Development of systemic sclerosis in a patient with systemic lupus erythematosus and topoisomerase I antibody

We describe a patient with systemic lupus erythematosus (SLE) associated with topoisomerase I (topo I, Scl-70) antibody, a specific marker for systemic sclerosis (SSc). SSc patients who produce this antibody have severe cutaneous and visceral involvement, and eventually have a poor prognosis. It is rare to find this antibody in patients with other collagen diseases. Only four SLE patients have been reported in the English language literature who were topo I antibody-positive but had no clinical evidence of scleroderma. The serum of our patient with SLE had precipitating topo I antibody from the onset of his disease. Twelve years after the onset of SLE, he developed proximal scleroderma and pulmonary fibrosis. This case reconfirms the prognostic significance of topo I antibody as a predictive marker, and indicates that SLE patients with topo I antibody require careful follow-up for future development of scleroderma.     

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.     

Substrate specificity of antinuclear antibodies in scleroderma.

Studies of antinuclear antibodies (ANA) were carried out in 39 cases of systemic scleroderma and for comparison in 19 cases of systemic lupus erythematosus (SLE) and 4 of mixed connective tissue disease (MCTD) using indirect immunofluorescence (IF) methods under standard conditions. The results on three different substrates--monkey esophagus, guineapig lip and rat liver--are reported. In 48.7% of scleroderma cases ANA showed a substrate specificity. The highest percentage of positive results in scleroderma was obtained on monkey esophagus (97.4%) and the lowest on rat liver (61.5%). In SLE and MCTD, in contrast, only about 13% of the sera displayed such specificity. If only sera with substrate specificity are considered, the positive results on monkey esophagus and rat liver are 94.7% and 21.1%, respectively. Titers of sera reacting positively on 2 or 3 substrates were mostly in agreement, although some sera both in systemic scleroderma and SLE showed higher titers on monkey esophagus. The IF pattern was usually the same regardless of the substrate, Tests for ANA in scleroderma should be performed on at least 2 substrates simultaneously.     

Concurrent linear scleroderma and systemic lupus erythematosus: a report of two cases.

Two patients with linear scleroderma (en coup de sabre) developed systemic lupus erythematosus (SLE). This association has been well documented in only one previous case. The presence of high titer antibodies to ribonucleoprotein (RNP) initially led to the diagnosis of the mixed connective tissue disease. Development of more serious clinical involvement and antibodies to Sm (case 1) or native deoxyribonucleic acid (nDNA) (case 2) helped establish a diagnosis of SLE. Use of these studies in the differential diagnosis of systemic rheumatic diseases is disucssed briefly. The presence of anti-RNAP antibodies in patients with localized scleroderma may herald a more serious rheumatic disease.     

COLLAGEN-LIKE PROTEIN IN SERUM OF PATIENTS WITH CONNECTIVE TISSUE DISORDERS

Collagen-like protein (CLP) was demonstrated in the serum of normal human individuals and of patients with connective tissue disorders. The average amount of CLP in normals was 9.1 ± 0.2 μg/ml, whereas in systemic scleroderma, circumscribed scleroderma, and systemic lupus erythematosus the amounts were significantly lower. Serum CLP levels were also found to be decreased in pseudoxanthoma elasticum, striae atrophicae, and impetigo herpetiformis, but variable in dermatomyositis, and within normal limits in pyoderma gangrenosum. There seemed to be a relationship between the behavior of collagen-like protein and the severity of clinical manifestations in systemic scleroderma and systemic lupus erythematosus.     

Prevalence and characteristics of anti-single-stranded DNA antibodies in localized scleroderma. Comparison with systemic lupus erythematosus

Prevalence, levels, and immunoglobulin classes of anti-single-stranded DNA antibodies were determined by an enzyme-linked immunosorbent assay in 52 patients with localized scleroderma (33 with morphea, four with generalized morphea, and 15 with linear scleroderma), in 60 healthy controls, and, for comparison, in 31 patients with systemic lupus erythematosus. Localized scleroderma revealed a significant prevalence of anti-single-stranded DNA antibodies, mainly characterized by high levels and IgM and IgA isotypes. Comparison of antibody characteristics in different clinical forms of localized scleroderma showed some significant differences (levels and immunoglobulin isotypes). Comparison with systemic lupus erythematosus showed that frequency, high levels, and IgG isotype of anti-single-stranded DNA antibodies significantly prevailed in systemic lupus erythematosus, while the IgM isotype significantly prevailed in localized scleroderma. However, generalized morphea and linear scleroderma did not significantly differ from systemic lupus erythematosus as regards antibody frequency and prevalence of high antibody levels.     

