Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Scleroderma, Limited”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2003

Association of IL1A gene polymorphisms with susceptibility to and severity of systemic sclerosis in the Japanese population.

OBJECTIVE: To analyze the frequencies of haplotypes of single-nucleotide polymorphisms (SNPs) of the IL1A gene (at -889, +4729, and +4845) in patients with systemic sclerosis (SSc) and in healthy control subjects, and to determine whether the IL1A gene haplotype is associated with SSc susceptibility or disease severity. METHODS: We studied 60 patients with SSc (34 with diffuse cutaneous SSc and 26 with limited cutaneous SSc) and 70 healthy control subjects. Polymorphisms of the IL1A gene were genotyped by direct sequencing using the ABI Prism 377 Sequence Detection System. The LDSupport program, which was recently developed in our laboratory, was used to estimate the haplotype frequencies of SNPs in the study population. RESULTS: We confirmed the presence of 2 SNPs at positions -889 (C/T) and +4845 (G/T) of the IL1A gene, as previously reported. We also identified a novel SNP at position +4729 (T/C). Six haplotypes, CTG (49.7%), TCT (14.7%), CCT (20.3%), TTG (13.2%), CCG (1.4%), and TTT (0.7%), were found in the healthy controls. In contrast, only 2 haplotypes, CTG (95%) and TCT (5%), were detected in the SSc patients. Notably, the CTG haplotype was present at a significantly higher frequency in the SSc patients than in the healthy controls (P < 0.0001). We also examined the relationship between the CTG/CTG diplotype frequencies and interstitial lung disease (ILD), a major complication of SSc, as an indicator of disease severity. All SSc patients with ILD had the CTG/CTG diplotype, whereas the frequency of this diplotype was only 67% in patients without ILD. CONCLUSION: Our observations suggest that the CTG haplotype of the IL1A gene may be an important marker for the susceptibility to, and the severity of, SSc.

5' Flanking Region↗
PubMed1992

Cytokine production and serum levels in systemic sclerosis.

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF-alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF-alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.

Cytokines↗
PubMed1988

Microvascular disease and limited joint mobility in diabetes. A comparison of fibrinolysis and prostacyclin in diabetes and systemic sclerosis.

The pathogenesis of Limited Joint Mobility (LJM) in diabetes is unknown, but the abnormality is said to be associated with an increased incidence of microangiopathy. To examine the possibility that LJM may be a manifestation of microvascular disease, fibrinolysis and blood prostacyclin metabolites were measured in diabetic patients with and without LJM, and compared with patients who have systemic sclerosis (PSS). The concentrations of plasma fibrinogen (p less than 0.01) and Plasminogen Activator Activity (PAA) (p less than 0.02) were increased in both diabetic groups, compared with non-diabetic controls, and were of similar magnitude to the changes observed in PSS. Antithrombin III (AT III) activity was significantly lower in diabetic patients with LJM than in those without LJM, but not significantly different from controls. Prostacyclin concentrations were raised in PSS patients compared to controls (p less than 0.02) but were not raised in diabetic subjects. Thus abnormal fibrinolysis was demonstrated in diabetic patients compared to non-diabetic controls, and prostacyclin concentrations in diabetics were lower than in PSS patients. The diabetic patients with LJM had lower AT III activity than diabetics without LJM, but overall a convincing difference between the two groups of diabetics was not proven. No sure inferences could be drawn on the vascular aetiology of LJM, while the impaired prostacyclin activity might contribute to the development of diabetic microangiopathy.

Adult↗
PubMed2000

Immunoglobulin isotypes of anti-myeloperoxidase and anti-lactoferrin antibodies in patients with collagen diseases.

