Candidiasis is by far the most common oral fungal infection and has a

variety of clinical manifestations, making the diagnosis difficult at times.

CANDIDIASIS
OTHER NAMES = CANDIDOSIS (BRITISH NAME), MONILIASIS OR THRUSH (OLDER NAME)
ETIOLOGY OR CAUSATIVE ORGANISM
Candida (Monilia) albicans
• Yeast like fungus
• Grow rapidly at 27-35 degree celcius
• Reproduces by asexual budding
• Infact, C. albicans may be a component of the normal oral microflora, with as many as 30% to 50% of people simply
carrying the organism in their mouths without clinical evidence of infection. This rate of carriage has been shown to
increase with age, and C. albicans can be recovered from the mouths of nearly 60% of dentate patients older than 60
years who have no sign of oral mucosal lesions.
• Like many other pathogenic fungi, C. albicans may exist in two forms—a trait known as dimorphism.
• Yeast form of the organism is believed to be relatively innocuous,
• Hyphal form is usually associated with invasion of host tissue i.e pathogenic

• Common inhabitant of oral cavity, GIT, vagina and skin when favorable condition develops, transform into pathogenic
fungus (Yeast
• Other members of the Candida genus, such as C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii, may also be
found intraorally, but they rarely cause disease.
PREDISPOSING FACTORS
1) Infancy, pregnancy, old age
2) Xerostomia (protective antifungal proteins – histamine, calprotectin are present in saliva)
3) Prolonged use of antibiotics, corticosteroids, cytotoxic drugs
4) Nutritional deficiency like Fe, vitamin A, vitamin B6 etc
5) Use of IV tubes, catheters, heart valves, poorly maintained dentures, heavy smoking
6) Radiation therapy
7) Acute or chronic illness (DM, TB, anemia)
8) Prolonged hospitalization for chronic illness
9) Immunodeficiency (AIDS), Addison’s disease, hypoparathyroidism, Myxedema
VIRULENCE FACTORS OF CANDIDA ALBICANS
• The ability to adhere to host tissue and prosthesis and form biofilms
• The potential to switch (e.g rough to smooth colony formation) and modify the surface antigens
• The ability to form hyphae that helps in tissue invasion
• Extracellular phospholipase, proteninase and haemolysin production which breakdown physical defense
barriers of the host
• At least three general factors may determine whether clinical evidence of infection exists
1) The immune status of the host
2) The oral mucosal environment
3) The strain of C. albicans
CLASSIFICATION OF ORAL CANDIDIASIS
Primary oral candidiasis (Primary oral candidiasis Infection exclusively confined to oral and perioral tissues)
1) Acute form
 Acute Pseudomembranous candidiasis or Thrush
 Acute Atrophic (erythematous) candidiasis or antibiotic sore mouth

2) Chronic form
 Chronic hyperplastic candidiasis or Candidal leukoplakia = white keratotic
 Nodular
 Plaque like
 Pseudomembraneous
 Erythematous

3) Candida-asoociated lesions
 Angular cheilitis
 Denture sore mouth or denture stomatistis
 Median rhomboid glossitis

4) Keratinized primary lesions superinfected with candida

 Leukoplakia
 Lichen planus
 Lupus erythematous

Secondory oral candidiasis (Oral lesions as a manifestation of systemic mucocutaneous candidiasis)

5) Oral manifestations of systemic mucocutaneous Candidiasis due to diseases such as thymic aplasia and candidiasis endocrinopathy syndrome
ACUTE
PSEUDOMEMBRA
NOUS
CANDIDIASIS
ALSO KNOWN AS THRUSH
• Best recognized and most common form of candidal infection or candidiasis

Pathogenesis
• Overgrowth of candida albicans causes desquamation of the oral epithelial cells and accumulation of
bacteria, keratin and necrotic tissue
• Debris thus accumulated combines to form a psudomembrane which adheres closely to the mucosa

Associated factors
• Infants = Underdeveloped immune systems, oral lesions start between 6th and 10th day of birth, cause is
infection is contracted from the maternal vaginal canal where the candida albicans flourishes during
pregnancy
• Broad spectrum antibiotics (thus eliminating competing bacteria) or by impairment of the patient’s
immune system.
• The immune dysfunctions seen in leukemic patients or those infected with human immunodeficiency
virus (HIV) are often associated with pseudo-membranous candidiasis.
Antibiotic exposure is typically responsible for an acute (rapid) expression of the condition; immunologic
problems usually produce a chronic (slow onset, long-standing) form of pseudomembranous candidiasis
Clinical features
• Sex = Any (slightly more common in females)
• Age = Any age
• Common sites = Buccal mucosa , dorsal tongue
and palate (most common sites)
• Appearance
• Characterized by the presence of adherent soft,
white or creamy slightly elevated plaques that
resemble cottage cheese or curdled milk/milk
curds on the oral mucosa
• The white plaques are composed of tangled
masses of hyphae, yeasts, desquamated epithelial
cells and debris
• The white plaque can be wiped away by scrapping
with a tongue blade or rubbing them with a dry
gauze sponge (differentiate it from leukoplakia)
• The underlying mucosa may appear normal or
erythematous . If the bleeding occurs , then the
mucosa has probably also been affected by
another process such as erosive lichen planus or
cancer chemotherapy

