1: Lancet 1982 Sep 25;2(8300):697-702

Toxic epidemic syndrome, Spain, 1981. Toxic Epidemic Syndrome Study Group.

The initial symptoms of a new multisystem disease probably caused by ingestion of denatured rapeseed oil were acute pleuropneumopathy, fever, headache, exanthems, myalgia, and eosinophilia. Later features were severe myalgia and thromboembolic accidents. The present phase of the illness is typified by scleroderma-like involvement, pulmonary arterial hypertension, and a neuromuscular syndrome. Nearly all the patients with these late changes are women. The pathological lesion is a peculiar form of non-necrotising vasculitis which primarily affects the intima.

PMID: 6126635 [PubMed - indexed for MEDLINE]

1: Am J Respir Crit Care Med 1998 Nov;158(5 Pt 1):1524-7

8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases.

Montuschi P, Ciabattoni G, Paredi P, Pantelidis P, du Bois RM, Kharitonov SA, Barnes PJ.

Imperial College School of Medicine at the National Heart and Lung Institute, Department of Thoracic Medicine, Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom.

Oxidative stress contributes to the pathophysiology of interstitial lung diseases, such as cryptogenic fibrosing alveolitis (CFA), fibrosing alveolitis associated with systemic sclerosis (FASSc) and sarcoidosis. F2-isoprostanes are a series of prostaglandin (PG) F2-like compounds produced in vivo independent of cyclooxygenase, as products of the radical-catalyzed lipid peroxidation. Measurement of the concentrations of F2-isoprostanes has proved to be valuable in assessing oxidative stress in vivo. The aim of this study was to measure 8-epi-PGF2alpha concentrations, one of the most abundant F2-isoprostane in humans, in bronchoalveolar lavage (BAL) in normal subjects and to compare them to those observed in patients with CFA (n = 9), FASSc (n = 8) and sarcoidosis (n = 10). 8-epi-PGF2alpha was detectable in BAL fluid in normal subjects (9.6 +/- 0.8 pg/ml) and its concentrations were increased approximately 5-fold in patients with CFA (47.4 +/- 7.0, p < 0.001) and FASSc (43.2 +/- 3.3, p < 0. 001). 8-epi-PGF2alpha was also increased in patients with sarcoidosis, although to a lesser extent (12.0 +/- 0.70 pg/ml, p < 0. 01). No correlation between 8-epi-PGF2alpha and either lung function tests or BAL cell types was observed in any group of patients. Our study shows that the level of oxidative stress is enhanced in patients with interstitial lung diseases as reflected by increased concentrations of 8-epi-PGF2alpha in BAL fluid.

PMID: 9817703 [PubMed - indexed for MEDLINE]

1: Curr Opin Rheumatol 1997 Nov;9(6):538-43

Role of metal-catalyzed oxidation reactions in the early pathogenesis of scleroderma.

Rosen A, Casciola-Rosen L, Wigley F.

Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

The observation that revelation of immunocryptic epitopes in self-antigens may initiate the autoimmune response has prompted the search for processes that induce novel autoantigen structure as potential initiators of autoimmunity. Recent studies have demonstrated that the autoantigens targeted in diffuse scleroderma are unified by their enrichment in nucleolini and by their susceptibility to fragmentation in a novel metal-dependent reaction that requires the generation of reactive oxygen species. Several other studies highlight the importance of reactive oxygen species as mediators of damage during ischemia-reperfusion and present evidence for increased generation of these radicals in patients with scleroderma. Together, these studies suggest a model for the pathogenesis of scleroderma in which metals and free radicals play a central, autoamplifying role.

Publication Types: Review Review, tutorial

PMID: 9375283 [PubMed - indexed for MEDLINE]

1: Postepy Hig Med Dosw 1997;51(3):285-303

[The role of free radicals in the etiopathogenesis of systemic sclerosis].

[Article in Polish]

Komosinska K, Olczyk K, Winsz K.

Katedra i Zaklad Chemii Klinicznej i Diagnostyki Laboratoryjnej Slaskiej Akademii Medycznej w Sosnowcu.

