HOME

TheInfoList



OR:

Oral candidiasis, also known as oral thrush among other names, is
candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...
that occurs in the mouth. That is, oral candidiasis is a
mycosis Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...
(yeast/fungal infection) of ''Candida'' species on the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
s of the mouth. ''
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
'' is the most commonly implicated organism in this condition. ''C. albicans'' is carried in the mouths of about 50% of the world's population as a normal component of the oral microbiota. This candidal carriage state is not considered a disease, but when ''Candida'' species become pathogenic and invade host tissues, oral candidiasis can occur. This change usually constitutes an opportunistic infection by normally harmless micro-organisms because of local (i.e., mucosal) or systemic factors altering host immunity.


Classification

Oral candidiasis is a
mycosis Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...
(fungal infection). Traditionally, oral candidiasis is classified using the Lehner system, originally described in the 1960s, into acute and chronic forms (see table). Some of the subtypes almost always occur as acute (e.g., acute pseudomembranous candidiasis), and others chronic. However, these typical presentations do not always hold true, which created problems with this system. A more recently proposed classification of oral candidiasis distinguishes ''primary oral candidiasis'', where the condition is confined to the mouth and perioral tissues, and ''secondary oral candidiasis'', where there is involvement of other parts of the body in addition to the mouth. The global
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
/
acquired immunodeficiency syndrome Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
(HIV/AIDS) pandemic has been an important factor in the move away from the traditional classification since it has led to the formation of a new group of patients who present with atypical forms of oral candidiasis.


By appearance

Three main clinical appearances of candidiasis are generally recognized: pseudomembranous, erythematous (atrophic) and hyperplastic. Most often, affected individuals display one clear type or another, but sometimes there can be more than one clinical variant in the same person.


Pseudomembranous

Acute pseudomembranous candidiasis is a classic form of oral candidiasis, commonly referred to as thrush. Overall, this is the most common type of oral candidiasis, accounting for about 35% of oral candidiasis cases. It is characterized by a coating or individual patches of pseudomembranous white slough that can be easily wiped away to reveal erythematous (reddened), and sometimes minimally bleeding, mucosa beneath. These areas of pseudomembrane are sometimes described as "curdled milk", or "cottage cheese". The white material is made up of debris, fibrin, and desquamated epithelium that has been invaded by yeast cells and hyphae that invade to the depth of the stratum spinosum. As an erythematous surface is revealed beneath the pseudomembranes, some consider pseudomembranous candidiasis and erythematous candidiasis stages of the same entity. Some sources state that if there is bleeding when the pseudomembrane is removed, then the mucosa has likely been affected by an underlying process such as lichen planus or chemotherapy. Pseudomembraneous candidiasis can involve any part of the mouth, but usually it appears on the tongue, buccal mucosae or palate. It is classically an acute condition, appearing in infants, people taking antibiotics or immunosuppressant medications, or immunocompromising diseases. However, sometimes it can be chronic and intermittent, even lasting for many years. Chronicity of this subtype generally occurs in
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
states, (e.g.,
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
, HIV) or in persons who use corticosteroids topically or by aerosol. Acute and chronic pseudomembranous candidiasis are indistinguishable in appearance.


Erythematous

Erythematous (atrophic) candidiasis is when the condition appears as a red, raw-looking lesion. Some sources consider denture-related stomatitis, angular stomatitis, median rhomboid glossitis, and antiobiotic-induced stomatitis as subtypes of erythematous candidiasis, since these lesions are commonly erythematous/atrophic. It may precede the formation of a pseudomembrane, be left when the membrane is removed, or arise without prior pseudomembranes. Some sources state that erythematous candidiasis accounts for 60% of oral candidiasis cases. Where it is associated with inhalation steroids (often used for treatment of
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
), erythematous candidiasis commonly appears on the palate or the dorsum of the tongue. On the tongue, there is loss of the
lingual papillae Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...
(depapillation), leaving a smooth area. Acute erythematous candidiasis usually occurs on the dorsum of the tongue in persons taking long term corticosteroids or antibiotics, but occasionally it can occur after only a few days of using a topical antibiotic. This is usually termed "antibiotic sore mouth", "antibiotic sore tongue", or "antibiotic-induced stomatitis" because it is commonly painful as well as red. Chronic erythematous candidiasis is more usually associated with denture wearing (see denture-related stomatitis).


