Introduction Flashcards
What is characteristic of AD ?
- Chronic skin disorder
- Intense pruritis
- Disruption of skin barrier function(defective)
- Type 2 inflammation
(Increased Th2s and decreases Th1s)
So skin changes (hyperplasia/hyperkeratosis/spongiosis)
So immune changes (more Th2/less Th2s)
Which if these two is the primary driver?
…characterised by pruritic lesions on flexural surfaces but can be all over the body.”
AD Prevalence and QOL impact?
3-10% in adults; 20% in children (30% Australia)
Almost 1 in 2 develop AD in adulthood, and 7% having moderate and severe forms. And the overall prevalence rate has increased 2 to 3 fold in past decade.
Most have co-morbid atopic disorders.
High mental health disorders, a psychological burden and a social burden.
What are some examples of mental health disorders?
Mmmmm.
Natural Course of Disease?
Initially presents as intermittent flares, but leads to CONTINUOUS symptoms in Moderate to Severe forms, that necessitate treatments.
Chronic lesions - epidermal hyperplasia, prominent hyperkeratosis, minimal spongiosis
How do topical treatments have their limits ?
- Modest therapeutic window (mostly mild and some moderate level of severity).
- Intermittent use limitation, due to toxic effects.
Systemic therapies, particulary immunosuppressants, are more effective in advanced AD than topical Txs. Are these adequate for long term use?
Although generally more effective short term, the have
1) More Severe Toxic Effects.
2) Marked Rebound of Disease on Discontinuation. [How serious have you seen these rebounds?]
3) and limited to one agent here that had been approved- ciclosporin
Name the three key side effects of topical treatments.
Mmmmm
So, name the toxic effects of systemic immunosuppressants.
Mmmmm.
Give me an overview of the pathogenesis of AD.
Two interactive pathological features: A. Persistent Underlying Inflammation even in non-lesional skin. Amplified signalling of Th2 pathway. Constantly hyperactive immune system coupled with B. Weakened epidermal barrier structures and functions. The prominent driver of AD is the Th2 cytokines pathway and its downstream effects.
Additional pathways may well Th22-mediated processes.
Name the key cytokines in the Th2 pathway.
Interleukin (IL) -4
Interleukin (IL) -13
What do cytokines like IL-4 and IL-13 actually do ?
They are pro-inflammatory agents promoting 1) downregulation of AMPs and barrier function and integrity;
and 2) trigger inflammatory cells to the region of inflammation, infection and trauma. They are made in several immune cells not just CD4+ cells (Th2 cells), These include ILC2s, Mast Cells, Eosinophils, Basophils and Macrophages.
So Monoclonal Antibodies… why are they increasing in treatment popularity in different diseases?
Mmmmm.
So what if Dupixent is a fully human MAB… what if it wasn’t fully human?
Mmmmm.
So how does dupilimab basically work ?
It blocks Il-4 and IL-13 cytokines from binding to the key receptor responsible for the inflammatory cascade process…the Th2 pathway… at the IL-4Ralpha receptor. So, it Decreases cytokine-induced responses including Release of ProInfl cytokines, chemokines and IgE.
What is Type 2 Inflammation?
The primary mediators are IL 4. And IL 13
