Transcript pharmacotherapy of dermatophytoses

PHARMACOTHERAPY
OF SKIN DISEASE
ATOPIC DERMATITIS

Atopic dermatitis (AD) is a
pruritic disease of unknown
origin that usually starts in
early infancy (an adult-onset
variant is recognized); it is
characterized
by
pruritus,
eczematous lesions, xerosis
(dry skin), and lichenification
(thickening of the skin and an
increase in skin markings).
ATOPIC DERMATITIS
Epidemiology.

The prevalence rate of AD is rising, and AD affects 1530% of children and 2-10% of adults.

AD
may
be
(immunoglobulin
associated
E
[IgE])
allergic rhinitis, urticaria).
with
diseases
other
(eg,
atopic
asthma,
ATOPIC DERMATITIS
Pathophysiology


AD can be divided into 2 forms:
Extrinsic: IgE-mediated (70 to 80% of cases);
Intrinsic: Non–IgE-mediated (20 to 30% of cases).
ATOPIC DERMATITIS
Extrinsic
AD:
This
form
occurs
when
environmental exposures trigger immunologic
reactions in genetically susceptible people.
ATOPIC DERMATITIS
Extrinsic AD




Common environmental
triggers include:
foods (eg, milk, eggs,
soy,
wheat,
peanuts,
fish);
airborne allergens (eg,
dust
mites,
molds,
dander);
Staphylococcus
aureus
colonization on skin due
to
deficiencies
in
endogenous antimicrobial
peptides;
topical
products
(eg,
cosmetics).
ATOPIC DERMATITIS


Intrinsic AD: This form is not mediated
by IgE.
Intrinsic
AD
is
nonfamilial
and
idiopathic, and its pathophysiology is
generally not well understood.
ATOPIC DERMATITIS
A triphasic course of AD across the lifespan
has been proposed.
 Phase I develops before IgE sensitization has
taken place and occurs mostly in infants who
are likely genetically predisposed to the
disease.
 Phase II involves IgE sensitization to food,
environmental antigens, or both.
 Phase III is the product of chronic scratching
and is characterized by the formation of IgE
autoantibodies
against
proteins
of
keratinocytes and endothelial cells.
ATOPIC DERMATITIS



Symptoms and Signs
In the acute phase: red,
crusted lesions appear on the
face and spread to the neck,
scalp,
extremities,
and
abdomen.
In the chronic phase,
typically
erythematous
macules and papules that
lichenify
with
continued
scratching.
Intense pruritus is the key
feature.
ATOPIC
DERMATITIS

Lesions typically
appear in
antecubital,
popliteal fossae
and on the eyelids,
neck, and wrists
and may
occasionally
become
generalized.
ATOPIC DERMATITIS
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Antihistamines.
Antihistamines can help
relieve pruritus.
 Hydroxyzine hydrochloride 25 mg PO tid or
qid.
 Diphenhydramine
25 to 50 mg PO at
bedtime.
 Loratadine 10 mg po once/day,
 Fexofenadine 60 mg po bid or 180 mg po
once/day
 Cetirizine 5 to 10 mg po once/day
PHARMACOTHERAPY OF
ATOPIC DERMATITIS

Doxepin a tricyclic antidepressant also with H1
and H2 receptor blocking activity.
25 to 50 mg PO at bedtime may also help, but its
use is not recommended for children < 12 yr.
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Topical Steroids.
Corticosteroids are the mainstay of therapy.
Creams or ointments applied twice daily are
effective for most patients with mild or
moderate disease.
 Triamcinolone topical. A medium potency topical
steroid. Apply to affected area BID-QID.
 Hydrocortisone topical. 1% ointment 2-3 times
daily.
 Betamethasone topical. Apply to affected area
BID-QID.
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Systemic corticosteroids are indicated
for extensive or refractory disease.

