Urticaria Flashcards
(38 cards)
1
Q
CSU epidemiology
A
Chronic urticaria peaks in the fourth decade, and F>M 2:1
2
Q
Triggers or urticaria
A
- Idiopathic: 60%
- Physical: pressure, overheating
- Infections: URTI, etc
- Medications:
- Aspirin and other NSAIDs such as diclofenac (pseudoallergic)
- Aspirin exacerbates ~ 20-30%
- Histamine liberators: opioids, abx such as vancomycin, radiocontrast
- Rocuronium, etc
- Abx such as penicillin and cephalosporins
- Diet:
- Nickel allergy: suggestion nickel free diet works for CSU
- Wine and other ETOH –> aggravates in 30% of CSU
- Food: cheese, fish, strawberries
- Eggs, nuts, seeds –> can have food dependent exercise induced anaphylaxis too
- Wheat, hazelnuts, shellfish
- Wheat dependant: associated with IgE against gliadin
- Spices, green tea
- Menses: worsens pre-menstrually - progesterone sensitivity if predominantly premenstrual, can do skin prick and intradermal testing for that. CSU often goes into remission in last trim of pregnancy
- Stress
- Nickel allergy: CSU:
3
Q
Classification of urticaria
A
- Spotaneous
- Acute <6 weeks
- Chronic >6 weeks
- Intermittent
- Episodic
- Inducible - 19%
- Temperature
- Cold
- Hot
- Touch
- Stroke
- Vibration
- Contact
- Cholinergic
- Aquagenic
- Temperature
4
Q
% of acute urticaria which are idiopathic
A
60%
5
Q
Features of urticaria which would make you think of ddx
A
Fever and arthritis
>24 hours
resolves with brusing
6
Q
Dermographism can sometimes be triggered by what
A
Scabies and penicillin allergy
7
Q
Delayed pressure urticaria looks like what
A
Deep erythematous swelling at site of sustained pressure
Delay 30 minutes - 12 hours
Can look like angioedema
Systemic features: malaise, flu like sx, arthralgia
Lasts 6-9 years
8
Q
Vibratory angioedema looks like what
A
- jogging, rubbing with a towel, vibrating machinery
- can be acquired –> milder
- familial: inherited dominantly
- can cause generalized erythema and headache
9
Q
Cold contact urticaria - primary clinical features
A
- most common cause is idiopathic, more rarely respiratory infections, arthropod bites, HIV
- most frequently seen in young adults
- itching, burning and whealing occurs in minutes after rewarming the skin
- environment: rainy, windy weather, cold objects, drinking cold liquids
- Systemic: flushing, headache, syncope, abdominal pain can occur if large areas affected
- Cold baths and swimming should be avoided due to risk of anaphylaxis
- Mean duration 6-9 years, but may be more transient if post-infectious
10
Q
When you suspect secondary cold contact urticaria what investigations should you do
A
EPG, IEPG
HBV HCV HIV EBV
Cryoglobulins, cryofibrinogens, cold agglutinins
11
Q
Familial cold urticaria is called what, and what genes
A
- Also called familial cold autoinflammatory syndrome - cryopyrin associated periodic syndromes (CAPS)
- Mutation in NLRP3, NLRP12 and PLCG2
12
Q
Cholinergic urticaria clinical
A
- Triggered by factors that lead to sweating
- multiple transient, papular wheals that are 2-3 mm in diameter, and surrounded by an obvious flare
- within 15 minutes of sweat-inducing stimuli –> physical exertion, hot baths, emotional stress
- can be alcohol, spicy foods
- more common in young adults with atopy
- rare in elderly
- stimulus –> pruritus, small, monomorphic wheals that are symmetric, more prominent on the upper half of the body
- Systemic: faintness, headaches, palpitations, abdominal pain, wheezing, reduced FEV has been recorded
- cold urticaria, symptomatic dermographism or aquagenic can be associated with cholinergic
- rarer forms: cholinergic erythema (symmetric, small, erythematous macules appear to be persistent), cholinergic dermographism
13
Q
Adrenergic urticaria clinical
A
- blanched, vasoconstricted skin surrounding small, pink wheals induced by sudden stress as opposed to pale wheals surrounded by a pink halo
- can be reproduced with intradermal noradrenaline injections
14
Q
Causes of contact urticaria
A
- Allergic (immunological)
- Foods: Cow’s milk, Cod, Kiwi fruit, Peanuts, Spices, Celery
- Animals: Saliva, Moths, caterpillars, Urine
- Human: Semen
- Other: Fragrance, Latex
- Non‐immunological:
- Histamine liberators
- CobaltDimethyl
- sulfoxideVasoactive
- Nettle stings
- Jellyfish stings
- Undetermined action:
- Bleaching agent
- Ammonium persulphate
- FragranceBalsam of Peru
- Flavouring agents
- Cinnamic acid
