Understanding Chronic Urticaria: A Comprehensive Patient Guide to Hives

Table of Contents

• What is Chronic Urticaria?
• How Common is This Condition?
• Types of Chronic Urticaria
• What Causes Hives?
• Recognizing the Symptoms
• How Doctors Diagnose Urticaria
• Conditions Associated with Chronic Hives
• Treatment Options and Management
• What to Expect Long-Term
• Future Research Directions
• Key Takeaways for Patients
• Source Information

What is Chronic Urticaria?

Chronic urticaria refers to persistent hives (wheals), swelling (angioedema), or both that continue for at least 6 weeks. This differs from acute urticaria, which lasts less than 6 weeks and often has identifiable triggers like foods, medications, or infections.

Patients with this condition typically see allergy-immunology or dermatology specialists, but primary care providers often serve as the first point of contact for evaluation and treatment. The condition involves recurrent episodes that can significantly impact daily life due to unpredictable flare-ups and intense itching.

How Common is This Condition?

An estimated 500,000 people in the United States have chronic urticaria, representing a prevalence of 0.23% in the population. While the disorder can occur at any age, most affected patients are women, and patients of both sexes tend to be over 40 years old.

The impact on quality of life is substantial. The random occurrence of episodes, intense itching that disrupts sleep, and restrictions in physical and emotional functioning have been shown to significantly impair daily life. Research shows that the degree of impairment for chronic urticaria patients is similar to that reported by patients with coronary artery disease awaiting coronary artery bypass grafting.

Patients with chronic urticaria also show higher rates of coexisting psychiatric conditions compared to the general population or people with other chronic conditions. The validation of patient-reported outcome measures has helped healthcare providers better understand this significant disease burden in recent years.

Types of Chronic Urticaria

Medical experts categorize chronic urticaria into two main types based on consensus guidelines. Spontaneous urticaria (previously called chronic idiopathic urticaria) involves hives, swelling, or both that occur without obvious triggers. Inducible urticaria (previously called physical urticaria) involves symptoms elicited by specific factors like cold, heat, or pressure.

The most common forms of inducible urticaria include dermatographia ("skin writing") and cholinergic urticaria. Dermatographia affects up to 5% of the general population, though few people have symptoms severe enough to require medical attention. Cholinergic urticaria accounts for approximately 5% of all chronic urticaria cases and up to 30% of inducible cases.

What Causes Hives?

The lesions result from degranulation of cutaneous mast cells, which leads to the release of histamine - the major mediator of itchy wheals and angioedema. The process also involves release of cysteinyl leukotrienes, prostaglandins, platelet-activating factor, and other substances.

Proinflammatory cytokines and vasoactive factors are also released, causing vasodilation and leakage of plasma from blood vessels in and below the skin. Lesions show a predominantly lymphocytic infiltrate, with eosinophils and neutrophils also possibly present.

While acute urticaria usually has identifiable causes like drugs, foods, or infections, chronic urticaria typically has no identifiable cause. For inducible types, physical stimuli provoke histamine release, creating the characteristic itchy wheal-flare response. Some forms, like aquagenic urticaria (triggered by water), have unclear mechanisms but may involve water interacting with skin components to create compounds that activate mast cells.

Recognizing the Symptoms

Chronic urticaria is characterized by itchy wheals with circumferential redness that can appear anywhere on the body. Lesions range from a few millimeters to several centimeters in diameter and typically resolve within 24 hours without bruising.

Research shows that approximately two-thirds of patients experience both hives and angioedema, while the remaining one-third have only one or the other. Angioedema involves deeper swelling that typically affects the face, extremities, or torso.

The appearance can vary across different skin tones. On Black or brown skin, the erythematous (red), raised lesions may be less apparent due to similarity in hue with surrounding skin, though they remain equally symptomatic. Patients may not have active lesions during medical visits, but diagnosis can be based on history and photos taken during flare-ups.

How Doctors Diagnose Urticaria

The initial evaluation involves comprehensive history-taking to determine the timing, frequency, and nature of episodes. Physicians look for whether lesion appearance matches chronic urticaria characteristics. Painful or burning sensations combined with non-blanching lesions that persist over 24 hours and leave bruises might suggest alternative diagnoses like cutaneous vasculitis.

For inducible urticaria, doctors can confirm diagnosis through provocative challenge testing. Common tests include:

• Dermatographia: Stroking skin with a firm object produces wheals within 1-3 minutes
• Cold urticaria: Ice cube or ice pack application for 5 minutes causes urticaria during rewarming
• Cholinergic urticaria: Methacholine injection or hot water immersion produces small "punctate" wheals
• Delayed pressure urticaria: Weight application causes angioedema 2-12 hours later

Exercise-induced urticaria requires special attention as it can progress to anaphylaxis. Patients with this condition should exercise with a companion and cell phone, and may need epinephrine prescriptions.