• Symptoms, if present at all, are usually relatively

mild, consisting of a burning sensation of the
oral mucosa or an unpleasant taste in the mouth,
variably described as salty or bitter. Sometimes
patients complain of “blisters,” when in fact they
feel the elevated plaques rather than true
vesicles.
ACUTE
ERYTHEMATOUS
OR ATROPHIC
CANDIDI ASIS
ALSO KNOWN AS ANTIBIOTIC SORE MOUTH
• Typically follows a course of broad-spectrum antibiotic therapy.
• In contrast to the pseudomembranous form, patients with erythematous
candidiasis either do not show white flecks, or a white component is not a
prominent feature.
• Commonly involves tongue (central papillary atrophy of tongue) =
symmetric, erythematous lesion of dorsal aspect in posterior region
• Erythematous appearance = diffuse loss of the filiform papillae of the
dorsal tongue, resulting in a reddened, “bald” appearance of the tongue
• Patients often complain that the mouth feels as if a hot beverage had
scalded it. Burning mouth syndrome frequently manifests with a scalded
sensation of the tongue; however, the tongue appears normal in that
condition.
• Only variety of candidiasis, which is consistently painful (patient usually
describes a vague pain or burning sensation, if the discomfort is not
spontaneous, pain can be elicited by mild abrasive pressure by cotton
guaze)
• Lesions in this form of disease appears red or erythematous rather than
white, thus resembling the pseudomembranous type in which the white
membrane is wiped off
• Patients who suffer from xerostomia for any reason (e.g., pharmacologic,
postradiation therapy, or Sjö gren syndrome) have an increased
prevalence of erythematous candidiasis that is commonly symptomatic
as well.
• It is distinguished from erythroplakia by its diffuse border whereas in
erythroplakia, the borders are shaper and well demarcated
CHRONIC
HYPERPLASTIC
CANDIDIASIS
(CANDIDAL
LEUKOPLAKIA)
• Leukoplakia type of candidiasis

• This form of candidiasis is the least common and is also somewhat controversial.

• Similar to leukoplakia i.e like leukoplakia white patch that cannot be removed by scraping.
Some investigators believe that this condition simply represents candidiasis that is
superimposed on a preexisting leukoplakic lesion, a situation that may certainly exist at
times.
• In some instances, however, the candidal organism alone may be capable of inducing a
hyperkeratotic lesion Such lesions are usually located on the anterior buccal mucosa and
cannot clinically be distinguished from a routine leukoplakia
• Often the leukoplakic lesion associated with candidal infection has a fine intermingling of
red and white areas, resulting in a speckled leukoplakia. Such lesions may have an
increased frequency of epithelial dysplasia histopathologically of the lesion after
antifungal therapy
• Asymptomatic, Firm, white, persistent/adherent plaques that are not removable

• Common Sites = Anterior buccal mucosa

• Associated Factors and Comments = Idiopathic, immunosuppression; care must be taken

not to confuse this with other keratotic lesions with superimposed candidiasis
• This type has got malignant potential

