Dermatology Flashcards
1
Q
What is the skin-gut axis?
A
Due to the skin and gut having the same homing factors, there is a strong immunological connection between them
2
Q
What are examples of the skin-gut axis? (2)
A
- Food allergies that cause dermatological symptoms
- IBD causes dermatological symptoms
3
Q
How many % of IBD patients has erythema nodosum?
A
15%
4
Q
What are the main skin functions? (6)
A
- Protection & defence
- Signal reception
- Thermoregulation
- Communication
- Secretion
- Absorption
5
Q
In which ways is the skin involved in protection and defence? (2)
A
- Mechanical
- Immunological
6
Q
In which ways is the skin involved in signal reception? (4)
A
- Tactile
- Pressure
- Temperature
- Pain
7
Q
In which ways is the skin involved in thermoregulation? (2)
A
- Sweating
- Vasoconstriction & dilatation
8
Q
In which ways is the skin involved in communication? (2)
A
- Skin tint
- Odor
9
Q
Which substances are secreted by the skin? (3)
A
- Sweat
- Sebum
- Milk
10
Q
What does the skin absorb? (2)
A
- Light
- Pharmaceuticals
11
Q
What are the three layers of the skin?
A
- Epidermis
- Dermis
- Hypodermis
12
Q
What structures can be found in the dermis? (6)
A
- Connective tissue
- Fibroblasts
- Hair follicles
- Sweat glands
- Sebaceous glands
- Vasculature
13
Q
What structures can be found in the hypodermis? (2)
A
- Blood vessels
- Adipocytes
14
Q
Which 5 layers of keratinocytes can be found in the dermis (basal to apical)?
A
- Stratum basale
- Stratum spinosum
- Stratum granulosum
- Stratum lucidum
- Stratum corneum
15
Q
Which cells populate the stratum basale? (4)
A
- Basal cells
- Keratinocyte precursors
- Merkel cells
- Melanocytes
16
Q
What is the function of Merkel cells?
A
Touch sensation
17
Q
What is the function of melanocytes?
A
Melanin production
18
Q
Why does the stratum spinosum appear spiny?
A
Due to the presence of desmosomes joining the cells
19
Q
What is the main function of keratin in the epidermis?
A
Prevention of water loss
20
Q
Where are the Langerhans cells of the skin found?
A
In the stratum spinosum of the epidermis
21
Q
What is the appearance of keratinocytes in the stratum granulosum?
A
Flattened with high levels of keratin present, thickened membrane
22
Q
What is the stratum lucidum made up of? What is its function?
A
Keratinocytes filled with protein (eleidin), as an extra protection against abrasion
23
Q
In which type of skin is the stratum lucidum present?
A
Thick skin
24
Q
What is the stratum corneum made out of?
A
Dead, anuclear keratinocytes
25
What is the function of the stratum corneum?
Protection against microbes, dehydration & abrasion
26
By which process are the anuclear keratinocytes in the stratum corneum produced?
Specialized form of programmed cell death, in which nucleus and organelles disintegrate
27
Why do hair follicles form an area of close contact between microbiota and keratinocytes?
They are not keratinized
28
Where can thick skin be found?
Hairless skin on the soles of feet and palms/fingertips of the hand
29
What are the properties of thick skin? (4)
1. Contains no sweat/sebaceous glands
2. Thick stratum corneum
3. Stratum lucidum visible due to presence of eleidin
4. Dermis thinner than thin skin dermis
30
What are the properties of thin skin? (3)
1. Follicles & glands are non-keratinized
2. Thin epidermis due to a thin stratum corneum and absence of the stratum lucidum
3. Thick dermis
31
How do keratinocytes adhere to the basal membrane?
Hemidesmosomes
32
Which kinds of fibres can be found in hemidesmosomes? (2)
Collagen & integrins
33
Between which layers is the basal membrane of the skin located?
Epidermis & dermis
34
Which kinds of fibres can be found in the basal membrane of the skin? (3)
1. Type IV collagen
2. Laminin
3. Proteoglycans
35
How are keratinocytes interconnected?
Through desmosomes
36
How are desmosomes made up?
