Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

Aberrant immune response with consequent vascular and connective tissue remodeling - causal to scleroderma and associated syndromes such as Raynaud phenomenon and other fibrosing syndromes?

PubMed

Durmus, Nedim; Park, Sung-Hyun; Reibman, Joan; Grunig, Gabriele

2016-11-01

Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc)-associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases.

Linear scleroderma associated with ptosis and motility disorders.

PubMed Central

Suttorp-Schulten, M S; Koornneef, L

1990-01-01

A case is reported in which an 11-year-old girl developed progressive ptosis and a subsequent motility disorder of the right eye. The diagnosis linear scleroderma en coup de sabre was established. Atrophy of the upper levator palpebral and superior rectus muscle could be shown on CT scan. Images PMID:2223709

JUVENILE SCLERODERMA-what has changed in the meantime?

PubMed

Adrovic, Amra; Sahin, Sezgin; Barut, Kenan; Kasapcopur, Ozgur

2018-04-22

Juvenile scleroderma is a rarely seen chronic connective tissue disorder characterized by stiffening of the skin. The frequency of the disease was reported as one per million. According to organ involvement, the disease is divided into two main forms: systemic and localized scleroderma. Since it is uncommon in children, many aspects of the disease remain discussable. With this review, we aimed to revise recent findings and new developments in this rare condition. Skin manifestations are most prominent feature of the systemic form, followed by musculoskeletal and vascular involvement. Cardiovascular, gastrointestinal and renal disorders are rare in childhood. Combination of disease modifying antirheumatic drugs (methotrexate, mycophenolate-mofetil, cyclosporine) and steroid reprents the first line therapy. Bosentan is used for cases with pulmonary hypertension and for extensive digital ulcerations. Biological treatment emerges as a useful treatment option in most severe form of the disease. Localized scleroderma is characterized with sclerodermatosis of the skin. Internal organ involvement is not expected. Classification of the local scleroderma is made according to the size and localization of the skin changes. There are few different therapeutical options but there is no specific therapy for the localized scleroderma. Many data regarding disease features and treatment options in juvenile scleroderma are based on studies among adults. There is a striking need for multicentric, prospective studies among children with juvenile scleroderma.Emerging biological agents and new treatment options are showing promising results. Anyhow, juvenile scleroderma remains a mystery with many aspects of the disease waiting to be solved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Colchicine in therapy. State of the art and new perspectives for an old drug.

PubMed

Famaey, J P

1988-01-01

Colchicine is the most specific treatment in acute gouty attacks. In several European countries, oral colchicine is still used for routine treatment of acute gout. Its selectivity is used as a diagnostic tool. It is also active in the treatment of acute crises of chondrocalcinosis and more occasionally of other arthritic crises (e.g. sarcoidosis). Colchicine appears to be the necessary adjuvant prophylactic drug when starting a hypouricemic treatment with uricosuric or uricolytic drugs for avoiding acute gouty crisis due to sudden mobilisation of the uric acid pool. Besides gout, colchicine is the drug of choice for treating familial mediterranean fever. It appears to be helpful in the treatment of Behçet's disease. It seems also useful for treating fibrosing conditions such as liver cirrhosis and scleroderma. As an adjuvant therapy, it helps treating dermatological disorders which are associated with leucocyte migration as an essential pathogenic factor (e.g. psoriasis, dermatitis herpetiformis, necrotising vasculitis ...). It has been advocated as an adjuvant therapy in malignant diseases as a support in radiotherapy and as an useful drug in various other diseases where it has been tried occasionally (e.g. Paget's disease of the bone, idiopathic thrombocytopenic purpura, disc syndrome). This very old drug remains a modern therapeutic agent.

Presentations and treatment of childhood scleroderma: localized scleroderma, eosinophilic fasciitis, systemic sclerosis, and graft-versus-host disease.

PubMed

Hedrich, Christian Michael; Fiebig, Barbara; Hahn, Gabriele; Suttorp, Meinolf; Gahr, Manfred

2011-07-01

Juvenile scleroderma is a rare connective tissue disease that involves the skin and subcutaneous tissue. Among all presentations of juvenile scleroderma, localized scleroderma (JLSc) is the most frequent, followed by systemic disease (JSSc) and eosinophilic fasciitis (EF). In posttransplantation chronic graft-versus-host disease (GvHD), scleroderma-like skin involvement can occur. Systemic forms of juvenile scleroderma and GvHD can affect the internal organs, such as the lungs, the gastrointestinal tract, the heart, and kidneys and cause disability and severe, sometimes lethal, complications. Here, the authors give an overview of different presentations of juvenile scleroderma. They report their experience with the different forms and presentations of scleroderma, diagnostic workups, treatment, and outcome of all forms of childhood scleroderma in the context of the existing literature.

Dental Care in Scleroderma

MedlinePlus

Dental Care in Scleroderma People living with scleroderma face unique challenges while trying to maintain their oral ... They are more likely to be affected by dental conditions such as small mouth, dry mouth, jaw ...

Role of Semaphorin 7a signaling in TGF-β1 induced lung fibrosis and scleroderma-related interstitial lung disease

PubMed Central

Gan, Ye; Reilkoff, Ronald; Peng, Xueyan; Russell, Thomas; Chen, Qingsheng; Mathai, Susan K.; Homer, Robert; Gulati, Mridu; Siner, Jonathan; Elias, Jack; Bucala, Richard; Herzog, Erica

2012-01-01

Objective Semaphorin (Sema) 7a regulates TGF- β1 induced fibrosis. Using a murine model of pulmonary fibrosis in which an inducible, bioactive form of the human TGF- β1 gene is overexpressed in the lung, we tested the hypothesis that Sema-7a exerts its pro-fibrotic effects in part by promoting the tissue accumulation of CD45+ fibrocytes. Methods Fibrosis and fibrocytes were evaluated in TGF- β1 transgenic mice in which the Sema-7a locus had been disrupted. The effect of replacement or deletion of Sema-7a on bone marrow derived cells was ascertained using bone marrow transplantation. The role of the Sema-7a receptor β1 integrin was assessed using neutralizing antibodies. The applicability of these findings to TGF-β1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease. Results The appearance of fibrocytes in the lungs in TGF- β1 transgenic mice requires Sema-7a. Replacement of Sema-7a in bone marrow derived cells restores lung fibrosis and fibrocytes. Immunoneutralization of β1 integrin reduces pulmonary fibrocytes and fibrosis. Peripheral blood mononuclear cells from patients with scleroderma-related interstitial lung disease show increased mRNA for Sema-7a and the β1 integrin, with Sema-7a located on collagen producing fibrocytes and CD19+ lymphocytes. Peripheral blood fibrocyte outgrowth is enhanced in these patients. Stimulation of normal human peripheral blood mononuclear cells with recombinant Sema-7a enhances fibrocyte differentiation; these effects are attenuated by β1 integrin neutralization. Conclusion Interventions that reduce Sema-7a expression or prevent the Sema-7a - β1 integrin interaction may be ameliorative in TGF- β1-driven or fibrocyte-associated autoimmune fibroses. PMID:21484765

A Case of Localized Scleroderma in a Sculptor and His Wife

PubMed Central

Bakst, Richard; Kovarik, Carrie; Werth, Victoria P.

2011-01-01

SUMMARY The etiology of localized scleroderma is unknown, and its pathogenetic relationship to its systemic counterpart is unclear. Environmental exposures, notably to silica dust, have long been suspected in the pathogenesis of the disorder. However, its’ relationship to the localized variant has not been well described. Here we present two cases of localized scleroderma in a sculptor and his wife who have extensive exposure to silica dust. PMID:19955998

Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism

PubMed Central

Yamakoshi, Yoshiki

2016-01-01

Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer–Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method. PMID:27479094

Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism.

PubMed

Yamakoshi, Yoshiki; Motegi, Sei-Ichiro; Ishikawa, Osamu

2016-01-01

Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer-Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method.

Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

PubMed

Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

2009-08-01

Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

Determinants of mortality in systemic sclerosis: a focused review.

PubMed

Poudel, Dilli Ram; Jayakumar, Divya; Danve, Abhijeet; Sehra, Shiv Tej; Derk, Chris T

2017-11-07

Scleroderma (systemic sclerosis) is an autoimmune rheumatic disorder that is characterized by fibrosis, vascular dysfunction, and autoantibody production that involves most visceral organs. It is characterized by a high morbidity and mortality rate, mainly due to disease-related complications. Epidemiological data describing mortality and survival in this population have been based on both population and observational studies. Multiple clinical and non-clinical factors have been found to predict higher likelihood of death among thepatients. Here, we do an extensive review of the available literature, utilizing the PubMed database, to describe scleroderma and non-scleroderma related determinants of mortality in this population. We found that even though the mortality among the general population has declined, scleroderma continues to carry a very high morbidity and mortality rate, however we have made some slow progress in improving the mortality among scleroderma patients over the last few decades.

Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma.

PubMed

Budzyńska-Włodarczyk, Jolanta; Michalska-Jakubus, Małgorzata M; Kowal, Małgorzata; Krasowska, Dorota

2016-02-01

Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. To determine concentrations of interleukin (IL)-27, transforming growth factor (TGF)-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. The study encompassed 17 females with localized scleroderma (aged 25-67). The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

[When thinking to scleroderma?].

PubMed

Cogan, E

2007-09-01

Scleroderma encompasses an heterogeneous group of autoimmune disorders characterized by an hidebound thickened skin involvement. When the changes are limited to the skin, localized scleroderma is suspected. Although the latter is most often a benign disease, it may be exceptionally associated with involvement of multiple organs, mainly the neurological system. At the opposite, systemic sclerosis is a serious disorder associated with high morbidity and even mortality and defined by an extended skin sclerosis, multiple organ involvement and general symptoms. Raynaud phenomena is nearly always present at the beginning of the disease. Identifying initial manifestations of the disease (Raynaud phenomena, diffuse non pitting edema, symmetrical polyarthritis with tendon friction rubs, dysphagia associated with mucosal telangiectasia) may allow the clinician to rapidly transfer the patient to a specialized reference center in order to organize a multidisciplinary approach and to prompt optimum therapy.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide.

PubMed

Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

2011-07-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors.

Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

PubMed Central

2011-01-01

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors. PMID:21722364

Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

PubMed

Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

2012-06-01

Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

Neurologic Involvement in Scleroderma en Coup de Sabre

PubMed Central

Amaral, Tiago Nardi; Marques Neto, João Francisco; Lapa, Aline Tamires; Peres, Fernando Augusto; Guirau, Caio Rodrigues; Appenzeller, Simone

2012-01-01

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs. PMID:22319646

Esophageal dysmotility in scleroderma: a prospective study of 183 cases.

PubMed

Lahcene, M; Oumnia, N; Matougui, N; Boudjella, M; Tebaibia, A; Touchene, B

2009-01-01

The goal of the study was to evaluate the prevalence and risk factors of esophageal motor disorders in systemic sclerosis. In 183 consecutive cases of scleroderma, as diagnosed by American College of Rheumatology criteria (1980). Patients' mean age was 40.6+/-13.3 years, the gender ratio was 0.13 and the average duration of disease was 6.8+/-7.5 years. A localized, cutaneous form was observed in 148 patients (81%) and a diffuse form in 35 (19%). All patients underwent upper gastrointestinal endoscopy and standard esophageal manometry. Esophageal symptoms and reflux esophagitis were found in 108 (59%) and 68 (37%) of patients, respectively. Esophageal motor disorders were present in 148 patients (81%), and were associated with a hypotensive lower esophageal sphincter in 114 (62%). The presence of these motor abnormalities was not related to age, gender, skin extension or duration of disease. Esophageal motor disorders were present in almost all patients with esophageal symptoms or esophagitis, and were also found in 48 (64%) of the asymptomatic patients. Esophageal motor disorders are frequently seen in scleroderma, especially in cases with clinical symptoms, but are not associated with a specific form of the disease.

Lung Involvement in Systemic Sclerosis

PubMed Central

Hassoun, Paul M.

2011-01-01

Summary Scleroderma is a multisystem disease characterized by a severe inflammatory process and exuberant fibrosis. Lung involvement is a frequent complication and a leading cause of morbidity and mortality in this syndrome. Two major pulmonary syndromes are associated with scleroderma; a pulmonary vascular disorder evolving over time into relatively isolated pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD). Each syndrome, when present, is a cause of morbidity and significantly reduces survival of scleroderma patients when compared to patients free of lung complication. When pulmonary hypertension and ILD are combined, survival is further reduced. Current therapy appears to have no meaningful effect on either condition and, thus, there is a need for better understanding of underlying pathogenic mechanisms. This review focuses on clinical, diagnostic, and therapeutic features of PAH and ILD as well as other frequent but less debilitating lung complications of scleroderma. PMID:21195581

German guidelines for the diagnosis and therapy of localized scleroderma.

PubMed

Kreuter, Alexander; Krieg, Thomas; Worm, Margitta; Wenzel, Jörg; Moinzadeh, Pia; Kuhn, Annegret; Aberer, Elisabeth; Scharffetter-Kochanek, Karin; Horneff, Gerd; Reil, Emma; Weberschock, Tobias; Hunzelmann, Nicolas

2016-02-01

Localized scleroderma designates a heterogeneous group of sclerotic skin disorders. Depending on the subtype, severity, and site affected, adjacent structures such as adipose tissue, muscles, joints, and bones may be involved. This is an update of the existing German AWMF (Association of the Scientific Medical Societies in Germany) guidelines (classification: S2k). These guidelines provide an overview of the definition, epidemiology, classification, pathogenesis, laboratory workup, histopathology, clinical scoring systems, as well as imaging and device-based workup of localized scleroderma. Moreover, consensus-based recommendations are given on the management of localized scleroderma depending on its clinical subtype. Treatment recommendations are presented in a therapeutic algorithm. No financial support was given by any pharmaceutical company. The guidelines are valid until July 2019. © 2016 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.

Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8.

PubMed

Ah Kioon, Marie Dominique; Tripodo, Claudio; Fernandez, David; Kirou, Kyriakos A; Spiera, Robert F; Crow, Mary K; Gordon, Jessica K; Barrat, Franck J

2018-01-10

Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the secretion of CXCL4 is under the control of phosphatidylinositol 3-kinase δ and is due to the aberrant presence of TLR8 on pDCs of SSc patients, which is not seen in healthy donors or in lupus pDCs, and that CXCL4 primarily acts by potentiating TLR8- but also TLR9-induced IFN production by pDCs. Depleting pDCs prevented disease in a mouse model of scleroderma and could revert fibrosis in mice with established disease. In contrast, the disease was exacerbated in mice transgenic for TLR8 with recruitment of pDCs to the fibrotic skin, whereas TLR7 only partially contributed to the inflammatory response, indicating that TLR8 is the key RNA-sensing TLR involved in the establishment of fibrosis. We conclude that the pDC is an essential cell type involved in the pathogenesis of SSc and its removal using depleting antibodies or attenuating pDC function could be a novel approach to treat SSc patients. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Capillaroscopic findings in systemic sclerosis -- are they associated with disease duration and presence of digital ulcers?

PubMed

Lambova, Sevdalina; Müller-Ladner, Ulf

2011-11-01

The aim of the study was to evaluate capillaroscopic pattern in systemic sclerosis (SSc) patients and its association with disease duration as well as with presence of digital ulcers. Thirty six patients with SSc were included in the study. The severity of Raynaud's phenomenon (RP) at the hands was assessed with VAS (100mm), and the presence of digital ulcers at the hands was documented. Nailfold capillaroscopy was performed by a videocapillaroscope. RP was found as a clinical symptom in 100% (36/36) of the examined SSc patients. In SSc patients with a duration of the disease of less than 3 years, an early phase "scleroderma type" capillaroscopic pattern was found in 50% (5/10) of the cases. In the group of SSc patients with a duration of the disease of more than 3 years, late phase scleroderma type capillaroscopic pattern was found in 26.9% (7/26) of the cases, which was characterized by the presence of extensive, "desert-like" avascular areas and neoangiogenic capillaries. Scleroderma type capillaroscopic pattern was found in 97.2% (35/36) of the cases. Digital ulcers at the hands were found in 36.1% (13/36) of the patients. In 100% of those patients with digital ulcers (13/13), an active type scleroderma like pattern was observed, which is characterized by the presence of frequent giant capillaries, hemorrhages, and avascular areas. An active type scleroderma like pattern was found in 47.2% (17/36) of the patients without digital ulcers. The data show that the presence of digital ulcers at the hands of SSc patients is strongly associated with an active type scleroderma like capillaroscopic pattern. Observation of an active type scleroderma like pattern in patients without digital ulcers may therefore be used as a predictor for the development of trophic changes in the future, an indication for vasoactive medication for the prevention of the development of digital ulcers, and as an additional objective method for the evaluation of disease activity score in SSc.

Localized scleroderma: a series of 52 patients.

