Progressive Systemic Scleroderma Research Articles

Argumentaire « en faveur » de la greffe de cellules souches hématopoïétiques autologues dans la sclérodermie systémique

Autologous haematopoietic stem cell transplantation for systemic scleroderma, developed over more than 25 years, has shown in three randomised controlled clinical trials a significant impact not only in event-free survival, overall survival, cutaneous and pulmonary involvement, but also in the quality of life of patients living with recent severe diffuse cutaneous systemic scleroderma, compared with IV cyclophosphamid despite a transplant-related mortality between 2.4 and 10%. No immunosuppressants or biologics have shown such an impact on mortality in this disease. The risk of relapse is estimated between 9 and 24%, two years after transplant. On the basis of these results, French and international guidelines now position autologous haematopoietic stem cell transplantation as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma.

Atypical arthritis of the hands : Collagenosis-part2

Progressive systemic scleroderma (PSS) and mixed connective tissue disease (MCTD) represent vasculitic autoimmune diseases from the group of collagenoses with manifestations in various organ systems such as the skin, the internal organs and the joints. To present the atypical arthritis patterns of the hands in PSS and MCTD that differ from those in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in the context of clinical and serologic findings and in consideration of the classification of PSS and MCTD. Narrative review based on the current literature on the subject from the radiological and rheumatological point of view. In PSS, combinations of acral soft tissue atrophy, nonreactive acro-osteolysis, and interstitial calcifications can be visualized by projection radiography, which in the final stage can lead to a scleroderma claw hand. Digital pharmacoangiography of the hands can be used to reliably diagnose manifest vascular occlusions of the digital arteries. MCTD is characterized by various overlapping symptoms of at least two systemic autoimmune diseases and most frequently presents in the hand with symmetrical involvement of the PIP (proximal interphalangeal), MCP (metacarpophalangeal) and wrist joints with the manifestation of so-called "puffy fingers". The presented morphological atypical arthritis patterns of the hands in PSS and MCTD differ considerably from the typical patterns in the hands in RA and PsA. MRI is useful to diagnose early stages and pharmacoangiography can be used to differentiate between temporary and manifest digital vascular occlusions.

Preliminary Report of Endovascular Treatment for Critical Limb Ischemia Patients with Connective Tissue Disease: Cases Series and Review of the Literature

Only few studies have addressed the surgical revascularization in patients with both connective tissue disease (CTD) and critical limb ischemia (CLI), and the evidence for the endovascular treatment (EVT) is lacking in such patients. The main purpose of this study is to assess our outcome of EVT in patients with CTD and ischemic leg ulcers and review the current situation of the revascularization in such patients. Medical records of 10 consecutive patients with coexistent CTD and CLI-related leg ulcers (in 11 limbs) treated endovascularly at our institution between 2009 and 2013 were reviewed retrospectively. The patients had rheumatoid arthritis (n = 5), systemic lupus erythematosus (n = 1), progressive systemic scleroderma (n = 3), or polyarteritis nodosa (n = 1). EVT was technically successful in all the cases. No procedure-related morbidity or mortality occurred. During the mean follow-up period of 26 months, there were no major amputations, and sustained clinical improvement (ulcer healing and reduction in Rutherford category) was observed in eight limbs. The overall 1-year rates of amputation-free survival and freedom from reintervention were 89 and 81%, respectively. In our series of patients with CTD and ischemic leg ulcers, EVT had acceptable outcomes and may be recommended as a safe and reasonably effective initial treatment option for such patients.

Abstract 3039: Temporal Trends in the Prevalence of Dermatoses in Patients with Stroke and Transient Ischemic Attack in the United States

Background. We sought to determine the prevalence of skin conditions traditionally associated with acute ischemic stroke (AIS) and transient ischemic attacks (TIA) in the U.S. Methods. This is a cross-sectional study of data derived from the National Inpatient Sample from 1988-2008. We searched for admissions of patients <18 years, with a primary diagnosis of AIS, TIA, and the following secondary diagnoses (dermatoses): Psoriasis, Behcet’s Disease (BD), Dermatomyositis (DM), Systemic Lupus Eythematosis (SLE), Pseudoxanthoma Elasticum (PXE), Progressive Systemic Sclerosis or Scleroderma (SCD), and Bullous Pemphigoid (BP). Definitions were based on ICD9CM codes, and adjusted incidence rates for the U.S census and prevalence proportions were then calculated. Results. Over the 20-year period, we identified 9,085,147 admissions that corresponded to a primary diagnosis of AIS and TIA of which 53,060 had a secondary diagnosis of dermatoses, for a total prevalence of 0.6%. The adjusted rate of AIS/TIA increased from 71/100,000 in 1988 to 200/100,000 in 2008. Among the secondary diagnosis, the most prevalent condition after AIS/TIA admissions was SLE (54%), psoriasis (34%), SCD (9%), BP (2%), DM (1%), PXE (0.5%), and BD (0.14%). The prevalence of these dermatoses increased from 0.2% in 1988 to 0.8% in 2008 ( Figure 1 ). Conclusion. Despite an overall increase in the prevalence of dermatoses, these skin conditions remain a rare occurrence in AIS/TIA. The over-representation of traditional risk factors for AIS/TIA in patients with these dermatoses, may explain the observed epidemiological phenomenon.

