Fungal infections

Fungal Infections of the Oral
Cavity
Submitted by:
Shekhar kumar mandal
BDS III
Submitted to:
Department of Oral pathology
College of Medical Sciences,
Bharatpur-10, Chitwan

Contents:
Introduction
Candidiasis
 Histoplasmosis
Phycomycosis
Rhinosporidiosis
North American Blastomycosis
South American Blastomycosis
Cryptococcosis
Coccidioidomycosis

Geotrichosis
 Sporotrichosis
Aspergillosis
INTRODUCTION
Mycology, the study of fungal infections, has gained remarkable impetus in the past few decades,
owing at least in part to the fact that fungal diseases are far more common than was previously
suspected. Many erroneous conceptions of this branch of microbiology existed until only recently, but
careful scientific investigation of various aspects of mycology, such as epidemiology, pathogenesis,
immunology, diagnosis and treatment, has done much to eliminate the confusion.
Most fungi are soil saprophytes in which they play important role in degradation of organic compound.
There are about 2, 50,000 fungal species, and only 150-200 of them are capable of producing
disease. Organism of kingdom are usually saprophytic and lack chlorophyll.
STRUCTURE
Fungi basically consists of:-
 Cell wall
Rigid cell wall made up of chitin, glucans, mannans and complex polysaccharides.
 Cell membrane
Contains ergosterol as chief constituent.
Surrounds other cell component.
 Nucleus
True nucleus is present.
Usually two or more.
 Various other components
CLASSIFICATION
1. Zygomycetes:
Consists of sexually reproducing fungi.
e.g. rhizopus, mucor
2. Ascomycetes

e.g. Pichia, Sacharomyces
3. Basidiomycetes
e.g. Amanita, Agaricus
4. Deuteromycetes (Fungi imperfecti)
Candida, Cryptococccus
Morphology
Three main groups of fungi exist based on morphology:
 Yeasts
- usually round/oval unicellular fungi
- contains single nuclei
e.g. Candida albicans
 Filamentous/Mycelial fungi
- multi cellular structures with branching tubular cells
e.g Zygomycetes, Dermatophytes
 Dimorphic fungi
- Exist as yeast and filamentous
- E.g. Histoplasma capsulatum, Blastomyces
Reproduction
Reproduces by forming spores which may be either sexual or asexual
Pathogenecity
Pathogenecity of fungi depends upon
(1) Toxin production
Majority of fungi do not produce any toxin
(2) Physiologic alterations
Many pathogenic fungi shows increased metabolic activity (e.g. modified structure of cell
wall) which enhances the ability of fungus to invade tissue.
(3) Thermotolerance
Most pathogenic fungi can resist active oxygen species released in course of respiratory
burst of phagocyte.
Epidemiology
 Transmission
- Most are saprophytes in nature.
- Most infections are not contagious but acquired by exposure.
- Epidemics outbreak may occur due to environmental exposure.
 Incidence
Fungal disease are increasing due to :
- growing number of immunocompromised patients
- increased application of invasive surgical procedures and antibiotics.

Laboratory diagnosis
Specimens
Specimens from skin nail mucous membrane,scraping crusts, pus, blood as well as csf
may be taken.
Specimen is then divided in to 2 parts: one for microscopy and other for culture
Examination
a) Microscopy:
(i) Potassium hydroxide mount
- KOH dissolves keratin and cellular element but not fungi
- Fungal structure can be seen clearly.
(ii) Staining technique
Various stain like gram stain, papani colou stain, Periodic Acid Schiff, silver
stains can be used.
(iii)Direct immunofluorescence
(iv) Histological examination
b) Antigen detection
 Using latex agglutination technique
c) Culture and isolation
 Various culture media can be used like
 Sabouraud’s dextrose agar
 Blood agar
 Cormeal agar
d) Indirect methods
 Skin testing
 Serologic tests
Treatment
Antifungal agents used commonly:
 Amphotericin B
 Nystatin
 Fluconazole
 Ketoconazole

