Diffuse Form Of Systemic Sclerosis Research Articles

Validation of the Portuguese Version of the Scleroderma Health Assessment Questionnaire.

The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test-retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test-retest reliability (ICC 0.61-0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = -0.688) and EQ-5D-5L index score (r = -0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = -0.628). Mental score correlations were smaller. With the exception of the Raynaud's VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients.

ASSOCIATION OF RADIOGRAPHIC FINDINGS OF MUSCULOSKELETAL HAND INVOLVEMENT WITH CLINICAL AND SEROLOGICAL FEATURES OF SYSTEMIC SCLEROSIS

Musculoskeletal manifestations (MSM) frequently occur in systemic sclerosis (SSc) and imply a variety of rheumatic symptoms and clinical features, from arthralgia to arthritis, contractures, tendon friction rubs, tenosynovitis, myalgia, muscle tenderness, and myositis. The objective of the study was to determine the prevalence of joint manifestations in clinical findings, as well as frequency and type of radiographic changes in 56 patients with the limited and diffuse form of SSc; to define the correlation between musculoskeletal hand changes in SSc and specific antibodies (antinuclear antibodies- ANA), as well as with antibodies specific for particular forms of SSc (anti-topoisomerase-1 antibodies- ATA, anticentromere antibodies- ACA); and to test the correlation between specific cardiopulmonary manifestations in SSc, and frequency and type of musculoskeletal changes. The obtained results indicated a high frequency of joint manifestations in SSc, which were estimated by clinical and radiographic examinations. Joint involvement in SSc was underestimated in clinical trials, as it occurred more frequently than expected. Radiographic hand findings in tested SSc patients indicated the presence of arthritis, erosions, joint space narrowing, radiological demineralization, acro-osteolysis, flexion contractures, and calcinosis. Hand involvement was an important cause of morbidity, which seriously affected the quality of life in patients with SSc. Various forms of joint and bone involvements could represent the base for introducing an innovative approach to treating musculoskeletal hand damage in SSc.

Evaluation of Anti-Centromere Antibodies, Anti-SSA and Anti-SSB in Serum and Saliva of Patients with Systemic Sclerosis

Background: Systemic sclerosis (SSc) is a chronic autoimmune illness, which is consider by three main features: Sclerotic changes in the skin and internal organs, Vasculopathy of small blood vessels, Particular autoantibodies (1). The most important autoantibodies appeared significantly in SSc patients are anti-topoisomerase I autoantibody (Scl-70), anti-centromere autoantibody (ACA), and anti-RNA polymerase III autoantibody (RNAP3) (2). Anti-centromere antibodies (ACA) are infrequent in rheumatic conditions and in healthy persons but occur commonly in limited systemic sclerosis (CREST syndrome), and rarely appeared in the diffuse form of systemic sclerosis (3). Anti-Ro/SSA and antiLa/SSB, antibodies directed against Ro/La ribonucleoprotein complexes, can serve as a diagnostic hallmark of autoimmune disease specially Sjogren’s syndrome (4). Materials and methods: This study was carried out during the period from the middle of November 2015 until the end of November 2016 in Baghdad city. The sample of this study was divided into two groups : Forty systemic sclerosis patients: Those patients were treated at Rheumatology department in Baghdad teaching hospital in Baghdad city as well as Forty healthy control subjects, age matched with no signs and symptoms of any systemic diseases. Results: The serum anti-SSA in SSc patient was significant increased as well as the salivary anti-SSA in SSc patient was highly significantly increased than in the control subjects by using t-test. The present study found that there no statically difference in salivary ACA, anti-SSB and serum anti-SSB while serum ACA was significantly increased. Conclusions: autoantibodies play a role in pathogenesis of SSc patients represented by increased serum (ACA and anti-SSA) that it considered reliable indicator for SSc patients while unpredicted marker in saliva except anti-SSA. Anti-La/SSB is unreliable marker in both serum and saliva SSc patients. The presence of Anti-Ro/SSA antibodies in serum and saliva of SSc patient has been predictive marker for SSc overlapped Sjogren’s syndrome.

The role of klotho in systemic sclerosis.

The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc), through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan's Skin Score, Medsger's scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8) years) and 77 healthy controls (28 females, mean age 49.7±10.2 years). In the group of SSc patients, 19 (27.5%) suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine). The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001). However, Spearman's test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.