Morphea as a Consequence of Accelerated Partial Breast Irradiation

Morphea is a localized form of scleroderma usually unaccompanied by the typical systemic stigmata that characterize progressive systemic scleroderma. It rarely manifests at the site of whole breast external-beam radiation therapy. We present an unusual case of radiation-induced morphea (RIM) that occurred after accelerated partial breast irradiation (APBI) using intracavitary Contura brachytherapy. A 65-year-old white woman was treated for stage IIA invasive ductal carcinoma of the left breast with APBI to a dose of 34 Gy in 3.4-Gy fractions twice daily over the course 5 days with intracavitary brachytherapy. At 1.5 years after completion of APBI, the patient developed an area of tenderness, erythema, and induration at the site of irradiation. A skin biopsy was consistent with morphea. To our knowledge, this is the first case of RIM confined to the area of APBI.

A Case of Progressive Systemic Scleroderma Associated with Malignant Fibrous Histiocytoma

A Case of Progressive Systemic Scleroderma Associated with Malignant Fibrous Histiocytoma

A Case of Progressive Systemic Scleroderma with Synthesis of Elastic Fibers and Amyloid Deposition in the Sclerotic Dermis

A Case of Progressive Systemic Scleroderma with Synthesis of Elastic Fibers and Amyloid Deposition in the Sclerotic Dermis

Surgical result of critical limb ischemia due to tibial arterial occlusion in patients with systemic scleroderma

To analyze the outcome after surgery for critical limb ischemia (CLI) due to tibial artery occlusion in patients with systemic scleroderma. The medical records of scleroderma patients with CLI due to tibial artery occlusion were reviewed with respect to demographic data and perioperative variables. Eight patients were identified at The University of Tokyo Hospital from 1991 to 2007. The underlying collagen disease was progressive systemic scleroderma in 6 patients and CREST syndrome in 2 patients. The subjects were 1 man and 7 women with a mean age of 68 years. While hypercoagulability including positive anticardiolipin antibodies was found in only 1 patient, all patients were antinuclear antibody (ANA) positive and 6 of 8 patients had a high titer of centromere-type ANA. Five underwent pedal artery bypass and 1 underwent distal peroneal artery bypass, while 2 underwent primary limb amputation. Although 1 patient with bypass had early graft occlusion (with subsequent below-knee amputation), the other 5 patients with patent grafts quickly achieved pain relief and initial wound healing. However, four of the five patent grafts developed graft occlusion several months after surgery, with severe intimal thickening at the anastomosis. As a result, 2 of 6 patients with bypass (totally 4 of 8 patients) underwent limb loss and 1 patient developed persistent recurrent ulcer. Bypass surgery in patients with scleroderma and CLI can be successful in achieving early pain relief and ischemic wound healing. However, the long-term effectiveness is limited with high rates of graft failure and limb loss.

Clinical value of bronchoalveolar lavage in progressive systemic scleroderma (author's transl)

As an enlargement of conventional diagnostic methods the cell spectrum of bronchoscopically obtained bronchoalveolar lavage was investigated in 10 patients with progressive systemic scleroderma. Two cases showed marked lymphocytosis, one increased numbers of granulocytes, two patients had marginally increased percentages of inflammatory cells. Four of these patients were in a progressive active phase of scleroderma with humoral inflammation signs and round cell infiltrates of the skin. In contrast, the lavage cell picture of the other five patients was unremarkable. One of these had advanced pulmonary fibrosis, however without signs of progression. The results show that the lavage cell pattern reflects the acute phase with cellular inflammation of lung parenchyma disease such as occurs in progressive systemic scleroderma. Staging of pulmonary organ manifestation in progressive systemic scleroderma can be markedly improved by low-risk bronchoalveolar lavage.

