Evidence Supporting a Role for Immune Complex-Mediated Inflammation in the Pathogenesis of Bullous Lesions of Systemic Lupus Erythematosus

Abstract

Evidence supporting an immune complex pathogenesis of bullous lesions in systemic lupus erythematosus includes immune deposits, acute inflammation, and blister formation at the cutaneous basement membrane zone. Since cutaneous immune deposits are a general feature of lupus, an attempt has been made to determine whether deposits in lupus patients with blisters are functionally different from those in patients without blisters. Skin was obtained from 4 consecutive patients with blisters and 14 controls. The groups were matched for clinical and serologic features, duration and activity of disease, and treatment. Skin was examined by direct immunofluorescence for immune deposits and by the leukocyte attachment assay for quantification of complement-activating immune complexes. Clinically normal, viable skin from 1 patient with blisters and 1 patient without blisters was incubated in organ culture with normal human leukocytes and serum complement. All patients in both groups had immune deposits at the basement membrane zone with an equivalent incidence of the major Ig classes. Deposits in patients with blisters were slightly more intense and a linear pattern of fluorescence seen in 75% of these patients was not seen in controls. The leukocyte attachment assay showed significantly greater (p less than .02) cell attachment in patients with blisters (mean = 167) than in patients without blisters (mean = 64) and greater cell attachment in peribullous than normal skin from the same patient. Organ culture showed complement-dependent migration of leukocytes and histologic features similar to those in spontaneous lesions in skin from the patient with blisters but not in skin from the patient without blisters. These results provide evidence supporting immune complex and complement-dependent inflammation in the pathogenesis of bullous lesions in systemic lupus erythematosus.

Bullous SLE: A Phenotypically Distinctive but Immunologically Heterogeneous Bullous Disorder.

“…Studies have shown they are able to activate the C-system and mediate C-dependent migration and adherence of leukocytes to the BMZ. Furthermore, cutaneous immune deposits in the perilesional skin of patients with bullous SLE activate C and generate C-derived inflammatory mediators to a significantly greater degree than the deposits in uninvolved skin from the same patients or the deposits in SLE patients without blisters [6].…”

“…The bullous SEE phenotype is composed of a characteristic set of clinical, histologic, immunohistologic (DIF), and IEM features that develop in a patient who meets the American Rheumatism Association's (ARA) classification criteria for SLE [4,5,13]-Most patients have been young black women, but all ages, races, and both sexes are affected [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The clinical features include a widespread, non-scarring vesiculobullous eruption that may occur on, but is not confined to, sun-exposed skin.…”

“…Interestingly, the primary lesions of chronic discoid, subacute, and acute LE appear to be uncommon in bullous SLE. An important and interesting clinical feature of bullous SEE is that it may respond to treatment with dapsone [4,[6][7][8][12][13][14]16]. The response is usually dramatic, with cessation of new lesions within 24 to 48 h after administering the drug, and healing of old lesions within several days.…”

“…Two major patterns have been described [4,6,8] (Fig 3). In most patients the pattern is either granular (about 60% of cases) or linear (about 40% of cases).…”

“…There is also evidence that autoantibodies to type VII collagen are pathogenic in bullous SLE (and epidermolysis bullosa acquisita) and that their production is reg-l dated by tbe class II major bistocompatibility complex DR beta 1 allele, 1501 and possibly other DR beta 1 alleles that share a similar sequence of amino acids in the second hyper-; variable region. J Invest Dermatol 100: 28S-34S, 1993 D uring the past 20 years, there have been reports of a small number of patients with systemic lupus erythematosus (SLE) who developed a blistering disorder with a relatively distinctive comhination of clinical, histologic, immunohistologic and immunoelectron microscopic (IEM) features [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Those features include a widespread eruption of vesicles and hullae that often respond to treatment with dapsone; dermal-epidermal separation at the epithelial basement membrane zone (BMZ) and acute inflammation similar to that seen in dermatitis herpetiformis (DH); a linear, granular, or mixed linear and granular pattern of immunoglobulin (Ig) (IgG, IgM, IgA) deposits at the BMZ by direct immunofluorescence (L)IF); and Ig deposits in the upper dermis and on the lamina densa hy IEM.…”