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PubMedDate not supplied

Stimulation of lymphocyte reactivity by a low molecular weight cutaneous antigen in patients with progressive systemic sclerosis (scleroderma).

A low molecular weight cutaneous antigen was found to stimulate the release of macrophage migration inhibition factor from circulating lymphocytes of patients with diffuse scleroderma. The antigen had a molecular weight of approximately 3,500 and contained RNA and polypeptides, but no hydroxyproline. Lymphocytes from patients with the CREST syndrome, rheumatoid arthritis, and from normal controls did not respond to the antigen. An immune response to this antigen may be a factor in the pathogenesis of diffuse scleroderma.

Adult↗

PubMed1991

Endothelial and fibroblastic activation in scleroderma. The myth of the "uninvolved skin".

We studied the immunohistochemistry of the skin of scleroderma patients to determine the differences (if any) between clinically "affected" and "nonaffected" areas. We examined paired skin biopsy samples from clinically involved forearm skin ("affected") and clinically uninvolved proximal skin ("nonaffected") taken from 19 patients with diffuse scleroderma and from 15 normal control subjects. We stained the sections with antibodies to endothelial leukocyte-adherence molecule type 1 (ELAM-1; to detect endothelial activation) and to procollagen-1 (PC-1; to detect newly formed, unprocessed collagen). There was increased expression of ELAM-1 and PC-1 in sclerodermatous skin as compared with the controls, but there was no difference between clinically affected and nonaffected skin samples. In 10 of 11 patients whose condition was getting worse, endothelial and fibroblast activation preceded fibrosis. Endothelial and fibroblast activation are more widespread in the skin of scleroderma patients than is evident by inspection on physical examination. What appears to be "normal" skin in diffuse scleroderma is already pathologic, as shown by abnormal endothelial activation and procollagen production.

Adult↗

PubMed1992

Reactivity of anti-mitochondrial antibodies in primary biliary cirrhosis and systemic sclerosis.

Anti-mitochondrial antibodies (AMA) were detected by indirect immunofluorescence in the sera of 16 out of 17 (94%) patients with primary biliary cirrhosis (PBC). Immunoblotting experiments with mitochondrial polypeptides from the porcine liver as antigens revealed that three antigens were recognized by the sera from AMA-positive patients. These were a 70-kD protein recognized by nine out of 16 AMA-positive sera, a 50-kD protein recognized by 13 out of 16 AMA-positive sera and a 39-kD protein recognized by four out of 16 AMA-positive sera. The reactivity of these polypeptides was destroyed by brief exposure to trypsin. None of these antigens were recognized by any of the 30 control sera. These results show that the 70-kD, 50-kD and 39-kD proteins are the major mitochondrial autoantigens recognized by sera from patients with PBC. In addition, of 30 sera samples from patients with diffuse scleroderma, 13 reacted to the 70-kD and/or 50-kD antigens. Anti-centromere antibodies (ACA) were also detected in the sera of five of the 17 (29%) patients with PBC. The high prevalence of ACA in patients with PBC and the presence of anti-70- and 50-kD antibodies in patients with diffuse scleroderma provide evidence of an association between these two disorders.

Adult↗

PubMed1992

Significance of plasma endothelin-1 levels in patients with systemic sclerosis.

Endothelin-1 (ET-1) is a novel potent vasoconstrictor peptide discovered in the supernatant fraction of cultured endothelial cells. We measured plasma levels of ET-1 using a sensitive sandwich enzyme immunoassay. Plasma concentrations of ET-1 in 31 patients with systemic sclerosis (SSc) (1.90 +/- 0.47 pg/ml) were higher than those (1.31 +/- 0.10 pg/ml) in 25 age and sex matched healthy subjects. Patients with SSc with diffuse scleroderma had higher levels of ET-1 compared with those with limited scleroderma. Plasma ET-1 levels correlated inversely with carbon monoxide diffusing capacity (DLco). Measurement of plasma ET-1 levels may be useful as a predictor of prognosis of SSc.

Adult↗

PubMed1979

Skin thickness and collagen content in progressive systemic sclerosis and localized scleroderma.

Skin biopsies of uniform location and surface area (7 mm diameter) were obtained from the extensor aspect of the forearm of 147 patients with progressive systemic sclerosis (PSS) (107 with diffuse scleroderma, 40 with the CREST syndrome variant) and 58 individuals with normal skin. After careful removal of all subcutaneous fatty tissue, the skin cores were weighed and their water and hydroxyproline content determined. Despite recent claims to the contrary, it was found that there is a marked and highly significant increase in the thickness of the skin during the indurative phase of PSS, and that this is associated with a proportionate increase in total dermal collagen content. A similar degree of thickening was found in the skin of patients with eosinophilic fasciitis and acromegaly. A close correlation was observed between clinical estimation of the degree of skin thickening and the weight of the skin biopsy cores. Change in the weight of skin cores was observed during the course of illness of the patients with PSS and may serve as a useful measurement of alteration in the degree of skin thickening.

