CANDIDIASIS 

This is a spectrum of infections caused by yeast-like fungi-Candida. Infections by Candida were previously known as moniliasis.

Etiology:
 Candida albicans is a commensal of mucus membranes of GIT (mouth to rectum) and vagina as a part of normal flora. It is usually held in check by normal bacterial flora and by normal body defenses. It is not permanent member of skin flora but colonization can occur under variety of circumstances. Although many species have been implicated in human infections, Candida albicans is responsible for most cases. C. tropicalis, C. dubliniensis C. parapsilosis, C. krusei, and C. pseudotropicalis can cause infections in immunocompromised patients.

Virulence factors:  
Ability to bind to underlying epithelial cells, production of proteases, phosphatases, and production of pseudohyphae, ability to inhibit chemotaxis are considered its virulence factors.

Host predisposing factors:  
Most cases of candidiasis follow endogenous infection by commensal Candida. Candida can cause a variety of opportunistic infections in people who have the following predisposing conditions:
a.  Long-term antibiotic therapy eradicating resident bacterial flora
b.  Age; infants and elderly are more susceptible
c.  Disorders such as diabetes mellitus, Cushing's syndrome, Addison's disease and hypothyroidism may predispose to mucocutaneous infections
d.  Immunodeficient conditions, inborn or acquired predispose to systemic infections
e.  Women on contraceptives (oral or IUCD), pregnancy, menopause are more at risk of vaginitis

Clinical conditions:
A. Mucocutaneous candidiasis

• Oral thrush: This condition is also known as pseudomembranous candidiasis. It occurs in acute as well as chronic form. Characteristic feature is a patch of creamy white pseudomembrane on the buccal epithelium, gums or the palate. Extension to tongue, palate and esophagus can occur. Erosion and ulceration are complications. Seen more often in infants (esp. bottle fed) and immunosuppressed patients (AIDS).

• Erythematous candidiasis: The tongue and palate is affected and the mucosa appear red and glazed. Clinical signs are not conspicuous but can occur in AIDS.

• Stomatitis: Seen in people with poor oral hygiene and poorly fitting dentures. Candidal growth on dentures and inflammation of tissue due to accumulated toxic material under the denture result in erosive and painful lesions.

• Hyperplastic oral candidiasis: It is characterized by white plaques in mouth especially on cheeks and tongue. Unlike the oral thrush, the hyperplastic plaque cannot be easily removed. The mucosa appear atrophic and there is loss if papillae on tongue.

• Median rhomboid glossitis: This uncommon type of infection is characterized by appearance of diamond shaped plaque on the dorsum of tongue with loss of papillae.

• Cheilitis: Soreness at the angles of mouth extending outward in the folds of the facial skin.

• Oesophagitis: It is the extension of oral candidiasis (thrush) into the oesophagus. It is associated with diabetes, AIDS, corticosteroid therapy, neoplasms. It is characterized by retrosternal pain, dysphagia, GI bleeding and nausea. Pruritis ani, which is infection of peri-anal skin can occur as result from long-term antibiotic therapy or extension of intestinal candidiasis.

• Vaginitis: It can manifest as vaginitis or vulvo-vaginitis. It commonly presents with itching , pruritis, patches of pseudomembrane on vaginal mucosa, erythema of vaginal mucosa, vulval skin and thick creamy white discharge. Women on contraceptives, pregnancy, menopause are more at risk of vaginitis. 

• Balanitis: Symptoms and signs vary from tiny papules and pustules on glans penis to persistant ulceration. Superficial red erosions are frequent.

B. Cutaneous candidiasis

• Candida paronychia: This is common in patients whose hands are frequently immersed in water. Typically, many fingers are affected. The nail fold becomes red and swollen and there is loss of cuticle with detachment of nail fold from nail plate. Tenderness and nail dystrophy can occur.

• Candida onychomycosis: Chronic paronychia leads to onychomycosis. The commonest type of candida onychomycosis is distal and lateral subungual onychomycosis (DLSO). After the nail is invaded the nail plate becomes hardened, thickened, brownish coloured which is striated or grooved.

