Fungal Infections PDF

Fungal Infections Dr. Lisa Johnson References • Chapter 6 Neville at al. Fungal Infections Candidiasis Histoplasmosis Blastomycosis Mucomycosis/Zygomycosis Aspergillosis Coccidioidomycosis Paracoccidioidomycosis Cryptococcosis Toxoplasmosis The many faces of CANDIDIASIS Candidiasis • Mos...

Fungal Infections Dr. Lisa Johnson References • Chapter 6 Neville at al. Fungal Infections Candidiasis Histoplasmosis Blastomycosis Mucomycosis/Zygomycosis Aspergillosis Coccidioidomycosis Paracoccidioidomycosis Cryptococcosis Toxoplasmosis The many faces of CANDIDIASIS Candidiasis • Most common fungal infection from • • • • Candida albicans Sometimes: infection from other genus: • C. tropicalis, C. krusei, C. parapsilosis Dimorphism (two forms): • Yeast (normal in 30-50% of humans; • in >60% of those over 60 years of age) • Hyphal (disease form; invades tissues) Many clinical manifestations A red flag disease: ↑ risk with ↓ immunity Candida hyphae, GMS stain Candida colonies in AIDS Normal Microbiota of the Oral Cavity • Previously thought 35-80% of humans arbored C. Albicans in the oral cavity • Recent molecular studies suggest it is present in everyone within the normal microflora • Candidiasis therefore is a disruption in the normal homeostasis that exists between candida and its host Candidiasis Predisposing factors Local factors: • Smoking • Poor oral hygiene • Presence of oral appliances • Improper denture cleaning • Corticosteroid inhalers (due to local immune suppression) • Xerostomia • Diets rich in carbohydrates coughdoc.com Polident.com Candidiasis Predisposing factors Systemic Factors • Immunosuppression (HIV, leukemia, malnutrition, age: very young and very old) • Endocrine dysfunction (diabetes, pregnancy) • Autoimmune diseases – Sjogren’s syndrome • Systemic chemotherapy, radiation therapy • Likely due to xerostomia with combined immunosuppression • Drugs (systemic corticosteroids, immunomodulatory drugs, broad spectrum anti-microbials) Candidiasis Clinical Subtypes • Pseudomembranous (thrush) • Erythematous (atrophic) • Central papillary atrophy (aka Median rhomboid glossitis) • Denture stomatitis (chronic atrophic candidiasis, denture sore mouth) • Chronic multifocal candidiasis • Angular cheilitis • Hyperplastic candidiasis (Candidal leukoplakia) • Mucocutaneous candidiasis • Endocrine-candidiasis syndrome Clinical Forms of Candidiasis Table 6.1 Summary table to the clinical forms of oral candidiasis – Neville et al. Pseudomembranous Candidiasis Etiology Etiology: • • • • • • J Lovas DDS Broad-spectrum antibiotics (fast onset) Compromised immunity (slower onset) • Leukemia, AIDS, diabetes mellitus, infants Xerostomia Estrogen replacement therapy Topical corticosteroid therapy (inhaled or rinses/ointments) Poor denture hygiene and loose denture http://www.samhsa.gov/data/sites/default/files/SR-1887/SR-1887.htm Young healthy adults should NOT get pseudomembranous candidiasis Any evidence of pseudomembranous candidiasis in an otherwise healthy young adult should be investigated for underlying immunosuppression Pseudomembranous Candidiasis Clinical Presentation • White plaques, like cottage cheese • Tangled masses of hyphae (yeasts) • Desquamated epithelial cells • Distributed typically on the buccal mucosa, palate and tongue dorsum • Plaques can be rubbed off - underlying mucosa ranges from normal to erythematous, but typically not bleeding • Foul taste and burning sensation Colonies of candida can be scraped off easily (arrow) Pseudomembranous Candidiasis in (pipe) smoker J Lovas DDS • Before (L) & immediately after (R), removal of the “curds” Pseudomembranous Candidiasis Diagnosis • Presumptive diagnosis based on clinical presentation • Can be confirmed with exfoliative cytology (not an extremely common practice for this form of candidiasis given its classic clinical appearance) Cytologic Smears J Lovas DDS J Lovas DDS • Pre-label frosted side • Rub lesion FIRMLY with wet wooden tongue depressor / metal equivalent; Spread evenly on glass; use professional fixative • “Cytologic smear - rule out Candidiasis”, request PAS stain Candidiasis J Lovas DDS • Round dormant yeast and pseudohyphal form Important to note: • Candida albicans is part of the normal oral flora – thus are a few hyphae truly evidence of infection… Pseudomembranous Candidiasis Treatment • Antifungal regimen (to be discussed) • Consider investigation into immune status if unexpected demographic Erythematous Candidiasis Chronic Atrophic Candidiasis • No white colonies visible, only erythematous, burning, tender mucosa • More common than pseudomembranous candidiasis • Presents with chronic