Evaluation of the function of the tubular esophagus in patients with progressive systemic scleroderma based on a standardized symptom score

The oesophagus is the internal organ most often affected in progressive systemic scleroderma (PSS). Suitable methods for demonstrating oesophageal involvement are available in only a few centres. Aim of this study was to validate a standardized symptom score for assessing oesophageal function in patients with PSS. Oesophageal symptoms of dysphagia, odynophagia (pain on swallowing), heartburn and regurgitation were assessed in 27 consecutive patients with PSS. Intensity (0 to 3 points) and frequency (1 to 4 points) of these symptoms were quantified using a standardized system (after de Dombal and Hall): points per symptom (0 to 12) and points per patient (0 to 48). Results were compared with long-term manometric recordings as reference. The control group consisted of 20 healthy volunteers matched for age and sex. Healthy controls and patients with PSS had significantly different oesophageal motility: 22 of 27 patients fulfilled the criteria of oesophageal hypomotility. Using a total symptoms score of 8 points (points per patient) as limit of normal, the sensitivity of the scoring for the diagnosis of abnormal oesophageal function was 68%, with a specificity of 100%, positive predictive value of 100% and a negative predictive value of 42%. The reported method of symptom scoring provides a valid means of positive prediction of (abnormal) oesophageal function, making manometric investigation unnecessary. Absence or an only mild degree of oesophageal symptoms does not exclude abnormal motility so that manometry must be performed in such patients.

Centromere antibodies and antibodies against Scl 70 nucleoprotein in progressive systemic scleroderma. Diagnostic and prognostic significance

Frequency and diagnostic significance of two scleroderma-specific antinuclear antibodies were examined in 104 patients with progressive systemic scleroderma (PSS). Antibodies against an antigen in the centromere region of chromosomes (centromere antibodies) were demonstrated by indirect immuno-fluorescence on HEp-2 cells in 18 patients (17%) and antibodies against Scl-70 nucleoprotein (Scl-70 antibodies) by gel precipitation with soluble nuclear extracts (ENA) in 21 patients (20%). In none of the patients did both antibodies occur. In patients with Scl-70 antibodies severe illness was predominant with extensive cutaneous sclerosis in 86%, lung involvement in 85% and joint involvement in 89%. Humoral inflammatory signs were marked in this group. Patients with centromere antibodies predominantly had acroscleroderma (56%) with subcutaneous calcinosis (83%) and telangiectasias (83%), as known from the CREST syndrome. Humoral immune phenomena were rare. With regard to Raynaud's syndrome, involvement of the oesophagus, age and the duration of disease, there was no difference between the two groups. On the other hand, in patients with centromere antibodies lung involvement (22%) and joint involvement (35%) was significantly less common (P less than 0.01) than in all other scleroderma patients. Centromere antibodies and Scl-70 antibodies, which can be demonstrated already in the symptom-poor early phase of PSS, can thus be used as diagnostic parameters for different forms of PSS with differences in the degree of skin and organ involvement.

The value of electrogastrography for the diagnosis of gastroenterologic function

Abnormalities of gastric myoelectric activity can be measured by electrogastrography (EGG). Such dysfunctions can be associated with disorders of gastric motility. It was the aim of this study to investigate the relationship between gastric electrical activity and motility in patients with dyspepsia due to gastrointestinal or extraintestinal disease. 135 consecutive patients with dyspepsia (standardized score) were enrolled in this prospective study including patients with functional dyspepsia (FD) (n = 25), dyspepsia in diabetes mellitus type II (n = 27), hyperthyroidism (n = 23), progressive systemic scleroderma (PSS) (n = 20), chronic alcoholism (n = 20), and 20 patients with gastric lesions: gastric ulcer (n = 10) or gastric cancer (n = 10). The EGG measurements were performed over 60 min pre- and post-prandially state after ingestion of a solid-liquid test meal (370 kcal). The following parameters were measured: dominant electrical frequency (DF), percentage of DF in the normal frequency range (2-4 cpm), bradygastria (< 2 cpm), tachygastria (4-10 cpm), dominant frequency instability coefficient (DFIC), and power ratio. The data were compared with results in 40 healthy persons. The gastric emptying was determined by the gastric retention of 99mTc colloid after 60 min (gamma camera). Nearly 50% of FD patients had delayed gastric emptying (gastric retention after 60 min > 68%): they patients exhibited significantly more tachygastrias than those with normal gastric emptying (P < 0.05). Patients with diabetes mellitus type II, PSS and chronic alcoholism showed normal electrical activity, although gastric emptying was delayed in nearly 50%. The hyperthyroid patients had increased tachygastria without abnormal gastric motility. Gastric lesions did not produce pathological electrogastrograms. The dyspepsia score did not correlate with either EGG or radioscintigraphy in the various patient groups. Electrogastrography can detect tachygastrias, which are significantly increased in some patients with functional dyspepsia. Because of therapeutic consequences electrogastrography seems to be indicated in patients with functional dyspepsia.

