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Saturday, January 24, 2009

CANDIDIASIS, MUCOCUTANEOUS

CANDIDIASIS, MUCOCUTANEOUS - Susan Louisa Montauk, MD
BASICS
DESCRIPTION
A mucocutaneous disorder caused by infection with various species of Candida. Areas include
• Candida vulvovaginitis: Vaginal mucosa and/or cutaneous aspects of the vulva
• Candidal Balanitis: Glans penis
• Candidal Paronychia: Nail bed of a digit
• Oropharyngeal candidiasis: Oral cavity (thrush) and/or pharynx
• Candida esophagitis: Esophagus (commonly associated with immunosuppression)
• Gastrointestinal candidiasis: Gastritis, sometimes with ulcers, usually associated with thrush; may affect the small and large bowel
• Angular cheilitis: Fissures at mouth corners
• System(s) Affected: Gastrointestinal; Skin/Exocrine; Genitourinary
• Synonym(s): Monilia; Thrush; Yeast
ALERT
Vaginal antifungal creams and suppositories can weaken condoms and diaphragms.
Pregnancy Considerations
• No known fetal complications of maternal Candida
• Miconazole is usually the drug of choice.
GENERAL PREVENTION
• Antibiotics may 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.
EPIDEMIOLOGY
• Common in the United States, very common in with immunodeficiency and/or uncontrolled diabetes
• Predominant age
- Infants and seniors for thrush and cutaneous infections (infant diaper rash)
- Women of childbearing age predominate for vaginitis. It is uncommon to see prepubertal or postmenopausal yeast vaginitis because of atrophic changes in the vaginal wall.
• Predominant sex: Female > Male (because of vaginitis)
Incidence
Not well studied, but some estimate 50/100,000
Prevalence
Candida colonizes more than 1/2 of U.S. population
RISK FACTORS
• Immunosuppression (includes chronic medications such as corticosteroids and immune modulators for transplants or rheumatologic dz
• Antibacterial therapy
• Douches, chemical irritants, and other vaginitides can predispose to yeast vaginitis
• Dentures
• Birth control pills
• Hyperglycemia
Genetics
• Chronic mucocutaneous candidiasis is a heterogeneous, genetic syndrome that usually presents in childhood, but it's mode of inheritance has not been clarified.
• Family analysis has identified an isolated form of mucocutaneous candidiasis, as well as its chromosomal region, which affects nails only.
ETIOLOGY
C. albicans and, less frequently, C. tropicalis
ASSOCIATED CONDITIONS
• HIV and other leukopenias
• Diabetes mellitus
• Cancer and other immunosuppressive disorders
• Disorders that call for steroids (oral or intranasal) (1) and other immunosuppressive chemotherapy


