34. Mycology 💢 Flashcards
(179 cards)
1
Q
A
2
Q
What are the two main phyla of fungi?
A
Ascomycota Basidiomycota
3
Q
Which fungus out of the basidiomycetes causes the largest burden of disease?
A
Cryptococcus neoformans and Cryptococcus gatii Causes cryptococcal meningitis
4
Q
What three types of illness do fungi cause?
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Allergies Mycotoxicoses Mycoses
5
Q
Define mycotoxicosis.
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A toxic reaction to the ingestion/inhalation of toxins produced by fungi
6
Q
What is known as the most carcinogenic natural compounds and what produces it?
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Aflatoxin – Aspergillus flavus
7
Q
Define mycosis.
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Disease caused by fungi that is classified based on the level of tissue affected
8
Q
What are the four types of mycosis?
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Superficial Cutaneous Subcutaneous Systemic
9
Q
What are superficial mycoses? Give some examples.
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Mycoses that affect the skin and hair No tissue is invaded so there is no cellular response Black piedra White piedra Dandruff Tinea nigra
10
Q
What are cutaneous mycoses? Give some examples.
A
Produce keratinases – causes inflammation Trychopyton and Microsporum are main examples Other examples: Tinea capitis Tinea corporis Tinia pedis
11
Q
What are subcutaneous mycoses?
A
Chronic, localised infections of the skin and subcutaneous tissue following traumatic implantation of the aetiological agent.
12
Q
What type of fungal infection is a big problem in transplant settings?
A
Aspegillosis
13
Q
What are the three types of candida infection that can occur in the immunocompromised?
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Mucosal Systemic Superficial
14
Q
What are the three types of mucocutaneous candidiasis that occurs in people with HIV?
A
Oesophageal Vulvovaginal Oropharyngeal
15
Q
What are the main risk factors for systemic candida infections?
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Chemotherapy Gut-related surgery Catheters
16
Q
What are the three main targets for antifungal therapy?
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Cell membrane DNA synthesis Cell wall
17
Q
How do antifungals that target the cell membrane work? Give some examples.
A
Fungal cell membranes contain ergosterol instead of cholesterol Some antifungals inhibits ergosterol synthesis Examples: azole (itraconazole) Polyene antibiotics (Amphotericin B and Nystatin)
18
Q
How do antifungals that target DNA synthesis work? Give an example.
A
Pyrimidine analogues are used to interfere with DNA synthesis Example: Flucytosine (used for Cryptococcus)
19
Q
How do antifungals that target the cell wall work? Give an example.
A
They inhibit the assembly of fungal cell wall components such as glucans and chitin Example: Caspofungin (a type of Echinocandin)
20
Q
What components are found in fungal cell walls but not in mammalian cell walls?
A
Glucan Chitin
21
Q
What are the four main phyla of fungi and which most commonly causes human fungal infection?
A
Ascomycota – MAIN ONE Basidiomycota Chytridiomycota Zygomycota
22
Q
Give examples of how the morphogesis of fungi contributes to its ability to cause disease in the host.
A
Candida albicans exist as single spores but they can become hyphae, which allows tissue invasion Cryptococcus forms a capsule to evade phagocytosis Aspergillus sp. are inhaled as conidia and invade tissues as hyphae
23
Q
Which pattern recognition receptors are important in detection of fungal pathogens?
A
TLR
24
Q
Name 2 deficiencies that are associated with an increased risk ofchronic mucocutaneous candidiasis.
A
Dectin 1 (involved in activation of an inflammatory cytokine response) CARD 9 (downstream of Dectin 1)
25
Name 3 factors that are associated with increased risk of Aspergillosis in transplantation.
TLR4 S4 – loss of function Dectin 1 Plasminogen alleles
26
Which PRR is actively recruited to Aspergillus fumigatusphagolysosomes?
TLR9
27
What can plasminogen directly bind to?
Aspergillus fumigatus conidia
28
Which cells are the most important in defence against fungal infection?
Neutrophils
29
What do neutrophils release that enable them to trap Aspergillus?
NETs
30
Describe how fungal morphogenesis governs the dendritic cell modulation of adaptive immunity.
Hyphal forms = Th2 response Conidium = Th1 response
31
What cytokine therapy has been shown to enhance clearance ofinvasive fungal infection?
