FUNCTIONS OF SKIN IN MAINTAINING BODILY FUNCTIONS

a. Prevent dehydration. Without the stratum corneum, a highly effective waterproof layer, the body
would rapidly dry out and die.
b. Ultraviolet protection. Ultraviolet (UV) radiation from the sun can cause dermal damage and
promote skin cancer.
c. Temperature regulation. The blood flow through the dermis can be rapidly altered by valves
regulating blood flow through capillaries in the upper dermis or by short-circuiting blood through
dermal arterio-venous anastomoses. If the core body temperature goes up, the amount of blood
near the surface is massively increased, so heat radiates away from the body. If the core
temperature remains too high, the sweat glands are turned on and the latent heat of evaporation
results in some cooling. If the core body temperature drops, blood supply to the skin surface is
shut off. If this skin response is not sufficient to increase the core temperature, shivering starts and
erector pili muscles contract (‘goose pimples’), in a prehistoric but ineffective effort to increase
the insulation.
d. Sensation. The range of different skin sensations includes touch, soreness, pain, itch, tickle, heat,
cold and pressure. There is an obvious protective function, for example immediate withdrawal of a
hand after feeling a dangerously hot area.
e. Immunity. Langerhans cells in the epidermis are constantly on the alert for any unusual chemical
touching the skin. New foreign chemicals are learnt by Langerhans cells, and information passed
via the lymph nodes to circulating T cells. If the chemical is encountered again, a brisk
inflammatory response is triggered, ‘delayed hypersensitivity’, attacking the unwanted antigen.
f. Vitamin D production. Vitamin D is essential for calcium and phosphate regulation. Lack of
vitamin D causes rickets, poorly formed bone, typically with curved tibia, or osteomalacia.
Vitamin D is in the diet, mainly in milk and eggs, or is generated in the skin by ultraviolet B
(UVB) from the sun acting on 7-dehydrocholesterol. This only happens outdoors, as UVB does
not go through window glass. People with dark skin who live in the north and cover up their skin
risk developing rickets.

LAYERS OF THE SKIN

a. Epidermis - the outermost; keratinized stratified squamous epithelium consisting of four types of
epidermal cells: keratinocytes, melanocytes, Langerhans cells and Merkel cells. About 90% of
epidermal cells are keratinocytes, which are arranged in four or five layers and produce the protein
keratin. Keratin is a tough, fibrous protein that helps protect the skin and underlying tissues from
heat, microbes and chemicals. Keratinocytes also produce lamellar granules, which release a
water-repellant sealant that decreases water entry and loss and inhibits the entry of foreign
materials. It is made of 5 sublayers: : the stratum germinativum, stratum spinosum, stratum
granulosum, stratum lucidum and stratum corneum.
b. The Dermis - connective tissue layer that binds to the epidermis. The junction of the dermis with
the epidermis is irregular. The superficial layer of the dermis forms numerous raised projections,
called dermal papillae, that interdigitate with evaginations of epidermis, called epidermal ridges.
This region of skin is the papillary layer of the dermis. This layer is filled with loose irregular
connective tissue and connective tissue fibers, capillaries, blood vessels, fibroblasts, macrophages
and other loose connective tissue cells.

PRIMARY AND SECONDARY SKIN LESIONS

Primary Lesions
1. Macules: Up to 1 cm and are circumscribed, flat dis- colorations of the skin. Examples include
freckles, flat nevi, and some drug eruptions.
2. Patches: Larger than 1 cm and are circumscribed, flat discolorations of the skin. Examples include
vitiligo, some drug eruptions, senile freckles, melasma, and measles exanthem.
3. Papules: Up to 1 cm and are circumscribed, elevated, superficial, solid lesions. Examples include
elevated nevi, some drug eruptions, warts, and lichen planus. A wheal (hive) is a type of papule that is
edematous and transitory. Causes of wheals include drug eruptions, food allergies, numerous
underlying illnesses, and insect bites.
 4. Plaques: Larger than 1 cm and are circumscribed, elevated, superficial, solid lesions. Examples include
mycosis fungoides and lichen simplex chronicus.
5. Nodules: Range in size (up to 1 cm) and are solid lesions with depth. They may be above, level with,
or beneath the skin surface. Examples are nodular secondary or tertiary syphilis, basal cell cancers,
dermatofibromas, and xanthomas.
6. Tumors: Larger than 1 cm and are solid lesions with depth. They may be above, level with, or beneath
the skin surface. Examples include tumor stage of mycosis fungoides and larger basal cell cancers.
7. Vesicles: Up to 1 cm in size and are circumscribed elevations of the skin containing serous fluid.
Examples include poison ivy, early chickenpox, herpes zoster, herpes simplex, dyshidrosis, and contact
dermatitis.
8. Bullae: Larger than 1 cm and are circumscribed elevations containing serous fluid. Examples include
pemphigus, bullous pemphigoid, poison ivy, and second-degree burns.
9. Pustules: Vary in size and are circumscribed elevations of the skin containing purulent fluid. Examples
include acne, pustular psoriasis, and impetigo.
10. Petechiae: Range in size (up to 1 cm) and are circumscribed deposits of blood or blood pigments.
Examples are thrombocytopenia, vasculitis, and drug eruptions.
11. Purpura: A circumscribed deposit of blood or blood pigment that is larger than 1 cm in the skin.
Examples include senile purpura, drug eruptions, bleeding diatheses, chronic topical and systemic
corticosteroid use, and vasculitis.