Prednisone 60 mg or, for children 1
mg/kg, PO once/day for short courses
of 7 to 14 days
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Topical
calcineurin
inhibitors
is
a
topical
immune suppressants. They should be used
when patients do not respond to corticosteroids
or when corticosteroid adverse effects.
Pimecrolimus 1%
0,1%
and tacrolimus 0,03%,
are available for patients older than 2
years. Apply to affected area BID.
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Oral immunosuppressive agents. For
treatment of patients with severe
disease
in
whom
conventional
therapy is ineffective.
 Cyclosporine 2.5 mg/kg/day divided BID
PO x at least 4 weeks, may increase to no
more than 4 mg/kg/day.
 Methotrexate 2.5-5 mg/dose every 12
hours for 3 doses given weekly.
Satisfactory response seen 3-6 wk
following administration.
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Antistaphylococcal antibiotics can control S.
aureus nasal colonization and are indicated in
patients with severe disease unresponsive to
specific therapies and positive nasal cultures.
 Topical antistaphylococcal antibiotics
Mupirocin, fusidic acid applied for ≤ 2 wk
PHARMACOTHERAPY OF
ATOPIC DERMATITIS
Antistaphylococcal antibiotics
Oral antistaphylococcal antibiotics
 Dicloxacillin 250 mg qid for 1 to 2 wk
 Cephalexin 250 mg qid for 1 to 2 wk
 Erythromycin 250 mg qid for 1 to 2 wk
PHARMACOTHERAPY OF
ATOPIC DERMATITIS

Phototherapy.
Phototherapy with PUVA, UVA, or UVB is
successful in controlling AD.
PROGNOSIS
AD in children often abates by age 5 yr,
although
exacerbations
are
common
throughout adolescence and into adulthood.
AD frequently resolves completely by age 30.
ACNE

Acne vulgaris (acne) is the formation of
comedones, papules, pustules, nodules, and/or
cysts
as
a
result
inflammation
of
follicles
their
and
of
obstruction
pilosebaceous
accompanying
units
and
(hair
sebaceous
gland). It most often affects adolescents.
ACNE
Etiology. The main underlying cause of
acne is a genetic predisposition. The
condition is inherited in an autosomal
dominant pattern.
Triggers include:






Puberty, when surges in androgen
stimulate sebum production and
hyperproliferation of keratinocytes;
Hormonal changes that occur with
pregnancy
or
throughout
the
menstrual cycle;
Occlusive cosmetics;
Cleansing agents;
Clothing;
Humidity and sweating.
EPIDEMIOLOGY OF ACNE
Acne vulgaris affects 60-70%
of Americans at some time
during their lives.
Twenty percent have severe
acne
physical
scarring.
with
and
permanent
mental
PATHOPHYSIOLOGY OF ACNE


The
pathogenesis
of
acne
vulgaris
is
multifactorial.
Retention hyperkeratosis is the first recognized
event in the development of acne vulgaris.
PATHOPHYSIOLOGY OF ACNE




Following factors play a
role in the pathogenesis
of acne:
obstruction of
pilosebaceous duct by
cohesive keratinocytes,
sebum and hyperkeratosis;
increased sebum
production;
proliferation anaerobe
Propionibacterium acnes;
inflammation in the follicle.
SYMPTOMS AND SIGNS
Acne vulgaris is characterized by

comedones,

papules,

pustules,

and nodules in a sebaceous gland
distribution.
The face may be the only involved skin
surface, but the chest, back, and
upper arms are often involved.
Scarring is often evident.
ACNE
Comedones
Papules and pustules
Nodules
PHARMACOTHERAPY OF
ACNE
Retinoid-like Agents
stimulate cellular retinoid
receptors and help normalize keratinocyte
differentiation and are comedolytic. They have
anti-inflammatory properties.
Topical tretinoin
Apply a pea-sized amount topically qHS to the
skin where acne lesions appear, using enough
to lightly cover the entire affected area.
Begin
therapy
with
a
low-concentration
formulation
(0.025%
cream,
0.04%
microsphere gel, or 0.01% gel).

PHARMACOTHERAPY OF ACNE
Adapalene. Available as cream, lotion, and
gel. Apply thin film to affected areas of face
and/or trunk qPM after washing.
 Tazarotene
Cream 0.1% indicated for acne vulgaris and gel
0.1% indicated for mild-to-moderate acne
vulgaris; whereas, foam 0.1% indicated for
moderate-to-severe acne.
Cream/gel/foam 0.1%: Apply to affected area
qDay.

PHARMACOTHERAP
Y OF ACNE

Isotretinoin.
Oral
retinoid
indicated
for
recalcitrant, nodulocystic acne.
Treatment
is
weight-based,
usually
dosed
initially 0.5 mg/kg and increased to 1 mg/kg
in 2 divided doses for 15-20 weeks.
May
adjust
mg/kg/day.
dose
to
administer
up
to
2
PHARMACOTHERAPY OF ACNE
Antibiotics, Other.
Oral
antibiotics
are
useful
in
inflammatory acne, and improvement is
usually seen after several weeks of use.
Topical antibiotics are used in almost all
acne patients.
Monotherapy should be avoided to reduce
risk of antibiotic resistance.
Concurrent use of benzoyl peroxide
eliminates the risk of development of
resistance.
PHARMACOTHERAPY OF ACNE
Antibiotics, Other.
Tetracycline. May administer 250-500 mg PO bid.
 Minocycline 50 mg PO qDay-TID;
extended release: 1 mg/kg PO qDay x12 weeks;
capsules: 50 mg PO qDay-TID.
 Doxycycline
Initial: 200 mg/day divided BID PO/IV x1 day (IV may
be given qDay),
then maintenance: 100-200 mg/day divided q12hr
PO/IV (IV may be given qDay).

