Hypocomplementinemia. The paradigm of vasculitis.

Gkougkourelas I.

Complement plays a crucial role in the first innate immunity responses. Besides chronic or acute infections, low complement levels are observed in autoimmune diseases, cryoglobulinemia, cirrhosis, renal ailments (kidney graft rejection, glomeronephritis), hematological diseases (paroxysmal nocturnal hemolysis) and characteristically in hypocomplementinemic urticarial vasculitis.

According to the revised 2012 SLICC criteria for the diagnosis of Systemic Lupus Erythimatosus, low levels of complement fragments C3/C4 could lead to the diagnosis of SLE if other clinical and laboratory manifestations are concordant. Furthermore, in Systemic Lupus Erythimatosus Disease Activity Index low complement levels herald flare of the disease.

Urticarial vasculitis (UV) spectrum, ranges from common urticarial hives without systemic symptoms to rare fatal vasculitis. Complement plasma levels indices disproportionally  the severity of UV. Clinical suspicion should be raised when there is urticarial hives for more than 24 hours, mostly painful than pruritic and fairly different dermatological appearance from common hives. The typical dermatologic manifestations are urticarial patches with annular, semiannular  and concentric formation with scattered ecchymosis.

The anatomic location of vascular lesion is small vessels involvement of the skin, kidneys and other internal organs. It is hypothesized that antiC1q antibodies are formed leading to immune complex formation, complement activation and inflammatory reactions. Inflammatory cells are recruited within and around the vessel wall, giving rise to leukocytoclastic vasculitis seen in skin biopsies.

Diagnostic criteria are shown in the table 1. Differential diagnosis is made from SLE, Sjogren’s syndrome, drug reactions, neoplasia etc. Treatment is based on glucocorticosteroids and other Disease Modifying Anti Rheumatic Drugs like azathioprine, hydroxychlorokine and methotrexate. Biological agents such as rituximab and omalizumab are chosen when conventional therapy has failed.

Table 1: two major and two minor criteria are needed for the diagnosis

Criteria specifics Needed for the diagnosis
Major criteria Urticaria for more than 6 months The patient must have both
Minor criteria Venulitis of the dermis in biopsy The patient must have at least two of the minor criteria
Mild glomerulonephritis
Uveitis or episcleritis
Recurrent abdominal pain
Positive C1q precipitin test