Linear circumscribed scleroderma--case report. Classification and differentiation of circumscribed scleroderma

In linear scleroderma, a rare form of circumscribed scleroderma, the lesions are arranged in a band-shaped linear distribution and both the superficial and the deeper layers of the skin are attached to the underlying structures. This disease must principally be differentiated from eosinophilic fasciitis (Shulman's syndrome). On the basis of the clinical and laboratory data, systemic scleroderma can be excluded in nearly all the cases. Nevertheless, patients with linear scleroderma might develop systemic scleroderma or other systemic diseases of the connective tissue even after years. As a consequence, thorough physical examination as well as laboratory evaluation is necessary over a long follow-up period. We introduce a new classification of circumscribed scleroderma.     

Diffuse soft tissue calcifications (calcinosis cutis) in a patient with discoid lupus erythematosus

Soft tissue calcification is known to occur in dermatomyositis, systemic scleroderma and CREST syndrome, but rarely in systemic lupus erythematosus (SLE). Diffuse soft tissue calcifications have not been reported in discoid lupus erythematosus (DLE). In a patient with discoid lupus erythematosus, calcinosis cutis developed about 20 years after the onset of the disease. During the follow-up time of 25 years, manifestations suggestive of a systemic disease were observed in our patient. However, no specific diagnosis could be established. The clinical, light and electron microscopic as well as immunohistochemical findings of our patient are reported. On the basis of electron microscopic findings it is suggested that intracellular calcification occurred in this case.     

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.     

Extensive calcinosis cutis with systemic lupus erythematosus

Calcinosis cutis is a common clinical feature of dermatomyositis and scleroderma but is only rarely reported in association with systemic lupus erythematosus (SLE). We describe three patients with long-standing systemic lupus erythematosus in whom extensive calcinosis cutis developed. We identify characteristics our patients share in common with 23 previously described patients.     

Epidermal nuclear immunofluorescence: serological correlations supporting an in vivo reaction

Epidermal nuclear deposits of immunoglobulins (Ig) were studied by direct immunofluorescence in three groups of patients: ten scleroderma (SD, systemic sclerosis), seven dermatomyositis (DM) and seven systemic lupus erythematosus (SLE). Each patient had skin biopsies taken from three different sites (nailfold, forearm, buttock) on the same day that a serum sample was also obtained. Epidermal nuclear deposits were observed in nine of twenty-four patients (five SD, two DM, two SLE). A high serum ANA titre correlated significantly with the presence of epidermal nuclear Ig deposits. The nucleolar epidermal nuclear pattern was limited to the SD group, four of ten patients showing this pattern. Two of nine patients with positive results in the nailfold and forearm had negative findings in the buttock, supporting the view that deposition of Ig in the epidermal nuclei occurs in vivo.     

Diagnosis of systemic lupus erythematosus. Importance of antinuclear antibody titers and peripheral staining patterns.

Titers and patterns of antinuclear antibodies (ANA) in sera from 134 normal blood donors, 20 patients with rheumatoid arthritis, 15 patients with systemic scleroderma, and 32 patients with diagnosed or suspected systemic lupus erythematosus (SLE) were studied. The difference between the findings with sera of patients with SLE and normal subjects in terms of high (greater than 160) titers of ANA was greater than in terms of peripheral staining patterns. However, in comparing sera from patients with SLE with sera from patients with other connective tissue diseases, greater differences were found in the incidence of peripheral patterns of ANA compared to differences in the frequency of high ANA titers. Maximum specificity in the diagnosis of SLE was achieved when both titers and patterns of ANA were considered.     

The lupus band test in oral mucosa, conjunctiva and skin

The prevalence and clinical significance of subepithelial immunoglobulin and complement deposition (the lupus band) were examined in the uninvolved sun-protected skin of the forearm, the uninvolved sun-protected lip mucosa and sun-protected bulbar conjunctival mucosa in systemic lupus erythematosus (SLE) and chronic cutaneous lupus erythematosus (CCLE). In SLE, linear deposition of an immunoreactant at the BMZ was detected in 32% (6/19) of skin biopsies; 21% (4/19) of lip mucosal biopsies and 42% (5/12) of conjunctival biopsies. There was no significant difference in the sensitivity of the test at different sites in SLE and no correlation between a positive test in skin, lip or conjunctiva and clinical mucosal involvement. In CCLE, linear deposition of an immunoreactant at the BMZ was found in 3% (1/32) of skin biopsies; 3% (1/29) of lip mucosal biopsies and 50% (10/20) of conjunctiva and clinical mucosal involvement. In the conjunctiva, IgG was present in all but one of the biopsies and was the only immunoreactant in 90% (9/10) of positive CCLE biopsies and 60% (3/5) of positive SLE biopsies. In lupus erythematosus immunoreactants may be deposited in the basement membrane zone beneath non-keratinizing mucosal surfaces of the lip and the eye as well as the skin. In CCLE, the test may be positive in conjunctiva when skin and lip are negative.     