This article reviews the current concept in the ethiology and pathogenesis of systemic sclerosis. It is suggested that free radicals play a crucial role in pathomechanisms of scleroderma. In addition, the influence of some environmental agents (silica, bleomycin, alcohol, toxic oil) on free radical production and subsequent induction of scleroderma or scleroderma-like syndrome is also described.

Publication Types: Review Review, tutorial

PMID: 9333781 [PubMed - indexed for MEDLINE]

1: Arthritis Rheum 1995 Aug;38(8):1060-7

Increased susceptibility to oxidation of low-density lipoproteins isolated from patients with systemic sclerosis.

Bruckdorfer KR, Hillary JB, Bunce T, Vancheeswaran R, Black CM.

Department of Rheumatology, Royal Free Hospital School of Medicine, London, England.

OBJECTIVE. To examine the resistance to oxidation of low-density lipoproteins (LDL) from patients with systemic sclerosis (SSc) and primary Raynaud's phenomenon (RP) compared with healthy controls. METHODS. Plasma LDL were isolated from patients with diffuse cutaneous and limited cutaneous SSc (dcSSc and lcSSc, respectively), patients with primary RP, and healthy control subjects. The lipoproteins were assessed for their resistance to oxidation in the presence of cupric ions, using spectrophotometric assays. RESULTS. LDL from patients with dcSSc and lcSSc were more susceptible to oxidation than were those from healthy control subjects or patients with RP. CONCLUSION. Our findings suggest that free radicals may play a role in the pathology of SSc.

PMID: 7639801 [PubMed - indexed for MEDLINE]

1: Recenti Prog Med 1995 Apr;86(4):155-8

[Scleroderma induced by chemical agents. Description of a case and review of the literature].

[Article in Italian]

Biasi D, Carletto A, Caramaschi P, Pacor ML, Spinaci E, Bambara LM.

Istituto di Patologia Speciale Medica, Universita, Verona.

The authors describe a case of a 24 years old man affected by eosinophilic fasciitis likely due to chemical exposure. The patient handled and inhaled a compound containing sodium hypochlorite, sodium hydrate and cationic surface agents. The clinical picture was characterized by sudden onset, oedema and pain on the limbs; laboratory tests revealed an erythrocyte sedimentation rate of 55 mm/hour, polyclonal hypergammaglobulinemia and eosinophilia. The histologic examination of a deep musculo-cutaneous biopsy showed an infiltrate composed of lymphocytes and macrophages localized in the fascia and in the muscle; skin and subcutaneous tissue turned out normal. Corticosteroid treatment (prednisone at the starting dosage of 30 mg/day) produced the healing of the disease in 5 months. Afterwards the authors reviewed the literature about the different expressions of scleroderma that can be caused by chemicals; the most famous example is the "Spanish toxic oil syndrome". Various compounds were associated with development of scleroderma: plastic materials, solvents, silica powder, drugs, silicone prosthesis; the list will lengthen with reference to use of new products. It was hypothesized that the generation of free radicals was the common mechanism through which different aetiological agents can provoke scleroderma in genetically predisposed individuals. In these subjects free radicals can cause either direct tissue damages (endothelial lesion, thickening of intimal layer, fibrosis) and autoimmune phenomena.

PMID: 7617958 [PubMed - indexed for MEDLINE]

1: J Rheumatol 1994 Aug;21(8):1477-83

Micronutrient antioxidant status in patients with primary Raynaud's phenomenon and systemic sclerosis.

Herrick AL, Rieley F, Schofield D, Hollis S, Braganza JM, Jayson MI.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.

OBJECTIVE. To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud's phenomenon (RP) and in differentiating between patients with primary Raynaud's phenomenon (PRP) and those in whom Raynaud's is secondary to systemic sclerosis (SSc). METHODS. Four micronutrient antioxidants (selenium, vitamin E, beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects. RESULTS. Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers. CONCLUSION. Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value.

PMID: 7983650 [PubMed - indexed for MEDLINE]

1: Toxicology 2000 Nov 30;155(1-3):1-15

Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis.

Gabriele S, Alberto P, Sergio G, Fernanda F, Marco MC.

Department of Pediatrics, University of Florence, Institute of Internal Medicine, Italy.

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

Publication Types: Review Review, academic

PMID: 11154792 [PubMed - indexed for MEDLINE]

1: Clin Exp Rheumatol 2000 May-Jun;18(3):349-56

A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis.