Hyperplastic

This variant is also sometimes termed "plaque-like candidiasis" or "nodular candidiasis". The most common appearance of hyperplastic candidiasis is a persistent white plaque that does not rub off. The lesion may be rough or nodular in texture. Hyperplastic candidiasis is uncommon, accounting for about 5% of oral candidiasis cases, and is usually chronic and found in adults. The most common site of involvement is the commissural region of the
buccal mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
, usually on both sides of the mouth. Another term for hyperplastic candidiasis is "candidal leukoplakia". This term is a largely historical synonym for this subtype of candidiasis, rather than a true
leukoplakia Oral leukoplakia is a ''potentially malignant disorder'' affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque th ...
. Indeed, it can be clinically indistinguishable from true leukoplakia, but tissue biopsy shows candidal hyphae invading the epithelium. Some sources use this term to describe leukoplakia lesions that become colonized secondarily by ''Candida'' species, thereby distinguishing it from hyperplastic candidiasis. It is known that ''Candida'' resides more readily in mucosa that is altered, such as may occur with dysplasia and hyperkeratosis in an area of leukoplakia.


Associated lesions

''Candida''-associated lesions are primary oral candidiases (confined to the mouth), where the causes are thought to be multiple. For example, bacteria as well as ''Candida'' species may be involved in these lesions. Frequently, antifungal therapy alone does not permanently resolve these lesions, but rather the underlying predisposing factors must be addressed, in addition to treating the candidiasis.


Angular cheilitis

Angular cheilitis is inflammation at the corners (angles) of the mouth, very commonly involving ''Candida'' species, when sometimes the terms "''Candida''-associated angular cheilitis", or less commonly "monilial perlèche" are used. ''Candida'' organisms alone are responsible for about 20% of cases, and a mixed infection of ''C. albicans'' and '' Staphylococcus aureus'' for about 60% of cases. Signs and symptoms include soreness,
erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
(redness), and fissuring of one, or more commonly both the angles of the mouth, with edema (swelling) seen intraorally on the commissures (inside the corners of the mouth). Angular cheilitis generally occurs in elderly people and is associated with denture related stomatitis.


Denture-related stomatitis

This term refers to a mild inflammation and erythema of the mucosa beneath a
denture Dentures (also known as false teeth) are prosthetic devices constructed to replace missing teeth, and are supported by the surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable ( removable partial denture or ...
, usually an upper denture in elderly
edentulous Toothlessness, or edentulism, is the condition of having no teeth. In organisms that naturally have teeth, it is the result of tooth loss. Organisms that never possessed teeth can also be described as edentulous. Examples are the members of the ...
individuals (with no natural teeth remaining). Some report that up to 65% of denture wearers have this condition to some degree. About 90% of cases are associated with ''Candida'' species, where sometimes the terms "''Candida''-associated denture stomatitis", or "''Candida''-associated denture-induced stomatitis" (CADIS), are used. Some sources state that this is by far the most common form of oral candidiasis. Although this condition is also known as "denture sore mouth", there is rarely any pain. ''Candida'' is associated with about 90% of cases of denture related stomatitis.


Median rhomboid glossitis

This is an elliptical or rhomboid lesion in the center of the dorsal tongue, just anterior (in front) of the
circumvallate papillae Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...
. The area is depapillated, reddened (or red and white) and rarely painful. There is frequently ''Candida'' species in the lesion, sometimes mixed with bacteria.


Linear gingival erythema

This is a localized or generalized, linear band of erythematous gingivitis (inflammation of the gums). It was first observed in HIV infected individuals and termed "HIV-gingivitis", but the condition is not confined to this group. ''Candida'' species are involved, and in some cases the lesion responds to antifungal therapy, but it is thought that other factors exist, such as oral hygiene and human herpesviruses. This condition can develop into necrotizing ulcerative periodontitis.


Others


Chronic multifocal oral candidiasis

This is an uncommon form of chronic (more than one month in duration) candidal infection involving multiple areas in the mouth, without signs of candidiasis on other mucosal or cutaneous sites. The lesions are variably red and/or white. Unusually for candidal infections, there is an absence of predisposing factors such as immunosuppression, and it occurs in apparently healthy individuals, normally elderly males. Smoking is a known risk factor.