Candidiasis
(Candidosis,moniliasis,thrush)
 Candidiasis is caused by a yeast-like fungus, Candida (Monilia) albicans.
 Although other species, such as
 C.tropicalis,
 C. parapsilosis,
 C. stellatoidea, and C. krusei.
 C.guilliermondii,
 C. dubliniensis, and
 C. glabrata may also be involved.
 Candida exists in three forms namely, a) pseudohyphae,
 yeast,and
 chlamydospore forms.
 Reproduces by asexual budding and forms pseudohyphae.
 Grow rapidly at 25–37°C.
 Common inhabitant of the oral cavity, gastrointestinal tract, and vagina of clinically normal
persons.
 When the favorable condition develops, the organism transforms into pathogenic form, that is
yeast form transformed into hyphae. Thus it appears that the mere presence of the fungus is
not sufficient to produce the disease. There must be actual penetration of the tissues, although
such invasion is usually superficial and occurs only under certain circumstances.
 This disease is said to be the most opportunistic infection in the world.
 It is reported that more than 90% of the HIV infected individuals develop oral candidiasis
during some part of their disease.
Predisposing factors
 Acute and chronic diseases like tuberculosis, diabetes mellitus, and anemia
 Immunodeficiency like AIDS
 Nutritional deficiency like Fe, vitamin A and vitamin B6 deficiencies, etc.
 Prolonged hospitalization for chronic illness and debilitating diseases
 Prolonged use of antibiotics, corticosteroids, and cytotoxic drugs
 Radiation therapy
 Use of intravenous tubes, catheters, heart valves and poorly maintained dentures, heavy
smoking
 Old age, infancy, and pregnancy
 Xerostomia:- The protective antifungal proteins present in the saliva like histatins and
calprotectin are absent in patients with xerostomia.
Immunopathogenesis of Candidiasis.
Various anticandidal factors and antiadherence factors also play a major role in its development.

- Salivary IgA affects the adherence of Candida to mucosal cells.
- T cells and neutrophils also play a role in preventing and clearing them infection.
- Other factors of less significant role are complement, transferrin, lactoferrin, vitamins A, C, and
serum antibody.
Clinical Features
 Candidal infection may range from mild superficial mucosal involvement to severe, fatal
disseminated form seen in immunocompromised individuals.
 Classified into two major categories:
i) Mucocutaneous Candidiasis
- Includes oral and oropharyngeal candidiasis, candidal esophagitis,
intestinal candidiasis
ii) Systemic Candidiasis
- Involves chiefly eyes, kidneys and skin through hematogenous spread
 The classification proposed by Samaranayake in 1991 and modified by Axéll et al, in 1997
divides candidiasis into two major categories namely:
 Primary oral candidiasis
Infection exclusively confined to oral and perioral tissues
 Secondary oral candidiasis
Oral lesions as a manifestation of systemic mucocutaneous candidiasis.
Classification of Candidiasis
1) Acute forms:
i) Acute pseudomembranous candidiasis
ii) Acute atrophic candidiasis
2) Chronic forms
i) Chronic hyperplastic candidiasis
ii) Chronic mucocutaneous candidiasis
-Chronic familial mucocutaneous candidiasis
- Chronic localised mucocutaneous candidiasis
- Candidiasis endocrinopathy syndrome
- Candidiasis diffuse mucocutaneous
iii) Chronic atrophic candidiasis
Oral Manifestations
A. Primary oral Candidiasis
1) Pseudomembranous Candidiasis
 Also known thrush and is one of the most common forms of the candidiasis.
 Especially prone to occur in the debilitated or the chronically ill patients or in infants.

 The oral lesions are characterized by the appearance of soft, white, slightly elevated
plaques most frequently occurring on the buccal mucosa and tongue, but also seen on the
palate, gingiva, and floor of the mouth .
 The plaques resembles milk curds, consist chiefly of tangled masses of fungal hyphae with
intermingled desquamated epithelium, keratin, fibrin, necrotic debris, leukocytes, and bacteria.
The white plaque can usually be wiped away with a gauze, leaving either a relatively
normal appearing mucosa or an erythematous area.
 In severe cases, the entire oral cavity may be involved.
 Concomitant involvement of oral cavity and esophagus is common in HIV patients.
2) Erythematous Candidiasis/Acute Mucocutaneous Candidiasis
 Also known as antibiotic sore mouth, includes central papillary atrophy of the tongue and
cheilocandidiasis.
 Occurs as a sequela to a course of broad spectrum antibiotics, corticosteroids or any
disease which suppresses the immune system, more commonly HIV disease.
 Appears red or erythematous rather than white, thus resembling the pseudomembranous
type in which the white membrane has been wiped off.
 Distinguished from erythroplakia by its diffuse border wherein erythroplakia the borders
are sharp and well demarcated.
 Only variety of oral candidiasis, which is consistently painful.
 The erythematous appearance occurs due to the loss of filiform papillae and increased
vascularity.
 A strong relationship exists between this lesion and chronic smoking and C. albicans.
3) ChronicHyperplastic Candidiasis/Candidal leukoplakia/Nodular candidiasis
 Firm, white persistent plaques, usually on the lips, tongue, and cheeks and appear similar to
leukoplakia.
 May persists for periods of years.
 Various data have indicated a definite relationship between chronic candidiasis and oral
epidermoid carcinoma, basing this relationship on the finding that chronic candidiasis itself
is a cause of leukoplakia and thus must be regarded as having possible premalignant
potential.
 May be associated with iron and folate deficiency and defective cell mediated immunity.
4) Candida Associated Lesion:

