Fungal Skin Diseases Flashcards
A fungus in the sexual state is termed a ____ and in the asexual state is termed an _____.
teleomorph
anamorph
Define hyphae
Hyphae are cylindrical, thread-like structures that grow at the tips and can either branch or
fork. They can also fuse, which is referred to as hyphal fusion or anastomosis.
Define mycelium
Micelium are an interconnected network of hyphae that develops as hyphae grow. They can be septate or coenocytic
Define conidida
Conidia are responsible for asexual reproduction and are nonmotile spores generated by mitosis and can come in many shapes and sizes
What are two major physiological barriers to fungal growth?
Temperature
- The optimal growth range for fungi is considerably lower than body temp.
• Oxidation-reduction potential
What are the different species classifications of dermatophytes?
• Zoophilic dermatophytes
- Microsporum canis, M. equinum, and T. equinum are adapted to living on animals, rarely found in the soil, and will occasionally infect humans.
- Sylvatic dermatophytes
• T. mentagrophytes, M. persicolor are zoophilic dermatophytes adapted to living on rodents or hedgehogs.
• Anthropophilic dermatophyte
- Epidermophyton, T. tonsurans, T. rubrum - adapted to humans, rarely infects animals as a reverse zoonosis.
• Geophilic dermatophyte
- Microsporum gypseum occurs in the soil as saprophytes, but under favorable conditions, can infect humans and animals if skin or immune system is compromised.
Define arthrospores
- typical infective portion. Form by segmentation and fragmentation of fungal hyphae.
Fungal Proteolytic Acantholytic Dermatoses
Pathogenic dermatophytes secrete numerous endo- and exoproteases that belong to several families such as subtilisins, fungalysin metalloproteases, dipeptylpeptidases and amino or carboxypeptidases. Trichophyton enzymes have been shown to induce acantholysis when added in vitro to human skin explants. Superficial acantholytic pustular Trichophyton dermatophytosis has been reported in two horses and four dogs.
Superficial Pustular Dermatophytosis in Dogs and Horses
- Trichophyton spp. invade primarily the stratum corneum of the epidermis and/or follicular infundibula, and they can recruit neutrophils that will later accumulate in a subcorneal location.
- The histopathological findings of this fungal dermatosis also resemble those of PF with subcorneal pustular neutrophil-predominant pustules containing acantholytic keratinocytes.
- Lymphocyte-rich interface dermatitis may be seen also in dogs with this disease
- dermatophytes might not be detected with conventional hematoxylin-eosin - special stains (e.g. periodic acid Schiff [PAS] or Gomori’s methenamine silver [GMS]) and serial sections of the sample are needed to visualize the organisms in the stratum corneum.
- Hair invasion by dermatophytes, if present, is minimal.
What do the walls of fungi consist of?
chitin, chitosan, glucan, mannan.
What is a single vegetative filament of fungus?
hypha or hyphae (numerous)
Hyphae are septate if they have visions between cells, or sparsely seepage is they have many nuclei in the cell. The latter is known as what?
Coenocytic
What is the term should ben used only for an asexual propagule or unit that give rise to genetically identical organisms.
conidium
a conidiophore is a simple or branched mycelium bearing conidia or conidiogenous cells.
What is a fungal cell that fives rise to conidium?
Conidiogenous cell
The asexual state of fungal is called the ____ and the sexual state is known that the ___ state.
anamorph
telomorph
Dermatophytes are primary found in the anamorphic states.
What are the features that distinguish oomycetes from fungi?
- Their cell wall are composed primarily from B 1,3 - glucan polymers and cellulose with very little chitin ( in contrast for fungal cell walls which contain large amount of chitin and ergosterol)
- Utilization of mycolaminarin (a b - 1,3-glucan) for energy storage
- Diploidy at the vegetative state
- Complex life cycle involving sexual and asexual reproduction
- Asexual reproduction involve formation of sporangium that produces motile zoospores bearing two flagella. zoospores adhere to the surface of plants or animals, germinate, and then penetrate into tissues of the host.
What are the most common species of saprophytic molds found on dogs?
Alternaria, Aspergillus, Auerobasidium, Chrysosporium, Cladosporium, Mucor, Penicillium and Rhizopus.
What are the most common species of saprophytic molds found on cats?
