Anita Åkesson

Mortality and causes of death in a Swedish series of systemic sclerosis patients

OBJECTIVES To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment. METHODS Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 deceased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients. RESULTS The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (lSSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer. CONCLUSIONS Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and lSSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.

Daily activities and hand function in women with scleroderma.

Objective: To give a detailed description of hand function and the ability to perform daily activities among patients with systemic sclerosis. Methods: Thirty patients with scleroderma answered a self‐administered activities of daily living (ADL) questionnaire. Hand function was estimated with respect to hand mobility, dexterity, and grip force. Perceived symptoms were reported on a visual analogue scale (VAS), and skin thickness was assessed by means of the modified Rodnan skin score. Results: Finger flexion and extension were the most impaired aspects of hand mobility. Dexterity was on average reduced to 68–80%, and grip force to 46–65% compared with values for healthy persons. The predominant self‐perceived problem was Raynauds phenomenon, whereas pitting scars/ulcers were perceived as the least problem. Activities building on hand and arm function were harder to perform than activities depending on lower limb function. Raynauds phenomenon, stiffness, grip force, and dexterity were factors with the strongest associations with ADL difficulties. Assistive devices and alternative working methods improved ADL ability. Conclusion: Impaired hand function was related to ADL difficulties and the use of assistive devices improved ADL. This emphasizes the importance of treatments that improve hand function and of testing ergonomic tools.

DISEASE SEVERITY OF 100 PATIENTS WITH SYSTEMIC SCLEROSIS OVER A PERIOD OF 14 YEARS: USING A MODIFIED MEDSGER SCALE

OBJECTIVE To assess organ involvement according to a modified Medsger severity scale and its relation to outcome and prognosis in patients with systemic sclerosis. METHODS One hundred consecutive patients observed in Lund with systemic sclerosis were followed up for a period of 14 years. The mean follow up time was 7.7 years. Initial assessment and an annual evaluation was performed for each patient, with a mean visit frequency of 5.6 per patient. RESULTS Age at referral, high total skin score, truncal skin involvement, low vital capacity, low static lung compliance, low Cr-EDTA clearance, and ECG abnormalities at the initial assessment predict poor outcome. A severity scoring system for five organ systems indicates a slow progression of organ dysfunction after recruitment into the study. The female: male ratio was 2:1, the mean age at onset of symptoms was 42.3 (range 3–82), and the mean age at recruitment was 47.2 years (range 17–82). Thirty patients died during the follow up period at the mean age of 61.3 years (range 33–85). The causes of death were directly related to systemic sclerosis in at least 10 patients, infections in six, cancers in nine, and other causes in four patients. The standardised mortality ratio was 3.5 and 3.7 for men and women, respectively. CONCLUSION A high severity score for function of vital organs was shown to predict shortened survival. In this study a severity score based on simple clinical assessment variables was able to predict poor outcome from extensive skin changes, ECG changes, and compromised lung and renal function. Organ dysfunction mainly became manifest during the first five years of the disease, whereafter organ function remained largely stable.

Evaluation of paraffin bath treatment in patients with systemic sclerosis

Objective: To investigate the effects of treatment with paraffin bath in patients with systemic sclerosis (scleroderma). Methods: In 17 patients with scleroderma one hand was treated daily with paraffin bath in combination with hand exercise. The other hand was treated with exercise only and was considered a control. Hand function was estimated before treatment and after 1 month of treatment, concerning hand mobility and grip force, and perceived pain, stiffness and skin elasticity. Results: At the follow-up, finger flexion and extension, thumb abduction, volar flexion in the wrist, and perceived stiffness and skin elasticity had improved significantly in the paraffin-treated hand compared with the baseline values. The improved hand function was independent of skin score and disease duration. Improvements in function were significantly greater in the hand which was treated with paraffin bath and exercise than in the hand treated with exercise only concerning extension deficit, perceived stiffness and skin elasticity. Conclusions: In this pilot study hand exercise in combination with paraffin bath seemed to improve mobility, perceived stiffness and skin elasticity. However, further studies with larger sample size are needed to attain more reliable results of the effect of paraffin bath treatment in patients with scleroderma.