Secondary Lesions
1. Scales: Shedding, dead epidermal cells that may be dry or greasy. Examples are seborrhea (greasy) and
psoriasis (dry).
2. Crusts: Variously colored masses of skin exudates of blood, serum, pus, or any combination of these.
Examples include impetigo, infected dermatitis, nummular eczema, or any area of excoriation.
3. Excoriations: Abrasions of the skin, usually superficial and traumatic. Examples are scratched insect
bites, scabies, eczema, and dermatitis herpetiformis.
4. Fissures: Linear breaks in the skin, sharply defined with abrupt walls. Examples include congenital
syphilis, interdigital tinea pedis, and hand eczema.
5. Induration: Woodiness or hardness as seen in infiltrating tumors such as dermatofibrosarcoma
protuberans, cutaneous metastasis, lymphoma, scleroderma, or hypertrophic scars.
6. Ulcers: Variously sized and shaped excavations in the skin extending into the dermis or often deeper
that usually heal with a scar. Examples include stasis ulcers of legs, ischemic leg ulcers, pyoderma
gangrenosum, and tertiary syphilis.
7. Scars: Formations of connective tissue replacing tissue lost through injury or disease. Examples are
discoid lupus, lichen planus in the scalp, and third- degree burns.
8. Keloids: Hypertrophic scars beyond the borders of the original injury (Fig. 3-3B). They are elevated,
can be progressive, and usually are the result of some sort of trauma in the skin. Keloids are more
common in darker-skinned people. They are com- mon on the upper torso, neck, and with body
piercing (especially with piercings of the earlobe). Rarely, keloids can occur spontaneously. Any type
of full- thickness skin trauma can heal with a keloidal scar. They are unsightly and can be numb,
pruritic, or painful.
9. Lichenification: A diffuse area of thickening and scaling with a resultant increase in skin lines and
markings. It is often seen in atopic dermatitis or any area chronically rubbed or scratched.

PERTINENT DATA TO ASK DURING HISTORY IN A PATIENT WITH SKIN PROBLEMS

In the history, determine the onset, progression, distribution, duration, and recurrence of the lesions. Note
the presence of prodromal and associated symptoms, including pruritus, fever, cough, coryza, vomiting,
diarrhea, jaundice, lymphadenopathy, altered mental status, arthritis, and failure to thrive. Identify any
precipitating factor or agent, including infection, medications, trauma, sunburn, frostbite, water immersion,
food, and agents contacting the skin in the area of involvement. Note predisposing conditions, such as atopic
disease (atopic dermatitis, allergic rhinitis, asthma), malignant neoplasia, collagen vascular disease, liver
disease, renal disease, and mucocutaneous diseases. A helpful acronym to remember the specific questions to
ask patients when taking a skin history is 'OLD CARTS', which gives a systematic approach to questioning in a
 skin assessment, this includes onset, location, duration, character, aggravating factors, relieving factors, timing
and severity.

Past history should include:

• General health problems, such as diabetes and tuberculosis (TB).
• Past skin problems, especially in childhood (e.g. eczema).
• Asthma, hay fever.
• Significant allergies or intolerances.

Family history
• Are there any family members with skin disease? Some disorders are infectious; others have strong genetic
backgrounds.
• Ask about atopic disorders and psoriasis.
• Ask about skin cancer.

Occupation and hobbies

• The skin is frequently affected by materials encountered at work and in the home.
• Is there a history of excess sun exposure?

Therapy
• Ask about systemic medication.
• Ask about topical remedies. Many patients apply multiple creams, lotions, and ointments.
• Topicals may be prescribed medicines or self-administered.
• Check on toiletry, bathing, and cosmetic use.
• Ask, ‘What do you use to wash with?’

