Urticarial vasculitis and hypocomplementemic urticarial vasculitis syndrome

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Terminology

A variety of cutaneous, serologic, and systemic features have characterized UV, resulting in different names for this disease entity. These names include hypocomplementemia with cutaneous vasculitis and arthritis [1], urticaria and arthralgia with necrotizing angiitis [6], unusual SLE-like syndrome [7], and hypocomplementemic vasculitic urticarial syndrome (HUVS) [8]. It is likely that there is a continuum of disease, varying from urticaria with minimal vasculitis, to urticaria with marked

Incidence and epidemiology

UV is relatively uncommon [9], but its true incidence depends on the definition of vasculitis. Patients presenting with chronic urticaria have a prevalence of UV ranging from 2% to 20% [10], [11], [12], [13], [14]. When a strict definition of vasculitis is used, as in this article, the prevalence is 5% [3], [9], [15].

UV is more common among women, who women accounting for 60% [19] to 80% [16] of cases. There is a peak incidence in the fourth decade of life [16], [17], [18], [19]. UV is also

Histopathology

A biopsy of an active lesion remains the gold standard for diagnosing UV [27]. The histopathology of UV often reveals LCV [2], [4], [10]. Leukocytoclasis, defined as the fragmentation of neutrophils resulting in scattered nuclear fragments or nuclear dust, frequently is seen in the infiltrate. Erythrocytes may extravasate and can be seen perivascularly and in the interstitium. Swelling of the endothelial cells also occurs and may be so extensive as to occlude the lumen of affected vessels.

Differential diagnosis

The differential diagnosis of UV includes acute urticaria, chronic urticaria, and chronic neutrophilic vasculitis manifesting as palpable purpura. Several clinical and histologic characteristics are used to differentiate among these different diseases.

In acute urticaria, marked dermal edema is seen. There is no endothelial cell swelling, no leukocytoclasis, and no red blood cell extravasation; however, a sparse leukocytic perivascular infiltrate may be noted [4], [27].

Chronic urticaria can have

Immunopathology

Most patients with UV have deposits of immunoglobulins, complement, or fibrin within vessel walls seen by immunofluorescence. A granular deposit of immunoglobulins and complement can be appreciated within the basement membrane zone of the skin [39].

Kano et al, in an experiment with exercise-induced UV, proposed a sequence of events leading to frank LCV. This sequence includes the deposition of immune complexes, mast cell activation and release of tumor necrosis factor α (TNF-α), influx of

Hypocomplementemic urticarial vasculitis syndrome

The presence of hypocomplementemia in association with UV has been recognized to represent a more serious and systemic form of UV by McDuffie at Mayo Clinic [1]. HUVS, sometimes referred to as McDuffie syndrome, is an uncommon autoimmune disorder with systemic manifestations that resemble SLE [41]. McDuffie et al [1] and Agnello et al [7], [42] described patients with this syndrome of hypocomplementemia associated with recurrent erythematous; urticarial and sometimes hemorrhagic skin lesions;

Pathophysiology

UV is considered to be an immune complex disease, similar to cutaneous vasculitis [39]. A type III hypersensitivity reaction is believed to characterize the pathogenesis of UV [9]. One question that has been posed addresses the issue of whether immune complexes cause UV or whether complexes are produced as a consequence of vasculitis [39]. Dienstag et al studied patients with UV and hepatitis B virus infection. They found deposits of the hepatitis B virus surface antigen and IgM within vessel

Clinical features

In patients with UV, features of urticaria or vasculitis may predominate. Distinct clinical patterns have been described Table 1, Table 2. Classically the urticarial plaques may be persistent or long lasting and may resolve with purpura or hyperpigmentation (see Table 1) [17]. Callen et al described the lesions of UV as long lasting when they persisted for more than 4 hours [70]. Most authors who have studied UV have found that the long-lasting lesions of UV persisted for more than 24 hours,

Systemic manifestations

Many patients with UV have systemic involvement (see Table 2) that manifest in a target-organ fashion, similar to cutaneous vasculitis [39]. Some of the most common systemic manifestations of UV include the so-called “AHA syndrome,” which consists of arthralgias and arthritis (A), hives (H), and angioedema (A). These symptoms may surface with exacerbating situations, such as emotional stress, anxiety, exercise, and excessive alcohol consumption [75].

As noted earlier, there is overlap in the

Causes and associations

Most cases of UV have an unknown cause (Table 3). There are a few associations with connective tissue diseases, including SLE [35], [107], [108], [109], [110] and Sjögren's syndrome [111]. Alecander et al found that 32% of patients with Sjögren's syndrome had UV [111]. In Sjögren's syndrome and essential mixed cryoglobulinemia, an urticarial-like eruption can be seen. These lesions are more purpuric than urticarial and have an association with the lower extremities. The lesions can be

Investigation

In approaching a possible case of UV, clinicians first should establish the diagnosis and then evaluate for systemic involvement and the possibility of an associated disease or causal factor (Table 4) [72].

To diagnose UV, the first step is obtaining a lesional sample for histologic examination. When considering aspects of biopsy, early lesions are preferred in UV, and multiple biopsies sometimes are needed to make the diagnosis [9]. To diagnose UV, the criteria for vasculitis must be fulfilled

Treatment

UV is often a difficult disease to treat, and the treatment employed often is dictated by the severity of disease. As the spectrum of UV can range from cutaneous lesions alone to severe systemic involvement, the therapeutic options are broad. Antihistamines are the mainstay for patients with UV and only cutaneous involvement. Several systemic immunosuppressants and chemotherapeutic drugs are available for patients with severe systemic involvement. If an underlying disease is identified, it

Prognosis

UV is a complicated disease with an unpredictable course. The time span for developing new lesions ranges from weeks to many years [2]. The outcome of UV is usually favorable, and few patients experience terminal problems. The benign course of UV, however, more often is associated with the idiopathic, normocomplementemic form of the disease. In the largest series reported, these patients had no other disease manifestations over a 12-year span [71]. The average duration of disease is 3 years [19]

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