Extracellular cadherins are connected to intracellular keratin fibres
37
Of which structures the epidermal tight junctions made up? (3)
Claudin, JAM and occludin
38
What is the size limit for passive uptake through the skin? How can larger molecules be taken up?
<500 Da
Larger molecules can be taken up through active uptake via cytoplasm
39
True or false: keratin in the skin is the same throughout all layers
False; there are multiple types of keratin that are specific to specific layers/cell types
40
How are keratin fibres made up structurally?
Heterodimers of keratin filaments
41
What are the functions of keratin in the skin? (2)
1. Barrer integrity by interacting with keratinocytes
2. Aid in metabolic functions
42
When is regulation of keratin expression disrupted?
Disruption of homeostasis
43
Where is skin pigmentation produced?
By melanocytes in the stratum basale
44
What is the embryonic origin of melanocytes?
Neural crest -> differs from skin, which is derived from the ectoderm
45
What are the functions of melanocytes? (2)
1. Pigmentation
2. Thermoregulation
46
How does melanin end up in keratinocytes? When is it transported intracellularly by keratinocytes?
It is exocytosed by melanocytes in melanosomes, which are absorbed by keratinocytes. Exposure of keratinocytes to UV-light causes them to relocate to the top of their nucleus to shield if from UV.
47
What induces production of melanin by melanocytes?
UV light
48
In which type of skin are Merkel cells especially present?
Thick skin
49
Which two rough layers can be distinguished in the dermis?
1. Papillary dermis
2. Reticular dermis
50
What are the properties of the papillary dermis? What kind of connective is present?
Superficial layer, invading deep into the dermis, made up out of loose and highly vascular connective tissue
51
What are the properties of the reticular dermis? What kind of connective tissue is present?
Deep layer forming the bulk of the dermis, made up out of dense connective tissue
52
Which cells can be found in the dermis? (5)
1. Fibroblasts
2. Macrophages
3. Dermal DCs
4. Mast cells
5. Adaptive immune cells
53
Which ECM components are highly abundant in the dermis? (2)
1. Collagen
2. Elastin
54
How many layers of blood vessels can be discerned in the dermis? What kind of vessels do they contain?
1. Superficial of the papillary dermis, containing capillaries
2. Middle layer, containing arterioles, venules and lymphatics
3. Deep layer, containing arteries and veins
55
In which homeostatic processes is skin vasculature important? (3)
1. Thermoregulation
2. Immune surveillance
3. Transport of nutrients and paracrine factors
56
What are the first immune barriers of the skin?
Physical barriers
57
The physical barriers of the skin are an active barrier. Why?
They are formed by an interplay between microbiota, keratinocytes, fibroblasts, adipocyes, Langerhans cells, dermal DCs and ILCs
58
How do skin-resident microbiota deter pathogens? (2)
1. Production of AMPs
2. Interaction with keratinocytes and dermal immune cells, shaping homeostatic immune cell function of the skin
59
What are the functions of fibroblasts in skin immunity? (2)
1. Express a wide range of TLRs, allowing them to detect pathogens and produce AMPs and cytokines
2. Attraction of immune cells & modulation of their functions
60
How do fibroblasts produce IL-1β?
Through their NLRP3 inflammatsome
61
What are Langerhans cells?
DCs that populate the dermis
62
What are Langerhans cell markers? (2)
CD1a/c & CD207
63
How are Langerhans cells replaced under physiological vs. pathogical conditions?
They are self-renewing under physiological conditions, but can be repopulated by moDCs in case of homeostasis disruption
64
Where are the cell bodies and where are the dendrites of Langerhans cells located?
Cell body: stratum spinosum
Dendrites stretch into the stratum corneum
65
Langerhans cells are more closely related to [DCs/macrophages]. Why? (3)
Macrophages, because they have macrophage-like characteristics:
1. Embryonic origin
2. Self-renewing population
3. Requires tissue-derived signals
66
Which tissue-derived signals are required for correct Langerhans cell function?
TGF-β
67
What do Langerhans cells do after sensing antigen? What happens in physiological/pathogenic circumstances?
