The Recognition, Evaluation, and Treatment of Eczema and Rosacea
Recognition, Evaluation, and
Treatment of Eczema and Rosacea
Joel Wagner Pharm. D.
Clinical Professor/Emeritus Professor
Thomas J. Long School of Pharmacy
and Health Sciences
Conflict of Interest Disclosure
No Conflicts of Interest to Disclose
Statement of Need
This presentation will help pharmacists
develop a logical, systemic approach for the
treatment of atopic dermatitis and rosacea.
The presentation will cover several new
drugs for the treatment of atopic dermatitis
Information on the new drugs will include
their mode of action, side effects, and
Goals and Objectives
The purpose of this presentation is to help
Develop the skills necessary to recognize the skin
lesions associated with eczema and rosacea
Recognize the different stages of eczema and
Develop a treatment regimen for eczema and
rosacea dependent upon the stage of the disease
that the patient has developed and the type and
severity of the lesions.
Describe the lesions and the characteristics of rashes
associated with rosacea and eczema
Describe the eczematous process and the 3 stages of
Relate the 3 stages of eczema to their most effective
Describe the 3 types of rosacea
Relate the 3 types of rosacea to their most effective
Provide patient education and counseling for commonly
prescribed medications in eczema and rosacea
What is eczema?
a. Eczema is an itchy, inflammatory skin disease.
b. Eczema is not really a disease in itself, but a
term that describes an eczematous rash or
eczematous process rather than a specific
c. Eczema refers to a number of skin diseases
that have similar rashes.
d. All of the above
So What is Atopic Dermatitis?
Atopic dermatitis is the most common of the
inflammatory skin diseases.
It is an intensely pruritic, chronic
inflammatory condition of the skin.
Many people and physicians refer to atopic
dermatitis as eczema
Usually occurs in a patient with a personal
or family history atopy.
Atopy refers to the genetic tendency to develop
allergic diseases such as chronic allergic
rhinitis, asthma, and extremely dry, irritated
These three conditions are known as the atopic
Atopy is also typically associated with an
heightened allergic response to common
What Causes Atopic Dermatitis?
Atopic dermatitis is thought to be caused by
a genetic defect in the filaggrin protein in the
This defect is associated with disrupting the
The epidermal disruption results in contact
between immune cells in the dermis and
antigens from the external environment
leading to inflammation, intense itching, and
Signs and Symptoms of Atopic
The most common skin lesions are,
erythematous, scaly, papules, patches
Most common symptom is severe,
unrelenting itching which may lead to
difficulty in sleeping.
Itching is intensified by the itch-scratch
Disease stimulates peripheral nerve endings
which the brain identifies as itching.
This leads to vigorous scratching or rubbing.
Scratching leads to greater peripheral nerve
stimulation which causes even more itching.
Cycle continues until the pain of nail induced
skin damage supplants the sensation of
The presence of nighttime scratching usually
warrants a diagnosis of atopic dermatitis.
Age Related Presentation
Atopic dermatitis presents differently in
infants, children, and adults.
Infantile Atopic Dermatitis
A child may be 2 or 3 months old when atopic
Infantile atopic dermatitis is associated with the
Dry, scaly, itchy, skin
Lesions form on the scalp, face, and sometimes on
Lesions, because if intense inflammation, can
become wet and oozy.
Causes intense itching that may come and go.
Childhood Atopic Dermatitis
Usually develops in the 2-12 year old
Lesions often begin the antecubital or
Other common places include the
neck, wrists, ankles and feet.
Adult Atopic Dermatitis
Rash appears in the antecubital or popliteal
fossa and nape of neck.
Can be especially noticeable on the neck
Can be especially bad around the eyes.
May cover much of the body.
Non-stop itching is the principal symptom.
Stages of Atopic Dermatitis
There are 3 forms or stages of atopic
These stages are
Chronic phase occurs if the disease process
continues for a relatively long period of time.
Acute Atopic Dermatitis
Acute eczematous rash is
characterized by erythematous,
weeping vesicles and bulla
Most common symptom is unrelenting
Acute stage is usually associated with
contact dermatitis rather than atopic
Chronic Atopic Dermatitis
Lichenification is the characteristic lesion
of chronic atopic dermatitis
Characterized by scaly and thickened
skin with exaggerated skin markings
Lichenification is caused by constant
Pigmentation changes may occur which
are also caused by constant rubbing.
