the organisms to grow rapidly in hyperglycemic and acidic media.[10] The normal body physiology often inhibits growth by controlling pH and glucose. However, in hyperglycemic and acidic states such as diabetic ketoacidosis, this environment promotes the growth of these fungi.[11] Iron also enhances the pathogenicity and growth of these fungi, particularly those patients are taking deferoxamine. These fungi possess siderophore which increases iron uptake, which stimulates tissue invasion.[12] Invasive mucormycosis is often associated with uncontrolled diabetes mellitus and other severe immunodeficiencies with abnormality in cell-mediated immune system. Different risk factors for mucormycosis are cytotoxic chemotherapy, organ transplantation, and acquired immunodeficiency syndrome. The infection is transmitted by inhalation of sporangiospores or by direct contamination of the skin wounds, particularly in burns. In the head-and-neck region, the nasal cavity and paranasal sinuses are the most common sites for primary infections of mucormycosis.[13]
| Clinical Presentations | | |
The underlying medical diseases and associated risk factors often decide the severity of mucormycosis. All species of Mucorales give rise to almost similar clinical presentations.[14] Mucormycosis of the head-and-neck region often begins in the nose and paranasal sinuses or palate and progress to the orbit or brain if not treated early. Rhino-orbito-cerebral mucormycosis is the most common type of this fungus infection. Rhizopus spp. is seen in 70% cases of culture-positive mucormycosis.[5] Clinical presentations include headache, fever, lethargy, orbital pain, sudden loss of vision, proptosis, ophthalmoplegia, dilated pupil, chemosis, corneal anesthesia, sinusitis, epistaxis, facial palsy, periorbital cellulitis, sensory loss in trigeminal nerve distribution, and seizures. Thrombosis in cavernous sinus and internal carotid artery are also two reported complications.[15] Rhino-orbito-cerebral mucormycosis is often seen in patients of diabetic ketoacidosis or poorly controlled diabetes mellitus, leukemia, beta thalassemia, trauma, burn, organ transplant, deferoxamine therapy, and even sinonasal polyposis.[16] Black necrotic eschar is often seen in nasal mucosa or palate [Figure 1]. The indicators for poor prognosis are delayed treatment, intracranial involvement with hemiplegia or hemiparesis, bilateral sinus involvement, facial necrosis [Figure 2], orbital involvement, underlying leukemia, or deferoxamine therapy.[17] Disseminated mucormycosis affects two or more noncontiguous organs of the body. Hematological diseases such as leukemia or lymphoma with neutropenic status often lead to disseminated mucormycosis. The mortality rate is very high in disseminated mucormycosis.
| Investigations | | |
The timely diagnosis needs proper identification of the fungus in tissue with confirmation by culture. However, unfortunately, culture often results no growth. Diagnostic endoscopic imaging is helpful for diagnosis of rhino-orbito-cerebral infections. Computed tomography (CT) or magnetic resonance imaging is useful to find out intracranial and sinus spread of infections.[11] In case of lungs involvement, chest X-ray or CT scan often demonstrates the fungal invasions. For intracranial involvement, CT scan of the brain often shows poorly enhancing lesions, whereas cerebrospinal fluid (CSF) studies are often normal. Tissue biopsy is usually confirmatory for the diagnosis for mucormycosis.[18] Severe mucormycosis is often a clinical diagnosis where the treatment should be started as early as possible before doing microbiological confirmation for getting optimum clinical outcome.[19]Mucorales are ubiquitous saprophytes seen in decaying organic matter and soil. These fungi grow in routine fungal culture media such as Sabouraud Dextrose Agar, Inhibitory Mold Agar, or Potato Agar at a wide range of temperature between 25°C and 55°C.[20] Other microscopic techniques such as 20% potassium hydroxide, Gomori's Methenamine silver staining, periodic acid–Schiff, and hematoxylin and eosin staining are very useful for direct microscopic detection of Mucorales. Mucorales are usually described as broad, ribbon-like, aseptate hyphae with right-angled branching hyphae [Figure 3]. Angioinvasion with surrounding tissue infarction is often seen in histopathological picture. Polymerase chain reaction may be used for the diagnosis of mucormycosis for identification of fungus. | Figure 3: Histopathology microphotograph showing broad nonseptate hyphae with 90° branching Eosin stain with 400 X magnification
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| Treatment | | |