IFN-gamma
32
Describe the principles of adoptive immunotherapy for fungal infection.
If a patient is receiving a stem cell transplant, you can generate anti-fungal T cells, which can be cultured in large numbers and administered to the patient
33
Give an example of gene therapy for chronic granulomatous disorder.
Restoration of gp91 function This is involved in the generation of NADPH oxidase – this generates reactive oxygen species, which is required to kill microbes NOTE: another type of gene therapy = restoration of neutrophil NET formation
34
What types of hypersensitivity reaction are associated with fungal allergies?
Type 1, 3 and 4
35
What are two predisposing conditions for allergic bronchopulmonary aspergillosis (ABPA)?
Asthma Cystic fibrosis
36
What is the obligatory criteria for ABPA?
Total baseline serum IgE \> 1000 IU/ml Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
37
List some supportive criteria for ABPA.
Eosinophilia \> 500 cells/ul Serum precipitating or IgG antibodies to Aspergillus fumigatus Consistent radiographic abnormalities
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List some radiological features of ABPA.
Dilated bronchi with thick walls Proximal bronchiectasis Ring or linear opacities Upper or central region predilection Lobar collapse due to mucous impaction Fibrotic scarring
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What might be seen in a CT scan of a patient with ABPA?
Hyper dense mucous sign
40
Describe the main treatment options for ABPA.
Corticosteroids Itraconazole may be used as a steroid-sparing agent Recombinant anti-IgE antibodies (omalizumab) may be useful
41
List three other examples of fungal allergies, including associated features of each.
Aspergillus rhinosinusitis ï‚· May be allergic or invasive ï‚· Obliterated sinuses ï‚· Treated with oral corticosteroids Severe asthma with fungal sensitisation ï‚· Fungal sensitisation as a potential cause of severe asthma ï‚· Requires exclusion of ABPA ï‚· Treatment with anti-fungal unclear Hypersensitivity pneumonitis (extrinsic allergic alveolitis) ï‚· Allergy requires long-term exposure to allergen (often occupational)
42
What test is used to diagnose fungal allergies?
Skin prick testing
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Which type of hypersensitivity is each of the previously mentioned fungal allergies?
ABPA – type 1 or 4 Asthma – type 1 Rhinitis – type 1 Hypersensitivity pneumonitis – type 4
44
Different mechanisms of antifungals?
1. alter cell membrane permeability 2. block nucleic acid synthesis 3. disrupt microtubule functions
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Antifungals that alter cell membrane permeability?
Azoles (ketoconazole), polyenes (Nystatin), Terbinafine
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Antifungals that block nucleic acid synthesis?
Flucytosine
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Antifungals that disrupt microtubule functions?
Griseofulvin
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What topical drugs are used for cutaneous fungal infections?
azoles and polyenes
49
What are the systemic drugs used for superficial fungal infections?
Griseofulvin, Terbinafine, and Itraconazole (azole)
50
Systemic drugs used for systemic fungal infections? \*Bad systemic infections
Amphoteracin B (Amphoterrible -\> don't use) Azoles Flucytosine (5-FC)
51
What are the topical azalea antifungals and their MOA?