To investigate the prevalence and clinical relevance of immunoglobulin (Ig) isotypes of antimyeloperoxidase (MPO) and antilactoferrin (LF) antibodies in collagen diseases, enzyme-linked immunosorbent assay was employed to detect the Ig isotypes of both antibodies. The purified proteins of MPO and LF were used as two major representative antigens for anti-neutrophil cytoplasmic antibodies (ANCA) with a perinuclear staining pattern by an indirect immunofluorescent technique. We examined 131 serum samples from 79 patients with rheumatoid arthritis (RA), 32 with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM), and 5 with idiopathic crescentic glomerulonephritis who served as positive controls and 36 healthy subjects who served as controls. A limited number of patients with RA (4-10%), SLE (6-9%), and PSS (7-14%) but not PM/DM showed positive IgG or IgA anti-MPO antibody (MPO-ANCA) but not IgM MPO-ANCA. However, 10-20% of RA, 40-60% of SLE, 20-36% of PSS but none of the PM/DM patients showed positive IgG, IgA, or IgM anti-LF antibody (LF-ANCA). MPO- and LF-ANCA positivity in RA patients was correlated with markers of disease activity such as the erythrocyte sedimentation rate, C-reactive protein, and serum Ig levels. IgG LF-ANCA but not MPO-ANCA positivity in SLE patients also was correlated with the disease activity index but not with clinical features. Neither MPO- nor LF-ANCA positivity in PSS patients was correlated with any clinical features. Overall, both MPO- and LF-ANCA were found mainly in RA, SLE, and PSS patients but not in PM/DM patients. The Ig isotypes of MPO- and LF-ANCA frequently belonged to both IgG and IgA and rarely to the IgM class. Both MPO- and LF-ANCA positivity reflected disease activity in RA and SLE rather than specific organ involvement.

Adult↗
PubMed2000

Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.

OBJECTIVE: To determine the serum levels and clinical correlation of connective tissue growth factors (CTGF) in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc, n = 32), diffuse cutaneous SSc (dSSc, n = 28), systemic lupus erythematosus (SLE, n = 30), polymyositis/dermatomyositis (PM/DM, n = 20), and healthy control subjects (n = 30) were examined by ELISA for detection of CTGF. RESULTS: Serum CTGF levels in patients with SSc were significantly higher than those in patients with SLE or PM/DM, and in controls. CTGF levels in patients with dSSc were significantly higher than those in patients with lSSc. As for clinical correlation of CTGF, SSc patients with elevated CTGF had pulmonary fibrosis, decreased DLCO, and decreased vital capacity more frequently than those with normal CTGF levels. Further, DLCO and vital capacity were inversely and directly correlated with serum CTGF levels in patients with SSc. The dSSc patients with disease duration of 1-3 years had significantly elevated levels of CTGF compared with dSSc patients with duration < 1 year or more than 3 years. CONCLUSION: Serum CTGF levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. In addition, it appears that production of CTGF is involved in the development or maintenance of fibrosis rather than in initiation of fibrosis in SSc. These data suggest that CTGF plays a critical role in the development of fibrosis in SSc.

Adolescent↗
PubMed1994

Severe systemic sclerosis with anti-topoisomerase I antibodies is associated with an HLA-DRw11 allele.

SSc is an autoimmune connective tissue disease in which strong HLA associations have not been described. Anti-topo I antibodies are recognized, in general, in SSc patients with diffuse cutaneous involvement, whereas anti-ACAs are found in individuals with limited cutaneous involvement. We studied 95 Caucasian SSc patients, 44 with anti-topo I antibodies and 51 with neither anti-topo I nor ACA, for HLA-DR associations by using DNA typing techniques. We analyzed 181 normal Caucasian individuals in the same fashion. A significant association was observed in the anti-topo-I-positive patients with DRw11 (p = 1.7 x 10(-6), RR 4.2). The distribution of DRw11 alleles in these patients was significantly different from that observed in controls and could be accounted for by an increase in the frequency of the DRB1*1104 allele (p = 1.2 x 10(-9), RR 9.5). The DRw11 alleles were also associated with SSc with more tendon friction rubs (p = 0.006), which is a marker of more severe disease. In addition, a strong association was observed with anti-topo I antibodies and a particular sequence (aa 71-77) of the DQB1 chain (p = 0.02, RR 2.2). HLA associations in the case of SSc patients with anti-topo I antibodies are complex and involve at least two genes: HLA-DRw11, which appears to play a major role in determining the severity of the disease, and a DQ sequence, which associates with the development of the anti-topo I antibodies.

Adult↗
PubMed2005

-238 and +489 TNF-alpha along with TNF-RII gene polymorphisms associate with the diffuse phenotype in patients with Systemic Sclerosis.