Herrick AL, Hollis S, Schofield D, Rieley F, Blann A, Griffin K, Moore T, Braganza JM, Jayson MI.

University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK. Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

OBJECTIVE: To evaluate the effects of a combination of micronutrient antioxidants (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol in patients with limited cutaneous systemic sclerosis (SSc). METHODS: The study was designed as a placebo-controlled double-blind crossover study. A carryover effect was detected retrospectively for some of the prescribed antioxidants, and so the data were analysed as: (a) a between group comparison of the first 10 week treatment period; and (b) a within group comparison of the first and second 10-week periods in those who received placebo treatment first. Study end-points were plasma von Willebrand factor (vWF), thermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical parameters (fatty acid profiles, antioxidants and markers of free radical injury). RESULTS: Thirty-three patients were recruited. The median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the active-first group and 10 years (range 4 to 53 years) in the placebo-first group. In the 10-week study, there were no differences between the active and placebo groups in the change from baseline for vWF, for the parameters of the rewarming curve, or for patients' symptoms. Despite a rise in circulating antioxidant levels, there was no fall in markers of free radical mediated injury. In the 20-week cross-over study, patients did not experience any clinical benefit from active treatment compared to placebo. CONCLUSION: No clinical benefit could be demonstrated from active treatment. There are several possible explanations for this negative result, including the short duration of therapy. It is possible that antioxidant therapy, to be effective, needs to be given early in the SSc disease process, before the onset of irreversible tissue damage.

Publication Types: Clinical trial Randomized controlled trial

PMID: 10895372 [PubMed - indexed for MEDLINE]

1: J Invest Dermatol 1999 Nov;113(5):843-7

Effect of superoxide dismutase on bleomycin-induced dermal sclerosis: implications for the treatment of systemic sclerosis.

Yamamoto T, Takagawa S, Katayama I, Mizushima Y, Nishioka K.

Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.

Bleomycin has a chemical toxicity capable of inducing superoxide radicals, which are suggested to play an important part in bleomycin-induced pulmonary fibrosis. We have recently established a mouse model for scleroderma induced by repeated local injections of bleomycin. In this study, we examined the inhibitory effect of superoxide dismutase on the development of dermal sclerosis induced by bleomycin using this mouse model. PC-superoxide dismutase, which is a lecithinized superoxide dismutase with high tissue accumulation and long half-life in blood, was administered (3000 U per kg; dissolved in 5% mannitol) 3 h before the injection of bleomycin in C3H mice for 3 wk. Systemic PC-superoxide dismutase markedly inhibited the development of dermal sclerosis, which was also accompanied by a decrease in the number of infiltrating mast cells and eosinophils. Furthermore, the hydroxyproline content in the skin was significantly reduced, as compared with mice treated with bleomycin only or bleomycin and 5% mannitol. In a separate experiment, after the development of dermal sclerosis following treatment with bleomycin for 3 wk, PC-superoxide dismutase was administered for 2 wk. Histologic examination again revealed a reduction of dermal sclerosis, followed by a significant associate in the number of both mast cells and eosinophils. The hydroxyproline content in the skin was not significantly decreased, however, even after injections of high amounts of PC-superoxide dismutase (30,000 U per kg). These results support the involvement of oxygen free radicals in bleomycin-induced dermal sclerosis, and also indicate that administration of superoxide dismutase may be effective in the therapeutic approach in systemic sclerosis.

PMID: 10571743 [PubMed - indexed for MEDLINE]

1: Mol Cell Biochem 1999 Jun;196(1-2):85-91

Oxidative stress in Systemic Sclerosis.

Simonini G, Cerinic MM, Generini S, Zoppi M, Anichini M, Cesaretti C, Pignone A, Falcini F, Lotti T, Cagnoni M.

Department of Pediatrics, University of Florence, Italy.