clotrimazole, ketoconazole, miconazole - fungicidal, impairs the formation of fungal cell membranes therefore increasing permeability (so intracellular contents leak out leading to cell death)
52
Clinical uses of Topical azole antifungals
tinea corporis (body), tinea cruris (jock itch), tinea pedis (athletes foot), cutaneous candidiasis (yeast infection) \*Tinea=condition caused by dermatophytes
53
CIs of topical azole antifungals (c,k,m)
pregnancy, lactation -caution w/ liver failure - don't use ketoconazole if hx of sulfa allergy
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Application of topical azole antifungals
lotion or powder -\> apply 2x daily for 2-4 weeks continue for 1 week after lesions clear
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MOA of topical azole antifungals
inhibit CYP450, inhibit synthesis of ergosterol (cell membrane of fungi) SE: pruritis, irritation, burning or stinging
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Clotrimazole
Names: Gyne-Lotrimin, Mycelex 3&7, Trivagizole 3 Indications: - cutaneous candidiasis (topical) - vulvovaginal candidiasis (topical) -oropharyngeal candidiasis (thrush -\> oral formulation) CI: hypersensitivity to clotrimazole or any other component of formula
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Oropharyngeal candidiasis dosing
troche dissolved slowly 5x / day for 14 days
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Clotrimazole MOA
binds to phospholipids in the fungal cell membrane altering permeability and loss of intracellular elements -very little systemic absorption from topical -oral: inhibitory concentrations in saliva for up to 3 hours post dissolution of troche
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Drug interactions for clotrimazole
topical= none oral drug interactions similar to other azaleas due to inhibition of P450 enzymes
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Adverse effects of Clotrimazole
Topical: vulvovaginal burning oral: abn. LFTs, pruritus, N/V monitor: periodic LFTs
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Ketoconazole (topical)
formula: cream, foam, gel or shampoo indications: tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis, + seborrheic dermatitis and tinea versicolor
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Topical azoles: miconazole (micatin, monistat, desenx, lotrimin AF)
formulations: aerosol, powder aerosol, intravaginal supp, cream, ointment, lotion indications: tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis, tinea versicolor + vulvovaginal candidiasis -intravaginal sups may interfere with warfarin
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Topical Polyene: Nystatin (mycostatin)
Indications: cutaneous and mucocutaneous infections caused by candida -oral and intestinal candidia infections CIs: hypersensitivity reaction
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Mycostatin MOA
binds to sterols in fungal cell membrane and changes the cell wall permeability leading to the leakage of intracellular contents
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Mycostatin dosing
cream, ointment and powder:100,000 U/g 2-3x daily oral suspension - 400,000-600000 U QID intestinal infections: tablets- 500000-1,000,000 U po q8H
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Mycostatin pharmokinetics/dynamics
onset of action -\> relief of sxs: w/in 24-72 hours systemic absorption- none (why its used to tx intestinal infections) -no drug interactions
67
Adverse effects of mycostatin
contact dermatitis - develop blisters -SJS -oral: N/V/D
68
Systemic drugs for superficial fungal infections
Griseofulvin, terbinafine, itraconazole -for hair, skin and nails
69
Griseofulvin indications
used to tx tine infections of skin, hair and nails -most commonly used for tx of tine capitis (scalp)
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Griseofulvin MOA
inhibits fungal cell division binds to himan keratin making it resistant to fungal invasion (goes down into hair follicles as hair grows out, takes a long time to work)
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Duration fo Griseofulvin therapy
tinea corporis: 2-4 weeks tinea cruris: 2-6 weeks tinea capitis: 4-6 weeks tinea pedis: 4-8 weeks tinea unguium (nails): 4-6 months or longer administration: fatty meal (PB or ice cream) may increase GI absorption - with food or milk to decrease GI upset
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CIs and precautions with administration of Griseofulvin
-liver failure -porphyria (porphyrin accum) -preg (X) - caution if hx of pcn allergy -breast feeding not recom.
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What periodic monitoring is required if pt is on long term tx of griseofulvin
renal fxn, liver fxn, and CBC to watch for granulocytopenia \* get CBC and CMP
74
Drug interactions of Griseofulvin
many due to its effects on CYP1A2, CYP2C9, CYP3A4 -warfarin, oral contraceptives, alcohol, barbiturates, cyclosporine and others
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Adverse reactions of griseofulvin
photosensitivity, SJS, toxic epidermal necrolysis, erythema multiforme, jaundice, elevated LFTs, granulocytopenia, dizziness, fatigue, HA, N/V/D, drug induced lupus like syndrome
76
Dose adjustments of griseofulvin dependent on?
smaller particle size the greater bioavailability requiring dose adjustments between 2 formulations - microsize: suspensions, grifulvin V tablets -ultramicrosize: Gris-PEG tablets (tablets are spendy)!
