Sandbox: oral candida

# Pathophysiology

## Pathogenesis
Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.

### Candida Virulence factors
The main virulence factors that mediate the infection:
- Secreting molecules that mediate adherence into host cells
- Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the fungus.
- Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated ellipsoid form) or in a yeast form (rounded to oval budding form. While the role of polymorphism is not clearly understood in the virulence of Candida, its noted that the species that are capable of producing the most severe form of the disease has this ability.
- Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.
Any condition that compromises cell mediated immunity, worsens the general status of the patient or provide a favorable medium for Candida to form biofilms  put the patient at increased risk for having candidiasis.
Candidal gene VPS4 plays an important role in oropharyngeal candidiasis specifically. Moreover, fungi with mutations affecting this gene was found to be less virulent.

## Gross pathology:
Oropharyngeal Candidiasis can be in one of 4 forms:

### Pseudomembranous candidiasis:
On speculum examination typical curdy white discharge is present. Usually present in newborns or in patients with deficient immunity, administering corticosteroids, etc.

### Atrophic candidiasis:
Appears as erythema  or edema without the characteristic white plaques. Usually seed in patients with dental dentures.

### Chronic hyperplastic candidiasis (Candidal leukoplakia):
Persistent tough, adherent, white lesions that are indistinguishable from other leukoplakia except through biopsy.
Seen more in smokers, patients with iron deficiency anemia or deficient cell mediated immunity.

### Chronic mucocutaneous  candidiasis (CMCC):
- CMCC is a syndrome characterized by chronic or recurrent superficial candida infection in the skin and mucous membranes in association with endocrinal and autoimmune syndromes.
- Characterized by inability of T cells to react to candidal antigens. Presents with: Recurrent or chronic candidal infections. Infection is usually superficial though invasive candidiasis is encountered especially in new born.
- Enocrinopathies as hypoparathyroidism and adrenal insufficiency may accompany chronic candidiasis.

## Microscopic pathology:
- Microscopic examination of the wet mount with 10% KOH or saline demonstrates hyphae, pseudohyphae and blastospores.

# History and symptoms:
Oropharyngeal Candidiasis can manifest in a variety of ways.
- Many cases are asymptomatic (mild disease or poor general condition)
- Dysphagia or odynophagia
- If candidiasis is of the pseudomembranous subtype, patient may complain of white patches on the mouth and tongue.
- Difficulty tasting food
- feeling of mouth fullness and discomfort

## Thrush and Breastfeeding
Because of the increased use of antibiotics in laboring women to reduce the transmission of Group B streptococcal infection to the infant, thrush has become more prevalent. Symptoms include:
- An oral rash in the infant's mouth
- A diaper rash that does not heal with conventional diaper rash treatments and ointments
- Burning, painful nipples for the breastfeeding mother
The rash and pain experienced by the mother can range from severe to mild and may complicate breastfeeding. Because thrush is assumed to be benign, it may be difficult to obtain treatment for an outbreak in the diaper area of an infant or mother's nipples. Over the counter yeast infection cream, that comes in the 7-day package, can be applied to the skin with good results within 24 - 48 hours. It should be washed off nipples before breastfeeding.

# Physical examination:
Appearance of the skin and mucous membranes on examination vary according to the subtype of oropharyngeal candidiasis.

## Pseudomembranous oropharyngeal candidiasis:
- Candida lesions appear as white plaques on the mouth and tongue.
- Trying to remove the patches with tongue depressor will leave an erythematous area and sometimes bleeding (which differentiates it from lichen planus).

## Atrophic oropharyngeal candidiasis:
- Its also called denture stomatitis.
- On inspection, lesions appear as erythematous areas with no white plaques.
- Lesions are usually found in the site of the areas of fitting contact of the dental dentures (hence its name).

## Hyperplastic oropharyngeal candidiasis (candidal leukoplakia):
- Plaques are usually found on both sides of the buccal mucosa (less often on the tongue)
- Appear as rough irregular nodular lesions on an erythematous base
- Non homogenous (speckled) leukoplakias are seen frequently

## Chronic mucocutaneous candidiasis:
- This syndrome is characterized by recurrent or persistent candidal infection in the mouth, tongue, scalp and nails.
- Due to chronicity of the infection, its usually associated with disfigurement and thickness of the affected areas. Nails appear brittle and broken.
- In rare cases, condition might progress into systemic candidiasis (usually if accompanied by another immunodeficiency).
- Patients frequently have accompanying autoimmune disorders as hypoparathyroidism, diabetes mellitus or Graves disease.

# Lab findings:
Diagnosis of oropharyngeal candidiasis is usually clinical and confirmatory diagnostic tests are rarely needed.
Oral smears Smears are obtained through gentle scraping of the lesions and spreading the debris directly on a glass slide.
In cases of hyperplastic candidiasis, biopsy is indiccated.
Both smears and biopsies can be stained by periodic acid Schiff stain which stains the walls of the fungi red.
Candida also can be stained using gram stain (strongly gram positive)

## Histopathologic examination:
Blastospores (yeast form) and pseudohyphae in the superficial epithelial layer is very characteristic for candidiasis.
Blastospores can be present in other opportunistic fungal infections ( Cryptococcus neoformans or Histoplasma capsulatum) that can have similar presentation and present in immunocompromised patient. If candida is suspected clinically while only blastospores are evident in histopathologic examination, exmamining more smears searching for pseusohyphae is indicated.

### Pseusdomembranous candidiasis:
Epithilium appears thickened wiith parakeratosis (superficial separation of a layer of the epithelium). Epithilium is usually infilitrated by PMNs and lamina propria is infiltrated by chronic inflammatory cells.
Pseudohyphae appear as weakly basophilic structures that is embedded within the epithelium.

### Atrophic candidiasis:
Atrophic candidiasis is similar to pseusdomembranous candidiasis but the difference is in the absence of parakeratosis. Epithelium is usually atrophic and thin.

### Hyperplastic candidiasis:
Epithelium is ususallly hyperplastic, hyperkeratotic and acanthotic with dysplasia in some cases.

# Causes:

## Most common causes:
Candida albicans is the most common cause of oropharyngeal candidiasis.

## Less common causes:
Other candida strains can cause oropharyngeal candidiasis:
- Candida krusei
- Candida glabrata
- Candida tropicalis