Acromegaly↗

PubMed1992

Lower extremity amputation in scleroderma.

Scleroderma or Systemic Sclerosis (SSC) is a disorder characterized by fibrosis of the skin and multiple internal organs. The pathological lesion is a triad of small artery intimal proliferation, medial thinning and adventitial scarring. Autoamputation of fingers and toes is often seen, but only a few cases of limb amputation in scleroderma patients have been reported. The Pittsburgh Scleroderma databank includes 1,030 patients with SSC. Among these were seven patients who sustained lower limb amputation. There were four patients with the CREST variant of SSC, two with diffuse scleroderma, and one who had SSC/rheumatoid arthritis/polymyositis overlap who sustained limb amputation. Of the seven, three were male and five had a significant smoking history. Ages ranged from 46 to 71 years. All patients underwent amputation for nonhealing ulcerations. No problems with postoperative wound healing were seen. Pathologic changes typical of SSC in addition to atherosclerotic peripheral vascular disease were described in one case. Three patients were successfully fitted with prostheses and became independent ambulators. Four patients could not be fitted with prostheses. No skin problems were reported related to prosthetic use. Our review demonstrates that SSC patients who undergo amputation can become successful prosthetic users and should be considered for prosthetic prescription.

Aged↗

PubMed1990

Functional and phenotypic analysis of T lymphocytes cloned from the skin of patients with systemic sclerosis.

Activated T lymphocytes often accumulate in the lower dermis of patients with systemic sclerosis (scleroderma) and may play a role in the development of dermal fibrosis. We propagated and cloned these cells directly from skin biopsies in four of eight cases of early, untreated systemic sclerosis with diffuse scleroderma. The cloning frequency estimates were f = 0.20 and f = 0.48 for T cells derived from the skin of two patients versus f = 0.68 and f = 0.96 for autologous blood T lymphocytes. All but one of 24 skin-derived scleroderma clones were CD4+. Clonal analyses performed with CD4+ clones from patients and normal controls showed that all but one skin-derived clones synthesized either interferon-gamma (60%), glycosaminoglycan-stimulatory factor (26%) or both (9%) when induced in vitro by a mitogen, concanavalin A, but not by autologous dermal fibroblasts. In contrast, blood-derived clones had a different functional phenotype. All skin-derived clones produced tumour necrosis factor-alpha. Our results demonstrate that T lymphocytes obtained from the skin of patients with systemic sclerosis synthesized cytokines which could modulate functions of human dermal fibroblasts.

Adult↗

PubMed1977

Histocompatibility antigens in progressive systemic sclerosis (scleroderma).

A study was undertaken to determine the distribution of major histocompatibility (HLA) antigens in progressive systemic sclerosis (PSS) (scleroderma). A total of 106 patients with PSS and 208 normal controls were tested for the presence of 18 different HLA antigens by the microcytotoxicity technique. These patients were equally divided between patients with classical diffuse scleroderma (53 patients) and those with the CREST syndrome variant of the disease (53 patients). When the P values were multiplied by 18, to correct for the number of antigens studied, no significant alteration in the frequency of any HLA antigen was found for the entire group of scleroderma patients or for either of the two subpopulations.

Calcinosis↗

PubMed1992

Hemolytic uremic syndrome in a patient with systemic sclerosis treated with cyclosporin A.

The case is presented of a 48-year-old female suffering from diffuse cutaneous systemic sclerosis (diffuse scleroderma) since 8 years, who went into renal failure as part of hemolytic uremic syndrome following 3 weeks' treatment with 3.8 mg/kg cyclosporin A. Hemolytic uremic syndrome has previously been described in transplant patients receiving cyclosporin A. There are also four cases reported in the literature of renal failure developing in middle aged females with diffuse cutaneous systemic sclerosis after short-term use of low dosage cyclosporin A treatment. It is suggested, that it may be wise not to use cyclosporin A to this category of patients, in which it can not be ruled out, that even a low dose therapy may trigger the rapid onset of scleroderma renal crisis or as in our case provoke hemolytic uremic syndrome.

Acute Disease↗

PubMed1992

[Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis].