PubMed

Toledano, C; Rabhi, S; Kettaneh, A; Fabre, B; Fardet, L; Tiev, K P; Cabane, J

2009-05-01

Localized scleroderma also called morphea is a skin disorder of undetermined cause. The widely recognized Mayo Clinic Classification identifies 5 main morphea types: plaque, generalized, bullous, linear and deep. Whether each of these distinct types has a particular clinical course or is associated with some patient-related features is still unclear. We report here a retrospective series of patients with localized scleroderma with an attempt to identify features related to the type of lesion involved. The medical records of all patients with a diagnosis of localized scleroderma were reviewed by skilled practitioners. Lesions were classified according to the Mayo Clinic Classification. The relationship between each lesion type and various clinical features was tested by non-parametrical methods. The sample of 52 patients included 43 females and 9 males. Median age at onset was 30 y (range 1-76). Frequencies of patients according to morphea types were: plaque morphea 41 (78.8%) (including morphea en plaque 30 (57.7%) and atrophoderma of Pasini-Pierini 11 (21.1%)), linear scleroderma 14 (26.9%). Nine patients (17.3%) had both types of localized scleroderma. Median age at onset was lower in patients with linear scleroderma (8 y (range 3-44)) than in others (36 y (range 1-77)) (p=0.0003). Head involvement was more common in patients with linear scleroderma (37.5%) than in other subtypes (11.1%) (p=0.05). Atrophoderma of Pasini-Pierini was never located at the head. Systemic symptoms, antinuclear antibodies and the rheumatic factor were not associated with localized scleroderma types or subtypes. These results suggest that morphea types, in adults are not associated with distinct patient features except for age at disease onset (lower) and the localization on the head (more frequent), in patients with lesions of the linear type.

Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland.

PubMed

Herrick, Ariane L; Ennis, Holly; Bhushan, Monica; Silman, Alan J; Baildam, Eileen M

2010-02-01

Childhood scleroderma encompasses a rare, poorly understood spectrum of conditions. Our aim was to ascertain the incidence of childhood scleroderma in its different forms in the UK and Ireland, and to describe the age, sex, and ethnicity of the cases. The members of 5 specialist medical associations including pediatricians, dermatologists, and rheumatologists were asked to report all cases of abnormal skin thickening suspected to be localized (including linear) scleroderma or systemic sclerosis (SSc) in children <16 years of age first seen between July 2005 and July 2007. We received notification of 185 potential cases, and 94 valid cases were confirmed: 87 (93%) with localized scleroderma and 7 (7%) with SSc. This gave an incidence rate per million children per year of 3.4 (95% confidence interval [95% CI] 2.7-4.1) for localized scleroderma, including an incidence rate of 2.5 (95% CI 1.8-3.1) for linear scleroderma, and 0.27 (95% CI 0.1-0.5) for SSc. Of the 87 localized cases, 62 (71%) had linear disease. Of localized disease cases, 55 (63%) were female, 71 (82%) were classified as white British, and the patients' mean age when first seen in secondary care was 10.4 years. Of the 7 SSc cases, all were female, 6 (86%) were white British, and the mean age when first seen was 12.1 years. The median delay between onset and being first seen was 13.1 months for localized scleroderma and 7.2 months for SSc. These data provide additional estimates of the incidence of this rare disorder and its subforms.

Paraneoplastic scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia: a report of 10 cases.

PubMed

Magro, Cynthia M; Iwenofu, Hans; Nuovo, Gerard J

2013-07-01

Systemic plasma cell dyscrasias have diverse manifestations in the skin and include an inflammatory paraneoplastic process. We encountered cases of scleroderma and eosinophilic fasciitis in the setting of an underlying plasma cell dyscrasia. Ten cases of scleroderma-like tissue reactions in the setting of an underlying plasma cell dyscrasia were encountered. The biopsies were stained for Transforming growth factor (Transforming growth factor) beta, IgG4, kappa, and lambda. Patients presented with a sclerodermoid reaction represented by eosinophilic fasciitis (5 cases), morphea (3 cases), and systemic scleroderma (2 cases). The mean age of presentation was 70 years with a striking female predominance (4:1). Acral accentuation was noted in 8 cases. In 6 of the cases, the cutaneous sclerosis antedated (4 cases) by weeks to 2 years or occurred concurrently (2 cases) with the initial diagnosis of the plasma cell. The biopsies showed changes typical of eosinophilic fasciitis and/or scleroderma. In 5 cases, light chain-restricted plasma cells were present on the biopsy. There was staining of the plasma cells for Transforming growth factor beta in 3 out of 5 cases tested. In any older patient presenting with a sudden onset of eosinophilic fasciitis or scleroderma especially with acral accentuation, investigations should be conducted in regards to an underlying plasma cell dyscrasia.

Uroporphyrin I Stimulation of Collagen Biosynthesis in Human Skin Fibroblasts

PubMed Central

Varigos, George; Schiltz, John R.; Bickers, David R.

1982-01-01

Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [3H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5- to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities). No changes in morphology of the treated cells occurred. These studies indicate that porphyrins possess previously undemonstrated biological effects that are independent of their photosensitizing properties. This novel dark effect of uroporphyrin I may account for the sclerodermatous lesions seen in the skin of patients with porphyria cutanea tarda and erythropoietic porphyria. PMID:7054234

Evaluation of liver function tests in scleroderma patients.

PubMed

Salem, Gehan Ibrahim Abdelrazek; Abdulrahman, Awni Ali

2012-08-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs, and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This study was done to evaluate the frequency of liver disease in patients with scleroderma and, secondarily, to study the frequency of infection of hepatitis B and C virus in these patients and determine frequency of serum auto-antibodies in this disease. We studied patients with scleroderma, localized or systemic, in the outpatient clinic of rheumatology and dermatology departments, at King Khalid University Hospital. As for a comparison, healthy persons coming to the clinic with the same mean age were considered as control group. Forty patients with the diagnosis of scleroderma included in this work, 35% had elevated gamma-glutamyl-transferase (γ-GT), 30% had elevated alkaline phosphatase (AP) and in 17.5%, the alanine-amino-transferase (ALT) was above the reference values. The ALT had changed to be more in scleroderma patients than in controls. Twenty percent (20%) of the patients tested positive for anti-smooth muscle antibodies (anti-SMA) and only one patient had anti-mitochondrial antibodies (AMA). There was no statistical difference between the two groups regarding antibody testing. Anti-HCV antibodies were observed in one patient, and HBsAg was detected in another scleroderma patient. There was no patient with clinically significant hepatic disease. In this study, although changes in liver enzymes in patients with scleroderma were not uncommon, there was no scleroderma patient with clinical manifestations of liver disease.

Steven Kossards postmenopausal frontal fibrosing alopecia (PFFA)--a therapeutic dilemma.

PubMed

Tchernev, G; Tronnier, M

2010-01-01

Steven Kossard described a new type of hair loss that he named frontal postmenopausal fibrosing alopecia (PFFA). In some of his patients he observed a symmetric regression of the frontal hair line. The eyebrows of the patients were also often affected. The histology of the lesions showed lichen planopilaris. Several cases of frontal fibrosing alopecia have been described- almost all of them in elderly women. We report a women with postmenopausal frontal fibrosing alopecia of Kossard. In our patient there were no other clinical signs of lichen planus on the rest of the body After systemic and local therapy with corticosteroids we were able to observe a termination in the disease. In the subsequent 6-month control period no regrowth of the hair follicles was found. Even if there is no proof for a hormonal basis of the disease, the effectiveness of finasteride in some patients may indicate that androgens might be partially responsible of the pathogenesis of the disease. The local and systemic medication with corticosteroids are not able to bring to a permanent remission and secondary growth of the hair follicles in the affected areas and this brings to the necessity of more invasive or innovative therapeutic methods, like skin transplantation and additional application of medicaments like blockers of the 5/alpha reductase, which have proven their capacity in the androgenetic male alopecia.

Scleroderma renal crisis in a case of mixed connective tissue disease.

PubMed

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

PubMed

Khamaganova, Irina

2017-01-01

Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases.

Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

PubMed Central

Khamaganova, Irina

2018-01-01

Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases. PMID:29445726

New directions for patient-centred care in scleroderma: the Scleroderma Patient-centred Intervention Network (SPIN)

PubMed Central

Thombs, Brett D.; Jewett, Lisa R.; Assassi, Shervin; Baron, Murray; Bartlett, Susan J.; Costa Maia, Angela; El-Baalbaki, Ghassan; Furst, Daniel E.; Gottesman, Karen; Haythornthwaite, Jennifer A.; Hudson, Marie; Ann Impens, PhD; Korner, Annett; Leite, Catarina; Mayes, Maureen D.; Malcarne, Vanessa L.; Motivala, Sarosh J.; Mouthon, Luc; Nielson, Warren R.; Plante, Diane; Poiraudeau, Serge; Poole, Janet L.; Pope, Janet; Sauve, Maureen; Steele, Russell J.; Suarez-Almazor, Maria E.; Taillefer, Suzanne; van den Ende, Cornelia H.; Erin Arthurs, BSc; Bassel, Marielle; Delisle, Vanessa; Milette, Katherine; Leavens, Allison; Razykov, Ilya; Khanna, Dinesh

