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(ch18) Urticaria And Angioedema Flashcards

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1
Q

Which urticaria is more prevalent in men

A

M>F Delayed pressure urticaria

F>M chronic urticaria, dermatogrqphism and cold urticaria

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2
Q

Wheals vs angioedema

A

Wheals: superficial demis , pruritic and last<24h

Angioedema: deep dermis, subcut/submucosal , painful and last 2-3 days

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3
Q

Epidemiology of Urticaria
& What is the lifetime incidence or urticaria? Male or female?

A

Acute urticaria 20% of population
1% may develop chronic urticaria

1-5%. 2:1 female for chronic urticaria

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4
Q

Most common cause of urticaria in children?

A

Viral or idiopathic

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5
Q

Most common malignancy to cause urticaria

A

Lymphoma

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6
Q

what is unique about Skin and intestinal submucosa mast cells

A

Has neutral proteases tryptase and chymase (MCTC)

While other mast cells contain only tryptase

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7
Q

types of urticaria

A

1) Acute < 6 weeks
2) Chronic >6 weeks, ≥ 2x/w
3) Episodic >6w, <2x/w

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8
Q

Causes of acute urticaria

A

IUD Fack
Idiopathic (50%)
URTI (40%)
Drugs (9%)
Foods (1%)

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9
Q

Causes of Chronic urticaria

A

Ordinary”
Øphysical, Øvasc(60%) **
- autoimmune (30-50%)
- pseudoallergic (drug or food)
- infection-related
- idiopathic

Physical (35%)
- Mechanical: dermatographic, Delayed pressure, vibratory
- Temperature: heat or cold
- Sweating/stress: cholinergic, adrenergic, exercise
- Solar
- aquagenic

Vasculitis (5%)

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10
Q

Episodic urticaria causes

A

Contact
-immunologic: oral allergy syndrome, protein contact dermatitis
-non-immunologic

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11
Q

URTICARIAL SYNDROMES

A
  1. Hereditary Periodic fever syn
  2. Acquired auto-inflammatory syndromes
  3. Episodic angioedema with eosinophilia
  4. Systemic capillary leak syndrome
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12
Q

list Hereditary Periodic fever syns

A

1-Cryopryin-associated periodic syndromes (CAPS)

2- HyperIgD Syndrome(HIDS)

3-TNF-receptor-associated periodic syndrome(TRAPS)

4-Familial Mediterranean Fever

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13
Q

List Cryopryin-associated periodic syndromes (CAPS)

A

A. Muchkle-Wells
B. Familial cold autoinflammatory syndrome
C. Neonatal-onset multi-system inflammatory diseseases

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14
Q

List Acquired auto-inflammatory syndromes

A
  1. Schnitzler’s syndrome
  2. Adult-onset Still disease
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15
Q

what is the percentage of urticaria that will resolve within 1 year?

A

50% clear within a year and 20% persist for years (chronic)

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16
Q

mast cell degranulation stimuli

A
  1. Cross-linking of 2 or more adjacent FcεRI
    a- Allergen + IgE- FcεRI complex
    b- Anti- FcεRI Ab (IgG) + FcεRI
    c- Anti-IgE Ab (IgG    ) + IgE- FcεRI complex
  2. Non-immunologic stimuli
    - Substance P + receptor.
    - Stem cell factor + receptor.
    - C5a + receptor.
    - Codeine + receptor.
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17
Q

Mast cell mediators?
-Preformed

A

Preformed:
Histamine, Heparin,
tryptase/chymase
neutrophil chemotactic factor,
eosinophil chemotactic factor

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18
Q

Mast cell mediators?
-Newly formed

A

PGD2,
Leukotrienes B4,C4 D4, E4,
Platelet activating factor

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19
Q

Mast cell mediators?
-Cytokines

A

Can also be considered as performed:
TNFa,
IL-3, 4, 5, 6, 13
GM-CSF

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20
Q

which mediator inhibit mast cell?

A

Mast cell inhibitor = PGE2

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21
Q

what does histamine do?

