Download uni-7- Viral infections, and Fungal infections

Unit 7.
• Viral infections:
1, Verruca vulgaris, Verruca plana
2, Molluscum contagiosum
3, Herpes simplex
4, Herpes zoster
-Etiology, Clinical features, Diagnosis & Treatment. 1 hr
• Fungal infections:
1, tinea capitis
2, tinea corporis
3, tinea of feet & hands
4, onychomycosis
5, pityriasis versicolor
- Etiology, Clinical features, Diagnosis and Treatment 1 hr
Verruca vulgaris (common warts)
Verruca plana (flat warts)
Etiology:
Human Papillomaviruses
HPV Types and Morphology and Site of Skin Lesions
Lesion
Location
HPV Genotype
Common wart
Mostly hands
2, 4
Plantar wart
Bottom of feet
1
Mosaic wart
Hands and feet
2
Flat wart
Arms, face, knees 3, 10, 28, 41
Butcher wart
Hand
7
Extragenital Bowen
disease
Upper and lower
extremities, head
2, 3, 5, 16, 18, 20, 31, 33,
34, 54, 56, 58, 61, 62, 73
Macular plaques of
epidermodysplasia
verruciformis
Light-exposed
areas
5, 8, 9, 12, 14, 15, 17, 19,
20, 21, 22, 23, 24, 25, 36,
47, 50
Clinical features
verrucae vulgaris
•occur on any skin surface
--usually on hands and fingers
•skin-colored-, circumscribed-, rough-,
hyperkeratotic papulonodules with minimal irregular
scaling
•asymptomatic, rare painful
•Autoinoculation
Clinical features
Flat warts, or verrucae plana
multiple small flat papules
--most occur in groups
--less than 5 mm in diameter
may induce pigmentation
most on the face & hands
Spontaneously regression
usually occurs
Diagnosis of warts
Most cutaneous warts can be recognized clinically
Histology
marked hyperkeratosis
acanthosis
parakeratosis
papillomatosis
Differential Diagnosis of Warty Lesions on Hands and Feet
Palms and soles
Single Lesions
Multiple Lesions
Consider
•Verruca vulgaris
•Callus, corn, clavus
•Epidermal inclusion cyst
•Milkers nodules (palms)
•Orf (palms)
Consider
•Arsenical keratoses
•Verruca vulgaris
•Palmoplantar keratoderma
•Pyogenic granuloma
•Psoriasis
•Pits in basal cell nevus
syndrome
Rule Out
•Secondary syphilis
Rule Out
•Amelanotic acrolentiginous melanoma
•Carcinoma cuniculatum
Dorsum of hands Consider
and feet
•Verruca vulgaris
•Periungual warts
•Actinic keratosis
Rule Out
•Squamous cell carcinoma
•Keratoacanthoma
•Tuberculosis verrucosa cutis
•Fish tank granuloma
Consider
•Verruca vulgaris
•Verrucae planae
•Actinic keratosis
•Acrokeratosis verruciformis
•Stucco keratosis
Differential Diagnosis of Plane Warts
Face
•Perioral dermatitis
•Adenoma sebaceum
(mild)
•Syringomas
•Flat seborrheic
keratosis
•Actinic keratosis
•Trichoepitheliomas
Hand
•Acrokeratosis
verruciformis
•Lichen planus
•Stucco keratosis
•Seborrheic keratosis
Trunk, Extremities
•Epidermodysplasi
a verruciformis
•Pityriasis
versicolor
•Superficial actinic
porokeratosis
•Seborrheic
Treatment of warts
•Cryotherapy with liquid nitrogen (-196ºC) √
•Laser Carbon dioxide lasers √
pulse dye laser
•Antimitotics
Podofilox (Condylox, Podophyllotoxin)
Podophyllum resin (Pod-Ben-25, Podofin)
podophyllotoxin.
•Interferons
Alfa-, beta-, & gamma•Immunostimulants Imiquimod (Aldara) √
•Antineoplastic agents
Fluorouracil (Efudex)
•Desiccants Trichloroacetic acid 85% (Tri-Chlor)
Molluscum Contagiosum
pathogene：
a large DNA poxvirus
Molluscum contagiosum virus (MCV)
Molluscum Contagiosum
Clinical feature
asymptomatic;
some pruritus, tenderness, & pain.
self-limited
but can persist for several years.