Migrate to LN to interact with T-cells
Physiological circumstances: induction of Tregs through release of IL-10
Pathogenic conditions: induction of inflammatory cytokines
68
Which intracellular pathway is upregulated by keratinocytes in inflammation? What does this lead to?
STAT3-signaling is upregulated, leading to IL-23 production by LCs -> Th17-response induced
69
How do Langerhans cells migrate out of the skin?
Through lymphatic vessels in the deeper dermis
70
The majority of the cells in the dermis are [mesenchymal cells/leukocytes]
Leukocytes -> 70% of the cells in the dermis are leukocytes
71
What is the largest population of leukocytes in the dermis? How many % of total leukocytes?
Macrophages (~55%)
72
How many % of cells in the dermis are non-phagocytes? Which cell types does this concern? (3)
5%, consisting of:
1. T-cells
2. ILCs
3. Mast cells
73
Which three populations of phagocytes can be identified in the skin?
1. Macrophages
2. CD14+ DCs
3. CD1a+ DCs
74
What are the characteristics of macrophages in the skin? (2)
1. No migration upon stimulus
2. High phagocytic capacity
75
What are the characteristics of CD14+ DCs of the skin? (2)
1. Migration can be induced
2. Phagocytic capacity lower than macrophages
76
What are the characteristics of CD1a+ DCs of the skin? (2)
1. Migration can be induced
2. Phagocytic capacity lower than macrophages
77
How do APCs interact with the PNS?
PNS produces factors that influence moDC function (immune regulatory)
78
Which neurotransmitter is released by the PNS to intact with APCs?
CGRP
79
What are the homeostatic functions of dermal mast cells? (2)
1. Induction of differentiation & proliferation of immune cells, keratinocytes & fibroblasts
2. Mediation of vasodilatation & constriction
80
Mast cells are involved in the defence against many types of pathogens. Against which types, and is their function benefical or detrimental? (3)
1. Antibacterial = benefical
2. Antiviral = mixed beneficial/detrimental
3. Antiparasitic = mixed beneficial/detrimental
81
What are the antibacterial functions of dermal DCs? (2)
1. Direct killing of bacteria through NETs, AMPs & phagocytosis
2. Recruitment of neutrophils
82
What are the benefical (2) and detrimental (2) effects of mast cells in case of viral infection?
Beneficial:
1. Inhibition of viral replication of several viruses
2. Recruitment of NK-cells & T-cells
Detrimental:
1. Mast cells can be infected by viruses, faciltating viral migration
2. Degranulation can result in viraemia
83
What are the beneficial (3) and detrimental (1) effects of mast cells in case of parasitic infection?
Beneficial:
1. Direct killing of parasites through NO-production
2. Killing of parasites through extracellular traps
3. Recruitment and activation of DCs
Detrimental: cause vascular leakage -> allows parasites to spread
84
What are the types of ILC present in the skin?
ILC1, ILC2, ILC3
85
What is the signature transcription factor of ILC1s?
T-bet
86
What is the signature transcription factor of ILC2s?
Gata3
87
What is the signature transcription factor of ILC3s?
RORγT
88
Which two markers are expressed by dermal ILCs?
1. CCR6
2. CCR10
89
What are the functions of CCR6 on dermal ILCs? (2)
1. Facilitation of barrier function
2. Facilitation of microbiome homeostasis
90
What are the functions of CCR10 on dermal ILCs?
Facilitation of effector and regulatory T-cell homeostasis
91
Which cytokines do dermal ILC2s produce? (2)
IL-5, IL-13
92
In which physiological (2) and pathological (1) processes are ILC2s involved?
Physiological: tissue repair & barrier integrity
Pathological: progression of atopic inflammation
93
Which cytokines do dermal ILC1s produce? (2)
IFN-γ, TNF
94
In which pathological processes are ILC1s involved?
Contact hypersensitivity
95
Which cytokines do dermal ILC3s produce? (2)
IL-17, IL-22
96
In which pathological processes are ILC3s involved?
Psoriatic inflammation
97
Which micro-organisms make up the skin microbiome?