burning • Diffuse loss of filiform papillae on the tongue Etiology: • Idiopathic • Antibiotics • Steroids • Dry mouth • Estrogen Rx Fig 6-3 Neville et al Denture Stomatitis Subtype of Erythematous Candidiasis ● Erythema +/- petechia, symptomatic/asymptomatic ● Localized to denture-bearing areas of maxillary removable dental prosthesis ● R/O: allergy to denture base or Improper design of denture causing traumatic localized pressure Treatment: ● Sometimes simply removing the denture more frequently will result in resolution ● Disinfection of the denture may be required ● Antifungal regimen may also be required when symptomatic J Bouquot Chi, Angela, Brad Neville, Douglas Damm, Carl Allen. Oral and Maxillofacial Pathology, 4th Edition. Saunders, 052015. VitalBook file. Burning red macules under denture Median Rhomboid Glossitis (aka Central papillary atrophy) Subtype of Erythematous Candidiasis Clinical presentation: ● <1% of adults, but rare in children ● ***quite common in smokers ● ● ● ● Midline and posterior dorsal tongue Well defined, symmetrical erythematous zone due to loss of filiform papillae Usually asymptomatic Often has kissing lesion of erythematous candidiasis in the palate Image from: Chi, A., Neville, B., Damm, D., Allen, C. (052015). Oral and Maxillofacial Pathology, 4th Edition [VitalSource Bookshelf version]. vbk://9781455770526 Retrieved from jcda.ca Median Rhomboid glossitis Variations in presentation: • May have white keratotic surface change • May see pseudoepitheliomatous hyperplasia creating surface nodularity Pseudoepitheliomatous Hyperplasia Median Rhomboid Glossitis Treatment • No active treatment is required if asymptomatic, especially when present in a smoker due to high recurrence rate • When symptomatic treated with an antifungal rinse or ointment (to be discussed) • With nodular presentation may consider biopsy Angular Cheilitis Subtype of Erythematous Candidiasis Angular Cheilitis Clinical Presentation: ● ● ● ● Involves the angles of the mouth Erythematous, irritated, fissured and scaling at the angles of the mouth Typically quite painful Contributing factors: • Loss of VDO • Saliva pooling at corners of the mouth • Abnormally high levels of intraoral candida (eg. Xerostomia) • Immunosuppression and anemia Images from: Chi, A., Neville, B., Damm, D., Allen, C. (052015). Oral and Maxillofacial Pathology, 4th Edition [VitalSource Bookshelf version]. Retrieved from vbk://9781455770526 J Bouquot Cheilocandidiasis may evolve from angular cheilitis • Chronic candida infection of skin • • • • • • • • around the lip vermilion Usually children, teenagers Starts as erythema, crusting May involve only one lip Never goes >4 mm from vermilion Vermilion may be crusted a bit Lasts for months, years Inside mouth: maybe chronic atrophic candidiasis signs Rx: topical antifungal cream +/- a topical antimicrobial Juxtavermilion crusting Linear Gingival Erythema • Distinctive linear band of erythema that extends 2-3 mm apically from the gingival margin - does not respond to scaling and is disproportionate to the amount of plaque/calculus present • Often see other areas of gingival erythema • Responds to antifungal therapy - may represent an unusual presentation of candidal infection Chronic Hyperplastic Candidiasis • Uncommon presentation with white non wipeable patches/plaques • Most common location is the anterior buccal mucosa approaching the commissures – typically seen bilaterally Etiology: • May be candidiasis superimposed on a preexisting premalignant lesion • May be candidal organism inducing hyperkeratosis (like we say in median rhomboid glossitis) • Diagnosed via biopsy as it cannot be clinically distinguished from a premalignant white patch PAS stain shows spores and hyphae • Lesional tissue should resolve with antifungal therapy • WHO does consider this a premalignant condition Other forms of candidiasis ● There are other more extensive rare forms of candidiasis involving oral, skin and even endocrine abnormalities: • • • • • • Iron-deficiency anemia Hypothyroidism Hypoparathyroidism Hypoadrenocorticism (Addison’s disease) Diabetes mellitus Perionychial infection Chi, Angela, Brad Neville, Douglas Damm, Carl Allen. Oral and Maxillofacial Pathology, 4th Edition. Saunders, 052015. VitalBook file. Treatment of Candidiasis Antifungal Therapies Suspensions Ointments Systemic Antifungal therapies Nystatin Suspension Advantages: • Commercially available • Can be swallowed as minimal GI absorption • Inexpensive Disadvantages: • Relies on contact with the organism to be effective thus must be used many times per day • Usually sweetened with sucrose due to bitterness