77
Terbinafine (Lamisil)
oral/systemic formula: -oncychomycosis of toenails and fingernails -tinea capitis CIs: Hypersensitivity
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Terbinafine MOA
creates ergosterol deficiency within the cell wall leading to cell death
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Dosing of Terbinafine
oral: onychomcosis of the fingernails -\> 250 mg/day x 6 weeks oncychomycosis of the toenails: 250 mg day x 12 weeks
80
Terbinafine pharmacodynamics/kinetics
effective half life 36 h - distribution to the sebum and skin -99% plasma bound (drug interactions) -hepatic metabolism
81
drug interactions of Terbinafine
due to inhibition of CYP450 enzymes there are some sig. drug interactions including metoprolol (B blocker), and tramadol - pain med (oral formulation)
82
Terbinafine SEs
HA, diarrhea, LFTs, burning, contact dermatitis, dryness, pruritus, rash
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Itraconazole (sporanox) indications for superficial infections
\*\*Onychomycosis
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Itraconazole (sporanox) CIs
hypersensitivity to intraconazole or other azoles -concurrent administration with other drugs that act at CYP450 system -Ventricular dysfunction (negative inotrope) -CHF -pregnancy or intend to become pregnant
85
Itraconazole (Sporanox) Pharmacodynamics/Kinetics
requires gastric acidity for optimal absorption -better absorbed with food (capsule) -solution better absorbed on an empty stomach -99.\*% protein bound -half life: 21 hours -metabolized by liver
86
Itraconazole (Sporanox) drug interactions
significant list of drug interactions: -proton pump inhibitors, anxiolytics, pain meds, antiplatelet agents, anthypertensives, cholesterol lowering meds -drug interaction checker is a must when using these drugs
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Itraconazole (sporanox) adverse effects
Nausea, diarrhea, edema (from L. ventricular dysfunction), HA, rash, Abnorm. LFTs, heart failure, arrhythmia, hearing loss, and many more
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Itraconazole (sporanox) monitoring
baseline LFTs, monthly LFTs (if long term therapy), serum concentrations to assure therapeutic levels (obtain after 2 weeks of therapy, draw anytime during the dosing interval)
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Systemic drugs for systemic fungal infections (the worst of the worst)
Amphoteracin B (stay away from), azoles: ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine (5-FC)
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Amphoteracin B (Amphoterrible!!)
systemic antifungal for use in SEVERE fungal infections -IV only indications: severe systemic and CNS infections that are progressive and potentially life threatening. SEs: anaphylaxis, infusion reaction, leukoencephalopathy (damage to brain white matter), nephrotoxicity
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Amphotericin B MOA
bind to ergosterol and alters cell membrane permeability and may also stimulate the macrophages monitor: renal and liver fxn (CMP), electrolytes, PT/PTT, CBC
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Drug interactions with Amphotericin B
aminoglycosides, antifungal agents, corticosteroids, cyclosporine
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Itraconazole (Sporanox) indications - for systemic infections
(for superficial -\> onychomycosis) systemic: aspergillosis, blastomycosis, esophageal and oropharyngeal candidiasis (oral soln), coccidioidomycosis, histoplasmosis
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Itraconazole (sporanox) CIs
hypersensitivity to intraconazole or other azoles -concurrent admin with other drugs that act at CYP450 system -ventricular dysfunction (negative inotrope) -CHF -pregnancy or intend to become pregnant
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Itraconazole (sporanox) pharmodynamics/kinetics
requires gastric acidity for optimal absorption -better absorbed with food (capsule) but soln is better absorbed on an empty stomach, -99.8% protein bound, half life: 21 hours -metabolized by the liver
96
Itraconazole (Sporanox) drug interactions
sig. list of drug interactions -proton pump inhibitors, anxiolytics, pain meds, antiplatelet agents, antihypertensives, cholesterol lowering meds - drug interaction checker is a must when using these drugs (same as for topical infections -same drug)
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Itraconazole (sporanox) adverse effects (for systemic use)
Nausea, diarrhea, edema, HA, rash, Abnorm. LFTs, Heart failure, arrhythmia, hearing loss, and many others
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Itraconazole (sporanox) monitoring
Baseline LFTs, monthly LFTs (if long term therapy), serum concentrations to assure therapeutic levels: obtain after 2 weeks of therapy, draw anytime during dose interval
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Fluconazole (diflucan) indications
- Blastomycosis (CNS disease) - candidiasis: candidemia, endocarditis, orpharyngeal, prophylaxis, vaginal and more - coccidioidomycosis: meningitis, pneumonia, prophylaxis -crypococcosis: meningitis, pneumonia
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Fluconazole (Duflucan) CIs
hypersensitivity to fluconazole or other azaleas -coadmin. of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide, or quinidine)