2014-01-01

Systemic sclerosis (SSc), or scleroderma, is a chronic multisystem autoimmune disorder characterised by thickening and fibrosis of the skin and by the involvement of internal organs such as the lungs, kidneys, gastrointestinal tract, and heart. Because there is no cure, feasibly-implemented and easily accessible evidence-based interventions to improve health-related quality of life (HRQoL) are needed. Due to a lack of evidence, however, specific recommendations have not been made regarding non-pharmacological interventions (e.g. behavioural/psychological, educational, physical/occupational therapy) to improve HRQoL in SSc. The Scleroderma Patient-centred Intervention Network (SPIN) was recently organised to address this gap. SPIN is comprised of patient representatives, clinicians, and researchers from Canada, the USA, and Europe. The goal of SPIN, as described in this article, is to develop, test, and disseminate a set of accessible interventions designed to complement standard care in order to improve HRQoL outcomes in SSc. PMID:22244687

UVA1 a promising approach for scleroderma

PubMed Central

Keyal, Uma; Bhatta, Anil Kumar; Wang, Xiu Li

2017-01-01

Scleroderma is a complex connective tissue disease characterized by fibrosis, vasculopathy, and immune system dysfunction. The heterogeneity of disease presentation and poorly understood etiology has made the management of scleroderma difficult. The available treatment options like immunosuppressive agents are associated with potentially hazardous side effects and physiotherapy, which to a certain degree helps to minimize the loss of function in digits and limbs, has only limited success. Also, studies investigating antifibrotic therapies have failed to report any significant improvement. Hence, there is currently no effective therapy for scleroderma. Recently, phototherapy has been extensively studied and found to be effective in treating scleroderma. Initially psoralen + ultraviolet A (PUVA) significantly enriched the therapeutic panel, but more recently ultraviolet A1 (UVA1) is seen to replace PUVA therapy. This might be because of UVA1 therapy being free of side effects seen with psoralens such as nausea, vomiting or photokeratitis. In addition, UVA1 is seen to lower risk of phototoxic reactions with deeper penetration of radiation. The present review will put some light on the use of UVA1 for treating cutaneous lesion in scleroderma and we aim to find the most benefitted group of patients and most effective dose of UVA1 for different types of scleroderma. PMID:28979701

Clinicopathological study of 81 cases of localized and systemic scleroderma.

PubMed

Succaria, F; Kurban, M; Kibbi, A-G; Abbas, O

2013-02-01

Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Autoantibodies in scleroderma and their association with the clinical profile of the disease. A study of 66 patients from southern Brazil.

PubMed

Skare, Thelma Larocca; Fonseca, Adriano Erlon; Luciano, Alan Campos; Azevedo, Pedro Ming

2011-01-01

Scleroderma is a fairly rare connective tissue disease whose autoantibody profile is associated with different clinical manifestations. The prevalence of autoantibodies in scleroderma is influenced by race and genetics. To study the prevalence of anti-Scl-70, anti-centromere (ACA) and anti-U1-RNP antibodies in patients with scleroderma in southern Brazil and verify their association with clinical manifestations of the disease. A retrospective study involving 66 patients with scleroderma for the presence of anti-Scl-70, anti-centromere and anti-U1-RNP and of clinical manifestations such as Raynaud's phenomenon, digital micro scars, digital necrosis, telangiectasias, calcinosis, pulmonary fibrosis, pleuritis, pericarditis, cardiomyopathy, arthralgia and arthritis, skin sclerosis, joint contractures, tendon friction rubs, pulmonary hypertension, esophageal disorders and renal crisis. The prevalence of anti-Scl-70 was 17.8% , that of ACA was 33.3% and the prevalence of U1 RNP was 11.8%. Anti-Scl-70 was associated with the diffuse form of the disease (p = 0.015), presence of cardiomyopathies (p = 0.016) and digital micro scars (p = 0.05). Anti-centromere was more common in the limited form, although it was not statistically significant, and had a protective role associated with cardiomyopathies (p = 0.005). Anti-U1-RNP was more common in the overlap forms (p = 0.0004). The prevalence and profile of clinical associations of autoantibodies in Brazilian patients with scleroderma are similar to those found in the literature.

Biomarkers in Scleroderma: Progressing from Association to Clinical Utility.

PubMed

Ligon, Colin; Hummers, Laura K

2016-03-01

Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma's evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to benefit from specific therapies, and identify promising therapeutic targets for intervention. High-throughput technologies have recently identified fibrotic and inflammatory effectors in scleroderma that exhibit strong prognostic ability and may be tied to disease evolution. Increasingly, the use of collections of assayed circulating proteins and patterns of gene expression in tissue has replaced single-marker investigations in understanding the evolution of scleroderma and in objectively characterizing disease extent. Lastly, identification of shared patterns of disease evolution has allowed classification of patients into latent disease subtypes, which may allow rapid clinical prognostication and targeted management in both clinical and research settings. The concept of biomarkers in scleroderma is expanding to include nontraditional measures of aggregate protein signatures and disease evolution. This review examines the recent advances in biomarkers with a focus on those approaches poised to guide prospective management or themselves serve as quantitative surrogate disease outcomes.

Raynaud phenomenon

MedlinePlus

Raynaud's phenomenon; Sjögren syndrome - Raynaud; Rheumatoid arthritis - Raynaud; Systemic lupus erythematosus - Raynaud ... and autoimmune conditions (such as scleroderma , Sjögren syndrome , ... , and systemic lupus erythematosus ) Certain blood disorders, such ...

Mixed Connective Tissue Disease

MedlinePlus

Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

Clinicohistopathological correlations in juvenile localized scleroderma: studies on a subset of children with hypopigmented juvenile localized scleroderma due to loss of epidermal melanocytes.

PubMed

Sung, Joanne J; Chen, Tina S; Gilliam, Anita C; McCalmont, Timothy H; Gilliam, Amy E

2011-08-01

Localized scleroderma or morphea is a connective tissue disorder characterized by fibrosis of the skin and subcutaneous tissue. Excessive accumulation of collagen underlies the fibrosis, yet the pathogenesis is unknown. A subset of localized scleroderma/morphea, juvenile localized scleroderma (JLS), affects children and adolescents. The clinical and microscopic features of JLS have not been fully characterized. The goal is to better characterize the microscopic features of JLS. We collected a distinctive data set of 35 children with JLS, 19 (54%) of whom presented with hypopigmented lesions, and performed a retrospective chart and pathology review. We had adequate tissue for immunostaining studies on 8 of these individuals. We found that: (1) CD34 and factor XIIIa immunostaining, reported previously in adult morphea and scleroderma, when used with clinical information, is valuable for confirming a diagnosis of JLS; and (2) presence of hypopigmented lesions in JLS correlates with immunostaining studies. Decreased numbers of MelanA(+) melanocytes were present at the dermoepidermal junction in lesional skin in two of 3 children with hypopigmented JLS and in two of 4 children with nonhypopigmented JLS. The number of cases is small, a function of the small number of children who have biopsy specimens with material sufficient for multiple immunostaining procedures. These results provide a useful immunostaining method for confirmation of the diagnosis of JLS. They suggest a complex autoimmune phenotype in some children with JLS. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

[Chemically-induced scleroderma].

PubMed

Haustein, U F; Ziegler, V; Herrmann, K

1992-08-01

Scleroderma-like diseases can be induced by a number of chemical compounds, such as plastics, solvents and drugs. Contaminated rapeseed oil was the cause of the toxic oil syndrome and L-tryptophan induces the so-called eosinophilia-myalgia-syndrome. On the other hand, paraffin and silicon can trigger so-called adjuvant disease, while long-term exposure to silica can lead to idiopathic scleroderma (associated with silicosis in some cases). In addition to the clinical features, some pathogenetic data in the literature, such as genetic factors (HLA, chromosomal anomalies, enzyme deficiencies) and the metabolism of chlorinated ethylenes via reactive epoxide intermediate products, and our own findings are reported. Silica-induced scleroderma cannot be distinguished from the idiopathic form by epidemiological, clinical or immunological studies or by parameters referring to the blood vessels or collagen metabolism. In cell culture studies it has been shown that macrophages/monocytes release IL1, IL6 and TNF after ingestion of silica, which affects fibroblasts, T-helper cells and endothelial cells. Comparative results from the silicosis literature are reported. Finally, the possibly stimulating role of ionizing irradiation (uranium mining) in favouring the development of scleroderma is discussed.

A survey of dentists' knowledge and attitudes with respect to the treatment of scleroderma patients.

