Candidiasis Mucocutaneous

Description of Medical Condition

A mucocutaneous disorder caused by infection with various species of Candida. Candida is normally present, in very small amounts, in the oral cavity, gastrointestinal tract, and female genital tract.

Candida vulvovaginitis — infection on the vaginal mucosa, often associated with cutaneous vulvar involvement
Orophatyngeal candidiasis — infection of the oral cavity (“thrush”) and/or pharynx.
Candida esophagitis — usually associated with an immunosuppressed host
Gastrointestinal candidiasis — gastritis, sometimes with ulcers, usually associated with thrush. The small and large bowel can also be affected.
Angular cheilitis — fissures formed by Candida infection at the corners of the mouth.

System(s) affected: Skin/Exocrine, Gastrointestinal

Genetics: Chronic mucocutaneous candidiasis is a heterogeneous clinical syndrome that usually presents in childhood and can have an autosomal recessive, dominant or sporadic mode of inheritance. Sera from HIV-infected patients with thrush have been screened for C. albicans genomic expression. Identified genes include some encoding immunogenic antigens. Notably, when disrupted, genes can confer defects in morphogenesis, adherence, and mortality. Additionally, family analysis has identified an isolated form of mucocutaneous candidiasis that affects nails only, and its chromosomal region. This and multiple other studies suggest that there are distinct phenotypes that respond in varying degrees to Candida replication in their host.

Incidence/Prevalence in USA: More common, particularly vaginal. Very common in persons with immunodeficiency.

Predominant age:

Infants and older geriatrics predominate for thrush and cutaneous infections
Women during their child bearing years predominate for vaginitis

Predominant sex: Female > Male (due to the entity of Candida vaginitis)

Medical Symptoms and Signs of Disease

In pediatrics

Oral lesions — white, raised, painless, distinct patches within oral cavity
Perineal — etythematous maculopapular rash with white “satellite” pustules
Angular cheilitis — painful fissures in mouth corners

In adults (whether or not immunocompromised)

Vulvovaginal lesions — thin to thick whitish, “cottage cheese”-like discharge; etythematous patches in vagina or on perineum. Range from asymptomatic to intense pruritus with “burning” irritation

In immunocompromised hosts

Oral lesions — white, raised, painless, distinct patches; erythematous slightly raised patches; thick dark brownish coating; deep fissures
Esophagitis — dysphagia, odynophagia, retrosternal pain. Usually associated with thrush.
Gastrointestinal — ulcerations, pain
Balanitis — erythema, linear erosions and scaling
Angular cheilitis (see Pediatrics)

What Causes Disease?

Species of Candida albicans and, less frequently, Candida tropicalis

Risk Factors

Immunosuppression
Antibacterial therapy
Douching and other intravaginal chemicals
Other vaginitides
Dentures
Chronic steroids (oral or inhaled)
Hyperglycemia
Exogenous estrogen
See Associated Conditions

Diagnosis of Disease

Differential Diagnosis

Baby formula can mimic thrush
Hairy leukoplakia can mimic thrush but does not rub off to an erythematous base and is usually on the lateral sides of the tongue.
Other yeasts may present like Candida
Some of the symptoms of Trichomonas vaginalis (TV) can mimic those of Candida vulvovaginitis (CV). Specific symptom overlaps include: Both may have 1) initial symptoms post-menstrually, 2) marked vulvar irritation, 3) labial erythema, 4) external dysuria, and 5) vaginal tenderness.
Iron deficiency and staph infections can mimic angular cheilitis

Laboratory

Potassium hydroxide 10% microscopic slide preparation (“KOH prep”). Breaks down epithelial cell walls allowing yeast forms to be more easily identified. Best if heated. Lack of slide identification does not rule out and, conversely, one may identify a scant number of fungal forms without symptoms or pathogenesis.
Gram stain reveals gram positive yeast forms
Culture — blood orSabouraud’s agar. A positive may be result of normal flora.

