Mixed connective tissue disease syndrome.

Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologic features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ('speckled') epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixed connective tissue disease.     

The cutaneous pathology associated with seropositivity for antibodies to SSA (Ro): a clinicopathologic study of 23 adult patients without subacute cutaneous lupus erythematosus

Antibodies to Ro/SSA are found in patients with subacute cutaneous lupus erythematosus (SCLE), complement deficiency lupus erythematosus, systemic lupus erythematosus (SLE), neonatal lupus erythematosus, and Sj?gren syndrome (SS). Most studies describing the cutaneous pathology associated with anti-Ro antibodies have been of patients with SCLE. Over a 42-month period, we encountered skin biopsy specimens from 23 anti-Ro-positive patients who did not have SCLE: 15 had SLE variably manifesting as SCLE-like rashes; malar erythema; a dermatomyositis-like rash; vascular disease involving cutaneous, cardiac, peripheral, and central nervous systems; restrictive pulmonary disease; periorbital edema; and myositis. Two patients had primary Sj?gren syndrome, one had primary antiphospholipid antibody syndrome, and two had rheumatoid arthritis; all five had clinical evidence of cutaneous vasculopathy encompassing livedo, perniosis, and palpable purpura. Three additional patients presented with folliculocentric purpura without other stigmata to permit classification as a specific connective tissue disease. In the SLE patients, biopsy specimens of photodistributed eruptions showed an interface dermatitis accompanied by superficial vascular plexus density reduction. Vasculopathic reactions in patients with and without SLE comprised neutrophilic, lymphocytic, or pauciinflammatory thrombogenic subtypes. Although at times a marker of SCLE, the identification of anti-Ro antibodies may isolate a subset of patients at higher risk of multiorgan vasculopathy, myositis, and progressive pulmonary disease. We postulate that many of the features seen in these patients reflect the sequelae of antibody mediated endothelial cell injury.     

Immunoglobulin M predominance in cutaneous lupus erythematosus

BACKGROUND: Direct immunofluorescence (DIF) is a valuable tool in the diagnosis of cutaneous lupus erythematosus (LE). Our goal was to characterize the most frequent immune reactants in the skin biopsies of cutaneous LE and identify the most common immunofluorescence staining patterns. METHODS: DIF results of immunoglobulin G (IgG), IgA, IgM, C3, and fibrinogen from 199 patients between 1989 and 1998 were retrospectively analyzed. Confirmatory clinical and serological diagnosis of LE subtype was available for 95 patients. Intensity of staining was ranked from 0 to 4+ but only included as significant if >/=2+. Laboratory values were gathered and analyzed for all patients who had distinct granular immune deposition for Ig and/or complement. RESULTS: The most commonly detected individual Ig was IgM in 149 (75%) specimens. IgM and C3 combination was the most common pair expressed with 98 (49%) specimens. The most common triplet was IgM, C3, and fibrinogen in 63 (32%) specimens. The most common quadruplet was the combination of IgG, IgM, C3, and fibrinogen in 42 (21%) specimens. All the five immunoreactants were detected in only 25 (13%) specimens. Systemic LE patients had a higher percent of abnormal laboratory values compared to discoid LE (DLE) and subacute LE (SCLE) patients (p = 0.02). Fibrinogen staining was found to be significantly higher in DLE patients and lowest in SCLE patients (p = 0.05). CONCLUSIONS: This study demonstrates a marked predominance of IgM +/- C3 in cutaneous LE. When used in conjunction with other data, DIF is an extremely powerful tool in the routine evaluation of the LE patient. Our report emphasizes the importance of IgM expression in the diagnosis of LE by DIF and how positive staining with multiple conjugates can raise its sensitivity.     