ATOPIC DERMATITIS

Atopic dermatitis (AD), or eczema, is the most common chronic relapsing skin disease seen in infancy and
childhood. It affects 10–30% of children worldwide and frequently occurs in families with other atopic diseases.
Infants with AD are predisposed to the development of food allergy, allergic rhinitis, and asthma later in
childhood, a process called the atopic march. AD is a complex genetic disorder that results in a defective skin
barrier, reduced skin innate immune responses, and polarized adaptive immune responses to environmental
allergens and microbes that lead to chronic skin inflammation.
AD is associated with multiple phenotypes and endotypes that have overlapping clinical presentations.
Atopic eczema is associated with IgE-mediated sensitization (at onset or during the course of eczema) and
occurs in 70–80% of patients with AD. Nonatopic eczema is not associated with IgE-mediated sensitization and
is seen in 20–30% of patients with AD. Both forms of AD are associated with eosinophilia. In atopic eczema,
circulating T cells expressing the skin-homing receptor cutaneous lymphocyte-associated antigen produce
increased levels of T-helper type 2 (Th2) cytokines, including interleukin (IL)-4 and IL-13, which induce
isotype switching to IgE synthesis. Another cytokine, IL-5, plays an important role in eosinophil development
and survival. Nonatopic eczema is associated with lower IL-4 and IL-13 but increased IL-17 and IL-23
production than in atopic eczema. Age and race have also been found to affect the immune profile in AD.
Compared with the skin of healthy individuals, both unaffected skin and acute skin lesions of patients with
AD have an increased number of cells expressing IL-4 and IL-13. Chronic AD skin lesions, by contrast, have
fewer cells that express IL-4 and IL-13, but increased numbers of cells that express IL-5, granulocyte-
macrophage colony-stimulating factor, IL-12, and interferon (IFN)-γ than acute AD lesions. Despite increased
type 1 and type 17 immune responses in chronic AD, IL-4, and IL-13 as well as other types 2 cytokines (e.g.
TSLP, IL-31, IL-33) predominate and reflect increased numbers of Type 2 innate lymphoid cells and Th2 cells.
The infiltration of IL–22–expressing T cells correlates with the severity of AD, blocks keratinocyte
differentiation, and induces epidermal hyperplasia. The importance of IL-4 and IL-13 in driving severe
persistent AD has been validated by multiple clinical trials now demonstrating that biologics blocking IL-4 and
IL-13 action lead to clinical improvement in moderate to severe AD.
In healthy people, the skin acts as a protective barrier against external irritants, moisture loss, and infection.
The proper function of the skin depends on adequate moisture and lipid content, functional immune responses,
 and structural integrity. Severely dry skin is a hallmark of AD. This results from compromise of the epidermal
barrier, which leads to excess transepidermal water loss, allergen penetration, and microbial colonization.
Filaggrin, a structural protein in the epidermis, and its breakdown products are critical to skin barrier function,
including moisturization of the skin. Genetic mutations in the filaggrin gene (FLG) family have been identified
in patients with ichthyosis vulgaris (dry skin, palmar hyperlinearity) and in up to 50% of patients with severe
AD. FLG mutation is strongly associated with the development of food allergy and eczema herpeticum.
Nonetheless, up to 60% of carriers of a FLG mutation do not develop atopic diseases. Cytokines found in
allergic inflammation, such as IL-4, IL-13, IL-22, IL-25, and tumor necrosis factor, can also reduce filaggrin
and other epidermal proteins and lipids. AD patients are at increased risk of bacterial, viral, and fungal infection
related to impairment of innate immunity, disturbances in the microbiome, skin epithelial dysfunction, and
overexpression of polarized immune pathways, which dampen host antimicrobial responses.
AD typically begins in infancy. Approximately 50% of patients experience symptoms in the 1st yr of life,
and an additional 30% are diagnosed between 1 and 5 yr of age. Intense pruritus, especially at night, and
cutaneous reactivity are the cardinal features of AD. Scratching and excoriation cause increased skin
inflammation that contributes to the development of more pronounced eczematous skin lesions. Foods (cow’s
milk, egg, peanut, tree nuts, soy, wheat, fish, shellfish), aeroallergens (pollen, grass, animal dander, dust mites),
infection (Staphylococcus aureus, herpes simplex, coxsackievirus, molluscum), reduced humidity, excessive
sweating, and irritants (wool, acrylic, soaps, toiletries, fragrances, detergents) can trigger pruritus and
scratching.
Acute AD skin lesions are intensely pruritic with erythematous papules. Subacute dermatitis manifests as
erythematous, excoriated, scaling papules. In contrast, chronic AD is characterized by lichenification, or
thickening of the skin with accentuated surface markings, and fibrotic papules. In chronic AD, all 3 types of
skin reactions may coexist in the same individual. Most patients with AD have dry, lackluster skin regardless of
their stage of illness. Skin reaction pattern and distribution vary with the patient’s age and disease activity. AD
is generally more acute in infancy and involves the face, scalp, and extensor surfaces of the extremities. The
diaper area is usually spared. Older children and children with chronic AD have lichenification and localization
of the rash to the flexural folds of the extremities. AD can go into remission as the patient grows older,
however, many children with AD have persistent eczema as an adult.
There are no specific laboratory tests to diagnose AD. Many patients have peripheral blood eosinophilia
and increased serum IgE levels. Serum IgE measurement or skin-prick testing can identify the allergens (foods,
inhalant/microbial allergens) to which patients are sensitized. The diagnosis of clinical allergy to these allergens
requires confirmation by history and environmental challenges.