Progressive systemic scleroderma. Clinical spectrum and prognostic parameters in 131 patients

The course of progressive systemic scleroderma was analysed from data collected on 131 patients. Classification was according to the extent of cutaneous involvement, type I (28%): sclerosis as far as the wrist-joint; type II (65%): sclerosis beyond the wrist-joint; type III (7%): sclerosis beginning to affect the trunk. In addition, they were subdivided into those with or without signs of systemic inflammation. The sex ratio was 3.5 females to 1 male. In half of the patients the disease manifested itself between the age of 30 and 50 years, with a clear peak about the 40th year. Serological evidence of inflammatory and immunological phenomena was present in nearly 50%, predominantly in those with type II or III. Oesophageal involvement was present in 84%, of the lung in 56% of all patients. ECG and echocardiographic changes were demonstrated in 34% of patients, while liver, intestines and kidneys were only rarely affected. The degree of organ involvement increased from type I to type III. Signs of systemic inflammation were predominantly associated with a clinically severe course.

The clinical picture and therapy of progressive systemic scleroderma

The clinical picture and therapy of progressive systemic scleroderma

Esophageal disease in progressive systemic sclerosis

Progressive systemic sclerosis (PSS) or scleroderma is characterized by fibrosis of the skin and visceral organs. Gastrointestinal disease occurs in up to 90% of patients, with the esophagus being the most commonly affected organ. Heartburn, dysphagia, and regurgitation occur in most patients. Esophageal manometry aids in diagnosing PSS. Endoscopy rules out complications, such as Barrett's esophagus, Candida esophagitis, and cancer. Lifestyle modifications should be implemented, including avoidance of alcohol, nicotine, and NSAIDs. Proton pump inhibitor therapy should be instituted, although it is unclear whether the dose should be adjusted according to symptoms or to 24-hour pH monitoring. Prokinetic agents are useful in the early stages of PSS when gastrointestinal musculature is still intact. Metoclopramide improves reflux, lower esophageal sphincter pressure, and gastric emptying but has an inconsistent effect on esophageal peristalsis. A decision on when to perform antireflux surgery, if at all, is controversial. Esophageal disease in PSS is a common and difficult-to-treat problem.

Anti‐chromatin and anti‐C1q antibodies in systemic lupus erythematosus compared to other systemic autoimmune diseases

Objective: To evaluate the prevalence, sensitivity, and specificity of anti‐chromatin and anti‐C1q antibodies in systemic lupus erythematosus (SLE) and lupus nephritis compared to small vessel vasculitis and other connective tissue diseases. To provide long‐term follow‐up data for anti‐chromatin antibodies in lupus nephritis.Methods: We determined the significance of anti‐nuclear antibodies (ANA), anti‐ double‐stranded DNA (anti‐dsDNA), anti‐chromatin, and anti‐C1q antibodies, as well as complement factors C3 and C4, in relation to disease activity in SLE patients with (n = 47; long‐term follow‐up data for 33 patients) and without (n = 31) biopsy‐confirmed lupus nephritis, microscopic polyangiitis (n = 37), Wegener's granulomatosis (n = 66), primary Sjögren's syndrome (n = 17), limited scleroderma (CREST syndrome) (n = 6), and progressive systemic scleroderma (PSS) (n = 11).Results: Anti‐chromatin antibodies were more specific and sensitive than anti‐C1q antibodies in distinguishing SLE patients from those with other systemic autoimmune diseases [anti‐chromatin: sensitivity 64.1%, specificity 99.2%, odds ratio (OR) 219.6; anti‐C1q: sensitivity 50%, specificity 72.6%, OR 2.65]. Anti‐C1q antibodies were present in 75% of patients with Sjögren's syndrome and 35.1% of patients with microscopic polyangiitis. Anti‐chromatin antibodies could identify SLE in patients with positive ANA but negative anti‐dsDNA antibodies. Persisting anti‐chromatin antibodies indicated SLE disease activity, even if anti‐dsDNA antibodies had become negative. In long‐term follow‐up, those SLE patients with negative anti‐dsDNA antibodies but persisting ANA and anti‐chromatin antibodies relapsed if immunosuppression had been tapered. Anti‐chromatin antibodies correlated with the SLE disease activity index (SLEDAI) as a marker of disease activity.Conclusions: The measurement of anti‐chromatin, but not anti‐C1q, antibodies in patients with systemic autoimmune diseases increases diagnostic sensitivity and specificity for SLE and assists in treatment decisions in anti‐dsDNA‐negative patients.

