Managing Urticarial Vasculitis: A Clinical Decision-Making Algorithm Based on Expert Consensus

Abstract

Urticarial vasculitis (UV) is a rare and difficult-to-treat, small-vessel leukocytoclastic vasculitis presenting with recurrent long-lasting wheals. So far, no guidelines and treatment algorithms exist that could help clinicians with the management of UV. In this review, we describe evidence on systemic treatments used for UV and propose a clinical decision-making algorithm for UV management based on the Urticarial Vasculitis Activity Score assessed for 7 days (UVAS7). Patients with occasional UV-like urticarial lesions and patients with UV with skin-limited manifestations and/or mild arthralgia/malaise (total UVAS7 ≤7 of 70) can be initially treated using the step-wise algorithm for chronic urticaria including second-generation H1-antihistamines, omalizumab, and cyclosporine A. Patients with UV with more severe symptoms (UVAS7 >7), especially those with hypocomplementemic UV, may require a multidisciplinary approach, particularly if underlying diseases, for example, systemic lupus erythematosus, cancer, or infection, are present. Immunomodulatory therapy is based on clinical signs and symptoms, and the drug availability and safety profile, and includes systemic corticosteroids, dapsone, hydroxychloroquine, anti-interleukin-1 agents, and other therapies. The level of evidence for all UV treatments is low. Prospective studies with current and novel drugs are needed and could provide further insights into UV pathogenesis and treatment.

Fig. 1

Treatment algorithm for urticarial vasculitis (UV). ANA anti-nuclear antibodies AZA azathioprine, Blood hematotoxicity, CBC complete blood count, CMP complete metabolic panel, COL colchicine, CP cyclophosphamide, CRP c-reactive protein, CsA cyclosporine A, CSU chronic spontaneous urticaria, DAP dapson, ENA extractable nuclear antigen antibodies, ESR erythrocyte sedimentation rate, h hours, HCQ hydroxychloroquine, IgE immunoglobulin E, IL1 interleukin-1, Liver liver function, MMF mycophenolate mofetil, MTX methotrexate, NSAIDs non-steroidal anti-inflammatory drugs, nurs nursing, Oma omalizumab, Preg pregnant, Renal renal function, sgAHs second-generation anti-histamines, SGC systemic glucocorticosteroids, UVAS Urticarial Vasculitis Activity Score, UVAS7 Urticarial Vasculitis Activity Score assessed for 7 days. 1. Examples for systemic symptoms: fever, arthralgia, abdominal pain, eye inflammation. 2. Possible investigations: CBC, CRP, ESR, hepatic panel, ANA/ENA, C3, C4, CH50, C1q, creatinine, urinalysis, serum and urine protein, electrophoresis, serum immunofixation electrophoresis. If C3/C4 complement levels are below normal range class UV as HUV. 3. Neutrophilic urticarial dermatosis in autoinflammatory disease or other vasculitis. 4. Comorbidities: systemic lupus erythematosus, malignancies, active infections. 5. Consider triggers: e.g., drug withdrawal, (treatment of) underlying disease. 6. For UV diagnosis, the following should be present: leukocytoclasia, fibrin deposits, and extravasated erythrocytes [68]. 7. (Re)assess UVAS7 for past 7 days every 4 weeks and de-escalate if possible to avoid adverse events. If wheals are the only symptom present, consider treating as mild UV even if UVAS7 is higher than 7. 8. If mild disease activity with predominantly itchy wheals, treatment with sgAHs and omalizumab can be considered before taking a skin biopsy. 9. Mild UV: skin-limited symptoms with or without mild arthralgia and/or mild general symptoms. 10. When treating sgAH and omalizumab-non-responsive UV, cyclosporine may be substituted with other treatments/add-ons, e.g., low-dose SGC, HCQ or dapsone, based on the patient profile, risk-benefit assessment, and physician and patient preferences (shared decision making). 11. Unless when using paracetamol. 12. When using anakinra. 13. Based on a set schedule. 14. Do not use if neutrophils <1500/mm³. 15. Do not use if platelets <50,000/mm³