Chronic mucocutaneous candidiasis

This refers to a group of rare syndromes characterized by chronic candidal lesions on the skin, in the mouth and on other mucous membranes (i.e., a secondary oral candidiasis). These include Localized chronic mucocutaneous candidiasis, diffuse mucocutaneous candidiasis (Candida granuloma), candidiasis–endocrinopathy syndrome and candidiasis thymoma syndrome. About 90% of people with chronic mucocutaneous candidiasis have candidiasis in the mouth.


Signs and symptoms

Signs and symptoms are dependent upon the type of oral candidiasis. Often, apart from the appearance of the lesions, there are usually no other signs or symptoms. Most types of oral candidiasis are painless, but a burning sensation may occur in some cases. Candidiasis can, therefore, sometimes be misdiagnosed as
burning mouth syndrome Burning mouth syndrome (BMS) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. No related signs of disease are found in the mouth. People with ...
. A burning sensation is more likely with erythematous (atrophic) candidiasis, whilst hyperplastic candidiasis is normally entirely asymptomatic. Acute atrophic candidiasis may feel like the mouth has been scalded with a hot liquid. Another potential symptom is a metallic, acidic, salty or bitter taste in the mouth. The pseudomembranous type rarely causes any symptoms apart from possibly some discomfort or bad taste due to the presence of the membranes. Sometimes the patient describes the raised pseudomembranes as "blisters." Occasionally there can be
dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...
(difficulty swallowing), which indicates that the candidiasis involves the
oropharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...
or the
esophagus The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to ...
, as well as the mouth. The trachea and the larynx may also be involved where there is oral candidiasis, and this may cause hoarseness of the voice.


Causes


Species

The causative organism is usually ''
Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...
'', or less commonly other Candida species such as (in decreasing order of frequency) '' Candida tropicalis'', '' Candida glabrata'', '' Candida parapsilosis'', '' Candida krusei'', or other species ('' Candida stellatoidea'', '' Candida pseudotropicalis'', '' Candida famata'', '' Candida rugosa'', '' Candida geotrichium'', '' Candida dubliniensis'', and '' Candida guilliermondii''). ''C. albicans'' accounts for about 50% of oral candidiasis cases, and together ''C. albicans'', ''C. tropicalis'' and ''C. glabrata'' account for over 80% of cases. Candidiasis caused by non-''C. albicans'' Candida (NCAC) species is associated more with immunodeficiency. For example, in HIV/AIDS, ''C. dubliniensis'' and ''C. geotrichium'' can become pathogenic. About 35-50% of humans possess ''C. albicans'' as part of their normal oral microbiota. With more sensitive detection techniques, this figure is reported to rise to 90%. This candidal carrier state is not considered a disease, since there are no lesions or symptoms of any kind. Oral carriage of ''Candida'' is pre-requisite for the development of oral candidiasis. For ''Candida'' species to colonize and survive as a normal component of the oral microbiota, the organisms must be capable of adhering to the epithelial surface of the
mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
lining the mouth. This adhesion involves adhesins (e.g., hyphal wall protein 1), and extracellular polymeric materials (e.g., mannoprotein). Therefore, strains of ''Candida'' with more adhesion capability have more pathogenic potential than other strains. The prevalence of ''Candida'' carriage varies with geographic location, and many other factors. Higher carriage is reported during the summer months, in females, in hospitalized individuals, in persons with blood group O and in non-secretors of blood group antigens in saliva. Increased rates of ''Candida'' carriage are also found in people who eat a diet high in carbohydrates, people who wear dentures, people with xerostomia (dry mouth), in people taking broad spectrum antibiotics, smokers, and in immunocompromised individuals (e.g., due to HIV/AIDS, diabetes, cancer,
Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
or malnutrition). Age also influences oral carriage, with the lowest levels occurring in newborns, increasing dramatically in infants, and then decreasing again in adults. Investigations have quantified oral carriage of ''Candida albicans'' at 300-500
colony forming unit In microbiology, colony-forming unit (CFU, cfu or Cfu) is a unit which estimates the number of microbial cells (bacteria, fungi, viruses etc.) in a sample that are viable, able to multiply via binary fission under the controlled conditions. Count ...
s in healthy persons. More ''Candida'' is detected in the early morning and the late afternoon. The greatest quantity of ''Candida'' species are harbored on the posterior dorsal tongue, followed by the palatal and the buccal mucosae. Mucosa covered by an oral appliance such as a denture harbors significantly more candida species than uncovered mucosa. When ''Candida'' species cause lesions - the result of invasion of the host tissues - this is termed candidiasis. Some consider oral candidiasis a change in the normal oral environment rather than an exposure or true "infection" as such. The exact process by which ''Candida'' species switch from acting as normal oral commensals (saprophytic) state in the carrier to acting as a pathogenic organism (parasitic state) is not completely understood. Several ''Candida'' species are polymorphogenic, that is, capable of growing in different forms depending on the environmental conditions. ''C. albicans'' can appear as a yeast form ( blastospores), which is thought to be relatively harmless; and a hyphal form associated with invasion of host tissues. Apart from true hyphae, ''Candida'' can also form pseudohyphae — elongated filamentous cells, lined end to end. As a general rule, candidiasis presenting with white lesions is mainly caused by ''Candida'' species in the hyphal form and red lesions by yeast forms. ''C. albicans'' and ''C. dubliniensis'' are also capable of forming germ tubes (incipient hyphae) and chlamydospores under the right conditions. ''C. albicans'' is categorized serologically into A or B serotypes. The prevalence is roughly equal in healthy individuals, but type B is more prevalent in immunocompromised individuals.