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FLuconazole (Diflucan) route and dose
IV and oral dose dep. in disease process
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Fluconazole (diflucan) pharmacokinetics/dynamics
distribution: widely thoughout the body, good penetrate into CSF, eye, peritoneal fluid, sputum, skin and urine, protein binding: 11-12% in plasma Half life:w/ normal renal function about 30 hours
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Fluconazole (Diflucan) Drug interactions
Extensive list: Most commonly used drugs that fluconazole interacts with: -statins (cholesterol) - sildenafil (viagra) -warfarin -sulfonylureas (antidiabetic meds) - proton pump inhibitors -Ca channel blockers, B blockers (antiHTNs) -Diclofenac (NSAID) -Fentanyl, benzodiazepines -macrolides
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Fluconazole (Diflucan) Adverse effects
pregnancy: C/D HA, dizziness N/V/D elev LFTs QT prolongation
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Fluconazole (Diflucan) monitoring
Baseline LFTs periodic LF, RF and K
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Systemic ketoconazole (Nizoral) FDA warning
Rare cases of serious hepatotoxicity including hepatic failure and death associated with ketoconazole. Occurred in pts receiving high doses for short tx durations and in pts receiving low doses for long durations -risk of decreased adrenal corticosteroid secretion at doses \>/= 400 mg/day -risk of QT prolong. if on other drugs known to prolong QT -significant inhibitor of CYP450 enzymes: statins,, Ca channel blockers, antidepressants, macrocodes, and b-blockers
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Ketoconazole indications (oral) for systemic infections
use restricted only for tx of systemic life threatening fungal infections when other safer agents cannot be used: -blastomycosis, coccidiomycosis, histoplasmosis, chromomycosis, paracoccidiodmycosis \*shouldnt be used for candida or dermatophyte infections
108
Monitoring of ketoconazole for systemic infections
close monitoring warranted -baseline and weekly monitoring of liver function SEs: mult. serious drug interactions -edema, orthostatic hypotension, fatigue, insomnia, pruritus, hot flashes, nausea, vomiting, myalgia, weakness, and more
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Voriconazole and posaconazole (systemic infections)
newer systemic tri-azole antifungals -oral or IV for aspergillosis -may be used for oral pharyngeal candidiasis resistant to other txs
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Flucytosine (5-FC) (systemic infections)
class: pyrimadines (diff. class diff. coverage), for severe systemic fungal infections
111
What is Tinea versicolor also known as?
- Pityriasis versicolor
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What is Tinea versicolor?
- common superficial skin infection that may become chronic - superficial yeast infection caused by Pityrosporum ovale aka Malassezia furor - Malassezia is normally found on human skin (overgrowth) - organism oxidizes fatty acids in the skin and inhibits tyrosinase in the melanocytes leading to loss of pigmentation
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Pathogenesis of Malassezia?
transformation of Malassezia from yeast cells to a pathogenic mycelial form is assoc with the development of clinical disease - not related to poor hygiene
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Who commonly gets Tinea versicolor and what are the risk factors?
- very common, - mostly common in teens (\>15), and young adults, athletes - RFs: heat, humidity, excessive sweating, use of topical skin oils, HIV infection
115
How is Tinea versicolor characterized?
- by hypo pigmented lesions on the trunk that are asymptomatic - sometimes can be pruritic - velvety tan, pink or white macules - hypo pigmented areas that don't tan with rest of the skin - 4-5 mm or confluent - Trunk, upper arms, neck and groin - lesions may scale if scraped (looks like dry skin)
116
Lab findings of tinea versicolor?
- skin scrapings seen on KOH prep show budding spores and large hyphae "spaghetti and meatballs" (KOH kills epithelial cells) - fungal culture not helpful - DDX: vitiligo, seborrheic dermatitis (seen in HIV), pityriasis alba
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Tx of Tinea versicolor?
DOC: Selenium sulfide lotion or shampoo 2.5% (Rx) - apply once daily - apply with a cotton ball, allow to dry 15 min prior to bathing - once daily for 7 days - to prevent recurrence maintenance therapy 2x a month (have chronic recurring condition) - other txs: tablets: Fluconazole (Diflucan) -\> 300 mg tablets or Intraconazole (sporanox) tablets 200 mg or Ketoconazole shampoo
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Maintenance therapy for Tinea versicolor?
- up to 80% of cases will have recurrence in subsequent 2 years w/o maintenance therapy - Selenium sulfide lotion or shampoo 2x monthly - pt education: may take months for hypopigmented areas to normal (they may not ever)
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3 species of fungi that cause human infection? (dermatophytes)
- Trichophyton - Microsporum - Epidermophyton
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localized sxs of dermatophytes do to the fact that they grow in skin, hair and nails?