Distribution of selenium and glutathione peroxidase in plasma compared in healthy subjects and rheumatoid arthritis patients

The distribution of selenium and glutathione peroxidase activity in plasma was compared in samples from healthy adult controls and patients with rheumatoid arthritis. Plasma was separated by gel filtration, and selenium was measured in the eluted fractions by means of graphite furnace atomic absorption spectrometry with Zeeman background correction. Most of the selenium in plasma of healthy controls was seen in proteins that migrated close to immunoglobulin G, and that had an apparent molecular weight at the peak of 174 kDa. One major peak of glutathione peroxidase activity with an apparent molecular weight of 99 kDa was unmatched by any significant peak in selenium content. Thus, there was only limited correspondence between the elution patterns of selenium and glutathione peroxidase activity. Also, in patients with active rheumatoid arthritis, selenium was distributed amongst plasma proteins with a wide range of molecular weights. The major selenium peak was less pronounced in patients, but the amount of selenium in other parts of the chromatogram was not different from that in controls. Further work is necessary to define the occurrence of different selenoproteins in plasma in patients and in healthy subjects.

Small intestinal manometry in patients with systemic sclerosis.

Objectives The study explores, by the use of manometry, the frequency and severity of small intestinal involvement in patients with systemic sclerosis, and relates the manometric findings to clinical symptoms, radiology, and some intestinal regulatory peptides. Methods Stationary antroduodeno-jejunal manometry was used to study small bowel involvement in 10 patients with systemic sclerosis and dysmotility of the oesophagus or signs of malabsorption. Measurements were made during fasting, after a meal, and after octreotide administration and were then compared with a sex-matched control group of healthy individuals. Plasma samples were taken in order to analyse levels of motilin, peptide YY, cholecystokinin, and somatostatin. Results Manometry was abnormal, with signs of intestinal pseudo-obstruction in eight out of 10 patients. In the control group, one individual had an abnormal manometry, as a result of burst activity. The mean contractile amplitudes during fasting and periods after food, spontaneous phase III periods, and octreotide-induced activity complexes were significantly reduced in the systemic sclerosis group when compared with controls. None of the patients, including two with advanced manometric intestinal disturbances, had small intestinal dilatation when examined by radiography. The plasma peptide levels did not differ significantly between the two groups. Conclusions In eight out of 10 patients the manometric criteria for intestinal pseudo-obstruction were fulfilled, with a motility pattern consistent with both neuropathy and myopathy. The release of motility-regulating peptides was unaffected.

Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease

The pathogenesis of systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. IL-15 is a pleiotropic cytokine that has impact on immune, vascular and connective tissue cells. We therefore investigated IL-15 in the circulation of patients with early SSc and explored possible associations of serum IL-15 with vasculopathy and fibrosis. Serum levels of IL-15 were analysed in 63 consecutive patients with SSc of disease duration less than 4 years and without disease-modifying treatment. Thirty-three age-matched healthy control individuals were enrolled. Serum IL-15 levels were increased in the sera of SSc patients compared with that of healthy control individuals (P < 0.01). Serum IL-15 levels correlated with impaired lung function, assessed both by the vital capacity (P < 0.05) and by the carbon monoxide diffusion capacity (P < 0.05). The association between IL-15 and the vital capacity remained after multiple linear regression analysis. Patients with intermediate serum IL-15 levels had a higher prevalence of increased systolic pulmonary pressure compared with patients with either low or high serum IL-15 levels (P < 0.05). Moreover, increased serum IL-15 levels were associated with a reduced nailfold capillary density in multivariable logistic regression analysis (P < 0.01). Serum IL-15 levels also correlated inversely with the systolic blood pressure (P < 0.01). We conclude that IL-15 is associated with fibrotic as well as vascular lung disease and vasculopathy in early SSc. IL-15 may contribute to the pathogenesis of SSc. IL-15 could also be a candidate biomarker for pulmonary involvement and a target for therapy in SSc.

