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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

Research Article CODEN: IJRPJK ISSN: 2319 9563

International Journal of Research


in
Pharmaceutical and Nano Sciences
Journal homepage: www.ijrpns.com

ORAL CANDIDIASIS - REVIEW


L. Lekshmi*1, M. R. Anithalekshmi1, Linku Abraham1, Mohana.M.Nair1, Neema Aniyan1,
Nikhila.M.Nair1, Rinu Varghese1, Shajan Abraham1
1*
Department of Pharmaceutics, Nazareth College of Pharmacy, Thiruvalla, Kerala, India.

ABSTRACT
Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida
species, the commonest being Candida albicans. The incidence varies depending on age and certain
predisposing factors. Candida fungi are found almost everywhere in the environment. Some may live
harmlessly along with the abundant "native" species of bacteria that normally colonize the mouth,
gastrointestinal tract and vagina. Usually, Candida is kept under control by the body's immune defense.
Candidiasis is classified using the Lehner system. Some of the subtypes almost always occur as acute and
others chronic. Major signs and symptoms of oral candidiasis include White patches, or red lesions in oral
cavity, pruitus, and vulval erythematic, curd-like discharge from vagina. Management involves taking a
history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for
laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of
infections. The only prevention is Good Oral Hygiene.

KEY WORDS
Oral Cavity, Oral Candidiasis, Candida albicans and Oral Hygiene.

INTRODUCTION
Oral candidiasis is the one of the most common,
Author for Correspondence: opportunistric, treatable human fungal infection of
the oral cavity seen in all stages of life1. Oral
Lekshmi L, candiasis is also known as oral candidosis, oral
Department of Pharmaceutics, thrush, or opharyngeal candidiasis, moniliasis,
Nazreth College of Pharmacy, candidal stomatitis, muguet. It is common and
Thiruvalla, Kerala, India. under diagnosed among the elderly, particularly in
those who wear denatures and in many cases is
Email: lekshmilatha5@gmail.com avoidable with a good mouth care regimen. It is an
oral mucosal infection seen in persons with human
immunodeficiency virus (HIV), infection or

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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

acquired immune deficiency syndrome (AIDS). It acquired from the mother's vaginal canal during
can also be a mark of systemic disease, such as birth. At very young ages, the immune system is yet
diabetes mellitus and is a common problem among to develop fully and there is no individual immune
the immunocompromised2. Oral can be a frequent response to candida species, infants antibodies to
and significant source of oral discomfort, pain, loss the bacteria are normally supplied by the
of taste, and aversion to food. Oral candidiasis is mother's breast milk.
caused by the overgrowth or infection of the oral Denture Wearing
cavity by a yeast-like fungus, Candida. Candida is Denture wearing and poor denture hygiene is
commensal organism and part of the normal oral another risk factor for both candidal carriage and
flora in about 30%-50% of the population, and is oral candidiasis. Dentures provide a relative acidic,
capable of producing opportunistic infections within moist and anaerobic environment because the
the oral cavity when appropriate predisposing mucosa covered by the denture is sheltered from
factors exist. More than 20 species of Candida, oxygen and saliva. Poorly fitting dentures may also
Candida albicans are the most common and cause minor trauma to the mucosa, which is
important causative agent of oral candidiasis. Some increase the permeability of the mucosa and
other candidia species are C tropicalis, C glabrata, increase the ability of C. albicans to invade the
Cpseudotropicalis, C guillierimondii, C krusei, C tissues. These conditions all favor the growth of C.
lusitaniae, C parapsilosis, and C stellatoidea3. albicans.
Candida albicans Dry Mouth
C. albicansis the most common fungal pathogen in Both the quality and quantity of saliva are important
humans, able to cause various Infections oral defenses against candida. Decreased salivary
(Candidiasis) that may be severe enough to kill the flow rate or a change in the composition of saliva,
host if the infection is systemic. Two important can cause the salivary hypo function or hypo
factors that affect the pathogenicity of C. albicans salivation. It is an important predisposing factor for
are the ability to switch between yeast growth and candidiasis.
filamentous growth, i.e. the hyphal switch, and the Diet
ability to form biofilms which enables C. albicans Malnutrition, malabsorption or Poor diet,
to adhere to the surface of substrates. In biofilms especially hematinic deficiencies (iron, vitamin
cells show an increased resistance to the immune B12, folic acid) can predispose to oral
system and to antifungal drugs4. candidiasis, by causing diminished host defense and
Causes epithelial integrity.
The causative organism is Candidia species usually Smoking
Candida albicans, C. albicans accounts for about Heavy smoking is an important predisposing factor
50% of oral candidiasis and together, C. for candidasis, but the relationships are unknown.
albicans, C. tropicalis and C. glabrata account for One hypothesis is that cigarette smoke contains
over 80% of cases. Candidiasis caused by non-C. nutritional factors for C. albicans, or that local
albicans Candida species is associated more with epithelial alterations occur that facilitate
immunodeficiency. Such as HIV/AIDS. Certain colonization of candida species.
drugs can alter the natural organisms in the mouth, Antibiotics
which can then promote the growth of Candida. Broad-spectrum antibiotics eliminates the
These include the extended use of antibiotics, competing bacteria and disrupt the normally
steroids and oral contraceptives with high estrogen balanced ecology of oral micro-organisms. Acute
content. oral candidiasis occurring due to medication
Immunodeficiency/Immunocompromise with corticosteroids or broad-spectrum
Acute pseudo membranous candidiasis occurs in antibiotics (tetracycline).
about 5% of newborn infants. Candida species are

