Lecture 72: Pathophysiology of skin disorders: eczema, psoriasis, dermatitis + pharmaceutical care of skin conditions

What are the three primary layers of the skin from superficial to deep?

Epidermis, dermis, and hypodermis (subcutaneous layer)

What is the dermis made up of?

Blood vessels, nerves and connective tissue

What is the purpose of the hypodermis (SC)?

It anchors the skin to underlying structures and stores fat

What are the 6 functions of the skin?

1. Regulates body temperature through sweat production and blood flow

2. Stores blood and acts as a reservoir for fluids and electrolytes

3. Protects against pathogens, chemicals, and physical injuries

4. Detects sensations through specialized nerve endings

5. Excretes waste products and absorbs certain substances

6. Synthesizes vitamin D

What is the definition of atopic dermatitis?

A chronic, pruritic, relapsing inflammatory skin disorder associated with atopy (excess IgE) and impaired epidermal barrier function

Which four conditions typically constitute the 'Atopic March' sequence and what does this show?

Atopic dermatitis, food allergy, allergic rhinitis, asthma

Refers to how children with early eczema (atopic dermatitis) often go on to develop other allergic conditions over time

What is the typical clinical distribution of atopic dermatitis in infants?

Face, scalp, and extensor surfaces (elbow, knee etc)

Which body areas are most commonly affected by atopic dermatitis in children?

Flexural surfaces (e.g. knee and elbow flexures)

What are the common clinical features of atopic dermatitis in adults?

Hand involvement, facial rash, and chronic lichenification

Define the clinical term 'lichenification' in the context of chronic eczema

Thickening of the skin with exaggerated markings caused by chronic scratching or rubbing

Describe the process of skin barrier dysfunction (pathophysiology of atopic dermatitis)

1. Filaggrin (structural protein in outer skin) gene mutations causes impaired stratum coreum (leaky barrier)

2. This increases transdermal water loss as water escapes more easily

3. Enhances penetration of allergens and irritants into the skin which triggers Th2-mediated inflammation (IL-4, IL-5, IL-13)

4. Promotes IgE production and pruritus

5. Dry skin and itch-scratch cycle → itch impairs skin barrier

What is the primary function of the protein filaggrin in the skin barrier?

It binds keratinocytes together to maintain an intact barrier and hydrate the stratum corneum

Which lipid component is essential for water retention in the epidermis and is often reduced in atopic dermatitis?

Ceramide

What does the hygiene hypothesis suggest about exposure to pathogens?

Decreased exposure to pathogens in early life increases the risk of atopic diseases

What are the timing ranges of the 4 types of hypersensitivity reactions?

I = 30 mins

II = minutes to hours

III = 3-8 hours

IV = 48-72 hours

In contact dermatitis, which specific immune cells are primed by previous antigen exposure?

Th1 cells

What is the pathogenesis of allergic contact dermatitis (delayed-type hypersensitivity reaction)?

1. Allergen penetrates skin and binds to host proteins

2. Antigen is taken up and presented by APCs to T-cells in lymph nodes → sensitization and formation of memory TH1 cells

3. On re-exposure, memory TH1 cells migrate to the site of skin contact.

4. TH1 cells release cytokines (e.g. IFN-γ, TNF-α).

5. Cytokines recruit and activate macrophages and other inflammatory cells.

6. Local inflammation so fluid, serum proteins and leukocytes accumulate → erythema, edema, vesicles (eczema) after 24–72 hours

When would someone be diagnosed with persistent eczema?

Eczema diagnosed from 6 months until 10 years of age

How does Crohn’s Disease potentially manifest on the skin?

As specific granulomatous lesions, reactive immunological manifestations, or secondary complications of treatment

Why should patients with eczema avoid using standard soaps and detergents?

They act as irritants that disrupt the skin barrier

What are the 4 primary aims of atopic dermatitis treatment?

Reduce inflammation and pruritus, restore skin barrier, prevent infection, and improve quality of life

What is the recommended first-line therapy for atopic dermatitis of all severities and what does it do?

Emollients

The provide hydration and restore the epidermal barrier

Smooth onto skin liberally in direction of hair growth, not rubbed in

What instructions should be given to patients for how to apply emollients?

1. Use instead of soap, add to bath water or use in shower

2. One for the face and hands and a different one for the body

3. Use all of the time not just symptomatic

4. After bath/shower, gently pat skin dry and apply emollient while skin is moist

5. Use at least twice a day

6. Don’t put fingers into pots if possible, use spoon/pump dispenser to reduce infection

7. Don’t share tubs with others

What is non-pharmacological advice to give to patients when managing inflammatory skin conditions?

Using lukewarm baths, minimizing bedding, avoiding cosmetics that may irritate the skin, use gloves to handle chemicals etc

What is the first-line treatment for managing inflammation and pruritus in flares in atopic dermatitis?

Topical corticosteroids

Non-steroidal options for more sensitive areas include calcineurin inhibitors (tacrolimus) or phosphodiesterase-4 inhibitors (crisaborole)

How do you prescribe topical corticosteroids for patients?

Use the weakest effective potency

Step-down treatment plan when controlled

What is some counselling advice to give to patients when prescribing topical corticosteroids?

Inform patient to apply once or twice daily to affected areas

Smooth onto skin in direction of hair growth

What are some effects of topical steroid use?

Skin thinning and striae (stretch marks)

Telangiectasia (enlarged capillaries so seen through skin)

Perioral dermatitis (facial rash), acne

Higher risk in children and the elderly

Burning/stinging sensation usually improves with use

What is the recommended order of application when using both an emollient and a topical corticosteroid?

Apply the emollient first, wait 30 minutes, and then apply the corticosteroid

What is the clinical role of oral antihistamines in the management of atopic dermatitis?

They are primarily used to manage sleep disturbance caused by severe pruritus

Tacrolimus belongs to which class of topical medications used for moderate-to-severe eczema?

Topical calcineurin inhibitors

Which topical preparation consists of an ointment suspension used for localised delivery of noxious chemicals?

Pastes

What is a characteristic disadvantage of using paraffin-based emollients?

They are highly greasy, though they are the most effective at reducing water loss

Under what clinical conditions should a patient with dermatitis be referred to specialist care?

When the dermatitis is treatment-resistant or relapses rapidly upon cessation of therapy

What is the definition of psoriasis?

A chronic, immune-mediated inflammatory skin condition characterised by
well-demarcated erythematous plaques with silvery scale due to rapid keratinocyte proliferation

What are the factors determining whether a patient has psoriasis or eczema?

Psoriasis is lifelong/chronic but eczema may come and go

Psoriasis common in adults and eczema in children

Psoriasis = hereditary, eczema = environmental

Psoriasis characterised by thick, silvery scales whereas eczema is red, inflamed skin

How does the keratinocyte turnover rate in psoriasis compare to normal skin?

It is accelerated to 3–4 days, compared to the normal 28 days

What is the characteristic clinical appearance of a psoriasis plaque and where are the common sites for this to appear?

Well-demarcated plaques with silvery scales

Head, elbows, knees

Which lifestyle factors are known to aggravate psoriasis symptoms?

Stress, excessive alcohol consumption, and smoking

Which specialist treatments are indicated for moderate-to-severe psoriasis?

Phototherapy (narrow-band UVB) and systemic agents

What does the term 'excoriation' refer to in a clinical skin exam?

Skin abrasions or sores produced by scratching

When might antibiotics be used in patients with atopic dermatitis?

In cases where patient develops a secondary infection