PHARMACOTHERAPY OF ACNE
Antibiotics, Other.
 Clindamycin.
Oral: 75-300 mg/day in divided doses.
Topically. Apply thin film twice daily except for the
gel form. Apply gel form once daily.
 Erythromycin.
Oral: 250–500 mg bid
Topically: Apply bid after washing the skin and drying it.
PHARMACOTHERAPY OF ACNE
Aldosterone
Antagonists,
Selective.
Aldosterone antagonists may reduce free
testosterone
levels
and
compete
with
androgens binding at the sebaceous gland.
 Spironolactone
To treat acne in women may administer 25-200 mg
once daily.
PHARMACOTHERAPY
OF ACNE
Estrogens/Progestins
Hormonal therapies can be used in females with
acne, especially those with premenstrual acne
flares in whom other therapies have failed.
 Ethinyl estradiol, drospirenone, and levomefolate.
Suppresses ovarian production of androgens.
1 active tablet (3 mg drospirenone/0.02 mg EE) PO qDay
for 24 days, then 1 inert tablet PO qDay for 4 days.
 Ethinyl estradiol and drospirenone.
For treatment of moderate acne vulgaris 1 active tablet
(3 mg drospirenone/0.02 mg EE) PO qDay for 24 days,
then 1 inert tablet PO qDay for 4 days.
PHARMACOTHERAPY OF ACNE
Acne Products
These agents may have antibacterial and
comedolytic properties.
 Erythromycin and benzoyl peroxide.
The combination drug may be applied topically twice
daily.
 Clindamycin and tretinoin.
Apply daily to affected areas.
 Clindamycin and benzoyl peroxide.
Apply once daily or twice daily.
PHARMACOTHERAPY OF ACNE
Acne Products
Azelaic acid.
Apply twice daily. Improvement may be seen
within 4 weeks.
 Benzoyl peroxide.
Apply sparingly to affected areas qDay after
thoroughly washing skin; may gradually
increase to BID/TID if needed.

PHARMACOTHERAPY OF ACNE
Treatment for comedones
A mainstay of treatment for
comedones is daily topical
tretinoin as tolerated. Daily
adapalene
gel,
tazarotene
cream or gel, azelaic acid
cream, and glycolic or salicylic
acid in propylene glycol are
alternatives for patients who
cannot tolerate topical tretinoin.
PHARMACOTHERAPY OF
ACNE
Mild inflammatory acne

Mild inflammatory acne should be treated with
topical benzoyl peroxide, topical antibiotics:
erythromycin, clindamycin, glycolic acid, or a
combination. Topical retinoids are often used
concomitantly.

Treatment should be continued for 6 wk or
until lesions respond. Maintenance treatment
may be necessary to maintain control.
PHARMACOTHERAPY OF ACNE
Moderate acne






Moderate acne responds best to oral systemic therapy
with antibiotics.
Full benefit takes ≥ 12 wk.
Topical therapy as for mild acne is usually used
concomitantly with oral antibiotics.
Tetracycline is usually a good first choice: 250 or 500
mg bid for 4 wk or until lesions respond, after which it
may be reduced to the lowest effective dose.
Minocycline 50 or 100 mg bid.
Erythromycin and doxycycline
are considered 2nd-line drugs.
PHARMACOTHERAPY OF ACNE
Severe acne

Oral isotretinoin
patients
with
is the best treatment for
moderate
acne
in
whom
antibiotics are unsuccessful and for those with
severe inflammatory acne.

Dosage of isotretinoin is usually 1 mg/kg
once/day for 16 to 20 wk.
PHARMACOTHERAPY OF ACNE
Cystic acne

Intralesional injection of 0,1 mL triamcinolone
acetonide suspension 2,5 mg/mL (the 10
mg/mL
suspension
must
be
diluted)
is
indicated for patients with cystic acne.

