1) Atopic Dermatitis

Atopic dermatitis (AD) also known as atopic eczema or eczema is a type of dermatitis, an inflammatory,
relapsing, non-contagious and itchy skin disorder. It has been given names like "prurigo Besnier,"
"neurodermatitis," "endogenous eczema," "flexural eczema," "infantile eczema," and "prurigo diathsique".
Atopic dermatitis is very common worldwide and increasing in prevalence. It affects males and females equally
and accounts for 10%-20% of all referrals to dermatologists (doctors who specialize in the care and treatment
of skin diseases). Atopic dermatitis occurs most often in infants and children, and its onset decreases
substantially with age. Scientists estimate that 65% of patients develop symptoms in the first year of life, and
90% develop symptoms before the age of 5. Onset after age 30 is less common and often occurs after
exposure of the skin to harsh conditions. People who live in urban areas and in climates with low humidity
seem to be at an increased risk for developing atopic dermatitis.
About 10% of all infants and young children experience symptoms of the disease. Roughly 60% of these
infants continue to have one or more symptoms of atopic dermatitis even after they reach adulthood.
2) Causes of AD

The cause of atopic dermatitis is not known, but the disease seems to result from a combination of genetic
(hereditary) and environmental factors. There seems to be a basic hypersensitivity and an increased tendency
toward itching. Evidence suggests that the disease is associated with other so-called atopic disorders such as
hay fever (seasonal allergies) and asthma, which many people with atopic dermatitis also have. In addition,
many children who outgrow the symptoms of atopic dermatitis go on to develop hay fever or asthma. Although
one disorder does not necessarily cause another, they may be related, thereby giving researchers clues to
understanding atopic dermatitis. It is important to understand that food sensitivities do not seem to be a major
factor with most atopic dermatitis. This is an area of active research. Patients with atopic dermatitis seem to
have mild immune system weakness. They are predisposed to develop fungal foot disease and cutaneous
staphylococcal infections, and they can disseminate herpes simplex lip infections (eczema herpeticum
1
) and
smallpox vaccination (eczema vaccinatum
2
) to large areas of skin.






3) Characteristics of Atopic Dermatitis:

Atopic dermatitis (AD) is a chronic pruriginous inflammatory skin disease, characterized by intense dryness,
suggestive of an allergic diathesis of genetic origin. It is characterized by impaired skin barrier function,
resulting from a lipid deficiency in the intercorneocyte matrix, rendering the atopic skin more sensitive to
environmental allergens and facilitating their penetration. AD is characterized by two different, chronic,
stages: Eczema and Remission. Only the AD symptoms can be treated, as there is currently no curative
treatment. Eczema outbreaks combining sensations of dryness and squames
3
, with a rough appearance and
rash, located particularly in the vicinity of the lesions. It should be noted that there is an occasional risk of
superinfection of these lesions by the pathogenic flora, in particular by Staphylococcus aureus, when the
skin barrier is breached by pruritus or itching. The most recent studies show the involvement of one essential
factor: the NF kappa B factor, responsible for amplifying the inflammatory response. The NF kappa B factor
is a protein complex that controls transcription of DNA and is involved in cellular responses to stimuli such as
stress, cytokines, free radicals, ultraviolet irradiation. In brief, NF-B can be understood to be a protein
responsible for cytokine production and cell survival.

The mechanism of Atopic dermatitis witnesses an innate abnormality in the epidermal lipid metabolism
which leads to
1) A failure of the intercorneocyte cement due to a lack of: Ceramides, Essential fatty acids, Cholesterol
and cholesterol esters.

2) Shortage of filaggrins are filament-associated proteins which bind to keratin fibers in the epidermal cells.
The gene for filaggrin resides on Chromosome 1 (1q21.3). This gene was first identified as the gene
involved in ichthyosis vulgaris.
4
Also, the shortage of filaggrin results in the increase in skin pH which
encourages serine protease activity these are enzymes which digest lipid-processing enzymes and the
proteins that hold epidermal cells together. Serine proteases also generate active cytokines like IL-1a and
Il-1beta and promote skin inflammation.