Conditions Associated with Chronic Hives

While most chronic urticaria cases are idiopathic, associations have been reported with various conditions including:

• Infections (hepatitis B and C, Epstein-Barr virus, herpes simplex, mycoplasma, Helicobacter pylori, helminthic infestation)
• Rheumatologic diseases (systemic lupus erythematosus, juvenile rheumatoid arthritis)
• Thyroid disease (both hypothyroidism and hyperthyroidism)
• Neoplasms (particularly lymphoreticular cancers and lymphoproliferative disorders)
• Ovarian tumors and oral contraceptive use

However, these associations are rare. For patients with unremarkable medical history and physical examination, routine extensive laboratory testing is not recommended as it's not cost-effective and rarely changes management. In one study of 356 cases, only one patient had test results that led to meaningful treatment changes.

Treatment Options and Management

Treatment follows a stepped approach similar for both adults and children. Factors that can lower the threshold for breakthrough episodes include alcohol, stress, opiates, and menstrual cycles. Patients should avoid NSAIDs (nonsteroidal anti-inflammatory drugs) which may exacerbate symptoms, using acetaminophen instead for pain or fever relief.

Step 1: Start with second-generation H1-antihistamine monotherapy taken regularly rather than as needed. These medications cause fewer side effects than first-generation antihistamines. However, this approach achieves complete control in less than 50% of patients.

Step 2: Dose escalation of second-generation antihistamines up to four times the FDA-approved dose. Adjunctive therapies may include additional H1-antihistamines or antileukotriene agents. Short-term oral glucocorticoids can restore control but may lead to relapse after withdrawal.

Step 3: For treatment-resistant cases, options include:

1. Omalizumab: The only FDA-approved biologic for antihistamine-resistant chronic urticaria, supported by high-quality evidence from multiple randomized controlled trials. At 300 mg every 4 weeks, it shows clinically meaningful improvements in symptoms and quality of life.
2. Cyclosporine: Shown effective in several randomized controlled trials if omalizumab fails after 6 months.
3. Alternative agents: Including dapsone, hydroxychloroquine, stanozolol, mycophenolate, sulfasalazine, and colchicine, though evidence varies for these options.

Ongoing clinical trials are investigating new treatments targeting interleukin-4/interleukin-13, interleukin-5, thymic stromal lymphopoietin, Siglec-8, more potent anti-IgE antibodies, and Bruton's tyrosine kinase inhibitors.

What to Expect Long-Term

Prospective studies show that one year after starting treatment, 35% of chronic urticaria patients become symptom-free, while 29% experience reduced symptoms. Remission rates differ significantly between types: 47% for chronic spontaneous urticaria but only 16% for chronic inducible urticaria.

Factors associated with longer disease duration include the presence of angioedema, greater disease severity, and autoimmune thyroid disease. The unpredictable course and varying treatment responses mean patients should maintain regular follow-up with their healthcare providers.

Future Research Directions

Research continues to explore why some patients develop chronic urticaria. A subset of patients have various autoantibodies, but their exact role in causing disease, guiding treatment, or predicting outcomes remains unclear.

Emerging data suggest that treatment responsiveness and disease course may relate to the presence of autoantibodies, inflammatory markers, clinical markers, and serum IgE levels. Future laboratory testing might help predict disease duration and likelihood of response to specific therapies, though currently, routine extensive testing isn't recommended.

Key Takeaways for Patients

While healthcare providers often cannot identify a specific cause for chronic urticaria, effective management strategies can significantly improve quality of life. Treatment follows a stepped approach, and patients should:

• Take medications regularly as prescribed rather than only during flare-ups
• Avoid known triggers including NSAIDs, alcohol, and stress when possible
• Work with their healthcare provider to identify any inducible triggers through testing
• Maintain realistic expectations about treatment timelines and outcomes
• Consider carrying epinephrine if they have exercise-induced urticaria or risk of anaphylaxis

The field continues to evolve with new treatments under investigation, offering hope for patients with difficult-to-control symptoms.

Source Information

Original Article: Chronic Urticaria
Author: David M. Lang, M.D.
Publication: The New England Journal of Medicine 2022;387:824-31
DOI: 10.1056/NEJMra2120166

This patient-friendly article is based on peer-reviewed research from The New England Journal of Medicine. It maintains all significant findings, data points, and clinical recommendations from the original publication while translating medical terminology for patient understanding.