5. Inflammatory dermatoses

Question 1

Outline the arrangement of the layers of the skin (skin miroanatomy)

Answer 1

• Superficial layer of the skin is the epidermis which sits on a layer of basement membrane
• Below this is the dermis followed by fat, then fascia and muscle

Question 2

What structures can be found in the dermis? What is the dermis made of?

Answer 2

• Within the dermis there are adnexal structures such as the hair follicles, sebaceous glands etc.
• Sweat glands are also found in the dermis – eccrine sweat glands are found all across the body whereas apocrine sweat glands are just in the axilla and the groin and produce a more viscous, smelly sweat
• The rest of the dermis is made of collagen, elastin, connective tissue, fibroblasts and immune cells
○ Most of the cells of the dermis are fibroblasts

Question 3

What is a pilosebaceous unit made of?

Answer 3

The hair follicle, sebaceous gland and the arrector pili muscle are together known as a pilosebaceous unit

Question 4

What is sebum? What is its function and what is it produced by?

Answer 4

This is an oil that lubricates the hair and produces chemicals that suppress the growth of bacteria and fungi
Produced by sebaceous glands

Question 5

What are the 5 layers of the epidermis?

Answer 5

'Come let's get sun burnt'
    ○ Stratum corneum
	○ Stratum lucidum
	○ Stratum granulosum
	○ Stratum spinosum
	○ Stratum basale
The top layer is the stratum corneum - a layer of differentiated keratinocytes that have lost their nuclei and mainly consist of keratin. It forms the barrier function of the skin
The basal layer of keratinocytes is resting on the basement membrane

Question 6

How do new cells replace the old cells of the epidermis?

Answer 6

The keratinocytes proliferate and as they move up through the layers of the epidermis, they differentiate and eventually end up in the stratum corneum

Question 7

What are the main cell types of the epidermis?

Answer 7

○ Keratinocytes
○ Melanocytes - sit on the basement membrane and produce melanin
○ Langerhans cells - APCs found within the epidermis
○ Merkel cells - involved in sensation

Question 8

Outline the structure of the stratum corneum

Answer 8

• Under the epidermis, there are blocks of keratinocytes that act as a barrier
• Between the keratinocytes there is a glue made up of lipids and proteins which helps to form the barrier
• Filagrin is one of the proteins that helps to hold the keratinocytes together

Question 9

What are the signs of having a filagrin mutation?

Answer 9

10% of the population have a mutation in the gene that produces filagrin. Their skin is more dry and they are more likely to have eczema
One of the signs of having a filagrin gene mutation is having palmar hyperlinearity. This is when there are many lines across the palm that are all criss crossing

Question 10

What are some examples of atopic disease and what do they all have in common?

Answer 10

Atopic – tendency to develop hypersensitivity/allergies

Examples of atopic diseases include eczema, asthma and hay fever – they are all immunologically related

Question 11

What happens in atopic eczema?

Answer 11

• There is a defective barrier formation of the skin
• This allows the penetration of allergens such as house dust mites or irritants and pathogens which are taken into the skin and are taken up by APCs.
• CD4 lymphocytes are activated causing a T helper 2 type response where other T cells are recruited – Ig E is produced which stimulates mast cells to degranulate and an inflammatory response occurs

Question 12

What is the difference in the mechanisms of acute and chronic atopic eczema?

Answer 12

If atopic eczema goes from acute to chronic then there is a shift towards a T helper type 1 response rather than Th2

Question 13

Outline the concept of the atopic march

Answer 13

People who have atopic diseases tend to develop eczema first (in their first year of life) followed by food allergies, followed by asthma later on and rhinitis or hay fever even further on
What is probably happening is that the eczema is making them more sensitised to environmental allergens which then manifests as these other atopic diseases later on in their life

Question 14

What can eczema be classed as?

Answer 14

Acute, subacute or chronic

Question 15

How would infant atopic eczema present?

Answer 15

In babies it is present in areas that they can easily rub such as the face which causes exacerbation of the inflammation
They are also more likely to have food allergies because eczema around the mouth would cause food allergens to enter

Question 16

How does the pattern if infant atopic eczema change as they grow older?

Answer 16

It remains on the face, but as the child gets older, it particularly affects the antecubital fossa, the popliteal fossa, hands, face and neck (flexural areas, and areas where there is build up of sweat).

Question 17

What is the difference in appearance of acute and chronic eczema?

Answer 17

• Acute eczema is very red and may be slightly blistery and sore (often colonised with bacteria)
• Chronic eczema will change its appearance to look less red and more skin coloured – it will appear excoriated and lichenified
• Lichenification: the skin looks thickened and there is accentuation of the skin lines.

Question 18

What is erythrodermic eczema?

Answer 18

If the eczema is widespread (affecting more than 90% of the body surface), it is erythrodermic

Question 19

How can eczema worsen?

