(ch18) Urticaria And Angioedema Flashcards
Which urticaria is more prevalent in men
M>F Delayed pressure urticaria
F>M chronic urticaria, dermatogrqphism and cold urticaria
Wheals vs angioedema
Wheals: superficial demis , pruritic and last<24h
Angioedema: deep dermis, subcut/submucosal , painful and last 2-3 days
Epidemiology of Urticaria
& What is the lifetime incidence or urticaria? Male or female?
Acute urticaria 20% of population
1% may develop chronic urticaria
1-5%. 2:1 female for chronic urticaria
Most common cause of urticaria in children?
Viral or idiopathic
Most common malignancy to cause urticaria
Lymphoma
what is unique about Skin and intestinal submucosa mast cells
Has neutral proteases tryptase and chymase (MCTC)
While other mast cells contain only tryptase
types of urticaria
1) Acute < 6 weeks
2) Chronic >6 weeks, ≥ 2x/w
3) Episodic >6w, <2x/w
Causes of acute urticaria
IUD Fack
Idiopathic (50%)
URTI (40%)
Drugs (9%)
Foods (1%)
Causes of Chronic urticaria
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%)
Episodic urticaria causes
Contact
-immunologic: oral allergy syndrome, protein contact dermatitis
-non-immunologic
URTICARIAL SYNDROMES
- Hereditary Periodic fever syn
- Acquired auto-inflammatory syndromes
- Episodic angioedema with eosinophilia
- Systemic capillary leak syndrome
list Hereditary Periodic fever syns
1-Cryopryin-associated periodic syndromes (CAPS)
2- HyperIgD Syndrome(HIDS)
3-TNF-receptor-associated periodic syndrome(TRAPS)
4-Familial Mediterranean Fever
List Cryopryin-associated periodic syndromes (CAPS)
A. Muchkle-Wells
B. Familial cold autoinflammatory syndrome
C. Neonatal-onset multi-system inflammatory diseseases
List Acquired auto-inflammatory syndromes
- Schnitzler’s syndrome
- Adult-onset Still disease
what is the percentage of urticaria that will resolve within 1 year?
50% clear within a year and 20% persist for years (chronic)
mast cell degranulation stimuli
- 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 - Non-immunologic stimuli
- Substance P + receptor.
- Stem cell factor + receptor.
- C5a + receptor.
- Codeine + receptor.
Mast cell mediators?
-Preformed
Preformed:
Histamine, Heparin,
tryptase/chymase
neutrophil chemotactic factor,
eosinophil chemotactic factor
Mast cell mediators?
-Newly formed
PGD2,
Leukotrienes B4,C4 D4, E4,
Platelet activating factor
Mast cell mediators?
-Cytokines
Can also be considered as performed:
TNFa,
IL-3, 4, 5, 6, 13
GM-CSF
which mediator inhibit mast cell?
Mast cell inhibitor = PGE2
what does histamine do?
vasodilation and increased permeability
C1 esterase inh function
Prevents spontaneous activation of classic complement pathway
C1 esterase inh function
CCC
1. Complement cascade – inhibits cleaving C1s & C4 🡪 Ø classic complement activation
- Coagulation cascade (extrinsic) – inhibits factor XIIa (Hageman factor) 🡪 Ø fibrin clot
- Contact cascade (intrinsic) - inhibits kallikrein 🡪 ↑ HMW kininogen/bradykinin 🡪 Ø endothelial activation
Deficiency results in low C1 and C4
risk factors of urticaria
Africian American
HAE
idiopathic angioedema
acquired C1 inh deficiency
Autoimmune CSU
Associated HLA?
HLA-DR4
HLA-DQ8
Autoimmune CSU
Associated dis?
As/w other AI dis AI thyroid , Vitligo, RA, Celiac, pernicious anemia
Infections As/w CSU
H.pylori (remission with eradication)
Strongyloidiasis
Urticaria etiologies/pathomechanisms
- Idiopathic
-
Immunologic
-Autoimmune
-Allergic
-Vasculitic
-C1 esterase inhibitor deficiency -
Non-immunlogic
-Direct mast cell degranulators (e.g. opiates
-Vasoactive stimuli
-ASA, NSAIDs, dietary pseudoallergens
-ACE-inhibitors
Most common physical urticaria?
Dermatographism - immediate Symptomatic subtype
familial vibratory urticaria gene?
ADGRE2
Reflex cold vs 1ry cold urticaria
-1ry after rewarming
I can be diopathic > post-URTI, arthropod, HIV.
- reflex: generalized cooling of body 🡪 widespread whealing
what food As/w food & Exercise induced anaphylaxis
α-gliadin in wheat
Solar and aquagenic urticaria duration
<1h
non-mmunologic contact urticaria mediator
PGD2
tx NSAIDs
what allergens cross react with Birch pollen?
Birch pollen x-react: kiwis, mangoes
apples, apricots, almond
Gene mutation in HAE
SERPING1
which angioedema has low C1q
Acquired C1 inh deficiency
which complement can be low during attacks of HAE
C2
which HAE has normal levels
HAE, type 3 (estrogen dependent
Triggers of HAE
- trauma (emotional or physical)
- estrogens
which type of HAE As/w facial angioedema distinguishing feature?
