Esophageal Candidiasis in Patients with AIDS

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?

Esophageal Candidiasis

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

Overview

• Occurs in 20–40% of patients with AIDS

• Patients usually have CD4 <100 cells/mm3

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.