Version August 2025
ALGORITHM —
INITIAL EVALUATION —
C1q is usually measured during the assessment of suspected hypocomplementemic urticarial vasculitis syndrome (HUVS) or angioedema without an obvious trigger or underlying cause (to identify acquired angioedema due to C1 esterase inhibitor deficiency [AAE-C1-INH]). Although C1q concentrations are often subnormal in patients with immune complex diseases that activate the complement system, such as systemic lupus erythematosus (SLE), C1q is not usually measured in SLE patients. (See "Urticarial vasculitis", section on 'Hypocomplementemic urticarial vasculitis syndrome' and "An overview of angioedema: Clinical features, diagnosis, and management" and "Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".)
Suspected hypocomplementemic urticarial vasculitis syndrome — HUVS may be suspected in patients with approximately six months of urticaria along with systemic findings (eg, arthritis or arthralgias, mild glomerulonephritis). A skin biopsy showing cutaneous leukocytoclastic vasculitis (LCV) is essential to the diagnosis. (See "Urticarial vasculitis", section on 'Hypocomplementemic urticarial vasculitis syndrome'.)
Levels of C1q <50 percent of normal due to autoantibodies against C1q may be observed in HUVS. HUVS can occur independently or can be associated with other conditions, including SLE. A large percentage of patients with HUVS are antinuclear antibody (ANA) positive. Due to overlapping features of HUVS and SLE, such as arthritis and glomerulonephritis, distinguishing patients with HUVS from those with SLE can be challenging. In the setting of active SLE with low complement C3 and C4, low C1q concentrations cannot be used to diagnose concurrent HUVS. (See "Urticarial vasculitis", section on 'Associated conditions' and "Systemic lupus erythematosus in adults: Clinical manifestations and diagnosis", section on 'Evaluation'.)
Review (obtain):
●Complete blood count (CBC) with differential and platelet count
●Serum creatinine and blood urea nitrogen (BUN)
●Urinalysis and urine protein/creatinine ratio (UPCR)
●ANA
●C4 and C3 antigenic levels (commonly reduced in both HUVS and SLE)
●Anti-C1q antibody assay (usually positive in HUVS and active SLE, helpful in following patients with lupus nephritis)
Obtain rheumatology/specialty consultation to assist with evaluation and management. To help distinguish SLE from HUVS, rheumatologists obtain tests that are specific for SLE:
●Anti-double-stranded DNA (anti-dsDNA)
●Antibody to Sm nuclear antigen
●Antiribosomal P
Consider dermatology referral and skin biopsy.
Suspected acquired C1 inhibitor deficiency — AAE-C1-INH is a rare disorder. It should be considered in patients with recurrent episodes of angioedema (without urticaria) affecting cutaneous tissues and mucous membranes of the upper respiratory and gastrointestinal tracts. Symptoms typically begin in the fourth decade of life or later. Most patients with AAE-C1-INH have low levels of C1q, usually <50 percent of normal. (See "Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".)
Obtain:
●Allergy/clinical immunology consultation to help with this evaluation.
●Repeat complement tests, including C1q, ideally at least one month apart. If replacement therapy with C1 inhibitor (C1-INH) is used, C1-INH should be discontinued for at least one week before obtaining diagnostic complement studies.
●Serum protein electrophoresis (SPEP) and urinary protein electrophoresis (UPEP).
Complement abnormalities may fluctuate between normal and abnormal when a complement-related disorder first develops, becoming more consistently abnormal over the ensuing months. Therefore, mild abnormalities associated with a consistent clinical presentation should be followed over time.
REFERENCE RANGE —
Interpretation of a specific abnormal result should be based upon the reference range reported with that result.
CITATIONS —
The supporting references for this content are accessible in the linked topics.
