Hypocomplementemic Urticarial Vasculitis

Hypocomplementemic urticarial vasculitis (HUV) is an immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C1q with or without low C3 and C4), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation, and glomerulonephritis are common systemic manifestations.

Epidemiology

Prevalence is unknown but less than 200 cases have been reported in the literature. Women are more frequently affected than men (female to male ratio of 8:1).

Clinical description

Patients most commonly present during the fourth decade of life but onset during childhood has been described. Patients present with generalized urticarial eruptions located on the trunk, proximal extremities and face that are often associated with itching or pain and persist for more than 24 hours, with hyperpigmentation after resolution. Angioedema is common and may also be a presenting feature. Cardiorespiratory manifestations include cough, dyspnea, pleural and pericardial effusions, and emphysema, with chronic obstructive pulmonary disease reported in 20-50% of patients. Renal disease is present in around half of patients and is generally mild with proteinuria and hematuria caused by glomerulonephritis. However, renal insufficiency and end-stage renal failure have been reported and renal involvement tends to be more severe in patients with childhood onset. Other systemic findings include gastrointestinal symptoms (abdominal pain, nausea, diarrhea, vomiting), musculoskeletal manifestations (arthritis and transient arthralgia affecting the hands, elbows, knees, ankles, and feet), ocular inflammation (episcleritis, uveitis and conjunctivitis) and, more rarely, neurological findings (pseudotumor cerebri, aseptic meningitis, cranial and peripheral nerve palsies and transverse myelitis). A few patients with the rare combination of HUV, Jaccoud's arthropathy and valvular heart disease have also been reported. HUV may also be associated with an increased susceptibility to pyogenic infections.

Etiology

HUV generally occurs sporadically but occurrence in siblings has been described. Both genetic and environmental factors are likely to play a role in the etiology of HUV and anti-C1q autoantibodies are believed to be involved in the pathogenesis of the disorder.

Diagnostic methods

Diagnosis requires the presence of two major criteria (recurrent urticaria for > 6 months and hypocomplementemia) and at least two minor criteria (leukocytoclastic vasculitis on biopsy, arthralgia and arthritis, ocular inflammation, abdominal pain, glomerulonephritis and positive anti-C1q autoantibodies).

Differential diagnosis

The relationship of HUV to systemic lupus erythematosus (SLE) is complex with many overlapping features (manifestations of HUV are present in 10% of SLE patients and 50% of patients with HUV will later be diagnosed as having SLE). Other syndromes such as mixed cryoglobulinemia, Muckle-Wells syndrome, Cogan syndrome and Schnitzler syndrome should be excluded (see these terms).

Management and treatment

There is no specific treatment and management requires tailored therapy with steroids and immunosuppressives. For example, patients with cutaneous disease and arthralgias but no major organ involvement may be managed with low-dose prednisone, hydroxychloroquine, or dapsone; whereas patients with major organ involvement, such as glomerulonephritis, may require high doses of corticosteroids and cytotoxic agents similar to the treatment for active SLE. Response to treatment is usually accompanied by a decrease in circulating anti-C1q titer and normalization of C3 and C4 levels, although C1q often remains low.

Prognosis

The prognosis for HUV patients is variable and is influenced primarily by the severity of pulmonary, cardiac and renal disease. When present, pulmonary disease is the major cause of death. Acute laryngeal edema can be life-threatening. Although uncommon in childhood, the prognosis is worse for early onset HUV patients because of more frequent severe renal involvement.