Surgical debridement is critically important for the management of localized forms of mucormycosis as antifungal treatment alone is not effective. Surgery should be radical with aim for removal of all devitalized tissues and it should be repeated on the basis of disease progression. As the tissue involvement in mucormycosis is often more than expected, so incisions must be extended for adequate debridement. Early debridement of the affected tissue gives a better prognosis for successful treatment in mucormycosis.[21] Liposomal amphotericin B treatment has better tissue penetration and considered as first-line treatment.[3] However, monotherapy such as surgery alone or amphotericin B alone has limited efficacy, whereas the combination therapy with liposomal amphotericin B or posaconazole and surgical debridement are recommended treatment.[22] Amphotericin B has potential toxicity on renal function, and so dose should be individually adjusted between 0.5 mg/kg/day and 1.0 mg/kg/day on the basis of body weight and renal functions of the patients. The total cumulative dosage of amphotericin B is 2–4 g often advocated to the adult patient. Hyperbaric oxygen therapy and certain cytokines such as granulocyte macrophage-CSF and interferon gamma act as adjuvant treatment and these are under assessment. Hyperbaric oxygen therapy has a fungistatic effect and helps revascularization of the necrotic or ischemic tissue.[23] The survival rate of mucormycosis patients has been improved by new antifungal agents and combination therapy. Despite advancement in treatment modality and care, the overall mortality rate of mucormycosis patients remains high due to delay in diagnosis. A delayed diagnosis of mucormycosis of more than 5 days is associated with increased chance of death.[24] For a successful outcome, correction of predisposing factors, timely diagnosis, surgical debridement, and systemic antifungal are needed in combination. The systemic amphotericin B has its own side effects which need vigilant monitoring. Amphotericin B in classic desoxycholate form in the dose of 1–1.5 mg/kg/day or more preferably in the liposomal form of amphotericin B is highly useful for mucormycosis. The liposomal form has less nephrotoxicity and also allows higher doses in 5–15 mg/kg/day for prolonged period. Liposomal form better concentrates in macrophages including deep infected tissue with higher CNS penetration.[25] Posaconazole, a new type of triazole, is useful in failure cases with better efficacy in vitro and in vivo with good tolerance and very fewer side effects. Isavuconazole is a new type of extended spectrum of triazole, which acts against molds, yeast, and dimorphic fungi and also approved for the treatment of invasive aspergillosis and mucormycosis.[26] Total duration of antifungal drug treatment in mucormycosis varies with evolution but at least advised for 12 weeks.[27] For prevention of the mucormycosis, the risk factors should be properly addressed. The mucormycosis is often seen in patients of uncontrolled diabetes mellitus which need a very good control for preventing this dreaded disease.
| Prognosis | | |
The prognosis of mucormycosis depends on the patient risk factors such as severe immunodeficiency and part of the body affected by the fungi. The mortality rate in pulmonary mucormycosis is up to 87%, whereas rhino-orbital-cerebral form causes mortality of 25%–62%.[28] The clinical predictors for mortality include disseminated form of infection, infection with Cunninghamella species, renal failure, inability to get source control, cavernous sinus or brain involvement, and poor patient response to antifungal treatment.[29] Despite advancement in treatment modality and care, the overall mortality rate of mucormycosis patients remains high due to delay in diagnosis. A delayed diagnosis of mucormycosis of more than 5 days is associated with increased chance of death.[24]
| Conclusion | | |
Mucormycosis is a rare and dreaded fungal infection in the head and neck region. It is a rapidly progressive disease with fatal outcome unless diagnosed early and treated promptly. Delayed diagnosis and treatment may lead to fatal complications and death. Treatment includes both medical and surgical. It need early and adequate treatment with amphotericin B, surgical resection, and control of risk factors can improve the prognosis. Prognosis depends on multiple factors and needs early initiation of treatment. A multidisciplinary approach often needed and consists of otorhinolaryngologists, ophthalmologists, neurologists, and dentists for successful management of patients with mucormycosis. Identification of risk factors and doing all preventing measures can reduce the incidence of life-threatening mucormycosis in head and neck area.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
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