免疫酶组织化学法检测红斑狼疮皮损狼疮带研究

目的:探讨用免疫组化方法检测红斑狼疮皮损中的免疫球蛋白沉积对其诊断的价值。方法:用辣根过氧化物酶(HRP)标记抗体法分析研究387例红斑狼疮患者皮损中免疫球蛋白(IgG、IgA、IgM)及补体(C3、C1q)的沉积情况以及与临床诊断、组织病理学诊断的符合率。结果:临床诊断为红斑狼疮,且组织病理学诊断亦符合红斑狼疮的患者皮损中最常见、最易检出的狼疮带成分均为IgG、IgM,其次为C1q,C3与IgA不易检出;而临床诊断为红斑狼疮,但组织病理学诊断不符合的患者,皮损中几种免疫球蛋白和补体的检出率之间尚无明确差别。结论:免疫组化法检测狼疮带对红斑狼疮患者的临床和组织病理学诊断有重要参考价值,且此法简便易行,具有较好的可重复性。     

Circumscribed scleroderma with immunologic evidence of systemic lupus erythematosus

An 8-year-old girl initially manifested clinical and histopathologic findings of circumscribed scleroderma. She had both linear and plaque lesions. Although she was free of constitutional symptoms, laboratory evaluation revealed substantial evidence of systemic lupus erythematosus (SLE). This included a positive anti-nuclear antibody test (rim pattern), positive LE cell preparation test, elevated anti-double-stranded DNA activity, positive lupus band test (IgM and C3) in involved and uninvolved skin, and renal biopsy findings consistent with SLE. Sclerodermatous change as an initial sign of SLE is rare. We review previous reports of an association of circumscribed scleroderma, especially the linear form, with serologic evidence of systemic autoimmune disease.     

Lupus band test: anatomic regional variations in discoid lupus erythematosus

Seventy-one patients with discoid lupus erythematosus were studied for anatomic regional variations in the lupus band test. The test was positive in 82% of biopsies from the scalp, face, neck, and upper extremity. Only three out of fourteen biopsies (21%) from the trunk were positive. Discoid lupus erythematosus could be confirmed or strongly suspected in the light microscopic sections from all cases. Truncal lesions should not be selected for the lupus band test in discoid lupus erythematosus if there are other choices.     

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.     

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus

Background:Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon.Case Report:We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.     

Different patterns of soluble adhesion molecules in systemic and cutaneous lupus erythematosus

Abstract Circulating isoforms of cellular adhesion molecules (CAMs) have been described recently, and elevated levels of certain sCAMs have been reported in various inflammatory diseases such as systemic lupus erythematosus (SLE). There are previously no reports on sCAMs in cutaneous LE. Sera from 61 patients with LE: systemic (SLE: n= 24), chronic cutaneous (discoid LE, DLE: n= 19) or subacute cutaneous (SCLE: n= 8), chronic biologically false positive (CBFP) reactors for syphilis (n= 10) and 32 controls were examined for sICAM-1, sVCAM-l and sE-Se-lectin with specific ELISA kits. Protocol forms were reviewed. We found significantly elevated levels of sE-Selectin in patients with DLE and widespread cutaneous symptoms, and a correlation between active cutaneous disease as well as polymorphous light eruption (PLE) and elevated levels of sE-Selectin. In contrast, patients with systemic LE did not have elevated levels of sE-Selectin, but in concordance with earlier reports, sICAM-1 and sVCAM-l levels were elevated compared to controls in SLE. as well as in SCLE patients, which has not been reported previously. Since activated endothelial cells are the only source for E-Selcetin, the elevated sE-Selectin level in patients with widespread and active cutaneous disease suggests a more important role for endothelial cells in the pathogenesis of cutaneous LE than previously assumed.     

Subacute lupus erythematosus of the skin--clinical aspects and laboratory findings

The data of 20 patients with subacute cutaneous lupus erythematosus (SCLE) were evaluated according to clinical and laboratory criteria. We found the following laboratory deviations: elevated BSR, leucopenia, anti-dsDNA, anti-SSA/Ro and anti-SSB/La antibodies, positive LE cells, and elevated levels of IgE and immune complex. Aside from the characteristic skin eruptions in SCLE, the patients showed arthralgia, myalgia, and pronounced photosensitivity. Therapy: corticoids, chloroquine, and light protection. Regular follow-up examinations are extremely important in these patients.     

