Involvement In Progressive Systemic Sclerosis Research Articles

Serum interleukin-6 level and its association with pulmonary involvement in progressive systemic sclerosis; a case-control study

BackgroundPrimary Systemic Sclerosis (PSS) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Interstitial lung disease (ILD) is a late demonstration of PSS and cytokines can contribute to the disease pathology. The purpose of the current study was to determine the association between serum interleukin-6 level and pulmonary involvement in progressive systemic sclerosis.Methods and materialsDemographic data and serum interleukin-6 levels were measured for 30 PSS patients with pulmonary involvement (case group) and 30 PSS patients without pulmonary involvement (control group) following informed consent. The disease duration and activity, C-reactive protein (CRP), chest x-ray and highresolution CT scan (HRCT) findings, ejection fraction (EF) and echocardiography findings, and pulmonary artery pressure (PAP) were also determined in both groups.ResultsThe age of patients in case and control groups was 52.5 ± 9.3 and 43.9 ± 9.7 years, respectively (p = 0.001). No significant difference was found between serum levels of IL-6 in case and control groups (73.1 ± 95.4 vs 46.7 ± 83.6 pg/ml, p = 0.267). However, IL-6 level was significantly higher in male case patients compared to male controls (p = 0.007). The duration of PSS was 11.6 ± 6.4 and 7.4 ± 4.2 years in case and control groups, respectively (p = 0.002). The quantitative CRP and PAP was also significantly higher in case patients (p = 0.01 and p < 0.001, respectively). There was found reticulonodular pattern in 20 (66.7%) of the cases, whereas 28 (93.3%) of the controls had normal Chest X-rays (CXR) (p < 0.001). EF was significantly lower in case patients compared to control patients (p = 0.001).ConclusionThe serum level of IL-6 did not appear to have a relationship with pulmonary involvement, hence it could not be regarded as a potential therapeutic target.

Pulmonary involvement in systemic sclerosis: A clinical profile.

Background:Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients.Objectives:This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS) and to describe the clinical and radiological picture of pulmonary involvement in PSS.Materials and Methods:This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR), pulmonary function test (PFT), and 6 min walk test (6MWT) were performed on all patients. High resolution computed tomography was done on those who consented.Results:Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%). 90 (90%) of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05). Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05).Conclusion:The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29%) were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

The central nervous system (CNS) involvement in progressive systemic sclerosis (PSS) is rare, which has been considered to be either uncommon or a secondary consequence of hypertension, uremia, pulmonary dysfunction and steroid treatment (1-3). White matter hyper intensities (WMHI) on MRI were more common in patients with PSS than in the control group, which might be asymptomatic and inadequate of the disease duration (2, 3). We report a unique case of PSS where WMHI have arisen in both the middle cerebellar peduncles and left temporal lobe, and made rapid progress into tumefactive WMHI in the subcortices of both precentral gyri. To the best of our knowledge, tumefactive form of PSS has not been reported.

Esophageal involvement in progressive systemic sclerosis.

Progressive systemic sclerosis (PSSc) is a chronic disease of unknown etiology characterized by progressive, abnormal accumulation of fibrous tissue in the skin and many organs. Characteristically, there is induration and thickening of the skin (scleroderma), abnormalities involving muscles, joints, and viscera. The first description was likely by William and Robert Watson in 1754.

Les atteintes pulmonaires de la sclérodermie

Pulmonary involvement in progressive systemic sclerosis can affect either the parenchyma or the vasculature. Both forms are fatal within a few months or years, due to respiratory and/or cardiac failure. Patients must be screened for pulmonary hypertension by ultrasonography, to be confirmed by right heart catheterization if necessary, as early diagnosis and immediate treatment improves the prognosis. The interstitial pulmonary disease progresses slowly, leading to respiratory failure, secondary pulmonary hypertension, and heart failure. Immunosuppressive treatments are disappointing but if prescribed early may prevent or delay the otherwise ineluctable aggravation. Pulmonary involvement threatens the vital and functional prognosis of patients with scleroderma, who may also develop several other complica- tions (especially infections and adverse effects of drugs) that are not dealt with here. This paper focuses on the most significant disease manifestations and current therapeutic options.