RhoA/Rho-kinase activation promotes lung fibrosis in an animal model of systemic sclerosis

ABSTRACTBackground: Systemic sclerosis (SSc) is a connective-tissue disease characterized by vascular injury, immune-system disorders, and excessive fibrosis of the skin and multiple internal organs. Recent reports found that RhoA/Rho-kinase (ROCK) pathway is implicated in various fibrogenic diseases. Intradermal injection of hypochlorous acid (HOCl)-generating solution induced inflammation, autoimmune activation, and fibrosis, mimicking the cutaneous diffuse form of SSc in humans. Our study aimed firstly to describe pulmonary inflammation and fibrosis induced by HOCl in mice, and secondly to determine whether fasudil, a selective inhibitor of ROCK, could prevent lung and skin fibroses in HOCl-injected mice. Methods: Female C57BL/6 mice received daily intradermal injection of hypochlorous acid (HOCl) for 6 weeks to induce SSc, with and without daily treatment with fasudil (30 mg·kg−1·day−1) by oral gavage. Results: HOCl intoxication induced significant lung inflammation (macrophages and neutrophils infiltration), and fibrosis. These modifications were prevented by fasudil treatment. Simultaneously, HOCl enhanced ROCK activity in lung and skin tissues. Inhibition of ROCK reduced skin fibrosis, expression of α-smooth-muscle actin and 3-nitrotyrosine, as well as the activity of ROCK in the fibrotic skin of HOCl-treated mice, through inhibition of phosphorylation of Smad2/3 and ERK1/2. Fasudil significantly decreased the serum levels of anti-DNA-topoisomerase-1 antibodies in mice with HOCl-induced SSc. Conclusions: Our findings confirm HOCl-induced pulmonary inflammation and fibrosis in mice, and provide further evidence for a key role of RhoA/ROCK pathway in several pathological processes of experimental SSc. Fasudil could be a promising therapeutic approach for the treatment of SSc.

FRI0488 Analysis of REAL Life Vasoactive Therapy in over 3000 Patients with Systemic Sclerosis (SSC) Reveals Considerable Undertreatment and Significant Changes of Treatment Practice since 2004

BackgroundVasculopathy is a major pathophysiological problem in patients with systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcerations (DU), pulmonary arterial hypertension (PAH). It is not...

Desmoglein-2-Integrin Beta-8 Interaction Regulates Actin Assembly in Endothelial Cells: Deregulation in Systemic Sclerosis

BackgroundThe inability of endothelial cells of patients affected by the diffuse form of Systemic sclerosis (SSc) to perform angiogenesis is a marker of the disease. We previously demonstrated that desmoglein-2 reduction is a major difference between (SSc)-microvascular endothelial cells (MVECs) and normal (N)-MVECs. Here we investigated the role of desmoglein-2 in human N-MVECs and SSc-MVECs angiogenesis.Methodology/principal findingsAngiogenesis was studied by Matrigel invasion, capillary morphogenesis in vitro and Matrigel plug assay in vivo. Gene profiling was studied by Affymetrix technology and signal transduction by Western blotting. Colocalization was validated by immunoprecipitation and confocal microscopy. SiRNAs were used to validate the roles of specific molecules. We observed that desmoglein-2 co-localizes with integrin-beta8 in N-MVECs. This complex is required to signal through Rac, FAK, SMAD1/5 and MAP-kinases, promoting an angiogenic program. Inhibition of desmoglein-2 by DSG2-siRNA impaired actin stress fibres formation, capillary morphogenesis in vitro and angiogenesis in vivo. Transcriptome profiling after DSG2 inhibition revealed alterations of several genes involved in actin organization. siRNA inhibition of integrin-beta8 and RAC2 also resulted into capillary morphogenesis impairment in N-MVECs, due to reduced expression of the same actin-assembly genes that were down-regulated by DSG2 silencing. SSc-MVECs showed down-regulation of the same genes in DSG2-siRNA treated N-MVECs, suggesting that impairment of desmoglein-2/integrin-beta8 complex contributes to angiogenesis derangement in SSc. Transfection of DSG2 in SSc-MVEC partially restored their angiogenic properties in vitro.Conclusions/significanceWe have shown that impairment of actin assembly as a result of desmoglein-2/integrin-beta8 complex formation is a major factor contributing to angiogenesis deregulation in Systemic sclerosis.