Diagnosis or differentiation from leukoplakia

• Biopsy shows presence of candidal fungal hyphae associated with the lesion

• Complete resolution after antifungal therapy while leukoplakia does not resolve
DENTURE
STOMATITIS
ALSO KNOWN AS CHRONIC ATROPHIC CANDIDIASIS OR DENTURE SORE MOUTH
• A form of erythematous candidiasis
• Condition is characterized by varying degrees of erythema, sometimes accompanied by petechial
hemorrhage, localized to the denture-bearing areas of a maxillary removable dental prosthesis
• It is usually painless and asymptomatic and rarely symptomatic
Risk factors
• The major risk factor for the development of this condition is wearing an upper complete denture,
particularly when it is not removed during sleep and cleaned regularly (major risk factor)
• Older dentures are more likely to be involved.
• Other factors include xerostomia (dry mouth), diabetes or a high carbohydrate diet
• The local environment under a denture is more acidic and less exposed to the cleansing action of saliva,
which favors high Candida enzymatic activity and may cause inflammation in the mucosa
• Poorly fitting dentures may cause pressure on the mucosa and mechanical irritation
• The clinician should also rule out the possibility that this reaction could be caused by improper design
of the denture (which could cause unusual pressure on the mucosa), allergy to the denture base, or
inadequate curing of the denture acrylic.
Appearance and symptoms
• Red, asymptomatic
Sites
• Confined to palatal denture-bearing mucosa
ANGULAR
CHEILITIS
ALSO KNOWN AS ANGULAR CHEILOSIS, PERLECHE,
CHEILOCANDIDIASIS
• Seen in individuals with denture related chronic atrophic candiadiasis
• Clinically the lesions are moderately painful, erythematous, fissured, eroded, encrusted and scaled
• It is especially prevelant in individuals who have deep folds at the commissures as a result of mandibular overclosure and in these
circumstances , small accumulation of saliva gather in the skin folds at the commissural anglkes and are subsequently colonized by
yeast organisms and often by staphylococcus aureus
• It also occurs in individuals who habitually lick their lips and deposit small amount of saliva in the commissural angles
• Sometimes this condition is seen as a component of chronic multifocal candidiasis, but it often occurs alone, typically in an older
person with reduced vertical dimension of occlusion and accentuated folds at the corners of the mouth. Saliva tends to pool in these
areas, keeping them moist and thus favoring a yeast infection. Patients often indicate that the severity of the lesions waxes and wanes.
• Microbiologic studies have indicated that 20% of these cases are caused by C. albicans alone, 60% are due to a combined infection
with C. albicans and Staphylococcus aureus, and 20% are associated with S. aureus alone. Infrequently, the candidal infection more
extensively involves the perioral skin, usually secondary to actions that keep the skin moist (e.g., chronic lip licking, thumb sucking,
chronic use of petrolatum-based salves), creating a clinical pattern known as cheilocandidiasis .
• A circumoral type of atrophic candidiasis may be noted in those with severe lip-licking habits with extension of the process onto
surrounding skin . The skin is fissured and demonstrates a degree of brown discoloration on a slightly erythematous base . This
condition is to be distinguished from perioral dermatitis which characteristically shows less crusting and a circumferential zone of
uninvolved skin immediately adjacent to the cutaneous –vermilion junctoion
• Appearance = Red, fissured lesions; irritated, raw feeling
• Site = Angles of mouth
• Associated factors = Idiopathic, immunosuppression, loss of vertical dimension
CENTRAL
PAPILLARY
ATROPHY OF THE
TONGUE OR
MEDIAN RHOMBOID
GLOSSITIS
• Occurring in 0.01% to 1.00% of adults.
• Developmental defect of the tongue resulted from a failure of the embryologic tuberculum impar to be covered by the lateral processes of the tongue
(past)
• Consistent relationship between the lesion and C. albicans (recent)
• Associated factors = Idiopathic, immunosuppression
• Clinically, central papillary atrophy appears as a well demarcated erythematous or atrophic or red zone or patch that affects the midline posterior
dorsal tongue anterior to foramen cecum and circumvallate papillae and often is asymptomatic . The erythema is due in part to the loss of the filiform
papillae in this area. The lesion is usually symmetrical, and its surface may range from smooth to lobulated. Often the mucosal alteration resolves with
antifungal therapy, although occasionally only partial resolution can be achieved.
Chronic multifocal candidiasis.
• Some patients with central papillary atrophy may also exhibit signs of oral mucosal candidal infection at other sites. This presentation of
erythematous candidiasis has been termed chronic multifocal candidiasis. In addition to the dorsal tongue, the sites that show involvement include
the junction of the hard and soft palate and the angles of the mouth. The palatal lesion appears as an erythematous area that, when the tongue is at
rest, the dorsal tongue lesion contacts the palate, resulting in what is called a “kissing lesion” because of the intimate proximity of the involved areas
• Appearance and symptoms = Red areas, often with removable white plaques; burning sensation, asymptomatic
• Common sites = Posterior palate, posterior dorsal tongue, angles of mouth
• Associated factors and comments = Immunosuppression, idiopathic
MUCOCUTANEOUS
CANDIDIASIS
• Severe oral candidiasis may also be seen as a component of a relatively rare group of
immunologic disorders known as mucocutaneous candidiasis. Several distinct immunologic
dysfunctions have been identified, and the severity of the candidal infection correlates with the
severity of the immunologic defect. Most cases are sporadic, although an autosomal recessive
pattern of inheritance has been identified in some families. Several recent studies have
suggested that the cytokine IL-17 is critical in mucosal immunity related to C. albicans, and
mutations of the gene responsible for producing this cytokine result in mucocutaneous
candidiasis. The immune problem usually becomes evident during the first few years of life,
when the patient begins to have candidal infections of the mouth, nails, skin, and other mucosal
surfaces. The oral lesions are usually described as thick, white plaques that typically do not rub
off (essentially chronic hyperplastic candidiasis), although the other clinical forms of
candidiasis may also be seen. In some patients with mucocutaneous candidiasis, mutations in
the autoimmune regulator (AIRE) gene have been documented, with the resultant formation of
autoantibodies directed against the person’s own tissues. In most instances, the immunologic
attack is directed against the endocrine glands; however, the reasons for this tissue specificity
are currently unclear. Autoimmune destruction of the T-lymphocytes that produce interleukin-
17 (IL-17) and IL-22 appears to be responsible for the candidal infections seen in these
individuals. Young patients with mucocutaneous candidiasis should be evaluated periodically
because any one of a variety of endocrine abnormalities (i.e., endocrine-candidiasis syndrome,
autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy [APECED]
syndrome/autoimmune polyendocrinopathy syndrome, type 1), as well as iron-deficiency
anemia, may develop in addition to the candidiasis. These endocrine disturbances include
hypothyroidism, hypoparathyroidism, hypoadrenocorticism (Addison disease), and diabetes
mellitus. Typically, the endocrine abnormality develops months or even years after the onset of
the candidal infection. One recent study has documented increased prevalence of oral and
esophageal carcinoma in this condition, with these malignancies affecting approximately 10% of
adults with APECED syndrome. This finding represents another justification for periodic
reevaluation of these individuals. Interestingly, the candidal infection remains relatively
superficial rather than disseminating throughout the body. Both the oral lesions and any
cutaneous involvement (usually presenting as roughened, foul-smelling cutaneous plaques and
nodules) can be usually controlled with continuous use of relatively safe systemic antifungal
drugs. As with any long-term antibiotic treatment, development of drug-resistant organisms can
occur, however.
• Appearance and symptoms
• White plaques, some of which may be removable; red areas
• Common sites
• Tongue, buccal mucosa, palate
• Associated factors and comments
• Rare; inherited or sporadic idiopathic immune dysfunction
CHRONIC LOCALISED MUCOCUTANEOUS
CANDIDIASIS
• Severe form of the disease 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
• It is characterized by long standing and persistent candidiasis of the oral mucosa , nails , skin and
vaginal mucosa
• This form of candidiasis is often resistant to treatment , with only temporary remission following
the use of standard antifungal therapy
• It begins early in life , usually within the first two decades
• The disease begins as a pseudomembranous type of candidiasis and is followed by nail and
cutaneous involvement
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
CANDIDIASIS
ENDOCRINOPATHY
SYNDROME/ENDOC
RINE CANDIDIASIS
SYNDROME
• 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
Appearance and Symptoms
• White plaques, most of which are not removable

