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Lecture 3 - Fungal
Skin Diseases
I. Terminology
A. Mycosis: disease caused by fungi.
Mycoses may be systemic, subcutaneous,
or superficial. Superficial mycoses involve the superficial layers of the
skin, hair, and nails and are the most common type noted with dermatologic
disease.
B. Dermatophytes: fungi that invade and
grow in dead keratinized tissue.
1.  Zoophilic dermatophytes: are
adapted to animals and rarely inhabit the soil. Ex. Microsporum canis,
Trichophyton equinum.
2.  Geophilic dermatophytes: normally
inhabit the soil and tend to cause a more pronounced inflammatory reaction in
the host. Ex. Microsporum gypseum.
3.  Anthropophilic
dermatophytes: are adapted to humans and also tend to cause a more
inflammatory skin reaction.
C. Dermatophytosis: An infection of the
keratinized tissues, nail, hair, and stratum corneum by dermatophytes.
D. Onychomycosis: fungal infection of
the claws.
II. Superficial mycosis: dermatophytosis
A. Overview: most common cause of
fungal skin disease in the dog and cat.
B. Etiologic agents: Microsporum canis
= most common agent.
1.  Canine: most cases are due
to M. canis, and less often M. gypseum and T. mentagrophytes.
2.  Feline: almost all cases are
due to M. canis (less often as above).
C. Source of exposure
1.  M. canis
M. canis is usually acquired by exposure to an infected cat (although
environmental contamination or fomites can also be responsible).
2.  Others
M. gypseum is often encountered via the soil (digging, etc.) and T.
mentagrophytes via exposure to reservoir host (rats, their environment).
D. Predisposing factors: higher
incidence in warm and humid climates.
Predisposing factors to development of
disease include young age, immunosuppression (FeLV, FIV, etc.) poor
nutrition, and perhaps genetic factors.
E. Pathogenesis
1.  Transmission
a.  Typically occurs by contact
with a carrier or infected animal, fomite (bedding, grooming instruments,
environment) or soil (M. gypseum).
b.  Fungistatic activity of
sebum and sweat, mechanical skin barrier and cell mediated immunity help
defend against fungal invasion in most animals.
2.  Exposure does not
necessarily result in infection
Many normal, asymptomatic animals can harbor dermatophytes on their hair (of
healthy cats sampled at shelters, about 15% carried dermatophytes).
3.  Fungal invasion
a.  Liberated arthrospores from
fungal hyphae adhere to keratin and germinate within several hours.
b.  Moisture favors germination.
Arthrospores typically do not penetrate healthy intact epidermis. Minor
trauma to the skin and disruption of the stratum corneum (clipping, moisture,
insect bites) facilitates penetration.
c.  Keratinases produced by
fungal hyphae digest dead keratinized tissue, and allow for hair penetration.
The growing (anagen) hair and keratinocytes provide nutrition (keratin) to
the fungus necessary for fungal growth.
4.  Spontaneous resolution of
infection
a.  Spontaneous resolution
occurs with strengthening of the immune response (CMI,) turnover of the
epidermis, and transition of hairs to telogen phase (hairs no longer produce
keratin and are shed).
b.  Time course: incubation
period is 7-14 days, infection progresses for 6-8 weeks, and healing
typically occurs in 2-3 months. Recovered cats may be susceptible to
reinfection.
F. Clinical signs
1.  Signalment: disease is more
common in the young as well as immunocompromised patient.
Persians and Himalayans are predisposed.
2.  Asymptomatic carrier: many
cats (especially longhairs) are inapparent carriers with no lesions.
3.  Skin and hair response
Enzymes and antigenic substances released by the dermatophyte incite an
inflammatory reaction. Hairs are weakened, become brittle and break. Hair
loss, scaling and a variety of cutaneous signs may be present.
a.  Classic "ringworm"
lesions
Focal circular to patchy areas of alopecia with minimal scaling and
inflammation. Lesions tend to predominate on head and forelimbs and pruritus
is usually mild.
b.  Folliculitis
Most infections are follicular, and resemble bacterial folliculitis.
Furunculosis, secondary pyoderma, miliary dermatitis and onychomycosis are
alternate presentations.
c.  Other lesions
i.  Hair loss: may be inapparent
to profound, and symmetric or asymmetric.
ii.  Pruritis: typically mild,
but in some cases may be significant.
iii.  Unilateral or bilateral
pinnal pruritis (infected hairs usually on ear margin).
iv.  Crusting, scaling and
hyperpigmentation: in varying degrees of severity.
v.  Comedones: chin acne-like
lesions in young cats.
vi.  Miliary dermatitis,
eosinophilic plaques, and granulomatous skin lesions in some cats.
vii.  Folliculitis or
furunculosis (especially of the nose or digits) in some dogs.
