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PubMed1992

Pulmonary manifestations of scleroderma.

Scleroderma is a severe systemic collagen vascular disease of unknown cause characterized by marked vascular and connective tissue abnormalities. The lungs are commonly involved in scleroderma, ranking only behind the skin, the peripheral vasculature, and the esophagus in frequency of organ involvement. Respiratory symptoms are, in a very few cases, the presenting manifestation of the disease. Abnormalities of pulmonary function in affected patients include a restrictive ventilatory defect, air flow obstruction, and a depressed diffusing capacity for carbon monoxide, which may be an isolated early finding. Interstitial lung disease and honeycombed lung are the most common pulmonary parenchymal abnormalities seen on chest radiographs. Enlargement of the cardiac silhouette and pulmonary artery due to scleroderma-induced pulmonary vascular disease is also noted. High-resolution computed tomography (HRCT) apparently is a sensitive, potentially useful technique for detecting occult interstitial lung disease in patients with scleroderma. Bronchoalveolar lavage usually shows an increase in total cell count and in the percentage of granulocytes; occasionally, there is a predominantly mononuclear (lymphocytic) cell alveolitis. Premortem and postmortem studies reveal two predominant lung lesions: (1) interstitial lung disease and (2) pulmonary vascular disease. Pulmonary vascular disease may occur in the absence of interstitial lung disease, particularly in patients with limited, as opposed to diffuse, scleroderma. The overall mortality rate in scleroderma is 50% at 7 years, and pulmonary complications are the major cause of death. No prospective, well-controlled studies have established that treatment alters the natural course of pulmonary disease in patients with scleroderma. Both D-penicillamine and cyclophosphamide have shown promise for treating patients with interstitial lung disease, and nifedipine may be useful for treating patients with early pulmonary vascular disease.

Humans↗

PubMed1996

A multicenter trial of recombinant human interferon gamma in patients with systemic sclerosis: effects on cutaneous fibrosis and interleukin 2 receptor levels.

OBJECTIVE: To evaluate the acute toxicity, potential efficacy, and effects on the soluble interleukin 2 receptor (sIL-2R) of recombinant human interferon gamma (rIFN-gamma) in patients with systemic sclerosis (SSc). METHODS: A multicentered, pilot clinical trial of rIFN-gamma was performed on 20 patients (15 women, 5 men, mean age 45 years) with active cutaneous SSc (mean disease duration 36 months) to evaluate it potential as a novel therapy for this untreatable disorder. After one week of rIFN-gamma 0.01 mg/m2/day, subjects self-administered rIFN-gamma 0.1 mg/m2/day intramuscularly for a total of 18 weeks. The major outcome variable was a modified skin score (0 = normal skin, 3 = hidebound skin) measured and summed from 15 anatomic areas of the body. sIL-2R levels were measured by ELISA at entry and exit from the study. RESULTS: The clinical results were modest at best. Nine of 20 patients achieved at least a 20% reduction in skin score, with one patient showing almost total remission of all skin abnormalities. The mean skin score at entry for all subjects was 22.8 +/- 8.9 and over the course of the trial improved marginally compared to baseline (mean change -4.72 +/- 6.62; p = 0.008). However, 8 subjects did not change appreciably while in the trial. Antibodies to Scl-70 were observed in only 5 patients (all with diffuse scleroderma) and were not associated with either response to or complications from therapy. The adverse reactions were frequent and occasionally severe. Ten subjects were withdrawn because of exacerbation of Raynaud's symptoms (n = 5), constitutional symptoms (n = 2), development of renal crises (n = 2), and mild pancytopenia (n = 1). Minor laboratory abnormalities were common and included elevation of cholesterol, triglycerides, hepatic transaminases, and reduction in white blood cell count. Compared to controls, mean sIL-2R was markedly elevated at entry (1309 +/- 495 U/ml; p = 0.0001) and did not change appreciably at exit. Spearman correlation analysis showed a trend but no statistically significant association of skin score with sIL-2R (R = 0.408; p = 0.074). However, sIL-2R was significantly correlated with erythrocyte sedimentation rate (R = 0.542; p = 0.0165). A subset analysis revealed that skin score (p = 0.0001) and sIL-2R (p = 0.00170) were significantly higher at baseline for patients with diffuse scleroderma compared to patients with limited disease. CONCLUSION: rIFN-gamma may be beneficial for some patients with SSc, but the benefit appears marginal for most individuals and the side effects frequent. Although sIL-2R was elevated in many of the patients with SSc, it did not appear to be correlated with activity of cutaneous disease or response to therapy.