Subacute cutaneous lupus erythematosus

A large part of James N. Gilliam's abbreviated investigative career was devoted to testing a hypothesis that strong relationships do exist between the cutaneous and systemic manifestations of lupus erythematosus (LE). As a result of clinical observations made during his early studies designed to test this hypothesis, he introduced the term “subacute cutaneous lupus erythematosus” (SCLE) to designate a clinically distinctive nonscarring type of histologically confirmed cutaneous LE that he felt might represent a cutaneous marker for a discrete subset of LE patients.¹ A series of studies carried out in our and other laboratories have since confirmed that patients who develop SCLE skin lesions do indeed share other clinical, pathologic, serologic, and immunogenetic features. Dr. Gilliam died on June 6, 1984, before the full impact of his initial clinical observations had been fully recognized. I would, therefore, like to dedicate the following discussion of the clinical and laboratory features of patients with SCLE skin lesions to his memory.     

Cutaneous lupus erythematosus: a review

This article will review and update information about the pathogenesis, clinical presentation, diagnosis, and treatment of cutaneous lupus erythematosus. Lupus erythematosus (LE) can present as a skin eruption, with or without systemic disease. Cutaneous LE is subdivided into chronic cutaneous LE, subacute cutaneous LE and acute LE. The prevalence of systemic lupus erythematosus (SLE) is 17-48/100,000 population worldwide. Skin disease is one of the most frequent clinical complaints of patients suffering from SLE. It has been found to occur in up to 70% of patients during the course of the disease. The most frequent mucocutaneous manifestations of SLE are malar rash (40%), alopecia (24%), and oral ulcers (19%). It has been suggested that risk factors that are more likely to signal transition of cutaneous into systemic LE are high ANA titers (> 1:320) and the presence of arthralgias. CLE patients who exhibit these symptoms should be monitored closely, since they may be at increased risk to develop SLE.     

Anti‐annexin 1 antibodies: A new diagnostic marker in the serum of patients with discoid lupus erythematosus

Abstract: Annexin 1 is an anti‐inflammatory molecule and has also been described to be a common target of autoantibodies. In this study, we determined whether antibodies against annexin 1 can be detected in sera of patients with cutaneous lupus erythematosus (CLE). Levels of anti‐annexin 1 antibodies were evaluated by a new established enzyme‐linked immunosorbent assay and found to be significantly higher in sera of patients with CLE when compared to normal healthy donors (NHD). Moreover, the percentage of sera positively tested for anti‐annexin 1 antibodies was elevated in patients with CLE when compared to NHD. In particular, the percentage of positive sera for anti‐annexin 1 antibodies was significantly higher in patients with discoid lupus erythematosus (DLE); however, disease activity did not correlate with the antibody levels. The results of this study indicate that anti‐annexin 1 antibodies in sera of patients with DLE might be a valuable aid in the diagnosis of this subtype.     

Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset

We have characterized the clinical and laboratory features of 27 patients who had in common a recurring, superficial, nonscarring type of cutaneous lupus erythematosus (LE) that occurred in a characteristic distribution (subacute cutaneous lupus erythematosus [SCLE]). This clinically distinct form of cutaneous LE has not previously been analyzed as a separate entity and thus, its clinical importance has not been fully appreciated. We found that these patients frequently had a mild systemic illness marked by musculoskeletal complaints and serologic abnormalities. Forty-eight percent had systemic LE by American Rheumatism Association criteria; however, none had serious CNS or renal disease. Thus, those with SCLE are a subset of patients with LE who generally have an illness intermediate in severity between discoid LE and severe systemic LE.     

Comparative immunofluorescence study of actinic keratosis and chronic discoid lupus erythematosus

Regarding systemic (SLE) and chronic discoid lupus erythematosus (CDLE), the diagnostic value of the lupus band test ist generally accepted. In the literature, however, there are but few obligatory criteria concerning the definition of a positive lupus band. In order to illustrate the influence of sunlight on the evolution of junctional deposits of immunoglobulins, we examplarily studied actinic keratosis (AK) as a chronic light-dependent dermatosis. The junctional deposits in AK were qualitatively and quantitatively compared with the lupus band typical for CDLE. In CDLE we mostly found more distinct band-like junctional deposits of immunoglobulins and complements. Light-dependent, non-specific junctional patterns of immunofluorescence similar to LE, therefore, require clear morphological criteria of immunohistology.     

Chilblain lupus erythematosus: report of 15 cases.