Hereditary Angioedema Type III (estrogen dependent
Drugs that can induce angiodema
ACEi (>NSAIDs or ASA), ?contrast
MOA of drug induced angiodema
inhibition of endogenous kininase II aka ACE that normal degrades bradykinin 🡪 ↑ bradykinin 🡪 orofacial life-threatening angioedema
drugs co administered with ACEi increase risk of Angiodema?
1) Black patients
2)ACEi+DDP4 inh(glipitins)
3)ACEi+sirolimus
which of periodic fever syndromes AD inheritance?
CAPS and TRAPs are AD
HIDS and Familial Mediterranean fever are AR
how recurrent is fever in periodic fever syndromes?
Familial Mediterranean fever 1-3d
HIDS 3-7d
TRAPS >7d
which periodic fever syndromes has AA amyloidosis?
Muckle-Wells
gene mutations of periodic fevers?
1 .Familial Mediterranean fever-MEFV
- HIDS- MVK
- TRAPS- TNF-receptor 1
- CAPS- NLRP3
which urticarial syndrome As/W IgG para proteinemia + IL2
Systemic capillary leak syndrome
which urticarial syndrome As/W elevated IL-5
Episodic angioedema with eosinophilia
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
Schnitzler syndrome responds to? tx
IL-1 blockade, e.g. anakinra
Acquired C1 inh deficiency As/w
B-cell lymphoproliferative d/o,
plasma cell dyscrasias
autoimmune CTD
ER tx of C1 Esterase Inhibitor Deficiency
- C1 inh concentrate 20 units/kg
- FFP
-Oral danazol - Oral tranexamic acid
- Icatibant
- Ecallantide
prophylactic tx for C1 Esterase Inhibitor Deficiency
C1 inh as prophylaxis 1 hr prior to surgery.
Minor surgeries- oral tranexamic acid
Contraindicated tx in 1 Esterase Inhibitor Deficiency
OCP, hormone replacement
Mainstay tx for urticaria
H1 Antihistamines
Antihistamines safe in pregnancy and breastfeeding?
loratadine and cetirizine (cat B)
which H1 cause seizures in breastfeeding
hydroxyzine
which anti-h has both H1+H2
Doxepin (TCA)
for can be good for cholinergic
Tx for DPU
- Sulfasalazine
Avoid in Aspirin sensitivity - Dapsone (G6PD)
-prednisone
biologic in urticaria
Omalizumab (humanized anti-IgE Ab)
tx fo urticarial vasculitis
Dapsone (neutrophilic vasculitis)( Ø G6PD)
Colchicine (neutrophilic vasculitis)
what does elevated IgE give as prognosis in Omalizumab
↑IgE->early response & early relapse
which meds has risk of Arrythmia
mizolastine+ Erythromycin/ketoconazole
Epi+ Doxepin/B-blockers
Mention two long lasting second generation H1 antihistamines
- Desloratadine
- Fexofenadine
mention 5 subtypes of dermographism?
- Delayed
- Cholinergic
- Red
- Associated with mastocytosis
- Localized
- how do you differentiate cholinergic from adrenergic urticarial?
- Adrenergic urticarial presents with a halo of vasoconstriction
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
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
what is the mediator of angioedema?
- Bradykinin is the main mediator in angioedema
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
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
What is the role of aspirin?
Usually an aggravator of urticaria, but not often a cause
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
nonimmunologic contact urticaria causes?
Sorbic acid, Benzoic acid
Cinnamic aldehyde
Which physical urticaria does not produce angioedema?
Dermographism. Angioedema can occur with all the other types
Which types often co-occur?
Dermographism + cholinergic urticaria
C+C: Cold and cholinergic urticaria
D+D: Delayed pressure urticaria and delayed dermographism
What is the definition of delayed dermographism?
Onset at least 30 minutes after stimulus
What are possible associations with primary cold urticaria?
After respiratory infections, insect bites or HIV infection
primary cold urticaria test?
Test with ice cube test
negative in reflex urticaria
causes of secondary cold urticaria?
Cryoglobulinemia, cryofibrinogenemia with underlying causes of hep B/C, lymphoproliferative or EBV
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
What are causes of immunologic contact urticaria?
IgE mediated
Grass, animals, food, latex.
How do you test for cholinergic urticaria?
Exercise until you sweat or sitting in a hot water bath for 10 minutes at 42C
How do you test for delayed pressure urticaria?
Apply a 2.5kg weight to the back or thigh for 20 minutes
What first generation antihistamine is safest in pregnancy?
Chlorpheniramine
What are the main AE of 1st gen?
Sedation and anticholinergic effects
What are possible drug interactions?
CYP3A4 (cardiac arythmias):
erythromycin, ketoconazole, cimetidine, cyclosporine
What is the proposed advantage of the low-pseudoallergen diet?
Lower rate of flare
What is the prognosis of chronic urticaria?
50% will clear within 1 year. 20% will still have symptoms at 20 years
