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(ch18) Urticaria And Angioedema Flashcards

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
Q

Autoimmune CSU
Associated HLA?

A

HLA-DR4
HLA-DQ8

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26
Q

Autoimmune CSU
Associated dis?

A

As/w other AI dis AI thyroid , Vitligo, RA, Celiac, pernicious anemia

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27
Q

Infections As/w CSU

A

H.pylori (remission with eradication)

Strongyloidiasis

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28
Q

Urticaria etiologies/pathomechanisms

A
  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
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29
Q

Most common physical urticaria?

A

Dermatographism - immediate Symptomatic subtype

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30
Q

familial vibratory urticaria gene?

A

ADGRE2

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31
Q

Reflex cold vs 1ry cold urticaria

A

-1ry after rewarming
I can be diopathic > post-URTI, arthropod, HIV.

  • reflex: generalized cooling of body 🡪 widespread whealing
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32
Q

what food As/w food & Exercise induced anaphylaxis

A

α-gliadin in wheat

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33
Q

Solar and aquagenic urticaria duration

A

<1h

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34
Q

non-mmunologic contact urticaria mediator

A

PGD2
tx NSAIDs

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35
Q

what allergens cross react with Birch pollen?

A

Birch pollen x-react: kiwis, mangoes
apples, apricots, almond

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36
Q

Gene mutation in HAE

A

SERPING1

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37
Q

which angioedema has low C1q

A

Acquired C1 inh deficiency

38
Q

which complement can be low during attacks of HAE

A

C2

39
Q

which HAE has normal levels

A

HAE, type 3 (estrogen dependent

40
Q

Triggers of HAE

A
  • trauma (emotional or physical)
  • estrogens
41
Q

which type of HAE As/w facial angioedema distinguishing feature?

A

Hereditary Angioedema Type III (estrogen dependent

42
Q

Drugs that can induce angiodema

A

ACEi (>NSAIDs or ASA), ?contrast

43
Q

MOA of drug induced angiodema

A

inhibition of endogenous kininase II aka ACE that normal degrades bradykinin 🡪 ↑ bradykinin 🡪 orofacial life-threatening angioedema

44
Q

drugs co administered with ACEi increase risk of Angiodema?

A

1) Black patients

2)ACEi+DDP4 inh(glipitins)

3)ACEi+sirolimus

45
Q

which of periodic fever syndromes AD inheritance?

A

CAPS and TRAPs are AD

HIDS and Familial Mediterranean fever are AR

46
Q

how recurrent is fever in periodic fever syndromes?

A

Familial Mediterranean fever 1-3d

HIDS 3-7d

TRAPS >7d

47
Q

which periodic fever syndromes has AA amyloidosis?

A

Muckle-Wells

48
Q

gene mutations of periodic fevers?

A

1 .Familial Mediterranean fever-MEFV

  1. HIDS- MVK
  2. TRAPS- TNF-receptor 1
  3. CAPS- NLRP3
49
Q

which urticarial syndrome As/W IgG para proteinemia + IL2

A

Systemic capillary leak syndrome

50
Q

which urticarial syndrome As/W elevated IL-5

A

Episodic angioedema with eosinophilia

51
Q

Schnitzler syndrome diagnositc criteria

A

Strasbourg criteria
urticarial vasculitis +Monoclonal IgM gammopathy
and 2 of the following:
Fever, arthralgias, HSM, ↑ESR, ↑WBC, bone abnormality, bone pain

52
Q

Schnitzler syndrome responds to? tx

A

IL-1 blockade, e.g. anakinra

53
Q

Acquired C1 inh deficiency As/w

A

B-cell lymphoproliferative d/o,
plasma cell dyscrasias
autoimmune CTD

54
Q

ER tx of C1 Esterase Inhibitor Deficiency

A
  • C1 inh concentrate 20 units/kg
  • FFP
    -Oral danazol
  • Oral tranexamic acid
  • Icatibant
  • Ecallantide
55
Q

prophylactic tx for C1 Esterase Inhibitor Deficiency

A

C1 inh as prophylaxis 1 hr prior to surgery.

