HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS SYNDROME

Abstract

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a form of urticarial vasculitis (UV) characterized as a clinicopathologic entity comprised of chronic urticaria clinically and vasculitis pathologically. When patients with UV have an associated hypocomplementemia, they are more likely to manifest systemic complications of the disease and are characterized as having HUVS. HUVS is affected by both genetic and environmental factors; however, the exact cause remains unknown. HUVS is a rare disease with approximately 100 cases described, is more common in women, usually affects people in their 40s, and is rare in children but associated with a more complicated course when found in the pediatric population. Patients with HUVS have chronic urticaria for more than 6 months, hypocomplementemia, and a various array of systemic manifestations including musculoskeletal, respiratory, renal, gastrointestinal, cardiac, ophthalmologic, central nervous system, and rheumatologic features. Biopsies of active urticarial lesions show leukocytoclastic vasculitis with extravasation of white blood cells and endothelial cell damage. Patients almost invariably have low levels of the C1q component of complement as well as the presence of an IgG antibody directed against a collagen-like region of C1q, also refered to as C1q precipitans. Biopsies of certain organs, especially the kidney, may show deposits of these immune complexes within the basement membrane of inflamed tissue. The pathogenesis of HUVS is largely unknown, although hypotheses exist about exacerbating factors of the disease. HUVS is believed to be an autoimmune disease, much like systemic lupus erythematosus, with the formation of autoantibodies that cause immune complexes, deposition in certain parts of the body, and activation of the immune system causing inflammation and destruction. For example, immune complexes are thought to deposit in the lung, causing aggregation and activation of neutrophils, which actively secrete elastase, causing destruction of the lung architecture and the development of chronic obstructive pulmonary disease (COPD). There is no specific therapy for HUVS; however, many therapeutic agents have been found to be beneficial. Pruritus is treated with antihistamines and cutaneous manifestations have responded to dapsone, colchicine, antimalarials, nonsteroidal anti-inflammatory drugs (NSAIDs), interferon alpha, and corticosteroids. Severe systemic aspects of HUVS have been treated with chemotherapeutic/immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil, cyclosporine, and methotrexate, as well as combinations of previously mentioned agents. The prognosis of HUVS is relatively good; however, morbidity and mortality do occur, and are more likely to be seen in pediatric patients. Death from disease is rare, and is most commonly due to laryngeal edema or COPD.