Computer based quantitative analysis of capillary abnormalities in systemic sclerosis and its relation to plasma concentration of von Willebrand factor.

OBJECTIVES--To evaluate an objective and quantitative method for assessment of capillary abnormalities in systemic sclerosis (SSc). METHODS--Nailfold capillaries were investigated by capillary microscopy and photographed in 17 consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc) and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy controls. Investigators having no access to clinical data made drawings from magnified projections of coded photographs and analysed them using a computer program. Capillary density (capillary loops/mm in the distal row) and median capillary loop area were calculated. Presence of functional or organic arterial changes was evaluated by measurement of finger pressure with finger cooling. Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme linked immunosorbent assay (ELISA). RESULTS--In 16 of 17 SSc patients and 13 of 17 controls the technical quality of the photographs was sufficient for computer analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse relation was found between capillary density and median capillary loop area in SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and 409 IE/l in lSSc) compared with controls matched for age and sex (median 276 IE/l). Computer based analysis showed capillary density below the control range and median capillary loop area above the control range in 14 of 16 SSc patients. Measurement of finger pressure with finger cooling showed organic vascular changes in nine of 13 SSc patients. CONCLUSION--Computer based quantitative analysis has low interobserver variability and is a quantitative and sensitive method of assessing capillary abnormalities in SSc.

Liver Function in Some Common Rheumatic Disorders

Liver function was studied primarily by determination of serum gamma glutamyl transferase and alkaline phosphatase. In subsamples of patients the investigation was extended by determination of serum amino-transferases, isoenzyme analysis of alkaline phosphatase, 99mtechnetium scintigraphy, and liver biopsy. In 183 in-patients with rheumatoid arthritis, the serum gamma glutamyl transferase level was elevated in 47% and serum alkaline phosphatase (of liver origin) in 24%. A concomitant increase in serum aminotransferases was found in 15% of patients with elevated gamma glutamyl transferase level. A closely similar pattern was found in 45 patients with non-rheumatoid arthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and undefined arthritis), and in 5 patients with polymyalgia rheumatica. In 23 patients with non-rheumatic inflammation (pneumonia), liver dysfunction was common, though the pattern of serum enzyme changes was different. In rheumatoid arthritis, liver scanning showed irregular or low uptake, but biopsy only indicated reactive hepatitis. Hepatotoxicity could not be traced to any single drug or combination of drugs given. On the contrary, chloroquine appeared to reduce serum gamma glutamyl transferase, and corticosteroids had a similar effect on serum alkaline phosphatase. In patients not treated with corticosteroids, both serum gamma glutamyl transferase and alkaline phosphatase were weakly to moderately correlated with laboratory indices of disease activity (ESR and serum orosomucoid). The frequently occurring isolated increase of serum gamma glutamyl transferase and/or serum alkaline phosphatase in arthritis may be an unspecific reaction to inflammation.

Early pulmonary disease in systemic sclerosis : a comparison between carbon monoxide transfer factor and static lung compliance

OBJECTIVES--Pulmonary disease is responsible for considerable morbidity and mortality in systemic sclerosis (SSc). Static lung compliance (Cst) has been observed to be decreased more often in SSc than the vital capacity, indicating that it is a sensitive measure of lung restriction. In this study Cst was compared with the carbon monoxide transfer factor (TLCO), a widely used measure of the function of the alveolar capillary unit, and with lung volumes in 59 patients with confirmed or suspected SSc. METHODS--Cst was calculated from the oesophageal pressure at different lung volumes and the TLCO was measured with the single breath method. RESULTS--The TLCO was found to be the earliest sign of pulmonary disease and was already decreased at a disease duration of one year or less. Surprisingly, no relation was found between the TLCO and smoking habits, nor the degree of peripheral vascular disease. The TLCO correlated with the Cst and vital capacity. CONCLUSIONS--An early pulmonary lesion can be identified in patients with SSc with decreased TLCO at a time when no fibrotic changes are manifested.