Large speckle-like thready and thready antinuclear antibody patterns as markers for different clinical presentations in lupus erythematosus

Fifty-one patients with lupus erythematosus were studied retrospectively. They were chosen on the basis of their antinuclear antibody (ANA) immunofluorescent pattern. Only those with the thready or the large speckle-like thready patterns were studied. Autoantibody profiles consisting of ANA, anti-single-stranded deoxyribonucleic acid (ssDNA) antibody, and anti-extractable nuclear antigen (ENA) antibody determinations were obtained. The patients with the thready ANA pattern and anti-ENA (Sm) antibodies had a significantly higher incidence of pulmonary, joint, and renal involvement than the anti-ENA negative patients with the large speckle-like thready pattern. There was also a significantly higher incidence of Raynaud's phenomenon in patients with the thready pattern than in those with the large speckle-like thready pattern. Photosensitivity was seen significantly more frequently in the patients with the large speckle-like thready pattern than in those with the thready pattern.     

Localized and systemic scleroderma

Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.     

Scleroderma

Sclerodermas may occur in two basic forms: localized sleroderma (LSc) and systemic scleroderma (SSc). Pseudoscleroderma as well as overlap syndromes have to be differentiated from these two variants. From the clinical point of view, localized scleroderma can be subdivided into type I = plaque-like LSc (= morphea), type II = linear LSc, and type III = deep LSc. According to the degree of the cutaneous involvement, systemic scleroderma can likewise be classified into type I = sclerodactylia, type II = acrosclerosis, and type III = scleroderma with primary involvement of the trunk (diffuse scleroderma). In LSc, we never find systemic involvement; SSc, in contrast, is almost always associated with Raynaud's phenomenon, changes of the esophagus, as well as an increased titer of antinuclear antibodies (Hep-2 cell test). Only 23% of our patients with LSc showed elevated ANA titers. We present and discuss data of 56 patients with LSc and 52 patients with SSc. Evidence in the literature as well as our own findings suggest that the pathogenesis of LSc is different from that of SSc. The influence of various mediators and cytokines on the collagen metabolism might be regarded as a theoretical approach in order to develop new therapeutic regimens. This is even more important since there is still no efficient mode of treatment for neither localized nor systemic scleroderma.     

Early detection of scleroderma spectrum disorders in patients with Raynaud's phenomenon.

Fifty patients with the chief complaint of Raynaud's phenomenon (RP) presented at our scleroderma clinic from March to December 1990. Physical examination, routine laboratory tests (blood, urine and chest X-ray), determination of the pattern of RP, antinuclear antibody (ANA) tests and examination for nailfold bleeding were performed. Three patients were diagnosed as having systemic sclerosis sine scleroderma, 15 patients as having RP with positive anticentromere antibody and 6 patients as having an incomplete form of mixed connective tissue disease. Thus, a total of at least 24 patients out of 50 (48%) were shown to have a scleroderma spectrum disorder. A definite RP pattern (triphasic or biphasic and bilateral), positive ANA and positive nailfold bleeding were strongly correlated statistically, suggesting that these are simple useful findings for the early detection of scleroderma spectrum disorders in patients with RP. We expect that there are many undiagnosed patients with an early-stage scleroderma spectrum disorder in the general population.     

Juvenile linear scleroderma associated with serologic abnormalities

We investigated 24 juvenile cases of linear scleroderma for the presence of systemic disease and serologic abnormalities. Thirteen of 24 patients had antinuclear antibodies (ANA) at titers of 1:40 or greater. Rheumatoid factor (titers greater than or equal to 1:20) was detected in seven of 17 patients tested, five of whom also had ANA. Two of five patients with ANA and rheumatoid factor had systemic diseases, such as nephritis and Raynaud's phenomenon. One patient with ANA developed typical dermatomyositis. Consequently, patients with linear scleroderma may be at some risk for developing systemic collagen-vascular diseases. On initial presentation, patients with linear scleroderma should give a complete history and receive a thorough physical examination as well as undergo laboratory evaluations for the presence of ANA and rheumatoid factor. Long-term observation with periodic reevaluation is appropriate for many members of this group.     