- digest keratin so see scaling, nails thicken, and crumble and will see hair loss
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Risk factors for Tinea?
- warm, moist, occluded environments, family hx, compromised immune system, alteration in normal flora - spread by contact: humans, animals, inanimate objects
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Where are Tinea infections located in the epidermis?
- in the stratum corneum (superficial 1/2) and are caused by a variety of fungal species - caused by dermatophytes: Trichophyton rubrum Trichophyton tonsurans Trichophyton mentagrophytes Microsporum canis Epidermophyton floccosum
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Classification of Tinea?
- Tinea corporis: body "ring worm" - Tinea cruris: groin "jock itch" - Tinea pedis: feet "athlete's foot" - Tinea capitis: scalp - Tinea unguium: nails
124
sxs of a Tinea infection?
- generally include localized pruritus, burning and stinging - if inflammatory reaction may have erythema and vesicles in addition to sxs listed above
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Dx of Tinea infection?
- microscopic eval: skin margin scraping and KOH prep - fungal culture: takes 2 weeks (do when it is recurrent infection) - Wood's lamp: will ID microsporum species
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Tinea Corporis?
- Face, limbs, and trunk ring shaped lesion with well demarcated margins - central clearing - scaly, erythematous border - transmitted by contact by humans, animals, sports equipment -tx: topical azole antifungal (apply 1-2 x daily for 2-4 weeks) continue for a week after lesions clear
127
Tinea cruris?
- groin, inguinal folds, spares the scrotum - borders distinct - lesions are large, erythematous, macular with central clearing - hallmark: pruritus with burning Tx: topical azole antifungal (Better to use powder, already a moist area)
128
Tinea pedis?
interdigital: scaling, maceration, fissures b/t toes plantar: diffuse scaling of soles acute vesicular: vesicles and bull on the sole of foot, great toe and instep tx: topical azole antifungal (dry spray, allow feet to be exposed to air)
129
Tinea capitis?
- most cases in children - inflamed scaly, alopecic patches - diffuse scaling with round alopecic patches due to broken hair shafts - tender, pustular nodules - tx: griseofulvin for 8 weeks, or terbinafine for up to 4 weeks (cannot use topical therapy: must be systemic therapy)
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Tinea unguium
- also known as onychomycosis - typically toenails but can affect fingernails as well - oncholysis may occur - infection usually moves distal to proximal - usually asymptomatic - tx with oral terbinafine (lamisal) 250 mg qday x 6 wks for fingernails and 12 weeks for toenails (have to have systemic tx) (monitor LFTs, and CBC) alt: itraconazole (sporanox) - are a variety of topical Rx meds that are available but they have limited efficacy (50%) - systemic antifungals are very toxic and there are a lot of drug interactions -\> just let go fungal infections in elderly sometimes
131
Cutaneous candidiasis?
intertrigo: axillae, under breasts, groin, intergluteal folds balantitis: glans penis candidal folliculitis: follicular pustules candidal paronychia: nail folds Thrush: mouth and tongue diaper dermatitis \*\* will be more inflamed and red compared to Tinea (this will be in a round pattern)
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RFs for candidiasis?
- infection - recent abx therapy - diabetes - systemic and topical steroids - immunosupression - warm, moist conditions - break in the skin
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Tx of candidiasis?
- Thrush: oral lozenge or swish and swallow -\> nystatin, and clotrimazole cutaneous: powder for macerated areas (Nystatin) topical clotrimazole (lotrimin), ketoconazole -if failure of topical therapy: oral fluconazole (Diflucan)
134
Systemic candidiasis dx?
- may be difficult to isolate - blood cultures are positive about 50% of the time - May isolate organisms from urine or sputum (tx individualized (infection vs. colonization) - isolated candida from blood cultures is considered a sign of serious disease until proven otherwise - Fundoscopic exam to exclude endophthalmitis
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Hepatosplenic candidiasis?
- secondary to aggressive chemotherapy and prolonged neutropenia - fever and variable abdominal pain may be present
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Invasive disease of systemic candidiasis?