OBJECTIVE: To investigate possible associations of TNF-alpha and TNF-RII gene polymorphisms with diffuse or limited skin involvement phenotype in a cohort of Systemic Sclerosis (SSc) patients. METHODS: One-hundred and fourteen consecutive SSc patients attending the referral centres of three academic hospitals in Italy (University of Naples, Pavia and Udine), 56 with the diffuse (dcSSc) and 58 with limited (lcSSc) skin involvement subsets, and 170 healthy blood donors (HBDs) were included in the study. The extracted DNA was genotyped for the following polymorphisms: TNF-alpha (-238, +489) and TNF-RII (+196), using the polymerase chain reaction (PCR) and the restriction enzymes BamHI, HpyCH4 IV and NlaIII, respectively. RESULTS: The AG/AA (presence of allele A) genotypes in position -238 and the AG genotype in position +489 of the TNF-alpha gene were found significantly increased in SSc, as a whole, when compared with healthy blood donors (chi(nu=2)(2)=4.48, p=0.03 for -238 and chi(nu=2)(2)=7.82, p=0.02 for +489, respectively). The rare GG genotype in exon 6 (codon 196) of the TNF-RII gene was also found increased in SSc compared to HBDs, even though the difference did not show statistical significance (chi(nu=2)(2)=3.56, p=0.17). The strength of the association was mainly due to the dcSSc phenotype (Fisher test, p=0.04 for -238, chi(nu=2)(2)=10.07, p<0.01 for +489 and chi(nu=2)(2)=6.25, p=0.04 for the +196 TNF-RII, respectively). CONCLUSIONS: TNF-alpha and TNF-RII gene polymorphisms seem to contribute to the development of SSc and in particular to the diffuse phenotype.

Autoantibodies↗
PubMed2006

Systemic sclerosis-associated Sjögren's syndrome and relationship to the limited cutaneous subtype: results of a prospective study of sicca syndrome in 133 consecutive patients.

OBJECTIVE: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in a 2-center prospective series of patients with systemic sclerosis (SSc), using the American-European Consensus Group criteria for SS. METHODS: Consecutive SSc patients hospitalized for followup care were evaluated for sicca symptoms. When the initial clinical evaluation yielded positive findings, a labial salivary gland biopsy was performed; histologic analysis evaluated focal lymphocytic sialadenitis and/or glandular fibrosis. Computed tomography and respiratory function tests were used to assess pulmonary fibrosis. RESULTS: We included 133 SSc patients (mean +/- SD age 55 +/- 13 years; mean +/- SD disease duration 6.5 +/- 6 years). Eighty-one patients had limited cutaneous SSc (lcSSc). Ninety-one patients (68%) had sicca syndrome. Histologic analysis revealed fibrotic involvement in 50 of these 91 patients, but labial salivary gland fibrosis was not associated with any organ involvement we evaluated. Nineteen of the 133 patients (14%) had SS. In this subgroup, lcSSc was present at a significantly higher frequency (18 of 19 patients) than in the remaining patients with sicca syndrome (39 of 72 patients) and the patients without sicca syndrome (24 of 42 patients). This subgroup also had a significantly higher frequency of anticentromere antibodies (18 of 19 patients) than did the remaining patients with sicca syndrome (19 of 72 patients) and the patients without sicca syndrome (5 of 42 patients). In addition, this subgroup had a significantly lower prevalence of pulmonary fibrosis (2 of 19 patients) than did the remaining patients with sicca syndrome (29 of 72 patients) and the patients without sicca syndrome (19 of 42 patients). CONCLUSION: There was a 68% prevalence of sicca syndrome in this prospective series of SSc patients. Sicca syndrome was related primarily to glandular fibrosis, the hallmark of SSc. The prevalence of secondary SS, as defined by the American-European Consensus Group criteria, was 14% and was markedly associated with lcSSc. We believe that lcSSc should be regarded as a specific autoimmune subgroup of SSc.

Adult↗
PubMed1998

Autoantibodies against calpastatin in sera from patients with systemic sclerosis.