G. Zoonosis
The zoonotic potential of
dermatophytosis is high, with about 50% of exposed humans developing skin
lesions (particularly the young).
H. Diagnosis
1.  Wood's light exam
a.  Basis
About 50% of M. canis strains fluoresce under Wood's (ultraviolet light).
Fluorescence occurs due to tryptophan metabolites elaborated by the growing
fungus.
b.  Technique
Warm up Wood's light for 5 - 10 minutes prior. Move the light through all
regions of the haircoat. Look for evidence of apple-green fluorescence within
the hair shaft (not scales).
c.  Interpretation
i.  Positive fluorescence of
hairs: usually indicates M. canis. Culture to confirm. Positive fluorescence
of scale is non-diagnostic.
ii.  Negative fluorescence: does
not rule out dermatophytosis (50% of M. canis cases do not fluoresce nor do
most other dermatophytes).
2.  Microscopic exam of hair and
scale
a.  Technique
Select hairs (by positive fluorescence) or perform skin scraping/hair pluck
at center and periphery of lesions
Place hairs on slide with a small amount of mineral oil and cover with
coverslip. Alternatively, can prepare with potassium hydroxide to clear
excess keratin debris.
b.  Interpretation: negative
finding does not rule out disease.
Evaluate for infected (irregular and swollen) hairs under 10X objective.
Under 40X objective, may note hyphae or grape-like clusters of ectothrix
spores on hair shaft.
3.  Fungal culture
a.  Technique of choice for
definitive diagnosis of dermatophyte infection
i.  Pluck hairs from center and
periphery of lesion and push root ends into culture media.
ii.  In asymptomatic or mildly
affected animals, use toothbrush technique to harvest samples.
Use new toothbrush (mycologically sterile in packaging), brush entire
haircoat and gently push collected material into culture media.
b.  Fungal
culture media: Dermatophyte test media (DERMAKIT)
i.  Constituents
DTM contains Sabouraud's dextrose agar, the pH indicator phenol red, and
agents to inhibit the growth of bacteria as well as saprophytic fungi.
"Derm duets" have one side of DTM media and a sporulating media on
the opposite side which supports development of macroconidia.
ii.  Monitoring: Observe
daily for 14 - 21 days.
Fungal cultures should be incubated at room temperature (30 degrees C), not
exposed to bright light (UV light can hinder growth) and not allowed to
desiccate (30% humidity).
iii.  Dermatophyte growth
Dermatophytes produce fluffy white colonies and simultaneously turn
the media red (use protein source and produce alkaline metabolites). Most
non-pathogenic fungi use carbohydrate source, forming acid metabolites that
do not cause a color change in the media.
Assess the DTM plates daily for a color change - as it is possible for
un-observed non-pathogenic to grow, exhaust carbohydrate source and then use
protein source to turn media red.
iv.  Follow-up microscopic exam
Collect fungal sample to identify causative dermatophyte. Place a piece of
scotch tape on surface of fungal colony and transfer to a slide containing a
drop of lactophenol cotton blue stain. Apply coverslip and view under
microscope to identify macroconidia.
4.  Biopsy
Special fungal stains can be used on tissue samples to demonstrate fungi -
however, DTM culture is the preferred method for diagnosis in most cases.
I. Treatment
1.  Overview
a.  Treatment goals include
promoting immune response, hastening resolution of infection, and minimizing
environmental contamination.
b.  Many healthy dogs and short
hair cats undergo spontaneous resolution of infection within four months.
c.  Due to risk of contagion,
re-infection, and zoonosis, most authors agree that confirmed dermatophytosis
should be treated.
d.  Patients with focal lesions
are considered to have generalized infection (as spores can often also be
found in non-affected areas of haircoat).
2.  Preparation for topical
therapy
a.  Clipping of haircoat is
often recommended in dogs or cats with medium to long hair. Be gentle and use
a no. 10 clipper blade to minimize skin trauma and spread of infection. As
hairs may contain infective spores, hairs should be carefully collected and
disposed of.
b.  Shampoo therapy: most
beneficial in those with significant skin lesions or secondary pyoderma.
Antifungal choices include Dermazole (miconazole 2%), MalaSeb
(miconazole/chlorhexidine), and Chlorhexiderm shampoo. Owners should wear
gloves.