- Cinnamic aldehyde
- Preservatives
- Benzoic acid
- Sorbic acid
15
Q
Hereditary periodic fever syndomres that have urticarial lesions
A
- Cryopyrin-associated periodic syndromes (CAPS): mutation in NLRP3, develop wheals at an early age, and very resistant to antihistamines
- HIDS - hyperimmunoglobulinaemia D with periodic fever syndromes (HIDS)
- TNF receptor associated periodic syndrome (TRAPS): erythematous and oedematous urticarial plaques, periorbital oedema
- Familial Mediterranean fever: more erysipelas-like
Schnitzler
Stills - Episodic angioedema with eosinophilia: hypereosinophilia, weight gain, fever, increased IL-5
- Systemic capillary leak syndrome: rare, acquired, episodic massive plasma exudation from blood vessels –> life-threatening hypotension, angioedema, IgG paraproteinaemia
- Urticarial vasculitis
16
Q
Investigations for acute urticaria
A
- Infection: throat swab if pharyngeal symptoms, other appropriate samples is suspect viral or bacterial
- Withdraw suspected drugs
- Foods: investigate for IgE sensitization where appropriate
17
Q
Investigations for chronic urticaria
A
- If responsive to H1 antihistamines: FBC, ESR, other as indicated by presentation –> eosinophilia for parasite, ESR for systemic AI
- If unresponsive to H1 antihistamines:
- Thyroid antibodies and TSH: 14% of CSU have thyroid issues
- Complement: C4 - angioedema without weals
- Non organ specific antibodies: if associated autoimmune disease possible
- Basophil histamine release assay or basophil activation tests? If functional autoantibodies suspected
- Helicobacter pylori: stool antigen or breath test
- Stool: OCP if foreign travel
- CXR if considering lymphoma
- Optional tests for extensive work up: vitamin D, and week trial of low pseudoallergen diet
- If angioedema is the major component, measuring plasma C4 should be performed as a screening test for hereditary or acquited C1 esterase inhibitor deficiency
- If > 24 hours consider biopsy –> urticarial vasculitis and delayed pressure urticaria
- ?Demonstration of autoreactivity - intradermal injection of autologous serum
18
Q
How to diagnose inducible urticarias
A
- Symptomatic dermographism: stroke back lightly
- Delayed pressure urticaria: 2.5 kg weight to thigh or back
- Cholinergic urticaria: immerse in bath
- Cold contact: melting ice cube
- Aquagenic: bath or shower, owet gauze
- Localized heat - heated cylinder
Phototesting
19
Q
How do you do phototesting for solar urticaria
A
The most sophisticated are done with a monochromator, but none exists in New Zealand.
Tungsten-halogen solar simulator and fluorescent bulbs can be used to detect abnormal sensitivity to short wave ultraviolet radiation(UVB) and to long wave ultraviolet radiation (UVA). One centimetre areas of skin (usually the lower back or buttocks) are exposed to different doses of UVB and UVA. These areas are examined 24 hours later, and minimal erythemadoses (MED) recorded. These are the lowest doses of UVB and of UVA which produce a clearly identifiable pink mark.
20
Q
Pharmacokinetics cetirizine
A
oorly metabolized in liver, excreted in urine unchanged, rapidly absorbed, slightly sedative - best to take at night
21
Q
Loratadine metabolized by what
A
CYP450
22
Q
A/E of anti-hisatmines to be concerned of
A
A/E minimal: QT prolongation in classic anti-histamines, but the ones we use all fine and no real cardiotoxicity
23
Q
Drug interactions for anti-histamines
A
- mizolastine and erythromycin and ketaconazole: risk of cardiac arrhythmias
- P450 3A4 inhibitors or substrates - cimetidine and cyclosporine
24
Q
Anti-histamines in preganncy
A
- Loratadine and Cetirizine are category B, and preferred in second and third trimester
- Chlorpheniramine has been used, but avoid close to birth as sedative effects can occur in breast milk
- No antihistamine can be safely recommended
- Anti-histamines do cross the placenta
25
Other treatments for urticaria a part from antihistamines and xolair
```
Prednisone - acute crisis
Adrenaline for anaphylaxis
Doxepin
Monetlukast: leukotriene receptor antagonist, benefits aspirin sensitive urticaria
Danazol
Sulfasalazine - helpful for delayed pressure urticaria
Colchicine: for neutrophilic urticaria and urticarial vasculitis
Dapsone: DPU
Plasmapharesis
IVIG
Cyclosporin
MTX MMF AZA
```
Pseudoallergen free diet
Induction of tolerance
Phototherapy
26
Recurrent angioedmea without weals epidemiology
