W24 Inflammatory skin conditions and treatment options (GN) Flashcards
What is Acne vulgaris?
Different manifestation forms? (2)
- Common chronic (or recurrent) skin condition
-Affects 80-90% of adolescents
-It affects the face, chest and back - Disease of the pilosebaceous unit
-hair follicle and the attached sebaceous glands - Triggered by androgen-induced sebum production
Different manifestation forms:
* non-inflammatory comedones - clogged skin follicles (blackheads and whiteheads),
* and inflammatory lesions (papules, pustules, nodules and cysts)
Pathophysiology of Acne Vulgaris
Onset of acnes
* During adolescence, increase in testosterone (androgen) production
* Genetic factors induce an Over production of 5α-reductase enzyme in the skin
- converting testosterone to dihydrotestosterone (DHT)
* DHT binds to receptors in sebaceous glands with higher affinity, leading to:
Effects:
* Hyperproliferation of follicular epidermis
* Abnormal keratinisation = accumulation of shed keratin
* Increased sebum production
Pathophysiology of Acne Vulgaris
NON-INFLAMMATION STAGE (STAGE 1)
- Keratin and sebum clog the hair follicles = microcomedone
- Blackheads (open comedones) = clog on the skin surface (air oxides sebum lipids and melanin) = becoming dark)
- Whitehead (closed comedomes) = below the skin surface = not exposed to air
- Further hyperkeratinization, and sebum production enlarge the follicle = microcomedone progresses into comedomes
Pathophysiology of Acne Vulgaris:
Inflammation and infection stages (2-4)
- The clogged follicle ruptures into the dermis = stimulating inflammation
- Sebum production stimulates the overgrowth of Cutibacterium acnes
- normal microbiota resident of hair follicles
- C. acnes digest sebum triglycerides releasing free fatty acids (pro-inflammatory) =
exacerbate inflammation and redness - Increasing inflammatory lesions
- Papule and pustule (superficial inflammation)
- Nodule or cyst (deeper inflammation)
What are the Severity degrees of Acne Vulgaris? (3)
What is scarring?
What are the aggravating factors? (4)
Mild= Few inflammatory lesions
Moderate= Many inflammatory papule/pustule lesions, no/few pseudocysts
Severe= Presence of distinct nodules/pseudocysts and scarring
Scarring
*-Fibrous process in which new collagen is laid down to heal large acne
-Can be avoided with early treatment
Aggravating factors (apart from genetics)
* High glycaemic food
* Cosmetics and facial massage
* A premenstrual flare-up
* Anxiety
Treatment of acne vulgaris – aims and options
What is the aim of treatment of acne?
What is used to treat acne?
Aims:
* Decrease the number of skin lesions and reduce the severity of the lesions or
complications (preventing scarring)
Options:
* Topical drugs are most commonly used
* Oral drugs = severe acne
* Benzoyl Peroxide - topical
* Retinoids – topical/oral
* Antibiotics - topical/oral
* Azelaic acid - topical
* Combined oral contraceptive
What are the desired therapeutic effects in the treatment of inflammatory skin conditions?
Inhibition of…(5)
- Follicular epidermal hyperproliferation
- Overgrowth of Cutibacterium acnes
- Overproduction of sebum
- Stimulation of inflammatory process (lesions of grade 2 or higher)
- Unclogging blocked pores/comedolytic (comedones)
Benzoyl Peroxide
- Alone in mild/moderate acne - different strengths (2.5 - 10%) - starting with the lowest
- Combination with adapalene – any acne severity
Mechanism of action / effects:
* Lipophilic = penetrates the epidermis layers = converted into benzoic acid and hydrogen peroxide
* Benzoic acid has comedolytic and anti-inflammatory effects
* Hydrogen peroxide has antibacterial properties (not an antibiotic) generating free
radical = oxidising bacterial components (growth inhibition) and free fatty acids
Adverse effects
* Bleaching effect on fabrics & hair
* It has mild keratolytic action, causing peeling of the skin and irritation
* Increase the risk of sunburn - avoid UV exposure
Retinoids
- Adapalene, tretinoin, isotretinoin (vitamin A analogues)
- Isotretinoin administered orally, for severe or unresponsive acne
Mechanism of action / effects:
* Penetrates the stratum corneum and slightly the dermis
* Interact with intracellular keratinocyte receptors = acts as transcription factor = modulating gene expression, leading to:
* Keratinisation normalisation
* Reduced sebum secretion
* Anti-inflammatory effect
* Comedolytic
Adverse effects
* teratogenic effect – avoid in pregnancy, breastfeeding
* UV light sensitivity
* skin peeling and irritation
* Isotretinoin toxicity – Monitoring needed
Topic/oral antibiotics
Topical:
* Clindamycin (Lincosamine) or Erythromycin (macrolide)
- Combined with topical retinoids or benzoyl peroxide
Oral antibiotics (moderate to severe acne)
* Lymecycline / doxycycline (Tetracyclines)
* Combined with topical retinoids or azelaic acid
* CONTRAINDICATED IN pregnancy
Mechanism of action / effects:
* Protein synthesis inhibition – targeting bacterial ribosomes
* Bacteriostatic effect
Azelaic Acid
* In combination with oral antibiotics (moderate/severe acne)
Mechanism of action / effects:
* normalising follicular keratinisation inhibiting the 5α-reductase enzyme
(reducing the conversion from cholesterol to DHT)
* Antimicrobial activity against C. acnes, likely interfering with the protein synthesis
* Modest anti-inflammatory effects decreasing the release of ROS from neutrophils
Adverse effects
* Low skin irritation
* Asthma exacerbation (i.e., dyspnoea, wheezing)
What is Psoriasis?
Clinical manifestations?
- Chronic inflammatory skin disease
- Immune-mediated^
- It is NOT communicable
Clinical manifestations
* Well-demarcated , erythematous plaques with silver scale appearance
* Epidermal thickening = plaques
* Red itchy patches clear borders (psoriatic plaques
* Can affect the skin in any area of the body
- Many forms of the disease; by far the most common is plaque psoriasis
^a condition that results from an abnormal immune system response
What is the pathophysiology of Psoriasis?
- Different factors stimulate an abnormal migration of T cells into the dermis
- T cells releases large amounts of inflammatory cytokines:
Overactivation of keratinocytes (by IL-17)
* Hyperproliferation
* Defective cell differentiation
* Accelerated keratinisation cycle (7 days)
* Release more pro-inflammatory cytokines
Sustain inflammation & immune dysregulation
* Abnormal immune cell infiltration in the skin
* Cytokines overexpression (IL-17, IL-23 & TNF-α)
* Chronic inflammation amplification, contributing to damage to the epidermis (different psoriasis forms)
* Formation of new capillaries closer to the surface.
Psoriasis:
- The crosstalk between keratinocytes and
immune cells is key in sustaining psoriasis - Cytokines could stimulate osteoclast precursor migration into the joints to destroy the joints (psoriatic arthritis)
Management of Psoriasis
Topical Treatments
* Emollients
* Vitamin D Preparations
* Corticosteroids
* Salicylic acid
* Coal Tar
* Dithranol
Phototherapy = next lectures
* UVB
* PUVA
Systemic Treatments
* Methotrexate
* Calcineurin inhibitor
(Ciclosporin)
Biologics
* Etanercept
* Efalizumab
* Infliximab
* Adalumimab
* Ustekinumab
* Secukinumab
* Ixekizumab