OBJECTIVE: To determine the prevalence and clinical correlation of anti-calpastatin antibodies in patients with systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n=36), diffuse cutaneous SSc (dSSc; n=27), and healthy control subjects (n=29) were examined by an ELISA using human recombinant calpastatin as antigens. RESULTS: IgG anti-calpastatin antibodies were positive in 15 (24%) of 63 patients with SSc, which was similar to the frequency of IgM anti-calpastatin antibody positivity (14/63, 22%). The presence of anticentromere antibodies was associated with the presence of IgG and/or IgM anti-calpastatin antibodies. The patients with SSc positive for IgG anti-calpastatin antibodies had significantly higher erythrocyte sedimentation rates (ESR) compared with those negative for IgG anti-calpastatin antibodies. Furthermore, the levels of IgG anti-calpastatin antibodies correlated positively with the levels of ESR. The patients with dSSc positive for IgM anti-calpastatin antibodies had significantly higher frequency of inflammatory joint and muscle involvement compared with those negative for IgM anti-calpastatin antibodies. Four (80%) of 5 patients with dSSc with both joint and muscle involvement produced IgM anti-calpastatin antibodies. CONCLUSION: The presence of anti-calpastatin antibodies may be a clue to mechanisms of the inflammatory change occurring in SSc. Furthermore, the presence of anti-calpastatin antibodies could be a novel and useful serologic tool for recognizing patients with dSSc with inflammatory joint and muscle involvement.

Adolescent↗
PubMed1983

Factors limiting exercise performance in progressive systemic sclerosis.

In order to evaluate to which extent various organs limit physical performance in PSS, maximal working capacity was studied in 22 patients. Special attention was given to cardiac and pulmonary function, joint mobility, and muscular strength. A model for scoring these parameters is given. Working capacity was on the average 51% of the predicted normal value. Ventilation at maximal workload was high despite normal arterial blood gases and presumably normal physiologic dead space. This can be explained by an increased demand on ventilation from an increased muscle metabolism. This may be due to impeded mobility of respiratory and locomotive organs. The maximal heart rate was low and patients with low physical capacity had only a small decrease in base excess. One third of the patients developed arrhythmia during exercise, which contributed to a low performance. Other myocardial involvement was common, seen in the Q-waves, low voltage, left axis deviation, and increased heart volume. In PSS, these ECG changes probably reflect myocardial fibrosis that has developed without clinically manifest infarction. Special attention must be given to arrhythmias at work, which are overlooked in a resting ECG. Ventricular tachycardia plays an important role in sudden death, which, when it occurs, almost always does so within the first years after the onset of PSS. There was no close linkage between cardiac dysfunction and pulmonary fibrosis or joint-muscle impairment. The scoring system showed an equal distribution in reduction of working capacity as to circulation, pulmonary function, and locomotive function.+2

Adult↗
PubMed1997

Antiendothelial cell antibodies: useful markers of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SS) encompasses a wide spectrum of clinical presentations. Antiendothelial cell antibodies (AECA) in patients with primary Raynaud's phenomenon (PRP), limited SS (lSSc), or diffuse SS (dSSc) may help to determine the long-term prognosis of the disease. METHODS: Twenty-seven normal controls, 13 patients with PRP, 36 with lSSc, and 31 with dSSc were included in the study. Sera were examined for the presence of AECA, using a cellular enzyme-linked immunosorbent assay (ELISA). Angiotensin-converting enzyme (ACE) activity, plasma von Willebrand factor antigen (vWfAg), and thrombomodulin (Tm) concentrations were also evaluated. The medical records of 50 of the lSSc and dSSc patients were reviewed and the organ system involvement noted. RESULTS: Antiendothelial cell antibodies were present in 3 patients with PRP, 16 patients with lSSc, and 26 patients with dSSc. These autoantibodies were mainly of the IgG isotype. There was no difference in ACE activity between patients and controls. In contrast, vWfAg and Tm concentrations were higher in patients with PRP relative to controls, and higher in patients with lSSc compared with those with PRP. The presence of AECA was associated with digital scars and ulcers (P < 0.004 and P < 0.003, respectively), severe RP (P < 0.01), grade 3 tortuosity of vessels (P < 0.0004), and lung involvement (P < 0.02). CONCLUSION: The significant trend for AECA to increase with disease severity across the three groups of patients studies suggests that the AECA test can identify subsets of SSc with differing prognoses.

Adolescent↗
PubMed2002

Protease nexin-1 messenger RNA levels are not affected by serum or interferon beta in cultured systemic sclerosis fibroblasts.

