There are a number of systemic disorders that can manifest with urticarial skin lesions, including urticarial vasculitis, connective tissue diseases, hematologic diseases, and autoinflammatory syndromes. All of these conditions may enter into the differential diagnosis of ordinary urticaria. In contrast to urticaria, urticarial syndromes may manifest with skin lesions other than wheals, such as papules, necrosis, vesicles, and hemorrhages. Lesions may have a bilateral and symmetrical distribution; individual lesions have a long duration, and their resolution frequently leaves marks, such as hyperpigmentation or bruising. Moreover, systemic symptoms, such as fever, asthenia, and arthralgia, may be present. The most important differential diagnosis in this group is urticarial vasculitis, which is a small-vessel vasculitis with predominant cutaneous involvement. Systemic involvement in urticarial vasculitis affects multiple organs (mainly joints, the lungs, and the kidneys) and is more frequent and more severe in patients with hypocomplementemia. Clinicopathologic correlation is essential to establishing a correct diagnosis.

After completing the learning activity, participants should be able to distinguish urticarial lesions suggesting diagnoses other than common urticaria; assess patients with urticarial lesions, and suspect systemic diseases presenting with urticarial skin lesions.