The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder with excessive fibrosis of the skin and various internal organs. Although SSc is a heterogeneous disease, it has been reported that the particular antinuclear antibodies (ANA) are often indicative of clinical features, disease course and overall severity. OBJECTIVE: To clarify the association of clinical and prognostic features with serum ANA in Japanese patients with SSc. METHODS: We studied 203 Japanese patients diagnosed with SSc, who visited our hospital during the period 1983-2005. Six SSc-related ANA were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation assays. RESULTS: Patients with SSc were classified into six ANA-based subgroups and a group without ANA. As expected, antitopoisomerase I antibody (Ab, n=64), anti-RNA polymerases (RNAP) Ab (n=12) and anti-U3 RNP Ab (n=5) were associated with diffuse cutaneous SSc, whereas anticentromere Ab (ACA, n=75), anti-Th/To Ab (n=7) and anti-U1 RNP Ab (n=10) were frequently detected in patients with limited cutaneous SSc. Clinical features of the ANA-negative group (n=10) were heterogeneous. Consistent with previous findings in Caucasian and/or black African patients, antitopoisomerase I Ab was associated with the involvement of vascular and pulmonary fibrosis, leading to decreased survival rate. However, no patients with anti-RNAP Ab developed renal crisis and the frequency of isolated pulmonary hypertension in patients with ACA, anti-Th/To Ab or anti-U3 RNP Ab was similar to that in other ANA-based subgroups. CONCLUSION: These results indicate that the clinical relevance of SSc-related ANA in Japanese patients differs in some aspects from that in Caucasian and/or black African patients.     

Immunologic changes in linear scleroderma in children. Apropos of 11 cases

Immunologic data collected in 11 children (6 girls and 3 boys under fourteen) presenting with linear scleroderma were analysed in a retrospective study: 2 children presented with superficial linear scleroderma, 6 with monomelic scleroderma, 1 with dimelic scleroderma, 1 with the "en coup de sabre" variety associated with dimelic homolateral involvement, and another with "en coup de sabre" scleroderma combined with facial hemiatrophy: Antinuclear antibodies (ANA) were demonstrated in 9/11 cases (i. e. 81 p. 100). The immunofluorescence staining pattern was homogeneous in all nine with a low titer (less than 250 in 5 of them). ANA to single stranded DNA was present in 1/3. The demonstration of ANA in these 9 children was correlated with deep or extensive sclerosis with muscular involvement in 7. But neither the presence nor the titer of ANA were correlated with the subsequent development of osteoarticular sequelae. The level of total complement appeared to be lowered in 3/8 cases. No renal involvement was demonstrated. Blood tests for circulating immune complexes were positive in 4/8 patients. Skin biopsy for direct immunofluorescence was performed in 6 children and demonstrated immunoglobulin deposits in 4: three had IgM fixation on the dermo-epidermal junction, and one had speckled fixation of IgG on epidermal nuclei (this has not previously been reported in localized scleroderma). There data highlight: a--the high frequency of ANA in linear scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical evaluation of scleroderma spectrum disorders using a points system

We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynaud's phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynaud's phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP.     

Jo-1 positive paraneoplastic systemic sclerosis in a patient with metastatic melanoma

A link between systemic sclerosis (SSc) and malignancy is suggested by epidemiological evidence, but the underlying mechanism connecting both diseases has been a source of ongoing controversy. Here, we describe the first case of paraneoplastic SSc secondary to a primarily diagnosed melanoma. Two months after diagnosis of metastatic melanoma, a 40-year-old female presented with high serum titers of antinuclear antibodies (ANA), but no symptoms of autoimmune disease. Five months later, the onset of Raynaud's phenomenon together with highly positive Jo-1 antibodies was observed. The following clinical course of scleroderma was correlated to melanoma remission and progression. Finally, the patient developed severe pulmonary fibrosis, massive pleural effusion, severe thoracic scleroderma and necrosis of the fingertips, simultaneously with a progression of melanoma to disseminated lymph node metastases and a small brain metastasis. This rare case of SSc concurrent with melanoma suggests that besides other possible mechanisms, paraneoplastic etiology can be responsible for the association between SSc and cancer.     

Eosinophilic fasciitis: an early variant of scleroderma

Eosinophilic fasciitis, originally reported as a syndrome distinct from scleroderma, appears now to be an early inflammatory variant of scleroderma. No less than one half of the cases reported as eosinophilic fasciitis have convincing features of scleroderma, including Raynaud's phenomenon, esophageal dysmotility, restrictive lung disease, diffuse hyperpigmentation, synovitis, flexion contractures, dermal sclerosis, colonic diverticula, scleroderma kidney, positive latex fixation test, and the presence of serum antinuclear antibodies (ANA). Clinical presentations of scleroderma range from isolated acrosclerosis to rapidly progressive systemic sclerosis. As clinical experience and long-term follow-up data on eosinophilic fasciitis accumulate, it appears that the syndrome may well represent another variant in the scleroderma spectrum. Reported here is a case which presented clinically and histologically as eosinophilic fasciitis, but which progressed over 3 years to diffuse, histologically confirmed scleroderma.     