The aim of the present study was to analyze the effect of serum and human recombinant beta interferon (rIFNbeta) treatment on PN-1 mRNA levels in cultured dermal fibroblasts obtained from the skin of healthy donors and from lesional skin of systemic sclerosis (SSc) patients with the limited (CREST syndrome) or the diffuse form of SSc. Total RNA was isolated from fibroblasts derived from the skin of healthy individuals and from lesional skin of patients with CREST syndrome and the diffuse form of SSc cultured under different conditions (1% or 10% serum-supplemented medium) and treated with 500 IU/ml of rIFNbeta. PN-1 gene expression was assessed by Northern blot analysis. We detected variable PN-1 mRNA levels in normal control fibroblasts as well as in SSc fibroblasts under the different culture conditions (1% or 10% serum-supplemented medium). Accumulated PN-1 mRNA levels found in normal cultured fibroblasts were similar to or even higher than in SSc fibroblasts. PN-1 messenger levels were not significantly altered by IFNbeta treatment in normal or SSc cultured fibroblasts despite the presence of an IFN-stimulated responsive element (ISRE) in the promoter of the PN-1 gene. Our findings suggest that PN-1 expression in SSc fibroblasts at the mRNA level requires further investigation in a large number of SSc patients to better characterize the role of this serpin in the pathogenesis of SSc. We conclude that the transcriptional regulation of PN-1 is not associated with IFNbeta, an antifibrotic cytokine naturally produced by fibroblasts.

Adolescent↗
PubMed2005

Clinical correlations of potential activity markers in systemic sclerosis.

The objectives of the project were the following: (1) to establish a group of patients with a confirmed diagnosis of systemic sclerosis (Ssc), (2) to perform a detailed entrance examination of each patient, (3) to determine concentrations of potential activity markers, and (4) to make a comprehensive examination of each patient 1 year after inclusion into the study. A total of 49 patients were examined, 36 with a limited form of SSc, 9 with diffuse SSc, and 4 with other forms of SSc. We determined plasma or serum levels of the N-terminal propeptide of procollagen type III (NPIIIP), interleukin-6 (IL-6), soluble receptor for interleukin-2 (sIL-2r), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), von Willebrand factor antigen (vWFAg), and big endothelin-1 (BET-1) using commercial kits, and urinary excretion of pyridinoline (PYR) and deoxypyridinoline (D-PYR) using high-performance liquid chromatography. Correlations of these markers with selected clinical data were calculated. The mean levels of all potential activity markers were increased compared with normal values, but differences were not significant. The levels of NPIIIP, D-PYR, and IL-6 were normal. The measured values after 1 year did not differ from the entry values. At entry, NPIIIP concentrations correlated with the finger-to-palm distance, and D-PYR corresponded with findings on a simplified health assessment questionnaire (FQ). IL-6 levels correlated with the leukocyte count, sIL-2r with the FQ, and ET-1 with the diffuse lung capacity for carbon monoxide. In general, we found only a few clinical correlates of potential activity markers. Our data confirmed the correlations of collagen metabolism markers with skin involvement and FQ, as was reported previously. Larger studies in this field are needed.

Adult↗
PubMed1993

Esophageal function in systemic sclerosis: a prospective evaluation of motility and acid reflux in 36 patients.

