Noncandidal Fungal Infections of the Mouth

Updated: Mar 01, 2018
  • Author: Manuel Valdebran, MD; Chief Editor: William D James, MD  more...
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Overview

Background

This article focuses on noncandidal oral fungal infections (deep mycoses). Candidiasis (candidosis) is by far the most common fungal infection of the mouth (oral cavity). Other Medscape articles on candidiasis include Chronic Mucocutaneous Candidiasis,Mucosal Candidiasis, and Cutaneous Candidiasis.

This article discusses the following noncandidal oral mycoses: aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, zygomycosis (mucormycosis), oral geotrichosis, Rhodotorula infection, and fusariosis. Although these noncandidal fungal infections are considerably less common than oral candidiasis, they commonly produce subclinical infection, especially pulmonary infections. Immunocompromised persons are at particular risk from these mycoses, and clinical manifestations of infection by these organisms often suggest impaired immune competence. [1] It is in such people that oral lesions are most likely to manifest. Patients at greatest risk from mycoses include those with leukemia, leukopenia, solid tumors, transplants, or HIV disease. [2, 3, 4] Also at risk are premature infants.

In rare cases, mycoses can produce clinical disease in healthy persons, including oral lesions. Systemic mycoses in healthy individuals are more common in endemic areas than elsewhere, and they are often asymptomatic and may spontaneously resolve. In otherwise healthy persons, acute pulmonary and primary mucocutaneous symptomatic lesions may resolve without treatment. However, chronic pulmonary infection tends to progress and disseminated infections can be fatal.

Noncandidal fungal infections have the potential for serious injury to the oral cavity, perioral tissues, and, sometimes, the paranasal sinuses, orbit, and cranial base. Orofacial lesions caused by the main systemic mycoses may occasionally be seen in isolation, but they are typically associated with lesions elsewhere, mainly in the respiratory tract. The oral lesions associated with these deep fungal infections are chronic and progress to form solitary, chronic deep ulcers with the potential for local destruction and invasion and systemic dissemination. They can mimic other infections and malignant neoplasms.

Chronic oral ulceration, chronic maxillary sinus infection, or bizarre mouth lesions, especially in patients with HIV disease, those with lymphoproliferative disorders, persons with diabetes mellitus, or those who have been in endemic areas, may suggest the diagnosis and patients should be treated in consultation with a physician with appropriate expertise.

Most of these mycoses are diagnosed on the basis of a history of foreign travel or an immunocompromised state. Investigations include smears, biopsy, staining with periodic acid-Schiff (PAS) or Gomori methenamine silver, culture of the affected tissues, polymerase chain reaction (PCR), serodiagnosis (sometimes), physical examination, and chest radiography. Definitive diagnosis is achieved by means of microbiologic or histologic identification and serodiagnosis. DNA probes are available for several species. Unfortunately, specific laboratory studies for an accurate diagnosis of many mycoses is available only in a few laboratories.

Prompt identification and treatment, usually with systemic antifungal drugs, are essential; delayed treatment or no treatment can result in considerable orofacial destruction, systemic dissemination, or death.

It is important to highlight that these organisms usually invade other organs as a primary site of infection. [5] Lesions in the oral cavity may be the result of hematogenous spread of the disease; therefore, a diagnosis of a deep-seated fungal oral infection should prompt the clinician to investigate systemic involvement as well as to determine the integrity of the immune system of the affected individual.

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Pathophysiology

Aspergillosis

More than 160 species and variants of Aspergillus organisms have been discovered, although only 10 are pathogenic in humans. Aspergillus fumigatus is the most common pathogen, but Aspergillus flavus, Aspergillus glaucus, Aspergillus nidulans, Aspergillus terreus, Aspergillus repens, Aspergillus parasiticus, and Aspergillus niger are also encountered. A flavus is the most virulent.

Aspergillus species are the most common environmental fungi, being prolific saprophytes in soil and decaying vegetation. Inhalation of the conidia is likely very common, but unless the inhalation is massive or unless the host is immunocompromised, clinical disease is rare. Aspergillosis is found worldwide and its prevalence is increasing. It is now the most prevalent mycosis second only to candidosis.

The organisms exist as prolific saprophytes in soil and decaying vegetation. Inhalation of the organisms allows for their germination and colonization in the mucosa of the respiratory tract, including the mouth. Lesions may be established primarily in the oral mucosa, but they more commonly begin in the mucosa of the maxillary sinus. They may appear in the oral cavity after local invasion and/or destruction of the surrounding structures. Inhalation of the spores is common, although clinical disease is rare unless the individual is immunocompromised by medication (eg, chemotherapy, [4] organ transplantation immunosuppression) or disease (eg, HIV infection, leukemia, lymphoma). Rarely, aspergillosis has followed dental interventions. [6]

Blastomycosis

Blastomycosis is a term sometimes used to include a range of granulomatous systemic mycoses, including North American blastomycosis (Gilchrist disease), South American blastomycosis (paracoccidioidomycosis or Almeida disease), coccidioidomycosis, and cryptococcosis. However, the nomenclature is now restricted mainly to the North American and South American forms of blastomycosis, which involve the viscera, lymph nodes, and mucocutaneous tissues.