Physical:
Papules—
rounded or dome-shaped, pink, fleshcolored, waxy, smooth, umbilicated
contain a caseous plug
may be present in groups or widely
disseminated
2-5 mm (rarely up to 1 cm) in diameter
Immunocompromised conditions
Histology
Molluscum Contagiosum
Cytoplasmic viral inclusions become progressively larger
toward the epidermal surface (hematoxylin and eosin, 200X)
Molluscum Contagiosum
Treatment
• Topical applications：
Imiquimod cream 5% √
Trichloroacetic acid
Cantharidin
Tretinoin cream (0.1%) or gel (0.025%)
• Cryotherapy with liquid nitrogen
• expression & rupture of central core-with tweezers, lasers, curettage
Herpes Simplex
Etiology：
Herpes simplex viruses (HSVs)
-- DNA viruses Herpes
labialis is caused by HSV type 1
genital herpes is usually caused by HSV type 2
•present as grouped vesicles on an erythematous base
•recurrent infection
Clinical features
Herpes Simplex
Primary infection:
a prodrome of fever
sore throat
lymphadenopathy
Painful vesicles on the lips, gingiva
lesions ulcerate and heal within 2-3 weeks
Recurrences:
Pain, burning, itching, or paresthesia precedes
recurrent vesicular lesions
ulcerate or form a crust
last approximately 1 week
Genital herpes:
Herpes Simplex
HSV-2 is most common cause
Primary infection:
occurs within 2 days to 2 weeks after exposure to virus
Symptoms typically last 2-3 weeks.
Men–
painful, erythematous, vesicular lesions ulcerate on penis
Womenvesicular/ulcerated lesions on the cervix
painful vesicles on the external genitalia bilaterally
Associated symptoms-fever, malaise, edema, inguinal lymphadenopathy, dysuria,
vaginal or penile discharge
Recurrences:
Herpes Simplex
Diagnosis
Depend on clinical features
Laboratory Studies
Tzanck smear:
multinucleated giant cells
Serologic assays:
to detect antibodies against HSV-1 and HSV-2
Herpes simplex virus: positive Tzanck smear
Histopathology of HSV infection
Classification of Herpes Simplex Infections According to Viral
Isolation and Paired Serologic Test Results
Serology (Acute)
Classification
Serology (Convalescent)
Virus Isolated
HSV-1
HSV-2
HSV-1
HSV-2
Primary HSV-1
HSV-1
–
–
+
–
Primary HSV-2
HSV-2
–
–
–
+
Primary HSV-1 plus
previous HSV-2 infectiona
HSV-1
–
+
+
+
Primary HSV-2 plus
previous HSV-1 infection
HSV-2
+
–
+
+
Recurrent HSV-1
HSV-1
+
– or +
+
– or +
Recurrent HSV-2
HSV-2
– or +
+
– or +
+
Herpes Simplex
Treatment
Most HSV infections are self-limited.
antiviral therapy—
may shortens the course
prevent dissemination and transmission.
Intravenous, oral, and topical antiviral medications:
acyclovir, its prodrug valacyclovir, and famciclovir.
Immunocompromised pateints with recurrent HSV
infections-intravenous cidofovir
Herpes Zoster (HZ)
shingles
Etiology
varicella-zoster virus (VZV)—
human herpes virus 3
a virus morphologically & antigenically identical to
the virus causing varicella (chickenpox).
Clinical features of HZ
•Symptomsprodromal sensory phenomena
along 1 or more skin dermatomes
lasting 1-10 days (averaging 48 h)
noted as pain or paresthesias
prior to onset of cutaneous findings
severe pain--"the band of roses from hell."