Pulmonary involvement in progressive systemic sclerosis

Pulmonary involvement in progressive systemic sclerosis

Gastric and Enteric Involvement in Progressive Systemic Sclerosis

Progressive systemic sclerosis (PSS) is a chronic multisystem disease characterized by excess deposition of connective tissue in skin and internal organs, associated with microvasculature changes and immunologic abnormalities. Involvement of the gastrointestinal tract may occur in 2 stages, a neuropathic disorder followed by a myopathy. Gastric emptying is delayed in 10% to 75% of patients and correlates with symptoms of early satiety, bloating, and emesis. Compliance of the fundus is increased although perception of fullness is normal. Myoelectric abnormalities have been found in some studies. Treatments include metoclopramide, cisapride, and erythromycin. Bleeding from telangiectasias and watermelon stomach is treated endoscopically. Small bowel involvement in PSS occurs in 17% to 57% of patients. The migrating motor complexes are reduced or absent, predisposing to bacterial overgrowth. Malabsorption may also be due to pancreatic insufficiency. Barium enemas demonstrate pancolonic involvement in 10% to 50% of patients with PSS. Wide-mouthed diverticuli, involving all layers of the intestinal wall, are characteristic. Pseudoobstruction may respond to octreotide or prucalopride therapy. Complications include pneumatosis cystoides intestinalis, stercoral ulcerations, and perforation. Fecal incontinence may be due to dysfunction of the internal anal sphincter, a smooth muscle responsible for most of the resting anal sphincter pressure. Anal manometry may show a reduction or loss of the rectoanal inhibitory reflex. Treatments include biofeedback, sacral nerve stimulation, and surgery. PSS involves the gastrointestinal tract from the mouth to the anus. Studies are needed to define effective treatments in these diseases, which cause great morbidity.

Abnormal appearance of the internal anal sphincter at ultrasound: a specific feature of progressive systemic sclerosis?: The debate is not closed

Endosonography is now an effective tool for the assessment of anorectal pathologies. We present a case of rectal prolapse in a patient with progressive systemic sclerosis, with low resting anal pressure, no rectoanal inhibitory reflex in manometry, and a thin, heterogeneous, difficult to delineate, internal sphincter on endoanal ultrasound. We also provide a review of the literature on anorectal involvement in progressive systemic sclerosis.

Analysis of transmural trends in myocardial integrated backscatter in patients with progressive systemic sclerosis

Cardiac involvement in progressive systemic sclerosis (PSS) is common and has a strong negative impact on the prognosis, especially when autoantibodies are present. To determine whether ultrasonic tissue characterization can detect early ultrastructural changes in the sclerodermal myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB). "A-THIB" was defined as the absolute difference in integrated backscatter between the left (subendocardial) and right (subepicardial) ventricular halves of the myocardium in the septum and posterior wall, and was measured in 11 patients with PSS and 10 age- and sex-matched healthy participants. A-THIB in patients with PSS was higher than that in healthy participants (1.3 +/- 1.3 vs 4.0 +/- 1.4 dB for the septum and 1.1 +/- 0.7 dB vs 2.8 +/- 0.4 dB for the posterior wall; mean +/- SD, respectively, P <.0005). Septal A-THIB was higher in patients with PSS with than without anti-Scl70 or antinucleolar antibodies (3.2 +/- 1.1 vs 5.0 +/- 1.0 dB, P =.0165). Early changes in the myocardium of patients with PSS, possibly related to increased interstitial collagen deposition, can be detected by quantitative analysis of THIB.

Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings.

To determine whether electrogastrography (EGG) can discern sonographically demonstrated motility disorders in patients with progressive systemic sclerosis (SSc) and to evaluate EGG as a possible diagnostic tool. Prospective study with control group and testing for reliability. 15 SSc patients [women aged 33-70 years (mean 53.3 years)] and 15 healthy volunteers. Bipolar cutaneous EGG was recorded to obtain the following parameters: period dominant frequency (PDF), percentage of gastric dysrhythmia and normogastria (defined as 2-4/min), period dominant power (PDP) and its change after a standardized meal of 500 kcal (2093 kJ), and instability coefficients of dominant frequency and power (DFIC, DPIC). Simultaneously, real-time sonography was performed in the aortomesenteric plane (3.5-MHz curved-array probe). In 10 patients and 13 control subjects, the distance from the anterior wall of the gastric antrum to the abdominal skin was measured. Three patients (20%) showed hypomotility of the gastric antrum sonographically. The percentage of bradygastria was significantly lower in these patients, but the PDF, DFIC and DPIC values were not significantly different. The distance between the cutaneous electrodes and the antrum bore a greater relationship to the PDP values than did the sonographically demonstrated number of gastric contractions. Although cutaneous EGG can be performed in SSc patients without apparent derangement in frequency and stability of the signal, it offers no advantage over sonography in diagnosis and follow-up.