Common sites
• Tongue, buccal mucosa, palate

Associated Factors and Comments

• Rare; endocrine disorder develops after candidiasis
CHRONIC MYOSITIS (THYMOMA ASSOCIATED )
MUCOCUTANEOUS CANDIDIASIS
• The role of the thymus relates to a deficiency in T cell – mediated immunologic
function , hence providing an opportunity for the proliferation of candida
DIFFERENTIAL DIAGNOSIS
1) Candidal white lesions
• Slough associated with chemical burns
• Traumatic ulceration
• Mucous patches of syphilis
• White keratotic lesions

2) Red lesions
• Drug reactions
• Erosive lichen planus
• DLE (Discoid lupus erythematosus)
HISTOPATHOLOGIC FEATURES
• The candidal organism can be seen microscopically in either an exfoliative cytologic preparation or in tissue sections obtained from a
biopsy specimen.
• On staining with the periodic acid-Schiff (PAS) method or the Grocott-Gomori methenamine silver (GMS) method, the candidal hyphae
and yeasts can be readily identified. Both techniques stain carbohydrates, contained in abundance by fungal cell walls; the organisms
appear bright-magenta with the PAS stain or black with the GMS stain.
• To make a diagnosis of candidiasis, one must be able to see hyphae or pseudohyphae (which are essentially elongated yeast cells).
These hyphae are approximately 2 µm in diameter, vary in their length, and may show branching. Often the hyphae are accompanied
by variable numbers of yeasts, squamous epithelial cells, and inflammatory cells.
• A 10% to 20% potassium hydroxide (KOH) preparation may also be used to rapidly evaluate specimens for the presence of fungal
organisms. With this technique, the KOH lyses the background of epithelial cells, allowing the more resistant yeasts and hyphae to be
visualized. The disadvantages of the KOH preparation include the following:
 Lack of a permanent record
 Greater difficulty in identifying the fungal organisms, compared with PAS staining
 Inability to assess the nature of the epithelial cell population with respect to other conditions, such as epithelial dysplasia or pemphigus vulgaris