Answer 19

• Often, there is colonisation of the skin with staphylococcus aureus
• S. aureus acts as a super antigen which activates the eczema causing worsening of eczema
• This is treated with antibiotics (colonisation), emollients, topical and oral steroids

Question 20

What is Eczema Herpeticum and how is it treated?

Answer 20

• Because the barrier function is defective, certain viruses can proliferate and spread on the skin
• Eczema herpeticum: the herpes simplex virus has proliferated on the surface of the skin
• Patients with this can become very unwell – it can progress to encephalitis causing brain damage & death
• The patient will need to be admitted to hospital and given medicine (acyclovir)

Question 21

List 3 other types of eczema

Answer 21

• Seborrhoeic – overgrowth of yeast along with eczema
• Allergic contact dermatitis
• Discoid

Question 22

What is Seborrhoeic eczema and how does it present?

Answer 22

• This is the same as dandruff. Mild seborrhoeic eczema dermatitis affecting JUST the scalp is DANDRUFF. However, this can affect the face, in which case we see poorly defined areas of redness and greasy, scaly skin.
• The main sites affected are the nasolabial folds, eyebrows, forehead, within the beard area, the chest and back. This is not itchy (generally), but can be sore.

Question 23

What are the causes of seborrhoeic eczema?

Answer 23

Caused by an overgrowth of naturally occurring yeast on the skin, along with a reaction to this.

Question 24

How can seborrhoeic eczema be treated? What makes it better/worse?

Answer 24

• It can be treated with anti-dandruff/anti-fungal shampoo, antifungal cream and topical steroids
• This gets worse in times of stress, staying up late or drinking too much alcohol
• It improves when the patient is not stressed, sleeps well, is exposed to sun and goes on holiday

Question 25

What is allergic contact dermatitis?

Answer 25

In allergic contact dermatitis, patients are very allergic to certain allergens when they come into contact with the skin.

Question 26

What increases the possibility of getting allergic contact dermatitis?

Answer 26

Patients with atopic eczema are more likely to acquire allergic contact dermatitis. Often, in atopic eczema, patients are sensitised to a number of different allergens in the environment.

Question 27

What is Discoid eczema? What are its causes and treatment?

Answer 27

• It occurs in discoid areas (often on the legs, but can be anywhere
• Each individual disc looks like eczema
• But the intervening skin may look normal
• The cause of this is often just dry skin with secondary dermatitis
• Treatment involves:
○ Emollient use
○ Topical steroid
○ Avoidance of soap/shower gel

Question 28

What is psoriasis?

Answer 28

• Psoriasis is another inflammatory dermatoses, in which patients present with psoriatic plaques.
• The characteristics of these is that they are salmon pink with a scaly layer on them and they are well defined

Question 29

What causes psoriasis and what is the mechanism behind it?

Answer 29

• Psoriasis is a genetic condition, but it is polygenetic – a number of different genes can cause it. 15-20% of patients have a family history of psoriasis.
• Psoriasis can also have an environmental trigger as well as genetic susceptibility. This may include an infection, stress or certain drugs.
• T cells in the dermis will stimulate a cytokine release, especially releasing TNFa which leads to neutrophils going to the epidermis causing an overproduction of keratinocytes
• This leads to thickening of the epidermis which is seen as psoriasis

Question 30

Outline the pathology of psoriasis

Answer 30

• The epidermis becomes thicker – this is called acanthosis
• The stratum corneum also becomes thicker – this is hyperkeratosis
• The individual cells in the stratum corneum are not losing their nuclei – this is parakeratosis
• There is an influx of neutrophils within the epidermis (this can form pustules) - inflammation
• There’s dilatation of blood vessels in the dermis leading to redness
• There are lymphocytes within the dermis
• This immune reaction is being driven by lymphocytes and excess cytokines/TNF-alpha

Question 31

How is psoriasis distributed?

Answer 31

• Psoriasis is commonly seen at the scalp, elbows, knees, and genital areas, around the umbilicus and at the natal cleft of the buttocks. It is also seen on the hands and feet.
• Psoriasis is also a very symmetrical condition (this is one of the ways you can distinguish it from fungal infections). It can be triggered by pressure and trauma to areas of skin which is why it can occur on the soles of the feet

Question 32

What are the nail signs of psoriasis?

Answer 32

○ Subungal hyperkeratosis – build-up of keratin below the nail
○ Dystophic nail (roughening) and loss of cuticle
○ Onycholysis – the nail lifts up from the nail bed
○ Pitting – small bumps in the nail
NOTE:nail signs also occur in a fungal infection but they are only 1-3 nails that are affected. In psoriasis it is most/all of the nails that are affected

Question 33

What is Guttate psoriasis? How would it be diagnosed and treated?