Cardiorespiratory Responses to Incremental Exercise in Patients With Systemic Sclerosis

Patients with systemic sclerosis are known to have histologic pulmonary abnormalities despite normal chest radiograph or conventional pulmonary function or both. In an attempt to detect early features of lung involvement in progressive systemic sclerosis, we investigated patients with systemic sclerosis using cardiopulmonary exercise testing. We have studied 78 patients who fulfilled the American Rheumatism Association criteria for the classification of systemic sclerosis, and according to the classification of LeRoy, 44 had limited cutaneous systemic sclerosis and 34 had diffuse cutaneous systemic sclerosis. A significantly decreased diffusing capacity (65 +/- 3% of that predicted) was present only in the group with diffuse cutaneous systemic sclerosis. The patients with lung involvement showed a significant reduction in exercise capacity (54 +/- 3% of that predicted) and in oxygen uptake (70 +/- 3% of that predicted). Additionally, we could demonstrate an increased functional dead space ventilation (0.34 +/- 0.02) and widened alveolar-arterial oxygen difference during exercise (44 +/- 3 mm Hg). By cardiopulmonary exercise testing, 12 of the 78 patients (15%) with normal single-breath diffusing capacity for carbon monoxide had increased dead space to tidal volume ratio. Our results suggest that occult pulmonary impairment may be present in patients with normal pulmonary function and that cardiopulmonary exercise testing enables detection of such impairment. Our study results show the limitations of resting data in predicting abnormalities during exercise in patients with systemic sclerosis.

Increased endothelial and epidermal thrombomodulin expression and plasma thrombomodulin level in progressive systemic sclerosis.

To clarify the relation between systemic and cutaneous vascular endothelial injury in progressive systemic sclerosis (PSS), we examined thrombomodulin (TM) expression in PSS skin lesions immuno-histopathologically and compared it with plasma soluble TM levels measured by specific enzyme-linked immunosorbent assay. The plasma soluble TM level in PSS patients was significantly higher than that of normal controls and was as high as the levels of SLE patients. In relation to disease activities, the plasma TM levels of sclerotic phase PSS patients were significantly higher than that of atrophic phase PSS patients. The plasma samples with anti-Scl-70 antibody showed a high TM level than samples with anti-centromere antibody or anti-RNP antibody. Barnett's types or systemic corticosteroid treatment did not affect the TM level. Histopathologically, the dermal endothelial TM expression significantly increased in the sclerotic skin and moderately increased in the non-sclerotic skin of PSS compared with that of normal control skin. In addition, immunoreactive TM expression in the epidermis also increased in PSS. Disease activity-dependent elevation of plasma TM levels and immuno-histopathological expression of TM suggested generalized endothelial and epidermal cell involvement in PSS, and compensation in part by overproduction of TM by endothelial cells.

Signal-averaged electrocardiography and echocardiography in the evaluation of myocardial involvement in progressive systemic sclerosis

To assess the myocardial involvement in progressive systemic sclerosis we evaluated the presence of late potentials by signal-averaged electrocardiography (signal-averaged ECG) and the left ventricular function by M-mode, two dimensional and Doppler echocardiography. Fifteen outpatients, 7 with diffuse progressive systemic sclerosis and 8 with CREST syndrome variant, without clinical or electrocardiographic evidence of cardiac disease were studied and compared with 18 normal subjects. Late potentials occurred in 5 out of 15 progressive systemic sclerosis patients (33%) with a significant difference versus controls ( P < 0.05) and were present only in the patients with diffuse progressive systemic sclerosis ( P ≤ 0.001 vs. controls). All progressive systemic sclerosis patients showed a normal left ventricular systolic function. Abnormal left ventricular filling was found in 9 progressive systemic sclerosis patients (5 with diffuse progressive systemic sclerosis and 4 with CREST). A more severe impairment of the mean values of diastolic function indexes was found in diffuse progressive systemic sclerosis than in CREST. In all diffuse progressive systemic sclerosis patients at least one method showed altered results, whereas half the CREST patients showed no pathological findings with both techniques. These results confirm a lower myocardial involvement in the CREST syndrome than in diffuse progressive systemic sclerosis and consequently this is probably related to a better prognosis.