PubMed

Leader, David; Papas, Athena; Finkelman, Matthew

2014-06-01

Scleroderma or systemic sclerosis causes dry mouth, a major risk factor for tooth decay, and shrinks the mouth opening, complicating care. A 2011 survey determined that 28% of systemic sclerosis patients have difficulty finding dentists prepared to treat them, and 63% do not recommend their current dentist to other systemic sclerosis patients. We use a survey to gauge dentists' knowledge and attitudes regarding the care of scleroderma patients. We conducted an Internet-based survey of all 4465 members of the Massachusetts Dental Society to determine their knowledge and attitudes of treating systemic sclerosis patients. Data were analyzed using SPSS and Qualtrics research suite. Surveys were accessed by 351 dentists and completed by 269. Responses were primarily from Eastern Massachusetts (80%), but represented the Boston area less than expected. Most dentists believed they have an ethical responsibility to treat patients who have scleroderma (93%). More than half of dentists believed that in not knowing about systemic sclerosis they might harm a patient (51%). If contacted by a patient who has scleroderma, 50% of dentists would gather information on the disease or the patient's condition. Dentists who felt prepared (71%) were more likely to correctly answer questions related to diagnosis and classification of scleroderma than those who felt unprepared (P = 0.004, Mann-Whitney U test). Results indicate the potential value of creating a health communication effort targeting oral health providers to improve scleroderma patient satisfaction and access to care.

Update on the classification and treatment of localized scleroderma.

PubMed

Bielsa Marsol, I

2013-10-01

Morphea or localized scleroderma is a distinctive inflammatory disease that leads to sclerosis of the skin and subcutaneous tissues. It comprises a number of subtypes differentiated according to their clinical presentation and the structure of the skin and underlying tissues involved in the fibrotic process. However, classification is difficult because the boundaries between the different types of morphea are blurred and different entities frequently overlap. The main subtypes are plaque morphea, linear scleroderma, generalized morphea, and pansclerotic morphea. With certain exceptions, the disorder does not have serious systemic repercussions, but it can cause considerable morbidity. In the case of lesions affecting the head, neurological and ocular complications may occur. There is no really effective and universal treatment so it is important to make a correct assessment of the extent and severity of the disease before deciding on a treatment approach. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

Frontal fibrosing alopecia: clinical presentations and prognosis.

PubMed

Tan, K T; Messenger, A G

2009-01-01

Frontal fibrosing alopecia is an uncommon condition characterized by progressive frontotemporal recession due to inflammatory destruction of hair follicles. Little is known about the natural history of this disease. To determine the clinical features and natural history of frontal fibrosing alopecia. We studied the cases notes of patients diagnosed with frontal fibrosing alopecia from 1993 to 2008 at the Royal Hallamshire Hospital, Sheffield. There were 18 patients aged between 34 and 71 years. Three were premenopausal. All had frontotemporal recession with scarring. This was associated with partial or complete loss of eyebrows in 15 patients while four had hair loss at other sites. One had keratosis pilaris-like papules on the face, and one had follicular erythema on the cheeks. Three patients had oral lichen planus, of whom two also had cutaneous lichen planus affecting other sites of the body. Treatments given included intralesional triamcinolone acetonide, 0.1% tacrolimus ointment and oral hydroxychloroquine. Progression of frontotemporal recession was seen in some patients, but not all. In one patient the hair line receded by 30 mm over 72 months, whereas in another patient there was no positional change in the hair line after 15 years. Frontal fibrosing alopecia is more common in postmenopausal women, but it can occur in younger women. It may be associated with mucocutaneous lichen planus. Recession of the hair line may progress inexorably over many years but this is not inevitable. It is not clear whether or not treatment alters the natural history of the disease - the disease stabilized with time in most of the patients with or without continuing treatment.

Fox-2 protein regulates the alternative splicing of scleroderma-associated lysyl hydroxylase 2 messenger RNA.

PubMed

Seth, Puneet; Yeowell, Heather N

2010-04-01

Scleroderma (systemic sclerosis [SSc]) is a complex connective tissue disorder characterized by hardening and thickening of the skin. One hallmark of scleroderma is excessive accumulation of collagen accompanied by increased levels of pyridinoline collagen crosslinks derived from hydroxylysine residues in the collagen telopeptide domains. Lysyl hydroxylase 2 (LH2), an important alternatively spliced enzyme in collagen biosynthesis, acts as a collagen telopeptide hydroxylase. Changes in the pattern of LH2 alternative splicing, favoring increased inclusion of the alternatively spliced LH2 exon 13A, thereby increasing the levels of the long transcript of LH2 (LH2[long]), are linked to scleroderma disease. This study was undertaken to examine the role played by RNA binding protein Fox-2 in regulating exon 13A inclusion, which leads to the generation of scleroderma-associated LH2(long) messenger RNA (mRNA). Phylogenetic sequence analysis of introns flanking exon 13A was performed. A tetracycline-inducible system in T-Rex 293 cells was used to induce Fox-2 protein, and endogenous LH2(long) mRNA was determined by reverse transcriptase-polymerase chain reaction. An LH2 minigene was designed, validated, and used in Fox-2 overexpression and mutagenesis experiments. Knockdown of Fox-2 was performed in mouse embryonic fibroblasts and in fibroblasts from SSc patients. Overexpression of Fox-2 enhanced the inclusion of exon 13A and increased the generation of LH2(long) mRNA, whereas knockdown of Fox-2 decreased LH2(long) transcripts. Mutational analysis of an LH2 minigene demonstrated that 2 of the 4 Fox binding motifs flanking LH2 exon 13A are required for inclusion of exon 13A. In early passage fibroblasts derived from patients with scleroderma, the knockdown of Fox-2 protein significantly decreased the endogenous levels of LH2(long) mRNA. Our findings indicate that Fox-2 plays an integral role in the regulation of LH2 splicing. Knockdown of Fox-2 and other methods to decrease the levels of fibrosis-associated LH2(long) mRNA in primary scleroderma cells may suggest a novel approach to strategies directed against scleroderma.

A rare case of hidebound disease with dental implications.

PubMed

Bali, Vikram; Dabra, Sarita; Behl, Ashima Bali; Bali, Rajiv

2013-07-01

Systemic sclerosis (also called as Scleroderma or hidebound disease) is a chronic sclerotic disease of unknown etiology which causes diffuse, increased deposition of extra cellular matrix in connective tissue with vascular abnormalities, resulting in tissue hypoxia. The disease is characterized by diffuse fibrosis; degenerative changes; and vascular abnormalities in the skin (scleroderma), articular structures, and internal organs. Aesthetic and facial dysfunctions are followed by important oral and facial manifestations. Most oral manifestations begin with tongue rigidity and facial skin changes. Bone resorption of mandibular angle and widening of periodontal ligament space on periapical radiographs are important radiological findings. Other systemic changes include the involvement of internal organs, which lead to serious complications as well as disorders in the cardiac muscle and Raynaud΄s phenomenon. This is a case report of 30-year-old female patient with the classical features of this disease. This case is reported for its rarity and variable expressivity. The main aim of this article is to describe thorough presentation of the case report, various forms of scleroderma, pathogenesis, oral, extraoral, periodontal manifestations of scleroderma, and its treatment options. A brief review of the literature, focusing on dental alterations is also presented.

Targeting miR-155 to Treat Experimental Scleroderma.

PubMed

Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

2016-02-01

Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155(-/-) mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.

Imaging of matrix-disorder in normal and pathological human dermis using nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Zhuo, Shuangmu; Chen, Jianxin; Xie, Shusen; Zheng, Liqin; Jiang, Xingshan

2009-11-01

In dermis, collagen and elastin are important structural proteins of extracellular maxtrix. The matrix-disorder is associated with various physiologic processes, such as localized scleroderma, anetoderma, photoaging. In this work, we demonstrate the capability of nonlinear optical microscopy in imaging structural proteins in normal and pathological human dermis.

Neuroimaging and clinical findings in a case of linear scleroderma en coup de sabre.

PubMed

Duman, Ikram E; Ekinci, Gazanfer

2018-06-01

Linear scleroderma "en coup de sabre" is a subset of localized scleroderma with band-like sclerotic lesions typically involving the frontoparietal regions of the scalp. En coup de sabre and Parry-Romberg syndrome are variants of linear morphea on the head and neck that can be associated with neurologic manifestations. On imaging, patients may have lesions in the cerebrum ipsilateral to the scalp abnormality. We present a case of an 8-year-old girl with a left frontoparietal "en coup de sabre" scalp lesion and describe the neuroimaging findings of frontoparietal white matter lesion discovered incidentally on routine magnetic resonance imaging. The patient had no neurologic symptoms given the lesion identified.

Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

PubMed

Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

2018-03-01

Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Pediatric Scleroderma –Systemic and Localized Forms

PubMed Central

Torok, Kathryn S.

2012-01-01

Synopsis statement Pediatric scleroderma includes two major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, with an initial inflammatory phase associated with endothelial activation, and a later fibrotic phase evidenced by collagenization of tissue and appreciable skin thickness, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, and though not fatal like SSc, up to a quarter of the patients may have extracutaneous disease manifestations, such as arthritis and uveitis. While any organ may be affected in SSc, vascular (Raynaud’s phenomenon), cutaneous (skin thickening), GI, pulmonary and musculoskeletal involvement are most commonly seen in children. Auto-antibody profiles in childhood onset SSc can assist in predicting internal organ involvement. Treatment for both forms of scleroderma targets the active inflammatory stage and halts disease progression; however, progress still needs to be made towards the development of a more effective anti-fibrotic therapy to help reverse disease damage. PMID:22560576

Targeting miR-155 to Treat Experimental Scleroderma

PubMed Central

Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

2016-01-01

Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155−/− mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications. PMID:26828700

Localized scleroderma en coup de sabre in the Neurology Clinic.