Anticentromere antibody: an immunological marker of a subset of systemic sclerosis

Our clinical and immunological studies of 114 cases of systemic sclerosis, 54 of Raynaud's disease and 46 of other connective tissue diseases, centered on the diagnostic and prognostic significance of anticentromere antibodies (ACA). The ACA occurred in 21 of 84 patients with acrosclerosis, in four of 54 patients with Raynaud's disease but in none of 30 patients with diffuse scleroderma or transitional form, acrosclerosis-diffuse scleroderma, or 46 cases of other connective tissue diseases. The ACA-positive patients had no contracture or immobilization of the fingers, the indurations and/or indurative oedema were confined to fingers and usually no other types of ANA were detected. However, systemic involvement and the course of the disease were comparable in ACA-negative and ACA-positive acrosclerosis patients. The studies indicate that there is a subset of acrosclerosis with minimal indurations confined to the fingers, and ACA appears to be its serological marker. We propose to use the term CREST for this subset, which to date has not been exactly defined and is regarded by some authors as synonymous with acrosclerosis.     

Immunologic Markers of Systemic Scleroderma in Children

Abstract: This study was performed on seven children with systemic scleroderma, three with the diffuse and four with the limited type. All three patients with diffuse scleroderma had high titers of clumpy pattern antinucleolar antibody on HEp-2 cells. The course of the disease was severe, and two children died. Four children with limited scleroderma had mild disease, and Scl-70 antibody, an immunologic marker that in adults is associated mostly with diffuse scleroderma. In one child Scl-70 antibody and anticentromere antibody coexisted, although previously the two were believed to be mutually exclusive. This study shows that limited scleroderma of childhood with slight cutaneous involvement may be associated with the Scl-70 marker. The findings in 10 adults in whom Raynaud's phenomenon developed in childhood and indurations appeared some years later, point to the sinificance of careful observation of these children, with repeated testing for immunologic markers of SSc. An important new finding is the association of different types of systemic sclerodermas with specific immunologic markers.     

Anticentromere-protein-B-DNA complex activities in anticentromere antibody-positive patients

Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often those with scleroderma). In this study, we analysed activities of anti-CENP-B-DNA complex in anticentromere antibody (ACA)-positive patients using DNA immunoprecipitation with purified CENP-B. The activities correlated with ACA titres and were closely associated with Raynaud's phenomenon. Patients with CREST symptoms (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) showed higher activities than those with no symptoms. Our results suggest that autoimmune responses to native CENP-B may have an important role in the pathogenesis of scleroderma.     

Antihistone antibodies in linear scleroderma variants

BACKGROUND: Linear scleroderma occurs as two clinically distinct variants: the frontoparietal en coup de sabre type, and the torso-extremity type. Antihistone antibodies (AHAs), which traditionally are markers for drug-induced lupus, may also be linked to linear scleroderma. METHODS: Retrospective review of all patients presenting with linear scleroderma who had AHA titers measured. RESULTS: A total of 35 patients were identified. Twenty patients with linear scleroderma of the torso and/or extremities comprised 14 pediatric patients (相似文献   

Localized scleroderma in adults and children. Clinical and laboratory investigations on 239 cases

We examined, retrospectively, 239 patients (113 adults and 126 children) with LS, referred to our department from 1980 up to 2001. Clinical parameters evaluated were age, sex, LS variant, extracutaneous manifestations, duration of disease and follow-up. We also considered laboratory findings, most notably erythrocyte sedimentation rate, blood eosinophilia, antinuclear antibodies (ANA) and various circulating autoantibodies. Plaque morphea was the most common form in both groups (74 adults and 61 children). In contrast, linear scleroderma affected children much more frequently than adults (22 children vs 7 adults). When the limbs were involved, this variant could lead to severe orthopedic complications (10 children vs one adult patient). On the other hand, linear scleroderma of the scalp and face comprising scleroderma en coup de sabre and Parry-Romberg syndrome was also more frequent in children (14 children vs 5 adults) causing ocular (8 cases), oral (7 cases) and neurologic (8 cases) abnormalities. Typical of childhood were mixed forms (18 pediatric patients), characterized by combination of different LS variants, which usually followed a more protracted and complicated course and showed ANA positivity (11 cases). Among adults, Raynaud's phenomenon was found in 8 patients; interestingly, anticentromere antibodies were detected in 4 of these subjects, identifying a subset at risk for progression to systemic disease. Children and adults developed LS with analogous clinical and immunological features. However, the prevalence of LS variants differed between adult and pediatric populations, leading to different extracutaneous complications.     

