Urticaria

Question 1

Aeitologies of urticaria

Answer 1

idiopathic
immunological (autoimmune, immune complex, allergic, complement)
Non immunological: direct mast cell releases, ACEI, aspirin, nsaids etc

Question 2

Associations with urticaria

Answer 2

Thyroiditis, SLE, ?coeliac, H Pylori

Question 3

Aggravating factors

Answer 3

URTIs, drugs e.g. salicylates, nsaids, ACEI, penicillin.
Pressure, overheating, premenstrual
Alcohol, stress, unrelated viral infections
tartrizine, azo dyes

Question 4

T/F C1 esterase inhibitor deficiency and ACEI induced angioedema are due to mast cells

Answer 4

F - acei : kinins

Question 5

T/F mast cells are responsible for autoinflamamtory syndromes

Answer 5

F - IL1 and 18 activated by caspase 1

Question 6

H2 is responsible for itch, wheal, flare and erythema

Answer 6

F H2 for erythema and wheal only

Question 7

What medication class may help in aspirin sensitive people?

Answer 7

leukotriene antagonists.

Question 8

How are mast cells activated via immunological means?

Answer 8

linkage of 2 adjacent alpha subunits of IgE receptors of a mast cell

Question 9

What type of hypersensitivy reaction is urticarial vasculitis

Answer 9

type III

Question 10

How long does an IgE mediated urticaria last?

Answer 10

max 60 min

Question 11

What are pseudoallergans

Answer 11

sensitization of the immune system is not involved, but clinically the same symptoms appear. e.g. aspirin, food additives, natural salicylate, contrast dye, muscle relaxants, plasma expanders

Question 12

Non allergic causes of acute urticaria

Answer 12

histamine liberators (eg codeine, vancomycin)
Pseudoallergans eg aspirin, food additives
Alcohol
foods with vasoactivate amines: cheese, fish, tomatos, pineapple, avocados
Histamine from strawberries, scombroid fish

Question 13

Tests for Chronic urticaria

Answer 13

FBC, ESR/CRP (increased in inflammatory syndromes, UV), thyroid abs and TFTs, ANA
Bx on wheal 12 hours old ?vasculitis
stool OCP
Consider: H pylori, strongyloides
consider pseudo allergen free diet for 2-3 weeks
?Anti-FceR(autoab to Fc receptor of IgE)
consider serum EPP, urine Bence jones - if fever, bony pain, raised CRP, neutrophils in bx.

Question 14

Tests in acute

Answer 14

often none
maybe specific IgE, skin prick
URTI/bacterial screen

Question 15

Q to ask re chronic urticaria

Answer 15

Can you induce the symptoms?
Fever?Joint pain/malaise? Family hx?
wheals last longer than 24 hours?
Angioedema alone? 
Medications eg NSAID, ACEI

Question 16

Treatment ladder for chronic urticaria

Answer 16

1st line = 2nd generation antihistamines. If persist > 2 weeks:
2nd line:Increase dose up to 4 x max
If persists after 1-4 weeks:
3rd line: omalizumab or cyclosporin A or montelukast

Can use short courses of CS if required.
Consider Doxepin or promethazine nocte

General measures: avoid overheating, stress, alcohol, drugs with potential to worsen e.g. codeine, aspirin, ACEI

1% menthol in aqueous

Other possibilitys: IVIg, plasmapheresis
Thyroxine in euthyroid with thyroid autoimmunity
nbUVB
Colchicine and dapsone if inflammatory infiltrate is neutrophil predominant

Question 17

Tx of urticarial vasculitis

Answer 17

Dapsone, prednisone

Question 18

How to use CsA in chronic urticaria

Answer 18

4mg/kg once daily 16 weeks.

helpful in about 2/3

Question 19

How to use omalizumab

Answer 19

150-300mg sub cut every 4 weeks for 6/12
add on to antihistamines
keep in hospital to observe for 2-4 hours - risk of anaphylaxis
baseline platelets - risk of thrombocytopenia

Question 20

Investigations if you suspect urticarial vasculitis

Answer 20

Bx DIF: vascular C3, fibrin and immunoglobulins
C3, C4, C1q, ANA, ENA, dsDNA, ANCAs
Hep B,C, HIV, EBV
serum EPP - schnitzlers if fever, bone pain, lymphadenopathy
due to risk of systemic involvement: ESR, Urinalysis
chest X-ray if symptomatic, RFTs
elfts

Question 21

Important points on hx if you suspect UV

Answer 21

sx: burning, pain, how long they last, resolve with bruising?
angioedema?
fevers, malaise, bony pain
abdo pain, nausea, vomiting
Drugs e.g. cimetidine, diltiazem

Question 22

In what % of patients does chronic urticaria last >5 years?