Herpes Zoster
classic lesions-grouped vesicles
--develops upon the
erythematous base
--initially clear
but eventually cloud,
rupture, crust, & involute
clinical variations of HZ:
•Herpes zoster ophthalmicus (HZO)
•Zoster oticus
--also termed geniculate zoster
zoster auris
Ramsay-Hunt syndrome, Hunt syndrome:
•Glossopharyngeal and vagal zoster
(herpes pharyngis, herpes laryngis):
•Disseminated zoster:
•Recurrent zoster:
Complications of Herpes Zoster
Cutaneous
•Bacterial
superinfection
Visceral
Neurologic
•Pneumonitis •Postherpetic neuralgia
•Scarring
•Zoster
gangrenosum
•Cutaneous
dissemination
•Hepatitis
•Meningoencephalitis
•Esophagitis •Transverse myelitis
•Gastritis
•Peripheral nerve palsies
•Pericarditis •Motor
•Cystitis
•Autonomic
•Arthritis
•Cranial nerve palsies
•Sensory loss
•Deafness
•Ocular complications
•Granulomatous angiitis (causing contralateral
hemiparesis
Dx, & DDx of Herpes Zoster
Most Likely
•Zosteriform herpes simplex
•Contact dermatitis
•Insect bites
•Burns
Consider
•Papular urticaria
•Erythema multiforme
•Drug eruptions
•Scabies
Always Rule Out
Bullous pemphigoid
Pemphigus vulgaris
Dermatitis herpetiformis
Epidermolysis bullosa herpetifo
Herpes zoster, histopathology. A. Intraepidermal vesicle, acantholysis, reticular
degeneration; underlying dermis shows edema and vasculitis. B. Multinucleated
giant cells with characteristic nuclear changes.
Treatment of HZ
Systemic antiviral agents-Acyclovir
its derivatives –
valacyclovir, famciclovir, penciclovir,
& desciclovir
Systemic steroids:
only in some sever cases
Varicella-zoster vaccine (Zostavax，Merck)
Treatment of HZ
Patient
Normal
Regimen
Age <50 years
Symptomatic treatment alone, or
Famciclovir 500 mg PO every 8 h for 7 days or
Valacyclovir 1 g PO every 8 h for 7 days or
Acyclovir 800 mg PO 5 times a day for 7 daysa
Age 50 years, and patientsFamciclovir 500 mg PO every 8 h for 7 days or
of any age with cranial
Valacyclovir 1 g PO every 8 h for 7 days of
nerve involvement (e.g., Acyclovir 800 –mg PO 5 times a day for 7 daysa
ophthalmic zoster)
Immunocompromised
Mild compromise,
Famciclovir 500 mg PO every 8 h for 7–10 days or
including HIV-1 infection Valacyclovir 1 g PO every 8 h for 7–10 days or
Acyclovir 800 mg PO 5 times a day for 7–10 daysa
Severe compromise
Acyclovir 10 mg/kg IV every 8 h for 7–10 days
Acyclovir resistant (e.g., Foscarnet 40 mg/kg IV every 8 h until healed
advanced AIDS)
Fungal infections: =mycoses
•Phyton– from Latin/Greek word for plant
•Dermato-phytes–
are a group of keratinophilic fungi-invade keratinized tissue (hair, nails, skin)
•Dermato-phytosis–
is a superficial dermatophytes infection
common disorders worldwide
Has a variety of clinical manifestations
Medical mycoses
can be divided into four categories:
(1) cutaneous
(2) subcutaneous
(3) systemic
(4) opportunistic
The Major Mycoses and Causative Fungi
Category
Superficial
Cutaneous
Subcutaneous
Mycosis
Pityriasis versicolor
Tinea nigra
White piedra
Black piedra
Dermatophytosis
Candidiasis of skin,
mucosa, or nails
Sporotrichosis
Chromoblastomycosis
Causative Fungal Agents
Malassezia species
Hortaea werneckii
Trichosporon species
Piedraia hortae
Microsporum species, Trichophyton species,
and Epidermophyton floccosum
Candida albicans and other Candida species
Sporothrix schenckii
Phialophora verrucosa, Fonsecaea pedrosoi,
and others
Mycetoma
Pseudallescheria boydii, Madurella
mycetomatis, and others
Phaeohyphomycosis
Exophiala, Bipolaris, Exserohilum, and other
dematiaceous molds
Endemic (primary, Coccidioidomycosis
Coccidioides posadasii and Coccidioides
systemic)
immitis
Histoplasmosis
Histoplasma capsulatum
Blastomycosis
Blastomyces dermatitidis
Paracoccidioidomycosis Paracoccidioides brasiliensis
The Major Mycoses and Causative Fungi
Category
Mycosis
Opportunistic Systemic candidiasis
Causative Fungal Agents