3.  Topical antifungal dips
(allow to dry on coat):
a.  Lime sulfur dip (Lym- dyp®)
i.  Considered to be one of the
most effective topical treatments available. Safe for use in puppies and
kittens.
ii.  Directions: Follow labeled
directions (30 mls in 1 liter warm water), sponge over entire haircoat and
let dry. Repeat once to twice weekly for 4 to 8 weeks (until 3 negative
cultures at weekly intervals).
iii.  An Elizabethan collar can
be placed after dipping to discourage self grooming and removal of dip.
b.  Other options
0.2% enilconazole rinse (Imaverol) is another effective topical antifungal
dip. Not always available and can be irritating to the skin in some.
c.  What else? All in-contact
animals (dogs and cats) must be treated, as well as the environment to insure
therapeutic success.
d.  Literature reference:
Treatment of dermatophytosis in dogs and cats: review of published studies
Vet Dermatol. April 2004;15(2):99-107.
4.  Systemic therapy
a.  Overview
i.  In general, recommended
in conjunction with topical therapy. Systemic therapy shortens duration
and severity of clinical disease. Topical therapy decreases environmental
contamination and minimizes reinfection.
ii.  Indicated in dogs and cats
that do not respond to topical therapy within 2 - 4 weeks and always in the
treatment of infected catteries.
iii.  Duration: treatment is
continued until 3 successive weekly negative fungal cultures are obtained
(usually a minimum of 6 - 10 weeks).
b.  Griseofulvin (Fulvicin U/F®)
i.  Drug of choice: aborts
infection (fungistatic), inexpensive, and approved for use in cat.
ii.  Formulation: Two different
dosage forms available (microsize and ultramicrosize) - be sure to use
correct dose for formulation administered. Give with fatty meal to facilitate
absorption. Typically given for a minimum of 6 weeks.
iii.  Adverse effects: GI upset,
leukopenia, anemia, teratogenic. Monitor CBC and liver enzymes before
initiation of therapy and at intervals during therapeutic course.
iv.  Contraindications: do not
use in pregnant animals, in kittens < 12 weeks of age or in FeLV or FIV
positive cats (increased risk of BM suppression).
c.  Itraconazole (Sporanox):
also has excellent activity against dermatophytes.
i.  Itraconazole is similar in
efficacy to griseofulvin (although more expensive). Contraindicated in pregnant
animals.
ii.  GI side effects, anorexia
and hepatotoxicity have been noted in some. Liver enzymes should be checked
before therapy and during the treatment protocol. Itraconazole is given for
30 to 60 days. All in contact animals should be treated.
d.  Other options
i.  Ketoconazole is another
potential treatment option in the dog, but only variably effective.
ii.  Terbinafine (Lamisil) may
be considered for dermatophytes resistant to griseofulvin and itraconazole,
expensive and limited studies available.
iii.  Lufeneron (Program):
controlled studies have failed to confirm beneficial effects in treatment of
dermatophytosis.
5.  Environmental control
Crucial in prevention of reinfection and absolutely necessary in the
elimination of infection from a cattery (infected hairs and spores can remain
viable for months to years in environment)
a.  Mechanical clean-up
Removal of hairs from environment, fomite disposal or treatment (brushes,
bedding, etc.). Detailed clean-up protocols are available (consult references).
b.  Disinfectants: a 1:10
dilution of household bleach is effective for treatment of walls, counters,
and floors.
c.  Catteries
Infected catteries necessitate treatment of all cats, meticulous attention to
disinfection of the environment and quarantine/culture of newcomers. The
protocol is very detailed and labor intensive (consult references).
III. Superficial mycosis: Malassezia
pachydermatis (formerly Pityrosporum canis)
A. Etiology
1.  Normal commensal skin and
ear inhabitant in low numbers.
2.  Overgrowth is often
associated with underlying disease that increases skin moisture or cerumen
production (allergies, seborrhea, pyoderma, etc.).
B. Incidence and clinical signs
1.  Uncommon (but increasingly
recognized) in dogs, rare in cats.
2.  Clinical signs
a.  Otitis externa: moist brown
or waxy discharge.
b.  Generalized seborrheic
dermatitis: with significant pruritis, scaling, erythema, crusting,
greasiness and malodor.
C. Diagnosis and treatment
1.  Diagnosis via cytology (skin
scrapings) - note excessive numbers of budding "peanut-shaped"
yeast.
2.  Treatment
a.  Must address underlying
trigger (or disease) to effect long term resolution.
b.  Topical therapy:
i.  Localized lesions: Cleanse
region and apply an effective topical product (Ex: Nystatin®, Miconazole®,
Clotrimazole®).
ii.  Generalized lesions:
shampoo with selenium sulfide (Selsun blue), 2% miconazole, or chlorhexidine,
and follow with lime sulfur dips twice weekly until cure.
c.  Systemic therapy
(ketoconazole, itraconazole): may be indicated in more refractory cases.