For
acne
with
endocrine
abnormalities,
antiandrogens are indicated. Spironolactone,
which
has
some
antiandrogen
effects,
is
sometimes prescribed to treat acne at a dose
of 50 to 100 mg po once/day.
PHARMACOTHERAPY OF ACNE


Scarring
Small scars can be treated with chemical
peels,
laser
resurfacing,
or
dermabrasion.
Deeper, discrete scars can be excised.
SCABIES

Human scabies is an
intensely pruritic skin
infestation caused by
the host-specific mite,
Sarcoptes scabiei var
hominis.
SCABIES
Etiology

Scabies is caused by the
mite Sarcoptes scabiei var.
hominis, an obligate human
parasite
that
burrowed
tunnels
stratum corneum.
lives
in
in
the
SCABIES
EPIDEMIOLOGY


Scabies
is
easily
transmitted from person to
person through via direct
and prolonged contact with
an infected individual.
In developed countries,
scabies epidemics occur
primarily in institutional
settings such as prisons
and
long-term
care
facilities such as nursing
homes and hospitals.
SCABIES
Pathophysiology



The entire life cycle of the mite lasts
30 days and is spent within the
human epidermis.
After copulation, the male mite dies
and the female mite burrows into
the superficial skin layers and lays a
total of 60-90 eggs.
The ova require 10 days to progress
through larval and nymph stages to
become mature adult mites.
SYMPTOMS AND SIGNS

The primary symptom
is
intense
classically
night.
pruritus,
worse
at
SYMPTOMS AND SIGNS

Classic
scabies:
erythematous
papules
initially appear in finger
web
spaces,
flexor
surfaces of the wrist and
elbow,
axillary
folds,
along the belt line, or on
the
lower
buttocks.
Papules can spread to
any area of the body,
including the breasts and
penis. The face remains
uninvolved in adults.
SYMPTOMS AND SIGNS
PHARMACOTHERAPY OF
SCABIES
Treatment for scabies includes
 administration
of
a
scabicidal agent,
 an antipruritic agent such as
a sedating antihistamine,
 and
an
appropriate
antimicrobial
agent
if
secondarily infected.
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
 Permethrin
Permethrin 5% cream is the drug of choice,
especially for infants >2 mo and small
children.
Apply from the neck down;
wash off after 8-14h;
one application is usually sufficient, but a
second application is recommended after 1wk.
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
 Lindane
In 1% lotion or cream.
Stimulates nervous system of
parasite, causing seizures and
death.
Apply 30-60 mL from the neck
down; wash off after 8-12h.
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
 Precipitated sulfur 6 to 10% in petrolatum,
applied for 24 h for 3 consecutive days, is
safe and effective.
Sulfur should only be used when a patient
cannot tolerate permethrin, lindane, or
ivermectin.
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
 Crotamiton
A 10% cream or lotion for treatment of scabies.
Apply from the neck down on 2 consecutive nights;
thoroughly massage into the skin of the whole body
from the chin down, paying particular attention to
all folds and creases;
a second application is advisable 24h later; wash off
24h after second application
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
Benzyl benzoate.
Ester of benzoic acid and benzyl
Neurotoxic to mites. Used in Europe.

alcohol.
PHARMACOTHERAPY OF
SCABIES
Scabicides/Antiparasitics
 Ivermectin is indicated for patients who do not
respond to topical treatment, are unable to adhere
to topical regimens, or are immunocompromised
with Norwegian scabies.
Typical scabies: 200-250 mcg/kg given at diagnosis
and repeated in 7-14 days.
Crusted scabies may require 3 or more doses given
at 1- to 2-week intervals.
PHARMACOTHERAPY OF
SCABIES



Symptomatic treatment may
require oral antihistamines and
topical antipruritics/anesthetics:
menthol (Sarna) and pramoxine
(Prax).
More severe symptoms may
require a short course of topical
or oral steroids.
Secondary infections may require
antibiotics
and
should
be
prescribed based on culture and
sensitivity data.
SCABIES




All family members and close contacts must
be evaluated and treated for scabies, even if
they do not have symptoms.
All carpets and upholstered furniture should
be vacuumed and vacuum bags immediately
discarded.
Instruct patients to launder clothing, bed
linens, and towels used within the last week
in hot water the day after treatment is
initiated and again in 1 week.
Items that cannot be washed may be
professionally dry cleaned or sealed in plastic
bags for 1 week.
DERMATOPHYTOSES

Dermatophytoses
fungal
infections
are
of
keratin in the skin and
nails.
DERMATOPHYTOSES
Etiology


Human
infections
are
caused by Epidermophyton,
Microsporum,
and
Trichophyton spp.
Dermatophytes may infect
humans
(anthropophilic),
infect nonhuman mammals
(zoophilic),
or
reside
primarily
in
the
soil
(geophilic).
DERMATOPHYTOSES
Epidemiology