Denture Stomatitis (Chronic atrophic candidiasis)
 Considered to be synonymous with the condition better known as denture sore mouth, a
diffuse erythema and edema of the denture-bearing area, often occurring with angular
cheilitis.
 Women are affected more frequently than men.
 May be the most common form of the oral disease.
Fig:Pseudomembranous candidiasis Fig: Denture stomatitis
B. Secondary Oral Candidiasis
1. Chronic Mucocutaneous Candidiasis
 Characterized by chronic candidal involvement of skin, nails, scalp and mucous
membrane.
 Abnormalities in their immune system, impaired cell mediated immunity, isolated IgA
deficiency and reduced serum candida-cidal activity.
 Usually resistant to common form of treatment.
 Usually occurs in children.
2. Chronic Localized Mucocutaneous Candidiasis
 Severe form of the disease also occurring early in life, but there is no genetic transmission.
 Widespread skin involvement and granulomatous and horny masses on the face and scalp.
 Increased incidence of other fungal and bacterial infections.
 The mouth is the common primary site for the typical white plaques, and nail involvement is
usually present.
3. Candidiasis Endocrinopathy Syndrome
 Genetically transmitted condition characterized by Candida infection of the skin, scalp, nails,
and mucous membranes, classically the oral cavity, in association with either hypoadrenalism
(Addison’s disease), hypoparathyroidism, hypothyroidism, ovarian insufficiency or diabetes
mellitus.
4. Chronic Diffuse Mucocutaneous Candidiasis

 It is the least common form of the disease and appears to be of late onset (over55 years of
age).
 They exhibit extensive raised crusty sheets involving the limbs, groin, face, scalp and
shoulders as well as mouth and nails.
Id Reaction.
It is a hypersensitivity reaction to candidal antigen, which manifests as vesicular and papular rash
on the skin of patients with chronic candidiasis.
Histologic Features
Fragments of the plaque material may be smeared on a microscopic slide, macerated with 20%
potassium hydroxide and examined for the typical hyphae .
In addition, the organisms may be cultured in a variety of media like :-
1) Blood agar,
2) Cornmeal agar and
3) Sabouraud’s broth, to aid in establishing the diagnosis.
Presence of the yeast cells and hyphae or mycelia in the superficial and deeper layers of involved
epithelium . These are more easily visualized if the sections are stained with PAS or methenamine
silver, since the organisms are positive in both instances.
Fig: Tubular hyphae of Candida albicans embedded in the parakeratin layer
Treatment
1) Superficial Infections: Topical Therapy
New specific antifungal agents such as Nystatin have been beneficial in the treatment of candidiasis.
Given in dose of 5 lac U tab.
Other drugs of value are clotrimazole, and miconazole.
It has been found that occasional cases of candidiasis have remained refractory to treatment by
nystatin. These have frequently been associated with one of the endocrinopathies just described in
connection with immunologic abnormalities.
2) Systemic Infections:
Amphotericin B is administered along with 5 fluorocytosine. Combined therapy may act
synergestically.

Histoplasmosis: (Darling’s disease)
Histoplasmosis is a generalized fungal infection caused by the organism Histoplasma capsulatum.
Epidemiology
It is widespread in its distribution and endemic in the Mississippi Valley and Northeastern United
States.
Etiopathogenesis
Usually acquired by inhalation of dust containing spores of the fungus, the contamination probably
occurring from excreta of birds such as pigeons, starlings, and blackbirds.
It is classified clinically into
i) Acute primary pulmonary,
ii) Chronic pulmonary and
iii) Disseminated forms.
In the disseminated forms, the infection spreads to extra pulmonary sites including oral cavity.
Clinical Features
 Characterized by:-
 Chronic low-grade fever,
 Productive cough,
 Splenomegaly,
 Hepatomegaly and
 Lymphadenopathy
 Organisms have a special predilection for the reticuloendothelial system and chiefly involve
 spleen,
 liver,
 lymph nodes, and
 bone marrow.
 Anemia and leukopenia may also be present.
 The infection by this organism may be extremely mild, manifesting only local lesions.
 Histoplasmosis often terminates fatally; however, particularly the generalized form.
Oral Manifestations
 Reviewed by Levy and by Stiff.
 Appear as nodular, ulcerative or vegetative lesions on the buccal mucosa, gingiva, tongue,
palate, or lips.
 Covered by a nonspecific gray membrane which is indurated with raised and rolled out
borders resembling carcinoma.
 The organism may be readily isolated by inoculating the emulsified tissue onto blood agar
containing penicillin and streptomycin. Occasionally cases have been mistaken for carcinoma

