Course Code: PDA303T

Course Title:
Pharmacotherapeutics II

Course Leader: Mr. Subeesh K Viswam

subeesh.pp.ph@msruas.ac.in

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Course Details

Programme: Pharm D
Department: Pharmacy Practice
Head of the Department: Dr. E.Maheswari
Faculty: Pharmacy
Dean: Prof. (Dr.) V Madhavan (
dean.ph@msruas.ac.in)

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Lecture 4
Atopic Dermatitis

At the end of this lecture, student will be

able to

Explain pathophysiology of atopic dermatitis

Describe clinical manifestations of atopic
dermatitis
Explain the etiology of atopic dermatitis

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Atopic Dermatitis

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Definition

Commonly known as eczema, atopic

dermatitis is a chronic pruritic skin disorder
most commonly associated with a personal
or family history of allergic diseases,
including rhinitis, asthma, or conjunctivitis
Most patients experience mild to
moderate symptoms, while up to 10%
have severe manifestations
The inflammatory disorder generally
presents in early infancy with onset before
age 5 5
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Etiology

The exact cause of atopic dermatitis is

unknown. Immunologic and physiologic
abnormalities can occur.
Several factors support the involvement of
immunologic functions:
The association of atopic dermatitis with
other allergic disorders
Substantial elevations of serum ige
Positive wheal and flare reactions to a wide
variety of scratch tests

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Etiology

- Increased susceptibility to bacterial, viral,

and fungal infections
- Association with immunodeficiency
disorders
Physiologic abnormalities include evidence
of altered adrenergic and cholinergic
responses
Heredity plays a role with a possible
inherited defect in some bone marrow-
derived cells
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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Epidemiology

Atopic dermatitis occurs in 10% to 20% of

children and 1% to 3% of adults
The prevalence of the disease has increased
severalfold in industrialized countries over
the last 30 to 40 years
It is more commonly noted in urban regions
and members of higher social classes
Such variations in occurrence suggest the
role of environment in disease expression or
manifestation
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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 ATOPIC DERMATITIS IN CHILDREN

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology
Genetic susceptibility, environmental
factors, pharmacologic features, and
immunologic mechanisms may all
contribute to the development of atopic
dermatitis
Immunologic mechanisms have received
the most investigation but the primary
event that initiates the reaction is yet to
be identified
Abnormalities of humoral- and cell-
mediated immunity are present
Two of the most important immunologic
alterations identified are an impairment of11
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology

Identification of cytokines (interferons and

interleukins) has allowed further delineation
of possible mechanisms and development
of possible new treatment strategies
For example, mononuclear leukocytes in
patients with atopic dermatitis produce
lower levels of interferon gamma (IFN-)
and higher levels of interleukin-4 (IL-4)
IFN- mediates delayed hypersensitivity
reactions and IL-4 stimulates IgE synthesis

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology

Other interleukins, like IL-5 and IL-13, may

also be involved
IgE apparently is stimulated by specific
antigens, attaches to mast cells, and
triggers release of mast cell inflammatory
mediators (including histamine) that are
released on re-exposure to the antigens
Other factors must play a role since atopic
dermatitis occurs in patients with a
deficiency of immunoglobulins, including
agammaglobulinemia or Weskott-Aldrich13
syndrome
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology

Primary T-cell deficiencies, which frequently result

in increased concentrations of serum IgE
eczematoid lesions often resolve following bone
marrow transplantation
The demonstration of decreased numbers of T-
lymphocytes may indicate lack of sufficient T-cells
to control B-cell production of immunoglobulin,
thus producing high levels of IgE
In addition, phagocytic capacity is decreased and
chemotaxis of neutrophils and monocytes is
impaired

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology

The immunologic basis of the disease is

also demonstrated by the significant
numbers of Staphylococcus aureus
bacteria on the diseased and normal skin
of atopic patients
Exacerbations of eczema have developed
secondary to S. aureus skin infections
Increased binding of the microbe to skin is
thought to be related to the inflammation
associated with atopic dermatitis