Predisposing factors

The host defenses against opportunistic infection of candida species are * The oral epithelium, which acts both as a physical barrier preventing micro-organisms from entering the tissues, and is the site of cell mediated immune reactions. * Competition and inhibition interactions between candida species and other micro-organisms in the mouth, such as the many hundreds of different kinds of bacteria. * Saliva, which possesses both mechanical cleansing action and immunologic action, including salivary
immunoglobulin A Immunoglobulin A (Ig A, also referred to as sIgA in its secretory form) is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other typ ...
antibodies, which aggregate candida organisms and prevent them adhering to the epithelial surface; and enzymatic components such as
lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...
, lactoperoxidase and antileukoprotease. Disruption to any of these local and systemic host defense mechanisms constitutes a potential susceptibility to oral candidiasis, which rarely occurs without predisposing factors. It is often described as being "a disease of the diseased", occurring in the very young, the very old, or the very sick.


Immunodeficiency

Immunodeficiency is a state of reduced function of the immune system, which can be caused by medical conditions or treatments. Acute pseudomembranous candidiasis occurs in about 5% of
newborn An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
infants. Candida species are acquired from the mother's vaginal canal during birth. At very young ages, the immune system is yet to develop fully and there is no individual immune response to candida species, an infants antibodies to the fungus are normally supplied by the mother's breast milk. Other forms of immunodeficiency which may cause oral candidiasis include
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
/ AIDS, active
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and treatment,
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
or radiotherapy. Corticosteroid medications may contribute to the appearance of oral candidiasis, as they cause suppression of immune function either systemically or on a local/mucosal level, depending on the route of administration. Topically administered corticosteroids in the mouth may take the form of mouthwashes, dissolving lozenges or mucosal gels; sometimes being used to treat various forms of
stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...
. Systemic corticosteroids may also result in candidiasis. Inhaled corticosteroids (e.g., for treatment of
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
or chronic obstructive pulmonary disease), are not intended to be administered topically in the mouth, but inevitably there is contact with the oral and oropharyngeal mucousa as it is inhaled. In asthmatics treated with inhaled steroids, clinically detectable oral candidiasis may occur in about 5-10% of adults and 1% of children. Where inhaled steroids are the cause, the candidal lesions are usually of the erythematous variety. Candidiasis appears at the sites where the steroid has contacted the mucosa, typically the dorsum of the tongue (median rhomboid glossitis) and sometimes also on the palate. Candidal lesions on both sites are sometimes termed "kissing lesions" because they approximate when the tongue is in contact with the palate.