Minor surgeries- oral tranexamic acid

56
Q

Contraindicated tx in 1 Esterase Inhibitor Deficiency

A

OCP, hormone replacement

57
Q

Mainstay tx for urticaria

A

H1 Antihistamines

58
Q

Antihistamines safe in pregnancy and breastfeeding?

A

loratadine and cetirizine (cat B)

59
Q

which H1 cause seizures in breastfeeding

A

hydroxyzine

60
Q

which anti-h has both H1+H2

A

Doxepin (TCA)
for can be good for cholinergic

61
Q

Tx for DPU

A
  • Sulfasalazine
    Avoid in Aspirin sensitivity
  • Dapsone (G6PD)
    -prednisone
62
Q

biologic in urticaria

A

Omalizumab (humanized anti-IgE Ab)

63
Q

tx fo urticarial vasculitis

A

Dapsone (neutrophilic vasculitis)( Ø G6PD)
Colchicine (neutrophilic vasculitis)

64
Q

what does elevated IgE give as prognosis in Omalizumab

A

↑IgE->early response & early relapse

65
Q

which meds has risk of Arrythmia

A

mizolastine+ Erythromycin/ketoconazole

Epi+ Doxepin/B-blockers

66
Q

Mention two long lasting second generation H1 antihistamines

A
  • Desloratadine
  • Fexofenadine
67
Q

mention 5 subtypes of dermographism?

A
  • Delayed
  • Cholinergic
  • Red
  • Associated with mastocytosis
  • Localized
68
Q
  1. how do you differentiate cholinergic from adrenergic urticarial?
A
  • Adrenergic urticarial presents with a halo of vasoconstriction
69
Q

mention 5 causes of angioedema with no urticarial and normal C4 level

A
  • Capillary leak syndrome
  • Angioedema with eosinophilia
  • HAE III
  • Idiopathic
  • NSAID or ACE inhibitor induced
70
Q

mention the provoking factors for cholinergic urticaria

A

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
Q

what is the mediator of angioedema?

A
  • Bradykinin is the main mediator in angioedema
72
Q

What is the effect of histamine on blood vessels?

A

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
Q

What are the roles of basophils, neutrophils and eosinophils in urticaria?

A

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
Q

What is the role of aspirin?

A

Usually an aggravator of urticaria, but not often a cause

75
Q

What are examples of urticaria that are mast-cell independant?

A

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
Q

nonimmunologic contact urticaria causes?

A

Sorbic acid, Benzoic acid
Cinnamic aldehyde

77
Q

Which physical urticaria does not produce angioedema?

A

Dermographism. Angioedema can occur with all the other types

78
Q

Which types often co-occur?

A

Dermographism + cholinergic urticaria

C+C: Cold and cholinergic urticaria

D+D: Delayed pressure urticaria and delayed dermographism

79
Q

What is the definition of delayed dermographism?

A

Onset at least 30 minutes after stimulus

80
Q

What are possible associations with primary cold urticaria?

A

After respiratory infections, insect bites or HIV infection

81
Q

primary cold urticaria test?

A

Test with ice cube test
negative in reflex urticaria

82
Q

causes of secondary cold urticaria?

A

Cryoglobulinemia, cryofibrinogenemia with underlying causes of hep B/C, lymphoproliferative or EBV

83
Q

What is exercise-induced anaphylaxis?

A

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
Q

What are causes of immunologic contact urticaria?

A

IgE mediated
Grass, animals, food, latex.

85
Q

How do you test for cholinergic urticaria?

A

Exercise until you sweat or sitting in a hot water bath for 10 minutes at 42C

86
Q

How do you test for delayed pressure urticaria?

A

Apply a 2.5kg weight to the back or thigh for 20 minutes

87
Q

What first generation antihistamine is safest in pregnancy?

A

Chlorpheniramine

88
Q

What are the main AE of 1st gen?

A

Sedation and anticholinergic effects

89
Q

What are possible drug interactions?
CYP3A4 (cardiac arythmias):

A

erythromycin, ketoconazole, cimetidine, cyclosporine

90
Q

What is the proposed advantage of the low-pseudoallergen diet?

A

Lower rate of flare

91
Q

What is the prognosis of chronic urticaria?

A

50% will clear within 1 year. 20% will still have symptoms at 20 years

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