Answer 33

• Lots of little, raindrop like lesions on the skin
• This generally affects young people (teenagers), and can occur after a streptococcal infection or sore throat
• We can treat the patient with antibiotics and topical steroids to clear the psoriasis
• Look for signs of streptococcal infection such as doing a throat swab, blood test etc before you treat with ab

Question 34

What is Palmoplantar psoriasis?

Answer 34

This is where, instead of plaques forming on the body, pustules form on the palms of the hands and soles of the feet. The patients are otherwise well, however this can be itchy and sore.

Question 35

What is Generalised pustular psoriasis?

Answer 35

• The patient not only gets plaques but also get small white pustules on top of the inflamed skin
• Here, the condition makes patients very unwell. They are febrile and toxic. They have a high HR, and low BP. They are so unwell that they cannot function.
• They require hospital admission and are treated with immunosuppressants. Patients are also given emollients and topical steroid treatment. This condition is rare, but without treatment, mortality rate is high.

Question 36

What are the causes of pustules?

Answer 36

Infection
Psoriasis
Drug reactions

Question 37

What is acne and what is it caused by?

Answer 37

Acne is a disease of the pilosebaceous unit. It can occur at any age, but normally occurs at the onset of puberty, in teenagers and young adults. It is driven by hormones (androgenic stimulation causes hypertrophy of sebaceous glands so an excess production of sebum). There are both genetic and hormonal factors which cause acne

Question 38

How is a blackhead formed? How is this different to a whitehead?

Answer 38

There is a build-up of dead cells, and hyperkeratinisation (thickening of the infundibulum of the hair follicle). This forms a blackhead. A whitehead is the same as a blackhead, but it is covered with skin, so it can’t be seen.

Question 39

What are the steps in acne formation?

Answer 39

○ Comedone formation - This is caused by hyperkeratinisation of the infundibulum of the follicle
○ Excess sebum production – due to androgen stimulation
○ Secondary overgrowth of a bacteria (propionibacteria acnes) within the follicle
○ The follicle gets secondarily inflamed, and may rupture releasing products of inflammation in dermis

Question 40

What are the clinical features of acne?

Answer 40

• Blackheads (open comedones) – built up of keratin in the hair follicle pore
• Whiteheads (closed comedones) - blackheads with skin
• Inflammatory lesions – papules, pustules and nodules
  
  • As the lesions heal, it can heal with scarring
  • The areas affected are the areas where sebaceous glands predominant (face, neck, upper chest)

Question 41

What is the treatment of acne?

Answer 41

• Start off with topicals – benzoyl peroxide and topical antibiotics (erythromycin, clindamycin)
• Oral antibiotics – these have anti-inflammatory effects as well. In females you can use the contraceptive pill

Question 42

What is Bullous pemphigoid and what is the mechanism behind it?

Answer 42

• Autoimmune condition where an autoantibody is made against a component of the basement membrane causing the BM to split and blisters to form
• The condition begins with a rash (looks like eczema), followed by the development of blisters. The blisters progress, and without treatment, they become infected. Patients can then die from sepsis.
• In bullous pemphigoid, two proteins are involved (BPAg 1 and BPAg 2). They are the targets of autoantibodies.

Question 43

Where is the basement membrane situated and how are these structures embryologically developed?

Answer 43

Embryologically, the epidermis is derived from the ectoderm, and the dermis is derived from the mesoderm. The two are stuck together with a number of proteins. There are proteins that stick the epidermis on to the basement membrane (tonofilaments), and basement membrane on to the dermis (anchoring fibrils)

Question 44

Outline the pathology of bullous pemphigoid

Answer 44

• The BPAg proteins are located on the basement membrane
• The disease causes inflammation at the BM zone, and splitting of the epidermis from the dermis
• This is a deep blister, where the deep blister split is at the location of the basement membrane
• Treatment: high dose oral steroids, and other immunosuppressant drugs (methotrexate)
• Treatment must be maintained for a number of years, before the illness burns out

Question 45

What is Pemphigus vulgaris and how does it differ from bullous pemphigoid?

Answer 45

• In bullous pemphigoid, the blisters are deep
• In pemphigus, the blisters are superficial. There is an auto-antibody, but this time it is directed at a component of the hemidesmosomes (desmoglein 1 and 3) within the epidermis.
• It causes blisters, but these are much more superficial. Because of this, they break down and flake off causing erosion of the skin.

Question 46

What are desmosomes?

Answer 46

The connections between keratinocytes that holds them together

Question 47

What is the pathology behind pemphigus vulgaris?

Answer 47

• The antibodies are targeting around the keratinocytes, forming a meshwork patterns
• The split is within the epidermis – THIS IS CALLED ACANTHOLYSIS – splitting within the epidermis
• The progress of PV is similar to BP – it gets worse without treatment and can result in sepsis
• With modern treatments (oral steroids, immunosuppressants), this gets better
• Patients can live a relatively normal life afterwards