TYPICAL LOCATIONS OF ATOPIC DERMATITIS @ DIFFERENT AGES & ASSESSMENT OF

SEVERITY

Typical clinical appearance and locations of atopic dermatitis at different ages. Top row (A), In infants,
atopic dermatitis is generally acute, with lesions mainly on the face and the extensor surfaces of the limbs. The
trunk might be affected, but the napkin area is typically spared. Middle row (B) , From age 1-2 yr onward,
polymorphous manifestations with different types of skin lesions are seen, particularly in flexural folds. Bottom
row (C), Adolescents and adults often present lichenified and excoriated plaques at flexures, wrists, ankles, and
eyelids; in the head and neck type, the upper trunk, shoulders, and scalp are involved. Adults might have only
chronic hand eczema or present with prurigo-like lesions.
ATOPIC DERMATITIS TREATMENT

The treatment of AD requires a systematic, multifaceted approach that incorporates skin moisturization,
topical anti-inflammatory therapy, identification and elimination of flare factor, and, if necessary, systemic
therapy.
Cutaneous hydration:
Because patients with AD have impaired skin barrier function from reduced filaggrin and skin lipid levels,
they present with diffuse, abnormally dry skin, or xerosis. Moisturizers are first-line therapy. Lukewarm
soaking baths or showers for 15-20 min followed by the application of an occlusive emollient to retain moisture
provide symptomatic relief. Hydrophilic ointments of varying degrees of viscosity can be used according to the
patient’s preference. Occlusive ointments are sometimes not well tolerated because of interference with the
function of the eccrine sweat ducts and may induce the development of folliculitis. In these patients, less
occlusive agents should be used. Several prescription (classified as a medical device) “therapeutic moisturizers”
or “barrier creams” are available, containing components such as ceramides and filaggrin acid metabolites
intended to improve skin barrier function. There are minimal data demonstrating their efficacy over standard
emollients.
Hydration by baths or wet dressings promotes transepidermal penetration of topical glucocorticoids.
Dressings may also serve as effective barriers against persistent scratching, in turn promoting healing of
excoriated lesions. Wet dressings are recommended for use on severely affected or chronically involved areas of
dermatitis refractory to skin care. It is critical that wet dressing therapy be followed by topical emollient
application to avoid potential drying and fissuring from the therapy. Wet dressing therapy can be complicated
by maceration and secondary infection and should be closely monitored by a physician.

Topical Corticosteroids:
Topical corticosteroids are the cornerstone of anti-inflammatory treatment for acute exacerbations of AD.
Patients should be carefully instructed on their use of topical glucocorticoids to avoid potential adverse effects.
Because of their potential adverse effects, the ultrahigh-potency glucocorticoids should not be used on the face
or intertriginous areas and should be used only for very short periods on the trunk and extremities. Mid- potency
glucocorticoids can be used for longer periods to treat chronic AD involving the trunk and extremities. Long-
term control can be maintained with twice-weekly applications of topical fluticasone or mometasone to areas
that have healed but are prone to relapse, once control of AD is achieved after a daily regimen of topical
corticosteroids. Compared with creams, ointments have a greater potential to occlude the epidermis, resulting in
enhanced systemic absorption.
Adverse effects of topical glucocorticoids can be divided into local adverse effects and systemic adverse
effects, the latter resulting from suppression of the hypothalamic-pituitary-adrenal axis. Local adverse effects
include the development of striae and skin atrophy. Systemic adverse effects are related to the potency of the
topical corticosteroid, site of application, occlusiveness of the preparation, percentage of the body surface area
covered, and length of use. The potential for adrenal suppression from potent topical corticosteroids is greatest
in infants and young children with severe AD requiring intensive therapy.

Topical Calcineurin Inhibitors

The nonsteroidal topical calcineurin inhibitors are effective in reducing AD skin inflammation.
Pimecrolimus cream 1% (Elidel) is indicated for mild to moderate AD. Tacrolimus ointment 0.1% and 0.03%
(Protopic) is indicated for moderate to severe AD. Both are approved for short-term or intermittent long-term
treatment of AD in patients ≥2 yr whose disease is unresponsive to or who are intolerant of other conventional
therapies or for whom these therapies are inadvisable because of potential risks. Topical calcineurin inhibitors
may be better than topical corticosteroids in the treatment of patients whose AD is poorly responsive to topical
steroids, patients with steroid phobia, and those with face and neck dermatitis, in whom ineffective, low-
potency topical corticosteroids are typically used because of fears of steroid-induced skin atrophy.

Phosphodiesterase Inhibitor
Crisaborole (Eucrisa) is an approved nonsteroidal topical antiinflam- matory phosphodiesterase-4 (PDE-4)
inhibitor indicated for the treatment of mild to moderate AD down to age 2 yr. It may be used as an alternative
to topical corticosteroids or calcineurin inhibitors.