Acquired: ACE 1%, higher in Afro-Caribbean ethnicity
1/50 000 of gen pop
Very rare
Women for C1INIH deficiency - more common in women
27
Recurrent angioedema without weals pathogenesis
- Mediated by bradykinin
- Triggers ?stress
- When ACEI induced: inhibits kininase II resulting in an increase in bradykinin, occurs 3 weeks after starting
- Hereditary:
- Deficiency in C1INH: SERPING1 mutation --> type 1 and 2 deficient or non functional C1-esterase inhibitor respectively
- Type 3: F12 mutation in 20%
- ? could possibly be destabilized by H pylori
- Aggravated by oestrogen: OCP and HRT, not NSAIDs
Acquired C1 esterase inhibitor deficiency: can get from B cell lymphorpoliferative disorders and plasma cell dyscrasias or CT disease
28
C1 Esterase Inhibitor Deficiency treatment
- IV C1 inh concentrate
- Recombinant C1 inh
- Subcutaneous icatibant: specific bradykinin B2 receptor antagonist
- Subctuaneous ecallantide: kallikrein inhibitor in an emergency
- Antihistamine, steroids and adrenaline don't work
- For an acute life-threatening attack - higher doses of C1 inh concentrate thant eh 20 units/kg recommended
- Need to give C1 inh concentrate before surgery
- Minor procedures: oral tranexamic acid
29
Urticarial vasculitis definition
- Urticarial lesions that histopathologically demonstrate vasculitis as defined by a minimum of leukocytoclasia with vessel wall necrosis, but with or without fibrinoid deposits, perivascular inflammation or red blood cell extravasation
- So they don't need fibrinoid deposits
30
Urticarial vasculitis epidermiology
- 5 cases per million per year
- Prevalence of urticarial vasculitis in chronic urticaria patients is ~5%
- Peak incidence 5th decade, 60-80% in females
- Hypocomplementaemic is almost exclusively in women
- 70-80% are normocomplementaemic, and they follow a benign course with an average duration of 3 years
31
Urticarial vasculitis causes
- Autoinflammatory: CT diseases: Sjogren, SLE, serum sickness, cryoglobulinaemia
- Infections: HBV, HCV, EBV, Lyme
- Medications: cimetidine, cocaine, diltiazem, etanercept, fluoxetine, infliximab, methotrexate, NSAIDS, potassium iodide
- Malignancies: haem, solid organ is rare (colon, renal)
32
Urticarial vasculitis clinical
- erythematous, indurated wheals with or without angioedema that favour the trunk and proximal extremities
- >24 hours, burning and pain
- PIH residual
- Diascopy: haemorrhage
- Rarely - EM like, livedo reticularis, Raynauds, laryngeal oedema
- Important prognostic feature: hypocomplementaemia (normal complement --> skin limited disease, low complement --> systemic involvement)
- Extracutaneous:
- MSK most common: arthralgias of hands, elbows, knees, ankles and feet occur in half of all patients with urticarial vasculitis
33
Hypocomplementaemic urticarial vasculitis syndrome diagnostic criteria
- 2 major:
- Urticaria >6 months
- Hypocomplementaemia
- 2 minor:
- Vasculitis on biopsy
- Arthralgia, arthritis
- Uveitis or episcleritis
- GN
- Recurrent abdominal pain
- Positive C1 precipitin test with a low C1q level
34
HUVS - how is it different to SLE
- Ocular inflammation in HUVS: 30% episcleritis, iritis, uveitis, conjunctivitis
- COPD-like symptoms in HUVs 50%
- Angioedema >50%
35
HUVS other features
- up to 50% have frank arthritis
- 20% pulmonary --> cough, laryngeal oedema, haemoptysis, dyspnoea, asthma, COPD especially severe in smokers, worsened than what would be expected in smoking alone, then all the other sx
- Renal: 5-10%, proteinuria, microscopic haematuria
- GI: up to 30% abdominal pain, nausea, vomiting, diarrhoea
- Cardiac and CNS involvement rare
36
Investigations for Urticarial vasculitis
- elevated ESR
- Low C3 and C4
- Positive ANA
- HUVS: anti-C1q precipitin and depressed C1q levels, does not have anti-dsDNA and anti-Sm
37
Histology for urticarial vasculitis
- leukocytoclasia with vessel wall necrosis as a minimum
- +/- fibrinoid deposits, perivascular inflammation, RBC extravasation
- Interstitial neutrophilic infiltrate
- DIF:
- 70% Ig, C3 or fibrinogen around blood vessels
- 80% granular pattern of immunoreactants along the basement membrane zone, and with low complement --> SLE
38
Urticarial vasculitis treatment
Mild disease: anti-histamines, NSAIDs
Moderate: dapsone, colchicine, plaquenil
Severe systemic: MMF preferred, then MTX, azathioprine, cyclosporin
Emerging: ritux, anakinra, omalizumab