PubMed

Pinho, João; Rocha, João; Sousa, Filipa; Macedo, Cristiana; Soares-Fernandes, João; Cerqueira, João; Maré, Ricardo; Lourenço, Esmeralda; Pereira, João

2016-07-01

Localized scleroderma en coup de sabre (LScs) is a form of localized scleroderma thought to be an autoimmune disorder. Central nervous system involvement is not rare and neurological manifestations include seizures, focal neurological deficits, headache and neuropsychiatric changes. Patients attending the Neurology Clinic with the final diagnosis of LScs with neurological manifestations were identified and clinical and imagiological records reviewed. Five patients (0.024%) had LScs with neurological involvement, presenting with transient focal neurologic deficits, seizures, headache or migraine with aura. Neuroimaging studies confirmed localized skin depression and showed bone thinning, white matter lesions, brain calcifications, sulcal effacement and meningeal enhancement. Three patients experienced clinical improvement after immunosuppressive therapy, and in two of these patients neuroimaging findings also improved. Recognizing typical dermatologic changes is keystone for the diagnosis of LScs with neurological involvement. It is a diagnosis of exclusion and extensive etiological diagnostic evaluation should be performed. Treatment options, including conservative follow-up or immunosuppressive therapy, should be carefully considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

PubMed Central

Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

2014-01-01

This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

Scleroderma - resources

MedlinePlus

Resources - scleroderma ... The following organizations are good resources for information on scleroderma : National Institute of Arthritis and Musculoskeletal and Skin Diseases -- www.niams.nih.gov/health-topics/scleroderma Scleroderma ...

Scleroderma and pseudo-scleroderma: uncommon presentations.

PubMed

Haustein, Uwe-Frithjof

2005-01-01

Scleroderma is characterized by major clinical symptoms, but a number of unrelated disease may mimic these features more or less completely. Even scleroderma itself sometimes presents in an unusual manner. This article deals with uncommon presentations of true scleroderma and its variants and pseudo -scleroderma diseases.

Atypical Neuroimaging Manifestations of Linear Scleroderma "en coup de sabre".

PubMed

M Allmendinger, Andrew; A Ricci, Joseph; S Desai, Naman; Viswanadhan, Narayan; Rodriguez, Diana

2015-01-01

Linear scleroderma "en coup de sabre" is a subset of localized scleroderma with band-like sclerotic lesions typically involving the fronto-parietal regions of the scalp. Patients often present with neurologic symptoms. On imaging, patients may have lesions in the cerebrum ipsilateral to the scalp abnormality. Infratentorial lesions and other lesions not closely associated with the overlying scalp abnormality, such as those found in the cerebellum, have been reported, but are extremely uncommon. We present a case of an 8-year-old boy with a left fronto-parietal "en coup de sabre" scalp lesion and describe the neuroimaging findings of a progressively enlarging left cerebellar lesion discovered incidentally on routine magnetic resonance imaging. Interestingly, the patient had no neurologic symptoms given the size of the mass identified.

Atypical Neuroimaging Manifestations of Linear Scleroderma “en coup de sabre”

PubMed Central

M. ALLMENDINGER, Andrew; A. RICCI, Joseph; S. DESAI, Naman; VISWANADHAN, Narayan; RODRIGUEZ, Diana

2015-01-01

Linear scleroderma “en coup de sabre” is a subset of localized scleroderma with band-like sclerotic lesions typically involving the fronto-parietal regions of the scalp. Patients often present with neurologic symptoms. On imaging, patients may have lesions in the cerebrum ipsilateral to the scalp abnormality. Infratentorial lesions and other lesions not closely associated with the overlying scalp abnormality, such as those found in the cerebellum, have been reported, but are extremely uncommon. We present a case of an 8-year-old boy with a left fronto-parietal “en coup de sabre” scalp lesion and describe the neuroimaging findings of a progressively enlarging left cerebellar lesion discovered incidentally on routine magnetic resonance imaging. Interestingly, the patient had no neurologic symptoms given the size of the mass identified. PMID:26401155

Postmenopausal frontal fibrosing alopecia.

PubMed

Naz, E; Vidaurrázaga, C; Hernández-Cano, N; Herranz, P; Mayor, M; Hervella, M; Casado, M

2003-01-01

Recently a new entity, postmenopausal frontal fibrosing alopecia, was added to the established subtypes of scarring alopecias affecting postmenopausal women. This condition is characterized by a progressive frontal hairline recession associated with scarring. We studied the clinical and histopathologic features in four women with this disorder. Of note, a history of bilateral oophorectomy in two of them appears to be a new association. All four cases had frontoparietal recession of the hairline and two of them also had loss of their eyebrows. None of our four patients had any mucous membrane or other skin lesions. Histological examination showed perifollicular fibrosis and lymphocytic inflammation around the isthmus and infundibular areas of the follicles. No effective treatments have emerged for this type of postmenopausal alopecia, but progression of the hair loss and scarring appears to be self-limiting. We believe that this condition is a distinct clinicopathological variant of lichen planopilaris.

Tuberculosis-associated Fibrosing Mediastinitis: Case Report and Literature Review.

PubMed

Tan, Ronald; Martires, Joanne; Kamangar, Nader

2016-01-01

Fibrosing mediastinitis is a rare condition defined by the presence of fibrotic mediastinal infiltrates that obliterate normal fat planes. It is a late complication of a previous granulomatous infection, such as histoplasmosis or tuberculosis (TB). Due to its rarity, fibrosing mediastinitis is often under-recognized, and the clinical presentation is variable and dependent on the extent of infiltration or encasement of structures within the mediastinum. We present a case of fibrosing mediastinitis in a man with a prior history of TB, who presented with progressive dyspnea and was found to have chronic mediastinal soft tissue opacities and pulmonary hypertension. His diagnosis was delayed due to the lack of recognition of this clinical/radiographic entity. Fibrosing mediastinitis is a rare entity usually caused by granulomatous disease. Most cases develop as a late complication of histoplasmosis or TB. The presence of calcified mediastinal soft tissue infiltrates on advanced chest imaging can be diagnostic of fibrosing mediastinitis in patients with a prior history of a granulomatous infection once active processes such as malignancy are excluded.

Risk Factors for Scleroderma

MedlinePlus

... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2012-07-01

Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions PRINCIPAL INVESTIGATOR: Michael...SUBTITLE Identification of the Gene Scleroderma in the Tsk/2 Mouse Strain: Implications 5a. CONTRACT NUMBER for Human Scleroderma Pathogenesis and...Tsk2/+
 mouse
 model
 of
 scleroderma .”
 Drexel
 University
 College
 of
 Medicine,
Discovery
Day
Research
Symposium,
Philadelphia,
Pennsylvania

New fat-derived products for treating skin-induced lesions of scleroderma in nude mice.

PubMed

Serratrice, Nicolas; Bruzzese, Laurie; Magalon, Jérémy; Véran, Julie; Giraudo, Laurent; Aboudou, Houssein; Ould-Ali, Djaffar; Nguyen, Pierre Sébastien; Bausset, Olivier; Daumas, Aurélie; Casanova, Dominique; Granel, Brigitte; Andrac-Meyer, Lucile; Sabatier, Florence; Magalon, Guy

2014-12-17

Scleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman's technique or macro-fat). Here we compared the long-term efficacy of micro-fat "enriched" with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma. We used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections. MF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01). All tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

Frontal fibrosing alopecia: a survey in 16 patients.

PubMed

Moreno-Ramírez, D; Camacho Martínez, F

2005-11-01

Postmenopausal frontal fibrosing alopecia (PFFA) was described by Kossard et al. as a progressive recession of the frontal hairline affecting particularly postmenopausal women. Further cases of PFFA have been reported to date, all of them considering it as a variant of lichen planopilaris on the basis of its clinical, histological and immunohistochemical features. To describe clinical features, and response to treatment of 16 cases of frontal fibrosing alopecia diagnosed at our department in the last 6 years. In addition to clinical data, biopsies and laboratory tests (antinuclear antibodies, sex hormones, thyroid hormones) were performed in order to rule out other causes of scarring alopecia. Patients were treated with intralesional corticosteroids, finasteride, and minoxidil, depending on the stage of the disease and association to androgenetic alopecia. All patients presented progressive alopecia localized to the frontal and temporal hairlines. Eight patients (50%) had loss of eyebrows, and six patients (37.5%) had axillar alopecia. Ages ranged from 45 to 79. Three of these women were premenopausal. Androgenetic alopecia was evident in seven patients (43.8%). All patients biopsied showed perifollicular lymphocitic infiltrate with lamelar fibrosis limited to the upper portions of the follicle. The progression of the condition stopped in most patients after a variable period on treatment. When treatment was abandoned the alopecia progressed to 'clown alopecia' appearance. Cases of Kossard's type scarring alopecia affecting premenopausal women made us consider that this condition is not exclusive of postmenopausal women. Differential diagnosis should take into account conditions like female androgenetic alopecia, fibrosing alopecia in a pattern distribution, alopecia areata, and chronic lupus erythematosus. Except for the pattern of alopecia, lichen planopilaris and frontal fibrosing alopecia are indistinguishable, thus the latter is included as a variant of lichen planopilaris. Although the disease tends to spontaneous stabilization, intralesional and topical corticosteroids, and anti-androgens may stop the progression of the disease and improve the female androgenetic alopecia that usually is associated to FFA.

