Hypocomplementemic Urticarial Vasculitis Syndrome: Clinical and Serologic Findings in 18 Patients

Abstract

We identify and describe clinical findings in hypocomplementemic urticarial vasculitis syndrome (HUVS), an uncommon to rare illness related to systemic lupus erythematosus (SLE). A patient with recurrent, idiopathic urticaria-like lesions was diagnosed as having HUVS if a lesional biopsy showed leukocytoclastic vasculitis, the serum C1q was markedly decreased, and antibody to C1q was detected in the patient's serum. The clinical characteristics, serologic findings, and outcome of patients who met these criteria were determined from prospective and retrospective data, including hospital and office records, patient interviews, previously banked serum samples, and freshly drawn sera. Eighteen patients with HUVS were identified, and high incidences of angioedema, ocular inflammation, glomerulonephritis, and obstructive pulmonary disease were found. Renal and lung biopsies showed mesangial or membranoproliferative glomerulonephritis and severe pulmonary emphysema without vasculitis. Pulmonary function was measured in 17 patients, 11 of whom had dyspnea. All dyspneic patients had moderate to severe airflow obstruction, which progressed in all 11 and subsequently improved in only 1. Six of these 11 patients died of respiratory failure, 1 underwent lung transplantation, and 3 of the remaining 4 have moderately severe to life-threatening respiratory insufficiency. Treatment did not appear to alter the progression of obstructive lung disease. In contrast, renal insufficiency improved with treatment in 2 of 2 patients. Angioedema, ocular inflammation, obstructive lung disease, and glomerulonephritis appear to be common in HUVS, and lung disease causes substantial morbidity and mortality. The pathogenesis of HUVS may involve humoral autoimmunity, although it is not clear how autoimmunity would participate in development of obstructive lung disease. Cigarette smoking appears to be a risk factor for fatal lung disease in HUVS. All patients with HUVS should be made aware of this possibility and should be advised, encouraged, and helped to avoid tobacco smoke.

The Globular Heads of C1q Specifically Recognize Surface Blebs of Apoptotic Vascular Endothelial Cells

“…Anti-C1q autoantibodies have been identified in 30 -34% of humans with lupus (62) and approximately 50% of MRL lpr/lpr mice with lupus (63). Furthermore, the lupus-like disorder HUVS is defined by the presence of autoantibodies targeted to C1q, one of the criteria for diagnosis (24,62,64). HUVS is characterized by low serum levels of C1q, C4, and C3, and a prominent clinical manifestation is vascular inflammation.…”

Angioedema without urticaria: a large clinical survey

“…33,34 Hence, angioedema can be a major feature of the so-called hypocomplementemic urticaria vasculitis syndrome (HUVS). 35 Although we have seen some patients so diagnosed, the angioedema in each case coexisted with clinically significant urticaria; the patients were therefore not included in our study.…”

C1q Deficiency Promotes Pulmonary Vascular Inflammation and Enhances the Susceptibility of the Lung Endothelium to Injury

“…Although this study focused exclusively on the pulmonary circulation we presume that C1q also has important anti-inflammatory actions on the systemic endothelium. This hypothesis is supported by several lines of evidence including clinical observations demonstrating that low plasma C1q levels are associated with the development of systemic vasculitis (39,40) as well as by experimental studies in mice showing that endothelial barrier dysfunction is exacerbated in systemic blood vessels of C1q Ϫ/Ϫ mice during sepsis (41). Together, these support the notion that C1q has important anti-inflammatory actions in both the systemic and pulmonary circulations.…”