3) Shortage of involucrin which contributes to the formation of a cell envelope that protects corneocytes in
the skin. Involucrin is synthesized in the stratum spinosum and cross linked in the stratum granulosum by
the transglutaminase enzyme that makes it highly stable. Thus it provides structural support to the cell,
thereby allowing the cell to resist invasion by micro-organisms.

But what triggers AD..



Mutations of the gene encoding TLR2 are associated with severe forms of AD (with recurring bacterial
infections) as when an allergen crosses the epidermal barrier, it comes in contact with toll-like receptors
(TLRs) expressed by skin cells, the 1
st
line of defense against infections

Reduced activity of beta-defensins 2 and 3
5
. This reduction in the skin's natural antimicrobial peptides
6
is
induced by the strong presence of pro-inflammatory cytokines
7
(IL3,IL4,IL5,IL13) produced by the Th2
lymphocytes
8


Reduced innate immunity (beta-defensins 2 and 3) is why, in 90% of cases, atopic skin is colonized by
staphylococcus aureus bacteria. The toxins produced by S.aureus increase inflammation and cause the
production of specific IgEs. The ceramidases synthesized by S.aureus alter the skin's barrier function.

The hyper-reactivity of the immune system triggers the release of numerous pro-inflammatory
mediators and immunoglobulin E (IgE)
9


In the case of extrinsic or allergic atopy (actual AD), specific immunoglobulins Es (IgEs) are released Other
symptoms: rhinitis, asthma.etc.

Reactivity to environmental allergens:
Respiratory allergens: pet hairs (cats, dogs), pollen, dust mites
Food allergens: eggs, peanuts, milk, soya bean, wheat flour etc.
Contact allergens: perfume, nickel, latex etc.


4) Treatment to Atopic Dermatitis

1. Anti-inflammatory (dermocorticosteroids). This is used for short term only and during inflammatory
eczemas. They should be advised with a proper emollient since they induce dryness.

2. Antiseptic (Antibiotics only in case of super infection). They can't be used for so long or they will be
harming the cutaneous flora (bacterium that lives on top of the skin)

3. Anti Pruritus, anti- itching or Anti-histamines.

4. With severe cases, immunomodulators or topical immunosuppressive could be used.





1
is a rare but severe disseminated infection that generally occurs at sites of skin damage produced by, for example, atopic
dermatitis, burns, long term usage of topical steroids or eczema
2
is a rare severe adverse reaction to smallpox vaccination.
3
Squames begin life as normal cells in the lower layers of the epidermis but, as they travel towards the surface, they
progressively lose all recognizable contents.
4
Ichthyosis is characterised by persistently dry, thickened, rough, fish scale skin. There are at least 20 varieties of ichthyosis,
including inherited and acquired forms.
5
The beta defensins are antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization.
6
A peptide is a chemical compound containing two or more amino acids (amino acid polymers) that are coupled by a
peptide bond. This bond is a special linkage in which the nitrogen atom of one amino acid binds to the carboxyl carbon atom
of another.
7
Cytokines are cell signaling molecules that aid cell to cell communication in immune responses and stimulate the
movement of cells towards sites of inflammation, infection and trauma.
8
Lymphocytes are small white blood cells that play an role in the bodys immune response (that is, in the bodys fight
against germs and diseases).There are two main types of lymphocytes, known as B cells and T cells (also known as B
lymphocytes and T lymphocytes). The B cells produce antibodies that attack foreign molecules (germs and the toxins they
produce). The T cells are more complicated, but they can attack the bodys own cells when they are diseased (for example,
when the cells have been invaded by cancer or viruses).

Substances secreted by lymphocytes (called lymphokines) contribute to inflammation. Wherever there is chronic
inflammation in the body, lymphocytes are present.
9
IgE: specific antibodies synthesized during the allergic reaction.