Urticarial Vasculitis: Symptoms, Types, Causes and Treatment

Urticarial vasculitis (UV) is a rare and intriguing skin condition that straddles the worlds of allergy, autoimmune disease, and vasculitis. Unlike ordinary hives, UV is marked by persistent, sometimes painful rashes and deeper immune system involvement. In this comprehensive guide, we’ll explore its key symptoms, the distinct types, underlying causes, and the latest evidence-based approaches to treatment. Whether you are a patient, caregiver, or healthcare provider, this article aims to provide a clear, engaging, and thorough overview of urticarial vasculitis.

Symptoms of Urticarial Vasculitis

Urticarial vasculitis can be easily confused with common urticaria (hives), but several features set it apart. Recognizing these symptoms is crucial for timely diagnosis and management.

Symptom	Description	Distinguishing Feature	Source(s)
Lesion Duration	Lasts >24 hours, sometimes up to 5 days	Longer than ordinary urticaria	1 2 3 4 6
Appearance	Raised, red plaques; may burn, itch, or hurt	Can resolve with purpura/hyperpigmentation	1 2 3 4 5
Systemic Symptoms	Fever, joint pain, abdominal pain, angioedema	Extracutaneous involvement	1 2 3 4 5
Post-inflammatory Change	Lesions may heal with darkening or bruising	Hyperpigmentation, ecchymosis	3 4 5 8

Table 1: Key Symptoms

How Symptoms Present

Urticarial vasculitis typically begins with red, raised wheals resembling classic hives. Unlike ordinary urticaria, these lesions persist beyond 24 hours and may last several days. They can be painful, tender, or even burn, and commonly leave behind bruising or dark patches (hyperpigmentation) as they resolve 1 2 3 4 5.

Skin Manifestations

• Duration: The most critical clue is duration—UV lesions last longer than 24 hours, whereas ordinary hives fade within a day 2 3 4.
• Resolution: Lesions can resolve with purpura or bruising, which is not typical for simple urticaria 1 3.
• Sensation: While itching is common, pain and burning are also frequently reported 1 3.

Systemic Features

UV is unique among skin conditions for its potential to affect other organ systems:

• Angioedema (swelling of deeper skin layers)
• Arthralgias (joint pain)
• Fever
• Abdominal pain
• Pulmonary symptoms (e.g., cough, shortness of breath) 1 3 4 5

Systemic symptoms are more common in certain subtypes of UV (see below).

Chronicity and Recurrence

In most cases, urticarial vasculitis is chronic, with episodes recurring over weeks, months, or even years 3 8.

Types of Urticarial Vasculitis

Not all cases of urticarial vasculitis are alike. Classification is mainly based on blood tests that measure complement protein levels, which reflect immune system activity. This distinction is important because it influences both symptoms and prognosis.

Type	Complement Levels	Systemic Involvement	Source(s)
Normocomplementemic UV	Normal	Minimal/none	2 3 4 11
Hypocomplementemic UV	Low	More severe/multiorgan	1 2 3 4
Hypocomplementemic UV Syndrome (McDuffie)	Markedly low	Severe, syndromic	4

Table 2: Main Types of Urticarial Vasculitis

Normocomplementemic Urticarial Vasculitis (NUV)

• Definition: Normal levels of serum complement proteins.
• Clinical Features: Primarily skin-limited disease, with minimal or no systemic involvement.
• Prognosis: Generally more favorable; less risk of severe organ damage 2 3 4 11.

Hypocomplementemic Urticarial Vasculitis (HUV)

• Definition: Reduced complement levels in blood, especially C1q, C3, or C4.
• Clinical Features: Higher risk of systemic symptoms, such as joint pain, abdominal discomfort, pulmonary complications, and kidney involvement 1 3 4.
• Immunological Findings: Often associated with anti-C1q antibodies, reflecting an autoimmune process 4.
• Prognosis: More severe, higher risk of chronicity and multi-organ effects.

Hypocomplementemic Urticarial Vasculitis Syndrome (McDuffie Syndrome)

• Definition: A rare, syndromic variant of HUV with marked complement consumption.
• Clinical Features: Severe, multi-organ involvement, including kidneys, lungs, gastrointestinal tract, and eyes 4.

Histopathological Subtypes

Diagnosis is confirmed by skin biopsy, revealing features of leukocytoclastic vasculitis—fibrinoid necrosis of small vessel walls, neutrophilic infiltration, and sometimes immune complex deposition 1 4 6. The presence of these findings helps distinguish UV from chronic spontaneous urticaria (CSU) 6.

Causes of Urticarial Vasculitis

Understanding what triggers urticarial vasculitis helps in both management and prevention. For many patients, the cause remains mysterious, but several associations are well recognized.

Cause Category	Examples	Notes	Source(s)
Idiopathic	No clear cause	Most common	3 7 8 9
Autoimmune Disease	SLE, Sjögren’s, other connective tissue	May overlap with UV	3 4 8
Infections	Hepatitis, Influenza, COVID-19	Direct/indirect trigger	5 8
Drugs & Vaccines	Antibiotics, NSAIDs, vaccines (e.g., COVID-19)	Possible triggers	5 8
Malignancy	Lymphoma, myelodysplastic syndrome	Paraneoplastic	3 8 9

Table 3: Main Causes and Associations

Idiopathic Urticarial Vasculitis

• Most Common: For the majority, no specific cause can be identified. These cases are termed idiopathic 3 7 8 9.