Candida albicans and many other Candida
species
Cryptococcosis
Cryptococcus neoformans and Cryptococcus
gattii
Aspergillosis
Aspergillus fumigatus and other Aspergillus
species
Hyalohyphomycosis
Species of Fusarium, Paecilomyces,
Trichosporon, and other hyaline molds
Phaeohyphomycosis
Cladophialophora bantiana; species of
Alternaria, Cladosporium, Bipolaris,
Exserohilum and numerous other
dematiaceous molds
Mucormycosis (zygomycosis) Species of Rhizopus, Lichtheimia,
Cunninghamella, and other zygomycetes
Pneumocystis pneumonia
Pneumocystis jiroveci
Penicilliosis
Penicillium marneffei
Features of Important Fungal Diseases
Type
Cutaneous
Anatomic Location
Genus of Causative
Organism(s)
Dead layer of skin
Tinea versicolor
Malassezia
Epidermis, hair, nails Dermatophytosis (ringworm) Microsporum,
Trichophyton,
Epidermophyton
Subcutaneous Subcutis
Systemic
Internal organs
Opportunistic Internal organs
Representative Disease
Sporotrichosis
Mycetoma
Coccidioidomycosis
Sporothrix
Several genera
Coccidioides
Histoplasmosis
Blastomycosis
Paracoccidioidomycosis
Cryptococcosis
Histoplasma
Blastomyces
Paracoccidioides
Cryptococcus
Candidiasis
Aspergillosis
Mucormycosis
Candida
Aspergillus
Mucor, Rhizopus
Laboratory Test of fungal infaction
Laboratory
Test
Method
Potassium
hydroxide
preparation
Scales, subungual debris, KOH solution and gentle
or affected hair removed heating softens keratin
and placed on a glass slide. and highlights the
KOH 10% dropped on,
dermatophyte.
covered with cover slip.
The undersurface of the
glass slide is heated.
Sabouraud medium (4% Facilitates growth of
peptone, 1% glucose, agar, dermatophytes
water)
Culture
Function
Modified Sabouraud
Facilitates growth of
medium (addition of
dermatophytes and
chloramphenicol,
inhibits growth of noncycloheximide, and
Candida albicans,
gentamicin)
Cryptococcus, etc
Dermatophyte Scales from the advancing Medium contains the pH
test medium
border, subungual debris or indicator phenol red.
affected hair embedded in
the medium.
Histolopatholog Tissue may be obtained by Stains fungal cell wall to
y special stains: skin or nail biopsy
detect fungal elements in
PAS,GMS,ect. techniques
tissue sections
Findings
Long narrow septated and
branching hyphae
Microscopic morphology
of microconidia, culture
features: surface
topography and
pigmentation
Incubation at room
temperature for 5–14
days results in change in
color of medium.
Pink (PAS) or black
(GMS) fungal elements
noted in the stratum
corneun.
Microscopic examination of skin scrapings (scales) revealing
septate, branching hyphae.
Three genera of dermatophytes. A: Trichophyton tonsurans is characterized
by the production of elongated microcondia attached to a supporting hypha.
B: Microsporum gypseum produces individual thin- and rough-walled
macroconidia. C: Epidermophyton floccosum has club-shaped, thin- and
smooth-walled macroconidia that typically arise in small clusters.
Tinea
tinea -is derived from the Latin word for worm or larvae
•tinea capitis (scalp)
•tinea corporis (body surfaces)
•tinea of hands and feet
Tinea manuum and tinea pedis
•Onychomycosis ( Tinea unguium ) - Nail
•Pityriasis (Tinea) versicolor
Tinea cruris - Groin
Tinea barbae - Beard area and neck
Tinea faciale - Face
Majocchi’s granuloma -hair follicle & dermis
Risk factors for tinea infection:
•Moist conditions
•Communal baths
•Immunocompromised states ---•Atopy
•Genetic predisposition
•Athletic activity：
causes skin tears, abrasions,
or trauma such as wrestling, judo, or soccer
Skin Disease Location of
Lesions
Tinea corporis
(ringworm)
Nonhairy, smooth
skin
Clinical Features
Fungi Most Frequently
Responsible
Circular patches with advancing red, Trichophyton rubrum,
vesiculated border and central
Epidermophyton floccosum
scaling. Pruritic
Tinea pedis
Interdigital spaces on Acute: itching, red vesicular.