THE IMPACT OF ANTI B-CELL THERAPY ON ARTERIAL STIFFNESS IN SYSTEMIC SCLERODERMA

Background.Arterial wall stiffness is an independent predictor of cardiovascular mortality in different patient populations. Currently, there are several studies that show an increase of arterial wall stiffness in systemic sclerosis (SSc). The effect of immunosuppressive therapy on vascular wall stiffness in SSc patients is not investigated. The authors of this paper attempted to study the effect of rituximab and cyclophosphamide combination therapy on vascular stiffness in 5 patients with diffuse form of SSc.Design and methods.We assessed arterial stiffness in 5 patients with diffuse form of SSc before and after 6 months after combined immunosuppressive therapy.Conclusion.The parameters of arterial stiffness decreased in all patients with the moderate effect of the therapy.

AB0507 Frequency and evolution of digital ulcers in systemic sclerosis

BackgroundDigital ulcers are frequent and recurrent complication in systemic sclerosis (SSc) and are the main cause of pain, impaired function of the hand and disability in SSc.ObjectivesTo evaluate the frequency...

THU0066 Phenotypical and Functional Characteristics of in Vitro Expanded Adipose-Derived Mesenchymal Stem Cells from Patients with Systemic Sclerosis

BackgroundAdult stem cells, expecially those of mesodermal origin (MSCs), have received attention as an ideal source of regenerative capable cells because of their multipotentially and ability to replicate. Regenerative cells...

FRI0454 Hand function in systemic sclerosis: Effect of occupational therapy on the health status and quality of life

BackgroundHand involvement highly influences the activities of daily life in most patients with Systemic Sclerosis (SSc). Occupational therapy (OT) studies have rarely investigated for improving of hand function.ObjectivesTo evaluate the...

Autoantibodies Recognizing the Amino Terminal 1-17 Segment of CENP-A Display Unique Specificities in Systemic Sclerosis

Centromere-associated protein A (CENP-A), a common autoimmune target in a subset of systemic sclerosis patients, appears to have no role to explain why its corresponding auto-antibodies are more frequently found in the limited than the diffuse form of systemic sclerosis. Therefore, we investigated the fine specificity of anti-CENP-A antibodies as a first step to understanding their role in systemic sclerosis pathology. We focused on the amino-terminal portion of CENP-A spanning amino acids 1 to 17 (Ap1-17), which represents, along with Ap17-30, an immunodominant epitope of the protein. Peptide Ap1-17 was used to purify antibodies from 8 patients with systemic sclerosis. Anti-Ap1-17 antibodies specifically reacted with human CENP-A but did not cross-react with CENP-B or Ap17-30. Panning of a phage display peptide library with anti-Ap1-17 antibodies from 2 patients identified two novel, partially overlapping motifs, <5Rx(st)xKP10> and <9KPxxPxR15> as the result of the alignment of specific phage clone insert sequences. Anti-Ap1-17 IgG from the 8 patients had different reactivities to isolated phage clone insert sequences. Scanning the Swiss-Prot database revealed a large number of different types of proteins containing the two Ap1-17 antigenic motifs. These data show that anti-CENP-A1-17 antibodies are generated independently from anti-CENP-B antibodies and display great heterogeneity in their specificity by recognizing different motifs within that peptide sequence. This finding, along with the widespread interspecies and human tissue distribution of the two motifs, suggests that the number of motif-expressing proteins which can be the potential target of these antibodies is markedly higher than that estimated from the peptide-based epitope spreading model.

Anti-proteinase 3 antibodies in diffuse systemic sclerosis (SSc) with normotensive renal impairment: is it suggestive for an overlapping between SSc and idiopathic vasculitis?

OBJECTIVE: To test the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) and to verify a possible association of ANCA with normotensive renal involvement in SSc. PATIENTS AND METHODS: 51 patients affected by SSc, 35 with diffuse scleroderma (dSSc) and 16 with limited scleroderma (lSSc), were tested for ANCA by indirect immunofluorescence (IIF) on human ethanol and formalin-acetone-fixed granulocytes (before and after DNase treatment), by conventional enzyme linked immuno-sorbent assay (ELISA) and by capture-ELISA. RESULTS: Six out of 51 selected SSc patients had ANCA by IIF (11.7%) and five presented a perinuclear/nuclear atypical ANCA pattern. In all cases we only found anti-proteinase3 (aPR3) antibodies. All ANCA positive patients had diffuse form of SSc (17.1%), all were anti-Scl70 positive (aScl70), five patients had proteinuria, three had microscopic haematuria. All ANCA positive patients were normotensive with normal renin plasma levels, the mean erythrocyte sedimentation rate (ESR) was higher in this group compared to the other SSc patients. CONCLUSIONS: Our study shows that aPR3 is not rare in dSSc. According to the clinical and serological findings and to the recent literature, we can hypothesise that when ANCA are found in SSc, an overlapping of scleroderma with systemic necrotizing vasculitis should be suspected.