CUTANEOUS LUPUS ERYTHEMATOSUS: COMPARISON OF DIRECT IMMUNOFLUORESCENCE FINDINGS WITH HISTOPATHOLOGY

Background. Direct immunofluorescence (DIF) is considered to be a major advance in the diagnosis of connective tissue diseases, particularly lupus erythematosus (LE); however, the reliability of the technique depends on several factors, such as age and site of the lesion, type of immunofluorescence, type of immunoglobulin, etc. False positives and false negatives can occur. Objective and Methods. To determine the diagnostic value of DIF we studied 18 clinically established cases of cutaneous lupus erythematosus (CLE). Lesional biopsies were subjected to routine histopathologic examination and direct immunofluorescence. The results were compared. Results. Direct immunofluorescence was positive in 72.7% and histopathology in 66% cases. Combination of the two techniques (with one or both methods giving characteristic findings) was positive in 83% cases. The most common antibody was IgG, seen in 77.8% cases. A homogeneous pattern of immunofluorescence, with IgG, was seen in 55.5% of the cases. Although histopathology gave positive or suggestive results in all cases, DIF was negative in two cases of early cutaneous LE. Conclusion. Although DIF is an extremely useful diagnostic tool, it should always be used in conjunction with histopathology and the combination of the two methods yields the best results.     

Clinicopathological significance of cutaneous epidermal nuclear staining by direct immunofluorescence

Epidermal antinuclear antibody (ANA) staining was noted during routine direct immunofluorescence (DIF) of skin biopsies from 22 cases at St John's Dermatology Centre over a 2-year period. We have reviewed the clinical, serological and immunopathological features of these patients. They comprised 13 cases of lupus erythematosus (LE), 3 dermatomyositis, 1 morphoea, 1 systemic sclerosis, 1 CREST syndrome, 1 mixed connective tissue disorder and 1 probable cutaneous sarcoidosis. Five (38.4%) patients with LE had moderate to severe oral mucosal involvement. Epidermal nuclear staining (ENS) was seen following IgG deposition in 21 cases and IgA in only 1 case. Complement C3 staining was an additional feature in 1 patient. Circulating ANA was absent in 7 cases at the time of biopsy, confirming that this pattern of staining does not occur as a result of tissue con-lamination during processing. The presence of ENS by IMF corroborates a diagnosis of a connective tissue disorder, and our results suggest that it may also be associated with oral involvement in E.E.     

Relevance of complement fixing antinuclear antibodies

Background Connective tissue diseases (CTDs) are a heterogeneous group of disorders defined by the association of a variety of clinical manifestations with immunologic and other laboratory findings. Overlap of syndromes and aberrant findings appear rather frequently. Methods Sera of eight antinuclear antibody (ANA) negative, cases of subacute cutaneous lupus erythematosus (SCLE) with antibodies to Ro (SS-A) and a ninth case with clinical and laboratory signs of Sjögren’s syndrome and systemic lupus erythematosus (SLE) were tested for complement (C′) fixing antinuclear antibodies (C-ANAs). The ninth case was examined in depth by direct immunofluorescence (DIF) and a two-step “C + DIF” test of biopsies for C′ fixation to in vivo bound ANAs, as well as serum tests for C-ANA, ANA, and SCLE markers. Results Sera of five of the eight ANA negative, Ro(SS-A) positive SCLE cases had C-ANAs. The ninth case, a 50-year-old woman with clinical and laboratory signs of Sjögren’s syndrome and SLE, gave a strong positive C + DIF reaction in the skin biopsy for in vivo bound ANAs that fix C′, but negative ANAs and C-ANAs in routine serum tests; they revealed antimitochondrial antibodies. Serum tests on normal skin, however, revealed weak ANA and strong C-ANA reactions with in vitro fixed C′. Conclusions ANA negative cases of SCLE or Sjögren’s syndrome may have C-ANAs. A case with Sjögren’s syndrome and signs of SLE had both in vivo and in vitro C′ fixing ANAs. C-ANA tests can aid in the identification of such cases.     

A CASE OF SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS WITH A HIGH TITER OF RNP ANTIBODY

A 30-year-old man developed severe erosive lesions in his oral cavity and transient Raynaud's phenomenon followed by discoid lupus erythematosus (DLE)-like lesions and non-scarring erythema. He had a high titer of RNP antibody as well. Widespread DLE (w-DLE), subacute cutaneous lupus erythematosus (SCLE) and mixed connective tissue disease (MCTD) were suspected as his condition. Finally we diagnosed him as having SCLE accompanied with a high titer of RNP antibody.     

