Module 6

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Module 6

• Oropharyngeal Candidiasis
• in Persons Living with HIV/AIDS

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Oropharyngeal Candidiasis in Persons Living with
HIV/AIDS

• David A. Reznik, D.D.S.
• Chief, Dental Service
• Grady Health System
• Atlanta, Georgia

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Angular Cheilitis

• The clinical presentation of Angular cheilitis
  (AC) is erythema and/or fissuring of the corners
  of the mouth.
• AC can occur with or without the presence of
  erythematous and/or pseudomembranous candidiasis.
  
• Treatment involves the use of a topical
  antifungal cream directly applied to the affected
  areas four times a day for the two-week treatment
  period.

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Angular Cheilitis

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Angular Cheilitis

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Erythematous candidiasis (EC)

• EC presents as a red, flat, subtle lesion either
  on the dorsal surface of the tongue and/or the
  hard/soft palates.
• EC tends to be symptomatic with patients
  complaining of oral burning, most frequently
  while eating salty or spicy foods or drinking
  acidic beverages.

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Erythematous candidiasis (EC)

• Clinical diagnosis is based on appearance, taking
  into consideration the persons medical history
  and virologic status.
• The presence of fungal hyphae or blastospores can
  be confirmed by performing a potassium hydroxide
  preparation.

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Erythematous candidiasis (EC)

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Erythematous candidiasis (EC)

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Erythematous candidiasis (EC)

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Erythematous candidiasis (EC)
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Pseudomembranous candidiasis (PC)

• PC appears as creamy white curd-like plaques on
  the buccal mucosa, tongue and other oral mucosal
  surfaces that will wipe away, leaving a red or
  bleeding underlying surface.
• The most common organism involved with the
  presentation of candidiasis is Candida albicans,
  however there are increasing reports of the
  increased incidence of non-albicans species. 1
• 1. Powderly WG, Mayer KH, Perfect JR. Diagnosis
  and treatment of oropharyngeal candidiasis in
  patients infected with HIV a critical
  reassessment. AIDS Res Hum Retroviruses 1999 Nov
  115(16)1405-12.

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Clinical Diagnosis of PC

• The diagnosis of PC is based on clinical
  appearance taking into consideration the persons
  medical history.
• Potassium hydroxide preparation, fungal culture
  or biopsy, may be useful in obtaining an accurate
  diagnosis.

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Mild to Moderate Pseudomembranous Candidiasis

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Mild to Moderate Pseudomembranous Candidiasis
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Moderate to Severe Pseudomembranous Candidiasis
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Moderate to Severe Pseudomembranous Candidiasis
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Azole Resistant Pseudomembranous Candidiasis (C.
albicans)

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Azole Resistant Pseudomembranous Candidiasis (C.
glabrata)

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Trends in Candidiasis in the HAART-Era

• There has been a decline in the occurrence of PC
  in patients who are on successful highly active
  retroviral regimens containing protease
  inhibitors 2
• A review of the literature suggests that immune
  reconstruction alone does not account for this
  reduction, but rather the added effect of
  protease inhibitors on candidal virulence factors
  such as aspartyl protease.3

2 Patton LL, McKaig R, Straauss R, Rogers D,
Enron JJ Jr. Changing prevalence of oral
manifestations of human immunodeficiency virus in
the era of protease inhibitor therapy. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod
200090299-304. 3 Cauda, R, Tacconelli E,
Tumbarello M, Morace G, De Bernardis F,
Torosantucci A, Cassone A. Role of protease
inhibitors in preventing recurrent oral
candidosis in patients with HIV infection a
prospective case-control study. J Acquir Defic
Syndr Hum Retrovirl, Vol 21(1), May 99.
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Treatment of Candidiasis

• Treatment should be based on the extent of the
  infection with topical therapies (nystatin,
  clotrimazole) utilized for mild to moderate cases
  and systemic therapies (fluconazole) used for
  moderate to severe presentations.
• Antifungal therapy should last for two weeks to
  reduce the colony forming units to the lowest
  level possible to prevent recurrence.

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Azole Resistance

• As HIV disease progresses and immunosuppression
  becomes more severe, the incidence and severity
  of oropharyngeal candidiasis increase. The
  introduction of oral azoles, most notably
  fluconazole, has led to the increased incidence
  of azole resistant Candida albicans as well as
  the emergence of non-albicans species such as
  Candida glabrata, which are inherently resistant
  to this class of drug1

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Azole Resistance

• Factors that increase the probability of azole
  resistant strains of Candida presenting in the
  oral cavity include previous exposure to azoles,
  low CD4 count and the presence of non-albicans
  species.4,5
• To minimize the risk of resistance, topical
  therapies should be considered for first-line
  treatment of initial or recurrent cases of mild
  to moderate oropharyngeal candidiasis.1
• 4. Maenza JR, Keruly JC, Moore RD, Chaisson RE,
  Merz WG, Gallant JE. Risk factors for
  fluconazole-resistant candidiasis in human
  immunodeficiency virus-infected patients. J
  Infect Dis 1996 Jan173(1)219-25
• 5. Cartledge JD, Midgley J, Gazzard BG.
  Non-albicans oral candidosis in HIV-positive
  patients. J Antimicrob Chemother 1999
  Mar43(3)419-22.