Trichophyton rubrum,
(athlete's foot) feet of persons
Chronic: itching, scaling, fissures Trichophyton mentagrophytes,
wearing shoes
Epidermophyton floccosum
Tinea cruris (jock Groin
Erythematous scaling lesion in
Trichophyton rubrum,
itch)
intertriginous area. Pruritic
Trichophyton mentagrophytes,
Epidermophyton floccosum
Tinea capitis
Scalp hair. Endothrix: Circular bald patches with short hair Trichophyton mentagrophytes,
fungus inside hair
stubs or broken hair within hair
Microsporum canis,
shaft. Ectothrix:
follicles. Kerion rare. Microsporum- Trichophyton tonsurans
fungus on surface of infected hairs fluoresce
hair
Tinea barbae
Beard hair
Edematous, erythematous lesion
Trichophyton mentagrophytes,
Trichophyton rubrum,
Trichophyton verrucosum
Tinea unguium Nail
Nails thickened or crumbling
Trichophyton rubrum,
(onychomycosis)
distally; discolored; lusterless.
Trichophyton mentagrophytes,
Usually associated with tinea pedis Epidermophyton floccosum
Dermatophytid Usually sides and
Pruritic vesicular to bullous lesions. No fungi present in lesion.
(id reaction)
flexor aspects of
Most commonly associated with
May become secondarily
fingers. Palm. Any tinea pedis
infected with bacteria
site on body
Histopathology of Tinea
Histopathology of Tinea
Treatment of Tinea
Disease
Tinea
corporis
/cruris
Topical TreatmentSystemic Treatment
Allylamines
Adults:
Imidazoles
Terbinafine, 250 mg/day x 2–4 weeks
Tolnaftate
Itraconazole, 100 mg/day x 1 week
Butenafine
Fluconazole, 150–300 mg/wk x 4–6
Ciclopirox
wks
Griseofulvin, 500 mg/day x 2–4 wks
Children:
Terbinafine, 3–6 mg/kg/day x 2 wks
Itraconazole, 5 mg/kg/day x 1 week
Griseofulvin, 10–20 mg/kg/day x 2–4
wks
Treatment of Tinea
Disease
Tinea pedis
/manuum
Topical Treatment
Allylamine
Imidazoles
Ciclopirox
Benzylamine
Tolnaftate
Undecenoic acid
OnychomycosisCiclopirox
Amorolfine
Systemic Treatment
Adults:
Terbinafine, 250 mg/day x 2 weeks
Itraconazole, 200 mg twice daily x 1 week
Fluconazole, 150 mg/week x 3–4 weeks
Children:
Terbinafine, 3–6 mg/kg/day x 2 weeks
Itraconazole, 5 mg/kg/day x 2 weeks
Adults:
Terbinafine, 250 mg/day x 6–12 weeks
Itraconazole, 200 mg/day x 2–3 months
Fluconazole, 150–300 mg/week x 3–12
months
Children:
Terbinafine, 3–6 mg/kg/day x 6–12 weeks
Itraconazole, 5 mg/kg/day x 2–3 months
Fluconazole, 6 mg/kg/week x 3–6 months
Tinea capitis
•Etiology
species of genera Trichophyton and Microsporum
•three distinctly different forms
gray patch
black dot
favus
•3 types of Hair invasion
Ectothrix species: Conidia form on the exterior of the hair shaft.
Endothrix species: Conidia form within the hair shaft,
each is filled with hyphae and spores.
Favus species: Hyphae arrange within and around the hair shaft.
Kerion: Thick plaques and boggy skin
form often with bacterial infection superimposed
Clinical features of Tinea capitis
•begins as a small erythematous papule
around a hair shaft
on the scalp, eyebrows, or eyelashes.
•numerous red papules-with a typical ring form
with paler and scaly
•hairs appear-discolored, lusterless, and brittle
•Pruritus usually minimal
•Alopecia (hair loss)-with hairs breaking is common
•Inflammation may be mild or severe
Differential Diagnosis of Tinea Capitis
• Most Likely
Seborrheic dermatitis, contact dermatitis, pustular or
plaque psoriasis, atopic dermatitis, bacterial
pyodermas, folliculitis decalvans, lichen planopilaris,
and dissecting cellulitis of the scalp
• Consider
Alopecia areata, trichotillomania, pseudopelade
Rule Out
Subacute cutaneous lupus erythematosus, syphilis
Laboratory Studies for diagnosis
•Direct microscopic examination
plucked hairs are treated with KOH -Spores within or around the hair shaft can be detected.