Adult↗

PubMedDate not supplied

Oral rehabilitation of a patient with scleroderma associated with systematic lupus erythematosus: a case report.

This case report presents a patient who had a limited oral opening due to systematic lupus erythematosus (SLE) and describes how oral rehabilitation was achieved with a removable partial denture. Various techniques for the delivery of oral health care have been reported for patients who have limited mouth openings as a result of SLE and scleroderma. After a review of the literature, a new approach was required for this patient with SLE who had a very limited mouth opening. The retention for the removable partial denture (RPD) used the undercut in the abutment teeth and a magnet-retained sectional RPD. A set of tweezers was modified to help with the insertion and removal of the sectional RPD by the patient. This paper reports a new clinical and laboratory technique of fabricating a sectional RPD using magnets and customized tweezers for this patient.

Adult↗

PubMed2002

[Pulmonary hypertension associated with systemic sclerosis].

Pulmonary hypertension is a rare but well known life-threatening complication of scleroderma and particularly in its limited variant, the CREST syndrome (Calcification, Raynaud phenomenon, Esophageal dysmotility, Sclerodactily, Telangiectasia). The aim of this article is to analyze the available literature and to report the experience of a center for pulmonary vascular diseases. Dyspnea is the main symptom and is frequently severe. Echocardiography is an excellent tool to detect pulmonary hypertension. However, right-heart catheterization is necessary to confirm the diagnosis of pulmonary hypertension and to test vasoreactivity with a potent vasodilator such as nitric oxide. Hemodynamic parameters are less severe in patients with connective tissue diseases perhaps because of an earlier diagnosis. A significant lower proportion of patients presents an acute vasodilator response suggesting an early constitution of irreversible pulmonary vascular lesions. Continuous intravenous epoprostenol therapy seems to be less effective as compared with patients with primitive pulmonary hypertension and does not improve survival. In our experience, immunosuppressive therapy does not improve hemodynamic or clinical data. Novel therapies including oral, sub-cutaneous or inhaled stable prostacyclin analogues and endothelin receptor antagonists are currently evaluated in large placebo-controlled trials.

Antihypertensive Agents↗

PubMed2001

Evaluating the cutaneous involvement in scleroderma: torsional stiffness revisited.

OBJECTIVE: The pace, progression and extent of the skin lesions in scleroderma may parallel the risk of new internal organ involvement and the progression of existing internal lesions. Accurate assessment of cutaneous change permits an evaluation of patient prognosis and the response to therapy. The aim of this study was to assess a simple device for measuring skin stiffness for its ability to measure sclerodermatous skin in a quantitative and reproducible manner. Materials and methods. Torsional skin stiffness was measured in 56 normal subjects and 42 scleroderma patients (31 of whom had the limited form and nine the diffuse form, and two had mixed connective tissue disease). Data for the scleroderma patients were compared with data obtained by the use of the modified Rodnan clinical skin scoring technique. Intraclass correlation coefficients (ICCs) were calculated as a measure of intraobserver and interobserver variability. RESULTS: For the left and right hands respectively, the ICCs for intraobserver variability were 0.908 and 0.906 and those for interobserver variability were 0.871 and 0.628. There was a significant difference in mean angular rotation obtained by normal subjects compared with scleroderma patients (15.1 vs 11.3 degrees, P<0.001). There was a significant difference in the angular rotation with increasing severity of skin involvement (skin score 0, median rotation 16.3 degrees; score 1, 10.5 degrees; score 2, 8.5 degrees; score 3, 8.0 degrees; P<0.00001). CONCLUSIONS: The measurements obtained with the skin stiffness device are highly reproducible and are consistent with the current clinical method of assessment of skin involvement. The significant difference in angular rotation obtained by normal subjects and scleroderma patients indicates that the device can distinguish normal from sclerodermatous skin. The torsional stiffness measurements derived from the device may also be useful in longitudinal studies.

