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Case
• 32-year-old male with AIDS• CD4 50 cells/mm3• Reports severe pain and difficulty
swallowing • “It feels like food gets stuck below
my throat”• Denies other symptoms • Reports history of oral candidiasis
What is the most likely diagnosis?
Objectives
• Upon completion of this activity, participants should be able to: – Recognize symptoms of esophageal
candidiasis – Review methods for diagnosing
esophageal candidiasis – Discuss treatments for esophageal
candidiasis
Overview
• Candida ssp is an opportunistic fungus (yeast)
• Candida albicans is the most common etiology of esophagitis in patients with AIDS
• Candida tropicalis, Candida Krusei, Candida glabrata, and Candida parapsilosis can also cause esophagitis
Esophagitis – Other Causes
• Less common causes: HSV, CMV and aphthous ulcerations
• Rare causes: lymphoma, KS, PCP, Cryptosporidia, TB, histoplasmosis, M. avium
• Consider non-HIV-related causes if CD4 >200 cells/mm3 (e.g., gastro esophageal reflux disease—GERD, medication- and food-induced)
Clinical Presentation
• Odynophagia (painful swallowing) • Dysphagia (difficulty swallowing)• Diffuse retrosternal pain• Occasional nausea and vomiting• Oral candidiasis often present but
not required
Diagnosis
• Usually made clinically based on symptoms
• Endoscopy only if empirical azole therapy fails
• Response to empiric treatment precludes need for endoscopic esophageal candidiasis diagnosis
• When needed, diagnosis by endoscopy is made based on visual appearance of white pseudomembranous plaques in the esophagus
Diagnosis
• Brushings or biopsy can be taken during endoscopy for microscopy or culture
• Fungal culture of esophageal pseudomembranous plaques is useful for identification of Candida species and resistance testing (when available)
Treatment – Basic Principles
• No place for topical treatment• Treat empirically with systemic
drugs• Azoles are first-line of therapy
– Fluconazole included in class
• HAART reduces relapses
First Line Therapy
• Fluconazole 200 mg po daily (preferred) x 14–21 days
• Itraconazole solution 200 mg po daily x 14–21 days – Itraconazole also available in capsule but
better absorption with liquid formulation
– Ketoconazole rarely used due to erratic absorption
Second Line Therapy
• Amphotericin B 0.3-0.7 mg/kg IV daily– Or lipid formulations of amphotericin
• If available, can also use– Echinocandins
• Caspofungin, micafungin
– Alternative azoles with increased activity against fluconazole-resistant Candida
• Voriconazole, posaconazole, itraconazole
Treatment
• Assess response to therapy within 5–7 days
• Continue therapy for 14–21 days after clinical improvement
• Use intravenous drugs for patients unable to swallow
If no Response to Fluconazole
• Check medication adherence• Reconsider diagnosis • Refer for endoscopy• Consider resistance to azole
therapy – especially if repeated courses of azole treatment or if maintenance therapy used
Other Treatment Considerations
• Azoles prone to drug interactions through the cytochrome P450 (CYP450) pathway
• The CYP450 enzymes are involved in the metabolism of most commonly prescribed drugs
• Check package insert for drug interactions when prescribing azoles
Other Treatment Considerations
• Absorption of itraconazole capsules is pH dependent. Absorption affected by: 1. Antipeptic Ulcer Drugs
• H2 blockers• Proton pump inhibitors• Antacids
2. Antiretroviral Drugs• Buffered didanosine
• Liquid formulation better absorbed but must be taken on an empty stomach (preferred)
Other Treatment Considerations
• Fluconazole absorption is not affected by food or gastric pH
• Hepatotoxicity and gastrointestinal intolerance can occur with azole therapy
Other Treatment Considerations
• Amphotericin B is renally eliminated• Amphotericin B is not a substrate,
inhibitor or inducer of the CYP450 enzymes
• Thus, amphotericin B is not prone to drug interactions through the CYP450 enzymes
Other Treatment Considerations
• Common side effects of amphotericin B– Nephrotoxicty – Electrolyte abnormalities – Infusion-related chills– Injection site pain and irritation– Phlebitis
• Increased risk for amphotericin B-induced nephrotoxicity when given concurrently with other nephrotoxic drugs
Prophylaxis
• Prophylaxis/maintenance not generally recommended, but consider if frequent recurrences
• Fluconazole 100–200 mg po daily Itraconazole liquid 200 mg po daily can be used as an alternative
Additional Considerations
• Use analgesic therapy for pain relief
• Reinforce importance of maintaining adequate nutrition
• Avoid foods that are hot/cold/spicy to avoid exacerbating discomfort caused by dysphagia and odynophagia
• Favor pureed/mashed foods and liquids served at room temperature
Summary
• Candida albicans is the most common etiology of esophagitis in patients with AIDS
• Treat empirically with fluconazole • If no response to treatment, consider
alternative etiology, inadequate adherence, drug resistance
• Azoles are prone to drug interactions through the CYP450 pathway
• Azoles can cause gastrointestinal and hepatic toxicity
Summary
• Amphoterycin B for second line therapy
• Amphoterycin B is not prone to drug interactions through the CP450 pathway
• Common side effects include nephrotoxicity, infusion-related chills and fever, phlebitis and electrolyte abnormalities
Summary
• Prophylaxis usually not recommended
• Reinforce the importance of adequate nutrition
• Pain management is crucial • HAART reduces relapses
References
• Ally R, Schurmann D, Kreisel W, et al. 2001. A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 33:1447-1454.
• Arathoon EG, Gotuzzo E, Noriega LM, et al. 2002. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiasis. Antimicrob Agents Chemother. 46:451-457.
• Bonacini M, Young T, Laine L. 1991. The causes of esophageal symptoms in human immunodeficiency virus infection. A prospective study of 110 patients. Arch Intern Med. 151:1567-1572.
References
• Clinical Infectious Diseases 2004; 38:165-89.• Connoly GM, Hawkins D, Harcourt-Webster JN et al.
Oesophageal symptoms, their causes, treatment, and prognosis in patients with the acquired immunodeficiency syndrome. Gut. 1989;30:1033-1039.
• de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2006. A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS. Clin Infect Dis. 42:1179-1186.
• de Wet N, Llanos-Cuentas A, Suleiman J, et al. 2004. A randomized, double-blind, parallel-group, dose-response study of micafungin compared with fluconazole for the treatment of esophageal candidiasis in HIV-positive patients. Clin Infect Dis. 39:842-849.
References
• Maenza JR, Keruly JC, Moore RD, et al. 1996. Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients. J Infect Dis. 174:219-221.
• Vazquez JA. 2000. Therapeutic options for the management of oropharyngeal and esophageal candidiasis in HIV/AIDS patients. HIV Clin Trials. 1:47-59.
• Villanueva A, Arathon EG, Gotuzzo, et al. 2001. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 33:1529-1535.