Progressive facial hemiatrophy complicated by sclerodactyly, Raynaud’s phenomenon, anti-ribonucleoprotein antibody, and trigeminal nerve disturbance

A Japanese woman was diagnosed as having progressive facial hemiatrophy when she was 26 years old. After 30 years, Raynaud's phenomenon and sclerodactyly suddenly appeared; at the same time, positive rheumatoid factor and anti-ribonucleoprotein (anti-RNP) antibody were noted on serological examinations. When she was 60 years old, trigeminal nerve disturbance also appeared. The associations between progressive facial hemiatrophy, systemic scleroderma, and trigeminal nerve disturbance are interesting and should be discussed.

Maladie de Wegener après exposition à la silice: Étude des mécanismes physiopathologiques

CRYSTALLINE SILICA: Crystalline silica is an abundant mineral found in multiple occupational exposures. It is a recognised occupational risk factor for some systemic auto-immune diseases such as progressive systemic scleroderma and Caplan-Colinet's syndrome, or just suspected in Goujerot-Sjögren's syndrome, periarteritis nodosa and systemic lupus erythematosus. WEGENER'S GRANULOMATOSIS: A rare disease of unknown of unknown aetiology, the disease is characterised by granulomatous vasculitis affecting the upper respiratory tracks, lungs and kidneys, associated with glomerulonephropathy. THE ROLE OF SILICA PARTICLES: Studies have shown that crystalline silica may be implied in Wegener's disease. Associated with other factors, notably with a genetic predisposal, silica particles might, through the release of reactive oxygen radicals and inflammatory cytokines, trigger-off immunopathological mechanisms. The latter would be manifested by exocytosis of the proteinase 3 and myeloperoxidase antigens on the surface of the polynuclear neutrophils.

Ischaemic stroke in progressive systemic sclerosis

Progressive systemic sclerosis (PSS) or scleroderma is a multisystem disease affecting the skin, lungs, myocardium, kidneys and gastrointestinal tract. Primary involvement of cerebral arteries in PSS has been reported but is very rare. A 61-year-old woman suffering from scleroderma for six years was hospitalised for two subsequent episodes of transient acute dysarthria and left hemiparesis. After five hours from the first onset of symptoms, she was submitted to brain magnetic resonance (MR) protocol that showed a right subinsular ischaemic lesion and whole right middle cerebral artery (MCA) territory hypoperfusion. Intracranial and epiaortic MR angiography reported a focal stenosis in the M2 portion of MCA. She was immediately treated with i.v. high dose steroids and oral acetylsalicylic acid. At one-month follow up, MR findings were confirmed. We have documented a cerebral infarct in a PSS patient. In our opinion, the ischaemic stroke was caused by a localised autoimmune angiopathy.

Detection of Enhanced Monohydroxyeicosatetraenoic Acid and F2-Isoprostane Levels in Human Plasma Samples after Extracorporeal Photoimmunotherapy

To investigate the involvement of reactive oxygen species in extracorporeal photoimmunotherapy (photopheresis), we have introduced two highly sensitive and specific techniques for the detection and quantitative measurement of oxygenated nonenzymatically formed arachidonic acid isomers [mono-hydroxyeicosatetraenoic acids (HETEs) and F₂-isoprostanes] by gas chromatography-mass spectrometry/negative ion chemical ionization (GC-MS/NICI) in plasma samples of patients suffering from cutaneous T-cell lymphoma and progressive systemic scleroderma II. The analysis of HETEs involved hydrogenation, solid phase extraction on a C₁₈ cartridge, formation of pentafluorobenzyl bromide and trimethylsilyl ether derivatives. In the case of F₂-isoprostanes, the analytical procedure was similar to that of HETEs except that the hydrogenation step was omitted. In the plasma of healthy volunteers picomole amounts of 2-, 5-, 8–12-, 15-HETEs, 8-iso-PGF_2α and 9α,11α-PGF_2α were quantified by using 12-hydroxy-heptadecatrienoic acid and PGF_2α-d₄ as internal standards of HETEs and isoprostanes, respectively. Analysis of plasma samples obtained from patients before and after extracorporeal photoimmunotherapy revealed characteristic increases in both, HETE and isoprostane levels. The enhancement of indicators of lipid peroxidation is in correspondence with a moderate loss of α-tocopherol, the most important lipid-soluble antioxidant in human plasma. Thus, our data confirm the involvement of lipid peroxidation in extracorporeal photoimmunotherapy.