Alternaria, Aspergillus, Chrysosporium, Cladosporium, Mucor, Penicullium, Rhodotorula and Scopulariopsis,
Cats infected with what disease(s) ahem a greater diversity of guns isolated from their skin and mucosal surfaces?
FeLV/and/or FIV
What two anti fungal treatments are polyene antifungals that bind with ergosterol in fungal cell membranes, resulting in altered cell permeability and death. It is NOT effective against dermatophytes.
Nystatin and amphotericin B 3%
What class of antifungals inhibits synthesis of ergosterol, triglycerides, phospholipid, chitin and oxidative and peroxidative enzymes.
Azoles
What two anti-fungal treatments are considered allyamines that bind to stratum corneum and penetrate the hair follicles. They inhibit ergosterol biosynthesis and squalene epoxidase for treatment of Candida and Dermatophytes.
Naftine Cream and terbinafine
**Naftin cream has some antiinflammatory effects
What is the MOA of Griseofulvin?
Fungistatic, binds to keratin and inhibits cell wall synthesis, nucleic acid synthesis and cell mitosis by arresting division at metaphase, interfering with the function of spindle microtubules, morphogenic changes in fungal cells and possible antagonizing chitin synthesis in the fungafcell wall. This agent is primarily active against growing cells, although dormant cells may be inhibited from reproducing.
- *Fermentation product of Penicillium
- Can not use in cats with FIV/FeLV
What are the two forms of Griseofulvin and which is 2-4 times more bioavailable?
Micronized crystal is 2-4 times more bioavailable than the ultramicrobized Gris-PEG.
**Effective ONLY against dermatophytes and is teratogenic
After oral administration, Griseofulvin may be detected in the stratum corneum within 8 hour to 3 days. The high-test concentrations are attains in the ____ and lowest in the ____ layers.
Highest in the SC and lowest in the SB
The drug is carried to the stratum corneum by diffusion, sweating and TEWL and is deposited in keratin precursors cells and remains bound during the differentiation process.
What are the anti-inflammatory effects of Griseofulvin?
Supresses delayed-type hypersensitivity reactions and irritant reactions in the skin.
Systemically administered azaleas include imidazole and triazoles. They inhibit the cytochrome P450 enzyme ______, thereby inhibiting conversion of ____ to _____ and causing accumulation of C14 methylated steroids.
Lanosterol 14-Demethylase
Lanosterol to ergosterol sterol (found in cell membranes of fungi)
Other actions include an inhibition of intracellular triglyceride and phospholipid biosynthesis, inhibition of cell wall chitin synthesis and inhibition of oxidative and peroxidative enzymes.
The potency of each azole is related to its affinity for binding to the _______ moiety.
cytochrome P450
What are the common drug interactions of the azoles?
Interactions with azoles are well recognized - antihistamines (terfenadine, asstemizole), GI motility agents (cisapride), benzdiazapines, calcium channel blockers, anticonvulsants, antimycobacterial agents and CSA.
Ketoconazole inhibits ____ thereby blocking conversion of deoxycorticosterone to corticosterone.
11-hydroxylase
It also interacts with membrane phospholipids and inhibits yeast transformation to mycelial forms. Additional antifungal actions involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.
At higher concentrations, it may have a direct physiochemical effect on the fungal cell membrane = fungicidal action.
What are some of the contraindications for using ketoconazole?
Not as effective for aspergillosis and sporotrichosis
Avoid use with mitotane, rifampin, and theophylline.
Alters metabolism of diphenylhydantoin, rifampin, barbiturates and CSA.
Absorption is decreased if given with H2 blockers, antacids or PPI.
What effect can ketoconazole have on coat?
reversible lightening of coat
What are the anti-inflammatory effects of ketoconazole?
Supression of neutrophil chemotaxis and lymphocyte blastogenic response, inhibition of 5-lipooxygenase activity and inhibition of leukotriene production.
What is the MOA of itraconazole?
Inhibits cytochrome P450 14a demethylase, preventing ergosterol synthesis in fungal cell membranes; binds wearing to mammalian P450.
~ Bioavailability is only 40% with fasting; increases when give with food. Oral suspension is 70%.
Highly protein bound and concentrates in the lipophilic tissues of keratin.
Secrete in sebum
Increased potency, wider range of action and decreased toxicity compared to ketoconazole.
What are the contraindication of itraconazole?
Do not administer concurrently with cisapride, terfenadine = fatal cardiac arrhythmia. It can lead to vasculitis at higher doses.