thus can be cariogenic • Not a highly effective antifungal agent Nystatin Suspension (100,000 u/ml) Dispense: 280 ml Swish with 5 ml for 1-2 mins and expectorate or swallow, qid x 2 weeks. *Tend to have the patient swallow if the infection involves the oropharynx (ie soft palate, tonsils, posterior wall of the pharynx Nystatin Troches Advantages • Offers more targeted therapy • Tissues are exposed to the drug for longer period of time Disadvantages • Not commercially available • Requires a compounding pharmacy • Increased cost • No coverage with Pharmacare Nystatin Troches (100,000 u/ml) Dispense: 56 troches Suck on 1 troche, qid x 2 weeks. Nystatin Ointment Advantages Nystatin Ointment • Offers more targeted therapy (100,000 u/ml) • Tissues are exposed to the drug for longer period of time Dispense: 30 grams Disadvantages Apply to affected area, • Not commercially available qid x 2 weeks. • Requires a compounding pharmacy *Typically for more targeted area • Increased cost such as under a denture or in a high • No coverage with Pharmacare palatal vault *Can be applied with gauze application (like a band-aid) for 10 mins Clotrimazole Troches Advantages • More effective antifungal than nystatin Disadvantages • Not commercially available • Requires a compounding pharmacy • Increased cost • No coverage with Pharmacare • Can affect liver enzymes – not to be used for long term use • May cause stomach upset Clotrimazole troches (10 mg) Dispense: 50-60 troches Suck on 5 troches per day for 10-14 days. Clotrimazole Suspension Advantages • More effective antifungal Disadvantages • Not commercially available • Requires a compounding pharmacy • Increased cost • No coverage with Pharmacare • Can affect liver enzymes – not to be used for long term use • Some patients report burning • Solution cannot be swallowed 1% Clotrimazole Suspension Dispense: 280 ml Swish with 5 ml for 1-2 mins and expectorate qid x 2 weeks. Antifungal therapy Systemic Management Fluconazole (Diflucan@) 100 mg Disp: 15 tabs Take 2 tabs stat, then 1 tab daily for 13 days. * If any liver concerns or elderly consider shortening to 1 week only Side effects: • Rare cases of hepatotoxicity • Nausea, vomiting, diarrhea 1 oral tablet can be purchased OTC Antifungal therapy Systemic Management – 2nd line • Serious hepatotoxicity in 1 in 10,000 patients Ketoconazole 200 mg Disp: 14 tabs Take 1 tab daily for 14 days. • Need to monitor in patients with any hepatic history or in any patients on the med for longer than 28 days • Nausea, vomiting • Interacts with terfenadine (an antihistamine) and cisapride (used for increasing motility of the upper GI tract) - can cause life threatening interaction • Also affects the metabolism of cyclosporins, tacrolimus, methylprednisone, midazolam, triazolam, coumadin-like drugs, rifampin as it is a potent inhibitor of P-GP transporter and cytochrome P450 A34, thus it will increase the effective dose of these drugs Other Systemic Antifungals * reserved from recalcitrant cases and other forms of fungal infections • Itraconazole • Reserved for the Blastomycosis and histoplasmosis 200 mg daily up to 400 mg daily until clinically effective can use for aspergillosis as well. • Itraconazole oral suspension can also be used for candidiasis - with a swish and swallow twice daily for 12 weeks. • Amphotericin B • IV for life threatening fungal infections Angular cheilitis Treatment J Lovas DDS J Lovas DDS • 1:1 mixture Nystatin ointment + 2% Muciprocin (Bactroban) ointment • Nystatin + 0.1 % triamcinolone acetonide ointment or Viaderm ointment (triamcinolone, neomyacin, gramicidin and nystatin) (2nd line) • THEN MUST prevent re-injury and re-infection of the tissue with pure lanolin or pure petroleum jelly nightly or coconut oil Denture Stomatitis Note only will it require an antifungal for the patient, you must also disinfect their denture: • Bleach – 10 ml in 250 ml (1 cup) of water to soap for 30 minutes, then wash with soap and water. dentaltech.ie • For unresponsive or very old dentures could prescribe: • Benzalkonium Chloride 0.13% Solution (Shelf-stable for 6 months) 1000ml = $22.00 • Available at a compounding pharmacy Denture is to be soaked in the solution for 30 minutes and then vigorous cleaned with soap and water Non Pharmacologic Strategies To help promote recurrence • Restoration of carious lesions: dentinal tubules in carious lesion are thought to be a reservoir for candida • Maintain good salivary flow - avoid diurectics and ensure good H20 intake • Decrease or more ideally cease smoking • Swishing with coconut oil acts as a low grade antimicrobial agent (typically for xerostomic patients)