urticarial vasculitis is characterized by recurrent episodes of urticaria with biopsy evidence of leukocytoclastic vasculitis ( 1 ) .
although urticarial vasculitis is frequently idiopathic , it has been reported to be associated with infection , malignancy , certain drugs , and connective tissue diseases such as systemic lupus erythematosus ( sle ) and sjogren 's syndrome ( 2 ) . here , we report a case wherein urticarial vasculitis preceded the manifestations of sle .
in august 2005 , a 50-yr - old woman visited our hospital with a 3-month history of recurrent multiple urticarial rashes and wheals on the face , trunk and back .
treatment with antihistaminic and prednisolone resulted in improvement of her skin lesions , and she thereafter received prednisolone intermittently depending on her symptom recurrence .
after 1 yr , she visited our hospital due to a malar rash and pitting edema of both the legs and recurrent episodes of urticaria ( fig .
laboratory tests revealed the following findings : hemoglobin level , 9.6 g / dl ; white blood cell ( wbc ) count , 1,970/l ( neutrophils 62% ) ; platelets , 26910/l ; total protein , 6.3 g / dl ; albumin , 2.7 g / dl ; blood urea nitrogen ( bun ) , 14 mg / dl ; creatinine , 1.0 mg / dl ; and c - reactive protein , 1.4 mg / l . a high titer of antinuclear antibodies ( ana ) was detected ( 1:640 , speckled ) , while the test for double - stranded dna antibody was negative .
anti - smith , anti - ro , and anti - la antibodies were all positive . the c3 level ( 28.7 mg / dl ; normal range , 55 - 120 mg / dl ) , c4 level ( 6.3 mg / dl ; normal range , 20 - 50 mg / dl ) , ch50 level ( 6.7 u / ml ; normal range , 23 - 46 u / ml ) , and c1q level ( 6.6 mg / dl ; normal range , 10 - 20 mg / dl ) were markedly decreased , whereas the anti - c1q antibody level was increased to 23.3 u / ml ( normal level , < 10 u / ml ) . the c1 esterase inhibitor level was normal ( 25 mg / dl ; normal range , 6 - 25 mg / dl ) and cryoglobulin was not detected .
urinary analysis showed protein , + + ; red blood cell ( rbc ) count , 6 - 10/high - power field ( hpf ) ; and 24-hr urine protein , 1.1 g / day , and the creatinine clearance rate was 44.0 ml / min .
in particular , distinct infiltration of neutrophils and nuclear dust was noted at the walls of small vessels ( fig .
igg was positive along the capillary loop , and c1q and c3 were positive in the mesangium .
the diagnosis of sle was established because of the presence of a malar rash , proteinuria , leukopenia , high ana titer , and the presence of the anti - smith antibody .
an intravenous steroid pulse ( 1.0 g / day3 days ) followed by a high - dose oral steroid ( 1 mg / kg ) were administered after the disappearance of the vasculitic wheal and angioedema .
hematuria and proteinuria were resolved , and mycophenolate mofetil ( 500 mg , bid ) and hydroxychloroquine were added to the therapy . however , in july 2007 , the tapering of the steroid administration was accompanied by the recurrence of urticaria , angioedema , conjunctivitis , and episodes of abdominal pain . despite mycophenolate mofetil ,
dapsone and steroid therapy did not completely relieve , but instead attenuated the urticarial vasculitic lesions .
urticarial vasculitis resembles urticaria , is usually painful or nonpruritic , and typically persists for more than 24 hr ( 1 ) .
patients with urticarial vasculitis can be divided into two groups , those with normal complement levels and those with huv ( 1 , 2 ) . the latter are more likely to exhibit systemic manifestations , including constitutional symptoms ( fever , malaise , and fatigue ) , arthralgia , arthritis , serositis , glomerulonephritis , interstitial nephritis , and raynaud 's phenomenon ( 2 ) .
angioedema - like lesions are present in as many as 40% of patients , frequently involving the lips , tongue , periorbital tissue , and hands ( 2 ) .
some patients have ocular inflammation like conjunctivitis and episcleritis ( 3 ) . by definition ,
complement measurements with low c1q and c4 levels and variably decreased c3 levels indicated activation of the classical pathway .
c1q precipitins were identified and were later confirmed to be autoantibodies against c1q ( anti - c1q autoantibody ) ( 4 ) .
antibodies against c1q act as a diagnostic marker for huv ( 1 , 3 ) .
however , they are not specific to huv and have also been observed in sle .
anti - c1q antibodies were detected in 30% of patients with sle and 80% of sle patients with glomerulonephritis ( 5 ) .
this patient also showed decreased levels of c3 , c4 , ch50 , and c1q and increased levels of the anti - c1q antibody .
she simultaneously exhibited huv and sle with glomerulonephritis , both of which are possible causes of decreased complement and the presence of anti - c1q antibody .
in most cases , the histological findings of urticarial vasculitis include a majority of features of completely developed leukocytoclastic vasculitis ( 2 ) .
direct immunofluoroscence of skin biopsy samples from huv patients usually show immunoglobulin and complement deposition in a granular pattern in and around the blood vessels of the upper dermis and the basement membrane ( 2 ) .
she experienced recurrent urticaria with vasculitis , episodes of angioedema and eye inflammation , and the serum anti - c1q autoantibody was positive .
she also fulfilled the criteria of sle with urticarial lesions that persisted for more than 24 hr and left a brownish pigmentation , which is different from true urticaria .
some authors suggest the possible progression of huv to sle , and others have defined huv as an sle subtype ( 6 , 7 ) . at times , a hypocomplementemic patient initially diagnosed with an idiopathic huv has an underlying disease such as sle or sjogren 's syndrome ( 1 ) .
huv is associated with sle in most cases ( 54% ) , but normocomplementemic urticarial vasculitis is not strongly associated with sle ( 2% ) ( 8) . this patient suffered from urticaria and angioedema for several years .
serum complement levels were not checked initially , and a skin biopsy was performed 1 yr after disease onset ; the results revealed urticarial vasculitis .
however , in this case , we assume that urticarial vasculitis was the presenting symptom of sle .
huv has been reported to be recurrent in some patients , with an unpredictable response to therapy ( 1 , 2 ) .
intravenous methylprednisolone and cyclophosphamide or high - dose oral corticosteroids , colchicines , dapsone , hydroxychloroquine , and low - dose methotrexate have all been reported to be effective treatments ( 1 , 2 , 9 ) . in this patient , the skin lesions resolved initially with steroids , but were subsequently refractory to treatment .
mycophenolate mofetil , which was administered for lupus nephritis , did not affect urticarial vasculitis . in conclusion ,
although huv resembles sle both clinically and immunologically , an association huv and sle is not clear yet .
 urticarial vasculitis is characterized clinically by urticarial skin lesions and histologically by leukocytoclastic vasculitis . 
 hypocomplementemic urticarial vasculitis is associated with connective tissue diseases such as systemic lupus erythematosus ( sle ) . 
 we report a case of urticarial vasculitis that preceded manifestations of sle . 
INTRODUCTION
CASE REPORT
DISCUSSION