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Available Medications Used in the Management of
OPC

• Topical agents
• Clotrimazole troches 10 mg Dispense 70, dissolve
  one troche in mouth 5 times a day for 14 days
• Nystatin oral suspension 500,000 units Swish 5
  mls in mouth as long as possible then swallow, 4
  times a day for 14 days
• Nystatin pastilles 100,000 units dispense 56,
  dissolve 1 in mouth 4 times a day for 14 days

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Available Medications Used in the Management of
OPC

• Systemic agents
• Fluconazole 100mg dispense 15 tablets, take 2
  tablets on day 1 followed by 1 tablet a day for
  the remainder of the 14 day treatment period
• Itraconazole oral suspension 10mg/10ml dispense
  140ml, swish and swallow 10ml per day for 7 to
  14 days. Take medication without food.

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Efficacy of antifungal drugs used in the
treatment of OPC in HIV Patients

• Limitations in published literature
• HIV disease status (CD4 count, viral load ) not
  reported in 1/2 of the studies
• Antiretroviral therapy reported in only 2
  studies, none involving HAART or protease
  inhibitors
• Compliance with prescribed drug therapy not
  universally assessed
• Speciation of candidal organisms in treatment
  failures was rare drug susceptibility testing
  not performed
• Cost-effectiveness analysis not performed

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Efficacy of topical antifungal therapies

• Clinical trials have not been undertaken which
  compare the efficacy of the two most frequently
  prescribed topical antifungal medications used in
  the management of OPC in HIV individuals
• nystatin oral suspension
• clotrimazole troches
• The only comparison which can be referenced
  include two studies which were designed to look
  at the efficacy of two different formulations of
  fluconazole.

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Selected studies involving topical antifungal
therapies

• Pons et al, 1993, Fluconazole (100 mg) once daily
  for 14 days vs Clotrimazole 10 mg troche 5 X
  daily for 14 days
• 98 C. albicans at baseline
• 334 enrolled, 288 evaluated for efficacy
• Fluconazole arm 91 complete clinical response
  7 clinical improvement
• Clotrimazole arm 85 complete clinical response
  9 clinical improvement
• Difference in clinical response Group 1 vs 2 p
  ns

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Selected studies involving topical antifungal
therapies

• Pons et al, 1997, Fluconazole liquid suspension
  100 mg 1X daily for 14 days vs nystatin oral
  suspension 500,000 Units 4 X daily for 14 days
• 95 C. albicans at baseline
• 167 enrolled, 138 evaluated for efficacy
• Fluconazole suspension arm 87 complete cure,
  12 improvement
• Nystatin liquid arm 52 complete cure, 16
  improvement
• Difference in clinical response P lt .001

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Conclusions

• Oropharyngeal candidiasis is still a common oral
  opportunistic infection 2
• Judicious use of systemic antifungal therapies is
  warranted. 1
• 2.Patton LL, McKaig R, Straauss R, Rogers D,
  Enron JJ Jr. Changing prevalence of oral
  manifestations of human immunodeficiency virus in
  the era of protease inhibitor therapy. Oral Surg
  Oral Med Oral Pathol Oral Radiol Endod
  200090299-304
• 1.Powderly WG, Mayer KH, Perfect JR. Diagnosis
  and treatment of oropharyngeal candidiasis in
  patients infected with HIV a critical
  reassessment. AIDS Res Hum Retroviruses 1999 Nov
  115(16)1405-12.

31
Conclusions

• There is an increased incidence in fluconazole
  refractory oropharyngeal candidiasis 4,5
• Factors which lead to resistance include previous
  exposure to systemic azoles and low CD4 counts 4
• 4.Maenza JR, Keruly JC, Moore RD, Chaisson RE,
  Merz WG, Gallant JE. Risk factors for
  fluconazole-resistant candidiasis in human
  immunodeficiency virus-infected patients. J
  Infect Dis 1996 Jan173(1)219-25
• 5.Cartledge JD, Midgley J, Gazzard BG.
  Non-albicans oral candidosis in HIV-positive
  patients. J Antimicrob Chemother 1999
  Mar43(3)419-22