Tar Preparations
Coal tar preparations have antipruritic and anti-inflammatory effects on the skin; however, their anti-
inflammatory effects are usually not as pronounced as those of topical glucocorticoids or calcineurin inhibitors.
Therefore, topical tar preparations are not a preferred approach for management of AD. Tar shampoos can be
particularly beneficial for scalp dermatitis. Adverse effects associated with tar preparations include skin
irritation, folliculitis, and photosensitivity.
Antihistamines
Systemic antihistamines act primarily by blocking the histamine H1 receptors in the dermis, thereby
reducing histamine-induced pruritus. Histamine is only one of many mediators that induce pruritus of the skin,
so patients may derive minimal benefit from antihistaminic therapy. Because pruritus is usually worse at night,
sedating antihistamines (hydroxyzine, diphenhydramine) may offer an advantage with their soporific side
effects when used at bedtime. Doxepin hydrochloride has both tricyclic antidepressant and H 1- and H2-receptor
blocking effects. Short-term use of a sedative to allow adequate rest may be appropriate in cases of severe
nocturnal pruritus. Studies of newer, nonsedating antihistamines have shown variable effectiveness in
controlling pruritus in AD, although they may be useful in the small subset of patients with AD and
concomitant urticaria. For children, melatonin may be effective in promoting sleep because production is
deficient in AD.

Systemic Corticosteroids
 Systemic corticosteroids are rarely indicated in the treatment of chronic AD. The dramatic clinical
improvement that may occur with systemic corticosteroids is frequently associated with a severe rebound flare
of AD after therapy discontinuation. Short courses of oral corticosteroids may be appropriate for an acute
exacerbation of AD while other treatment measures are being instituted in parallel. If a short course of oral
corticosteroids is given, as during an asthma exacerbation, it is important to taper the dosage and begin
intensified skin care, particularly with topical corticosteroids, and frequent bathing, followed by application of
emollients or proactive topical corticosteroids, to prevent rebound flaring of AD.

Cyclosporine
Cyclosporine is a potent immunosuppressive drug that acts primarily on T cells by suppressing cytokine
gene transcription and has been shown to be effective in the control of severe AD. Cyclosporin forms a complex
with an intracellular protein, cyclophilin, and this complex in turn inhibits calcineurin, a phosphatase required
for activation of NFAT (nuclear factor of activated T cells), a transcription factor necessary for cytokine gene
transcription. Cyclosporine (5 mg/kg/day) for short- term and long-term (1 yr) use has been beneficial for
children with severe, refractory AD. Possible adverse effects include renal impairment and hypertension.

Dupilumab
A monoclonal antibody that binds to the IL-4 receptor α subunit, dupilumab (Dupixent) inhibits the
signaling of IL-4 and IL-13, cytokines associated with AD. In adults with moderate to severe AD not controlled
by standard topical therapy, dupilumab reduces pruritus and improves skin clearing.

Antimetabolites
Mycophenolate mofetil is a purine biosynthesis inhibitor used as an immunosuppressant in organ
transplantation that has been used for treatment of refractory AD. Aside from immunosuppression, herpes
simplex retinitis and dose-related bone marrow suppression have been reported with its use. Of note, not all
patients benefit from treatment. Therefore, mycophenolate mofetil should be discontinued if the disease does
not respond within 4-8 wk.
Methotrexate is an antimetabolite with potent inhibitory effects on inflammatory cytokine synthesis and
cell chemotaxis. Methotrexate has been used for patients with recalcitrant AD. In AD, dosing is more frequent
than the weekly dosing used for psoriasis.
Azathioprine is a purine analog with anti-inflammatory and anti proliferative effects that has been used for
severe AD. Myelosuppression is a significant adverse effect, and thiopurine methyltransferase levels may
identify individuals at risk.
Before any of these drugs is used, patients should be referred to an AD specialist who is familiar with
treatment of severe AD to weigh relative benefits of alternative therapies.

Phototherapy
Natural sunlight is often beneficial to patients with AD as long as sunburn and excessive sweating are
avoided. Many phototherapy modalities are effective for AD, including ultraviolet A-1, ultraviolet B, narrow-
band ultraviolet B, and psoralen plus ultraviolet A. Phototherapy is generally reserved for patients in whom
standard treatments fail. Maintenance treatments are usually required for phototherapy to be effective. Short-
term adverse effects with phototherapy include erythema, skin pain, pruritus, and pigmentation. Long-term
adverse effects include predisposi- tion to cutaneous malignancies.
Unproven Therapies

Interferon-γ

IFN-γ is known to suppress Th2-cell function. Several studies, including a multicenter, double-blind, placebo-
controlled trial and several open trials, have demonstrated that treatment with recombinant human IFN-γ results
in clinical improvement of AD. Reduction in clinical severity of AD correlated with the ability of IFN-γ to
decrease total circulating eosinophil counts. Influenza-like symptoms are common side effects during the
treatment course.