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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

Other factors Erythematous


Endocrine disorders, Presence of certain other Erythematous (atrophic) candidiasis is where the
mucosal lesions, Women undergoing hormonal condition appears as a red, raw-looking
changes, like pregnancy or those on birth control lesion. Some sources consider denture-related
pills5. stomatitis, angular stomatitis, median
Classification rhombiodglossitis, and antiobiotic-induced
Oral candidiasis is classified using the Lehner stomatitis as subtypes of erythematous candidiasis,
system, originally described in the 1960s, into acute since these lesions are commonly
and chronic forms. Some of the subtypes almost erythematous/atrophic. It may precede the
always occur as acute (e.g., acute pseudo formation of a pseudo membrane, be left when the
membranous candidiasis), and others chronic. membrane is removed, or arise de novo. The
Primary oral candidosis erythematous candidiasis accounts for 60% of oral
Acute form candidiasis cases. Where it is associated with
Pseudo membranous inhalation steroids, erythematous candidiasis
Erythematous commonly appears on the palate or the dorsum of
Chronic form the tongue. On the tongue, there is loss of
Erythematous the lingual papillae (depapillation), leaving a
Pseudo membranous smooth area on the tongue.
Hyperplastic (Plaque like) Acute erythematous candidiasis usually occurs on
Nodular the dorsum of the tongue in persons taking long
Candida associated lesions term corticosteroids or antibiotics, but occasionally
Denture stomatitis it can occur after only a few days of using a topical
Angular chealosis antibiotic. This is usually termed antibiotic sore
Median rhomboid glossitis mouth , antibiotic sore tongue or "antibiotic
Secondary oral candidosis induced stomatitis" because it is commonly painful
Oral manifestation of systemic mucocutanous as well as red.
candidosis Chronic erythematous candidiasis is more usually
Familialmucocutaneous candidiasis associated with denture wearing (see denture-
Diffuse chronic mucocutaneous candidiasis related stomatitis).
Familial mucocutaneous candidiasis Hyperplastic
Chronic granulomatous disease This variant is also sometimes termed "plaque-like
Candidosisendocrinopathy syndrome candidiasis" or "nodular candidiasis". The most
Acquired immune deficiency syndrome (AIDS) common appearance of hyperplastic candidiasis is a
Pseudo membranous persistent white plaque that does not rub off. The
Acute pseudo membranous candidiasis is a classic lesion may be rough or nodular in texture.
form of oral candidiasis; this is the most common Hyperplastic candidiasis is uncommon, accounting
type of oral candidiasis, accounting for about 35% for about 5% of oral candidiasis cases and is usually
of oral candidiasis cases. It is characterized by chronic and found in adults. The most common site
extensive white pseudo membranes consisting of of involvement is the commisural region of
desquamated epithelial cells, fibrin, and fungal the buccal mucosa, usually on both sides of the
hyphae these white patches occur on the surface of mouth.
the labial and buccal mucosa, hard and soft palate, Another term for hyperplastic candidiasis is
tongue, periodontal tissues, and or pharynx. The "candidal leukoplakia". This term is a largely
membrane can usually be scraped off with a swab to historical synonym for this subtype of candidiasis,
expose an underlying erythematousmucosa. rather than a true leukoplakia. It can be clinically
indistinguishable from true leukoplakia, but tissue