Bacteria, viruses, fungi
98
The skin virome is largely [site-dependent/host-dependent]
Host-dependent -> differs from person to person
99
The skin microbiome (bacteria) is largely [site-dependent/host-dependent]
Site-dependent
100
In which ways do commensal microbiota play an important role in shaping host immune responses? (2)
1. Induction of a TLR2 response in keratinocytes, resulting in steady-state production of AMPs
2. Interaction with DCs, shaping adaptive immune responses
101
To which bacterium does the immune system never develop tolerance?
S. aureus
102
S. aureus causes keratinocytes to produce IL-1 and other cytokines, resulting in: (3)
1. Production of AMPs by keratinocytes
2. Attraction of neutrophils
3. NK- and γδ-T activation
103
How big are antimicrobial peptides?
15-50 amino aicds
104
What are two important families of AMPs produced in the skin?
1. Defensins
2. Cathelicidins
105
By which cell type are cathelicidins produced?
Adipocytes
106
What are mechanisms of action of AMPs? (2)
1. Creating holes in bacterial walls
2. Sequestering of Fe
107
In psoriatic skin, the production of AMPs is [increased/decreased]. Therefore, psoriatic skin contains [low numbers of bacteria/high numbers of bacteria]
Increased -> psoriatic skin contains low numbers of bacteria
108
In atopic dermatitis, the production of AMPs is [increased/decreased]. Therefore, atopic skin contains [low numbers of bacteria/high numbers of bacteria]
Decreased -> atopic skin contains high numbers of bacteria, increasing the risk of bacterial infection
109
Which T-cell subsets can be found in the skin? (4)
1. Th1
2. Th2
3. Th3
4. Treg
110
Which cytokines induce Th1 cells? (4)
1. IL-27
2. IL-12
3. IL-18
4. IFN-γ
111
What is the signature transcription factor of Th1-cells?
T-bet
112
What are the major cytokines produced by Th1-cells? (4)
1. IFN-γ
2. IL-2
3. IL-10
4. TNF-α
113
What is the physiological function of Th1-cells?
Defence against intracellular micro-organisms
114
Which cytokine induces Th2-cells?
IL-4
115
What is the signature transcription factor of Th2-cells?
Gata3
116
What are the major cytokines produced by Th2-cells? (6)
1. IL-4
2. IL-5
3. IL-9
4. IL-10
5. IL-13
6. IL-25
117
What is the physiological function of Th2-cells?
Defence against parasitic infections
118
Which cytokines induce Th17-cells? (3)
1. IL-1
2. IL-6
3. TGF-β
119
What is the signature transcription factor of Th17-cells?
RORγT
120
What are the major cytokines produced by Th17-cells? (3)
1. IL-17 (A/F)
2. IL-21
3. IL-22
121
What is the physiological function of Th17-cells?
Defence against extracellular bacteria & fungi
122
Which cytokines induce Tregs? (2)
1. IL-2
2. TGF-β
123
What is the signature transcription factor of Tregs?
FoxP3
124
What are the major cytokines produced by Tregs? (3)
1. IL-10
2. TGF-β
3. IL-35
125
What is the physiological function of Tregs?
Tolerance & suppression of auto-immunity, auto-inflammation & allergy
126
Which Th-subsets are inhibited by Th1?
Th2, Th17
127
Which Th-subsets are inhibited by Th2?
Th1, Th17
128
Which Th-subsets are inhibited by Tregs?
Th1, Th2, Th17 (all subsets)
129
Which Th-subsets are inhibited by Th17?
None
130
What is meant when we talk about plasticity when it comes to Th-subsets?
Capacity to produce cytokines of another subset (but not a complete switch to another subset)
131
What is the term for a complete switch of a Th-cell from one subset to another?
Transdifferentiation
132
What are the histopathologic features of psioriasis? (6)
1. Acanthosis
2. Hyperkeratosis
3. Parakeratosis
4. Papillomatosis
5. Hypogranulosis
6. Influx of immune cells
133
What is acanthosis?
Thickening of the skin
134
What is hyperkeratosis?
Increased proliferation of keratinocytes, leading to increased shedding of skin
135
What is parakeratosis?