We have characterized a clinical significance of anti-U3RNP, anti-7-2RNP, anti-RNA polymerase I and anti-PM-Scl antibody, autoantibodies to nucleolar proteins detected by immunoprecipitation method in patients with systemic sclerosis (SSc). In 248 patients with SSc, anti-U3RNP antibody was positive in 9 (3.6%), anti-7-2RNP antibody was positive in 7 (2.8%) and anti-RNA polymerase I antibody was positive in 3 (1.2%). But none of 248 patients was positive for anti-PM-Scl antibody. Anti-U3RNP antibody positive SSc patients showed significantly lower frequency of joint and lung involvements, compared with anti-U3RNP antibody negative SSc patients. Anti-7-2RNP antibody was found only in patients with limited scleroderma. The anti-7-2RNP antibody could be detected before appearance of skin thickening, so this indicate the usefulness of detecting anti-7-2RNP antibody in the early stage of SSc. Two of 3 anti-RNA polymerase I antibody positive patients were classified as diffuse scleroderma. All anti-RNA polymerase I antibody positive patients had high incidence of internal organ involvements including lung, heart and kidney, so two of these patients died of heart failure. These data showed the close clinical association of antigenic specificities of anti-nucleolar antibodies analysed by immunoprecipitation method, and indicated the usefulness of detecting these anti-nucleolar antibodies in subgrouping of patients with SSc.

Adult↗

PubMed1991

Non-invasive evaluation of long-term cardiac effects of captopril in systemic sclerosis.

Impairment of left ventricular (LV) function has previously been reported in patients with systemic sclerosis (SScl). An intermittent vasospastic process in the myocardium may contribute to the development of myocardial dysfunction. Vasodilators may therefore be potentially useful in the treatment of cardiac dysfunction in patients with SScl. This study was designed to evaluate the long-term effects of captopril on the myocardial function of patients with SScl. Twenty-two patients with SScl (15 patients with diffuse scleroderma and 7 patients with CREST syndrome, i.e. calcinosis. Raynaud's phenomenon, oesophageal hypomotility, sclerodactyly, telangiectasia) were investigated by means of Doppler and echophonocardiography before and after treatment with captopril (1.3 mg kg-1 body weight d-1) for 11-15 months. There were no significant differences in heart rate, systolic and diastolic blood pressure, end-systolic blood pressure, total peripheral resistance or LV diameters before or after treatment. However, captopril treatment exerted significant effects on LV function: the pre-ejection period (PEP) and the ratio of pre-ejection period to LV ejection time decreased significantly (P less than 0.05). Mitral E-point septal separation decreased significantly (P less than 0.01), even after adjustment for LV end-diastolic diameter (P less than 0.01). The ejection fraction increased significantly (P less than 0.05), and the isovolumic relaxation time decreased (P less than 0.01). The left atrial emptying index increased (P less than 0.01). The Doppler peak late to early ventricular filling velocity decreased (P less than 0.05), and the isovolumic index was also reduced (P less than 0.05). We conclude that both systolic and diastolic LV function indices improved in patients with SScl after captopril treatment for a mean period of 1 year. The effects of captopril might be due to vasodilation of the myocardial vessels and/or a direct effect on the renin-angiotensin system of the heart.

Adult↗

PubMedDate not supplied

[L-tryptophan-associated chronic eosinophilia-myalgia syndrome treated with cyclosporin].

After 2 weeks of ingestion of 130 g L-Tryptophan a 52 year old female develops an Eosinophilia Myalgia Syndrome with acute onset of deep venous thrombosis of forearm and possible initial cardiac manifestation featuring intermittent sinustachykardia. This is followed by a severe chronic disease (follow-up 15 months) with diffuse scleroderma and sensomotoric polyneuropathia. The deep muscle biopsy-specimen shows mononuclear infiltration of fascia and interstitial myositis with rare eosinophils. A blood eosinophilia (900/ul) occurs only in the initial acute onset of the illness. Plasma level of Kynurenine is significantly high (4000 pmol/ml), collagenneosynthesis is activated (Procollagen type III peptid 0.927 U/ml). No significant clinical improvement was seen with Acathioprine (100 mg/d) and Prednisolon (40-60 mg/d), after treatment with Ciclosporin scleroderma regresses completely, polyneuropathy is persisting.

Biopsy↗

PubMed1977

[An case of acute diffuse seleroderma in an infant].

The authors report a case of diffuse scleroderma in a 15 months old infant. Dermatologic (clinical and pathological) findings are quite typical of the disease. On the other hand, in this case some particularities were observed: the age of the infant (second published case beginning before the age of two); the presence of a durable eosinophilia, the absence of visceral lesions and of biological abnormaliteis (of auto-immune nature specially), the evolution towards athrepsica and death within one year. Thus, because of these particularities, the diagnosis of scleroderma remains questionable and the diagnosis of progeria has been considered. The affection appeared in the course of a hepatitis leaving a hepatic fibrosis without inflammatory signs; no conclusion can be drawn about the relations between the hepatic affection and the fatal dermatologic disease.

Acute Disease↗

PubMed1975

[The indirect immunofluorescence test for the identification of auto-immune skin diseases (author's transl)].