• The histopathologic pattern of oral candidiasis may vary slightly, depending on which clinical form of the infection has been submitted
for biopsy. The features that are found in common include an increased thickness of parakeratin on the surface of the lesion in
conjunction with elongation of the epithelial rete ridges. Typically, a chronic inflammatory cell infiltrate can be seen in the connective
tissue immediately subjacent to the infected epithelium, and small collections of neutrophils (microabscesses) are often identified in
the parakeratin layer and the superficial spinous cell layer near the organisms. The candidal hyphae are embedded in the parakeratin
layer and rarely penetrate into the viable cell layers of the epithelium unless the patient is extremely immunocompromised
TREATMENT
• 1) Polyene antimycotics/polyene antibiotics
• They are antimicrobial polyene compounds that target fungi.
• These polyene antimycotics are typically obtained from some species of Streptomyces bacteria.
• The polyenes bind to ergosterol in the fungal cell membrane and thus weakens it, causing leakage of K+
and Na+ ions, which may contribute to fungal cell death.
• Amphotericin B, nystatin are examples of polyene antimycotics. They are a subgroup of macrolides.
Nystatin
• Nystatin was the first effective treatment for oral candidiasis.
• Nystatin is formulated for oral use as a suspension or pastille (lozenge).
• Nystatin has a very bitter taste, which may reduce patient compliance; therefore, the taste has to be disguised with sucrose and flavoring
agents.
• If the candidiasis is due to xerostomia, the sucrose content of the nystatin preparation may contribute to xerostomia-related caries in these
patients.
• The gastrointestinal tract poorly absorbs nystatin and the other polyene antibiotic, amphotericin; therefore, their effectiveness depends on
direct contact with the candidal organisms. This necessitates multiple daily doses so that the yeasts are adequately exposed to the drug.
• Nystatin combined with triamcinolone acetonide cream or ointment can be applied topically and is effective for angular cheilitis that does
not have a bacterial component.
Generic name Trade name Indications Dosage Side effects
Nystatin Mycostatin Oral candidiasis One or two Nausea ,
pastilles pastilles diarrhea ,
Mycostatin oral dissolved slowly vomiting with
suspension in the mouth 4 to large doses
5 times daily for
10 to 14 days
Amphotericin B
• For many years in the United States, the use of amphotericin B was restricted to intravenous (IV)
treatment of lifethreatening systemic fungal infections. This medication subsequently became available as
an oral suspension for the management of oral candidiasis. Unfortunately, the interest in this formulation
of the drug was scant, and it is no longer marketed in the United States.