Retention of nucleated keratinocytes in the stratum corneum (normally these are all anuclear)
136
What is papillomatosis?
Elongation of rete ridges -> elongation of the epidermis into the papillary dermis
137
What is hypogranulosis?
Loss of the stratum granulosum
138
Which immune cells can be seen to infiltrate the skin in histopathology of psoriasis? (2)
1. T-cells
2. Neutrophils
139
What do neutrophils in psoriatic skin form?
Munro's micro abcscesses
140
What causes psoriasis?
A combination of environmental factors & susceptibility genes
141
What happens during the initiation phase of psoriasis?
Pro-inflammatory crosstalk between injured/stressed keratinocytes, leading to release of nucleic acids and LL-37, which recruit various types of immune cells
142
Which cells are recruited by the pro-inflammatory crosstalk between keratinocytes in the initiation phase of psoriasis? (3) What is each of their effects?
1. Plasmacytoid DCs -> production of IFN-α
2. Activated dermal DCs -> travel to LN and activate Th1/Th17s
3. Inflammatory dDCs -> cause a local inflammatory environment
143
Which mediators do dDCs excrete in the initiation phase of psoriasis, creating a pro-inflammatory environment? (3)
1. IL-23
2. TNF
3. NO
144
What is the effect of the release of IL-23 released by dDCs during the initiation phase of psoriasis?
Activation of Th17/Tc17-cells
145
Which factors are produced by Th17-cells that have effects during the initiation phase of psoriasis? (2) What are their effects?
1. IL-17 -> promotes induction of T-cells and neutrophils
2. IL-22 -> induces epidermal hyperplasia by impairing keratinocyte terminal differentiation
Both also cause production of AMPs
146
Which cytokine axis is most important for psoriasis?
IL-23/IL-17 (=Th17)
147
How can knowledge of cytokines involved in psoriasis lead to treatments?
These can be targeted to block pathogenic processes
148
Which cytokines are being targeted in psoriasis treatments? (4)
1. IL-12
2. IL-23
3. TNF
4. IL-17A/F
149
What is the beneficial effect of IL-12 blocking in the treatment of psoriasis?
Downregulation of factors that promote Th1-cells
150
Which drug is used to block IL-12 in psoriasis? Which cytokine is also targeted by this drug, and why?
Ustekinumab, also targets IL-23 because IL-12 and IL-23 have a shared subunit
151
What is the beneficial effect of IL-23 blocking in the treatment of psoriasis?
Downregulation of factors that promote Th17-cells
152
Which drugs are used to block IL-23 in psoriasis? (4) Which of them also targets another cytokine?
1. Ustekinumab (also targets IL-12)
2. Guselkumab
3. Tildrakizumab
4. Risankizumab
153
What is the beneficial effect of TNF blocking in the treatment of psoriasis?
Downregulation of inflammation
154
Which drugs are used to block TNF in psoriasis? (3)
1. Etanercept
2. Infliximab
3. Adalimumab
155
What is the beneficial effect of IL-17A/F blocking in psoriasis?
Blocking of the effector cytokines of Th17-cells
156
Which drugs are used to block IL-17A signaling? (2) Which to block IL17-A/F signaling? (2)
IL-17A:
1. Secukinumab
2. Ixekizumab
Both IL17-A/F
1. Bimekizumab
2. Brodalumab (blocks IL-17R)
157
Targeting of which cytokine has proven to be especially effective in psoriasis? Why?
IL-17 -> leads to almost complete PASI reduction
158
How many % of patients don't respond to TNF, IL-12 and IL-23?
~20%
159
What is the main risk factor for atopic dermatitis?
Genetic susceptibility
160
Which gene has the strongest association with atopic dermatitis?
Filaggrin (FLG)
161
Genes involved in which functions can predispose for atopic dermatitis? (4)
1. Epidermal barrier
2. Environmental sensing
3. Immune regulation
4. Tissue response
162
What iniates atopic dermatitis?
Defective skin barrier, leading to permability -> triggers production of inflammatory cytokines
163
Which cytokines are involved in the initial phase atopic dermatitis? (4) Which type of reaction do they induce?