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology

Patients with atopic dermatitis also often

have increased susceptibility to and
recurrence of viral infections, which
include herpes simplex, molluscum
contagiosum, and warts
The influence of genetics in atopic
dermatitis cannot be discounted, as the
skin disorder is transmitted familially,
predominantly through the maternal
influence
A potential genotypic association has been16
identified in the IL-4 gene promoter region,
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Pathophysiology
Pharmacologic abnormalities in atopic
patients are evident in a number of
cutaneous responses
Exaggerated constrictor response of
cutaneous vessels, white dermographism,
delayed blanch to cholinergic stimuli, and
paradoxical response to application of
nicotinic acid are examples
A defect in the -adrenergic receptor was
once theorized when cyclic adenosine
monophosphate (AMP) responses in atopic
patients were noted to be subnormal to
isoproterenol,
Faculty of Pharmacy
prostaglandin E 1, and17
M. S. Ramaiah University of Applied Sciences
 Pathophysiology

Decreased cyclic AMP levels accentuate the

release of inflammatory mediators from mast
cells and basophils
Evidence suggests cyclic AMP
phosphodiesterase activity (responsible for
degradation of cyclic AMP) is increased,
accounting for diminished cyclic AMP
responsiveness upon challenge
This enzymatic abnormality might be a primary
defect in patients with atopic dermatitis and is
not dependent on the -receptor
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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 PATHOPHYSIOLOGY

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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Signs and Symptoms

Pruritus and eczematous lesions of a

chronic or relapsing nature are the hallmark
symptoms of atopic dermatitis
Pruritus generally worsens throughout the
day and leads to scratching, papule
development, and lichenification
Environmental factors, including allergens,
reduced humidity, and diaphoresis
(sweating) may compound the pruritus
Regardless of the disease stage, nearly all
patients will have dry skin
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Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Clinical Presentation
The skin lesions of atopic dermatitis are
often intensely pruritic
The erythematous papules often bear
evidence of excoriation and subsequent
serous exudate
Lesion location is typically dictated by
patient age
The face, scalp, and extensor surfaces of
the extremities are most often affected
during infancy
The eruption generally begins as
erythematous patches on the cheeks and21
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Clinical presentation
Intense itching is evident as the infant
scratches constantly and rubs against
garments and bedding
Many infantile cases clear over a period of
months to years. With increasing age and
disease duration, the lesions undergo
lichenification and affect the flexural
extremity folds
The lichenoid plaques are poorly
marginated and vary in color from bright
pink-red to brown or gray-brown
Areas commonly involved are the neck,
eyelids, forehead/scalp, anterior chest, and22
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 23
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Flare Factors in Atopic
Dermatitis
Dry skin (xerosis) Heat
Sweating Cold
Exercise Temperature
Infection change
Anxiety Allergic contact
Scratching dermatitis
Light touch Allergies to foods
or inhalants
Prickly clothes
(wool and acrylic) Coexisting diseases
(e.g., scabies)
Faculty of Pharmacy
Greasy ointments 24
M. S. Ramaiah University of Applied Sciences
 Diagnosis

Conversely, inhalant allergens, like dust

mites, seem to be more of a factor for
adults
Foods can exacerbate the dermatitis with
evidence that elimination of food allergens
results in improvement
The types of foods most commonly
involved include eggs, peanuts, milk, soy,
wheat, and fish
The disease should be differentiated from
a number of other conditions, including
cutaneous T-cell lymphoma, seborrheic25
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences
 Summary
It is a chronic pruritic skin disorder most
commonly associated with a personal or
family history of allergic diseases, including
rhinitis, asthma, or conjunctivitis
Increased susceptibility to bacterial, viral, and
fungal infections
Atopic dermatitis occurs in 10% to 20% of
children and 1% to 3% of adults
It is more commonly noted in urban regions and
members of higher social classes
The skin lesions of atopic dermatitis are often
intensely pruritic
The erythematous papules often bear evidence of
excoriation and subsequent serous exudate 26
Faculty of Pharmacy M. S. Ramaiah University of Applied Sciences