DIAGNOSIS
NOTE: Candida is normally present, in very small amounts, in the oral cavity, gastrointestinal tract, and female genital tract.
SIGNS AND SYMPTOMS
• In children
- Oral: White, raised, painless, distinct patches within the mouth
- Perineal: Erythematous maculopapular rash with white "satellite" pustules
- Angular cheilitispainful fissures in mouth corners
• In adults: Vulvovaginal lesions; thin to thick whitish "cottage cheese-like" discharge; erythematous patches in the vagina or on the perineum; symptoms range from none 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 symptoms: Ulcerations, pain
- Balanitis: Erythema, linear erosions, scaling
- Angular cheilitis (see "In children")
TESTS
Lab
• Potassium hydroxide 10% microscopic slide preparation (KOH prep): Breaks down epithelial cell walls; allows yeast forms to be visualized
- Best if heated
- Lack of slide identification does not rule out
- A scant number of fungal forms without symptoms does not imply pathogenesis
• Culture: Blood or Sabouraud agar is present; a positive test may be the result of normal flora.
• Drugs that may alter lab results
- Douches and spermicides
- Inadequately dosed antifungal medications
• Disorders that may alter lab results: Other vaginitides (may obscure vaginal slide findings)
Imaging
Barium swallowesophageal candidiasis may reveal a "cobblestone" appearance, fistulas or esophageal dilatation (from denervation)
Diagnostic Procedures/Surgery
• KOH prepa sample of the discharge or "coating" of the infected area or ulcer is needed.
• Esophagitis may require an endoscopic biopsy.
• HIV seropositivity plus thrush with dysphagia relieved by antifungal treatment is acceptable criteria for the diagnosis of Caplital esophagitis.
Pathological Findings
Slide preparation: Mycelia (hyphae) or pseudomycelia (pseudohyphae) yeast forms; Candida does not induce a heightened polymorphonuclear leukocyte response
DIFFERENTIAL DIAGNOSIS
• Baby formula can mimic thrush.
• Hairy leukoplakiadoes not rub off to erythematous base; usually on lateral tongue.
• Bacterial vaginitis
• Angular Cheilitis from vitamin B or iron deficit, other microbes, or edentulous "over" closure
• Symptoms of Trichomonas vaginalis that are similar to those of Candida vaginalis include
- Initial symptoms appearing postmenstrually
- Marked vulvar irritation
- Labial erythema
- External dysuria
- Vaginal tenderness
• Iron deficiency and staph infections can mimic angular cheilitis
TREATMENT
GENERAL MEASURES
Screen both well infants and patients with severe immunodeficiency at routine visits.
Diet
A few authorities say rectal colonization may be decreased with active-culture yogurt or other live lactobacillus; evidence is not yet strong.
Complementary and Alternative Medicine
Probioticscertain gut bacteria, in particular species of Lactobacillus and Bifidobacterium, may exert beneficial effects in the oral cavity by inhibiting cariogenic streptococci and Candida sp. (2)
MEDICATION (DRUGS) (3,4,5) [A,B]
First Line
Vaginal (choose one):
• Miconazole (Monistat) 2% cream: One applicator or one 100-200 mg suppository, intravaginally q.h.s.  7 days
• Clotrimazole (Gyne-Lotrimin, Mycelex): Intravaginal tablets (100 mg q.h.s.  6-7 days, 200 mg q.h.s.  3 days; 500 mg daily  1), or 1% cream (one applicator q.h.s.  6-7 days)
• Nystatin (Mycostatin, Nilstat): 100,000 U/g cream (one applicator) or 100,000 U tablets (one tablet) intravaginally 1  day  7-14 days
• Fluconazole (Diflucan): 150 mg tablet  1
Oropharangeal
• Clotrimazole (Mycelex): 10 mg troche, suck on over 20 minutes 5  day  7-14 days*
• Nystatin pastilles: 1-2 q.i.d.  7-14 days*