1. IL-1
2. TSLP
3. IL-25
4. IL-33
Induce a type II reaction
164
Which cells are recruited by the cytokines produced by keratinocytes in the initiation phase of atopic dermatitis? Which cytokines do they produce? (4)
Th2/Th22/ILC2, producing
1. IL-4
2. IL-5
3. IL-13
4. IL-31
165
What are the effects of the release of IL-4, IL-5, IL-13 and IL-31 in atopic dermatitis? (3)
1. Activation of mast cells & eosinophils
2. IL-31 drives itching
3. B-cell class switch to IgE
166
What is the effect of mast cells & eosinophils in atopic dermatitis?
Release of histamine, causing redness and itch
167
What are the stages of atopic dermatitis? (4)
1. Healty skin
2. Non-lesional skin
3. Acute lesional skin
4. Chronic lesional skin
168
What causes atopic dermatitis to progress?
Recruitment of additonal Th2-, Th22-, Th17- and Th1-cells, leading to a further loss of barrier function
169
Which two types of itch can be identified in atopic dermatitis?
1. Histamine-dependent itch
2. Histamine-independent itch
170
What is the mechanism of histamine-dependent itch?
Histamine activates processes in the brain through C-fibres
171
What is the mechanism of histamine-independent itch? Which cytokine is mainly responsible?
JAK-STAT pathways in neurons triggered, leading to itch-processes in the brain
Mainly caused by IL-31
172
Which groups of drugs are used in atopic diseases? Which are effective in atopic dermatitis? (7)
1. Anti-IL-4 = low effect in AD
2. Dual anti-IL-4/13 = effective in AD
3. Anti-IL-13
4. Anti-IL-5 = low effect in AD
5. Anti-IgE = low effect in AD
6. Corticosteroids = effective in AD
7. Antihistamines
173
What is the beneficial effect of blocking IL-4 in atopic disease?
Stops Th2 activation/differentiation
174
Which drugs can be used to block IL-4? (2) Are they used in atopic dermatitis?
1. Altrakincept
2. Pascolizumab
Development discontinued due to low effect
175
Which dual IL-4/IL-13 blocker is used against atopic diseases? What is its effect on AD?
Dupilumab -> very effective against atopic diseases, including AD
176
What is the beneficial effect of blocking IL-13 in atopic disease?
Inhibits B-cell class switch to IgE
177
Which drugs are used to block IL-13 in atopic disease? (2) In which circumstances are they effective?
1. Tralokinumab
2. Lebrikizumab -> effective in Th2-high subgroups of asthma
178
What is the beneficial effect of blocking IL-5 in atopic disease?
Reduces eosinophil recruitment
179
Which drugs are used to block IL-5 in atopic disease? (3) Are they effective agains AD?
1. Mepolizumab
2. Reslizumab
3. Benralizumab
Effective in asthma, not in AD
180
What is the beneficial effect of blocking IgE in atopic disease?
Lower triggering of mast cells
181
Which drug is used to block IgE in atopic disease? Is it effective in AD?
Omalizumab -> effective in allergic asthma, not in AD
182
What is the effect of corticosteroids in atopic disease?
Non-specific immmunosuppression -> effective against all atopic diseases
183
What is the downside of using corticosteroids for the treatment of atopic disease?
Toxic effects
184
Auto-inflammatory disease of the skin is [less/more] common than auto-immune disease of the skin
Less common -> auto-immune disease of the skin is more common than auto-inflammatory
185
What is a characteristic feature of all auto-inflammatory diseases?
Recurrent, generalized inflammation with episodic fever
186
What is the most prevalent auto-immune disease of the skin?
Atopic dermatitis
187
Why is the skin especially sensitive when it comes to sensations such as burning, itching, pain, etc.?
It contains high amounts of sensory neurons
188
What is often times a trigger of auto-immune/-inflammatory disease of the skin in susceptible individuals?
Damage to the skin, such as infection, wounds, etc.
