Urticaria (Hives): Comprehensive Study Notes

Epidemiology & Classification

Lifetime prevalence: $20\%$ of population will experience urticaria (hives) at least once
Temporal pattern
- Acute urticaria: lasts <6 weeks
- Chronic urticaria: lasts $\ge 6$ weeks
Benign & self-limiting in most cases, but can signal life-threatening anaphylaxis or (rarely) serious systemic disease

Pathophysiology

Core event: mast-cell / basophil degranulation → release of histamine + other mediators
- If mediator release is in superficial dermis → wheals / hives
- If in deep dermis / subcutis → angio-edema
Typical mechanism: IgE-mediated cross-linking of surface IgE → degranulation, but two alternatives exist:
- Non-IgE immune pathways (e.g., complement)
- Non-immunologic direct activation (e.g., drugs such as NSAIDs)
Autoimmune contribution (subset of chronic cases)
- Autoantibodies against IgE
- Autoantibodies against high-affinity IgE receptor (FcεRI)

Triggers & Etiology (non-exhaustive)

Infections (most common in children): viral URI, Mycoplasma, parasitic, etc.
Medications
- NSAIDs → non-immunologic (direct mast-cell) or IgE-mediated
- Antibiotics, radiocontrast, biologics
Foods / food additives
Inhalants: pollens, animal dander
Physical stimuli (often produce chronic inducible urticaria)
- Cold, heat, pressure, vibration, water, exercise, solar
Idiopathic: $80\text{–}90\%$ of chronic cases have no identifiable trigger

Clinical Presentation

Lesion morphology
- Wheal: raised, well-circumscribed, red or skin-coloured; often with central pallor
- Size/shape variable; wheals may coalesce with enlargement
- Pruritus: intense itching; may also burn/sting
- Duration of individual lesion: <24\text{ h} (key diagnostic feature)
- Resolution: no bruising/scarring unless excoriated or associated with urticarial vasculitis
Distribution
- Any skin surface; areas under pressure (belt lines, axillae) may flare more
Systemic associations
- Angioedema, respiratory compromise, hypotension signal possible anaphylaxis

Risk Factors & Epidemiologic Correlates

Personal or parental atopy increases risk of acute hives
Relationship between chronic hives and atopic disease remains unclear (conflicting data)

Differential Diagnosis (conditions with urticarial-like lesions)

Urticarial vasculitis
Viral exanthems / drug eruptions
Contact dermatitis
Scabies, insect bites
Bullous pemphigoid (early phase)
Hereditary angioedema (bradykinin-mediated, not histaminergic)
Table 2 (lecture) supplies detailed comparisons

Red Flags & Referral Criteria

Refer or seek urgent care if ANY of the following accompany presumed hives:

Angioedema (especially of airway, lips, tongue)
Respiratory distress: wheeze, stridor, dyspnea
Signs of systemic illness: fever, arthralgia, weight loss
Lesion atypia: hyperpigmented, bruised, blistered, purpuric, or >48\text{ h} duration
Persistent disease beyond $48\text{ h}$ without resolution of individual wheals
Suspected drug-induced etiology needing discontinuation/medical supervision (e.g., ACE-inhibitors, NSAIDs)

Management Goals

Identify & eliminate trigger where possible
Provide symptomatic relief (pruritus, sleep, QoL)
Prepare for / manage severe reactions (e.g., anaphylaxis)

Non-Pharmacologic Management

Trigger avoidance = cornerstone
General skin care
- Loose, non-occlusive clothing
- Cool baths / cool compresses
- Fragrance-free soaps, detergents
- Adequate sun protection
Behavioural
- Keep fingernails short to limit excoriation
- Avoid alcohol & NSAIDs (may worsen symptoms)