•Fungal cultures
can be performed for identification of the species.
•Wood light (UV light) examination may be performed.
•Histology is only needed for some cases
Tinea capitis
hyphae and spores around the hair shaft (KOH)
Tinea capitis
Wood lamp examination of
a gray-patch area on the
scalp
In Microsporum canis
infection, scalp hairs emit a
diagnostic brilliant green
fluorescence.
an endoectothrix invasion of a hair
shaft by Microsporum audouinii.
Intrapilary hyphae and spores around
the hair shaft are seen (HE with PAS).
Tinea capitis
Fungal hyphae and yeast cells of Trichophyton
rubrum seen on the stratum corneum of tinea capitis.
PAS stain
Treatment of Tinea capitis
antifungal medications-itraconazole, terbinafine, ketoconazole, griseofulvin
and fluconazole,
topical agents
Selenium sulfide shampoo
antifungal creams, lotions, solutions, powders, sprays
tinea corporis
is a superficial dermatophyte infection on the glabrous skin
(ie, skin regions except the scalp, groin, palms, and soles)
Etiology
caused by a variety of dermatophytes,
mainly T tonsurans & also M canis & T rubrum.
Clinical feature of Tinea corporis
Lesion-• begins as an erythematous, scaly plaque crust, vesicles
• characterized by annular with raised edges
• on the exposed skin of trunk and extremities
• may rapidly worsen and enlarge
Tinea of feet and hands
•Tinea pedis –
is the term used for a dermatophyte infection of the soles of the
feet and the interdigital spaces
•Tinea manuum–
fungal infection of the palms and finger webs
Clinical features of Tinea pedis
4 possible clinical presentations:
Interdigital tinea pedis
Chronic hyperkeratotic tinea pedis
Inflammatory/vesicular tinea pedis
Ulcerative tinea pedis
Lesions-•scaling, painful fissuring, maceration;
•erythema;
•vesicles; pustules; and bullae
Onychomycosis (OM)
Tinea unguim
• a fungal infection that affects the toenails or fingernails
• may involve any component of the nail unit
including the nail matrix, nail bed, or nail plate
The main subtypes:
distal lateral subungual onychomycosis (DLSO)
white superficial onychomycosis (WSO)
proximal subungual onychomycosis (PSO)
endonyx onychomycosis (EO)
candidal onychomycosis
*may have a combination of these subtypes
*Total dystrophic onychomycosis
refers to the most advanced form of any subtype
Clinical features of OM
• usually asymptomatic
first present for cosmetic reasons without any complaints
•may interfere with standing, walking, and exercising
•may report paresthesia, pain, discomfort, and loss of dexterity
•may report loss of self-esteem and lack of social interaction
•A careful history may reveal many environmental &
occupational risk factors
Diagnosis of onychomycosis
Direct microscopy
A 20% potassium hydroxide (KOH)
Culture
identify the species of organism
Histologic Findings
nail biopsy & PAS staining (periodic acid-Schiff stain)
most sensitive technique available to diagnose
Treatment
Topical antifungals
amorolfine (approved in other countries),
ciclopirox olamine 8% nail lacquer solution,
bifonazole/urea (available outside the United States)
Oral therapy
oral antifungal agents (itraconazole and terbinafine)
Derivatives of fluconazole
Surgical Care
Surgical approaches: mechanical, chemical, or surgical nail
avulsion
combination of oral, topical, and surgical therapy
can increase efficacy and reduce cost
pityriasis versicolor
Tinea versicolor
• Clinical features
a common, benign, superficial cutaneous fungal infection
characterized by hypopigmented or hyperpigmented
macules and patches on chest & back.
The color of lesion:
white to reddish brown or fawn colored
fail to tan in the summer
may chronically recur
• Etiology
the dimorphic, lipophilic organisms
in the genus Malassezia,
formerly known as Pityrosporum.
• diagnosis
usually confirmed by potassium hydroxide (KOH)
pityriasis versicolor
white to reddish brown or fawn colored macules
Treatment
topical agents
selenium sulfide, sodium sulfacetamide,
ciclopiroxolamine, as well as azole and
allylamine antifungals
Oral therapy
Ketoconazole, fluconazole, and itraconazole
does not prevent the high rate of recurrence
--repeated intermittently throughout the year.
Thank you & Qs