Prolong effects and increased toxicity of midazolam, CSA, GC, AH, quinidine, dioxin, vincristine, warfarin, sulfonyureas,. Concurrent antacids, H2 blockers and anticholinergics are contraindicated.
Because itraconazole is more specific for fungal than mammalian cytochrome P450 enzymes - it does not interfere with ______ synthesis.
sterol
What drug is considered a bis-triazole?
Fluconazole
Inhibits sterol and CP450 synthesis. It has a higher affinity fo fungal enzyme than KCZ or ITZ.
GI absorption is not affected by food or gastric pH.
Penetrates well into CNS and ocular tissue.
What are the contraindication with FCZ?
Reduce dose in renal insufficiency; avoid use in pregnant animals.
Cimetidine may interfere with absorption.
FCS potentiates activity of anticoagulants, thiazide diuretics, rifampin, CSA, glipizide, antihistamines, diphenyldantoin and theophylline.
Terbinafine inhibits ergosterol biosynthesis and squalene epoxidase, resulting in fungal cell wall ergosterol deficiency and intracellular accusation of what?
Squalene
What is Terbinafine MOA?
It is fungicidal (most dermatophytes, Asper and Sporothrix) and fungistatic - less effective against yeast.
Because it is generally not inhibitory to CP450 systems, it is more selective than azoles.
Drug delivery of Terbinafine is primarily via _____
Sebum
What are the contraindications for terbinafine?
Reduce dosage with renal and/or hepatic insufficiency. May be used in pregnancy. Few drug interactions (cimetidine increased blood contractions where as rifampin decreases it).
For terbinafine, what drug increases blood concentrations and which drug decreases blood concentrations?
Cimetidine increases blood concentrations.
Rifampin decreases blood concentration.
What anti-fungal is classified as a fluorinated pyrimidine?
Flucytosine
Fungal cell walls are susceptible to Flucyosine if they contain what enzyme? This enables 5-fluorocytosine to be taken into the fungal cell, where it is deaminated by cytosine deaminase to 5-fluoro-21-deoxyuridylic acid.
Cytosine permease
What are the indications for using flucytosine?
Used in combination with amphotericin B for Candida, Cryptococcus, Aspergillus and phaeohypomecosis. Not effective against dermatophytes.
What drug is a polyene anti fungal and originally isolate from a soil sample containing Streptomycin nodosus?
Amphotericin B
It is a fungistatic polyene antibiotic that disrupts fungal and bacterial cell membranes by irreversible binding with ergosterol. This results in altered cell permeability, leakage of intracellular constiuetnts and cell death.
It also binds to cholesterol in mammalian cell membranes and is relatively toxic.
It is administered IV and completed with lipids. It is taken up by macrophages that carry the drug to sites of fungal-induced inflammation.
Not effective against Dermatophytes
Do not use in renal or hepatic failure.
Amphotericin B stimulates lymphocytes, macrophage and neutrophil function and induces production of what inflammatory mediator?
TNFa
Which form of amphotericin b is used in dogs for systemic mycosis and leishmaniasis?
L-AMB and ABD (can use in cats too)
Amphotericin B is nephrotoxic due to what mechanism?
Amb increases intracellular Ca in vascular smooth muscle cells and stimulates eicosanoid synthesis, resulting in reduced renal blood flow. May also cause hypokalemia, weight loss and nonregenerative anemia.
What inorganic halogen is highly effective in the treatment of cutaneous sporotrichosis?
Iodides
What drug is a Benzoylphenyl urea, an insect growth regulatory that acts by inhibiting chitin synthesis, polymerization and depostion?
Lufenuron - inhibitor of chitin synthesis and cell wall synthesis
What is a cyclic hexapeptide that inhibits 1,3 - B-D-glycansynthase, thereby blocking cell wall synthesis in fungi.
Caspofungin - Echinocandin Class
What inflammatory mediatory has been shown to enhance activity of phagocytes abasing fungi, both in vitro and in rats?
IFN-y
Which species of microsporum is a natural resident and occasional pathogen of mice and voles?
Microsporum persicolor
Hair shafts containing infectious M. canis arthrospores can remain infectious int he environment for up to how many months?
18 months
When an animal is exposed to a dermatophyte, an infection may be established. The typical infective portion of the organisms is the ______.