Generic name Trade name Indications Dosage Side effects Drug

interaction
Amphotericin B Fungizone Oral 1 mL (100 mg) Rash, No significant
oral candidiasis rinse and hold gastrointestinal drug
suspension in the mouth symptoms interactions
for as long as
possible, q.i.d.,
p.c., and h.s. for
2weeks
ASPERGILLOSIS
INTRODUCTION
• Aspergillosis is a fungal disease that is characterized by noninvasive and invasive forms.
• Noninvasive aspergillosis usually affects a normal host, appearing either as an allergic reaction or a cluster of fungal hyphae.
• Localized invasive infection of damaged tissue may be seen in a normal host, but a more extensive invasive infection is often
evident in the immunocompromised patient.
• With the advent of intensive chemotherapeutic regimens, the AIDS epidemic, and both solid-organ and bone marrow
transplantation, the prevalence of invasive aspergillosis has increased
• Patients with uncontrolled diabetes mellitus are also susceptible to Aspergillus spp. infections.
• Rarely, invasive aspergillosis has been reported to affect the paranasal sinuses of apparently normal immunocompetent
individuals.
• Normally, the various species of the Aspergillus genus reside worldwide as saprobic organisms in soil, water, or decaying
organic debris. Resistant spores are released into the air and inhaled by the human host, resulting in opportunistic fungal
infection second in frequency only to candidiasis. Interestingly, most species of Aspergillus cannot grow at 37° C; only the
pathogenic species have the ability to replicate at body temperature.
• The two most commonly encountered species of Aspergillus in the medical setting are A. flavus and A. fumigatus, with A.
fumigatus being responsible for most cases of aspergillosis. The patient may acquire such infections in the hospital
(“nosocomial” infection), especially if remodeling or building construction is being performed in the immediate area. Such
activity often stirs up the spores, which are then inhaled by the patient.
CLINICAL FEATURES
• The clinical manifestations of aspergillosis vary, depending on the host immune status and the presence
or absence of tissue damage.
• In the normal host, the disease may appear as an allergy affecting either the sinuses (allergic fungal
sinusitis) or the bronchopulmonary tract. An asthma attack may be triggered by inhalation of spores by a
susceptible person. Sometimes a low-grade infection becomes established in the maxillary sinus,
resulting in a mass of fungal hyphae called a fungus ball, although aspergilloma and mycetoma are
terms that are also sometimes used. Occasionally, the mass will undergo dystrophic calcifiation,
producing a radiopaque body called an antrolith within the sinus.
• Another presentation that may be encountered by the oral health care provider is aspergillosis after tooth
extraction or endodontic treatment, especially in the maxillary posterior segments. Presumably, tissue
damage predisposes the sinus to infection, resulting in symptoms of localized pain and tenderness
accompanied by nasal discharge. Immunocompromised patients are particularly susceptible to oral
aspergillosis, and some investigators have suggested that the portal of entry may be the marginal gingiva
and gingival sulcus. Painful gingival ulcerations are initially noted, and peripherally the mucosa and soft
tissue develops diffuse swelling with a gray or violaceous hue. If the disease is not treated, extensive
necrosis, which is seen clinically as a yellow or black ulcer, and facial swelling evolve.
Disseminated aspergillosis
• Occurs principally in immunocompromised patients, particularly in those who have leukemia or who are
taking high daily doses of corticosteroids.
• Such patients usually exhibit symptoms related to the primary site of inoculation: the lungs.
• The patient typically has chest pain, cough, and fever, but such symptoms are vague. Therefore, obtaining
an early, accurate diagnosis may be difficult.
• Once the fungal organism obtains access to the bloodstream, infection can spread to such sites as the CNS,
eye, skin, liver, gastrointestinal tract, bone, and thyroid gland.
HISTOPATHOLOGIC FEATURES
• Tissue sections of invasive Aspergillus spp. lesions show varying numbers of branching, septate hyphae, 3
to 4 µm in diameter. These hyphae show a tendency to branch at an acute angle and to invade adjacent
small blood vessels. Occlusion of the vessels often results in the characteristic pattern of necrosis
associated with this disease.
• In the immunocompetent host, a granulomatous inflammatory response—in addition to necrosis—can be
expected. In the immunocompromised patient, however, the inflammatory response is often weak or
absent, leading to extensive tissue destruction.
• Noninvasive forms of aspergillosis have histopathologic features that differs from invasive aspergillosis,
however. The fungus ball, for example, is characterized by a tangled mass of hyphae with no evidence of
tissue invasion. Because the fungus ball develops in a paranasal sinus (where it is exposed to air), spore-
bearing structures called fruiting bodies are formed. Allergic fungal sinusitis, on the other hand,
histopathologically exhibits large pools of eosinophilic inspissated mucin with interspersed sheetlike
collections of lymphocytes and eosinophils. Relatively few fungal hyphae are identified, and then only with
careful examination after Grocott-Gomori methenamine silver staining.
DIAGNOSIS
• Although the diagnosis of fungal infection can be established by identification of hyphae within tissue
sections, this finding is only suggestive of aspergillosis because other fungal organisms may appear
similar microscopically.
• Ideally, the diagnosis should be supported by culture of the organism from the lesion; however, from a
practical standpoint, treatment may need to be initiated immediately to prevent the patient’s demise.
• Culture specimens of sputum and blood are of limited value, because they are often negative despite
disseminated disease.
TREATMENT
• Treatment depends on the clinical presentation of aspergillosis.
• For immunocompetent patients with a noninvasive aspergilloma, surgical débridement may be all that is
necessary.
• Patients who have allergic fungal sinusitis are treated with débridement and corticosteroid drugs.
• For localized invasive aspergillosis in the immunocompetent host, débridement followed by antifungal
medication is indicated.
• Although systemic amphotericin B deoxycholate therapy was considered appropriate in the past, studies
have shown that voriconazole, a triazole antifungal agent, is more effective for treating these patients.
• For patients who cannot tolerate voriconazole, alternative drugs include liposomal amphotericin B or
caspofungin.
• Immunocompromised patients who have invasive aspergillosis should be treated by aggressive
débridement of necrotic tissue, combined with systemic antifungal therapy
PROGNOSIS
• Th prognosis for immunocompromised patients is much worse compared with immunocompetent
individuals, particularly if the infection is disseminated. Even with appropriate therapy, only about one
third of these patients survive.
• Because aspergillosis in the immunocompromised patient usually develops while the individual is
hospitalized, particular attention should be given to the ventilation system in the hospital to prevent
patient exposure to the airborne spores of Aspergillus spp.
Th term zygomycosis is still used extensively in the literature, although recent molecular genetic
studies have indicated that the class Zygomycetes actually is comprised of several unrelated fungi

MUCORMYCOSIS/
ZYGOMYCOSIS/PHYCOMYCOSIS
OR BLACK FUNGUS
SUBTITLE
INTRODUCTION
• A rare opportunistic (often affect immunocompromized patients), frequently fulminant, fungal infection
that is often considered as an emergency situation and has poor prognosis
• Life threatening or dreaded clinical entity with high morbidity and mortality
• Mucormycosis is classified into different forms as per anatomic sites

1) Rhinocerebral (sinuses and brain)

