Oropharyngeal Candidiasis in Patients with AIDS

Case
29-year-old male with AIDS CD4 198 Complaining of painful cracks at the corners of the mouth What is your diagnosis?

Oropharyngeal Candidiasis: Angular Cheilitis

Learning Objectives
Upon completion of this activity, participants should be able to:
Describe symptoms of oropharyngeal candidiasis Discuss methods for diagnosing oropharyngeal candidiasis Review treatments for oropharyngeal candidiasis

Overview on Oropharyngeal Candidiasis Candida albicans is the most common cause of oropharyngeal candidiasis Oral candidiasis is broadly known as thrush Candida albicans is a mouth commensal

Overview
Common risk factors include CD4 <250, chronic antibiotic and/or steroid use, diabetes and cancer Differential diagnosis: oral HSV, hairy leukoplakia, and aphthous ulcerations Usually a recurrent process

Clinical Presentation
Discovered on routine examination Often asymptomatic but patients may experience:
Burning sensation in mouth Taste alteration Pain

Clinical Presentations of Oropharyngeal Candidiasis

Pseudomembranous Candidiasis

White/Grey Plaques on the Hard Palate (Pseudomembranous candidiasis)

Erythematous Candidiasis

Erythematous Candidiaisis Affecting the Hard Palate

Angular Cheilitis

Corners of the Mouth Angular Cheilitis

Diagnosis
Diagnosis usually clinical Easily removable white/grey plaques with erythematous base Scraping away these plaques reveals raw ulcerated area Can also present atypically as erythematous patches and angular cheilitis

Diagnosis
Fungal culture of mouth lesions not useful for diagnostic purposes since positive results may be due to high rates of mouth colonization Fungal culture of mouth lesions used for identification of Candida species and resistance testing

Diagnosis
If laboratory confirmation needed, exudates of epithelial scrapings may be examined microscopically for yeast and/or pseudohyphae by 10% KOH (potassium hydroxide) wet mount preparation

Treatment
Use oral topical treatments as initial therapy Systemic therapy seldom required and only use if absolutely necessary Relapse common, therefore prescribe intermittent treatment rather than continuous

Treatment
Preferred First Line Therapy Topical nystatin or clotrimazole

Second Line Therapy for Refractory Cases Fluconazole 100 mg po daily for 714 days after clinical improvement (preferred) Itraconazole 200 mg po daily for 7 14 days after clinical improvement

Second Line Therapy for Refractory Cases Topical amphotericin B OR Amphotericin B 0.3 mg/kg per day IV for 714 days after clinical improvement

Treatment
If no Response to Alternative Therapy Check adherence Reconsider diagnosis Consider resistance to azole and/or amphotericin

Drug Interactions
Azoles are prone to drug interactions through the cytochrome P450 (CYP450) enzymes The CYP450 pathway is involved in the metabolism of commonly prescribed drugs Check package insert for drug interactions when prescribing azoles concurrently with other drugs Azoles can be associated with hepatotoxicity and gastrointestinal intolerance

Drug Interactions: Absorption

Itraconazole capsules require gastric acid for absorption. Absorption affected by Buffered didanosine, proton pump inhibitors, H2 blockers and antacids Itraconazole liquid is better absorbed and should be taken on an empty stomach Fluconazole absorption is not affected by food or gastric pH

Treatment Side Effects

Clotrimazole
Generally well tolerated Occasionally can cause gastrointestinal toxicity

Nystatin
Bitter taste Can be associated with gastrointestinal toxicity

Maintenance Therapy
Generally not recommended Occasionally needed if recurrence frequent Topical therapy preferred

Maintenance Therapy
If refractory to topical therapy consider azoles
Fluconazole or itraconazole 100 mg po daily

Chronic use of azoles can lead to resistance Optimal prevention is immune reconstitution with ART

Additional Considerations
Reinforce importance of maintaining adequate nutrition Educate the patient on good mouth hygiene Counsel the patient on which foods may be difficult to chew as they can exacerbate mouth discomfort

Summary
Common in patients with AIDS Diagnosis usually clinical Treat with topical agents Preserve systemic treatment and only use if absolutely necessary Relapse common

Summary
Maintenance generally not recommended Reinforce the importance of good oral hygiene Optimal prevention is immune reconstitution with ART

References
Bartlett, J and Gallant, J. 2007. Medical Management of HIV Infection. Johns Hopkins University. Baltimore, MD. Boon, NA et al. 2006. Davidsons Principles and Practice of Medicine. Elsevier Science Health Science div. 20th Edition. pg 373-375. The Hopkins HIV Guide: http://www.hopkinshivguide.org Ramrez-Amador, V. et al. 2003. The Changing Clinical Spectrum of Human Immunodeficiency Virus (HIV)Related Oral Lesions in 1,000 Consecutive Patients: A 12Year Study in a Referral Center in Mexico. Medicine. 82: 39-50. Vazquez, JA. 2000. Therapeutic options for the management of oropharyngeal and esophageal candidiasis in HIV/AIDS patients. HIV Clin Trials. Jul-Aug; (1): 47-59.