In this retrospective study, the authors describe the clinical, histologic and laboratory features of 15 cases of chilblain or perniotic lupus. In winter, the patients (14 women, 1 man) develop chilblain-like lesions, chiefly in the toes (8 times) and fingers (11 times). Histologic features are identical to those of discoid lupus erythematosus. The damaged skin gives a positive fluorescent band test. Usually, these lesions occur in association with discoid lupus of the face. However, in 8 patients, they were the only cutaneous sign of lupus. This form of lupus can evolve to a systemic form, as was the case with 3 patients.     

Cutaneous Immunofluorescence Studies to Adult Rheumatoid Arthritis in Sun-exposed and Non-sun-exposed Areas

The incidence and significance of positive cutaneous immunofluorescence findings were assessed in biopsy specimens of both sun-exposed and non-sun-exposed skin of 34 adult patients with rheumatoid arthritis (RA) who were not receiving systemic corticosteroids. The incidence of lupus erythematosus (LE)-band was low (8.6%) in both groups. Twenty-eight percent of the patients had perivascular IgM and/or C3 deposits, and 74% had cytoid bodies in the papillary dermis. These studies indicate that the incidence of LE band is low in RA and that the detection of such a band in normal skin warrants close follow-up of RA patients for possible development of LE.     

The distribution of IgG subclasses in the lupus band suggests disease-specific alteration in subclass switching rather than polyclonal B-cell activation

Deposition of immunoglobulins in the skin of patients with lupus erythematosus (LE), demonstrable as a linear band ‘lupus band’ at the basement membrane zone (BMZ) by direct immunofluorescence, was first described in 1963. Four decades after the discovery of the lupus band, a basic question regarding the origin of immunoglobulins of the lupus band is still unanswered. Is the lupus band just a manifestation of polyclonal B‐cell activation commonly seen in systemic LE (SLE)? The distribution of IgG subclasses deposited in the skin of patients with SLE was identified using immunohistochemistry. The relative restriction of IgG of the lupus band to the IgG3 subclass demonstrated in this study provides evidence against polyclonal B‐cell activation as the only cause of the lupus band and suggests disease‐specific alteration in subclass switching.     

False-positive results in the detection of anti-LAV/HTLV-III antibodies by enzyme immunoassay

Two groups of sera were investigated with two different enzyme immunoassays for the detection of anti-LAV/HTLV-III-antibodies: 50 sera collected from patients with lupus erythematosus and 5 sera containing anti-HLA-DR4 antibodies. Of the 50 sera of the lupus erythematosus patients, 2 were positive in each of the tests. Of the 5 sera that contained anti-HLA-DR4 antibodies, one was positive. In addition, 11 sera showed positive results after heat treatment (56 degrees C, 1 h) in one of the tests. However, all sera in this group gave negative results in the other test. The positive results could not be confirmed with the immunoblot. These findings show that one must be aware of false-positive results when the sera of certain types of patients are investigated in anti-LAV/HTLV-III enzyme immunoassays. The sera of patients with lupus erythematosus, as well as that of polytransfused persons or multiparous women, that have been sensitized with HLA-DR4 antigens; heat treatment in one test has an effect on sera.     

Serologic studies in patients with lupus erythematosus and psoriasis

We present four patients with coexistent lupus erythematosus (LE) and psoriasis. This is an unusual combination. All four patients had antibodies to Ro, which were absent in twenty-four control psoriatics. Antibodies to Ro occur in only 25% to 30% of unselected SLE patients, but occur in approximately 60% of "antinuclear antibody (ANA)-negative" LE patients, many of whom are highly photosensitive. The increased frequency of anti-Ro in our patients suggests that this may be a specific serologic marker for the LE/psoriasis overlap. Also, since anti-Ro correlates with photosensitivity, LE/psoriasis overlap patients may be at increased risk for photosensitivity, which occurred in two of our patients, one of whom developed severe systemic disease following ultraviolet (UVB) phototherapy. Screening for anti-Ro antibodies may be appropriate in psoriatics prior to UVB phototherapy.     