Adult↗

PubMed2002

Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis.

OBJECTIVES: To determine the distribution of transforming growth factor beta1 (TGFbeta1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated. METHODS: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFbeta1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing. RESULTS: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, chi(2)=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, chi(2)=5, 1df, p=0.02 and controls v lSSc, chi(2)=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, chi(2)=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, chi(2)=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon. CONCLUSIONS: These results suggest that patients with SSc are genetically predisposed to high TGFbeta1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.

Codon↗

PubMed2001

Localized scleroderma or morphea?

Morphea is a frequently mild, benign, and self-limiting skin disease with a less than 1% reported chance of progressing to systemic scleroderma. Morphea is a sufficient and less terrifying name for these disorders than localized scleroderma.

Humans↗

PubMed1999

Connective tissue disease and silicosis.

BACKGROUND: To determine the prevalence of connective tissue disease in a cohort of individuals with silicosis, we reviewed the medical records and questionnaires from individuals reported from 1987 to 1995 to a state surveillance system for silicosis. Reporting of individuals with silicosis is required by state law. Cases were reported by hospitals, physicians, the state workers' compensation bureau, or from death certificates. Only individuals who met the criteria for silicosis developed by the National Institute for Occupational Safety and Health (NIOSH) were included in the analysis. RESULTS: A questionnaire was completed for all 583 cases. Medical records were available for 463. There were 24 people with rheumatoid arthritis, one with scleroderma, and one with systemic lupus erythematosus. All were men. The prevalence of rheumatoid arthritis was 5.2% (relative risk (RR) 2.73, 95% confidence limit (CL) 1.75-4.06). The prevalence of scleroderma was 0.2% (RR 15.65, 95% CL 0.21-87.03) and the prevalence of systemic lupus erythematosus was 0.2% (RR 11.37, 95% CL 0.15-63.23). This is an approximately 2.5-15-fold increased risk for these connective tissue diseases compared to estimated prevalences in the general population. Individuals with silicosis and connective tissue disease did not differ from individuals with silicosis but without connective tissue disease by race, age, type of industry where exposed to silica, history of tuberculosis, whether or not they had applied for workers' compensation, and whether or not they had progressive massive fibrosis on chest x-ray. CONCLUSION: Although the association between scleroderma and silicosis has been more widely reported in the literature, the prevalence of rheumatoid arthritis was greater than the prevalence of scleroderma or systemic lupus erythematosus among a cohort of individuals with silicosis.

Arthritis, Rheumatoid↗

PubMed2006

Systemic and localized scleroderma in children: current and future treatment options.