Blastomyces dermatitidis causes the North American form, whereas Paracoccidioides brasiliensis causes the South American form. As expected, North American blastomycosis is seen predominantly in the Mississippi, Missouri, and Ohio River valleys in the United States and in southern Canada. However, it is also seen in Africa, India, the Middle East, and Australia, and sporadic cases are seen worldwide. Serotype 1 is seen in North America, and serotype 2 is seen in Africa.

B dermatitidis, which is found in soil and spores, may be inhaled to produce respiratory tract and sometimes disseminated disease, for example in diabetes. [7] Serotype 1 is seen in North America, and serotype 2 is seen in Africa. Outdoor workers are particularly affected, but blastomycosis is increasingly recognized in persons with HIV disease.

Coccidioidomycosis

Coccidioidomycosis is seen mainly in arid parts of the Western hemisphere, such as the southwestern United States, Mexico, Central America, and parts of South America. Inhalation of spores of Coccidioides immitis, found in soil, produces subclinical infection in up to 90% of the population in such areas.

Cryptococcosis

Cryptococcosis is seen worldwide in humans and animals and can produce mucocutaneous lesions. [8] Aspiration of basidiospores, mainly capsular serotype A but sometimes serotype D of Cryptococcus neoformans (a ubiquitous yeast found especially in pigeon feces and present in soil), may lead to infection. Two varieties have been described, which are C neoformans var neoformans (synonymous with capsular serotypes A, D, and AD) and the less common C neoformans var gattii (synonymous with capsular serotypes B and C). C neoformans var neoformans is found in excreta from pigeons, canaries, parrots, and budgerigars and in rotting fruit and vegetables. C neoformans var gattii is associated with a particular tree, the Red River gum tree (Eucalyptus camaldulensis).

Note the image below.

Cryptococcosis. Left image shows solitary, destruc Cryptococcosis. Left image shows solitary, destructive lesion resulting in necrosis of alveolar bone and palatal mucosa; note the superficial pseudomembranous candidiasis of the palate. Right image shows nonspecific chronic ulceration of the buccal mucosa due to cryptococcosis; this is associated with submucosal induration and regional adenopathy. Courtesy of David Sirois, DMD, PhD.

Histoplasmosis

Histoplasmosis is the most frequently diagnosed systemic mycosis in the United States. Sporadic cases are seen worldwide.

Histoplasma capsulatum, the causal organism, is a soil saprophyte found particularly in northeastern and central states such as Missouri, Kentucky, Tennessee, Illinois, Indiana, and Ohio (mainly in the Ohio and Mississippi valleys). The organism has also been found in Latin America, India, the Far East, and Australia. H capsulatum var duboisii is the type mainly found in equatorial Africa.

Histoplasma species are commonly found in bird and bat feces. In endemic areas, the organism is a soil saprophyte, and more than 70% of adults appear to be infected, typically with subclinical manifestations, as a result of inhaling spores.

Histoplasmosis can be an issue in immunocompromised people, such as those with HIV disease, [9] but it can also be seen orally in HIV-infected [10] or occasionally in immunocompetent individuals. [11, 12]

Zygomycosis

Mucor and Rhizopus species are the most common agents to cause zygomycosis. [13] Fungi of the order Mucorales (of the class Zygomycetes) are responsible for most mucormycosis. However, in addition to Mucor and Rhizopus species, organisms from the genera Absidia, Apophysomyces, Mortierella, Saksenaea, Rhizomucor, and Cunninghamella may also be involved. Therefore, the condition is probably better termed zygomycosis.

These fungi are ubiquitous worldwide in soil, manure, and decaying organic matter. Classic zygomycosis occurs worldwide. In some warmer regions, other Zygomycetes such as Conidiobolus coronatus infect a range of animals and can also occasionally cause rhinofacial zygomycosis in humans. Most human cases have been recorded from the Caribbean, Latin America, and Central and West Africa. Sporadic cases are seen worldwide.

Mucoraceae are commonly cultured from the nose, throat, mouth, and feces of many healthy individuals, but infection is rare in otherwise healthy individuals. [14] Infection is typically seen in immunocompromised patients [15] and often may present with palatal perforation. [16]

Note the image below.

Mucormycosis. Top left image shows multiple, deep Mucormycosis. Top left image shows multiple, deep ulcerations (arrows) of the hard palate. Top right image shows destruction of the palate and the floor of the orbit (failed skin graft of the right eye after orbital enucleation); this infection originated in the maxillary sinus. Bottom image shows similar deep, destructive ulceration of the left posterior maxillary alveolar bone and mucosa due to mucormycosis of the maxillary sinus. Courtesy of David Sirois, DMD, PhD.