or even Vincent’s infection, while the lymphadenopathy has suggested Hodgkin’s disease
Fig:oral lesion of histoplasmosiss in tongue Fig:Small yeasts of H. capsulatum
Histologic Features
 Appears basically to be a granulomatous infection.
 Organisms are found in large numbers in phagocytic cells and
 Appear as tiny intracellular structures measuring little more than 1μ in diameter.
Treatment
 Pulmonary histoplasmosis usually, resolves spontaneously.
 Itraconazole/ Amphotericin B are 1st choice of drugs.
 Fluconazole can also be used.
Phycomycosis:
(Mucormycosis, zygomycosis)
 Caused by the order mucorales.
 Zygomycosis refers to the infection caused by both the order of fungus Mucorales and
Entomophthorales.
 It is worldwide in distribution and the organisms normally occur in soil, manure, fruits, and in
decaying matter.
 This is an opportunistic infection associated with
- debilitation, more frequently in cancer patients, especially malignant
lymphomas and
- in patients having renal failure, organ transplant, AIDS, and cirrhosis
- diabetes mellitus, especially those with diabetic ketoacidosis,
immunosuppressed patients,
- patients with burns or open wounds or after administration of steroids
and chemotherapeutic antimetabolites.

The three most important types causing infection in man are
 Rhizopus,
 Mucor
 Absidia.
Clinical Features
 Two main types of phycomycosis infection occur in human beings:
(1) superficial and
(2) visceral,
although it is sometimes also classified as localized and disseminated.
1) Superficial infection:-
Includes involvement of the external ear,the fingernails, and
the skin.
2) Visceral forms of phycomycosis:-
Three main types:
(a) pulmonary,
(b) gastrointestinal, and
(c) rhinocerebral: It is of greatest interest to the dental profession,
 May occur at any age,
 Infections of the head characterized by the classical syndrome of uncontrolled diabetes,
cellulitis, ophthalmoplegia and meningoencephalitis. The infection apparently enters the
tissues through the nasal mucosa and extends to the paranasal sinuses, pharynx, palate, orbit,
and brain.
 One early clinical manifestation of the disease is the appearance of a reddish-black nasal
turbinate and septum with a nasal discharge.
 Maxillary sinus may present clinically as a mass in the maxilla, resembling carcinoma of the
antrum, and radiographs may support the latter diagnosis .
Surgical exploration; however, will reveal only masses of necrotic tissue in which
the organisms can be demonstrated histologically.
Histologic Features
 Shows a variable amount of necrosis.
 This fungus has an apparent predilection for blood vessels; it is able to penetrate their walls
and thereby produce thrombosis.
 The organisms appear as large, nonseptate hyphae with branching at obtuse angles .
 Round or ovoid sporangia are also frequently seen in the tissue section.
A special stain like Grocott’s silver methenamine stain may use to confirm the diagnosis.
The majority of reported cases of phycomycosis have been diagnosed only at the time of autopsy.
Treatment and Prognosis
Treatment of the disease consists of:

 control of the predisposing factors such as diabetes,
 surgical excision if the lesion is localized, and
 administration of amphotericin B, since it is the only drug with proven efficacy.
Rhinosporidiosis
Rhinosporidiosis is a chronic granulomatous disease caused by a fungus called Rhinosporidium
seeberi, which affects chiefly the oropharynx and nasopharynx as well as the larynx, skin, eyes, and
genital mucosa. The mode of infection is not
known. This infection is common in India and Sri Lanka.
Clinical Features
 Nasal mucosa is the most common site involved.
 Lesions appear as small verrucae or warts, which ultimately become pedunculated.
 Genital lesions resemble condylomas.
Oral Manifestations
 Oronasopharyngeal lesions are often accompanied by a mucoid discharge and appear as
soft red polypoid growths of a tumor like nature,
 The lesions are vascular and bleed readily.
 Soft palate appears to be the most frequent site.
Histologic Features
 The organisms appear as sporangia containing large endospores, each approximately 5–7μ
in diameter.
 Nonspecific tissue reaction
 Consisting of a vascular granulation tissue with focal abscess formation and occasional
multinucleated giant cells.
 Both acute and chronic inflammatory cells are present in variable number

Treatment
 Surgical removal of the growths is recommended as treatment of choice.