In 63 patients affected by Systemic Sclerosis (SSc) (limited subset: 40; diffuse subset: 23; early: 30; advanced: 33) the peroxidation product diene-conjugates (DC) and antibodies against oxidised low density lipoproteins (Ab oxLDL) were tested in serum by a spectrophotometer (absorbance 234 mn) and by a standard ELISA respectively. The data were compared with those obtained by 21 healthy subjects. DC was significantly higher in patients (73.3 +/- 37.2 microM/l; p < 0.0001) than in controls (48.4 +/- 16.7) as well as in the limited (80 +/- 48.8; p < 0.05) than in the diffuse subset (64.5 +/- 36.4); and in early (84.1 +/- 31.4; p < 0.05) than in advanced stage of the disease (67.9 +/- 42.5). The levels of Ab oxLDL were significantly higher in SSc patients (309.5 +/- 367.2 mU/ml; p < 0.0001) in all its subsets (limited: 351.9 +/- 351.1, p < 0.0001; diffuse: 207.7 +/- 316.1, p < 0.05; early: 428.9 +/- 417.1, p < 0.001; advanced: 302.7 +/- 89.9, p < 0.0001) than in controls (89.3 +/- 29.1). These antibodies levels were higher in limited subset than in diffuse (p < 0.05) and in early SSc than in advanced SSc (p < 0.05). The highest values of parameters of oxidative stress are found in the early stages, when the episodes of reperfusion after ischemic episodes (Raynaud's phenomenon) are very frequent. Moreover, the damage is higher in the early stages of SSc, with intact microvessels, than in late stages, when microvessels are very reduced in number, destroyed by the worsening of the disease. These data show that the respiratory burst deduced by the lipoperoxidation is higher in SSc than in controls, and may be an important pathogenetic factors involved in tissue changes in SSc.

PMID: 10448906 [PubMed - indexed for MEDLINE]

1: Clin Rheumatol 2001;20(1):70-2

Clinical manifestation of POEMS syndrome with features of connective tissue disease.

Eidner T, Oelzner P, Ebhardt H, Kosmehl H, Stein G, Hein G.

Department of Internal Medicine IV, Friedrich-Schiller-University of Jena, Germany. Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare plasma cell disease with multiorgan involvement and varying clinical manifestations. We report a 38-year-old man who presented with scleroderma-like skin changes of the hands and feet, sicca and Raynaud's syndrome, pleural effusions, glomerulopathy, polyneuropathy, hepatosplenomegaly and lymphadenopathy. Steroid treatment was started on the assumption of a connective tissue disease and led to a temporary improvement. During the further course of the disease, hypothyreosis, monoclonal gammopathy and osteosclerotic bone lesions were detected, leading to the diagnosis of POEMS syndrome. This case emphasises the need to consider POEMS syndrome as a differential diagnosis in patients with signs of connective tissue disease and polyneuropathy.

PMID: 11254247 [PubMed - in process]

1: Med J Aust 1977 Jun 11;1(24):887

Treatment of scleroderma.

Meyers D.

A case of scleroderma is presented. Considerable relief of symptoms, healing of ulcers and increased skin and joint mobility occurred. The progressive improvement of the patient's condition was probably due more to potassium para-aminobenzoate (KPAB) than to resurpine.

PMID: 301981 [PubMed - indexed for MEDLINE]

1: Arthritis Rheum 2001 Mar;44(3):653-61

The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high-dose versus low-dose penicillamine in systemic sclerosis trial.

Clements PJ, Wong WK, Hurwitz EL, Furst DE, Mayes M, White B, Wigley F, Weisman M, Barr W, Moreland L, Medsger TA Jr, Steen V, Martin RW, Collier D, Weinstein A, Lally E, Varga J, Weiner SR, Andrews B, Abeles M, Seibold JR.

UCLA School of Medicine, Los Angeles, California 90095-1670, USA.