- skin, brain, meninges, myocardium, eyes, muscles - mortality is around 30% - tx: IV antifungal tx such as fluconazole
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What can be seen in disseminated candidiasis?
- tiny pustular lesions due to hematogenous dissemination of Candida albicans can be seen in pt also will see fever -\> sepsis - Can see large erythematous, nodular lesions with central necrosis in a pt with acute leukemia and disseminated candidiasis. - Muscle abscess containing yeast - go to the kidney: see abscesses in the kidney
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Where is histoplasmosis found in the United states?
- Major river valleys: In Ohio and Mississippi river valleys
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What is the source of histoplasmosis? - How are humans infected?
- found in the soil: from bird or bat droppings - inhalation of spores - infection occurs 7-21 days post exposure - lymphatogenous spread to other organs
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What is the fungus that causes histoplasmosis?
- Histoplasma capsulatum
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How are many cases of histoplasmosis detected?
- incidentally on X-ray because most cases are asymptomatic - past infection may be noted by calcifications on routine X-rays: lungs and spleen - This can't reactivate but a lot of people from this regions will have nodules in lungs
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What is acute pulmonary histoplasmosis?
- infection of the lungs - can be relatively severe: severe fatigue and fever - duration is 1 week - 6 months - rarely fatal
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Who does chronic pulmonary histoplasmosis effect? what will you see on a CXR?
- older pts and pts with underlying chronic lung disease - CXR: apical cavities, infiltrates, nodules
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What os progressive disseminated histoplasmosis and what can it be associated with?
- can be assoc. with underlying HIV (CD4 count hx is key)
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Presentation of progressive disseminated histoplasmosis?
- may be similar to septic shock - will have a fever, dyspnea, cough, and wt loss - can be fatal within 6 weeks or less
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What organs are involved in progressive disseminated histoplasmosis?
- ulcers in oropharynx - hepatosplenomegaly - GI involvement mimics inflammatory bowel disease - CXR shows a miliary pattern (small lesions everywhere)
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Dx studies for Histoplasmosis?
- CXR - CBC, CMP - alkaline phosphate, lactate dehydrogenase, and ferritin will all be elevated - Sputum culture most likely to be negative in acute disease and positive in chronic disease. - Bronchoalveolar lavage Ag testing - \*\*\*\*urine Ag test (\>90% sensitivity) - blood cultures: may takes weeks
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What is the most helpful test in dx histoplasmosis?
- urine ag test (\>90% sensitivity)
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Tx of histoplasmosis
- refer to ID specialist - Itraconazole 200-400 mg/d - duration: weeks to months - severe illness: IV amphoteracin B - AIDS related histoplasmosis: lifelong suppressive therapy with itraconazole
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Where is coccidioidomycosis endemic?
- Southwestern US, Mexico, Central America, South America
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How does coccidioidomycosis occur? Also called?
- infection occurs secondary to inhalation of molds from endemic areas - Valley fever, San Joaquin valley fever \*\* more severe cases in immunocompromised pt
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pt with coccidioidomycosis presents with what sxs?
- variety: can be asymptomatic pedal edema chest pain cough with blood tinged sputum fever, night sweats HA joint stiffness muscle pain anorexia erythema nodosum \*\*\*\*(hallmark)
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When does erythema nudism occur with coccidioidomycosis?
- may occur 2-20 days after onset of respiratory symptoms (these are swollen red nodules)
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disseminated coccidiodomycosis can affect what?
- skin (erythema nudosum, verrucous skin lesions) - lungs (cavities, infiltrates, empyema, pleural effusion) - Bones (lytic lesions) - soft tissues (abscesses) - lymph nodes (hilar and/or mediastinal lymphadenopathy, lymphadenitis and abscess formation) - meningitis
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Most common presentation of coccidioidomycosis?
acute pneumonia
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What will labs look like in coccidioidomycosis?
- leukocytosis - eosinophilia -ELISA fro IgM and IgG abs - Tissue or bone bx may reveal spores (pleural lesion: empyema, or lymph node) - blood cultures rarely positive - spinal fluid: complement fixing abs (dx in 90%), increased cell count, lymphocytosis, reduced glucose, culture positive in only 30%
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If you see multiple thin walled cavities, and patchy areas with ill defined borders on CXR what would be your differential?
- Coccidioidomycosis, lung abscesses, chronic pulmonary tb, chronic pulmonary histoplasmosis
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Tx of coccidioidomycosis?