Denture wearing

Denture Dentures (also known as false teeth) are prosthetic devices constructed to replace missing teeth, and are supported by the surrounding soft and hard tissues of the oral cavity. Conventional dentures are removable ( removable partial denture or ...
wearing and poor denture hygiene, particularly wearing the denture continually rather than removing it during sleep, is another risk factor for both candidal carriage and oral candidiasis. Dentures provide a relative acidic, moist and anaerobic environment because the mucosa covered by the denture is sheltered from oxygen and saliva. Loose, poorly fitting dentures may also cause minor trauma to the mucosa, which is thought to increase the permeability of the mucosa and increase the ability of ''C. albicans'' to invade the tissues. These conditions all favor the growth of ''C. albicans''. Sometimes dentures become very worn, or they have been constructed to allow insufficient lower facial height (occlusal vertical dimension), leading to over-closure of the mouth (an appearance sometimes described as "collapse of the jaws"). This causes deepening of the skin folds at the corners of the mouth (nasolabial crease), in effect creating intertriginous areas where another form of candidiasis, angular cheilitis, can develop. Candida species are capable of adhering to the surface of dentures, most of which are made from polymethylacrylate. They exploit micro-fissures and cracks in the surface of dentures to aid their retention. Dentures may therefore become covered in a
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
, and act as reservoirs of infection, continually re-infecting the mucosa. For this reason, disinfecting the denture is a vital part of treatment of oral candidiasis in persons who wear dentures, as well as correcting other factors like inadequate lower facial height and fit of the dentures.


Dry mouth

Both the quantity and quality of saliva are important oral defenses against candida. Decreased salivary flow rate or a change in the composition of saliva, collectively termed salivary hypofunction or hyposalivation is an important predisposing factor.
Xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...
is frequently listed as a cause of candidiasis, but xerostomia can be subjective or objective, i.e., a symptom present with or without actual changes in the saliva consistency or flow rate.


Diet

Malnutrition, whether by
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
, or poor diet, especially hematinic deficiencies (iron,
vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
, folic acid) can predispose to oral candidiasis, by causing diminished host defense and epithelial integrity. For example, iron deficiency anemia is thought to cause depressed cell-mediated immunity. Some sources state that deficiencies of vitamin A or pyridoxine are also linked. There is limited evidence that a diet high in
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
s predisposes to oral candidiasis. ''
In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' and studies show that Candidal growth, adhesion and biofilm formation is enhanced by the presence of carbohydrates such as
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
,
galactose Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
and sucrose.


Smoking

Smoking, especially heavy smoking, is an important predisposing factor but the reasons for this relationship are unknown. One hypothesis is that cigarette smoke contains nutritional factors for ''C. albicans'', or that local epithelial alterations occur that facilitate colonization of candida species.


Antibiotics

Broad-spectrum antibiotic A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial ...
s (e.g. tetracycline) eliminate the competing bacteria and disrupt the normally balanced ecology of oral microorganisms, which can cause antibiotic-induced candidiasis.


Other factors

Several other factors can contribute to infection, including endocrine disorders (e.g.
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
when poorly controlled), and/or the presence of certain other mucosal lesions, especially those that cause hyperkeratosis and/or
dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs ( macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopi ...
(e.g.
lichen planus Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, and is only named that because it looks like one. It is characterized by polygonal, fla ...
). Such changes in the mucosa predispose it to secondary infection with candidiasis. Other physical mucosal alterations are sometimes associated with candida overgrowth, such as
fissured tongue Fissured tongue is a benign condition characterized by deep grooves (fissures) in the dorsum of the tongue. Although these grooves may look unsettling, the condition is usually painless. Some individuals may complain of an associated burning sen ...
(rarely),
tongue piercing A tongue piercing is a body piercing usually done directly through the center of the tongue. Since its decline in popularity around 2011, it has seen a recent upsurge making it now the second most popular piercing amongst young women aged 18-25 ...
, atopy, and/or hospitalization.