Arthrospore
Arthrospores are formed by segmentation and fragmentation of fungal hyphae and may be carries by dust particles, air currents, fomites and ectoparasites include fleas.
Arhtrospores adhere strongly to keratin and can germinate within 6 hours after contact with the skin.
What is the difference between endothix and ectotrix?
Hair is invaded in both ectothrix and endothrix infections. Ectothrix fungi produce masses of arthrospores on the surface of hair shafts, whereas endothrixs do not.
Hyphae penetrate the hair cuticle and growth within the hair shaft until what keratogenous zone is reached?
Adamson fringe
How does spontaneous resolution of dermatophytosis occur?
Spontaneous resolution occurs when infected hairs enter the telogen phase or if an inflammatory reaction is incited. when hair enters telogen, keratin production slows and stops; because the dermatophyte required actively growing hairs for survival, fungal froth also slow and stops. Infectious arthrospores may remain on the hair shaft, but reinfection off that particular hair follicle doe snot occur until it reenters anagen.
What two species of dermatophytes produce tannins that diminish cell mediated immune response and indirectly inhibit stratum corneum turnover?
T. rubrum and T. metagrophytes
M. canis has been shown to possess multiple enzymatic properties, which can vary according to the strain of fungus. What is the keratinase produced by M. canis leading to more inflammation and pruritus?
u-chymotrypsin-type serine proteinase
What breeds may have a genetic breed predisposition to developing dermatophytosis?
Persians
Yorkie and Manchester terries have a predisposition to devilment of T. Mentagrophytes
Severe dermatophytosis and dermatophytic pseudomycetoma with marked lymph node involvement have been reported in Yorkies in association with what two species of dermatophytes?
M. canis
T. Metagrophytes
What two species of dermatophytes do not invade hairs and are visualized in scales?
M. persicolor and Epidermophyton floccosum
Using PCR, detection of what gene appears to be rapid and specific for dermatophytes?
chitin synthase 1 gene
It is recommended that therapy be continued until ____ successive fungal cultures performed at weekly intervals by brush technique are negative.
three
According to the text book, there ar show many lipid-dependent species of Malassezia
Textbook - six lipid dependent.
***Currently, the genus Malassezia includes 16 species, of which 15 are lipid-dependent and are most frequently recovered from humans, ruminants and horses (Malassezia furfur, M. globosa, M. obtusa, M. restricta, M.slooffiae, M. sympodialis, M. dermatis, M. nana, M. japonica,M. yamatoensis, M. equina, M. caprae and M.cuniculi, M. brasiliensis, M. psittaci).
The only non-lipid-dependent species, M.pachydermatis is commonly recovered from cats and dogs.
Malassezia belong to the ______ yeasts. They are characterized by a multilayered cell wall and reproduce by _______ budding
basidiomycetous
unilateral
In general what is important for adherence of M. Pachydermatis to corneocytes? What is the ligand on canine corneoctytes?
Trypsin sensitive proteins and glycoproteins on yeast cell walls
mannosyl-bearing carbohydrate residues on canine coenocytes serve as ligands for adhesions.
How many different Malassezia protein antigens have been identified by Western blotting?
14
Dogs with Malassezia have elevated serum concentrations of _________; compared to healthy dogs; however, these do not appear to be protective against infection.
immunoglobulin A and G
Basset hounds have an increased or decreased lymphocyte response to Malassezia compared to healthy dogs?
decreased
**Suggesting cell-mediated immunity may be more important that humoral responses in protecting from disease.
In this study, healthy basset hounds experiences significantly greater in vitro lymphocyte blastogenic response to M pachermatis antigen than basset hour with Malassezia dermatitis.
Histologically, how is Malassezia dermatitis characterized?
Characterized by prominent exocytosis of lymphocytes (CD-3 positive) and a sub-epithelial accumulation of mast cells, which suggest a hypersensitivity reaction.
Widespread Malassezia dermatitis in cats has been associated with which concurrent diseases?
FIV infections, thymoma, and pancreatic adenocarcinoma.
Genetic predisposition would appear to be important in which breeds?
WHWT, basset hound, Cocker spaniel, Shih Tzu, English setter, poodles, boxer, CKCS, Australian and silky terriers, GSD, and dachshund.
Over what percentage of dogs have concurrent dermatoses, especially allergies, keratinization defects, endocrinopathies and bacterial pyodermas?
70%
40% have concurrent staph pyoderma (of the 70%)