Scleroderma is a group of rare and complex diseases with varied clinical manifestations. The most obvious manifestation of the diseases is skin hardening and sclerosis. Scleroderma can be divided into two main subgroups: systemic and localized. The systemic form, also known as systemic sclerosis, involves diffuse skin involvement and potentially severe visceral involvement. Localized scleroderma on the other hand is more common in children and usually confined to a specific region of the body with no internal organ involvement. The juvenile forms of systemic sclerosis and localized scleroderma are important conditions in children because of the clinical severity and substantial mortality of systemic scleroderma and the major growth defects associated with childhood-onset localized disease even if the active disease itself is self-limited. The pathogenic pathways of the various forms of scleroderma are only partially defined, but the main defect in scleroderma is abnormal collagen deposition leading to eventual fibrosis in the skin as well as multiple organ systems such as the heart and lungs in juvenile systemic sclerosis. Therapeutics are divided into three main subgroups for systemic sclerosis: antifibrotics, anti-inflammatories, and vasodilators. For localized disease, anti-inflammatories, vitamin D analogs, and UV irradiation have been investigated. However, the infrequency of scleroderma in the pediatric population plus the fact that this disease is very often self-limiting makes randomized controlled trials very difficult. It is for this reason that most data on treatment modalities for this disease have been extrapolated from studies in adult patients. There is no one therapy for systemic sclerosis or localized scleroderma that has proven to be very effective or significantly disease modifying. However, current therapeutic strategies must be initiated early in the disease course for maximum beneficial clinical effects. New interventions such as autologous stem cell transplant and cytokine-directed therapies are under investigation as potential treatments for this complex disease.

Child↗

PubMed1996

Evidence of free radical-mediated injury (isoprostane overproduction) in scleroderma.

OBJECTIVE: Free radical-induced oxidative stress with consequent lipid peroxidation and resultant tissue damage has been suggested as a potential mechanism of the pathogenesis of scleroderma. However, because reliable measurement of lipid peroxidation in vivo is difficult, it has not been possible to adequately examine this hypothesis. We have previously described a series of bioactive prostaglandin F2-like compounds, termed F2-isoprostanes, produced in vivo in humans by the non-cyclooxygenase, free radical-catalyzed, peroxidation of arachidonic acid and have shown them to be a reliable measure of lipid peroxidation in vivo. In the present study, we determined whether scleroderma is associated with enhanced oxidative stress. METHODS: As a measure of oxidative stress, we determined urinary concentrations of a tetranor-dicarboxylic acid metabolite of F2-isoprostanes (F2IP-M) by mass spectrometry in 8 patients with scleroderma (representing a wide spectrum of disease, including limited disease with refractory digital ulceration or pulmonary hypertension, and diffuse disease) and in 10 healthy control subjects. RESULTS: F2IP-M concentrations were significantly higher in patients with scleroderma (mean +/- SEM 3.41 +/- 0.64 ng/mg of creatinine) than in healthy controls (1.22 +/- 0.14 ng/mg of creatinine) (P = 0.002). These elevations occurred in patients with limited disease and in those with diffuse disease. CONCLUSION: The increased level of urinary F2IP-M supports the hypothesis that free radical-induced oxidative injury occurs in scleroderma and provides a biologic marker whose relationship to disease activity and disease therapy may be important. These findings may also provide a rationale for exploring whether antioxidant therapy may influence the natural course of the disease.

Adult↗

PubMed1997

Scleroderma--demographics and survival.

Scleroderma is a rare disease with limited data on its occurrence. Published prevalence rates vary widely with contemporary studies based on hospital ascertained cases, reporting rates of 30-120/million population. The annual incidence of new cases is much lower with rates of 2-20/million/year. Rates are substantially higher in females with a peak onset in the fifth and sixth decade. The disease is associated with a substantially reduced survival with approximately 50% surviving 10 years. Again, there is wide variation among studies probably reflecting patient selection factors. Apart from an increased risk of death from scleroderma related causes, there is also an increased cancer mortality particularly of the lung.

Adult↗

PubMed1994

Scleroderma renal crisis with minimal skin involvement and no serologic evidence of systemic sclerosis.

We describe a 75-year-old male patient who developed end-stage renal failure secondary to scleroderma renal crisis. The patient had cutaneous involvement limited to his fingers and feet, and had repeatedly negative serologic tests for antinuclear antibodies. This case illustrates that scleroderma renal crisis should be considered in the differential diagnosis of unexplained acute renal failure in patients with suspected systemic sclerosis, even if they lack the typical extensive cutaneous changes and the expected serologic findings.

Aged↗

PubMed1988

Systemic scleroderma. Clinical and pathophysiologic aspects.

