What is the diagnosis and treatment for a patient presenting with hives, itchiness, and swelling, with elevated C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) levels?

Diagnosis: Chronic Spontaneous Urticaria (CSU) with Systemic Inflammation

Based on the presentation of hives, itching, and swelling with elevated inflammatory markers (CRP 5.6 mg/dL, ESR 25 mm/h), the most likely diagnosis is chronic spontaneous urticaria (CSU), and treatment should begin immediately with high-dose second-generation non-sedating H1-antihistamines, with consideration for omalizumab if antihistamines fail. 1, 2

Clinical Context and Diagnostic Reasoning

Understanding the Inflammatory Markers

• Your ESR of 25 mm/h is mildly elevated (normal <20 mm/h in men, <30 mm/h in women per American College of Physicians criteria) 3
• Your CRP of 5.6 mg/dL is significantly elevated and correlates with urticaria disease activity 2
• Elevated CRP is found in one-third of CSU patients and directly correlates with disease severity, quality of life impairment, and poor response to antihistamines 2
• ESR correlates moderately with urticaria activity scores (UAS7) in CSU patients 4

Why This is Urticaria, Not Other Inflammatory Conditions

The combination of hives, itching, and swelling with these inflammatory marker levels does NOT suggest:

• Still's disease - would require much higher ESR (typically >40 mm/h), spiking fevers, and markedly elevated ferritin 5, 6
• Giant cell arteritis - requires ESR >40 mm/h for diagnostic sensitivity, plus new headache, jaw claudication, or visual symptoms 3
• Polymyalgia rheumatica - needs bilateral shoulder/hip pain with morning stiffness >45 minutes 3

Immediate Treatment Algorithm

First-Line: High-Dose Antihistamines

Start with second-generation non-sedating H1-antihistamines at standard doses, which can be increased up to 4-fold if needed 1:

• Examples: cetirizine, loratadine, fexofenadine, desloratadine
• These are the mainstay of therapy for both acute and chronic urticaria 1
• Avoid first-generation sedating antihistamines for chronic management 7

Second-Line: Omalizumab

If symptoms persist despite maximized antihistamine therapy, add omalizumab (anti-IgE monoclonal antibody) 1

• This is the established second-line treatment for uncontrolled chronic urticaria 1

Role of Corticosteroids

Corticosteroids may be used for acute flares but should NOT be used long-term 7:

• Short-term prednisone (12.5-25 mg daily) can be considered for severe acute exacerbations 8
• The FDA label supports prednisone use for "severe or incapacitating allergic conditions" 8
• However, chronic steroid use carries significant risks and is not appropriate for ongoing CSU management 7

Essential Diagnostic Workup

Laboratory Tests to Order Now

Complete the following tests to rule out other causes and assess disease burden 9:

• Complete blood count with differential (assess for anemia, leukocytosis) 9
• Comprehensive metabolic panel (liver enzymes, renal function, glucose) 9
• Serum ferritin (if Still's disease remains a consideration) 5
• Thyroid function tests (thyroid disease commonly associated with CSU)
• Consider autologous serum skin test (ASST) - positive results correlate with higher CRP levels 2

What NOT to Order

• Do NOT routinely order extensive autoimmune panels (ANA, RF, anti-CCP) unless specific joint symptoms develop 9
• Do NOT order imaging studies unless clinical features suggest specific organ involvement 9

Monitoring Strategy

Follow-Up Inflammatory Markers

Repeat ESR and CRP in 2-4 weeks to determine if elevation is persistent or transitory 9:

• Rising inflammatory markers signal treatment failure and need for escalation 3
• CRP normalizes faster than ESR during inflammation resolution 6

Disease Activity Assessment

• Use validated urticaria activity scores (UAS7 or daily UAS) to track response 4, 2
• Monitor quality of life with DLQI or CU-Q2oL questionnaires 4

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Do not assume urticaria is always allergic - chronic urticaria is rarely due to allergy 7
• Do not overlook medication causes - ACE inhibitors cause angioedema in 3-5% of patients 7
• Do not ignore stress as a major contributor to both chronic urticaria and recurrent angioedema 7

Interpretation Caveats

• Women have higher baseline ESR values than men 3
• Anemia and renal insufficiency can artificially elevate ESR independent of inflammation 3, 9
• CRP elevation is clinically relevant in CSU - higher levels predict antihistamine resistance 2

When to Escalate Care

Refer to Specialist If:

• Symptoms persist despite 4-fold increased antihistamine doses
• Need for omalizumab initiation (typically requires allergy/immunology referral)
• Development of systemic symptoms suggesting alternative diagnosis (persistent fever, joint swelling, weight loss)
• ESR rises above 40 mm/h or CRP continues to climb despite treatment 3