|LETTER TO THE EDITOR
|Year : 2014 | Volume
| Issue : 2 | Page : 145-147
Oral mucormycosis: Need for early diagnosis!!
Sridhar Gontu Reddy, Kiran K Kumar, Chandhra P Sekhar, Ramana B. V. Reddy
Department of Oral Pathology and Microbiology, SIBAR Institute of Dental Sciences, Takkellapadu, Guntur, Andhra Pradesh, India
|Date of Web Publication||20-Jun-2014|
Sridhar Gontu Reddy
Department of Oral Pathology and Microbiology, SIBAR Institute of Dental Sciences, Takkellapadu, Guntur, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Reddy SG, Kumar KK, Sekhar CP, Reddy RB. Oral mucormycosis: Need for early diagnosis!!. J NTR Univ Health Sci 2014;3:145-7
We report two cases of mucormycosis of maxilla in an immunocompetent patient and an uncontrolled diabetic patient. A 29-year-old male immunocompetent patient presented with stiffness and blood discharge from nose, palatal ulceration, region, numbness in the left middle third of the face and black necrotic alveolus in relation to 22-24 [Figure 1]. Another case is an uncontrolled diabetic female patient aged 55 years presented with nonhealing sockets and necrotic alveolus in relation to the 13-16. Excisional biopsy of these cases were diagnosed as mucormycosis by H and E staining, fungal cultures and grocott's silver staining which showed filamentous ribbon like, nonseptate hyphae [Figure 2] and [Figure 3].
|Figure 1: Clinical photograph showing necrotic maxillary alveolus and palatal ulceration|
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|Figure 2: Photomicrograph showing large, no septae fungal hyphae seen in the marrow spaces (×40)|
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|Figure 3: Photomicrograph showing (grocott gomorii silver methylamine stain) nonseparate, nonbranching fungal hyphae (×40)|
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Mucormycosis is an invasive, potentially lethal fungal infection caused primarily by fungi of the order Mucorales and class zycomycoses  (Rhizopus arrhizus) first described by Paultauf in 1889. Mucorales are ubiquitous, present mainly in bread moulds, decaying foods, soil and in putrefying organisms. Mucormycosis occurs in uncontrolled diabetes mellitus, diabetic ketoacidosis, impaired host defenses, AIDS, patients under immunosuppressive therapy, nonhealing extraction sockets, organ transplanted individuals, hemodialysis and rarely healthy individuals. Apart from R. arrhizus there are cases reported with new species of Mucorales i.e. Cunninghamella spp., Rhizopus microsporus var, rhizopodiformis, Absidia corymbifera, Apophysomyces elegans, Mucor species, and Rhizomucor pusillus. ,
There are six clinical types of mucormycosis, the most common form is rhinocerebral mucormycosis which is of greatest interest to the dental profession.  An ulcer or extraction wound in the mouth can be a port of entry for fungal invasion of the hard palate, maxillary bone, paranasal sinus, orbit, intracranial cavity and brain and rarely in the mandible. , Other sites of infection include the nose, lungs, gastrointestinal tract, skin, kidneys, and central nervous system  Despite surgical and antifungal treatments the mortality rate is higher than 50% and even higher in immunocompromised patients.
Clinical features may range from nasal obstruction, bloody nasal discharge, facial pain or head ache, facial swelling or cellulitis, visual disturbances with concurrent proptosis, facial paralysis in case of facial nerve involvement. As the disease progresses in to cranial vault it may lead to blindness, lethargy, seizures, and death. 
The role of dentist is of immense importance because mucormycosis primarily occurs around rhinomaxillary or rhinocerebral areas involving facial tissues, palate, alveolar bone and mandibular bone. Inhalation through nasal passage or infection of extraction sockets with sporangiospores in immunocompromised patients always involve larger areas necrosis and with systemic dissemination.
In healthy individuals, neutrophils when exposed to the Mucorales there is up regulation of Toll-like receptors and expression of nuclear factor kappa beta.  In immunocompetent individuals Mucorales are killed by generation of oxidative metabolites and cationic peptide defensins, which are impaired in acidosis and hyperglycemia. Neutrophil dysfunctional states have high risk of developing mucormycosis not only by R. arrhizus species but also by less common varieties like corymbifera, A. elegans and Rhizomucor pussillus.
The factors influencing the pathogenicity of Mucorales are mainly:
- The availability of the iron.
- The interactions of mucorale to the endothelium.
Mucorales obtain iron from host using high affinity iron permeases or by the low molecular weight iron chelators or by the usage of iron present in the hemoglobin through FTR1 gene expression.  Elevated serum iron and iron chelator (deferoxamine) have high incidence of mucormycosis.  Iron usage by the Rhizopus is many folds than Candida, as it utilizes deferoxamine.
Diabetic ketoacidosis patients have high levels of serum iron and the pH ranging from 7.3 to 6.88, which is ideal environment for growth of Rhizopus. In acidosis, disruption of binding capacity between iron and transferrin causes elevation of serum iron (ferric form). Rhizopus adheres to the laminin and Type IV collagen in extra cellular matrix, and induces endocytosis causing the endothelial damage. Invasion of endothelial cells by the Mucorales lead to angioinvasion resulting in thrombosis subsequent to the tissue necrosis. 
Pathogenesis and mechanism of bone destruction is attributed to the reduced vascularity by thrombi formation and inhibition of angiogenesis due to elevated levels of GRP 78. 
Diagnosing mucormycosis by imaging studies (radiological or CT or MRI), culture studies or serological tests are not unswerving. Good clinical examination with history and astute approach in treating without delay can reduce morbidity and mortality. Antifungal treatment by amphotercin group has many toxic side effects. There are clinical trails using azoles and echinocandins, iron chelators, hyper baric oxygen and cytokine therapy but the data till date shows that these drugs also have side effects. 
Nonhealing of extraction sockets and immunocompromised states should alert high suspicion, judicious approach by the clinician and early diagnosis and appropriate management helps to reduce the size of defect and complications.
| References|| |
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|4.||Liu M, Spellberg B, Phan QT, Fu Y, Fu Y, Lee AS, et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest 2010;120:1914-24. |
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[Figure 1], [Figure 2], [Figure 3]