Long-term manometry of tubular esophagus in progressive systemic sclerosis.

Long-term manometry of the tubular esophagus was performed in 20 consecutive patients (18 females, 2 males; median age 56.5 years) with progressive systemic sclerosis (PSS) and a control group of 20 healthy subjects (18 females, 2 males; median age 56.5 years). The measurements were performed via a data logger of 1 MByte memory capacity with the help of two pressure sensors placed 8 and 18 cm above the lower esophageal sphincter. Esophageal contractions were analyzed with respect to pressure amplitudes in the esophagus distal and proximal, quotient of pressure amplitudes distal/proximal, number of contraction waves in a 24-h period, and kind of spreading (propulsive, simultaneous). In the PSS group there was a significant decrease in pressure amplitudes in the distal sensor (median 31.5 versus 39.5 mbar in controls, P < 0.02), in the quotient of pressure amplitudes distal/proximal (median 0.885 versus 1.25 in controls, P < 0.001), in the number of waves in 24 h (median 939.5 versus 1656 in controls, P < 0.01), and in the occurrence of propulsive waves (median 34% versus 57% in controls, P < 0.01). Fifteen patients (75%) had hypomotility disorders as compared to the control group, in which the lower limit of normal values was defined by the 5th percentile of descriptive analysis. These first data of long-term manometry in patients with PSS indicate that long-term manometry may be an effective method for identifying esophageal involvement in PSS.

Pulmonary involvement in progressive systemic sclerosis: sequential evaluation with CT, pulmonary function tests, and bronchoalveolar lavage.

Computed tomographic (CT) findings obtained in 53 patients with progressive systemic sclerosis were correlated with functional parameters and bronchoalveolar lavage (BAL) results, and lung changes over time were assessed in 17 patients. CT findings were normal in 21 patients (group 1) with otherwise normal lung function, except for subclinical alveolitis in seven patients. CT depicted pleural and parenchymal abnormalities in 32 patients, grouped according to the absence (group 2) or presence (group 3) of honeycombing. In group 2 (n = 13), mean values of functional parameters were normal, and BAL showed a significant increase in neutrophils compared to group 1 (P < .05). Among patients in group 3 (n = 19) with limited extent of honeycombing (n = 12), the mean diffusing capacity value was lower in patients with a moderate ground-glass profusion score (n = 4) than in those with a mild score (n = 8) (68% +/- 4 [standard error of the mean] vs 80% +/- 3). CT is the method of choice for evaluating parenchymal destruction, and profusion and extent of ground-glass opacities can help in predicting the severity of lung damage in areas devoid of destructive changes.

Clinical correlations and prognosis based on hyaluronic acid serum levels in patients with progressive systemic sclerosis

The serum levels of hyaluronic acid (sHA) were measured using an affinoimmunoenzymatic assay in patients with distal (n = 16) and proximal (n = 15) progressive systemic sclerosis (PSS) and in 31 controls. The severity of PSS was evaluated using a standardized organ-involvement score. The mean sHA was significantly higher in the patients with PSS than in controls (mean +/- SD:80 +/- 43.4 micrograms/l vs. 42.3 +/- 19.1 micrograms/l, P less than 0.001). sHA was significantly higher in patients with proximal PSS than in patients with distal PSS (106.4 +/- 44.6 micrograms/l vs. 55.4 +/- 23.8 micrograms/l, P less than 0.001). A positive correlation was found between sHA and the disease score (r = 0.67, P less than 0.001). sHA was also correlated with lung diffusion capacity for carbon monoxide (r = 0.70, P less than 0.001), but only in the those patients who had abnormal lung function, and therefore presumably had lung PSS involvement. We suggest that sHA could be an indicator of the degree of systemic involvement in PSS. Its prognostic value and possible use in the follow up of patients with PSS remain to be clarified.