Paracoccidioidomycosis

South American blastomycosis (paracoccidioidomycosis or Almeida disease) is found particularly in Brazil but also in Colombia, Ecuador, Mexico, Venezuela, Uruguay, and Argentina. [17, 18] In Brazil, the disease is endemic in the states of Sao Paulo, Rio de Janeiro, and Minas Gerais. P brasiliensis is responsible and is presumably being inhaled as spores. Subclinical infection is not uncommon in endemic areas. Sporadic cases are seen worldwide. Lesions are often nodular or ulcerative. [19, 20, 21]

Geotrichosis

Geotrichosis is caused by Geotrichum species. In particular, oral lesions may be caused by Geotrichumcandidum. These organisms can be found in various habitats such as plants, soil, milk, cheese, air. and water. Geotrichum species can be found in the microflora of humans, including the oral cavity in many as 30% of healthy individuals. [22, 23, 5] Although respiratory infections are the most frequently reported, oral and cutaneous involvement have been communicated in cases in which immunity is disturbed or severely compromised. [23]

Infections by Saprochaete capitate were formerly grouped as geotrichosis by G capitatum; however, utilizing molecular techniques they have been reclassified since 2004 as members of the Saprochaete genus. [24]

See the images below.

Culture of Geotrichum candidum on dextrose agar. C Culture of Geotrichum candidum on dextrose agar. Courtesy of Dr. Alexandro Bonifaz.
Pseudomembranous form affecting the tongue. Courte Pseudomembranous form affecting the tongue. Courtesy of Dr. Alexandro Bonifaz.

Rhodotorula infection

Rhodotorula is a pigmented yeast in the Cryptococcaceae family. The following species have been mainly described: Rhodotorula glutinis, Rhodotorula minuta, and Rhodotorula mucilaginosa. These organisms may be found in air, soil, lakes, ocean water, and dairy products; they may colonize plants, humans, and other mammals. [25]

Fusariosis

Species of Fusarium are found as plant pathogens causing various diseases on cereal grains. This group of fungi are found with some frequency in invasive fungal infections in immunocompromised individuals. The following species have been most commonly implicated causing infections in humans: Fusarium solani, Fusarium oxysporum, Fusarium verticillioides, and Fusarium moniliforme. [25]

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Etiology

Causative fungi include the following:

  • Aspergillosis - A flavus, A terreus, and A fumigatus

  • Cryptococcosis - C neoformans

  • Histoplasmosis - H capsulatum

  • Blastomycosis - B dermatitidis

  • Zygomycosis - Mucor species and Rhizopus species

  • Paracoccidioidomycosis - P brasiliensis

  • Geotrichosis - Geotrichum species

  • Rhodotorula infection - Rhodotorula species

  • Fusariosis - Fusarium species

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Epidemiology

Frequency

United States

Because of the ubiquitous presence of these fungi in the environment, exposure is common. However, clinical disease is uncommon except in persons with iatrogenic or pathologic immunosuppression.

International

Because of the ubiquitous presence of these fungi in the environment, exposure is common in endemic areas, and travelers may present with manifestations even years after exposure. However, clinical disease is uncommon except in persons with iatrogenic or pathologic immunosuppression.

Race

The deep mycoses can affect individuals of all races; no racial predilection is recognized.

Sex

The mycoses affect both sexes equally.

Age

The deep mycoses can affect individuals of all ages, although they are more common in adults than in children. Elderly individuals may be at increased risk, although this is often secondary to impaired immunity.

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Prognosis

Most fungal infections in apparently healthy individuals are self-limiting or subclinical and have a good prognosis. In a healthy individual, infection is typically self-limited, mainly pulmonary, although latency is commonly established, rather than elimination. Reactivation of latent infection may subsequently occur if the infected individual becomes immunosuppressed.

Primary infection or reactivation in individuals with impaired immune surveillance presents a different scenario in which the disease may continue as a locally invasive and destructive process. Once the organism breaks through local barriers and enters the blood or lymphoreticular system, dissemination is rapid and difficult to control.

If a deep fungal oral lesion develops, the likelihood of self-limiting disease is significantly reduced, and the lesion likely represents a potentially serious underlying infection. Although most deep fungal infections respond to aggressive antifungal therapy, infections can be fatal, particularly mucormycosis and aspergillosis. Deep fungal infections should be viewed as serious and potentially life threatening. Among patients who are immunosuppressed (eg, those with HIV/AIDS, diabetes, leukemia, lymphoma, or iatrogenic immunosuppression as in organ transplantation), death rates dramatically increase.

Regional destruction of the maxilla by paranasal infections can lead to considerable morbidity, including oroantral fistula with oronasopharyngeal insufficiency and orbital invasion, which may result in loss of the eye.

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