Answer 22

15%

Question 23

% causes of acute urticaria

Answer 23

20% allergic e.g. drugs/food
30% infections
50% unknown

Question 24

% causes of chronic urticaria

Answer 24

20% physical

80% unknown

Question 25

Types of physical urticarias

Answer 25

Mechanical: delayed pressure, symptomatic dermatographism, vibratory Thermal: cholinergic, cold contact, localised heat, systemic cold urticaria Other: aquagenic, solar, exercise induced anaphylaxis

Question 26

What treatment is recommended in delayed pressure urticaria

Answer 26

poorly responsive to antihistamines, but some help with 10mg tads cortisone as it also inhibits eosinophil migration, dapsone, colchicine, sulfasalzine, montelucast, nsaids (but may aggravate ordinary urticaria), topical steroids under occlusion

Question 27

How to test for aquagenic urticaria

Answer 27

water in bath for 15min or water soaked towels at body temp for 30min

Question 28

How to test for solar urticaria

Answer 28

Check porphyrins Uusally fade in 2 hours cf to PMLE which appears hours later and lasts days exposure to sunlight or solar stimulator - takes a few min, lasts less than 1 hour.

Question 29

How to test for cholinergic urticaria

Answer 29

warm in hot bath 42 degrees for 15 min - raises core temp 0.7-1degree, or exercise until sweating.

Question 30

How to test for delayed pressure urticaria

Answer 30

weight of 7kg hanging by broad strap, wheal at site 4-6 hours later, or 4.5kg weight rods with a 1.5cm diameter applied for 15 min.

Question 31

How to test for systemic cold

Answer 31

ice cube test negative | cold room at 4 degrees for 30 min in lightweight clothes.

Question 32

How to test for cold contact urticaria

Answer 32

consider cryoglobulins, cold agglutinins, cryofibrinogens, hep B, C, FBC, ANA ice cube in a thin plastic bag for up to 20min to skin. Whealing occurs within 15 min usually during rewarming.

Question 33

Angioedema without wheals - causes

Answer 33

Idiopathic Drugs usually ACEI, Angiotensin II receptor blockers Hereditary: C1 esterase inhibitor deficiency or impaired function or females with oestrogen dependant angioedema Acquired C1 esterase inhibitor deficiency.

Question 34

Causes of acquired C1 esterase inhibitor deficiency angioedema

Answer 34

1) lymphoproliferative: b cell lymphoma, nHL, multiple myeloma 2) SLE, autoimmune 3) Abs directed against inhibitor but no evidence of lymphoma

Question 35

Different types of hereditary angioedema

Answer 35

1) Reduced amts of C1 esterase inhibitor 2) inactive form : 15% normal, or increased but dysfunctional 3) women with family hx but normal levels - oestrogen dependent

Question 36

Treatment of hereditary angioedema

Answer 36

``` avoid oestrogen check for SLE, sjogrens Stanozolol 2mg alt days to 10mg daily Danazol 200mg mond to fri to 400mg daily Tranexamic acid 0.5-3mg daily C1 esterase inhibitor concentrate FFP Icatibant (bradykinin 2 receptor antagonist) 30mg SC ```

Question 37

Ix of angioedema

Answer 37

check meds C3, C4, C1q, CH50, C1 esterase inhibitor and function ANA, ENA, dsDNA (associations with SLE, Sjogrens) If C1q is LOW: consider acquired: serum EPP, hence ones, lymphoma,

Question 38

What do you expect in results of complement studies in hereditary angioedema type 1

Answer 38

Low C1 INH Low C4 normal C1q CH50 may reduce during attacks

Question 39

What do you expect in results of complement studies in hereditary angioedema type 2

Answer 39

Normal or elevated C1 INH but dysfunctional low C4 normal C1q

Question 40

What do you expect in results of complement studies in hereditary angioedema type 3

Answer 40

normal C1 INH, normal C4, normal C1q | mutation in factor XII gene

Question 41

Diagnostic criteria for schnitzlers

Answer 41