Tinea corporis is a common
infection more often seen in
typically hot, humid climates.
T. rubrum is the most
common infectious agent in
the world and is the source of
47% of tinea corporis cases.
70% of the population will be
infected with tinea pedis at
some time.
DERMATOPHYTOSES
Pathophysiology

Dermatophytes preferentially
inhabit
the
nonliving,
cornified layers of the skin,
hair,
and
nail,
which
is
attractive for its warm, moist
environment
conducive
fungal proliferation.
to
SYMPTOMS AND SIGNS
Symptoms vary by site (skin, hair,
nails).
Tinea corporis:
 Erythematous, scaly plaque that
may rapidly worsen and enlarge.
 Following central resolution, the
lesion may become annular in
shape.
 As a result of the inflammation,
scale, crust, papules, vesicles, and
even bullae can develop, especially
in the advancing border.
SYMPTOMS AND SIGNS
Tinea capitis is a dermatophyte
infection of the scalp:
 gradual
appearance of round
patches of dry scale, alopecia, or
both, “black dot ringworm,” in
which hair shafts break at the
scalp surface оr “gray patch
ringworm”.
SYMPTOMS AND SIGNS


Tinea pedis have the following 4 possible
clinical presentations:
Interdigital tinea pedis (pruritus, erythema,
maceration, fissuring, and scaling, most often
seen between the fourth and fifth toes),
Chronic hyperkeratotic tinea pedis (chronic
plantar erythema with slight scaling to diffuse
hyperkeratosis).
SYMPTOMS AND SIGNS


Tinea pedis
Inflammatory/vesicular tinea pedis (painful,
pruritic vesicles or bullae, most often on the
instep or anterior plantar surface),
Ulcerative tinea pedis (rapidly spreading
vesiculopustular lesions, ulcers, and erosions,
typically in the web spaces, and is often
accompanied by a secondary bacterial
infection).
SYMPTOMS AND
SIGNS
Onychomycosis is fungal infection of the nail
plate, nail bed, or both.
 Distal subungual, in which the nails thicken
and yellow, keratin and debris accumulate
distally and underneath, and the nail
separates from the nail bed (onycholysis).
PHARMACOTHERAPY OF
DERMATOPHYTOSES

Treatment varies by site but always
involves topical or oral antifungal drugs.
PHARMACOTHERAPY OF
DERMATOPHYTOSES


Topical therapy is recommended
for a localized infection because
dermatophytes rarely invade living
tissues.
Topical therapy should be applied to
the lesion and at least 2 cm beyond
this area once or twice a day for at
least 2 weeks, depending on which
agent is used.
PHARMACOTHERAPY OF
DERMATOPHYTOSES







Topical azoles:
econazole,
ketoconazole,
clotrimazole,
miconazole,
oxiconazole,
sulconazole,
sertaconazole
PHARMACOTHERAPY OF
DERMATOPHYTOSES
Allylamines
 Naftifine
 Terbinafine
PHARMACOTHERAPY OF
DERMATOPHYTOSES
Systemic therapy may be indicated for tinea
corporis that includes
 extensive skin infection,
 immunosuppression,
 resistance to topical antifungal therapy,
 comorbidities
of tinea capitis or tinea
unguium.
PHARMACOTHERAPY OF
DERMATOPHYTOSES
Systemic therapy
Griseofulvin
 It is the systemic drug of choice for tinea
corporis infections in children.
 A dose of 10 mg/kg/d for 4 weeks is effective.
PHARMACOTHERAPY OF
DERMATOPHYTOSES
Systemic azoles


Oral ketoconazole at 3-4 mg/kg/d may be
given.
Fluconazole at 50-100 mg/d or 150 mg once
weekly for 2-4 weeks is used with good
results.
PHARMACOTHERAPY OF
DERMATOPHYTOSES
Oral itraconazole in doses of 100 mg/d for 2
weeks shows high efficacy.
With an increased dose of 200 mg/d, the
treatment duration can be reduced to 1 week.
200 mg once/day for 2 to 4 wk or 200 mg bid
given for 1 wk, followed by 3 wk without the
drug (pulsed) for 2 to 3 mo, can be used for
treatment of onychomycosis.

PHARMACOTHERAPY OF
DERMATOPHYTOSES
Systemic Allylamines
 Oral terbinafine may be used at a dosage
< 20 kg are given 62,5 mg once/day;
those 20 to 40 kg, 125 mg once/day,
those > 40 kg, 250 mg once/day for 2 to 4 wk.