Urticaria is a frequent disorder classified as acute and chronic forms, which presents with wheals that can be associated with
angioedema. Several entities may manifest with urticarial skin lesions, encompassing a heterogeneous group of conditions that have to be differentiated from ordinary
urticaria. This review is focused on two of these urticarial syndromes: urticarial
vasculitis (UV), which represents the most important differential diagnosis with common
urticaria, and autoinflammatory diseases such as
cryopyrin-associated periodic syndromes (CAPS) and Schnitzler's Syndrome, both rare multisystem forms that may masquerade as common
urticaria. UV is a small-vessel
vasculitis with predominant skin involvement, characterized by wheals persisting for more than 24 hours, burning rather than
itching and resolving with
hyperpigmentation as well as by other cutaneous manifestations including
purpura, papules, vesicles,
bullae and necrotic-ulcerative lesions. Histology shows a classic pattern of
leukocytoclastic vasculitis, with possible presence of upper dermal
edema. CAPS are classified as three distinct entities:
familial cold autoinflammatory syndrome,
Muckle-Wells Syndrome and
chronic infantile neurological cutaneous and articular syndrome, which represent a spectrum of disorders caused by different mutations in a single gene, NLRP3 (
NOD-like receptor 3). This gene encodes for cryopyrin, an
inflammasome protein that activates interleukin-1β, leading to an overproduction of this pivotal proinflammatory
cytokine. Histologically, urticarial lesions are generally characterized by a perivascular neutrophilic infiltrate. Unlike
urticaria, neither UV nor urticarial autoinflammatory syndromes do respond to
antihistamines: thus, it is important not to misdiagnose such conditions in order to give the patients specific treatments, potentially preventing serious systemic complications.