Diagnosis

The diagnosis can typically be made from the clinical appearance alone, but not always. As candidiasis can be variable in appearance, and present with white, red or combined white and red lesions, the differential diagnosis can be extensive. In pseudomembraneous candidiasis, the membranous slough can be wiped away to reveal an erythematous surface underneath. This is helpful in distinguishing pseudomembraneous candidiasis from other white lesions in the mouth that cannot be wiped away, such as lichen planus, oral hairy leukoplakia. Erythematous candidiasis can mimic geographic tongue. Erythematous candidiasis usually has a diffuse border that helps distinguish it from erythroplakia, which normally has a sharply defined border. Special investigations to detect the presence of candida species include oral swabs, oral rinse or oral smears. Smears are collected by gentle scraping of the lesion with a spatula or tongue blade and the resulting debris directly applied to a glass slide. Oral swabs are taken if culture is required. Some recommend that swabs be taken from 3 different oral sites. Oral rinse involves rinsing the mouth with phosphate-buffered saline for 1 minute and then spitting the solution into a vessel that examined in a pathology laboratory. Oral rinse technique can distinguish between commensal candidal carriage and candidiasis. If candidal leukoplakia is suspected, a
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
may be indicated. Smears and biopsies are usually stained with
periodic acid-Schiff Periodicity or periodic may refer to: Mathematics * Bott periodicity theorem, addresses Bott periodicity: a modulo-8 recurrence relation in the homotopy groups of classical groups * Periodic function, a function whose output contains values tha ...
, which stains carbohydrates in fungal cell walls in magenta.
Gram stain In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish b ...
ing is also used as Candida stains are strongly Gram positive. Sometimes an underlying medical condition is sought, and this may include blood tests for full blood count and hematinics. If a biopsy is taken, the histopathologic appearance can be variable depending upon the clinical type of candidiasis. Pseudomembranous candidiasis shows hyperplastic epithelium with a superficial parakeratotic desquamating (i.e., separating) layer. Hyphae penetrate to the depth of the stratum spinosum, and appear as weakly basophilic structures. Polymorphonuclear cells also infiltrate the epithelium, and chronic inflammatory cells infiltrate the lamina propria. Atrophic candidiasis appears as thin,
atrophic Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
epithelium, which is non-keratinized. Hyphae are sparse, and inflammatory cell infiltration of the epithelium and the lamina propria. In essence, atrophic candidiasis appears like pseudomembranous candidiasis without the superficial desquamating layer. Hyperplastic candidiasis is variable. Usually there is hyperplastic and acanthotic epithelium with parakeratosis. There is an inflammatory cell infiltrate and hyphae are visible. Unlike other forms of candidiasis, hyperplastic candidiasis may show dysplasia.


Treatment

Oral candidiasis can be treated with topical anti-fungal drugs, such as
nystatin Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be ...
, miconazole,
Gentian violet Crystal violet or gentian violet, also known as methyl violet 10B or hexamethyl pararosaniline chloride, is a triarylmethane dye used as a histological stain and in Gram's method of classifying bacteria. Crystal violet has antibacterial, antif ...
or amphotericin B. Surgical excision of the lesions may be required in cases that do not respond to anti-fungal medications. Underlying immunosuppression may be medically manageable once it is identified, and this helps prevent recurrence of candidal infections. Patients who are immunocompromised, either with
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
or as a result of
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
, may require systemic prevention or treatment with oral or intravenous administered anti-fungals. However, there is strong evidence that drugs that are absorbed or partially absorbed from the GI tract can prevent candidiasis more effectively than drugs that are not absorbed in the same way. If candidiasis is secondary to corticosteroid or antibiotic use, then use may be stopped, although this is not always a feasible option. Candidiasis secondary to the use of inhaled steroids may be treated by rinsing out the mouth with water after taking the steroid. Use of a spacer device to reduce the contact with the oral mucosa may greatly reduce the risk of oral candidiasis. In recurrent oral candidiasis, the use of azole antifungals risks selection and enrichment of drug-resistant strains of candida organisms.
Drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
is increasingly more common and presents a serious problem in persons who are immunocompromised.
Prophylactic Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
use of antifungals is sometimes employed in persons with HIV disease, during radiotherapy, during immunosuppressive or prolonged antibiotic therapy as the development of candidal infection in these groups may be more serious. The candidal load in the mouth can be reduced by improving oral hygiene measures, such as regular toothbrushing and use of anti-microbial mouthwashes. Since smoking is associated with many of forms of oral candidiasis, cessation may be beneficial.