Cost-of-illness in systemic sclerosis: a retrospective study of an Italian cohort of 106 patients

It is increasingly important to determine the economic consequences of diseases considering the policy of limited health-care budgets. In this study we evaluated the annual direct and indirect costs of Systemic Sclerosis (SSc) and we tried also to identify any cost predictors. We studied 106 patients (103 female, 3 male), 57 affected by Limited Systemic Sclerosis (LSSc) and 49 affected by Diffuse Systemic Sclerosis (DSSc). Mean age was 57 years (SD +/- 13.8) and mean disease duration was 8,9 years (SD +/- 7.2). Direct Costs: data were calculated referring to DRG (Disease Related Group) expenses for the in-patients. We referred to national pharmacopoeia to calculate the pharmaceutical cost for the out-patients. Indirect costs: we estimated the expense comparing our cases to literature data. Intangible costs: these are attributable to pain and psychological suffering. It is very difficult to express the intangible costs in monetary terms and they are often conveyed as disability and poorer quality-of-life. We used the Health Assessment Questionnaire "HAQ" and the Short Form-36 "SF-36" to evaluate this issues. Our study confirms, the extremely high costs caused by Systemic Sclerosis (total cost's 2001 year is 1,173,842.93 Euro, and average yearly patient cost is 11,073.99 Euro). Considering an estimated prevalence of 375 cases/106, the total yearly economic impact of SSc in Italy should be 249 million euro. Intangible costs were calculated as modifications of the health status. Average value of the HAQ was significantly higher than the control population (0.94 +/- 0.72), average values in the SF-36 were significantly lower than the control population (49.99 +/- 19.16 for physical dimension and 58.42 +/- 27.71 for mental dimension). The diffuse form of SSc, anti-Scl 70 antibodies, high skin score and a poor health status (HAQ and SF-36) were found to be cost predictors. As reported in the literature, our study confirms, the extremely high costs for total and single patients caused by Systemic Sclerosis. The DSSc are more expensive than the LSSc approximately 11% (p=0.0067). The direct costs are 30% higher in the DSSc than the LSSc (p < 0.001). The indirect and intangible costs are not significantly different. Moreover, our study shows also the possibility of identifying different cost predictors.

Healthy children have a significantly increased skin score assessed with the modified Rodnan skin score

The modified Rodnan skin score (MRSS) is used as a primary outcome measure in most therapeutic trials in systemic sclerosis (SSc) in adults. Before we can apply this outcome measure in trials in juvenile patients with SSc, we need to evaluate this assessment method in children without sclerodermatous skin changes, to establish values for the normal paediatric population. To determine the MRSS in healthy paediatric population, patients of the paediatric rheumatology out-patient clinic with mechanical pain or with juvenile idiopathic arthritis at the age of 16 yr or under were assessed between 1 January and 31 March 2004. Patients with any sign of connective tissue disease or skin disorders, such as psoriasis or ectopic dermatitis, were excluded. The MRSS was determined at a standardized location and with a standardized pinching method. Two hundred and seventeen patients, including 100 females, were assessed. The mean age of the patients was 10.5 yr (2.9-16), the mean body mass index (BMI) was 18.3 (9.3-35.7), and the mean MRSS was 13.92 (range 4-25). The MRSS score showed a difference between males and females at every Tanner stage. There was a linear correlation between MRSS and body mass index independently of age and Tanner stage. The mean MRSS in healthy children is 13.92 units and this range would be expected in a patient with a diffuse form of SSc. The MRSS score in children correlates with the body mass index and the Tanner stage, so it should be corrected to these parameters, according to this pilot study.

Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis.