*Two days after disappearance of thrush
Esophagitis
Fluconazole:100 mg/d  14-21 days, load w/200 mg)
Itraconazole (Sporanox)
• Solution: 1-200 mg daily  7-14 days
• Capsules: 200 mg/d (take with food)  2-3 weeks
Gastrointestinal
Therapy not well defined
• Contraindications
- Vaginal antifungal creams and suppositories can decrease protective aspects of condoms and diaphragms.
- Any drug is contraindicated if it causes a severe allergic response or severe adverse reaction.
- Ketoconazole, itraconazole, or nystatin (if swallowed): Severe hepatotoxicity
- Amphotericin B: Renal failure
• Precautions
- Miconazole: Usually pregnancy drug of choice
- Fluconazole: Renal excreted; rare hepatotoxicity; resistance has often been noted
- Itraconazole: Doubling the dosage results in ~3-fold increase in itraconazole plasma concentrations.
• Possible interactions (rarely seen with creams, lotions, or suppositories)
- Fluconazole
 Rifampin: Decreased fluconazole concentrations
 Tolbutamide: Decreased tolbutamide concentrations
 Warfarin, phenytoin, cyclosporine: Altered metabolism; 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.
Second Line
Oropharyngeal
• Nystatin oral suspension (100,000 U/mL): Children: 5-10 mL q.i.d.  10 days directly to oral lesions); Adults: Swish "for as long as reasonable" and swallow 5-10 mL q.i.d.  14 days); prophylaxis = above dosages 2-5  day.
• Fluconazole: 100 mg/d  7-14 days (load immunocompromised patient with 200 mg)
• Itraconazole (Sporanox) Suspension: 200 mg (20 mL) daily swish and swallow  7-14 days* Capsules: 200 mg/d (take with food)  2-4 wks*
• Amphotericin B (Fungizone) oral suspension (100 mg/mL): 1 mL q.i.d., swish "for as long as reasonable" and swallow; use between meals
• Ketoconazole: 200-400 mg PO daily for 14-21 days
Esophagitis: Amphotericin B (variable dosing)
Vaginal:
• Terconazole (Terazol), particularly for recurrent cases that may involve imidazole resistance: 0.4% cream (one applicator intravaginally q.h.s.  7 days); 0.8% cream/80 mg suppositories (1 applicator or 1 suppository intravaginally q.h.s.  3 days)
• Itraconazole 200 mg capsule 1 b.i.d.  1 day
• Any of the antifungal creams or suppositories can be tried every month for a few days near menses to help curb recurrent infections.

*Two days after disappearance of thrush
FOLLOW-UP
DISPOSITION
Issues for Referral
• Patients without obvious reasons for recurrent superficial candidal infections (e.g., HIV, diabetes) may have chronic mucocutaneous candidiasis.
• GI candidiasis
PROGNOSIS
For immunocompetent individuals, a benign course and excellent prognosis are the norm. In immunosuppressed persons, Candida may become an "AIDS-defining illness" by the Centers for Disease Control and Prevention criteria and chronicity may cause much morbidity.
COMPLICATIONS
• Major complications rarely develop in immunocompetent persons.
• In immunosuppressed persons, complications depend on the severity of the immune status. Moderate immunosuppression (e.g., CD4 200-500 cells/mm3) may be associated with chronic candidiasis. In severe immunosuppression (e.g., CD4 100 cells/mm3), thrush may lead to esophagitis, then a full-systemic infection involving every organ system, particularly renal.
PATIENT MONITORING
Immunocompromised persons may benefit from regular symptom evaluation plus "routine" KOH preps during vaginal and oral exams.
REFERENCES
1. Kyrmizakis DE, et al. Acute candidiasis of the oro- and hypopharynx as the result of topical intranasal steroids administration. Rhinology. 2000;38(2):87-89.
2. Strus M. et al. The in vitro activity of vaginal Lactobacillus with probiotic properties against Candida. Infect Dis Obstet Gynecol. 2005;13(2):69-75.
3. Rex JH, et al. Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30(4):662-678. Epub 2000 Apr 20.
4. Eggimann P, Garbino J, Pittet D. Management of Candida species infections in critically ill patients. Lancet Infect Dis. 2003;3(12):772-785. Review.
5. Pappas PG, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161-189.
6. Friedlander SF, Rueda M, Chen BK, Caceres-Rios, HW. Fungal, protozoal, and helminthic infections. In: Schachner LA, Hansen RC, eds. Pediatric Dermatology. Edinburgh: Mosby; 2003:1093.
ADDITIONAL READING
• Betts RF, et al. A Practical Approach to Infectious Diseases. Boston, MA: Little, Brown  Co; 2002.
• Kauffman CL, Barnhill RL, eds. Fungal infections. In: Textbook of Dermatopathology, New York, NY: McGraw-Hill; 2004.
MISCELLANEOUS
• Other notes
- Transmission from person to person is rare.
- Occasionally Candida vaginitis may be sexually transmitted.
- Rarely, oral Candida leukoplakia may be precancerous.
- Skin testing is positive in 70-85% of individuals randomly checked in studies.
• See also: Candidiasis; HIV Infection; AIDS; Vulvovaginitis; Candidal

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