Autoimmune and Connective Tissue Disorders

• Systemic Lupus Erythematosus (SLE): UV sometimes occurs in patients with SLE, and both share similar immune findings (e.g., anti-C1q antibodies) 3 4 8.
• Sjögren's Syndrome and other autoimmune conditions have been linked as well 2 4.

Infections

• Viral Infections: Influenza and COVID-19 have been reported as triggers for UV 5 8.
• Other Pathogens: Hepatitis and other infections may also act as triggers.

Medications and Vaccines

• Medications: Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and some other drugs have been reported to cause UV 8.
• Vaccines: Rarely, vaccines (including COVID-19 vaccines) can induce UV, usually within days of administration 5.

Malignancy

• Cancer-Associated UV: Myelodysplastic syndromes and lymphomas can present with UV as a paraneoplastic phenomenon 3 8 9.

Pathogenesis

The underlying mechanism involves immune complex deposition in small blood vessels, activation of the complement cascade, and recruitment of neutrophils, leading to vessel wall inflammation and damage 4 7. This immune-driven process distinguishes UV from ordinary hives, which result from histamine-mediated swelling.

Treatment of Urticarial Vasculitis

Managing urticarial vasculitis can be challenging due to its varied severity and underlying causes. No universal guidelines exist, so treatment is individualized based on clinical presentation and systemic involvement.

Treatment Option	Indication	Efficacy/Notes	Source(s)
Corticosteroids	Skin/systemic symptoms	High efficacy, side effects with prolonged use	3 8 9
Immunosuppressives	Severe/refractory cases	Azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate mofetil	3 8 9
Biologics	Refractory cases	Omalizumab, rituximab, IL-1 inhibitors	8 9 11
Antihistamines	Mild skin disease	Often ineffective alone	3 9
Other agents	Mild/moderate/adjunct	Dapsone, colchicine, hydroxychloroquine, NSAIDs	3 5 8 9

Table 4: Treatment Approaches

First-Line Treatments

• Corticosteroids: Oral prednisone or similar drugs are very effective for controlling skin and systemic symptoms, especially in moderate to severe cases. However, long-term use is limited by side effects (e.g., weight gain, diabetes, osteoporosis) 3 8 9.
• Antihistamines: Sometimes used in mild cases, but often insufficient as monotherapy 3 9.

Steroid-Sparing and Immunomodulatory Agents

To reduce steroid dependency, other medications are often added:

• Dapsone
• Colchicine
• Hydroxychloroquine
• NSAIDs (for symptom relief) 3 5 8 9

Immunosuppressives

For patients with organ involvement or resistant disease:

• Azathioprine
• Cyclophosphamide
• Cyclosporine
• Methotrexate
• Mycophenolate mofetil 3 8 9

Biologic Therapies

In refractory cases, biologics have shown promise:

• Omalizumab: Anti-IgE antibody, shown to induce remission in some patients with normocomplementemic UV 8 11.
• Rituximab: Anti-CD20 antibody (B-cell depletion).
• Interleukin-1 inhibitors 8 9.

Other Options

• Plasmapheresis and intravenous immunoglobulin (IVIG) have been tried in selected cases.
• Topical agents (e.g., calamine lotion) can be used for symptomatic relief in mild cases 5.

Efficacy and Limitations

• No Approved Drugs: There are currently no medications specifically approved for UV; treatment is guided by clinical experience and case reports 9 10.
• Variable Response: Individual responses vary widely, necessitating a tailored approach.
• Prognosis: NUV tends to have a better prognosis and may require less aggressive therapy than HUV, which often needs prolonged immunosuppression 3 4 11.

Conclusion

Urticarial vasculitis is a complex, often misunderstood condition that blurs the boundaries between allergy and autoimmune disease. Recognizing its hallmark symptoms—persistent, sometimes painful hives that resolve with bruising, and the potential for systemic involvement—is key for diagnosis and treatment. Distinguishing between normocomplementemic and hypocomplementemic types helps guide therapy and anticipate prognosis. While most cases are idiopathic, associations with autoimmune diseases, infections, drugs, and malignancy are important to consider. Treatment remains challenging and highly individualized, but advances in immunosuppressive and biologic therapies offer new hope for patients with severe or refractory disease.

Key Points:

• Urticarial vasculitis presents with hives lasting >24 hours, often resolving with bruising or pigmentation, and may include systemic symptoms 1 2 3 4 5.
• Two main types: normocomplementemic (skin-limited, better prognosis) and hypocomplementemic (more severe, systemic involvement) 2 3 4 11.
• Most cases are idiopathic, but autoimmune diseases, infections, drugs, vaccines, and malignancies are recognized triggers 3 5 8 9.
• Treatment ranges from corticosteroids and antihistamines for mild disease to immunosuppressives and biologics for severe or refractory cases 3 8 9 11.
• Individualized management is essential, as no universal guidelines or approved therapies currently exist 9 10.