Omalizumab
Treatment of patients who have severe AD and elevated serum IgE values with monoclonal anti-IgE may
be considered in those with allergen-induced flares of AD. However, there have been no published double-
 blind, placebo-controlled trials of omalizumab’s use. Most reports have been case studies and show inconsistent
responses to anti-IgE.

Allergen Immunotherapy
In contrast to its acceptance for treatment of allergic rhinitis and extrinsic asthma, immunotherapy with
aeroallergens in the treatment of AD is controversial. There are reports of both disease exacerbation and
improvement. Studies suggest that specific immunotherapy in patients with AD sensitized to dust mite allergen
showed improvement in severity of skin disease, as well as reduction in topical corticosteroid use.

Probiotics
Perinatal administration of the probiotic Lactobacillus rhamnosus strain GG has been shown to reduce the
incidence of AD in at-risk children during the 1st 2 yr of life. The treatment response has been found to be more
pronounced in patients with positive skin-prick test results and elevated IgE values. Other studies have not
demonstrated a benefit.

Chinese Herbal Medications

Several placebo-controlled clinical trials have suggested that patients with severe AD may benefit from
treatment with traditional Chinese herbal therapy. The patients had significantly reduced skin disease and
decreased pruritus. The beneficial response of Chinese herbal therapy is often temporary, and effectiveness may
wear off despite continued treatment. The possibility of hepatic toxicity, cardiac side effects, or idiosyncratic
reactions remains a concern. The specific ingredients of the herbs also remain to be elucidated, and some
preparations have been found to be contaminated with corticosteroids. At present, Chinese herbal therapy for
AD is considered investigational.

Vitamin D
Vitamin D deficiency often accompanies severe AD. Vitamin D enhances skin barrier function, reduces
corticosteroid requirements to control inflammation, and augments skin antimicrobial function. Several small
clinical studies suggest vitamin D can enhance antimicrobial peptide expression in the skin and reduce severity
of skin disease, especially in patients with low baseline vitamin D, as during winter, when exacerbation of AD
often occurs. Patients with AD might benefit from supplementation with vitamin D, particularly if they have a
documented low level or low vitamin D intake.

PREVENTION OF RECURRENCE OF ATOPIC DERMATITIS

Avoiding Triggers:

Irritants
Patients with AD have a low threshold response to irritants that trigger their itch-scratch cycle. Soaps or
detergents, chemicals, smoke, abrasive clothing, and exposure to extremes of temperature and humidity are
common triggers. Patients with AD should use soaps with minimal defatting properties and a neutral pH. New
clothing should be laundered before wearing to decrease levels of formaldehyde and other chemicals. Residual
laundry detergent in clothing may trigger the itch-scratch cycle; using a liquid rather than powder detergent and
adding a 2nd rinse cycle facilitates removal of the detergent.
Every attempt should be made to allow children with AD to be as normally active as possible. A sport such
as swimming may be better tolerated than others that involve intense perspiration, physical contact, or heavy
clothing and equipment. Rinsing off chlorine immediately and lubricating the skin after swimming are
important. Although ultraviolet light may be beneficial to some patients with AD, high–sun protection factor
(SPF) sunscreens should be used to avoid sunburn.

Foods
Food allergy is comorbid in approximately 40% of infants and young children with moderate to severe AD.
Undiagnosed food allergies in patients with AD may induce eczematous dermatitis in some patients and
urticarial reactions, wheezing, or nasal congestion in others. Increased severity of AD symptoms and younger
age correlate directly with the presence of food allergy. Removal of food allergens from the diet leads to
 significant clinical improvement but requires much education, because most common allergens (egg, milk,
peanut, wheat, soy) contaminate many foods and are difficult to avoid.
Potential allergens can be identified by a careful history and performing selective skin-prick tests or in vitro
blood testing for allergen-specific IgE. Negative skin and blood test results for allergen-specific IgE have a high
predictive value for excluding suspected allergens. Positive results of skin or blood tests using foods often do
not correlate with clinical symptoms and should be confirmed with controlled food challenges and elimination
diets. Extensive elimination diets, which can be nutrition- ally deficient, are rarely required. Even with multiple
positive skin test results, the majority of patients react to fewer than 3 foods under controlled challenge
conditions.

Aeroallergens
In older children, AD flares can occur after intranasal or epicutaneous exposure to aeroallergens such as
fungi, animal dander, grass, and ragweed pollen. Avoiding aeroallergens, particularly dust mites, can result in
clinical improvement of AD. Avoidance measures for dust mite–allergic patients include using dust mite–proof
encasings on pillows, mattresses, and box springs; washing bedding in hot water weekly; removing bedroom
carpeting; and decreasing indoor humidity levels with air conditioning.