The presence of anti–basement membrane zone antibodies in the sera of patients with non–bullous lupus erythematosus

We performed indirect immunofluorescence (IF) studies using 1 mol/1 sodium chloride split skin to determine whether or not a positive IF is specific to patients with bullous lupus erythematosus (LE). We examined the sera from 21 patients with systemic LE (SLE), three of which were obtained from two SLE patients and one subacute cutaneous LE (SCLE) patient with bullous eruptions. As a comparison, we also studied the sera from patients with discoid LE (DLE,n= 7). SCLE (n= 1), systemic sclerosis (SSc, n= 20), bullous pemphigoid (n= 2) and normal individuals (n= 10). Sera from 16 SLE, four DLE and two SSc revealed a linear deposition of IgG isotype antibody at the epidermal side and/or the dermal side on indirect IF of split skin. The sera from three patients with bullous eruption and from 12 patients of SLE, SCLE, DLE without bullous eruption or SSc were further analysed by immunoblotting using five defined antigens, i.e, dermal extract, epidermal extract, three fusion proteins of 230 kDa bullous pemphigoid antigen (BPAG), 180 kDa BPAG, and human epidermolysis bullosa acquisita (EBA) antigen. Two SLE sera as well as one of the SCLE and the DLE serum reacted with 230 kDa BPAG in epidermal extract, and one of the SCLE and the DLE serum also reacted with the fusion protein of 180 kDa BPAG, No serum reacted with the dermal extract or the fusion protein of 230 kDa BPAG or EBA antigen. There was no consistent correlation between split–skin IF results and immunoblotting results. These results may suggest that even non–bullous LE patients often have autoantibodies to the basement membrane zone antigens, most of which are less pathogenic. Although we rarely examine the sera from non–bullous LE patients, we should keep this phenomenon in mind to avoid overestimating the results of split–skin test and immunoblotting.     

Neonatal lupus erythematosus: clinical character, investigation, and outcome

Neonatal lupus erythematosus is an uncommon maternal auto-antibody-associated disease characterized by cutaneous, cardiac, hepatic, hematological, neurological, and pulmonary involvement. A retrospective study was performed to review clinical manifestations, investigation results, outcomes of neonatal lupus erythematosus patients and their mothers at the Department of Pediatrics, Siriraj Hospital during 1993 to 2008. Seventeen neonatal lupus erythematosus patients (10 girls and seven boys) were identified. Cutaneous, cardiac, hepatobiliary, and hematological involvement was found in 70.6%, 64.7%, 52.9%, and 35.3% of infants, respectively. Skin lesions were erythematous patches (91.7%), subacute cutaneous lupus erythematosus (50%), petechiae (41.7%), persistent cutis marmorata (16.7%), and discoid lesions (8.3%). Congenital heart block was found in nine cases, and structural abnormalities were found in nine cases. All sera of patients were positive for antinuclear antibodies. Patients (87.5%) showed positive antiRo/SSA, and 50% had positive antiLa/SSB antibodies. Most neonatal lupus erythematosus mothers (64.7%) were asymptomatic. Five mothers were diagnosed with systemic lupus erythematosus, and one mother was diagnosed with mixed connective tissue disease. All maternal sera was positive for antinuclear antibodies and antiRo/SSA antibody. Seven patients required pacemaker implantation. The mortality rate was 11.8%, caused by congestive heart failure and pneumonia. Antinuclear antibody tests should be used as one of the screening tests in mothers or patients suspected of having neonatal lupus erythematosus.     

A Study of lupus erythematosus with particular reference to generalized discoid lupus

The classification of lupus erythematosus (LE) is difficult because of variable and multisystem involvement, occurrence of transitional forms, and overlapping with connective tissue disorders. One of the earliest attempts at classification was made by O'Leary (1934), who classified LE clinically into four main types: (1) chronic discoid lupus erythematosus (DLE), or fixed type with the typical erythematous, scaly, well-demarcated eruption, usually showing follicular plugging and atrophy, confined to the head region; (2) generalized DLE, or chronic disseminated type differing from the localized discoid type in that the erythematous plaques are found not only on the head area but also below the neck region (O'Leary considered that constitutional systems were generally lacking in these two types); (3) subacute disseminated LE; and (4) acute disseminated LE. The last two categories reflect what we now call systemic lupus erythematosus (SLE) of varying severity. Many authors have used O'Leary's clinical classification, but progress in laboratory medicine—in particular the discovery of the LE cell—has led to other schemes, the most widely accepted at present being that related to the American Rheumatism Association's (ARA) preliminary criteria for the diagnosis of SLE (Cohen et al., 1971). These criteria have been criticized by many authorities because they do not include important data, such as those relative to the antinuclear antibody test, serum anti-native-DNA, serum complement levels, many neurological abnormalities, renal biopsy changes, and cutaneous immunofluorescent (IF) findings. However, Dubois (1974b) pointed out that all categorizations of LE are arbitrary, and he accepted the ARA criteria as a successful method for differentiating LE. This report involves the clinical and laboratory findings in 123 patients with LE seen at the Mayo Clinic during the 3-year period 1971–1974 and an assessment of the validity and usefulness of O'Leary's classification.