Cancer and Scleroderma: A Paraneoplastic Disease with Implications for Malignancy Screening

PubMed Central

Shah, Ami A.; Rosen, Livia Casciola

2015-01-01

Purpose of review Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore potential links between cancer and scleroderma, and propose an approach to malignancy screening in scleroderma. Recent findings Emerging data have demonstrated that patients with scleroderma and RNA polymerase III autoantibodies have a significantly increased risk of cancer within a few years of scleroderma onset. Genetic alterations in the gene encoding RNA polymerase III (POLR3A) have been identified, and patients with somatic mutations in POLR3A have evidence of mutation specific T cell immune responses with generation of cross-reactive RNA polymerase III autoantibodies. These data strongly suggest that scleroderma is a by-product of anti-tumor immune responses in some patients. Additional epidemiologic data demonstrate that patients developing scleroderma at older ages may also have a short cancer-scleroderma interval, suggestive of paraneoplastic disease. Summary Scleroderma may be a paraneoplastic disease in unique patient subsets. Aggressive malignancy screening in these patients may aid in early cancer detection. Further study is required to determine whether cancer therapy could improve scleroderma outcomes in this patient population. PMID:26352736

Frontal Fibrosing Alopecia and Vitiligo: Coexistence or True Association?

PubMed

Katoulis, Alexandros C; Diamanti, Konstantina; Sgouros, Dimitrios; Liakou, Aikaterini I; Alevizou, Antigoni; Bozi, Evangelia; Damaskou, Vasileia; Panayiotides, Ioannis; Rigopoulos, Dimitrios

2017-01-01

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia characterized by a progressive band-like recession of the frontotemporal hairline and frequent loss of the eyebrows. It predominantly affects postmenopausal women. Coexistence of FFA and vitiligo is rarely reported in the literature. We retrospectively studied 20 cases diagnosed with FFA in a 14-month period in our Department. Among them, there were 2 cases, a 72-year-old woman and a 48-year-old man, who developed FFA on preexisting vitiligo of the forehead. Anatomical colocalization of the two dermatoses supports the notion that a causal link may exist and their association may not be coincidental. We suggest that interrelated immunologic events and pathologic processes may underlie both these skin conditions.

Caring for the Patient With Limited Systemic Scleroderma.

PubMed

Lachner, Kelly Denise

2016-01-01

Systemic scleroderma (systemic sclerosis) is a rare, autoimmune, collagen-vascular disease of unknown etiology that affects the connective tissues of the skin, internal organs, as well as the small blood vessels. There are 3 subclasses of systemic scleroderma: limited cutaneous, diffuse cutaneous, and sine scleroderma. Prognosis depends on the extent of organ involvement. Complications of systemic scleroderma can involve the cardiovascular, pulmonary, gastrointestinal, renal, integumentary, and the skeletal-muscular systems. Because systemic scleroderma is not common, many orthopaedic nurses may be unfamiliar with how to best provide care. This article provides information about the complexity of the different types of this disease and the basic nursing care of the patient with the most common subclass of systemic scleroderma, limited cutaneous systemic scleroderma.

Risk of cancer in patients with scleroderma: a population based cohort study

PubMed Central

Hill, C; Nguyen, A; Roder, D; Roberts-Thomson, P

2003-01-01

Background: Previous studies have suggested an increased risk of cancer among patients with scleroderma. Objective: To study a population based cohort of patients with scleroderma in South Australia. Methods: Subjects with scleroderma were identified from the South Australian Scleroderma Registry established in 1993. All subjects on the scleroderma registry were linked to the South Australian Cancer Registry to identify all cases of cancer until 31 December 2000. Standardised incidence ratios (SIRs) for cancer for subjects with scleroderma were determined using the age- and sex-specific rates for South Australia. Results: In 441 patients with scleroderma, 90 cases of cancer were identified, 47 of which developed after inclusion on the scleroderma registry. The SIRs for all cancers among these patients were significantly increased (SIR=1.99; 95% confidence interval (95% CI) 1.46 to 2.65) compared with the cancer incidence rates for South Australia. The SIRs for lung cancer (SIR=5.9; 95% CI 3.05 to 10.31) were also significantly increased. The SIRs for all cancers among the subgroups with diffuse scleroderma (SIR=2.73; 95% CI 1.31 to 5.02) and limited scleroderma (SIR=1.85; 95% CI 1.23 to 2.68) were significantly increased. Conclusions: This population based cohort study provides evidence that scleroderma is associated with cancer, and in particular, lung cancer. In addition, both diffuse and limited forms of scleroderma are associated with a similarly increased risk of cancer. PMID:12860727

Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti-Interferon-Inducible Protein 16 Antibodies.

PubMed

McMahan, Zsuzsanna H; Wigley, Frederick M; Casciola-Rosen, Livia

2017-06-01

To evaluate whether scleroderma patients who are double-positive for anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and anticentromere (anti-CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti-CENP antibodies alone. Sera from 165 scleroderma patients who tested positive for anti-CENP antibodies upon clinical evaluation were reassayed for both anti-CENP and anti-IFI-16 antibodies using enzyme-linked immunosorbent assay testing. Patients who were positive for anti-CENP antibodies alone were then compared to patients who were double-positive for both anti-IFI-16 and anti-CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double-positive antibody status was examined using chi-square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates. Of the 165 anti-CENP antibody positive patients, 21 (12.7%) also had anti-IFI-16 antibodies. Patients who were double-positive for anti-CENP and anti-IFI-16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double-positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1-11.1]; P = 0.03). Scleroderma patients who are double-positive for antibodies recognizing CENP and IFI-16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti-CENP and anti-IFI-16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma. © 2016, American College of Rheumatology.

Juvenile Scleroderma

MedlinePlus

... morphea, linear scleroderma, and scleroderma en coup de sabre. Each type can be subdivided further and some ... described for morphea. Linear scleroderma en coup de sabre is the term generally applied when children have ...

Challenges and strategies for coping with scleroderma: implications for a scleroderma-specific self-management program.

PubMed

Milette, Katherine; Thombs, Brett D; Maiorino, Kristina; Nielson, Warren R; Körner, Annett; Peláez, Sandra

2018-05-09

The purpose of this study was to explore challenges faced by patients with systemic sclerosis, also called scleroderma, in coping with their disease and the strategies they used to face those challenges. Five focus groups were held with scleroderma patients (4 groups, n = 34) and health care professionals who have experience treating scleroderma (1 group, n = 8). Participants' discussions were recorded, transcribed and analyzed using thematic analysis. Participants reported challenges accessing information (e.g., knowledgeable specialists), dealing with negative emotions (e.g., stress due to misunderstandings with loved ones), and accessing resources (e.g., helpful products or devices). Strategies for overcoming challenges were also discussed (e.g., advocating for own needs). When faced with significant challenges while coping with scleroderma, patients develop strategies to manage better and improve their quality of life. To help them cope, patients would benefit from easier access to supportive interventions, including tailored scleroderma self-management programs. Although the challenges experienced by patients with scleroderma are unique, findings from this study might help better understand patients' perspectives regarding coping and disease management for other chronic diseases as well. Implications for Rehabilitation People living with rare diseases, including the rare autoimmune disease scleroderma, face unique challenges and often do not have access to disease-specific educational or other support resources. People with scleroderma report that they face challenges in accessing information, including knowledgeable healthcare providers; managing difficult social interactions and negative emotions; and accessing resources. Strategies employed by scleroderma patients to overcome these challenges include seeking connections to other people with scleroderma or scleroderma patient organizations, actively seeking out local resources, and learning to communicate and advocate more effectively. Rehabilitation professionals can support people with scleroderma by providing them with information on connecting with scleroderma patient organizations or by facilitating local patient support networks.

Neurologic involvement in scleroderma: a systematic review.