189
True or false: most auto-immune or auto-inflammatory diseases of the skin are clearly fully adaptive (auto-immune) or innate (auto-inflammatory)
False; there are few 'pure' auto-immune/-inflammatory diseases -> most are mixed-pattern diseases
190
Which compartment of the immune system is dysregulated in auto-inflammatory disease? What are the predominant cell types? (3)
Innate compartment
1. Monocytes
2. Macrophages
3. Neutrophils
191
What is the pathogenesis of organ damage in auto-inflammatory disease?
Neutrophil/macrophage-mediated damage
192
Which compartment of the immune system is dysregulated in auto-immune disease? What are the predominant cell types? (2)
Adaptive compartment
1. T-cells
2. B-cells
193
What is the pathogenesis of organ damage in auto-immune disease?
Auto-antibody or auto-reactive T-cell mediated
194
How many auto-inflammatory diseases are currently known?
~110
195
True or false: auto-inflammatory disease is inherited
False; they can be inherited as well as acquired
196
Which treatments can be used for auto-inflammatory diseases? (4)
1. NSAIDs
2. Colchicine
3. Steroids
4. Biologicals interfering with pathogenic cytokines
197
Which four major groups of auto-inflammatory diseases can be identified? (4)
1. Inflammasomopathies and other disorders with abrrant IL-1 signaling
2. Type I interferonopathies
3. Disorders of NF-κB and/or aberrant TNF-activity
4. Diseases caused by other miscellaneous mechanisms
198
What is the most common auto-inflammatory disease?
Mediterranean fever
199
What is the difficulty in diagnosing Mediterranean fever?
Looks very similar to erysipelas = bacterial skin infection
200
What is the cause of Mediterranean fever?
TNF-receptor defects
201
Auto-inflammatory diseases form a risk for a specific group of diseases. Which group, and why?
Haematological diseases such as myelodysplastic syndrome and leukaemia, due to chronic stimulation of the bone marrow
202
Auto-inflammatory diseases can predispose for leukaemia. Why does this lead to particular difficulties in the clinical management of these diseases?
The sypmtoms of malignancy can overlap with auto-inflammatory symptoms -> hard to know whether you are dealing with auto-inflammation or leukaemia
203
What are mechanisms of neutrophil-induced damage in auto-inflammatory disease? (6)
1. Cytokine release
2. Phagocytosis
3. Oxidative burst
4. Ectodomain shedding
5. NETosis
6. Degranulation
204
Where do non-active neutrophils typically reside?
Bone marrow
205
Neutrophils in the blood follow a circadian rythm. How?
During the day, they are released by the bone marrow into the circulation. At night, they again home into the bone marrow.
206
How can disturbances in circadian rythm or stress cause exacerbation of auto-inflammatory disease?
Increased release of neutrophils from the bone marrow
207
What are the three main types of auto-immune disease of the skin?
1. Th1-mediated
2. Th2-mediated
3. Th17-mediated
208
What is the function of Th22-cells?
Repair of tissue damage caused by other Th-subsets
209
On which locations on the skin does psoriasis tend to occur? How is this for atopic dermatitis? What is the likely cause of this difference?
Psoriasis: outside of elbows/knees
Atopic dermatitis: inside of elbows/knees
Most likely caused by different microbiota in these locations
210
What can exacerbate psoriasis?
1. Injury
2. Infections
3. Drugs
211
Which drugs are notorious for causing psoriasis exacerbation? (2)
1. β-blockers
2. lithium
212
What are common comorbidities of psoriasis? (4)
1. Arthritis
2. Cardiovascular disease
3. Metabolic syndrome
4. Higher risk of depression & psychiatric disorders
213
How many % of psoriasis patients develop arthritis psoriatica?
~20%
214
What causes a higher risk of depression & psychiatric disorder in psoriasis patients?
IL-17
215
True or false: the severity of psoriasis correlates with the chance of comorbidities
True -> the more severe the psoriasis, the higher the chance of comorbidities
216
What is vitiligo?
Skin depigmentation disease caused by type II auto-immune disease attacking melanocytes
217
What is immune alopecia?
Hair loss due to immunological attack on hair follicles
218
Which cells are important in maintaining immune tolerance to hair follicles? Why is this tolerance needed?
Tregs -> tolerance needed to protect stem cells of the hair follicles from inflammation