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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

biopsy shows candidal hyphae invading the Although this condition is also known as "denture
epithelium. Some sources use this term to describe sore mouth", there is rarely any pain. Candida is
leukoplakia lesions that become colonized associated with about 90% of cases of denture
secondarily by Candida species, thereby related stomatitis.
distinguishing it from hyperplastic candidiasis. It is Median rhomboid glossitis
known that Candida resides more readily in mucosa This is an elliptical or rhomboid lesion in the center
that is altered, such as may occur with dysplasia and of the dorsal tongue, just anterior (in front) of
hyperkeratosis in an area of leukoplakia. the circumvallate papillae. The area is depapillated,
Associated lesions reddened (or red and white) and rarely painful.
Candida-associated lesions are primary oral There is frequently Candida species in the lesion,
candidiasis (confined to the mouth), where the sometimes mixed with bacteria.
causes are thought to be multiple. For example, Linear gingival erythema
bacteria as well as Candida species may be This is a localized or generalized, linear band of
involved in these lesions. Frequently, antifungal erythematous gingivitis (inflammation of the gums).
therapy alone does not permanently resolve these It was first observed in HIV infected individuals
lesions, but rather the underlying predisposing and termed "HIV-gingivitis", but the condition is
factors must be addressed, in addition to treating the not confined to this group. Candida species are
candidiasis. involved, and in some cases the lesion responds to
Angular cheilitis antifungal therapy, but it is thought that other
Angular cheilitis is inflammation at the corners factors exist, such as oral hygiene and human
(angles) of the mouth, very commonly herpes viruses. This condition can develop
involving Candida species, when sometimes the into necrotizing ulcerative periodontitis.
terms "Candida-associated angular cheilitis", or less Chronic multifocal oral candidiasis
commonly, "monilialperlche" are used. Candida This is an uncommon form of chronic (more than
organisms alone responsible for about 20% of one month in duration) candidial infection involving
cases, and a mixed infection of C. multiple areas in the mouth, without signs of
albicans and Staphylococcus aureus for about 60% candidiasis on other mucosal or cutaneous sites. The
of cases. Signs and symptoms include lesions are variably red and/or white. Unusually for
soreness, erythema (redness), and fissuring of one, candidal infections, there is an absence of
or more commonly both the angles of the mouth, predisposing factors such as immune suppression,
with edema seen intraorally on the commisures. and it occurs in apparently healthy individuals,
Angular cheilitis is generally occurs in elderly normally elderly males. Smoking is a known risk
people and is associated with denture related factor.
stomatitis. Chronic mucocutaneous candidiasis
Denture related stomatitis This refers to a group of rare syndromes
This term refers to a mild inflammation and characterized by chronic candidal lesions on the
erythema of the mucosa beneath a denture, usually skin, in the mouth and on other mucous membranes
an upper denture in elderly edentulous individuals (i.e., a secondary oral candidiasis). These include
(with no natural teeth remaining). Some report that Localized chronic mucocutaneous candidiasis,
up to 65% of denture wearers have this condition to diffuse mucocutaneous candidiasis (Candida
some degree. About 90% of cases are associated granuloma), candidiasis-endocrinopathy syndrome
with candida species, where sometimes the terms and candidiasis thymoma syndrome. About 90% of
"candida-associated denture stomatitis, or people with chronic mucocutaneous candidiasis
Candida-associated denture induced stomatitis" have candidiasis in the mouth6.
(CADIS), are used. Some sources state that this is
by far the most common form of oral candidiasis.
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SIGNS AND SYMPTOMS stain, which effectively reveals spseudomycelia and