Systemic scleroderma is a generalized disease of connective tissue involving mainly the skin, the gastrointestinal tract, the lungs, the heart, and the kidneys. It can be present in different forms, of which acroscleroderma, with limited cutaneous and extracutaneous involvement, and diffuse scleroderma within a more rapid progression are most characteristic. Circulating antibodies against antinucleolar antigens are present in most patients with systemic scleroderma. They are helpful for establishing a classification and for determining the prognosis of the disease; their involvement in the pathogenesis, however, is still unclear. Alterations of the blood vessels and induction of fibroblasts by potent mediators are thought to play an important role in the early phase of scleroderma. Therefore early diagnosis is required, which then can initiate vasoactive therapy. In patients with systemic scleroderma, who also suffer from additional myositis, interstitial lung diseases, or arthritis, anti-inflammatory treatment with prednisolone and azathioprine is suggested. Development and progression of fibrosis cannot yet be influenced sufficiently. Only D-penicillamine affecting cross-linking of collagen has been widely used in scleroderma and has some beneficial effect.

Anti-Inflammatory Agents↗

PubMed2003

Keloidal scleroderma.

Progressive systemic sclerosis (PSS) can involve the skin diffusely or in a limited way. Rarely cutaneous involvement can assume a hypertrophic form, described in the literature as keloidal scleroderma. The authors describe a PSS patient who presented cutaneous manifestations compatible with the diagnosis of this clinical situation. The clinical features, pathogenic mechanism and therapeutic approach are discussed and a broad review of the literature is given.

Adult↗

PubMed2006

Anti-th/to-positivity in a cohort of patients with idiopathic pulmonary fibrosis.

OBJECTIVE: To evaluate the presence and clinical relevance of anti-Th/To-positivity in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Antinuclear antibody (ANA) testing was performed in 285 patients with a clinical diagnosis of IPF and surgical lung biopsy-proven usual interstitial pneumonia. Twenty-five subjects (8.8%) were found to have a positive ANA with a nucleolar-staining pattern and were followed for 10 years. Immunoprecipitation analysis indicated that 13 of the 25 subjects had autoantibodies against Th/To antigen. RESULTS: All subjects presented with worsening dyspnea. Pulmonary physiology and gas exchange did not differ between those with and those without a positive ANA, those with and without a nucleolar-staining ANA, and those with and without anti-Th/To antibody positivity. Retrospective review of the clinical record revealed that none of the 25 subjects with a nucleolar-staining ANA had the characteristic cutaneous features of systemic sclerosis (SSc). Four of the 13 Th/To-positive subjects had 3 of 5 criteria of limited cutaneous SSc (CREST variant), and 9 met proposed criteria for SSc sine scleroderma. None of the 12 Th/To-negative subjects had 3 or more criteria of limited cutaneous SSc (CREST variant), and only one met proposed criteria for SSc sine scleroderma. Of the 25 subjects with nucleolar-staining ANA, cumulative survival was similar between those who were Th/To-positive and those who were Th/To-negative (log-rank test, p = 0.73). Cumulative survival was similar between the 13 Th/To-positive subjects and all other 272 IPF subjects (log-rank test, p = 0.34). CONCLUSION: Our findings indicate that a nucleolar-staining ANA is a common finding in patients with IPF, and that antibodies against Th/To are responsible for the majority of these. Given the high specificity of Th/To-positivity for SSc, our data suggest that these subjects may have SSc sine scleroderma, and that their prognosis is no different from those with IPF.

Adult↗

PubMed1992

Reproductive function prior to disease onset in women with scleroderma.

