What is the initial approach to managing a patient presenting with fever and urticaria?

Initial Management of Fever and Urticaria

When a patient presents with fever and urticaria, immediately assess for autoinflammatory disease, urticarial vasculitis, or acute schistosomiasis (Katayama syndrome) if there is recent tropical travel, as these require specific diagnostic workup and treatment distinct from ordinary urticaria. 1

Critical Initial Assessment

Key Historical Features to Obtain

• Duration of individual wheals: Ask specifically "For how long does each individual wheal last?" If >24 hours, suspect urticarial vasculitis rather than ordinary urticaria 1

• Travel history: Recent tropical travel (especially Africa) with freshwater exposure 2-9 weeks prior strongly suggests Katayama syndrome, particularly if accompanied by eosinophilia 1

• Systemic symptoms: Presence of joint/bone pain, malaise, or recurrent unexplained fever points toward autoinflammatory disease 1

• Family history and age of onset: Important for hereditary periodic fever syndromes 1

• Medication exposure: Recent ACE inhibitors, NSAIDs, or other drugs that commonly trigger urticaria 2

Physical Examination Priorities

• Assess for angioedema: Particularly involving mucous membranes, which may indicate drug-induced reaction or hereditary angioedema 1, 3

• Examine for urticarial rash characteristics: Note if lesions are pruritic, raised wheals that blanch, or if there is bruising/purpura suggesting vasculitis 4

• Check for hepatosplenomegaly: Present in Katayama syndrome and some autoinflammatory conditions 1

Diagnostic Algorithm Based on Clinical Presentation

If Recent Tropical Travel (Especially Africa)

The combination of fever, urticarial rash, and eosinophilia 2-9 weeks after freshwater swimming in Africa makes Katayama syndrome highly likely and justifies empirical treatment. 1

• Order complete blood count with differential to assess for eosinophilia (>0.45 × 10⁹/L) 1
• Check schistosomiasis serology, though sensitivity is low early in infection 1
• Stool, semen, and terminal urine microscopy for ova (often negative early) 1
• Chest radiograph may show pulmonary infiltrates 1

Treatment for Katayama syndrome:

• Praziquantel 40 mg/kg in divided doses 4 hours apart, repeated at 6-8 weeks 1
• Oral prednisolone 20 mg/day for 5 days to alleviate acute symptoms 1

If Wheals Last >24 Hours

Perform lesional skin biopsy to evaluate for urticarial vasculitis, which shows damage to small vessels with fibrinoid deposits. 1

• Check inflammatory markers: C-reactive protein and erythrocyte sedimentation rate 1
• Full vasculitis screen including serum complement assays 5
• Test for paraproteinemia in adults 1

If Recurrent Fever with Joint Pain/Malaise

Test for autoinflammatory disease with elevated inflammatory markers, paraproteinemia screening, and consider gene mutation analysis for hereditary periodic fever syndromes. 1

• Elevated CRP and ESR support autoinflammatory diagnosis 1
• Skin biopsy looking for neutrophil-rich infiltrates 1
• Gene mutation analysis for cryopyrin-associated periodic syndrome if strongly suspected 1

If Ordinary Urticaria with Fever (No Red Flags)

For acute urticaria (<6 weeks duration) with fever but no features suggesting vasculitis or autoinflammatory disease:

Immediate Pharmacological Management

First-Line Treatment

Start second-generation non-sedating H1 antihistamines immediately at standard doses. 2, 6

• Cetirizine 10 mg daily, OR 2, 6
• Fexofenadine 180 mg daily, OR 2, 6
• Loratadine 10 mg daily, OR 2, 6
• Desloratadine 5 mg daily, OR 2, 6
• Levocetirizine 5 mg daily 2, 6

Offer at least two different non-sedating antihistamines as responses vary between individuals. 2

Dose Escalation Strategy

If inadequate symptom control after 2-4 weeks, increase antihistamine dose up to 4 times the standard dose. 2, 6

• Over 40% of patients require higher than standard doses for adequate control 6

Adjunctive Therapies for Severe Cases

Add a sedating antihistamine at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg) to help with sleep and pruritus. 2

Consider adding an H2 antihistamine (ranitidine or famotidine), which may provide better control than H1 antihistamine alone. 2, 6

Role of Corticosteroids

Use a short course of oral corticosteroids only for severe acute urticaria or angioedema affecting the mouth, restricting to short courses to avoid cumulative toxicity. 2, 6

• Avoid prolonged use due to risks of hypertension, hyperglycemia, osteoporosis, and gastric complications 2, 6

Symptomatic Relief Measures

Apply cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream for symptomatic relief. 2

Critical Medications to Avoid

Discontinue any causative drugs immediately, particularly NSAIDs, aspirin, ACE inhibitors, or opioids. 2, 6

• NSAIDs and aspirin can exacerbate urticaria through leukotriene formation and histamine release 2, 6
• ACE inhibitors are particularly associated with angioedema 2
• Avoid cross-reacting medications (all NSAIDs in aspirin-sensitive patients) 2

Special Renal Considerations

In patients with moderate renal impairment, avoid acrivastine and halve the dose of cetirizine, levocetirizine, and hydroxyzine. 2

Common Pitfalls to Avoid

• Missing urticarial vasculitis: Failing to ask about individual wheal duration can delay diagnosis of vasculitis requiring different treatment 1, 5

• Overlooking Katayama syndrome: Not obtaining travel history in febrile patients with urticaria and eosinophilia can miss this treatable parasitic infection 1

• Inadequate antihistamine dosing: Many patients require higher than standard doses; don't abandon antihistamines before escalating to 4x standard dose 2, 6

• Continuing NSAIDs: Patients with urticaria should avoid all NSAIDs as they commonly worsen symptoms 2, 6

• Prolonged corticosteroid use: Restrict to short courses only for severe acute episodes 2, 6