Direct immunofluorescent findings in scleroderma syndromes

Cutaneous direct immunofluorescent findings were examined in 78 patients who had either vascular scleroderma (group 1, 52 patients) or scleroderma with features of myositis or lupus erythematosus (group 2, 26 patients). Group 2 had higher antinuclear antibody levels, erythrocyte sedimentation rates, serum IgG concentrations, frequency of positive LE clot test, and rheumatoid factor activity. Ninety-two percent of group 1 (48 patients) had negative direct immunofluorescent findings, whereas 77% of group 2 (20 patients) had positive findings at the basement membrane or in the blood vessels (or both). The 6 patients in group 2 who had negative immunofluorescent findings were all on systemic steroid therapy. Of the 17 patients in group 2 who had tests for antibody to extractable nuclear antigen, only 3 had high-titer antibody to ribonucleoprotein--a pattern characteristic of mixed connective tissue disease. Direct cutaneous immunofluorescence is proposed as a means of identifying those patients with scleroderma who may be steroid-responsive.     

Cyclosporin A in the therapy of inflammatory dermatoses]

The experience reported in the literature with cyclosporin A (CyA) in the treatment of various inflammatory and autoimmune dermatological diseases is reviewed and compared with the authors' own experience of treating 36 patients presenting with psoriatic arthritis [8], generalized pustular psoriasis [2], palmoplantar pustular psoriasis [12], Beh?et's disease [2], disseminated circumscribed scleroderma [2], acrodermatitis continua suppurativa [2], pemphigus vulgaris [1], lupus erythematosus [3], pyoderma gangrenosum [1], severe atopic eczema [2], and actinic reticuloid [1]. On the basis of the authors' own experience and the reported results, treatment with CyA appears to be primarily indicated in pyoderma gangrenosum, circumscribed scleroderma, psoriatic arthritis and acrodermatitis continua suppurativa. In diseases such as actinic reticuloid, Beh?et's disease, localized and generalized pustular psoriasis, treatment with CyA leads to good results with an acceptable risk-benefit ratio. In our view, it is doubtful whether treatment with CyA alone is indicated in alopecia areata, lichen ruber, dermatomyositis, atopic eczema, systemic scleroderma, bullous diseases, and lupus erythematosus, and in the last two it should be given only in combination with systemic steroids. Literature reports provide no support for the use of CyA in ichthyosis vulgaris, pityriasis rubra pilaris, and cutaneous T-cell lymphomas. The risk-benefit ratio of CyA treatment should be carefully considered, especially in diseases that are not life-threatening.     

Calcinosis cutis in systemic lupus erythematosus: a case report and review of the published work

Calcinosis cutis is a common clinical feature of dermatomyositis and scleroderma but rarely reported in association with systemic lupus erythematosus (SLE). Calcinosis cutis in SLE occurs without calcium and phosphorus metabolic abnormalities and may be localized or generalized. The pathophysiology remains unclear and no effective therapy is currently available. We report a 30-year-old woman with a 13-year history of SLE who developed multiple calcinosis cutis around both knees and we review the relevant published work.     

Localized Linear Bullous Eruption of Systemic Lupus Erythematosus in a Child

Abstract: A 9-year-old girl newly diagnosed with systemic lupus erythematosus (SLE) developed a localized linear papulovesicular eruption over the right dorsal hand and ulnar forearm. The skin findings were clinically suggestive of herpes zoster, lichen striatus, or lichen planus-lupus erythematosus overlap. However, histologic, immunofluorescent, Immunoelectron microscopic, and immunobiot studies revealed findings compatible with bullous SLE. Our patient is noteworthy because she is the first one reported with bullous SLE presenting in a localized linear pattern. She is also the second-youngest reported patient with bullous SLE.     

Unusual manifestation of scleroderma of the trunk

We present the case of an 81-year-old women with progressive systemic scleroderma. In addition to the typical manifestations of diffuse (truncal) scleroderma, including involvement of the esophagus, lungs and muscles, there were two unusual findings: large, non-sclerosing areas on the trunk simulating the disabling type of circumscribed scleroderma and high titers of anticentromere antibodies, while there were no anti-Scl-70 antibodies. The disease responded to treatment with griseofulvin.     

抗Scl-70和抗Jo-1抗体在系统性硬皮病和皮肌炎中的临床意义

为了提高对系统性硬皮病及皮肌炎的临床确诊率，通过ＥＮＡ抗原应用免疫印迹技术检测了１９例系统性硬皮病（ＳＳ）及２８例皮肌炎或多发性肌炎（ＤＭ／ＰＭ）患者抗Ｓｃｌ ７０及抗Ｊｏ １抗体，并与系统性红斑狼疮（ＳＬＥ）、混合性结缔组织病（ＭＣＴＤ）共６２例及５０例健康人作了对照研究。结果表明：７０ ＫＤ（抗Ｓｃｌ ７０）多肽抗体是系统性硬皮病的特异性标记抗体，阳性率３１．６％；５５ＫＤ（抗Ｊｏ １）多肽抗体是皮肌炎的特异性标记抗体，阳性率４６．４％。ＳＬＥ、ＭＣＴＤ及健康人全部阴性，从而有助于对系统性硬皮病及皮肌炎的鉴别诊断