We tested in a retrospective study the hypothesis that women with scleroderma have an increased risk, before disease presentation, of problems in pregnancy. Reproductive history, as reported from a validated postal questionnaire, was obtained from 204 women with scleroderma [mean year of birth (yob) 1942] and compared to that reported by 233 women with primary Raynaud's phenomenon (mean yob 1948) and 189 healthy women from a population register (mean yob 1950). Only pregnancies occurring before symptom onset in the scleroderma group were considered for analysis. All analyses were adjusted for job, social class, age at first pregnancy, smoking habit, and where relevant, parity. The results are expressed as odds ratios (OR) [with 95% confidence limits (CL)] giving the risk of developing scleroderma, with previous exposure to each of the specific reproductive variables analyzed, relative to the 2 comparison groups. The women with scleroderma were more likely than the population women to have had a delay in conception (> or = 12 months): OR 2.6 (1.1, 5.7) or be infertile: OR 2.3 (0.7, 7.2). These differences were not apparent when the scleroderma group was compared to the women with Raynaud's: OR's 0.7 and 1.1, respectively. Similarly there was a greater self report of maternal ill health in pregnancy in the group with scleroderma compared to the population women: OR 2.1 (1.2, 3.5) but not compared to the women with Raynaud's: OR 1.0 (0.7, 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed2000

Expression of DNA topoisomerases in chronic proliferative kidney disease.

BACKGROUND: Circulating autoantibodies to human topoisomerases have been reported in glomerular kidney disease associated with scleroderma and systemic lupus erythematosus. However, limited information is available about the expression of topoisomerases in the kidney under normal and pathological conditions. METHODS: The expression of DNA topoisomerases I and IIalpha was studied by immunohistochemistry on archival biopsies from 70 patients with chronic renal diseases. Normal kidney tissue was examined for comparison. Topoisomerase I was detected by means of monoclonal antibody (mAb) C21, and topoisomerase IIalpha was detected by means of mAb Ki-S4. In addition, mAb Ki-M1p was used to assess the density of monocytic infiltrates. All parameters were assessed in a semiquantitative manner. RESULTS: Glomerular topoisomerase IIalpha levels were increased in mesangial proliferative glomerulonephritis (MPGN), rapidly progressive glomerulonephritis (RPGN), and lupus nephritis (LN) and were reduced in membranous glomerulonephritis (MGN), chronic transplant nephropathy (CTN), and tubulointerstitial nephritis (TIN). Tubular epithelia displayed high topoisomerase IIalpha levels in mesangiocapillary glomerulonephritis (MCGN), RPGN, TIN, miscellaneous entities (MISC) and LN, and displayed low levels in MPGN and CTN. Topoisomerase I expression was high in the glomeruli of focal segmental glomerulosclerosis (FSGS), MCGN, and RPGN and was extreme in LN, whereas it was strikingly diminished in the glomeruli of MGN, CTN, and TIN. Almost all conditions displayed lower tubular topoisomerase I levels than normal kidney, except for LN, in which the enzyme content was markedly increased. Increased glomerular monocytic infiltrates were found in FSGS, MCGN, RPGN, TIN, and LN, and tubulointerstitial Ki-M1p+ cells were seen at high numbers in MCGN, RPGN, TIN, MISC, and LN. The expression of the topoisomerases I and IIalpha was significantly correlated; also, topoisomerases showed a positive association with the density of monocytic infiltrates. The parameter profiles exhibited significant differences between distinct types of chronic renal disease. CONCLUSION: Topoisomerase IIalpha expression is tightly linked to cell cycling, and topoisomerase I is likely a reflection of gene transcription. Rapidly progressing glomerular disease therefore appears to be accompanied by active mesangial cell proliferation and increased metabolic activity in glomerular cells. The correlation with inflammatory infiltrates is likely to reflect a positive feedback mechanism involving cytokines, growth factors, and adhesion molecules. Assessment of topoisomerases may therefore be of diagnostic help and might allow prognostic predictions. Provided that our observations are supported by clinicopathological follow-up studies, one might envisage the use of topoisomerase inhibitors in the therapy of chronic proliferative renal disease refractory to current treatment protocols.

Antibodies, Monoclonal↗

PubMed2001

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS: Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). RESULTS: An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION: Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Adolescent↗