Systemic sclerosis (SSc) is a connective tissue disorder which frequently involves the esophagus, with severe gastroesophageal reflux (GER) and dysphagia as clinical consequences of esophageal dysmotility. The relationship between the severity and extent of esophageal acid exposure and the specific manometric disturbances has received little attention. Similarly, a paucity of manometric data exists regarding pharyngeal/upper esophageal sphincter (UES) function in SSc patients. We prospectively studied 36 SSc patients using computerized solid-state manometric and ambulatory dual-pH (upper and lower esophageal) monitoring, to define further the relationship between esophageal dysmotility and severity of GER in these patients. Patients were separated for analysis into two subgroups based on the absence (group 1, N = 25) or presence (group 2, N = 11) of distal esophageal peristalsis. SSc disease variant (diffuse vs. limited) and duration of illness were inaccurate predictors of the presence and severity of esophageal involvement. The mean lower esophageal sphincter (LES) pressure for the SSc patients (15.8 +/- 1.2 mm Hg, mean +/- SE) was significantly lower (p < 0.01) than that for a control group (26.0 +/- 2.1 mm Hg). There was no significant difference between the mean LES pressure for group 1 (15.0 +/- 1.6 mm Hg) and group 2 (17.5 +/- 1.6 mm Hg) patients. Although distal esophageal aperistalsis was noted in 70% of patients, normal proximal esophageal contraction pressures were documented in all cases. Mean UES pressure was significantly (p < 0.01) lower in group 1 (52.5 +/- 4.6 mm Hg) than in group 2 (80.5 +/- 10.6 mm Hg). The mean duration of UES relaxation and the mean time interval between the onset of UES relaxation and onset of pharyngeal contraction were significantly (p < 0.05) shorter for group 1 than group 2 patients. Pharyngeal pressures, peristalsis, and other aspects of pharyngeal/UES coordination were normal. Excessive distal esophageal acid exposure was often seen in patients in both subgroups, but it was significantly (p < 0.01) greater in group 1. Excessive proximal esophageal acid exposure was documented only in patients with absent distal peristalsis. Linear regression analysis revealed a poor correlation between the severity of esophageal acid exposure and the LES pressure. Thus, the severity and extent of GER in SSc is most closely related to the integrity of distal esophageal peristalsis.

Esophageal Motility Disorders↗
PubMed2003

Neuron specific enolase concentration is increased in serum and decreased in platelets of patients with active systemic sclerosis.

OBJECTIVE: To determine frequency, origin, and clinical associations of elevated serum neuron specific enolase (NSE) in systemic sclerosis (SSc). METHODS: Serum was obtained from 75 patients with SSc, 20 systemic lupus erythematosus, 8 polymyositis, 10 idiopathic interstitial lung disease, and 10 healthy volunteers. NSE status was determined in serum (in all individuals) and in platelet lysate (in volunteers and 30 patients with SSc). RESULTS: Elevated serum NSE (mean 22.6 ng/ml, range 12.1-68.2 ng/ml) was observed in 26 patients with SSc (34.6%). Those with diffuse SSc had higher serum NSE than those with limited disease (16.5 +/- 13.4 vs 9.6 +/- 5.0 ng/ml, p = 0.006). No association was found between serum NSE and lung or esophagus involvement. Patients with long-standing disease had lower serum NSE than those with early disease (10.8 +/- 7.3 vs 16.1 +/- 13.6 ng/ml, p = 0.05). Serum NSE was 19.4 +/- 13.0 ng/ml in patients with total skin score (TSS) > 20, 8.3 +/- 2.1 ng/ml in patients with TSS < 5, and 6.0 +/- 3.1 ng/ml in volunteers (p = 0.01). NSE platelet lysate concentration was 3.6 +/- 2.9 ng/ml in patients with TSS > 20, 12.4 +/- 4.1 ng/ml in those with TSS < 5, and 14.1 +/- 6.5 ng/ml in healthy individuals (p < 0.001). Volunteers and SSc patients with low TSS had comparable S/PL-NSE index (serum/platelet lysate NSE concentration) (0.42 +/- 0.16 and 0.75 +/- 0.33, respectively), both lower than SSc patients with high TSS (7.45 +/- 5.57) (p < 0.001). CONCLUSION: Elevated serum NSE was observed in one-third of SSc patients but not in other autoimmune rheumatic diseases. The inverse relationship between serum and platelet lysate NSE concentration suggests platelet activation as the origin of high serum NSE in SSc. NSE S/PL was the best discriminatory variable between healthy volunteers and SSc patients as well as between patients with high and low TSS. High serum NSE and high NSE-S/PL index seemed to be associated with SSc disease activity. Further work is warranted to investigate a possible role for this marker in assessing disease activity and therapy response.

Adult↗
PubMed2003

Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline.