IV. Subcutaneous mycoses
A. Overview
The SQ (intermediate) mycoses are
fungal infections that have invaded viable tissues of the skin. Typically
acquired by traumatic inoculation of saprophytic organisms (from soil or
vegetation) into the skin. Skin lesions are usually localized and often
chronic.
B. Terminology
Chromomycosis, mycetoma,
pseudomycetomas, hyalohyphomycosis, phycomycosis, pythiosis and zygomycosis
are all terms used to define specific types of fungi that cause subcutaneous
mycosis.
C. Clinical appearance
In general, uncommon disease. Many of
the SQ mycosis result in localized nodular lesions that exhibit variable
swelling, ulceration and drainage. These lesions can resemble a granuloma,
foreign body reaction, mycobacterium, the common abscess, or focal neoplasm.
D. Diagnosis
Cytology, culture (bacterial and
fungal), and biopsy (often necessary to obtain definitive diagnosis).
Punch biopsy for culture should be
obtained from margin and center of lesion, placed in bacteriologic transport
media and delivered to lab within 24 hrs.
E. Treatment:
Variable depending on specific fungal
pathogen, but often entails complete surgical excision or systemic
anti-fungal therapy.
F. Sporotrichosis (Sporothrix
schenckii)
1.  Incidence: uncommon in cat
and uncommon to rare in dog. Clinical disease is found most often in the
Southern U.S.
2.  Pathogenesis
a.  This fungus is a soil
saprophyte and in the dog entry is likely via the skin from cutaneous
puncture wounds associated with thorns or splinters.
b.  In the cat, contaminated
claws or teeth from another cat may serve as source of inoculation (lesions
often noted on head, extremities, tail).
3.  Clinical signs
Cutaneous form (most common): note firm, raised nodules (especially on the
face) that often ulcerate. Other forms include the cutaneous lymphatic form
(involvement of regional LN's) and disseminated form.
4.  Zoonosis
Exudates contain infectious organisms that are transferable to people
(without skin penetration).
Wear gloves when handling suspected cases. Most reported zoonosis have
occurred from cats.
5.  Diagnosis
a.  Cytology:
"cigar-shaped"organisms noted on routine stains (more abundant in
cat exudates).
b.  Fluorescent antibody test:
useful in dogs with suspected disease and negative cytology findings.
6.  Treatment: consult reference
source for protocol.
The treatment of choice is oral iodides. For those that fail or cannot
tolerate iodide therapy, ketoconazole or itraconazole can be used.
V. Systemic mycoses
Overview
This course will only briefly touch
upon the dermatologic manifestations of systemic fungal diseases. Consult
your infectious disease notes for more complete information on the
pathogenesis, clinical signs, and treatment of the systemic mycoses.
A. Definition
Systemic (deep) mycosis are fungal
infections of the internal organs that may disseminate secondarily to the
skin. Animals with skin lesions are presumed to have systemic infections -
skin lesions that occur via direct cutaneous inoculation are rare.
B. Pathogenesis
Infection typically occurs via
inhalation. Causative fungi exist as saprophytes in the soil and vegetation.
These diseases are usually not contagious.
C. Clinical signs
1.  The cutaneous lesions
associated with systemic mycoses are characterized by papules, plaques,
ulcers, or nodule (or abscess) formation with associated pyogranulomatous
inflammation.
2.  Cell mediated immunity is
important in resistance. Affected animals may also exhibit regional
lymphadenopathy and other organ systems are frequently affected.
D. Diagnosis
Usually demonstration of organism on
aspiration or biopsy of affected organ (skin, lymph node, etc. ), specific
immunologic tests (in some cases) or deep culture (due to health hazards,
should only be performed in licensed labs.)
E. Treatment: systemic anti-fungal
therapy (consult infectious disease notes).
F. Deep mycosis most likely to have
skin involvement
1.  Cryptococcus neoformans:
most common deep mycosis of cats
Soil saprophyte, often associated with pigeon droppings. Skin lesions noted
in 20 -40% of cases.
a.  Feline: rapidly growing firm
nodules (often of face, pinna, paws) that ulcerate and drain. Regional
lymphadenopathy may also be present.
b.  Canine: may have more
ulcerative type of skin lesions (similar to blastomycosis).
2.  Blastomyces dermatitidis:
Uncommon in dogs, rare in cats.
Skin lesions may be noted in 40% of dogs with blastomycosis. The nasal
planum, face, and digits are preferred sites
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