The indirect immunofluorescence test has acquired great importance in the diagnosis of auto-immune skin diseases. Since it is sufficient only to send a sample of whole blood or blood serum to carry out the test, it is also of practical interest to the general practitioner. The test should be called upon if any of the following auto-immune skin diseases are suspected: pemphigus vulgaris (including p. vegetans, p. foliaceus, p. erythematosus), bullous pemphigoid (including benign mucosal pemphigoid) lupus erythematodes (systemic) and diffuse scleroderma.

Autoimmune Diseases↗

PubMed1978

Scleroderma, eosinophilia, and diffuse fasciitis.

Skin induration without internal organ involvement, blood and tissue eosinophilla, and fascilitis are features of diffuse fascilitis. However, cellular infiltrates (lymphocytes, plasma cells, and eosinophils) may also be present in the dermis, fat, and muscle. Blood eosinophilia (mild and transient) and skin eosinophilia were observed in about 20% of patients with systemic and localized scleroderma.

Adult↗

PubMed2026

Distinct Effects of Complement C4A and C4B Copy Numbers in Systemic Sclerosis Serological and Clinical Subtypes.

OBJECTIVE: Complement component 4 (C4), encoded by C4A and C4B within the major histocompatibility complex (MHC) on chromosome 6, regulates the immune response and clears immune complexes. The variable copy number (CN) of C4 genes and retroviral human endogenous retrovirus K (HERV-K) element influence its function. Given the relationship of C4 CN with systemic sclerosis (SSc) risk, we assessed associations with SSc clinical and serologic subtypes. METHODS: We compared imputed C4 CNs across SSc subgroups (4,049 anticentromere positive [ACA+]; 2,200 anti-topoisomerase I [ATA+]; 577 anti-RNA polymerase [ARA+]; 1,078 triple-negative [TN] patients; 6,295 limited cutaneous SSc [lcSSc]; and 2,946 diffuse cutaneous SSc [dcSSc]) and 17,991 controls. We evaluated associations with SSc subtypes, identifying C4-independent HLA alleles. RESULTS: Lower C4 CN and higher HERV-K CN were associated with increased risk in all SSc subgroups. ATA+ patients showed the strongest association, particularly with C4A (odds ratio = 1.88), and differences in C4A CN association were more pronounced between autoantibody subgroups (ATA+ vs ACA+, P = 4 × 10-11) than between clinical subgroups (dcSSc vs lcSSc, P = 1 × 10-4). In ACA+ patients, only low C4B CN showed a significant association to SSc risk (P = 1.23 × 10-5). We also observed sex-biased associations: dcSSc, ATA+, and ARA+ male patients showed stronger effects for C4A and ACA+ and lcSSc female patients for C4B. Finally, our results suggest that the HLA alleles associated with SSc subgroups are independent of C4 CN. CONCLUSION: This study highlights distinct genetic contributions of C4A and C4B in SSc subtypes susceptibility. Our findings suggest that lower C4 CNs, particularly C4A, increase the risk of the severe dcSSc subtype, potentially through a mechanism involving immune complex clearance.

Humans↗

PubMed1976

Skin capillary changes in early systemic scleroderma. Electron microscopy and "in vitro" autoradiography with tritiated thymidine.

Skin biopsy specimens obtained from involved and noninvolved areas in a patient with early diffuse systemic scleroderma were processed for histology, electron microscopy, and "in vitro" autoradiography with tritiated thymidine. The affected area revealed cellular infiltrates around the eccrine sweat glands, consisting of plasma cells and lymphocytes. The capillaries showed thickening of the basement lamina, damage of endothelial cells, and obstruction of their lumens. However, in some vessels, endothelial cells were preserved and appeared in prophase. Autoradiography with tritiated thymidine showed a marked increase in endothelial and periendothelial cell labeling. Blood immunological studies revealed an increase in B-lymphocytes, IgG, and IgA and the presence of antinuclear and antismooth muscle antibodies.

Adult↗

PubMed1977

Diffuse eosinophilic fasciitis. A new syndrome or variant of Scleroderma?

Recently, attention has been drawn to a scleroderma-like illness, characterized by transient eosinophilia, which is commonly antedated by unusual physical exertion, is apparently free from significant systemic changes, and in which the primary pathological alterations, consisting of intense inflammation and thickening with or without eosinophils, occur initially in the fascia, not the skin. These patients are said to respond well to oral corticosteroids and an occasional one may undergo spontaneous resolution. Clinicopathologic study of a patient with this syndrome, suggests an even deeper tissue genesis than that recently proposed for some of the cutaneoindurative disorders. Eosinophilic fasciitis probably represents an impressive, but perhaps relatively benign variant of diffuse scleroderma, according to reported cases.

Diagnosis, Differential↗