Infections
Patients with AD have increased susceptibility to bacterial, viral, and fungal skin infections.
Antistaphylococcal antibiotics are very helpful for treating patients who are heavily colonized or infected with
Staphylococcus aureus. Erythromycin and azithromycin are usually beneficial for patients who are not
colonized with a resistant S. aureus strain; a first-generation cephalosporin (cephalexin) is recommended for
macrolide-resistant S. aureus. Topical mupirocin is useful in the treatment of localized impetiginous lesions,
with systemic clindamycin or trimethoprim/sulfamethoxazole needed for methicillin-resistant S. aureus
(MRSA). Cytokine-mediated skin inflammation contributes to skin colonization with S. aureus. This finding
supports the importance of combining effective anti-inflammatory therapy with antibiotics for treating moderate
to severe AD to avoid the need for repeated courses of antibiotics, which can lead to the emergence of
antibiotic-resistant strains of S. aureus. Dilute bleach baths twice weekly may be also considered to reduce S.
aureus colonization. In one randomized trial, the group who received the bleach baths plus intranasal mupirocin
(5 days/mo) had significantly decreased severity of AD at 1 and 3 mo compared with placebo. Patients rinse off
after the soaking. Bleach baths may not only reduce S. aureus abundance on the skin but also have anti-
inflammatory effects.

Herpes simplex virus (HSV) can provoke recurrent dermatitis and may be misdiagnosed as S. aureus
infection. The presence of punched-out erosions, vesicles, and infected skin lesions that fail to respond to oral
antibiotics suggests HSV infection, which can be diagnosed by a Giemsa-stained Tzanck smear of cells scraped
from the vesicle base or by viral polymerase chain reaction or culture. Topical corticosteroids should be
temporarily discontinued if HSV infection is suspected. Reports of life-threatening dissemination of HSV
infections in patients with AD who have widespread disease mandate antiviral treatment. Persons with AD are
also susceptible to eczema vaccinatum, which is similar in appearance to eczema herpeticum and historically
follows smallpox (vaccinia virus) vaccination.

Cutaneous warts, coxsackievirus, and molluscum contagiosum are additional viral infections affecting
children with AD.
Dermatophyte infections can also contribute to exacerbation of AD. Patients with AD have been found to
have a greater susceptibility to Trichophyton rubrum fungal infections than nonatopic controls. There has been
particular interest in the role of Malassezia furfur (formerly known as Pityrosporum ovale) in AD because it is a
lipophilic yeast commonly present in the seborrheic areas of the skin. IgE antibodies against M. furfur have
been found in patients with head and neck dermatitis. A reduction of AD severity has been observed in these
patients after treatment with antifungal agents.

ATOPIC DERMATITIS COMPLICATIONS & PROGNOSIS

Complications
Exfoliative dermatitis may develop in patients with extensive skin involvement. It is associated with
generalized redness, scaling, weeping, crusting, systemic toxicity, lymphadenopathy, and fever and is usually
 caused by superinfection (e.g., with toxin-producing S. aureus or HSV infection) or inappropriate therapy. In
some cases the withdrawal of systemic glucocorticoids used to control severe AD precipitates exfoliative
erythroderma.

Eyelid dermatitis and chronic blepharitis may result in visual impairment from corneal scarring. Atopic
keratoconjunctivitis is usually bilateral and can have disabling symptoms that include itching, burning, tearing,
and copious mucoid discharge. Vernal conjunctivitis is associated with papillary hypertrophy or cobblestoning
of the upper eyelid conjunctiva. It typically occurs in younger patients and has a marked seasonal incidence
with spring exacerbations. Keratoconus is a conical deformity of the cornea believed to result from chronic
rubbing of the eyes in patients with AD. Cataracts may be a primary manifestation of AD or from extensive use
of systemic and topical glucocorticoids, particularly around the eyes.

Prognosis
AD generally tends to be more severe and persistent in young children, particularly if they have null
mutations in their filaggrin genes. Periods of remission occur more frequently as patients grow older.
Spontaneous resolution of AD has been reported to occur after age 5 yr in 40–60% of patients affected during
infancy, particularly for mild disease. Earlier studies suggested that approximately 84% of children outgrow
their AD by adolescence; however, later studies reported that AD resolves in approximately 20% of children
monitored from infancy until adolescence and becomes less severe in 65%. Of those adolescents treated for
mild dermatitis, >50% may experience a relapse of the disease as adults, which frequently manifests as hand
dermatitis, especially if daily activities require repeated hand wetting. Predictive factors of a poor prognosis for
AD include widespread AD in childhood, FLG null mutations, concomitant allergic rhinitis and asthma, family
history of AD in parents or siblings, early age at onset of AD, being an only child, and very high serum IgE
levels.

THE 7 CLASSES OF TOPICAL GLUCOCORTICOIDS

There are 7 classes of topical glucocorticoids, ranked according to their potency, as determined by
vasoconstrictor assays.