Course of Atopic Dermatitis
Course is unpredictable
Usually begins in infancy or childhood
and runs frequent courses of
exacerbation and remission
May spontaneously remit in childhood
but may return in adolescence or
Case Study 1
A 28-year-old male patient comes into
the dermatology clinic wanting
treatment for a very itchy rash that the
patient has developed on his feet.
The patient shows you the rash.
The patient describes the rash as very, very itchy.
The patient states that he unconsciously rubs and
scratches the rash.
The patients has had the rash for about 6 months
The patient had a similar problem when he was
younger but the problem seemed to resolve only to
reappear about 6 months ago.
The patient has a large number of allergies
including hay fever and asthma.
The patient has been treating the rash with
What should be the recommended initial
treatment for this patient’s rash?
a. Application of a low to mid potency topical
b. Application of a super-potent topical
c. Frequent use of moisturizers.
d. Oral diphenhydramine at bedtime.
e. Topical diphenhydramine
Primary Treatment of Mild Atopic Dermatitis
Low to mid potency topical corticosteroids
applied for 2 -4 weeks
Reassess after 4 weeks
Proper bathing and
Treatment Algorithm for Mild Atopic Dermatitis
If improvement, maintenance with
moisturizers and intermittent use of low to
to mid potency TCS applied on two
Which Topical Corticosteroid?
Infants and adult patients with involvement
of areas of the body where the skin is thin,
should be treated with low-potency topical
In areas of the body where skin is thicker,
can be treated with more potent topical
Cream base is generally preferred because of
easy spreading and more cosmetically
acceptable to most patients.
Apply at least 2 times/day for 2-4 weeks.
After lesions appear to have resolved,
application should be tapered to once daily
then every other day followed by
Maintenance therapy is twice-weekly
application of topical corticosteroids on
consecutive days in conjunction with
frequent application of moisturizers.
Why is it necessary to taper down the
frequency of application before
discontinuing a corticosteroid?
a. To prevent HPA access depression.
b. To prevent acute adrenal insufficiency.
c. To prevent a rebound flare reaction.
d. To prevent the development of an
What are the side effects associated with
the long-term continuous application of high
potency topical corticosteroids?
a. Development of HPA axis suppression.
b. Development of steroid psychosis.
c. Development dermal atrophy.
d. Development of osteoporosis.
e. Development of cataracts.
Dermal Atrophy Secondary to Continuous
Mometasone Application for 6 months
Moisturizers help retain and replenish
Thick creams, which have a low water content,
or ointments which have zero water content,
are treatment of choice.
Lotions, which have a high water and low oil
content, can worsen xerosis through
Should be applied at least two times per day
and immediately after bathing or hand-washing.
Bathing and Showering
To avoid xerosis, patients should
shower or bathe with warm instead of
After bathing or showering, thick,
occlusive, moisturizers should be
Washing with a drying soap such as
Ivory ® should be avoided.
Washing with moisturizing, super-fatted
soaps should be encouraged
The use of Cetaphil® cleanser may be
Topical antihistamines should be avoided.
CNS depression is the most important
characteristic if antihistamines are to be
used for itching secondary to AD.
Diphenhydramine is probably the treatment
of choice because it is the most sedative.
Non-sedative antihistamines are ineffective
in treating itching associated with atopic
Why should the use of topical
diphenhydramine be avoided?
a. Topical diphenhydramine is ineffective.
b. Topical diphenhydramine may dry the skin.
c. Topical diphenhydramine may cause
d. Topical diphenhydramine may cause
rebound erythema and itching.
Case Study 2
A 16-year-old female, is being seen in the
Twenty percent of her body is covered by an
eczematous rash with extensive involvement
of her neck, antecubital and popliteal fossae,
feet and arms.
Her chief complaint is extreme itching over all
the involved areas.
Case Study 2
The patient states that she is currently seeking
medical attention because of persistent,
The patient states that the itching is so severe
that she has found herself unconsciously
scratching the rash during the night.
The patient says that she has been using
moisturizers and topical desonide to treat the
itching for the past 4 months.