- Refer to ID specialist - Fluconazole or itraconazole daily for months - Amphotericin B IV for severe disseminated cases - may required prolonged therapy - surgical incision and drainage of abscess formation
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What causes Cryptococcosis?
- caused by Cryptococcus neoformans yeast that is found in the soil and on dried pigeon poop
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What is cryptococcus neoformans the most common cause of?
- most common cause of fungal meningitis
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RFs of cryptococcosis?
- chemo for hematologic cancer, Hodgkin lymphoma, corticosteroid therapy, transplant recipients, TNF inhibitor therapy, HIV (immunocompromised pts) - rare in immunocompetent persons
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3 forms of cryptococcosis infection?
- cutaneous - respiratory - meningeal
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Signs and sxs of cryptococcosis?
- pulmonary: can lead to respiratory failure - any organ can be infected - CNS predominates: (meningitis) HA usually first sx confusion mental status changes cranial nerve abnormalities N/V, fever
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Dx of cryptococcosis?
- cryptococcal antigen can be found in the infected organ and often in the serum of AIDS patients - resp: sputum culture or pleural fluid - lumbar puncture for meningeal involvement: increased opening pressure, increased protein, decreased glucose \*\* india ink prep shows budding, encapsulated fungal cells: meningitis \*\*cryptococcal capsular antigen testing (dx)
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Tx of cryptococcosis?
- referral to ID specialist - Amphotericin B IV x 2 weeks - followed by fluconazole x 8 weeks
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Sxs of cryptococcosis?
HA, abnormal mental status, meningismus, respiratory sxs
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Dx test for cryptococcosis?
- capsular polysaccharide Ag in CSF, sputum or urine is diagnostic
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where is Aspergillosis found?
- in dead leaves (or other decaying vegetation), compost piles, stored grain, and on marijuana leaves
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What is usually the cause of Aspergillosis?
- Aspergillus fumigatus - ubiquitous in nature
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When would tissue invasion of Aspergillus fumigatus occur?
- with immunosuppression: tx for autoimmune disease cancer bone marrow transplant solid organ transplant HIV - severe and prolonged neutropenia - high dose glucocorticoids
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What is the most common cause of non-candidal invasive fungal infection in bone marrow and solid organ transplant pts?
- Aspergillus fumigatus
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Manifestations of Aspergillosis?
- allergy (chronic allergic response) - airway or lung invasion (most common): tracheobronchitis, rhinosinusitis - cutaneous - extrapulmonary dissemination: brain, eyes, kidney, liver, heart, GI
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What does aspergillosis most commonly affect and what are the sxs assoc'd with this?
- most commonly affects the lungs - sxs: fever, chest pain, SOB, cough, hemoptysis
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What will you see on a CXR of aspergillosis?
- single or multiple nodules with or w/o cavitation, patchy or segmental consolidation, peribronchial infiltrates
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Dx of aspergillosis?
- allergic disease: high levels of IgE and IgG Aspergillus precipitins in the blood - Galactomannan Ag from serum or bronchioalveolar lavage fluid (parts of cell wall of Aspergillus sp) - beta-d-glucan assay (new): part of cell wall of mult types of fungus, use for invasive candidial infections and Aspergillus -\*\*\*PCR for aspergillus - culture - Bx - CT scan of lungs: ground glass infiltrates with "halo sign" then development of a cavitary lesion, converts to air-crescent sign after neutrophil recovery
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When does allergic bronchopulmonary aspergillosis occur?
- with preexisting asthma and worsening bronchospasm and pulmonary infiltrates - waxing and waning course - may result in bronchiectasis and fibrotic lung disease - will see high levels of IgE and IgG Aspergillus
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Tx of Allergic bronchopulmonary aspergillosis?
- antifungals and steroids (would generally want to stay away from steroids but since it involves airway we want to decrease inflammation and ease breathing)
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What are some features of invasive life-threatening aspergillosis?
- seen in profound immunodeficiency - pulmonary manifestations: patchy infiltrates, necrotizing pneumonia - sinus invasion - multi-organ involvement: tissues infarct as organism grows into blood vessels - Hematogenous spread is possible -
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Tx of invasive life-threatening aspergillosis?
- high dose multiple agent anti fungal therapy - systemic azole, amphotericin B