Signs and symptoms are dependent upon the type of hyphae when present. Angular cheilitis, with or
oral candidiasis. Often, apart from the appearance without oral signs and symptoms, should always
of the lesions, there are usually no other signs or raise the possibility or probability of candidiasis. In
symptoms. Most types of oral candidiasis are establishing the diagnosis, etiologic factors must be
painless, but a burning sensation may occur in some taken into consideration. Bacterial and viral
cases. Candidiasis can therefore sometimes be infections as well as immune pathologic diseases
misdiagnosed as burning mouth syndrome. A must also be considered, particularly if there is no
burning sensation is more likely with erythematous response to antifungal treatment. Epithelial
(atrophic) candidiasis, while hyperplastic dysplasia often manifests as white, red, and white-
candidiasis is normally entirely red lesions and must be ruled out8.
asymptomatic. Acute atrophic candidiasis may feel
like the mouth has been scalded with a hot TREATMENTS
liquid. Another potential symptom is a metallic, Priority in the treatment of oral candidosis is the
acidic, salty or bitter taste in the mouth. The pseudo alleviation of any identifiable predisposing factor.
membranous type rarely causes any symptoms apart Acquiring a thorough medical history is, therefore,
from possibly some discomfort or bad taste due to an essential Component in the management process.
the presence of the membranes. Sometimes the The regular and frequent use of a denture cleanser
patient describes the raised pseudo membranes as with anti-candidal properties such as 1% sodium
"blisters". Occasionally there can hypochlorite preparations, together with the
be dysphagia (difficulty swallowing), which removal of dentures overnight. Chlorhexidine
indicates that the candidiasis involves the or (0.2%) should be used if the denture has metal
opharynx or the esophagus, as well as the mouth. components since hypochlorite will otherwise cause
The trachea and the larynx may also be involved discolouration. Certain predisposing factors are;
where there is oral candidiasis, and this may cause however, more difficult if not impossible to
hoarseness of the voice7. eradicate such as where there is an underlying
disease (e.g. leukaemia or AIDS). In these cases,
DIAGNOSIS targeted antifungal therapy plays an important role
The diagnosis of Candida overgrowth is often made in the management strategy. Both the physical and
on the basis of clinical suspicion of the somewhat chemical reduction of Candida load in the oral
typical white, red, and white-red mucosal changes. cavity can be achieved by good oral hygiene
Associated angular cheilitis substantially enhances practices including tooth brushing and the use of
the probability of candidiasis. These findings are antimicrobial mouthwashes. Several mouthwashes
almost always associated with some degree of exhibit anti-candidal activity including triclosan,
discomfort or pain. The diagnosis can be confirmed chlorhexidinegluconate, and essential oil
by scrapings that are processed by potassium formulations. The latter tend to contain natural plant
hydroxide or Gram-stained before microscopic extracts such as thymol, eucalyptol, and
examination or by cultures with the cultures, bioflavonoid and these can have a direct anti-
quantitation and qualitation can be performed by candidal activity in vitro through cell membrane
candidal counts and speciation. Quantitation is done disruption and enzyme inhibition. When compared
by plating Candida brom cresol green (BCG) agar, with antibacterial agents, the availability of
incubating, and counting colony-forming units. antifungal agent is significantly lower. There as on
Qualitation is accomplished by using germ tube for this relates to the relatively recent recognition of
growth (for albicans) and carbohydrate the significance of human fungal infections and also
assimilations (for other species). Biopsy specimens the fact that fungal organisms are eukaryotic and
can be stained with the periodic acid-Schiff (PAS) share many features with mammalian cells making

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selection of suitable targets for antifungal agents Nystatin


problematic9. It is a drug which can be used as a primary line of
treatment. It is available as cream, oral suspensions,
CONVENTIONAL THERAPY liquid and pastille (lozenge) form. The liquid dose
The antifungal agent is based on the target of is 5 milliliters four times a day for one or two
activity. The treatment for 2 weeks after resolution weeks; it should be swished around the mouth
of the lesions. When the topical therapy fails then slowly, for as long as possible (i.e., a few minutes)
one has to start systemic therapy because failure of and then swallowed. One or two pastilles are taken
drug response is the initial sign of underlying four or five times a day for 7 to 14 days they should
systemic disease. Follow-up appointment after 3 to be dissolved in the mouth slowly and should not be
7 days is important to check the effect of drugs. chewed or swallowed whole. There is no significant
Main Goals of treatment are, drug interaction or side effects.
To identify and eliminate possible contributory Amphotercin B
factors: This drug is available as Lozenge (Fungilin 10mg)
To prevent systemic dissemination and oral suspension 100mg/ml which is to be
To eliminate any associated discomfort applied 3 to 4 times daily. Amphotericin-B inhibits
To reduce load of candida the adhesion of Candida to epithelial cells. The side
For infants and nursing mothers effect of the drug is nephrotoxicity
If you're breast-feeding an infant, you and your Clotrimozole
baby will do best if you're both treated. Otherwise, This drug decreases fungal growth by inhibiting the
you're likely to pass the infection back and forth. synthesis of ergo sterol. It is not indicated for
A mild antifungal medication for your baby systemic infection. This drug is available in Creams
and an antifungal cream for your breasts. and Lozenge 10mg. Main side effects of this drug is
If baby is using a pacifier or feeds from a unpleasant mouth sensation, increases liver enzyme
bottle, rinse nipples and pacifiers in a levels, nausea and vomiting.
solution of equal parts water and vinegar Second line of treatment:
daily and allow them to air dry to prevent The second lines of treatment are used for severe,
fungus growth. localized, immune suppressed patients and patients
If you use a breast pump, rinse any of the who respond poorly to primary line of treatment.
detachable parts that come in contact with Drugs mainly used in second line of treatment are,
your milk in a vinegar and water solution10. Ketoconazole
For adults with weakened immune systems Fluconazole
Antifungal medication Itraconazole
Treatment options are mainly categorized in to two Ketoconazole
lines, primary and secondary line of treatment. This It blocks ergosterol synthesis in fungal cell
comes in several forms, including lozenges, tablets membrane and is absorbed from the gastro intestinal
or a liquid that you swish in your mouth and then tract and metabolized in the liver. The dosage is
swallow. 200-400 mg tablets once or twice daily for 2 weeks.
Primary line of treatment Side effects are nausea, vomiting, liver damage and
Nystatin is the drug of choice as a primary line of also it interacts with anticoagulants. Ketoconazole
treatment. Usually for the mild and localized (as tablets) due to its potential liver toxicity is not
candidiasis this primary line of treatment is used introduced as initial therapy.
other drugs includes Clotrimazole which can be Fluconazole
taken as is Lozenges and Amphotercin B as oral This drug inhibits fungal cytochrome P450 sterol C-
suspension. 14 alpha demethylation. It is used in or opharyngial
candidosis and dosage is 50-100mg capsule once a