• Intertriginous candidiasis: This condition occurs in skin folds such as in axilla, groin, inframammary fold, intergluteal fold, interdigital space etc. Diabetes, obesity, chronic alcoholism, moisture, chronic water contact, tight fitting clothes, shoes etc are predisposing factors.

• Chronic mucocuatenous candidiasis: It is the persistent candidial infection of mouth, skin and nail that is refractory conventional topical therapy. Relapse may occur after treatment. A number of immunological defects have been observed in such patients. 

• Diaper rash: Also called napkin rash, it is characterized by rashes in buttocks and genitals of infants. The wearing of diapers causes a significant increase in skin wetness and pH. Dampness, lack of air exposure, and increases in skin friction begin to break down the skin barrier and favour Candida infection.

• Candidial granuloma: This condition is seen in certain genetically predisposed individuals. It is characterized by vascular papules that are covered with yellow crusts. These develop into protrusions ~2 cms in length. Lesions are composed of granulomatous tissue with giant cells and chronic inflammatory reaction. 

C. Systemic candidiasis 

• Bronchial and pulmonary candidiasis: It is a chronic bronchitis with cough and expectoration. On bronchoscopy small white curd like patched may be seen. Predisposing conditions include leukemia, lymphoma, prolonged antibiotic or steroid therapy. Consolidation of lobe and lobar pneumonia may occur.

• Meningitis: Most patients have underlying conditions such as IV catheter, antibiotic or cytotoxic therapy. It occurs a result of dissemination from some other foci. 

• Endocarditis: Most patients are not immunosuppressed but may have pre-existing valvular disease or indwelling catheter. Infection can also occur as a result of IV drug abuse or following surgery.

• Urinary tract infections: This can occur in disseminated candidiasis, diabetes, pregnancy or catheterization. It is more common in females. Pyelonephritis can occur as a result of ascending infection or hematogenous spread from other foci. 

• Disseminated infections: When the fungus becomes blood borne, dissemination can occur resulting in cutaneous and subcutaneous lesions. This is usually the terminal event in severely debilitated patients such as transplant recipients, or leukemia.

• Septicemia: Candidemia usually causes fever, but other symptoms are nonspecific. Sometimes it resembles bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.

D. Allergic
Various conditions such as candidid, eczema, asthma and gastritis have been attributed to allergy towards Candida antigens.

Laboratory diagnosis: 

Specimen:  
Specimen collection depends on the site of infection. Various specimens that can be collected include mucosal scraping, skin & nail scraping, urine, blood, CSF, sputum etc.

Microscopy:  
Candida can be demonstrated as gram positive yeast like budding cells (with or without pseudohyphae) on Gram smear. KOH mounts too can show yeast like cells. Calcofluor white stain is also useful in demonstration of Candida in specimens.

Culture:  
It grows readily on bacteriological medium as well as SDA at 37^oC after overnight incubation. Colonies are white, creamy and bacteria-like. A positive culture does not mean that the C. albicans is pathogenic, as it may be a commensal.

Identification: Different species of Candida can be identified by following tests:
1. Chlamydospore formation on Cornmeal Agar (Dalmau plate)
2. Germ tube test (Reynaud Braude)
3. Carbohydrate assimilation 
4. Auxanography 
5. Latex agglutination

Treatment:
Predisposing conditions such as neutropenia, malnutrition, or uncontrolled diabetes should be reversed or controlled whenever possible. IV amphotericin B, alone or in combination with flucytosine, is recommended for the most severely ill patients. Fluconazole has also been reported to be effective for Candida meningitis. Topical nystatin, the imidazoles, and ciclopirox are usually effective against candidal skin infections. For candidal diaper rash, the skin should be kept dry by changing diapers frequently and by generously applying nystatin powder or an imidazole cream. Oral itraconazole is effective for many forms of acute and chronic mucocutaneous candidiasis.