Drugs that may alter lab results:

Douches and spermicides
Inadequately dosed antifungal medication

Disorders that may alter lab results: Other vaginitides (may obscure vaginal slide findings)

Pathological Findings

Slide prep — Mycelia (hyphae) or pseudomycelia (pseudohyphae) yeast forms. A polymorphonuclear leukocyte response is not usually seen unless another pathogen or inflammatory agent is present

Imaging

Esophageal candidiasis will sometimes reveal a “cobblestone” appearance with a barium swallow and, less commonly, fistulas or esophageal dilatation (from denervation)

Diagnostic Procedures

For KOH prep, will need sample of discharge or “coating” of infected area or ulcer
Esophagitis may need endoscopic biopsy
HIV seropositivity plus thrush with dysphagia relieved by antifungal treatment is consistent with diagnosis of Candida esophagitis

Treatment (Medical Therapy)

Appropriate Health Care

Outpatient

General Measures

Screen both well infants and patients with severe immunodeficiency using appropriate history and physical at all routine visits

Activity

N/A

Diet

A few authorities say rectal colonization may be decreased with active culture yogurt or other live lactobacillus, but no clear correlation

Patient Education

Advise patients at risk for recurrence about antibacterial therapy overgrowth
Inform appropriate patients of over-the-counter vaginitis medications
Cotton underwear may allow for better perineal ventilation and, thus, a less suitable environment for yeast

Medications (Drugs, Medicines)

Drug(s) of Choice

Vaginal (one day therapies):
- Fluconazole (Diflucan) 150mg tablet once
- Clotrimazole (Canesten) 500mg (intravaginal) tablet
- Tioconazole (Monistat-1, Vagistat-1) 6.5% ointment 5 grams
- Butoconazole (Femstat, Gynazole-1) 2% cream 5 grams
Vaginal (conventional multi-day therapies):
- Miconazole (Monistat) 2% cream: one applicator or 100 mg suppositories, intravaginally q hs x 7 days
- Clotrimazole (Gyne-Lotrimin, Mycelex): intravaginal suppositories 100 mg q hs x 6-7 days or 200 mg q hs x 3 days. 1 % cream one applicator intravaginally q hs x 6-7 days.
- Nystatin (Mycostatin, Nilstat) 100,000 U/gram cream (one applicator) or 100,000 U tablets (one) intravaginally bid x 7 days
Oropharyngeal:
- Clotrimazole (Mycelex) 10 mg troche, slowly dissolve in mouth 5 times per day, preferably over 20 minutes for 7-14 days (2 days after disappearance of thrush) (first choice in most literature)
- Nystatin pastilles -1 or 2, qid for 7-14 days (2 days after disappearance of thrush)
- Nystatin oral suspension (100,000 units/mL): Children apply 5-10 mL qid x10 days directly to oral lesions. Adults swish and swallow 5-10 mL over 20 minutes qid x14 days. Prophylaxis for relapses consists of above dosages 2-5 times per day
- Fluconazole 100mg qd for 7-14 days
Esophagitis:
- Fluconazole (Diflucan) 200 mg, then 100 mg po qd x10-21 days
- Itraconazole solution 100-200 mg/day for 14-21 days
- Ketoconazole (Nizoral) 200-400 mg tablets — one po qd X14-21 days
Gastrointestinal (therapy not well defined)
- Fluconazole 200 mg tablets — one po qd X14-21 days OAmphotericin B (Fungizone) IV

Note: Resistant candidiasis is common in severely im-munocompromised hosts. Some patients with otherwise resistant oropharyngeal and/or esophageal infection benefit from amphotericin B, 50 mg 3 times a week or from itraconazole (Sporanox) 200 mg bid for the same number of days described under fluconazole dosing for the various sites of infection mentioned above.

Contraindications:

Severe allergic response or a severe adverse reaction
Ketoconazole, itraconazole or nystatin (if swallowed)
severe hepatotoxicity
Amphotericin B — renal failure

Precautions:

Vaginal — miconazole is usually drug of choice in pregnancy
Ketoconazole — rarely, men may have difficulty achieving erections secondary to this drug. May cause light sensitivity. Teratogen in pregnancy and probably excreted in milk. Not well studied in children. Anaphylaxis is reported. Hepatic toxicity has been noted, predominantly with long-term therapy.
Fluconazole — adjust dose with renal compromise. Hepatotoxicity is rare. Very expensive relative to most other oral agents. Resistance has often been noted.
Itraconazole — doubling the Itraconazole dose results in approximately a three-fold increase in the itraconazole plasma concentrations
Amphotericin B — renal toxicity and hypokalemia common. Careful monitoring is mandatory. Ketotic diabetics should have well controlled blood sugars prior to administration. Safety during pregnancy is not established.