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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

day for 2-3 weeks. Main side effects are nausea, Yogurt
vomiting and headache. It interacts with Incorporate yogurt with live-acting cultures into
anticoagulants and this drug is contraindicated in your diet to boost the level of healthy bacteria in
pregnancy, liver and renal disease your mouth. Swish the yogurt about your mouth and
Itraconazole then refrain from eating or drinking anything
It is one of the broad spectrum antifungal agents shortly afterwards.
and contraindicated in pregnancy and liver disease. Thorough Cleaning
The dosage of the drug is 100 mg capsule once a If you wear dentures 23 and have thrush, cleaning
day for 2 weeks. The main side effects are nausea, your mouth and dentures each night is a must. Make
neuropathy and rashes. sure to soak your dentures in a cleaner overnight.
Treatment for pregnant women Rinse them well after removing from the
Because many of the drugs used to treat fungal solution24and before placing back into your
infections can be toxic to the developing fetus, only mouth15.
topical treatments-such as creams - are used when
ever possible11,12. PREVENTION
The risk of getting oral thrush can be reduced by
LIFESTYLE AND HOME REMEDIES13 following the advice outlined below.
To ease the pain, discomforts, and inconvenience of Oral hygiene
oral thrush, consider the following home remedies: Your chances of getting oral thrush are
Practice Good Oral Habits reduced if you keep your mouth clean and
Brushing 22 at least twice a day and flossing at least healthy. You can do this by,
once can cut down on the amount of time you have Rinsing your mouth after meals
to suffer an oral thrush infection. Make sure to Visiting your dentist regularly for check-ups
frequently replace your toothbrush until the Eating a healthy balanced diet
infection is gone14. Keeping your dentures clean
Natural Home Remedies for Oral Thrush Brushing your teeth twice a day with a
Mix equal parts of a tincture consisting of liquorice, toothpaste that contains fluoride
myrrh, and Echinacea. Use one teaspoon of this
Flossing regularly
remedy as a mouthwash that is taken with water
Using a mouthwash as part of your routine.
every three to four hours.
Denture hygiene
Saltwater Rinses
If you wear dentures clean them every night before
Add teaspoon of salt into one cup of warm water.
you go to bed. They can be done by brushing them
After the salt has dissolved, swish the rinse in your
with warm, soapy water and scrubbed with a
mouth and then spit out.
nailbrush on the non-polished side of the dentures.
Anti-Fungal Home Mouthwashes
Dentures can then be soaked in any liquid that can
Blend warm water, cider vinegar and a pinch of salt
be used to sterilize babies bottles. However,
to create a home remedy that fights fungus. Swish
products containing bleach should not be used on
the wash around the mouth, making sure to reach all
dentures that contain metal. You should visit your
corners. Use it as a gargle for the throat.
dentist to correct dentures that do not fit properly.
Garlic and Onions
This can also reduce the risk of oral thrush and
Tap into the antifungal power of onions and garlic,
soreness underneath the dentures.
which can help kill candida in the mouth. Increase
Smoking
the amount of garlic used in your diet to eliminate
Smoking encourages yeast in your mouth to grow
yeast infection. Onions also help heal the white
and increases your chance of getting oral thrush.
patches (lesions) found in the mouth.

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Lekshmi L et al. / International Journal of Research in Pharmaceutical and Nano Sciences. 4(6), 2015, 409 - 417.

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Please cite this article in press as: Lekshmi L et al. Oral candidiasis - Review, International Journal of
Research in Pharmaceutical and Nano Sciences, 4(6), 2015, 409-417.

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