Denture hygiene

Good denture hygiene involves regular cleaning of the dentures, and leaving them out of the mouth during sleep. This gives the mucosa a chance to recover, while wearing a denture during sleep is often likened to sleeping in one's shoes. In oral candidiasis, the dentures may act as a reservoir of Candida species known as denture stomatitis which continually reinfects the mucosa once antifungal medication is stopped. Therefore, they must be disinfected as part of the treatment for oral candidiasis. There are commercial denture cleaner preparations for this purpose, but it is readily accomplished by soaking the denture overnight in a 1:10 solution of
sodium hypochlorite Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
( Milton, or household bleach). Bleach may corrode metal components, so if the denture contains metal, soaking it twice daily in
chlorhexidine Chlorhexidine (CHX) (commonly known by the salt forms chlorhexidine gluconate and chlorhexidine digluconate (CHG) or chlorhexidine acetate) is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgi ...
solution can be carried out instead. An alternative method of disinfection is to use a 10% solution of acetic acid (vinegar) as an overnight soak, or to microwave the dentures in 200mL water for 3 minutes at 650 watts. Microwave sterilization is only suitable if no metal components are present in the denture. Antifungal medication can also be applied to the fitting surface of the denture before it is put back in the mouth. Other problems with the dentures, such as inadequate occlusal vertical dimension may also need to be corrected in the case of angular cheilitis.


Prognosis

The severity of oral candidiasis is subject to great variability from one person to another and in the same person from one occasion to the next. The prognosis of such infection is usually excellent after the application of topical or systemic treatments. However, oral candidiasis can be recurrent. Individuals continue to be at risk of the condition if underlying factors such as reduced salivary flow rate or immunosuppression are not rectifiable. Candidiasis can be a marker for underlying disease, so the overall prognosis may also be dependent upon this. For example, a transient erythematous candidiasis that developed after antibiotic therapy usually resolves after antibiotics are stopped (but not always immediately), and therefore carries an excellent prognosis—but candidiasis may occasionally be a sign of more sinister undiagnosed pathology, such as HIV/AIDS or leukemia. It is possible for candidiasis to spread to/from the mouth, from sites such as the pharynx, esophagus, lungs, liver, anogenital region, skin or the nails. The spread of oral candidiasis to other sites usually occurs in debilitated individuals. It is also possible that candidiasis is spread by sexual contact. Rarely, a superficial candidal infection such as oral candidiasis can cause invasive candidiasis, and even prove fatal. The observation that Candida species are normally harmless commensals on the one hand, but are also occasionally capable of causing fatal invasive candidiases has led to the description " Dr Jekyll and Mr Hyde". The role of thrush in the hospital and ventilated patients is not entirely clear, however, there is a theoretical risk of positive interaction of candida with topical bacteria.


Epidemiology

In humans, oral candidiasis is the most common form of candidiasis, by far the most common fungal infection of the mouth, and it also represents the most common opportunistic oral infection in humans with lesions only occurring when the environment favors pathogenic behavior. Oropharyngeal candidiasis is common during cancer care, and it is a very common oral sign in individuals with HIV. Oral candidiasis occurs in about two thirds of people with concomitant AIDS and esophageal candidiasis. The incidence of all forms of candidiasis have increased in recent decades. This is due to developments in medicine, with more invasive medical procedures and surgeries, more widespread use of broad spectrum antibiotics and immunosuppression therapies. The HIV/AIDs global pandemic has been the greatest factor in the increased incidence of oral candidiasis since the 1980s. The incidence of candidiasis caused by NCAC species is also increasing, again thought to be due to changes in medical practise (e.g.,
organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpor ...
and use of indwelling catheters).


History

Oral candidiasis has been recognized throughout recorded history. The first description of this condition is thought to have occurred in the 4th century B.C. in "Epidemics" (a treatise that is part of the
hippocratic corpus The Hippocratic Corpus (Latin: ''Corpus Hippocraticum''), or Hippocratic Collection, is a collection of around 60 early Ancient Greek medical works strongly associated with the physician Hippocrates and his teachings. The Hippocratic Corpus cov ...
), where descriptions of what sounds like oral candidiasis are stated to occur with severe underlying disease. The colloquial term "thrush" refers to the resemblance of the white flecks present in some forms of candidiasis (e.g., pseudomembranous candidiasis), with the breast of the bird of the same name.


Society and culture

Many pseudoscientific claims by proponents of alternative medicine surround the topic of candidiasis. Oral candidiasis is sometimes presented in this manner as a symptom of a widely prevalent ''systemic candidiasis'', ''candida hypersensitivity syndrome'', ''yeast allergy'', or ''gastrointestinal candida overgrowth'', which are medically unrecognized conditions. (See: Alternative medicine in Candidiasis)


References


External links

{{Authority control Animal fungal diseases Mycosis-related cutaneous conditions Oral mucosal pathology Fungal diseases simple:Oral candidiasis