``` Major criteria (must have these) and 2 minor criteria Major: chronic urticarial rash, monoclonal IgM or IgG Minor: recurrent fever, abnormal bone remodelling, neutrophilic dermal infiltrate, leucocytoisis and/or elevated CRP ```

Question 42

What are Cryopryin associated periodic syndromes

Answer 42

NLRP3 gene mutation. Rare hereditary inflammatory disorder with 3 phenotypes. Due to a gain of function mutation affecting the cryopyrin protein 1) familial cold auto inflammatory syndrome AD 2) Muckle Wells - AD 3) Neonatal onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome

Question 43

If you suspect a CAPS what do you do?

Answer 43

``` check FBC - neutrophilic CRP, ESR - elevated urinary protein to detect amyloid call renal Bx: perivascular and sometimes peregrine neutrophilic infiltrate of the reticular dermis without mast cells or vasculitis Tx is anakinra ```

Question 44

What is familial mediterranean fever?

Answer 44

AR, MEVR1 gene self limiting attacks of fever, peritonitis, pleurisy and synovitis. Erysipelas like lesions on the lower leg. 1/4 may develop renal amyloidosis.

Question 45

Types of hereditary auto inflammatory syndromes

Answer 45

CAPS familial mediterranean fever hyperIgD syndrome TRAPS

Question 46

What are TRAPS

Answer 46

TNF receptor associated periodic syndrome AD disorder. Migratory erythema, febrile epidsodes, migratory muscle pain, amyloidosis

Question 47

Clinical features of muckle wells

Answer 47

sensioneural hearing loss in 2/3, headaches, abdominal pain, mouth ulcers, amyloidosis in 25% leading to kidney failure and death, delayed puberty.

Question 48

urticarial/angioedema like conditions associated with paraproteins

Answer 48

schnitzlers, acquired C1 esterase inhibitor deficiency angioedema, systemic papillary leak syndrome

Question 49

People with auto inflammatory syndromes do not have angioedema as an associated symptom T/F

Answer 49

T

Question 50

Diseases which may manifest urticarial lesions (according to the curriculum)

Answer 50

Arthropod bites - immediate, hypersensitivity reaction (papular urticaria) contact dermatitis, exanthematous drug eruption urticarial dermatitis Polymorphic eruption of pregnancy Mastocytosis in children Autoimmune bullous diseases Rare: autoimmune progesterone/oestrogen dermatitis, interstitial granulumatous dermatitis, eosinophilic cellulitis, neutrophilic eccrine hidradenitits, urticaria like follicular mucinosis.

Question 51

Angioedema not associated with urticaria

Answer 51

hereditary angioedema acquired C1 esterase inhibitor deficiency idiopathic recurrent angiodema

Question 52

Systemic diseases that can present with urticarial skin lesions (curriculum)

Answer 52

Vasculitides eg churg strauss, wegeners, PAN urticarial vasculitis SLE, Sjogrens, dermatomyositis Mixed connective tissue disease Juvenile RA Haematologic disease NHL (b cell), cryoglobulinaemia, hypereosinophilic syndromes, polycythaemia vera.

Question 53

In angioedema without wheals, but normal C4 - consider what?

Answer 53

idiopathic, drug induced, episodic angiodema with eosinophilia, hereditary type III, capillary leak syndrome

Question 54

What is urticarial dermatitis

Answer 54

Usually in elderly with both urticaria like and eczema like lesions. Often reported as dermal hypersensitivity reaction with minimal spongiosis, mixed inflammatory cells in the dermis. May be an early sign of BP, but could be related to drug, malignancy

Question 55

Neutrophilic urticarial dermatoses

Answer 55

Urticaria with neutrophilic dermatoses histopathologically Strongly associated with a systemic disease (schnitzler, adult onset stills, LE, hereditary auto inflammatory fever syndromes)

Question 56

Clinical features of adult onset Still's disease

Answer 56

High fevers often occur late afternoon, arthritis with carpal ankylosis, asymptomatic macular exanthema which accompanies the fevers (salmon pink in colour) and frequently koebnerises F>M (usually presents 60) Patients often have very elevated ferreting Think of it in 3 weeks of fever, elevated CRP, ESR, platelets, arthritis