2) Pulmonary (lungs)
3) Gastrointestinal (stomach and intestine)
4) Cutaneous (skin)
5) Disseminated (widespread) - Affects two or more noncontiguous organs of the body.
6) Miscellaneous (rare) e..g mucormycosis of kidney
EPIDEMIOLOGY
• 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.
• Show seasonal variations
• 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.
• Internationally 1% patients with low immunity
• Sex is not likely to affect
• No racial factors predispose
ETIOLOGY OR CAUSES
• The class Zygomycetes is classified into two orders: Mucorales and kingdom Fungi
Entomophthorales. These two orders give rise to two different
infections.
Phylum Zygomycota
• Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces,
Cunninghamella, and Saksenaea) cause mucormycosis Subphylum Mucormycotina
• Most commonly Rhizopus species are causative organisms for the
mucormycosis Class Zygomycetes
• Mucormycosis is caused by saprophytic or saprobic fungi of many
genera related to Phycomycetes (Zygomycetes) and order Mucorale
Order Mucorales

Family Mucoraceae
The Mucorales hyphae are broad (5–20 µm), nonseptate, thin-walled, branched
at right angles, and twisted. It can be demonstrated histologically by hematoxylin Genera Rhizopus
and eosin, periodic acid–Schiff reaction, or by Grocott-Gomori’s methenamine Mucor
silver nitrate staining. These fungi possess an enzyme called ketone reductase, Rhizomucor
which facilitates the organisms to grow rapidly in hyperglycemic and acidic Absidia
media. The normal body physiology often inhibits growth by controlling pH and
glucose. However, in hyperglycemic and acidic states such as diabetic
Apophysomyces
ketoacidosis, this environment promotes the growth of these fungi. Iron also
Cunninghamella
enhances the pathogenicity and growth of these fungi, particularly those Saksenaea
patients are taking deferoxamine. These fungi possess siderophore which
increases iron uptake, which stimulates tissue invasion.
PATHOGENESIS
• Mucormycosis which is an angioinvasive infection
• 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.
Angioinvasion (fungi invade blood vessels)
Vessel thrombosis (causing infarction and ischemia)
Tissue necrosis
ROUTES OF SPREAD
• Mucorales are abundantly seen in soil, decaying organic materials such as 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 infection is transmitted by inhalation of sporangiospores or by direct contamination of the skin
wounds, particularly in burns.
• There are three different modes of transmission such as
1) Inhalation
2) Ingestion
3) Percutaneous introduction of spores of mucormycosis i..e truamatic inoculation or burns = cutaneous
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.
RISK FACTORS OR PREDISPOSING FACTORS
1) Diabetes (most common)
• Mucormycosis is noted especially in insulin-dependent diabetics who have uncontrolled diabetes and are ketoacidotic
• Ketoacidosis inhibits the binding of iron to transferrin, allowing serum iron levels to rise. The growth of these fungi is
enhanced by iron

2) Deferoxamine
• Patients who are taking deferoxamine (an iron-chelating agent used in the treatment of diseases, such as thalassemia) are
also at increased risk for developing mucormycosis due to an iron overload

3) Immunocompromised patients
• Including bone marrow transplant recipients, cytotoxic chemotherapy, patients with AIDS, and those receiving systemic
corticosteroid therapy.

4) Hematological diseases such as leukemia or lymphoma with neutropenic status often lead to disseminated
mucormycosis.

• Invasive mucormycosis is often associated with uncontrolled diabetes mellitus and other severe
immunodeficiencies with abnormality in cell-mediated immune system.
• Mucormycosis is rarely apparent in healthy individuals in the oral region
 • Commonest form
• 50% of cases occur in patients with
DM
• 50% of cases of total cases of
mucormycosis
• Usually occurs during an episode of
DKA, with disruption of host
defence mechansims. Thereby
permitting growth of rhizopus. Such
growth is inhibited by correction of
acidosis
• Mucormycosis may involve any one
of several areas of the body, but the

RHINOCEREBRAL rhinocerebral form is most relevant

to the oral health care provider.

MUCORMYCOSIS • In the head-and-neck region, the

nasal cavity and paranasal sinuses
are the most common sites for
primary infections of mucormycosis
CLINICAL FEATURES
• Nasal obstruction or stuffiness