Speckled (particulate) epidermal nuclear IgG deposition in normal skin. Correlation of clinical features and laboratory findings in 46 patients with a subset of connective tissue disease characterized by antibody to extractable nuclear antigen.

Clinical and laboratory findings were correlated from 46 patients with IgG localization in epidermal nuclei in a speckled (particulate) pattern on direct immunofluorescence of normal skin. Cutaneous manifestations included lupus erythematosus (LE), swollen hands or sclerodactyly, alopecia, vasculitis, and dyspigmentation. Systemic manifestations included arthritis or arthralgia, Raynaud's phenomenon, serositis, vascular headaches, mild renal disease, myositis, and sicca syndrome. High titer (mean = 1:142, 800) serum antibody to extractable nuclear antigen (ENA) was found in 81%. Eighty-six percent had antibody to an RNase-sensitive antigenic component of ENA (ribonucleoprotein or RNP); 14% had antibody to an RNase-resistant ENA termed Sm. Deposition of IgG in a speckled pattern in epidermal nuclei is an immunopathologic marker for a subset of connective tissue disease characterized by antibody to ENA. Those with Sm specificity had systemic LE (SLE); Those with RNP specificity had Raynaud's phenomenon usually associated with overlapping features of SLE, scleroderma, and/or dermatomyositis.     

中药联合青霉胺治疗系统性硬皮病疗效观察

目的:研究益气活血温肾中药联合青霉胺小剂量递加疗法治疗系统性硬皮病的疗效及安全性.方法:随机将硬皮病患者分为中药组、西药组、中西药结合组,观察治疗前后的临床表现、实验室检查、肺和食管检查情况,进行临床疗效评价和不良反应观察.结果:中西药结合组对皮肤硬化、关节功能和肺纤维化改善均明显好于中药组和西药组,治疗前后雷诺现象和血内皮素积分差中药组和中西药结合组均大于西药组,血沉在治疗后中西药结合组较其他两组明显降低.中西药结合组治疗有效率较其他两组高,中药组不良反应最小.结论:益气活血温肾中药联合青霉胺小剂量递加疗法治疗系统性硬皮病,对其皮肤硬化、雷诺现象、肺纤维化均有明显的改善,且不良反应较西药组低,疗效亦优于单用中药或西药.     

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.     

伴雷诺现象的系统性红斑狼疮42例分析

目的：了解伴雷诺现象（RP）的系统性红斑狼疮（SLE）患者的临床特征。方法：对近4年在我院住院的42例拌RP的SLE患者进行临床分析,并与116例无RP的SLE患者进行对照。结果：与无RP组相比,有RP组出现脱发、肌炎／肌病、心脏受累和肺动脉高压的几率明显增高（分别为56.90％－83.33％,9.48％－23.81％,29.31％－59.52％,1.72％－21.43％,P＜0.05或0.01）。γ－球蛋白升高,抗核抗体、抗RNP及抗Sm抗体的阳性率也明显增高（分别为50.52％－73.68％,68.47％－87.80％,24.04％－70.00％,7.69％－35.00％,P＜0.05或0.01）。而两组患者在肾炎、神经系统受累及血液系统受累的发生率差异无显著性（P均＞0.05）。对125例患者进行了平均2.15年的随访,其中包括全部的11例肺动脉高压患者,死亡3例,其中1例死于肺动脉高压并发右心衰竭（有RP组）。结论：SLE患者出现雷诺现象提示较易发生肺动脉高压、心脏受累和免疫学异常,对伴雷诺现象的SLE患者应注意其心肺状态,以便早期诊断和治疗。     

成人皮肌炎患者抗核抗体与临床特征及肿瘤风险的关系

目的 探讨成人皮肌炎患者抗核抗体与临床特征及肿瘤风险的关系.方法 回顾性分析2008年4月至2018年4月在苏州大学附属第一医院皮肤科住院的101例皮肌炎患者的临床资料,分为抗核抗体阳性组和阴性组,比较两组之间肌病、肿瘤发生风险以及其他临床特征的差异.92例患者随访2年.采用卡方检验分析比较两组的临床特征,利用多因素回...