Significant possible interactions:

Rarely seen with creams, lotions or suppositories
Ketoconazole
- Antacids, H2 blockers (achlorhydria) — reduce ketoconazole concentration
- Antiretrovirals — many have problematic interactionswith ketoconazole; check drug reference
- Coumadin — potentiates anticoagulation
- Hypoglycemics — enhanced hypoglycemia
- INH/rifampin — reduce ketoconazole concentration
- Cyclosporine — increased cyclosporine concentration
- Phenytoin — metabolism altered; check levels
- Alcohol — disulfiram reaction possible
- Others — check drug interaction reference
Amphotericin B
- Onephrotoxic drugs — enhanced toxicity
- Corticosteroids — potentiates hypokalemia
- Ketoconazole — drug antagonism; do not give together
Fluconazole
- Rifampin — decreased fluconazole concentrations
- Tolbutamide — decreased tolbutamide concentrations
- Warfarin, phenytoin, cyclosporine — metabolism altered; check levels
Itraconazole — this potent cytochrome P450 3A4 isoenzyme system (CYP3A4) inhibitor may increase plasma concentrations of the many drugs metabolized by that pathway and cause serious cardiovascular events. Carefully assess all co-administered medications.

Alternative Drugs

Vaginal
- Terconazole (Terazol) particularly for recurrent cases that may involve imidazole resistance. 0.4% cream — one applicator intravaginally q hs x 7 days; 0.8% cream/80 mg suppositories — one applicator or one suppository intravaginally q hs x 3 days
- Any of the antifungal creams or suppositories can be tried every month for a few days near menses to help curb recurrent infections
Oropharyngeal
- Ketoconazole 200-400 mg po qd x 14-21 days
- Fluconazole 50-200 mg tablets — one po qd x 14-21 days, although a majority of fungal strains found in the oropharynx are likely to be resistant
Esophagitis
- Amphotericin B (variable dosing)

Patient Monitoring

Immunocom promised persons may need to monitor themselves regularly. Use symptoms to monitor as well as “routine” KOH preps and or visual investigations during vaginal or oral exams.

Prevention / Avoidance

Antibiotics can potentiate candidiasis
Candida overgrowth is more likely with pH changes from douching, chemicals (such as spermicides) or other vaginitides
Moist environments are conducive to overgrowth of Candida. Cotton underwear may help deter some Candida infections.

Possible Complications

Rarely develops major complications in immunocompe-tent persons
With immunocompromised, generally depends on severity of immune status (CD4 count is the most common marker). Moderate immunodepression (CD4 200-500) may be associated with chronic candidiasis. With severe immunodepression (CD4< 100) thrush can lead to esophagitis and, later, a full systemic infection can involve every organ system, particularly the kidney (candiduria).

Expected Course / Prognosis

For immunocompetent individuals, a benign course and excellent prognosis is the norm
In immunosuppressed persons, Candida may become an “AIDS defining illness” by CDC criteria and chronicity can cause much morbidity and, less commonly, mortality

Miscellaneous

Associated Conditions

Human immunodeficiency virus
Other immunosuppressive disorders/leukopenias
Cancer
Endocrine disorders

Age-Related Factors

Pediatric: Newborn thrush may be acquired in the birth canal

Geriatric: Thrush is common

Others: Vaginitis is common in women of childbearing age. Uncommon to see prepubertal or post-menopausal yeast vaginitis due to hormonal induced changes in the vaginal wall.

Pregnancy

No known fetal complications of maternal Candida
See specific “medication precautions” above
Miconazole is usually drug of choice in pregnancy

Synonyms

Monilia
Thrush
Yeast

International Classification of Diseases

112.0 Candidiasis of mouth

112.1 Candidiasis of vulva and vagina 112.9 Candidiasis of unspecified site

Other Notes

Most Candida infections are associated with endogenous flora
Transmission from person to person is rare
Occasionally Candida vaginitis may be sexually transmitted
Rarely, oral Candida leukoplakia can be precancer-ous
Skin testing, often used to diagnose or exclude anergy. is positive in 70-85% of individuals randomly checked in studies