PHYSICAL EXAMINATION OF THE SKIN

 To conduct a skin examination, dermatologists often use a magnifying lens as an essential tool. A thorough
examination of the entire body is crucial, especially when dealing with patients who have widespread skin
rashes. Feel the texture and consistency of the skin and any lesions by palpating them; this often yields valuable
diagnostic information and reassures patients that you are not hesitant to engage with their issue. For rare
contagious conditions, take appropriate safety measures. If you are uncertain about your diagnostic impression,
corroborate it with a biopsy. Lastly, don’t overlook the need for sufficient lightning during the examination.

ECZEMA HERPETICUM

Eczema herpeticum , also known as Kaposi's varicelliform eruption, is a rare but serious skin infection
caused by the herpes simplex virus (usually HSV-1, which commonly causes cold sores, or occasionally
HSV-2, which typically causes genital herpes). This condition typically occurs in individuals who already
have a preexisting skin condition, such as eczema (atopic dermatitis), which creates openings in the skin
that allow the herpes virus to enter and cause a widespread infection. It presents as painful, rapidly
spreading clusters of fluid-filled blisters or ulcers on the skin. It can be a severe and potentially dangerous
condition if left untreated.
Eczema herpeticum creates a compromised skin barrier, making the skin more susceptible to bacterial
infections. When impetigo occurs secondary to eczema herpeticum. It is usually “non bullous type” that is
more commonly seen, although bullous impetigo is also possible.

Staphylococcus aureus is the predominant organism of nonbullous impetigo; group A Beta hemolytic
streptococci (GABS) are implicated in the development of some lesions. The staphylococcal types that
cause nonbullous impetigo are variable but are not generally from phage group 2, the group that is
associated with scalded skin and toxic shock syndromes. Staphylococci generally spread from the nose to
normal skin and then infect the skin. In contrast, the skin becomes colonized with GABHS an average of 10
days before the development of impetigo. The skin serves as the source for the acquisition of GABHS and
the probable primary source for the spread of impetigo. Lesions of nonbullous impetigo that grow
staphylococci in culture cannot be distinguished clinically from those that grow pure cultures of GABHS.

Bullous impetigo is always caused by S. aureus strains that produce exfoliative toxins. The staphylococcal
exfoliative toxins (ETA, ETB, ETD) blister the superficial epidermis by hydrolyzing human desmoglein 1,
resulting in a subcorneal vesicle. This is also the target antigen of the autoantibodies in pemphigus
foliaceus.

Nonbullous impetigo accounts for more than 70% of cases. Lesions typically begin on the skin of the face
or on extremities that have been traumatized. The most common lesions that precede nonbullous impetigo
are insect bites, abrasions, lacerations, chickenpox, scabies pediculosis, and burns. A tiny vesicle or pustule
forms initially and rapidly develops into a honey-colored crusted plaque that is generally <2 cm in
diameter. The infection may be spread to other parts of the body by the fingers, clothing, and towels.
Lesions are associated with little to no pain or surrounding erythema, and constitutional symptoms are
generally absent. Pruritus occurs occasionally, regional adenopathy is found in up to 90% of cases, and
leukocytosis is present in approximately 50%.

Bullous impetigo is mainly an infection in infants and young children. Flaccid, transparent bullae develop
most commonly on the skin.

MANAGEMENT

a. Acyclovir is the most commonly used antiviral medication for treating eczema herpeticum.
Intravenous IV administration is often initiated, especially in severe cases.
b. Valacyclovir and Famciclovir are oral alternatives, but usually reserved for less severe cases or for step
down therapy.
c. Oral antibiotics are generally recommended for patients showing signs of widespread staphylococcal
or streptococcal infections, or when the skin condition is near the mouth where topical treatments
 could be ingested. An effective initial treatment can be Cephalexin, administered at a dose of 25-50
mg/kg/day, divided into 3-4 portions over 7-10 days. There is no evidence that a 10 day treatment plan
is more effective than one lasting 7 days. If the condition doesn’t improve within a week, bacterial
culture is advised to adjust antibiotic therapy based on sensitivity tests. For cases where MSRS is
suspected, alternatives like clindamycin, doxycycline, or sulfatmethoxazole-trimethoprin should be
considered.
d. Mupirocin is in the carboxylic acid class of medications. It works by blocking a bacteria's ability to
make protein, which usually results in bacterial death. The drug is a unique antimicrobial agent
because of its structure and mechanism of action. Mupirocin apparently exerts its antimicrobial activity
by reversibly inhibiting isoleucyl-transfer RNA, thereby inhibiting bacterial protein and RNA
synthesis.
e. The use of topical steroids on affected areas is generally avoided or minimized because of the risk of
exacerbating the infection.
f. Pain management, usually with acetaminophen or ibuprofen
g. Fever control
h. Fluid management, particularly if the patient is dehydrated.