North American Blastomycosis:
(Gilchrist’sdisease)
 Caused by Blastomyces dermatitidis.
 May occur either in a cutaneous form or in a systemic form involving bones, liver, lungs,
subcutaneous tissues, and other organs.
 It is becoming an important medical problem, particularly in central United States.
 Lesions usually begin as small red papules which gradually increase in size and form tiny
miliary abscesses or pustules which may ulcerate to discharge the pus through a tiny sinus.
 Crateriform lesions are typical
 Characterized by fever, sudden weight loss, and productive cough.
 Oral lesions bore enough resemblance to epidermoid.
Blastomycosis
South American Blastomycosis:
(Lutz’s disease, Paracoccidioidomycosis)
 Caused by infection with Blastomyces (Paracoccidioides) brasiliensis.
 The systemic lesions are similar to those of North American blastomycosis.
 Organisms may enter the body through the periodontal tissues and subsequently reach
regional lymph nodes, producing a severe lymphadenopathy.
 The chief difference between North American and South American blastomycosis is in the size
of the causative organisms. The fungus in the South American form are considerably larger
than that of the North American disease.
Cryptococcosis:
(Torulosis, Europeanblastomycosis)
 Chronic fungal infection caused by Cryptococcus neoformans (Torula histolytica) and
Cryptococcus bacillispora,
 May present widespread lesions in the skin, oral mucosa, subcutaneous tissues, lungs, joints,
and particularly the meninges.
 The organisms appear to be harbored by pigeons or inhalation of airborne microorganisms.
 Presence of oral lesions is the first evidence of this disease that appears multiple brown
papules which ultimately ulcerate.
 Pneumonitis, neurologic signs and symptoms with increased intracranial pressure are
associated with this disease.
 In tissue sections, appears as a small organism with a large clear halo, sometimes described
as ‘tissue microcyst’.

Coccidioidomycosis:
(Valleyfever,San Joaquin valleyfever)
 Transmitted to man and animals by inhalation of dust contaminated by the spores of the
causative organism, Coccidioides immitis.
Clinical Features
 There are two basic forms of the disease
 Primary form,
 Cough, pleural pain, headache, and anorexia.
 This form of the disease is self-limiting
 Disseminated form
 Occurs in only about 1% of the cases, there is a mortality rate of approx 50%
meningitis is the most frequent cause of death
 Lesions of the oral mucosa and skin are proliferative granulomatous and ulcerated lesions that
are nonspecific in their clinical appearance. These lesions tend to heal by hyalinization and
scar.
Geotrichosis
Fungal disease similar to candidiasis in its clinical features, but caused by organisms of the
Geotrichum species.
The oral lesions are identical to those of candidiasis or thrush, being a white, velvety, patch-
like covering of the oral mucosa, isolated or diffuse in distribution.
Differentiated histologically from Candidiasis by presence of rectangular spores with rounded
end.
Sporotrichosis
Caused by Sporotrichum schenckii
Risk factors:
Exposure to a wide variety of animals, both domestic and wild.
Accidental injury from the thorns of some plants or bushes.
Accidental laboratory or clinical inoculation of hospital workers.
Clinical Features
Involve the skin, subcutaneous tissues and oral, nasal and pharyngeal mucosa.
The lesions, often described as sporotrichotic ‘chancres,’ appear at the site of inoculation as
firm, red to purple nodules, which soon ulcerate.
Neighboring nodules with regional lymphadenopathy generally develop soon,

ASPERGILLOSIS
Fungal disease that is characterized by noninvasive and invasive forms.
Two most commonly encountered species of Aspergillus in the medical setting are A. fl avus
and A.fumigatus, with A. fumigatus being responsible for 90% of the cases of aspergillosis.
The patient may acquire such infections in the hospital (“nosocomial” infection), marginal
gingiva and gingival sulcus.
Disease may appear as an allergy affecting either the sinuses (allergic fungal sinusitis) or
the bronchopulmonary tract
Radiopaque body called an antrolith within the sinus is often demonstrated in this disease.
Painful gingival ulcerations are initially noted, and peripherally the mucosa and soft tissue
develops diffuse swelling with a gray or violaceous hu
Characteristic septate hyphae of Aspergillus species.

S
References
I. Teacher’s Note
II. Shafer's Textbook of Oral Pathology 7e - Rajendran, R
Sivapathasundaram, B
III. Oral and Maxillofacial Pathology 3e – N Brad W Neville,,
IV. Textbook of Microbiology- P Chakraborty
V. Textbook of Pharmacology- KD tripathy
VI. Internet:- eMed.com

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