Pharmacotherapy – Acute Urticaria

First-line: Daily second-generation H1 antihistamine
- Cetirizine, desloratadine, loratadine, fexofenadine, rupatadine, bilastine
- Benefits: longer acting, minimal sedation, fewer anticholinergic effects
Bedtime first-generation H1 (diphenhydramine, hydroxyzine) ONLY if
- Young/healthy patient
- Need nocturnal sedation for itch
- Use cautiously in elders: anticholinergic burden → cognitive decline, falls, urinary retention
Dose up-titration
- Some guidelines: increase 2–4× standard daily dose if partial response
- $\uparrow$ efficacy but $\uparrow$ risk of adverse events; not Health-Canada–approved
Adjunctive / Specialist measures (acute severe episode)
- Short oral corticosteroid burst (e.g., prednisone $20\text{–}50\,\text{mg}$ daily for $3\text{–}5$ d)
- H2 antihistamine (ranitidine, famotidine) – limited evidence
- Consider epinephrine auto-injector prescription if high anaphylaxis risk (e.g., food, insect sting)
Topical antihistamines NOT recommended → risk of contact dermatitis; little efficacy

Pharmacotherapy – Chronic Urticaria

Stepwise algorithm (each step ≈ 2–4 wk trial before escalation)
1. Standard-dose daily second-generation H1 (same agents as acute)
2. Increase dose up to 4× usual (off-label)
3. Add-on / switch options (specialist):
- Omalizumab (anti-IgE monoclonal) monthly injections
- Cyclosporine (calcineurin inhibitor)
- Leukotriene receptor antagonist (montelukast)
- H2 antihistamine (ranitidine, famotidine)
- Short oral corticosteroid bursts for flares (not long-term)
Treatment principle: schedule daily, not PRN, to maintain symptom suppression
2014 Cochrane review: no single second-gen H1 agent superior at standard dose; individual response varies

Special Populations & Formulations

Pediatrics: liquid / chewable cetirizine, loratadine, desloratadine, fexofenadine
Older adults: avoid/limit first-generation agents; select least sedating (desloratadine, loratadine, fexofenadine, bilastine)
Pregnancy: usually cetirizine, loratadine preferred; confirm with guidelines

Follow-Up & Monitoring

Pharmacist follow-up in $\approx 7$ days
- If resolved → discontinue pharmacotherapy
- If partial/none or worsened → refer (possible steroid course, dose increase, or specialist therapy)
- Always refer if new red-flag features appear

Ontario Pharmacist Prescribing (OCP Table)

Eligible agents mirrored from insect-bite protocol
Second-generation H1 antihistamines prioritized
Must apply professional judgment for drug discontinuation or initiation where outside OTC range (e.g., higher doses)

Knowledge-Check Scenario (Lecture Example)

70-year-old female, chronic hives; comorbid controlled hypertension (perindopril $8\,\text{mg qd}$ ), vitamin D, no prior treatment
Best initial therapy: desloratadine $5\,\text{mg qd}$
- Rationale: second-generation, least sedating
- Diphenhydramine inappropriate (first-gen, anticholinergic)
- Cetirizine more sedating → fall risk
- PRN dosing suboptimal; chronic urticaria needs scheduled medication

Practical / Ethical Considerations

Always distinguish benign hives from anaphylaxis; timely epinephrine saves lives
Educate on self-monitoring, trigger journal, safe NSAID / alcohol use
Recognize mental-health impact of chronic itch & sleep disturbance; address QoL
Avoid polypharmacy and anticholinergic load in geriatrics

Real-World Connections & Take-Home Points

Common OTC antihistamines empower self-management but pharmacist screening essential to catch red flags.
Chronic urticaria often idiopathic; one sees frequent referrals to allergists for step-up therapy (omalizumab revolutionized refractory cases).
Climate change & infection patterns may shift trigger prevalence (e.g., viral outbreaks → more pediatric hives).
Emphasize interprofessional collaboration (pharmacist ↔ primary care ↔ specialist) for dosage escalation beyond OTC labelling.

Summary Cheat-Sheet

Definition: itchy wheals <24 h each, total course <6 or $\ge6$ wk (acute vs chronic)
Pathway: mast-cell histamine release
Top triggers: infections (kids), meds (NSAIDs), foods, physical stimuli, idiopathic
First-line drug: daily second-generation H1
Escalation: $\times 4$ dose →
- Add omalizumab / cyclosporine / montelukast / H2 →
- Short steroids for severe flares
Refer if angioedema, systemic signs, atypical lesions, >48 h persistence, or therapy failure after $1$ wk.