A

vasodilation and increased permeability

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22
Q

C1 esterase inh function

A

Prevents spontaneous activation of classic complement pathway

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23
Q

C1 esterase inh function

A

CCC
1. Complement cascade – inhibits cleaving C1s & C4 🡪 Ø classic complement activation

  1. Coagulation cascade (extrinsic) – inhibits factor XIIa (Hageman factor) 🡪 Ø fibrin clot
  2. Contact cascade (intrinsic) - inhibits kallikrein 🡪 ↑ HMW kininogen/bradykinin 🡪 Ø endothelial activation

Deficiency results in low C1 and C4

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24
Q

risk factors of urticaria

A

Africian American

HAE

idiopathic angioedema

acquired C1 inh deficiency

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25
Autoimmune CSU Associated HLA?
HLA-DR4 HLA-DQ8
26
Autoimmune CSU Associated dis?
As/w other AI dis AI thyroid , Vitligo, RA, Celiac, pernicious anemia
27
Infections As/w CSU
H.pylori (remission with eradication) Strongyloidiasis
28
Urticaria etiologies/pathomechanisms
1. **Idiopathic** 2. **Immunologic** -Autoimmune -Allergic -Vasculitic -C1 esterase inhibitor deficiency 3. **Non-immunlogic** -Direct mast cell degranulators (e.g. opiates -Vasoactive stimuli -ASA, NSAIDs, dietary pseudoallergens -ACE-inhibitors
29
Most common physical urticaria?
Dermatographism - immediate Symptomatic subtype
30
familial vibratory urticaria gene?
ADGRE2
31
Reflex cold vs 1ry cold urticaria
-1ry after rewarming I can be diopathic > post-URTI, arthropod, HIV. - reflex: generalized cooling of body 🡪 widespread whealing
32
what food As/w food & Exercise induced anaphylaxis
α-gliadin in wheat
33
Solar and aquagenic urticaria duration
<1h
34
non-mmunologic contact urticaria mediator
PGD2 tx NSAIDs
35
what allergens cross react with Birch pollen?
Birch pollen x-react: kiwis, mangoes apples, apricots, almond
36
Gene mutation in HAE
SERPING1
37
which angioedema has low C1q
Acquired C1 inh deficiency
38
which complement can be low during attacks of HAE
C2
39
which HAE has normal levels
HAE, type 3 (estrogen dependent
40
Triggers of HAE
- trauma (emotional or physical) - estrogens
41
which type of HAE As/w facial angioedema distinguishing feature?
Hereditary Angioedema Type III (estrogen dependent
42
Drugs that can induce angiodema
ACEi (>NSAIDs or ASA), ?contrast
43
MOA of drug induced angiodema
inhibition of endogenous kininase II aka ACE that normal degrades bradykinin 🡪 ↑ bradykinin 🡪 orofacial life-threatening angioedema
44
drugs co administered with ACEi increase risk of Angiodema?
1) Black patients 2)ACEi+DDP4 inh(glipitins) 3)ACEi+sirolimus
45
which of periodic fever syndromes AD inheritance?
CAPS and TRAPs are AD HIDS and Familial Mediterranean fever are AR
46
how recurrent is fever in periodic fever syndromes?
Familial Mediterranean fever 1-3d HIDS 3-7d TRAPS >7d
47
which periodic fever syndromes has AA amyloidosis?
Muckle-Wells
48
gene mutations of periodic fevers?
1 .Familial Mediterranean fever-MEFV 2. HIDS- MVK 3. TRAPS- TNF-receptor 1 4. CAPS- NLRP3
49
which urticarial syndrome As/W IgG para proteinemia + IL2
Systemic capillary leak syndrome
50
which urticarial syndrome As/W elevated IL-5
Episodic angioedema with eosinophilia
51
Schnitzler syndrome diagnositc criteria
**Strasbourg criteria** urticarial vasculitis +Monoclonal IgM gammopathy and 2 of the following: Fever, arthralgias, HSM, ↑ESR, ↑WBC, bone abnormality, bone pain
52
Schnitzler syndrome responds to? tx
IL-1 blockade, e.g. anakinra
53
Acquired C1 inh deficiency As/w
B-cell lymphoproliferative d/o, plasma cell dyscrasias autoimmune CTD
54
ER tx of C1 Esterase Inhibitor Deficiency
- C1 inh concentrate 20 units/kg - FFP -Oral danazol - Oral tranexamic acid - Icatibant - Ecallantide
55
prophylactic tx for C1 Esterase Inhibitor Deficiency
C1 inh as prophylaxis 1 hr prior to surgery. Minor surgeries- oral tranexamic acid
56
Contraindicated tx in 1 Esterase Inhibitor Deficiency
OCP, hormone replacement
57
Mainstay tx for urticaria
H1 Antihistamines
58
Antihistamines safe in pregnancy and breastfeeding?
loratadine and cetirizine (cat B)
59