Treatment of Moderate Atopic Dermatitis
Mid to high-potency TCS applied for 4
weeks or for areas at risk for dermal
atrophy, low to mid potency TCS or TCI
Reassess after 4 weeks
Proper bathing and
Treatment Algorithm for Moderate Atopic Dermatitis
If improvement, maintenance with
moisturizers and intermittent use of TCS or
If no improvement switch to TCI if not
already done or to crisaborole
If no response consider dupilumab
Topical Calcineurin Inhibitors
Pimecrolimus (Elidel) and Tacrolimus (Protopic)
For short-term and intermittent long-term treatment
of mild to moderate atopic dermatitis in patients
who are unresponsive or intolerant of other
They can be used as an alternative to topical
corticosteroids for the treatment of mild to moderate
atopic dermatitis involving the face, including the
eyelids, neck, and skin folds.
Intermittent long-term treatment consists of using
TCIs two consecutive days/week.
How Do Calcineurin Inhibitors
Pimecrolimus and tacrolimus inhibit
calcineurin which is a calcium-
As a result, pimecrolimus and
tacrolimus prevent the release of
inflammatory cytokines into the skin
thus reducing inflammation.
Are Calcineurin Inhibitors
Produced relatively good results in about
50% of the patients treated.
Pimecrolimus maybe better tolerated than
tacrolimus with less stinging and burning
Several studies found that tacrolimus
ointment was more effective than
Consultation for Calcineurin
Patient should be warned about sun
avoidance and warned to wear protective
clothing when out in the sun.
May be applied topically to all skin surfaces
including the head, neck, and intertriginous
Wash hands with soap and water before and
If treating the hands, only wash hands before
Problems with Calcineurin
8% of the patients using the cream
complained of mild to moderate warmth or
Can’t be applied to active viral infections
and any infection at the treatment site
should be cleared before calcineurin
inhibitors are applied.
Must avoid excessive sun exposure and use
Calcineurin Inhibitors and
Between January 2004 and January 2009, the
FDA received 46 reports of cancer cases among
children who used topical calcineurin inhibitors.
This led the FDA to issue a black box warning
about a possible cancer risk.
No definite causal relationship has been
established and two case-control studies did not
detect an increased risk of lymphoma among
patients treated with topical calcineurin inhibitors.
Recommendations for Use
Use only for patients who have failed
with conventional therapy.
Use only for short-term or long-term
Long-term safety has not been
Avoid use in children under 2 years of
New Drugs for Moderate to
Severe Atopic Dermatitis
Crisaborole is used topically
It inhibits phosphodiesterase-4 (PDE-4).
By inhibiting the ability of PDE-4 to degrade
cAMP, crisaborole suppresses the release
of pro-inflammatory cytokines
Can be used in children older than 2 years
Is Crisaborle Effective?
In multicenter randomized trials, a total of 1522
patients ≥2 years of age were randomized to
receive crisaborole 2% ointment twice daily for 28
days or a vehicle.
At day 29, 50-60% of patients in the crisaborole
groups achieved success.
Improvement was noted in pruritus, skin
inflammation, excoriation, and lichenification.
Crisaborole-related adverse events occurred in 4.4
percent of patients and were mild and limited to
burning or stinging at the site of application.
Dupilumab is an interleukin-4 receptor
antagonist for the treatment of adult patients
with moderate to severe atopic dermatitis
not adequately controlled with topical
May be used in conjunction with topical
Recommended for adults and children over
12 years of age
Is Dupilumab Effective?
The efficacy of dupilumab 300mg or placebo
given by subcutaneous injection weekly or
every other week was evaluated in adult
patients with long-standing moderate to
severe atopic dermatitis not controlled by
At week 16, 50-60% of patients in the
dupilumab group were considered to have a
successful outcome vs 10 % in the placebo
What are the most common side effects
associated with the administration of
a. Injection-site reactions
c. Increased incidence of infections
d. Increased rate of malignancy development
e. All of the above
Serious adverse events were rare in all
Injection-site reactions and conjunctivitis
occurred more frequently in the dupilumab
groups than in the placebo group.
What about an increased infection rate and
the development of malignancies as is the
case with many other monoclonal
Increase infection rate and the development of
malignancies, as of yet, have not been reported.
Company states that laboratory monitoring of
the medication is not needed
Patients with severe and extensive disease
may require a “burst” of oral prednisone.
40mg to 60mg of prednisone are given as a
single dose early in the AM daily for 7-10
In most cases the dose is rapidly tapered to
avoid the development of a “flare” reaction.