OBJECTIVE: To explore the clinical implications of a score of > or =1.0 on the Disability Index of the Health Assessment Questionnaire (HAQ DI) at the first patient visit, and to examine the implications of improvement in HAQ DI score over 2 years in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: SSc skin and visceral involvement was assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD disease duration of 10 +/- 4 months) when they entered a multicenter drug trial and again 2 years later. Mortality and the occurrence of scleroderma renal crisis were assessed for a mean +/- SD of 4.0 +/- 1.1 years. Logistic and linear regression analyses were used to examine the relationship of the baseline HAQ DI score to morbidity, mortality, and visceral involvement, as well as the relationship of changes in the HAQ DI score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline HAQ DI score of > or =1.0 was predictive of mortality (odds ratio 3.22, 95% confidence interval 1.097-9.468) over 4 years. Multivariate linear regression demonstrated that a model which included the erythrocyte sedimentation rate at baseline (P = 0.005) and changes at 2 years in the swollen joint count (P = 0.002), total skin score (P = 0.005), and white blood cell count (P = 0.005) best explained the change in HAQ DI score over 2 years (R2 = 0.528). The HAQ DI score and total skin score at baseline were highly correlated (correlation coefficient 0.368), as were changes in the HAQ DI score and the total skin score over 2 years (correlation coefficient 0.492). Although the HAQ DI score was heavily influenced by hand dysfunction at baseline and at 2 years, improvement (reduction) in the HAQ DI score over 2 years was related to factors other than hand dysfunction. CONCLUSION: A baseline HAQ DI score of > or =1.0 predicted mortality over 4 years. Improvement in the HAQ DI score in these patients with diffuse scleroderma was associated with improvement in skin thickening, hand function, oral aperture, lung function, signs of arthritis, serum creatinine level, and the investigator's global assessment of improvement. The HAQ DI is a self-administered questionnaire that SSc patients can complete easily and rapidly and that gives the practicing physician important information about prognosis, patient status, and changes in disease course over time.

PMID: 11263780 [PubMed - in process]

1: Arthritis Rheum 2001 Mar;44(3):662-5

Cytochrome P2 polymorphisms and susceptibility to scleroderma following exposure to organic solvents.

Povey A, Guppy MJ, Wood M, Knight C, Black CM, Silman AJ.

University of Manchester, UK.

OBJECTIVE: To determine whether there are specific cytochrome P450 (CYP2) alleles that increase susceptibility to scleroderma in individuals who have been exposed to organic solvents. METHODS: CYP alleles at 2 loci, 2E1 and 2C19, were compared in 7 patients who had developed scleroderma after exposure to solvents versus 71 patients with scleroderma without solvent exposure ("sporadic" disease) and 106 population controls. RESULTS: The 2E1*3 allele was found in 2 of the 7 patients who had been exposed to organic solvents, with a greater frequency than occurred in either the disease controls or the population controls (odds ratio [95% confidence interval] 9.1 [1.5-59.1] and 10.2 [1.8-62.2], respectively). All 7 patients with solvent exposure carried the 2C19EM genotype, compared with 89% of patients with sporadic scleroderma. CONCLUSION: Our results suggest that alleles at CYP loci may be involved in increasing susceptibility to scleroderma among subjects who have been exposed to organic solvents.

PMID: 11263781 [PubMed - in process]

1: Minerva Cardioangiol 2001 Apr;49(2):127-30

Systemic sclerosis (scleroderma). A case of recovery of cardiomyopathy after vitamin E treatment.

Morelli S, Sgreccia A, Bernardo ML, Gurgo Di Castelmenardo A, Petrilli AC, De Leva R, Nuccio F, Calvieri S.

Universita degli Studi La Sapienza, Rome, Italy.

A 60-year-old woman with systemic sclerosis, systemic hypertension, and chronic renal failure, presented with clinical manifestations of heart failure. An echocardiogram showed a mildly dilated left ventricle and global hypokinesis. A six-month treatment including reduced sodium intake, furosemide, and nifedipine did not change the clinical and instrumental findings. Casually, vitamin E (600 mg daily) was added. After 6 months, clinical manifestations of heart failure were disappeared and the echocardiogram showed a normally-sized left ventricle with normal wall motion.

PMID: 11292956 [PubMed - in process]

1: Drugs 2001;61(3):419-27

Drug treatment of scleroderma.

Leighton C.

