What is the initial treatment for a patient presenting with generalized hives?

Initial Treatment for Generalized Hives

For isolated generalized hives without signs of anaphylaxis, start with a second-generation non-sedating H1 antihistamine—specifically cetirizine 10 mg once daily—as the first-line treatment, which can be increased up to four times the standard dose if symptoms are inadequately controlled. 1, 2, 3

Distinguishing Hives from Anaphylaxis

Before initiating treatment, you must rapidly assess whether this represents isolated urticaria or anaphylaxis, as management differs dramatically:

• Anaphylaxis requires immediate intramuscular epinephrine (0.3-0.5 mg of 1:1000 solution) if the patient has generalized hives PLUS respiratory symptoms (wheezing, stridor, throat tightness), cardiovascular symptoms (hypotension, syncope), or gastrointestinal symptoms (cramping, vomiting) occurring suddenly after allergen exposure 4
• Isolated generalized urticaria without systemic symptoms should be treated with antihistamines, not epinephrine 4
• A critical pitfall: even if a patient has only generalized hives after exposure to a known severe allergen (e.g., peanut in someone with prior anaphylaxis), some guidelines suggest preemptive epinephrine may be beneficial to prevent symptom escalation, though this remains controversial 4

First-Line Antihistamine Selection

Cetirizine 10 mg once daily is the preferred initial choice because it has the shortest time to maximum concentration, providing the most rapid relief, though it causes mild sedation in approximately 13.7% of patients 1, 3

Alternative non-sedating options if cetirizine is not tolerated:

• Fexofenadine 180 mg once daily is completely non-sedating at all doses, making it ideal when any sedation is unacceptable (e.g., drivers, machinery operators) 1, 2
• Loratadine 10 mg once daily is non-sedating with fast onset and 24-hour duration 1, 2
• Desloratadine 5 mg once daily has the longest elimination half-life but requires discontinuation 6 days before skin prick testing 1

Patients should trial at least two different non-sedating antihistamines, as individual responses and tolerance vary significantly 2, 3

Dose Escalation Algorithm

If symptoms remain inadequately controlled after 2 weeks on standard-dose antihistamines:

• Increase the antihistamine dose up to 4 times the standard dose (e.g., cetirizine 40 mg daily, fexofenadine 720 mg daily) when potential benefits outweigh risks 2, 3
• This dose escalation is supported by guidelines and should be attempted before adding other agents 2, 3

Role of Corticosteroids in Acute Urticaria

A short 4-day burst of prednisone 20 mg orally twice daily added to antihistamines significantly improves both symptom relief and clinical resolution in acute urticaria, with patients achieving lower itch scores at 2 and 5 days compared to antihistamines alone 5

However, critical caveats apply:

• Systemic corticosteroids should never be used as maintenance therapy for chronic urticaria and should only be reserved for short-term control during severe acute flares 2, 6
• Monitor blood glucose in diabetic patients, as prednisone causes reversible glucose metabolism abnormalities 2
• Monitor blood pressure in hypertensive patients due to fluid retention 2
• Avoid prolonged use in patients with osteoporosis due to bone loss risk 2
• Long-term corticosteroid use risks adrenal suppression, growth interference in children, dermal thinning, Cushing syndrome, cataracts, and impaired immune function 2, 6

Adjunctive Measures

While initiating antihistamine therapy:

• Identify and minimize aggravating factors including overheating, stress, alcohol, NSAIDs, aspirin, and codeine 2, 3
• Apply emollients regularly for any associated dry skin 2, 3
• Consider cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 2
• Avoid NSAIDs entirely in aspirin-sensitive patients 2, 3

Critical Pitfalls to Avoid

• Never use first-generation antihistamines (diphenhydramine, hydroxyzine) as first-line daytime therapy due to significant sedation, performance impairment, anticholinergic effects, and increased fall risk, particularly in elderly patients 1, 3
• First-generation agents should be reserved exclusively for nighttime use when sedation is beneficial 1, 3
• Do not add H2-antihistamines (cimetidine) routinely, as evidence for their benefit in urticaria is weak and unreliable 4, 7
• Do not use topical crotamiton cream or capsaicin for urticaria, as evidence does not support their efficacy 4, 2

When to Escalate Beyond Antihistamines

If high-dose antihistamines (up to 4 times standard dose) fail after adequate trial:

• Omalizumab 300 mg subcutaneously every 4 weeks is the next step for chronic urticaria, allowing up to 6 months for response 2, 3
• Cyclosporine 4 mg/kg daily is reserved for patients failing both high-dose antihistamines and omalizumab, requiring blood pressure and renal function monitoring every 6 weeks 2, 3

Special Populations

• Elderly patients: Use fexofenadine, loratadine, or desloratadine; avoid first-generation antihistamines entirely due to increased fall risk and anticholinergic complications 1
• Renal impairment: Prefer fexofenadine or loratadine; halve the dose of cetirizine and levocetirizine 1, 3
• Pregnancy: Avoid antihistamines if possible, especially in first trimester; if necessary, choose chlorphenamine due to long safety record 3