OBJECTIVES: To evaluate the effect of minocycline as treatment for cutaneous calcinosis in limited cutaneous systemic sclerosis (lcSSc). METHODS: Patients with lcSSc who had cutaneous calcinosis causing pain or ulceration, or both, were prescribed minocycline 50 or 100 mg daily regularly in an open label manner between November 1994 and April 2000. At routine clinical follow up the appearance of the calcinosis deposits was assessed clinically and radiographically, and the patients' assessment of the degree of discomfort, size, and frequency of ulceration was recorded. Demographic data, including disease duration, clinical features, and antinuclear antibody (ANA) titres, were also recorded. RESULTS: Nine patients have been treated to date. Eight of the nine patients were ANA positive, five of whom were positive for anticentromere antibodies. Eight patients have shown definite improvement and seven patients continue to receive treatment. The frequency of ulceration and inflammation associated with the calcinosis deposits decreased with treatment. The size of the calcinosis deposits also decreased but was less dramatic than expected. Improvement occurred at the earliest after one month of treatment with a mean (SD) of 4.8 (3.8) months. The mean (SD) length of treatment was 3.5 (1.9) years. An unexpected effect was the darkening of the calcinosis deposits to a blue/black colour. CONCLUSIONS: Minocycline may be effective in the control of calcinosis in systemic sclerosis. A low dose only is required and appears to be generally well tolerated. The mechanism of action may be mainly through inhibition of matrix metalloproteinases and anti-inflammatory effects. Calcium binding properties and antibacterial actions may also have a role.

Adult↗
PubMed2000

The disproportionate impact of chronic arthralgia and arthritis among women.

The heterogeneous group of diseases that causes chronic arthralgia and arthritis is the most common cause of activity limitation and disability among middle age and older women. For reasons that remain poorly understood this group of diseases affects women substantially more frequently than men. In particular, the prevalence rates of the most common causes of arthralgia and arthritis, osteoarthritis and rheumatoid arthritis, and the prevalence rates of less common diseases that cause arthralgia, including systemic lupus erythematosus, systemic sclerosis, and fibromyalgia, are between two and 10 times higher in women. Prevalence rates for most of these conditions increase with age, and may vary among populations. For example, in the United States, systemic lupus erythematosus is approximately three times as common among African-American women as among white women. All of these disorders typically have an insidious onset and variable course that can make diagnosis difficult. Yet, most patients with these diseases benefit from early diagnosis and early nonoperative treatments including patient education, patient participation in disease treatment, activity modification, assistive devices, and medications. Furthermore, early aggressive medical therapy may prevent development of permanent joint and visceral damage in patients with inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Failure to make the diagnosis of an underlying disease in patients with arthralgia may lead to inappropriate treatment or delay in treatment that can result in irreversible impairment. Because many women with these conditions seek medical care from orthopaedists, orthopaedic residency education and continuing medical education should place emphasis on early diagnosis and nonoperative treatment of patients with arthralgia and arthritis, and, when appropriate, early referral to rheumatologists.

Arthralgia↗
PubMed2002

Digital vascular response to topical glyceryl trinitrate, as measured by laser Doppler imaging, in primary Raynaud's phenomenon and systemic sclerosis.

OBJECTIVE: To investigate digital microvascular responses to topical glyceryl trinitrate (GTN) in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LCSSc) and healthy control subjects, using laser Doppler imaging. METHODS: Ten patients with PRP, 13 with LCSSc and 10 control subjects were studied. Baseline skin microvascular blood flow of the dorsum of the index, middle and ring fingers of the non-dominant hand was measured using scanning laser Doppler imaging. After the initial image, 2% GTN ointment was rubbed on the dorsum of one finger for 1 min; placebo ointment was rubbed on the dorsum of a second finger for 1 min, and the third finger remained untreated. Further laser Doppler scanning of these three fingers was conducted immediately, 10 and 20 min after ointment application. RESULTS: There was increased blood flow response to placebo compared with no treatment (P<0.001) and to GTN compared with placebo (P=0.004). The change in blood flow over time differed significantly between placebo and GTN (P<0.001), but not between placebo and no ointment application: blood flow increased with GTN and decreased with placebo/no treatment at 10 and 20 min. There were no differences in initial baseline blood flow or response between the subject groups. CONCLUSIONS: An exogenous supply of nitric oxide by topical GTN ointment causes local endothelial-independent vasodilatory responses in PRP, LCSSc patients and control subjects. As well as demonstrating the effectiveness of topical GTN in patients with PRP and LCSSc, this study illustrates the ability of laser Doppler imaging to quantify local vasodilatory effects.

Administration, Topical↗