which H1 cause seizures in breastfeeding
hydroxyzine
60
which anti-h has both H1+H2
Doxepin (TCA) for can be good for cholinergic
61
Tx for DPU
- Sulfasalazine Avoid in Aspirin sensitivity - Dapsone (G6PD) -prednisone
62
biologic in urticaria
Omalizumab (humanized anti-IgE Ab)
63
tx fo urticarial vasculitis
Dapsone (neutrophilic vasculitis)( Ø G6PD) Colchicine (neutrophilic vasculitis)
64
what does elevated IgE give as prognosis in Omalizumab
↑IgE->early response & early relapse
65
which meds has risk of Arrythmia
mizolastine+ Erythromycin/ketoconazole Epi+ Doxepin/B-blockers
66
Mention two long lasting second generation H1 antihistamines
- Desloratadine - Fexofenadine
67
mention 5 subtypes of dermographism?
- Delayed - Cholinergic - Red - Associated with mastocytosis - Localized
68
9. how do you differentiate cholinergic from adrenergic urticarial?
- Adrenergic urticarial presents with a halo of vasoconstriction
69
mention 5 causes of angioedema with no urticarial and normal C4 level
- Capillary leak syndrome - Angioedema with eosinophilia - HAE III - Idiopathic - NSAID or ACE inhibitor induced
70
mention the provoking factors for cholinergic urticaria
o Physical exertion o Hot baths o Sudden emotional stress o Moving from cold to hot room o Drinking alcohol o Eating spicy food o occurs more frequently in patients with atopic diathesis
71
what is the mediator of angioedema?
- Bradykinin is the main mediator in angioedema
72
What is the effect of histamine on blood vessels?
Vasodilation and increased permeability Also histamine, TNF-a and IL-8 upregulate adhesion molecules on endothelial cells, promoting the migration of inflammatory cells from the blood to the urticarial lesion
73
What are the roles of basophils, neutrophils and eosinophils in urticaria?
Basophils: releasing histamine Eosinophils: generate LTC4, LTD4 and LTE4 and major basic protein) which can cause histamine release from basophils Neuts and lymphs: unknown
74
What is the role of aspirin?
Usually an aggravator of urticaria, but not often a cause
75
What are examples of urticaria that are mast-cell independant?
Some contact urticarias (eg. Sorbic acid) are due to prostaglandins The cryopyrin associated periodic syndromes (CAPS) are due to the inflammasome and its production of IL-1B
76
nonimmunologic contact urticaria causes?
Sorbic acid, Benzoic acid Cinnamic aldehyde
77
Which physical urticaria does not produce angioedema?
Dermographism. Angioedema can occur with all the other types
78
Which types often co-occur?
Dermographism + cholinergic urticaria C+C: Cold and cholinergic urticaria D+D: Delayed pressure urticaria and delayed dermographism
79
What is the definition of delayed dermographism?
Onset at least 30 minutes after stimulus
80
What are possible associations with primary cold urticaria?
After respiratory infections, insect bites or HIV infection
81
primary cold urticaria test?
Test with ice cube test negative in reflex urticaria
82
causes of secondary cold urticaria?
Cryoglobulinemia, cryofibrinogenemia with underlying causes of hep B/C, lymphoproliferative or EBV
83
What is exercise-induced anaphylaxis?
Angioedema +/- anaphylaxis with exercise, but not with increase in core temperature produced by other means (eg bath) Need to differentiate from cholinergic urticaria and from food-and-excercise induced anaphylasis
84
What are causes of immunologic contact urticaria?
IgE mediated Grass, animals, food, latex.
85
How do you test for cholinergic urticaria?
Exercise until you sweat or sitting in a hot water bath for 10 minutes at 42C
86
How do you test for delayed pressure urticaria?
Apply a 2.5kg weight to the back or thigh for 20 minutes
87
What first generation antihistamine is safest in pregnancy?
Chlorpheniramine
88
What are the main AE of 1st gen?
Sedation and anticholinergic effects
89
What are possible drug interactions? CYP3A4 (cardiac arythmias):
erythromycin, ketoconazole, cimetidine, cyclosporine
90
What is the proposed advantage of the low-pseudoallergen diet?
Lower rate of flare
91
What is the prognosis of chronic urticaria?
50% will clear within 1 year. 20% will still have symptoms at 20 years

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