Poikilodermatous subacute cutaneous lupus erythematosus

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of lupus erythematosus with unique clinical, immunological and genetic features. Among the unusual variants of SCLE, there is a poikilodermic presentation. However, to date, only 1 case of poikilodermatous SCLE has been reported. OBJECTIVE: Our goal was to summarize the clinical characteristics and course as well as the pathological, laboratory and immunofluorescence findings of 4 patients with poikilodermatous SCLE. METHODS: A retrospective study was conducted including 54 patients diagnosed as having SCLE between 1980 and 2002. RESULTS: Four patients (7.4%) had SCLE. All patients were alive, and none developed severe systemic involvement in up to 36 years (median, 24 years) after the onset of disease. The most noteworthy laboratory finding was the cutaneous deposition of amyloid. CONCLUSION: Poikilodermatous SCLE represents an uncommon variant within the clinicopathological spectrum of SCLE following a favorable course, in spite of extensive cutaneous involvement. Photosensitivity is the pathomechanism explaining, theoretically, the development of both poikiloderma and cutaneous amyloidosis in such cases.     

Epidemiology of cutaneous lupus erythematosus in a tertiary referral centre in Singapore

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.     

Comparison of IgG subclass autoantibodies in patients with systemic lupus erythematosus and subacute cutaneous lupus erythematosus

Circulating antinuclear antibodies and in vivo bound immunoglobulins at the dermal-epidermal junction are frequently seen in patients with lupus erythematosus. The present study was designed to examine the distribution of the IgG subclasses of in vivo skin bound IgG and circulating antinuclear antibodies (ANA) in patients with systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE). Immunofluorescence studies on skin biopsies showed IgG1 to be the predominant IgG subclass in SCLE patients, present in 20 of 21 (95%) of the specimens. IgG2 was present in 4 patients (19%), IgG3 in 1 (5%), and IgG4 in 7 (33%). The frequencies of IgG2, IgG3, and IgG4 skin staining were significantly higher in the seven SLE patients who were studied: IgG1 in 7/7 (100%), IgG2 in 7/7 (100%) and IgG4 in 6/7 (86%). Immunoblot analysis for the IgG subclasses was performed on serum of 29 patients with SCLE who had antibodies to SSA/Ro antigen. Twenty-seven (93%) of these patients were positive for IgG1 anti-SSA/Ro antibody, while the frequencies for IgG2, IgG3, and IgG4 anti-SSA/Ro were very low. These studies indicate that there is a difference in the IgG subclass antibody response in patients with SLE and SCLE. The presence of more than one subclass antibody may be indicative of systemic disease.     

Relationships between antinuclear and anti-Ro/SS-A antibodies in subacute cutaneous lupus erythematosus

A certain degree of confusion has arisen regarding the relationship between patients having subacute cutaneous lupus erythematosus (SCLE) and those with "antinuclear antibody-negative" systemic lupus erythematosus (ANA-negative SLE). One of the confusing issues relates to published differences in the autoimmune serologic findings of these two patient groups. In order to clarify this issue, we have screened the sera from thirty-seven patients with SCLE for the presence of fluorescent antinuclear antibodies (FANA) on two different substrates--human Hep-2 tissue culture cells and mouse kidney sections. In addition, these same sera were assayed for anti-Ro/SS-A precipitin antibodies. Seventy-eight percent of the sera were FANA-positive at a titer of 1:10 or greater when tested on human Hep-2 cells, whereas 76% were positive at a titer of 1:80 or greater. Fifty-one percent were positive on mouse kidney sections at a titer of 1:10 or greater, whereas 46% were positive at a titer of 1:20 or greater. Twenty-two percent of these sera were completely FANA-negative on both human and mouse substrates. None of these sera that were negative on both substrates contained anti-Ro/SS-A antibodies. However, 69% of the sera that were FANA-positive on both human and mouse substrates were found to have detectable anti-Ro/SS-A antibodies. Ninety percent of the SCLE sera that were FANA-positive on human Hep-2 cells, but negative on mouse kidney sections, contained anti-Ro/SS-A antibodies. These sera gave a speckle-like, or particulate, nuclear immunofluorescence staining pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo cutaneous antinuclear antibody positivity in palisaded neutrophilic and granulomatous dermatitis

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is commonly associated with underlying systemic inflammatory and neoplastic diseases, infections, and drug reactions. In vivo cutaneous antinuclear antibodies (ANA) have been described in skin biopsies from patients with known autoimmune disorders, but not previously reported in the setting of PNGD. We present two patients with systemic lupus erythematosus (SLE) and histopathologically confirmed PNGD. Direct immunofluorescence (DIF) studies revealed in vivo cutaneous ANA positivity in both patients. DIF findings in the skin mirrored serum autoantibody results. ANA positivity in skin specimens is reported as highly predictive of systemic connective tissue diseases (SCTD), although specific testing is not currently recommended as part of the laboratory work-up or diagnostic criteria for these disorders. In this case report, positive ANA results in skin biopsies of PNGD reflect the serological findings and clinical evidence of SLE in both patients. In vivo cutaneous ANA positivity is an interesting and supportive finding in PNGD in the setting of SCTD.     