Defective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell-associated urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process. MVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc. The uPA/uPAR system was examined at the protein and messenger RNA levels. Angiogenesis was assayed on Matrigel-coated porous filters and plates to evaluate cell proliferation, invasion, and capillary morphogenesis. Cleavage of uPAR and the activity of matrix metalloproteinase 12 (MMP-12) were evaluated by Western blotting. Compared with MVECs from healthy skin, MVECs from SSc patients showed higher expression of uPAR. However, in SSc MVECs, uPAR undergoes truncation between domain 1 and domain 2, as shown by flow cytometry, enzyme-linked immunosorbent assay, and Western blotting, a cleavage that is known to impair uPAR functions. These properties of SSc MVECs were associated with poor spontaneous and uPA-dependent invasion, proliferation, and capillary morphogenesis. The uPAR cleavage occurring in SSc MVECs was associated with overexpression of MMP-12. SSc MVEC-conditioned medium impaired uPA-dependent proliferation and invasion as well as capillary morphogenesis in normal MVECs in vitro. Both a general hydroxamate inhibitor of MMP activity and anti-MMP-12 antibodies restored this SSc MVEC-induced impaired functioning. Overproduction of MMP-12 by SSc MVECs accounts for the cleavage of uPAR and the impairment of angiogenesis in vitro and may contribute to reduced angiogenesis in SSc patients.

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.

Long-term therapy with plasma exchange in systemic sclerosis: effects on laboratory markers reflecting disease activity

Plasma exchange (PEX) is a technique that has been applied to the treatment of many immunological disorders, including connective tissue diseases. The crucial role of some humoral factors in the pathogenesis of systemic sclerosis (SSc) could explain the good clinical results obtained in terms of slowing down the disease progression, but the efficacy of PEX in the treatment of SSc is not yet well defined, owing to the lack of controlled studies and validated parameters of disease activity. To demonstrate the long-term efficacy of PEX in the treatment of SSc we treated a group of 28 SSc patients affected with recent onset and/or rapidly progressive disease. Most of these had a diffuse form of SSc, with anti-Scl70 antibody as a disease marker. Before and after long-term PEX treatment we evaluated disease activity parameters including the serum levels of interleukin 2 soluble receptor (sIL-2R) and aminoterminal type III procollagen peptide (PIIINP), plus the percentage of DR+ T cells in the peripheral blood. We also assessed clinical parameters of total skin score and total visceral score. The same parameters were evaluated in 25 SSc patients who did not satisfy the admission criteria for PEX, treated long-term with drugs only. At baseline, serum PIIINP and sIL-2R levels and the percentage of DR+ T cells were significantly increased in PEX patients as compared to others. Following long-term PEX treatment, all the laboratory parameters significantly decreased and the clinical scores showed a slight but not significant improvement. Conversely, in the other group of SSc patients treated for the same period with drugs only, no significant change of laboratory parameters was detected and the clinical scores slightly worsened. Our data suggest that long-term PEX therapy seems to be effective in slowing down the clinical course of patients with severe and rapidly progressive SSc.

Esclerose sistêmica difusa com hipertensão pulmonar isolada: relato de caso

A esclerose sistêmica (ES) é uma doença incomum, caracterizada por alterações vasculares e fibrose em pele e vários órgãos. O envolvimento pulmonar é freqüente na ES; entretanto, hipertensão pulmonar (HP) na ausência de fibrose intersticial é raramente observada. Os autores descrevem um caso de ES difusa com HP isolada em paciente do sexo feminino, de 49 anos. O diagnóstico de HP pôde ser sugerido pelo exame físico e confirmado por ecodopplercardiograma, que permitiu estimar a pressão sistólica em artéria pulmonar em 80mmHg. Tratamento foi iniciado com nifedipina; entretanto, devido a efeitos colaterais da droga, não foi possível o aumento da dose além de 30mg ao dia; nesta dosagem, a nifedipina não acarretou redução da pressão arterial pulmonar.

Thrombotic thrombocytopenic purpura in a patient with a diffuse form of systemic sclerosis

This paper presents a patient with a rapidly progressive diffuse form of systemic sclerosis, in whom a clinical course thrombotic thrombocytopenic purpura (TTP) also developed. In spite of treatment with plasmapheresis, predonisolone, aspirin and vincristine, she died of pulmonary bleeding. From the analysis of four other reported cases of scleroderma with TTP and this case, the outcome of TTP seems to be closely related to clinical manifestations. It is suggested that a diffuse form of scleroderma with interstitional manifestations would develop a worse outcome; on the other hand, a limited form without interstitional manifestations has a successful outcome.