Chronic recurrent wheals – If not chronic spontaneous urticaria, what else?

Chronic urticarial rash, mostly due to chronic spontaneous urticaria (CSU), is seen in up to 1 – 4% of the general population. Urticarial vasculitis (UV) and autoinflammatory syndromes, i.e., cryopyrin-associated periodic syndromes (CAPS) and Schnitzler’s syndrome (SchS), can mimic CSU-like rash but represent rare disorders with systemic symptoms including fever, headache, conjunctivitis and arthralgia. Clinical and laboratory features can point to presence of any of these diseases in patients initially presented with chronic urticarial rash. These include long-lastung wheals (> 24 hours), lesional burning, systemic symptoms, and/ or increase in inflammatory markers (e.g., C-reactive protein, Serum Amyloid A, and/or S100A8/9). Lesional skin biopsy usually demonstrates leukocytoclastic vasculitis (UV) or neutrophil-rich infiltrat (CAPS and SchS). In contrast to CSU, where second generation H1-antihistamines and omalizumab allow to control symptoms in most patients, systemic immunosuppression and anti-interleukin (IL)-1 therapies are needed in case of UV and autoinflammatory diseases, respectively. The rarity and low awareness of CSU differential diagnoses may be related to the longer delays in diagnosis and therapy in those affected with UV, CAPS, and SchS. Knowledge of the differential diagnoses of CSU is important because only correct diagnosis allows adequate therapy. Complications such as the development of lymphoproliferative disease in SchS and amyloidosis in CAPS, and the presence of comorbid diseases, such as systemic lupus erythematosus in UV, must be considered and monitored.