This therapy is very safe and serious side
effects are almost unheard of
Therapy must be followed by a good topical
Failure to recognize this point will result in a rapid
exacerbation of the disease
One problem with this therapy is the possibility of
precipitating a “flare” reaction.
This can be avoided by tapering prednisone dosage
Long term administration of oral corticosteroids
have no place in the treatment of atopic dermatitis
What about treatment with systemic
What is Acne Rosacea?
Rosacea is an acne-like facial eruption
sometimes called “middle-age acne”
It is characterized by marked
involvement of the central face with
transient or persistent erythema,
telangiectasia, inflammatory papules
and pustules, or hyperplasia of the
Differences Between Acne and
“True” acne always begins with the
following three lesions:
Frequently closed comedones develop
into into inflammatory papules,
pustules, and nodules.
Lesions Associated with Rosacea
Rosacea is not associated with
Rosacea is associated with
What’s The Cause?
Flaw in the autonomic innervation of the
Aberration in endothelial growth factor,
substance P, serotonin, bradykinins,
histamine, neuropeptides, endorphins,
gastrin, and cytokines.
Perhaps involvement of demodex
Demodex folliculorum is a species of face
The mites live in human hair follicles.
Found in greater numbers around the
cheeks, nose, eyebrows, eyelashes, and
Not harmful, and classified as commensals
80% of adults are “infected” with demodex
Demodex and Rosacea
A study found a significant association
between the increased presence of
demodex folliculorum and the development
The study authors also proposed that
increased mite density in skin might trigger
inflammatory responses, leading to signs
and symptoms of rosacea.
Classification of Rosacea
Important because helps select
Important because can help to predict
Clinical Features Comments
Persistent erythema of the
Most difficult subtype to
Prolonged Flushing Certain topical therapy can
be irritating thus making
Presence of telangiectasia
Burning and stinging often
Responds poorly to treatment.
Best treatment is probably non-pharmacological
therapy along with proper skin care and avoiding
triggers which cause flushing.
In moderate to severe disease ablation of
superficial facial blood vessels by lasers can be
There is little evidence that the use of topical or
systemic antibiotics has any effect on
Trigger Factor Percentage of
Sun Exposure 81%
Emotional Stress 79%
Hot Weather 75%
Brisk Wind 57%
Strenuous Exercise 56%
Alcohol Consumption 52%
Spicy Foods 45%
Use of Alpha Hydroxy
Excessive Indoor Heat 41%
Common Trigger Factors for Rosacea
Proper Skin Care
Gentle skin cleansing.
Avoidance of irritating cosmetic products.
Frequent use of sunscreens.
Use of a soap-free cleanser such as Cetaphil.
Cosmetic coverage of excess redness with
matte-finish, water-soluble, facial powder
containing inert green pigment.
New Drugs for Treatment of
New Drugs for Treatment of
Brimonidine is a selective alpha-2 agonist available
as a 0.33% gel.
Oxymetazoline is an alpha receptor agonist
available as a 1% cream.
Topical application reduces erythema by direct
vasoconstriction of facial blood vessels.
Both are used to treat persistent facial erythema in
Applied one time/day
Based on your knowledge of using vasoconstrictors
in the eye and in the nose, what side effects do you
think the topical facial application of oxymetazoline
and brimonidine causes?
a. Skin irritation
b. Skin pain
c. Rebound erythema
d. Systemic absorption resulting in hypertension
e. No side effects reported
Statement By a Physician
“I will tell my rosacea patients about
RhoFade is what I tell my red eye
patients about Visine”:
“Feel free to use it once or twice a month
before taking important pictures or going
out on an important date, but other than
that, leave it in your medicine cabinet.”
Papulopustular Rosacea (Subtype II)
Clinical Features Comments
Erythema with papules
Easiest subtype to treat
Burning and stinging
Usually good response
to topical therapy
May resemble acne
vulgaris but without
May be associated with
Papulopustular Rosacea Treatment
Usually responds well to treatment
For mild cases, topical therapy can be used alone
For more severe cases systemic therapy is given
for 6-12 weeks and followed with maintenance
Maintenance topical therapy usually required to
No real evidence that use of combined topical
and systemic treatment for severe disease has
any increased benefits although combination
therapy is commonly used.
