What Is Urticarial Vasculitis?
Urticarial vasculitis is one of the members of a family of rare diseases characterized by blood vessel inflammation that can hamper blood flow and subsequent damage to vital organs and tissues. The condition usually affects the small cutaneous vessels causing erythematous and itchy patches and hives, causing a burning sensation and leaving the skin discolored. Although usually the skin gets affected, based on the type of urticarial vasculitis, other parts or organ systems of the body may also be affected, presenting with associated clinical features.
What Are the Types of Urticarial Vasculitis?
Based on the level of complement protein in the circulating blood, urticarial vasculitis is categorized into two types. These complement proteins have a supporting role in the stage of the immune response.
1. Normocomplementemic Urticarial Vasculitis: The complement protein levels are usually low, and this type presents a less severe systemic manifestation.
2. Hypocomplementemic Urticarial Vasculitis: The complement protein levels are on the downside in this type, with severe systemic involvement that affects the joints, lungs, kidneys, gastrointestinal tract, and eyes.
Who Is Susceptible to Urticarial Vasculitis?
Although the exact global prevalence is still under investigation, some studies estimate an occurrence of 45 cases per million inhabitants. This was a study conducted in the United States, whereas a study by the British that restricted specimens to diagnosed vasculitis cases found a prevalence of just over two percent in those individuals. The gender gap of individuals is in the factor of two, with males predominating while the median age group of diagnosed individuals was found to be 43 years, most of them within the range of 15 to 90 years. Although with a middle-age onset, the condition may erupt in any age group.
What Is the Cause of Urticarial Vasculitis?
The exact cause of urticarial vasculitis is still unknown and under study. The condition is associated with multiple conditions, including
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Inflammatory conditions like systemic lupus erythematosus.
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Immunoglobulinopathies like IgA and IgM monoclonal gammopathies.
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Leukemias.
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Viral infections like hepatitis B, hepatitis C, or glandular fever.
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Parasitic infections.
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Drug-induced conditions from ACE inhibitors (angiotensin-converting enzyme inhibitors), Penicillin, Sulfonamides, Fluoxetine, and Thiazides.
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Idiopathic (with no known cause- this forms the bulk of the caseload).
What Is the Pathophysiology of Urticarial Vasculitis?
Owing to the umbrella (small vessel vasculitis) that this condition comes under, the pathophysiology basically remains comparative. Urticarial vasculitis is a type III hypersensitivity reaction in which the antigen-antibody complexes get deposited in the lumen of the blood vessels (vascular lumina). Much like other type-III hypersensitivities, this condition results in complement activation and chemotaxis of neutrophils (neutrophil recruitment from chemical stimuli). Furthermore, these cells release proteolytic enzymes like collagenase and elastase that start damaging the inner surface of the vascular lumina. The role of eosinophils in the early stages of vasculitis lesions has been hypothesized.
In hypocomplementemic urticarial vasculitis, the patient is positive for C1q-autoantibodies and vascular endothelial cells, with rare findings of antineutrophilic cytoplasmic antibodies (ANCA).
What Are the Clinical Features of Urticarial Vasculitis?
The primary symptoms of urticarial vasculitis involve skin lesions (wheals) and hives (urticaria) that cause intense itching, pain, and burning sensation. The skin patches are bordered red with white centers, along with petechia (pinpoint subsurface bleeding showing up as red or purple pinpoint discolorations on the skin). These patches appear and stay for over 24 hours, leaving behind a bruise-like discoloration. Ecchymoses and hyperpigmentation are the results of the healing process.
Severe urticarial vasculitis presents with systemic manifestations with symptoms like:
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Fever.
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Joint pain.
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Swelling of tissues under the skin.
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Abdominal pain.
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Swollen lymph glands.
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Shortness of breath.
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Bloodshot eyes.
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Kidney inflammation.
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Photosensitivity.
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Lung involvement.
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Cardiac involvement.
How to Diagnose Urticarial Vasculitis?
Apart from the obvious cutaneous manifestations, the primary diagnostician or dermatologist can order various laboratory investigations. Elevated ESR (erythrocyte sedimentation rate) and hypocomplementemia (a marker for immune complexes) are the most common laboratory findings, out of which hypocomplementemia is the most valuable criterion. Anti-C1q antibodies are found in half of hypocomplementemic urticarial vasculitis and 100 percent of hypocomplementemic urticarial vasculitis syndrome cases. Elevated levels of anti-thyroid antibodies are common in chronic spontaneous urticaria cases. Other positives for antibodies may come from CH50, C3, and C4 antigens.
Additional tests for liver and kidney function, urinalysis, CBC (complete blood count), blood chemistry profile, creatinine, pulmonary function tests, antinuclear antibody test, and anti-DNase (anti-deoxyribonuclease- a blood test to look for bacterial protein) test may be prescribed. These tests can determine the severity of the systemic manifestations of the condition and the seriousness of the symptoms of the respective organ systems. DIF (direct immunofluorescence) of skin lesions younger than 24 hours may show deposition of C3, fibrins, immunoglobulins, and an additional lupus band (in case of underlying lupus erythematosus). DIF may also show IgM, IgG, and IgA along the basement membrane of the skin. Sjogren syndrome cases can return positive for anti-SSA and anti-SSB antibodies.
What Are the Histologic Findings of Urticarial Vasculitis?
A skin biopsy sample obtained within 48 hours of onset is sent to the laboratory for staining and microscopic examination. Pathologists report the following findings in early lesions:
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Perivascular neutrophilic infiltrate.
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Leukocytoclasis.
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Eosinophilic infiltration.
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Fibrin deposition.
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Extravasation of red blood cells.
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In comparatively older lesions, lymphocytic and neutrophilic infiltration may be stated in pathology reports.
How to Treat Urticarial Vasculitis?
The normocomplementemic variant of the condition usually does not require any special care as the lesions are often self-limiting. Systemic manifestations of urticarial vasculitis and extended degree of cutaneous symptoms require treatment. Antihistamines (like Levocetirizine, Loratidine, Fexofenadine, or Doxepin), antibiotics, and NSAIDs (non-steroidal anti-inflammatory drugs) can take the edge off the symptoms.
For long-term management of severe urticarial vasculitis that is in conjunction with systemic manifestations, pharmacological regimens may be recruited. Medications like Dapsone, Colchicine, Hydroxychloroquine, Indomethacin, Prednisone, etc., may be prescribed. Since the condition is basically immune-mediated, immunosuppressive agents like Azathioprine, Cyclophosphamide, or Ciclosporin may be considered.
What Is the Differential Diagnosis of Urticarial Vasculitis?
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Chronic idiopathic urticaria.
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Well’s syndrome (eosinophilic cellulitis).
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Erythema multiforme (skin reaction triggered by external stimuli).
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Timid lupus erythematosus (a photosensitive form of cutaneous lupus erythematosus).
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Urticarial bullous pemphigoid (a chronic skin disorder).
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Schnitzler syndrome (rare autoinflammatory condition).
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Urticarial multiforme (benign skin hypersensitivity reaction).
What Are the Complications of Urticarial Vasculitis?
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Chronic obstructive pulmonary disorder.
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Renal complications.
The drugs used for the treatment carry their own set of side effects, including, but not limited to, decreased immunity, osteoporosis, and recurrent infections.
Conclusion
Urticarial vasculitis is a rare cutaneous pathology and can be recognized easily within the same day of onset of the cutaneous lesions. This can help with prompt diagnosis and prevent progression to systemic manifestations. The bulk of the prevalent is mostly idiopathic. But even with an unknown etiology, treatment measures are in place to push back the symptoms into remission.