Détection de l'atteinte interstitielle pulmonaire de la sclérodermie : comparaison de la tomodensitométrie haute résolution, de la clairance pulmonaire du 99m Tc DTPA et de la gazométrie artérielle d'effort

Détection of Interstitial lung involvement in progressive systemic sclerosis : comparison of high-resolution computed tomography, 99mTc-DTPA clearance and exercise arterial oxygen tension.

Anorectal abnormalities in progressive systemic sclerosis.

Seventeen patients with progressive systemic sclerosis (PSS) were evaluated with manometry for anorectal function, and an additional 36 age-matched normal subjects were collected as a control group. The study group had a significant decrement of maximum basal pressure (MBP), 42.6 +/- 27.0 mm Hg, in PSS as compared with the control group, 71.2 +/- 24.9 mm Hg (P = .0004). The difference in the functional length (FL) of the anal canal, PSS:control = 2.4 +/- 1.0 cm:3.7 +/- 0.5 cm (P = .0001); the volume of first defecating sensation, PSS:control = 66.3 +/- 35.2 ml:125.1 +/- 43.8 ml; the voluntary component, the difference between maximum squeeze pressure (MSP) and MBP, PSS:control = 116.6 +/- 73.6 mm Hg:61.8 +/- 35.9 mm Hg (P = .0087), were also found to be statistically significant. Nevertheless, the MSP and maximal tolerable capacity (Vmax) showed no difference in these two groups (MSP, PSS:control = 159.3 +/- 88.1 mm Hg:132.9 +/- 44.9 mm Hg, P = .259), (Vmax, PSS:control = 193.1 +/- 67.7 ml:230.0 +/- 60.9 ml, P = .0526). Twelve (71 percent) of 17 patients did not have rectoanal inhibitory reflex, and paradoxical contraction during rectal balloon inflation was noted in ten patients. Nine patients had different degrees of anal incontinence and abnormal anometric profiles were found in six of eight asymptomatic patients. Therefore, only two patients (12 percent) had neither symptoms nor anometric evidence of anorectal involvement in PSS. Two patients with long-standing disease received posterior anal repair for stool incontinence, the postoperative results were satisfactory both subjectively and objectively. The average MBP increased from 0 to 20 mm Hg, average FL from 0 to 1.5 cm. Patients complained less frequently about stool incontinence or soiling, and their daily life is now more comfortable. The analysis indicates that anorectal function in PSS is affected much more frequently and earlier than thought. Anorectal manometry can be used as an adjuvant in diagnosing controversial cases. Once anal incontinence occurs, posterior anal repair can achieve good results after six months of follow-up.

The Progress of Oesophageal Involvement in Progressive Systemic Sclerosis during D-Penicillamine Treatment

In 21 patients with initial signs of progressive systemic sclerosis, oesophageal motility was monitored manometrically from the start of D-penicillamine treatment and over a period of up to 5 years. Urinary excretion of the collagen-specific amino acids hydroxyproline and hydroxylysine, and of proline was used as a guideline for monitoring the bioavailability of D-penicillamine. D-penicillamine therapy was found to be unable to arrest the progress of oesophageal involvement. A downward trend over time--statistically significant at p = 0.03, p = 0.02, and p less than 0.005--was found for lower oesophageal sphincter pressure, peristaltic wave pressure in the distal third, and peristaltic wave pressure in the middle third of the oesophagus, respectively.

Are Nailfold Capillary Changes Indicators of Organ Involvement in Progressive Systemic Sclerosis?

Nailfold capillary abnormalities in 40 patients suffering from progressive systemic sclerosis (scleroderma; PSS) were studied by widefield nailfold capillary microscopy. Capillary enlargement and loss were graded using the rating scales of Maricq and Minkin. Capillary changes were correlated with organ involvement and immunological abnormalities. A high correlation was found between the grade of nailfold capillary changes and the clinical severity of PSS. Nailfold capillary microscopy seems to be a useful method to get quick information in order to predict organ involvement in PSS.