Metronidazole Gel 0.75% and 1%
Metronidazole Cream 1% (Noritate)
Ivermectin 1% Cream (Soolantra)
Azelaic Acid 15% gel (Finacea)
Erythromycin 2% and clindamycin 1%
Applied 1-2 times/day
Well tolerated with few adverse
Does not seem to work by killing
bacteria or demodex falliculorum
Has direct anti-inflammatory activity
through it’s effect on neutrophil cellular
Azelaic Acid (Finacea)
Comparable to metronidazole in
The mechanism of action is not clear.
Applied 1-2 times/day as a 15% gel or a
Adverse reactions are similar to topical
metronidazole but may be more irritating
early on in the course of treatment.
Before Azelaic Acid Treatment After Azelaic Acid Treatment
Ivermectin is an agent with both anti-
inflammatory and antiparasitic properties.
The drug is commercially available for the
treatment of inflammatory lesions of rosacea
as a 1% cream.
Ivermectin 1% cream is applied once daily.
Adverse reactions are similar to topical
Is Ivermectin effective?
A 16-week randomized trial that compared
once-daily use of ivermectin 1% cream with
twice-daily use of metronidazole 0.75% in
patients with moderate to severe rosacea
Ivermectin was seemed to be more effective
for reducing inflammatory lesions when
compared to metronidazole.
Several small studies have shown that
topical sulfacetamide+sulfur is effective for
the treatment of rosacea.
Can be used as alternative the other topical
Not nearly as effective as metronidazole,
azelaic acid or ivermectin.
Side effects are similar to metronidazole and
Topical clindamycin and erythromycin
application has been associated with
improvement in papules, pustules and
erythema in several studies with a
small number of patients
Not considered first line treatment
Most Effective Topical
Based upon these observations, topical
ivermectin, metronidazole, and azelaic acid
are reasonable choices for first-line topical
therapy papulopustular rosacea.
Metronidazole or ivermectin is preferred in
patients who present with significant facial
sensitivity, due to the fairly frequent
occurrence of irritation early in the course of
therapy with azelaic acid.
Most Effective Topical
Reasonable evidence that 15% azelaic acid
gel is equal in effect to 0.75% metronidazole
Reasonable evidence that ivermectin may be
more effective than topical metronidazole.
Reasonable evidence that topical clindamycin
and erythromycin are less effective than
metronidazole, azelaic acid or ivermectin.
Some scant evidence that
sulfacetamide/sulfur lotion maybe effective in
Patients who present with numerous
inflammatory papules or pustules or
those with milder disease that fail to
respond to one or more topical
therapies may benefit from oral
Of the oral antibiotics, tetracyclines are
the best-studied agents.
Tetracycline, doxycycline, and
minocycline have been used for many
years for the management of rosacea.
These agents are most useful for
improving inflammatory papules and
pustules, and may also reduce
erythema in those patient who do not
respond to topical treatment.
Antibiotic Mechanism of Action
Since no definitive microbial cause of
rosacea has been identified, the
efficacy of oral antibiotics in rosacea is
often attributed to their anti-
Due to concern for the development of
antibiotic resistance, interest has grown in
the use of sub-antimicrobial doses of
Studies have shown that Oracea which is a
combination of 30mg of immediate release
doxycycline and 10mg of delayed release
doxycycline is effective for treatment of
Sub-antimicrobial Dose Study
One randomized trial with 91 patients
compared sub-antimicrobial dose
doxycycline (40 mg once daily) with
doxycycline 100 mg per day.
Both doses were similarly effective for the
treatment of inflammatory lesions, but the
lower dose was associated with a reduced
rate of gastrointestinal side effects.
My Recommendations for
Doxycycline 100mg/day administered for 6-
12 weeks or
Minocycline 100mg/day administered for 6-
12 weeks or
Doxycycline (Oracea) 40mg/day
administered for 6-12 weeks
Maintenance topical therapy with
metronidazole, ivermectin, or azelaic acid
after 6-12 weeks of systemic therapy.
Disorder characterized by a large, red,
bumpy, or bulbous nose.
Called “whiskey nose” or “rum blossom”
Occurs more in men than in women.
The exact cause of rhinophyma is unknown.
Pharmacological treatment is for the most
Treatment consists of surgical excision, or
carbon dioxide laser therapy.
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