Terbinafine-induced subacute cutaneous lupus erythematosus

BACKGROUND: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported. OBJECTIVE: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis. METHODS: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated. RESULTS: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4(1/2) months in 3 patients concomitant with subsidence of the SCLE eruption in all patients. CONCLUSION: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons.     

Investigating the presence of neutrophil extracellular traps in cutaneous lesions of different subtypes of lupus erythematosus

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin‐fixed paraffin‐embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR‐3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.     

Leukocytoclastic vasculitis in association with linear epidermal basement membrane zone immunoglobulin deposition: Linear vasculitis

Cutaneous leukocytoclastic vasculitis (LCV) has a distinctive clinical and light microscopic presentation; however, the etiologic basis of LCV is varied. Most cases are attributable to immune complex deposition within a vessel wall and represent an Arthus type III immune complex reaction. The prototypic immunoreactant profile is characterized by granular deposits of components of complement activation in concert with immunoglobulin within the cutaneous vasculature. We encountered nine patients with vasculitic and/or vesiculobullous clinical presentations exhibiting an LCV in association with an immunoreactant profile characterized by homogeneous linear deposits of immunoglobulin along the dermal epidermal junction in a fashion resembling an autoimmune vesiculobullous disease.Among the clinical presentations were palpable purpura, urticarial vasculitis, and vesiculobullous eruptions with supervening purpura. Two patients with Crohn disease presented with classic palpable purpura with biopsy-proven LCV, and direct immunofluorescence (DIF) studies demonstrated linear immunoglobulin G (IgG) with floor localization on the salt-split skin assay. Four patients with systemic lupus erythematosus (SLE) showed purpuric vesiculobullous lesions, with evidence of a neutrophilic interface dermatitis and LCV in three of the four. The remaining patient had urticarial nonbullous lesions showing small-vessel vasculitiswith a neutrophilic interface dermatitis. In all of the patients with SLE, DIF studies showed linear immunoglobulin deposits within the basement membrane zone (BMZ). These constellation of findings clinically, light microscopically, and by immunofluorescence were those of a vasculitic presentation of bullous systemic lupus erythematosus. Two patients had linear IgA disease, which was drug induced in one and paraneoplastic in the other, and the dominant morphology on biopsy in both cases was an LCV. One patient microscopically demonstrated drug-associated and eosinophilic enriched LCV with DIF studies showing striking linear deposits of IgG suggestive of bullous pemphigoid, which was consistent with a vasculitic presentation of drug-induced bullous pemphigoid. In all cases, typical granular vascular immunoglobulin and complement deposition compatible with immune complex mediated vasculitis was observed. It is likely that local immune complexes derived from BMZ antigen bound to antibody are pathogenically relevant. We propose the designation of linear vasculitis for this unique scenario of LCV and linear immunoglobulin epidermal BMZ staining, which in some cases represents a vasculitic presentation of conventional autoimmune vesiculobullous disease.     

Dystrophic calcinosis cutis in subacute lupus

Dystrophic calcinosis cutis is known to be associated with various connective tissue disorders but to the best of our knowledge has never been reported in subacute cutaneous lupus erythematosus (SCLE), a distinctive cutaneous subset in the spectrum of lupus erythematosus. It occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. We report a patient with SCLE who developed calcinosis cutis and had normal serum calcium and phosphorus levels and, interestingly, a normal concentration of blood ionized calcium. This latter, which represents the active form in the total amount of blood calcium, is a parameter only rarely assessed in patients with dystrophic calcinosis cutis. Thus, other pathogenic factors should be investigated to clarify the pathophysiology of the dystrophic type of calcification.     