Pharmacy Department, Royal Free Hospital, London, England. Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

Scleroderma or systemic sclerosis is a rare condition with many clinical manifestations including Raynaud's phenomenon. As with many other rarely encountered diseases, drug therapy for scleroderma is often empirical with little evidence in the form of randomised controlled trials to aid drug choice. Raynaud's phenomenon has been recognised for well over 100 years. A considerable number of clinical trials in this area have demonstrated unequivocally the use of nifedipine as a gold standard. Large studies have also demonstrated the efficacy of iloprost. However, this drug is not as yet licensed for scleroderma in the UK or elsewhere. This presents an additional problem as information regarding the use and administration of unlicensed drugs is often sparse and post-marketing surveillance to assess safety is not routinely performed. When looking at the other distinct conditions encountered by a patient with scleroderma it becomes evident that trials are often retrospective or limited in patient numbers. Studies investigating the use of methotrexate, antithymocyte globulin and cyclophosphamide in patients with scleroderma have been very small and in some cases not well designed. The major work on penicillamine was a retrospective trial. Again these drugs are not licensed for use in scleroderma. Drug therapy for pulmonary hypertension secondary to scleroderma closely follows that outlined for primary pulmonary hypertension. In the US there is a patient registry for primary pulmonary hypertension that has enabled well designed, large-scale studies to demonstrate the benefits of epoprostenol in severe primary pulmonary hypertension. Hence, research in this area has progressed considerably over the last decade. Clearly, a considerable amount of work is being carried out to elucidate new treatment regimens for scleroderma, however, evaluation of these studies is proving to be a difficult process. Designated hospital centres for scleroderma (there are currently 2 in the UK), better markers of disease activity and methods to measure improvement or deterioration in affected organs, should enable research into aetiology, disease progression and treatment to be carried out on a larger scale resulting, hopefully, in more conclusive answers.

PMID: 11293650 [PubMed - in process]

1: Bratisl Lek Listy 2000;101(11):614-6

[Skin manifestations of Lyme borreliosis--occurrence, diagnosis, therapy].

[Article in Slovak]

Svecova D, Buchvald J.

Dermatovenerologicka klinika LFUK v Bratislave. Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!

Eight genotypes of Borrelia burgdorferi are known currently. In Slovakia (Carpathian Euroregion) the most frequent genotypes are B. garini, B. afzelii, as well as B. valaisiana and B. lusitaniae. Infestation of the vector Ixodes ricinus is 3-30%. The most frequent early skin manifestation is erythema migrans (60-70%). Borrelia burgdorferi is suggested to be the causative agent in sclerodermia circumscripta, lichen sclerosus et atrophicus, maybe also in urticaria chronica, granuloma anulare, erythema anulare, erythema nodosum. It can be the causative agent also in neurological diagnoses as e.g. chronic oligosymptomatic encephalopathy, "sclerosis multiplex-like" syndrome and fatigue syndrome, arthralgia, myalgia, seronegative indifferentiated oligoarthritis and fibromyalgies. The serological diagnosis has to be coincide with clinical findings. Used serological examinations are ELISA, Immunoblot, indirect immunofluorescence examination. PCR is an important contribution in examination of synovial fluid (85% detection) and cerebrospinal liquor (24-100%). The importance of PCR is stressed in cases with mixed infections by several borrrelia genotypes. The first line treatment includes doxyciclin, amoxicilin, and erythromycin. The second line includes macrolides, cephalosporines. New perspectives are ascribed to active immunisation with recombined antigen OsA (LYMErix, ImuLyme).

PMID: 11218959 [PubMed - indexed for MEDLINE]

1: Ter Arkh 2000;72(10):60-4

[Effect of vazaprostan on microcirculation in patients with scleroderma systematic].

[Article in Russian]

Alekperov RT, Mach ES, Guseva NG.

AIM: To investigate the effect of vazaprostan (alprostadil) on skin blood flow in patients with sclerodermia systematica (SS). MATERIAL AND METHODS: A total of 51 patients with SS aged 33-70 years were included in the study. 33 of them received a 3-hour infusion of vazaprostan at the standard dose for 20 consecutive days. The rest 18 patients received low molecular dextran solution. Before and at the end of the treatment digital skin microcirculation was measured with a laser Doppler flowmeter. The laser probe was attached to the distal pad of the ring finger on the left hand. Baseline blood flow and vascular reactivity in the tests with sympathetic stimulation, local heating and during orthostasis were evaluated. RESULTS: Baseline blood flow and vascular response to functional tests were significantly reduced in all the patients. At the end of the treatment the flow increased only in patients treated with vazaprostan. Vascular reactivity was not changed after the treatment in both groups of patients. CONCLUSION: Vazaprostan increases baseline blood flow and contributes to the improvement of microcirculation in patients with SS.

PMID: 11220881 [PubMed - indexed for MEDLINE]