Lecture 34 - Chronic Spontaneous Urticaria

what timeline is considered urticarial vasculitis

> 48 hours

how often does a urticarial wheal usually take to resolve

24 hours

what are potential causes of acute urticaria

spontaneous

infection

food

medication

venom

latex

contact

what are potential causes of inducible chronic urticaria

dermatographism

cholinergic

cold induced

solar

aquagenic

exercise

delayed-pressure

what is urticaria driven by

Urticaria is driven by the release of inflammatory mediators from mast cells (histamine**, cytokines, etc.)

what is chronic urticaria characterized by

red , swollen(raised), itchy weals(hives), angioedema or both occurring intermittently for ≥6 weeks

Associated angioedema occurs in approximately 40% of patients

Recurrent angioedema may occur with or without weals

what is chronic spontaneous urticaria

CSU refers to a chronic form of urticaria with no identifiable trigger, with weals present on most days of the week

Can patients experience both spontaneous & inducible forms of urticaria at the same time

yes

what is an important medication to check if a patient is taking when assessing the cause of angioedema

ACEi - especially if they do not have wheals

what do wheals look like in chronic spontaneous urticaria

Can affect any part of the body and are usually widely distributed

Size ranges from a few millimeters to several centimeters and may coalesce

Characterized by central pallor with surrounding erythematous flare

Lesions are transient and typically last minutes to several hours

Individual wheals resolve or change shape within 24 hours

what is angioedema

Deeper swelling of dermis and subcutaneous tissue

More localized than wheals

Common sites include eyelids, lips, hands, feet, and genitalia

Severe cases may involve tongue, pharynx, uvula, or soft palate, posing airway risk

what are the 4 points of chronic spontaneous urticaria assessment

1. exclude differential diagnoses

2. assess disease activity and impact on QoL

3. identify possible triggers or underlying causes

4. know when to refer

what are important things to consider when trying to exclude differential diagnoses

Confirm lesions are transient wheals resolving within 24 hours and are typically pruritic

Consider alternative diagnoses if lesions last >24 hours, are painful/burning, or leave bruising or hyperpigmentation

what are examples of differential diagnoses

Urticarial vasculitis

Drug reactions (e.g., NSAIDs, ACE inhibitors, antibiotics)

Serum sickness–like reactions

Viral exanthems or infection-related urticaria

Dermatitis

what step therapy is recommended in guidelines for urticatia

1. standard dose 2nd gen antihistamines

2. up-dose 2nd gen antihistamines (up to 4x)

3. add biologic: omalizumab

4. consider cyclosporin if inadequate control

a short course of glucocorticoids may be considered in cases of severe exacerbation

what medications are associated with urticaria

NSAIDs

ACEi

antibiotics

what infections are associated with urticaria

viral illnesses

URTIs

what autoimmune conditions are associated with urticaria

thyroid disease

autoimmune urticaria

what physical triggers (inducible urticaria) can occur simultaneously with CSU

pressure

cold

heat

exercise

what lifestyle factors may trigger urticaria

stress

alcohol

sleep deprivation

what are s/s that warrant urgent referral

Signs of anaphylaxis

Airway involvement (tongue swelling, throat tightness, dyspnea)

Rapidly progressive angioedema

what are s/s that warrant specialist referral

Symptoms persist despite 4× antihistamine dosing

Suspected urticarial vasculitis (lesions >24 hours, painful, bruising)

Recurrent angioedema without wheals

what medications may be considered for patients who may require advanced therapy

Consider referral for omalizumab

Consider cyclosporine in refractory disease

do guidelines recommend 1st gen or 2nd gen antihistamines for urticaria

2nd generation

studies show efficacy and improved safety profiles

what are adverse effects of 1st gen antihistamines

CNS:

• decreased alertness, cognition, learning, memory, psychomotor performance

• increased impairment with or without sedation

Muscarinic: dry mouth, urinary retention, sinus tachycardia

Serotonin receptors: increased appetite, weight gain

alpha-Adrenergic receptors: dizziness, postural hypotension

Cardiac: increased QT interval, ventricular arrhythmias

do sedating first gen antihistamines improve sleep quality

No → Negatively Impact REM Sleep

no benefit in combining with 2nd gen antihistamines, and greater incidence of daytime somnolence

is it better to increase 1 antihistamine dose to 4x the typical dose OR stack different antihistamines

Guidelines recommend up dosing antihistamines (up to 4x daily)

what is the MOA of antihistamines in chronic spontaneous urticaria

Block H₁ histamine receptors on target cells (vascular endothelium, sensory nerves, smooth muscle)

Act as inverse agonists, stabilizing the inactive conformation of the H₁ receptor

Reduce histamine-mediated effects, including: vasodilation, increased vascular permeability, pruritus, wheal formation

Inhibit mast cell mediator effects, limiting downstream inflammatory signaling

Decrease sensory nerve activation, reducing itch

what is the overall effect of antihistamines in CSU

suppression of wheal formation and pruritus in CSU

what are Rx 2nd gen antihistamines

Bilastine (Blexten)

Cetirizine

Rupatadine (Rupall)

what are OTC 2nd gen antihistamines

Cetirizine

Desloratadine

Fexofenadine

Loratadine

what 2nd gen antihistamine has the highest risk of sedation

cetirizine (+rupatadine?)

what is the dose of bilastine

20mg daily

max: 80mg daily

Take 1 hour before or 2 hours after food

what is the dose of cetirizine

10mg daily

max: 40mg daily

what is the dose of deslortadine

5mg daily

max: 20mg daily

what is the dose of fexofenadine

180mg daily

max: 720mg daily

what is the dose of loratadine

10mg daily

max: 40mg daily

what is the dose of rupatadine

10mg daily

max: 40mg daily

Only antihistamine with PAF (platelet aggregating factor) blockade

what is omalizumab

SC injection

Anti-IgE monoclonal antibody → binds free IgE → ↓ mast cell & basophil activation

may take 4-12 weeks to work

what is the dose of omalizumab

150-300mg q4 weeks

what is cyclosporine

oral agent

Calcineurin inhibitor → ↓ T-cell activation → ↓ cytokine release

Reserved for severe refractory CSU; effective but limited by toxicity

what is the dose of cyclosporine

3-5mg/kg/day (divided)

how can antihistamine therapy be optimized

Counseling

Take daily (not PRN) for optimal control

May require up-dosing up to 4× standard dose per guidelines

Onset may take several days to weeks

what are safety counselling points for antihistamines

Generally well tolerated

Minimal sedation compared to first-generation agents

Avoid combining with first-generation antihistamines

What is the most likely diagnosis?

A. Urticarial vasculitis

B. Chronic spontaneous urticaria

C. Contact dermatitis

D. Drug hypersensitivity reaction

B. Chronic spontaneous urticaria

What is the next best management step according to international urticaria guidelines?

A. Add hydroxyzine at night

B. Increase cetirizine up to fourfold dose

C. Start systemic glucocorticoids

D. Add montelukast

B. Increase cetirizine up to fourfold dose

What is the most appropriate management recommendation at this time?

A. Add hydroxyzine at night

B. Increase bilastine up to fourfold dose and initiate a short course of oral glucocorticoids

C. Continue bilastine at the same dose and reassess in one week

D. Stop bilastine and switch to a different antihistamine

E. Increase bilastine up to fourfold dose

B. Increase bilastine up to fourfold dose and initiate a short course of oral glucocorticoids