Identification of retroviral DNA sequences in serum of cutaneous forms of lupus erythematosus patients

Discoid (DLE), discoid disseminated (DDLE) and subacute cutaneous lupus erythematosus (SCLE) are recognised as cutaneous forms of lupus erythematosus (LE). It has been suggested that expression of endogenous retroviral components might induce the biosynthesis of antiDNA antibodies in LE patients. Using the dot blot hybridisation, we detected the greatest correlation between biosynthesis of anti-double stranded DNA (anti-dsDNA), anti-single stranded DNA (anti-ssDNA) antibodies and the presence of human immunodeficiency virus type I (HIV-1) pol sequences in DNA isolated from serum of SCLE (n = 22) patients. The same studies conducted in the groups of DLE (n = 85) and DDLE (n = 51) patients, exhibited a lower correlation between production of anti-dsDNA, anti-ssDNA and the presence of homologous HIV-1 pol sequences than in SCLE patients. Our findings suggest that the presence of endogenous retroviral sequences in patient serum may exhibit a relationship with development of cutaneous forms of LE disease.     

Clinical significance and correlation of antinuclear antibodies and anti-DNA antibodies.

The clinical significance and correlation of antinuclear antibodies (ANA) and anti-DNA antibodies was studied using 142 ANA positive sera from different patients having various diseases. High titers of ANA were found briefly in systemic lupus erythematosus and sometimes in scleroderma or mixed connective tissue disease. The peripheral pattern of ANA was seen exclusively in systemic lupus erythematosus and occasionally in mixed connective tissue disease. Anti-DNA antibodies could be found in systemic lupus erythematosus, discoid lupus erythematosus, scleroderma, chronic active hepatitis, but a high titer of anti-DNA (over 60 unit/ml) was present only in patients with systemic lupus erythematosus, especially those having lupus nephritis. There was little correlation between ANA and anti-DNA antibodies.     

Circulating T- and B-cell abnormalities in cutaneous lupus erythematosus

Seven patients with subacute cutaneous lupus erythematosus (SCLE), 11 patients with discoid lupus erythematosus (DLE), and 17 age-, sex-, and race-matched controls were examined for the number of circulating peripheral blood T and B cells, immunoglobulin (Ig) synthesizing cells, and Ig secreting cells. A significant alteration in T-cell subsets was detected only in SCLE patients who manifested a decreased number of OKT8 cells. Circulating B cells were significantly increased only in the SCLE patients. The percentage of Ig synthesizing and secreting cells was significantly increased in both the DLE and the SCLE groups. The somewhat unexpected increase in Ig synthesizing and secreting cells in the DLE patients could not be accounted for by antimalarial treatment or the concurrence of the HLA-DR3 phenotype. There was, however, a weak but significant correlation between the degree of B-cell activation in the DLE patients and the number of American Rheumatism Association criteria for the classification of systemic lupus erythematosus (SLE) possessed by these patients. These data demonstrate that abnormalities in B-cell function similar to those seen in SLE can also be found in a group of lupus erythematosus patients whose clinical disease expression is limited predominantly to the skin.     

Unilateral nail dystrophy after C4 complete spinal cord injury

Summary Fifty-five patients with biopsy-proven cutaneous lupus erythematosus (LE) were identified in whom a prospective and retrospective review of the clinical and laboratory data allowed subclassification into systemic (SLE). subacute (SCLE). or discold (DLE) variants. In addition to conventional direct immunofluorescence. an indirect immunolluorescent technique. using a monoclonal antibody, was employed to assess deposition of the membranolytic attack complex (C_5b?9) in skin lesions. Deposition of C_5b?9 within the epidermis correlated with a diagnosis of SCLE with or without antibodies to Ro and was seen in SLE patients with antibodies to extractable nuclear antigens Ro. La, Sm. and RNP. and in DLE patients with positive antinuclear antibodies and/or extracutaneous manifestations. In the SLE group, vascular C_5b?9 deposition was present in six patients. Of these, tour had circulating lupus anticoagulant, one had lymphocytic vasculitis, and two had antibodies to Ro. In two patients with SLE there was keratinocyte decoration for immunoglobulin G but not for C_5b?9, in the absence of seropositivity for antibodies to Ro. La. Sm. and ribonucleoprotein (RNP). The immunohistological examination of skin lesions using a monoclonal antibody to C_5b?9 is a valuable adjunct in the subclassification of LE. The presence of C_5b?9 within skin lesions of patients with LE implies a pathogenic role for complement-mediated pore formation.