• Bloody nasal discharge or epistaxis

• Facial pain or headache

• Facial swelling or cellulitis

• Visual disturbances with concurrent proptosis, ophthalmoplegia, chemosis

• Fever

• Symptoms related to cranial nerve involvement (e.g., facial paralysis) are often
present.
• With progression of disease into the cranial vault, blindness, lethargy, and seizures
may develop, followed by death.
• If the maxillary sinus is involved, the initial presentation may be seen as intraoral
swelling of the maxillary alveolar process, the palate, or both. If the condition
remains untreated, palatal ulceration may evolve, with the surface of the ulcer
typically appearing black and necrotic. Massive tissue destruction may result if the
condition is not treated
• Black necrotic eschar on the nasal turbinates or palate – very characteristic
RADIOGRAPHIC FEATURES
• Radiographically, opacifiation of the sinuses may be observed in conjunction with patchy effacement of
the bony walls of the sinuses. Such a picture may be difficult to distinguish from that of a malignancy
affecting the sinus area.
DIAGNOSIS
History Baselines
• CBC for neutropenia
• Dyspnea, cough, fever, chest pain – Pulmonary
• RBS or blood glucose level – sugar control
• Abdominal pain, nausea, vomiting - GIT • Serum iron level

• Nasal obstruction or stuffiness, Bloody nasal discharge or epistaxis,
Facial pain or headache, Vision problem, Lethargy, Siezures –
Rhinocerebral
• Medical history = Diabetes, transplant history, leukemia, lymphoma
• Drug history = deferoxamine(iron chelating agents), cytotoxic or
immunosuppressive drugs
• Serum electrolytres , Urea and creatinine
• ABGs to correct acidosis
Biopsy of involved tissue for identification of a fungus with a confirmation by a fungal
culture
• Tissue biopsy is usually confirmatory for the diagnosis for mucormycosis. 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

Clinical examination Swab of tissue discharge

Imaging
• Facial swelling or cellulitis
• Plain x ray
• Black necrotic eschar on the nasal turbinates or palate – very • CT scan/MRI of head and neck (extent of involvement, so that surgical margins can be
characteristic planned)

• Facial paralysis • Ct scan brain (intracranial involvement)

• Chest xray amd CT
• Proptosis or chemosis
CSf examination
Bronchoalveolar lavage
Diagnosis of mucormycosis is usually based on the histopathologic findings. Because of the grave nature of this infection, appropriate therapy must be
instituted in a timely manner (often without the benefit of definitive culture results).
HISTOPATHOLOGIC FEATURES
• Histopathologic examination of lesional tissue shows extensive necrosis with numerous large (6 to 30 µm
in diameter), branching, nonseptate fungal hyphae at the periphery is the characteristic. The hyphae tend
to branch at 90-degree angles.
• The extensive tissue destruction and necrosis associated with this disease are undoubtedly attributable
to the preference of the fungi for invasion of small blood vessels. This disrupts normal blood flow to the
tissue, resulting in infarction and necrosis.
• A neutrophilic infiltrate usually predominates in the viable tissue, but the host inflammatory cell
response to the infection may be minimal, particularly if the patient is immunosuppressed.
TREATMENT AND PROGNOSIS
• Successful treatment of mucormycosis consists of rapid accurate diagnosis of the condition, followed by radical surgical dé bridement of the infected,
necrotic tissue and systemic administration of high doses of one of the lipid formulations of amphotericin B.
Radical surgical debridement
• 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.
• Evaluation of frozen sections of curetted tissue, which has been stained with Calcoflor white and examined with florescence microscopy, can also be used to
guide the extent of dé bridement.
Liposomal amphotericin B
• Liposomal amphotericin B treatment has better tissue penetration and considered as first-line treatment
• 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
• 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.
• Alternatives
• 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.

• Total duration of antifungal drug treatment in mucormycosis varies with evolution but at least advised for 12 weeks.
Control of the patient’s underlying disease or risk factor (e.g., diabetic ketoacidosis) must be
attempted.
Adjuvant treatment (under assessment)
• HBO therapy (fungistatic effect and helps revascularization of the necrotic bone or ischemic tissue)
• Cytokines such as granulocyte macrophage-CSF and interferon gamma

Prosthetic obturation

• If the patient survives, the massive tissue destruction that remains presents a challenge
both functionally and aesthetically. Prosthetic obturation of palatal defects may be
necessary.
• 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 with control of underlying risk factor are
recommended treatment i.e For a successful outcome, correction of predisposing factors, timely diagnosis, surgical
debridement, and systemic antifungal are needed in combination.
• A multidisciplinary approach often needed and consists of otorhinolaryngologists, ophthalmologists, neurologists,
and dentists for successful management of patients with mucormycosis.
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%.
• 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.
• 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.
• Despite such therapy, the prognosis is usually poor, with approximately 40% to 50% of patients who
develop rhinocerebral mucormycosis dying of their disease. Because their underlying systemic disease
can usually be controlled, diabetic patients typically have a better prognosis than those who are
immunosuppressed.
COMPLICATIONS
1) Cavernous sinus thromboisis
2) Carotid or jugular vein thrombosis causing hemiparesis
3) Multiple cranial nerve palsies
4) Vision loss
5) Necrotizing fasciitis
6) Frontal lobe abscess
7) Death