PubMed

Amaral, Tiago Nardi; Peres, Fernando Augusto; Lapa, Aline Tamires; Marques-Neto, João Francisco; Appenzeller, Simone

2013-12-01

To perform a systematic review of neurologic involvement in Systemic sclerosis (SSc) and Localized Scleroderma (LS), describing clinical features, neuroimaging, and treatment. We performed a literature search in PubMed using the following MeSH terms, scleroderma, systemic sclerosis, localized scleroderma, localized scleroderma "en coup de sabre", Parry-Romberg syndrome, cognitive impairment, memory, seizures, epilepsy, headache, depression, anxiety, mood disorders, Center for Epidemiologic Studies Depression (CES-D), SF-36, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), neuropsychiatric, psychosis, neurologic involvement, neuropathy, peripheral nerves, cranial nerves, carpal tunnel syndrome, ulnar entrapment, tarsal tunnel syndrome, mononeuropathy, polyneuropathy, radiculopathy, myelopathy, autonomic nervous system, nervous system, electroencephalography (EEG), electromyography (EMG), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Patients with other connective tissue disease knowingly responsible for nervous system involvement were excluded from the analyses. A total of 182 case reports/studies addressing SSc and 50 referring to LS were identified. SSc patients totalized 9506, while data on 224 LS patients were available. In LS, seizures (41.58%) and headache (18.81%) predominated. Nonetheless, descriptions of varied cranial nerve involvement and hemiparesis were made. Central nervous system involvement in SSc was characterized by headache (23.73%), seizures (13.56%) and cognitive impairment (8.47%). Depression and anxiety were frequently observed (73.15% and 23.95%, respectively). Myopathy (51.8%), trigeminal neuropathy (16.52%), peripheral sensorimotor polyneuropathy (14.25%), and carpal tunnel syndrome (6.56%) were the most frequent peripheral nervous system involvement in SSc. Autonomic neuropathy involving cardiovascular and gastrointestinal systems was regularly described. Treatment of nervous system involvement, on the other hand, varied in a case-to-case basis. However, corticosteroids and cyclophosphamide were usually prescribed in severe cases. Previously considered a rare event, nervous system involvement in scleroderma has been increasingly recognized. Seizures and headache are the most reported features in LS en coup de sabre, while peripheral and autonomic nervous systems involvement predominate in SSc. Moreover, recently, reports have frequently documented white matter lesions in asymptomatic SSc patients, suggesting smaller branches and perforating arteries involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Localized scleroderma: clinical spectrum and therapeutic update*

PubMed Central

Careta, Mariana Figueiroa; Romiti, Ricardo

2015-01-01

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma. PMID:25672301

Localized scleroderma: clinical spectrum and therapeutic update.

PubMed

Careta, Mariana Figueiroa; Romiti, Ricardo

2015-01-01

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.

Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation.

PubMed

Carrión, José A; Torres, Ferran; Crespo, Gonzalo; Miquel, Rosa; García-Valdecasas, Juan-Carlos; Navasa, Miquel; Forns, Xavier

2010-01-01

Significant liver fibrosis (F >or= 2) and portal hypertension (hepatic venous pressure gradient [HVPG] >or= 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa x month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. Figures were almost identical for patients with HVPG >or= 6 mmHg or HVPG < 6 mmHg at 1 year after LT. Multivariate analysis identified donor age, bilirubin level, and LSM as independent predictors of fibrosis progression and portal hypertension in the estimation group (n = 50) and were validated in a second group of 34 patients. The areas under the receiver operating characteristic curve that could identify rapid fibrosers and patients with portal hypertension as early as 6 months after LT were 0.83 and 0.87, respectively, in the estimation group and 0.75 and 0.80, respectively, in the validation group. Early and repeated LSM following hepatitis C recurrence in combination with clinical variables discriminates between rapid and slow fibrosers after LT.

Current and future direction in the management of scleroderma.

PubMed

Brady, Sean M; Shapiro, Lee; Mousa, Shaker A

2016-09-01

Scleroderma is a heterogeneous disease with a complex etiology. As more information is gained about the underlying mechanisms and the improved classifications of scleroderma subtypes, treatments can be better personalized. Improving scleroderma patients' early diagnosis before end organ manifestations occur should improve clinical trial design and outcomes. Two recently FDA-approved antifibrotics for idiopathic pulmonary fibrosis may be effective treatments in patients with pulmonary fibrosis secondary to scleroderma after further investigation. The potential impact of Nanobiotechnology in improving the efficacy and safety of existing antifibrotics and immunomodulators might present an exciting new approach in the management of scleroderma.

Exploring Sources of Emotional Distress among People Living with Scleroderma: A Focus Group Study

PubMed Central

Gumuchian, Stephanie T.; Peláez, Sandra; Delisle, Vanessa C.; Carrier, Marie-Eve; Jewett, Lisa R.; El-Baalbaki, Ghassan; Fortune, Catherine; Hudson, Marie; Impens, Ann; Körner, Annett; Persmann, Jennifer; Kwakkenbos, Linda; Bartlett, Susan J.; Thombs, Brett D.

2016-01-01

Background Systemic sclerosis, or scleroderma, is a chronic and rare connective tissue disease with negative physical and psychological implications. Sources of emotional distress and the impact they have on the lives of people with scleroderma are not well understood. Objectives To gain an in-depth understanding of the emotional experiences and sources of emotional distress for women and men living with scleroderma through focus group discussions. Methods Three semi-structured focus group discussions were conducted (two in English, one in French) with a total of 22 people with scleroderma recruited through the Scleroderma Society of Ontario in Hamilton, Ontario and a scleroderma clinic in Montreal, Canada. Interviews were recorded, transcribed, and then coded for emerging themes using thematic inductive analysis. Results Core themes representing sources of emotional distress were identified, including: (a) facing a new reality; (b) the daily struggle of living with scleroderma; (c) handling work, employment and general financial burden; (d) changing family roles; (e) social interactions; and (f) navigating the health care system. Collectively, these themes refer to the stressful journey of living with scleroderma including the obstacles faced and the emotional experiences beginning prior to receiving a diagnosis and continuing throughout the participants’ lives. Conclusion Scleroderma was portrayed as being an unpredictable and overwhelming disease, resulting in many individuals experiencing multiple sources of emotional distress. Interventions and supportive resources need to be developed to help individuals with scleroderma and people close to them manage and cope with the emotional aspects of the disease. PMID:27008209

Riedel thyroiditis: Fine needle aspiration findings of a rare entity.

PubMed

Weidner, Anna-Sophie; Molina, David; DeSimone, Robert A; Cohen, Marc A; Giorgadze, Tamar; Scognamiglio, Theresa; Hoda, Rana S

2015-09-01

Riedel thyroiditis is a rare fibrosing disorder characterized by extension of the fibroinflammatory process beyond the thyroid capsule. Due to the nature of this lesion, fine-needle aspiration often yields scant material and may be interpreted as non-diagnostic. In this report, we describe cytologic features that allow the cytopathologist to favor a diagnosis of Riedel thyroiditis, thereby guiding appropriate further work-up and management. © 2015 Wiley Periodicals, Inc.

Abnormalities in the Regulators of Angiogenesis in Patients with Scleroderma

PubMed Central

HUMMERS, LAURA K.; HALL, AMY; WIGLEY, FREDRICK M.; SIMONS, MICHAEL

2014-01-01

Objective To determine plasma levels of regulators of angiogenesis in patients with scleroderma and to correlate those levels with manifestations of scleroderma-related vascular disease. Methods Plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor-2 (FGF-2), matrix metalloproteinase-9 (MMP-9), endostatin, pro-MMP-1, hepatocyte growth factor (HGF), placental growth factor (PlGF), and FGF-4 were examined by ELISA in a cross-sectional study of 113 patients with scleroderma and 27 healthy controls. Simple and multivariate regression models were used to look for associations between factor levels and clinical disease characteristics. Results There were marked differences in the levels of pro-angiogenic growth factors between patients with scleroderma and controls, with significant elevations of VEGF, PDGF, FGF-2, and PlGF among patients with scleroderma (p < 0.0001). Levels of MMP were also higher in scleroderma patients compared to controls (MMP-9 and pro-MMP-1) (p < 0.0001). Levels of the pro-angiogenic and anti-fibrotic factor, HGF, were noted to be lower in patients with scleroderma, but had a positive correlation with right ventricular systolic pressure (RVSP) as measured by echocardiogram (p < 0.0001) and the Raynaud Severity Score (p = 0.05). Endostatin (an anti-angiogenic factor) was notably higher in patients with scleroderma (p < 0.0001) and also correlated positively with RVSP (p = 0.023). Conclusion These results demonstrate striking abnormalities in the circulating regulators of angiogenesis in patients with scleroderma. The levels of some factors correlate with measures of vascular disease among patients with scleroderma. Dysregulated angiogenesis may play a role in the development of scleroderma vascular disease. PMID:19228661

Is Localized Scleroderma Caused by Borrelia burgdorferi?

PubMed

Zinchuk, Alexander N; Kalyuzhna, Lidiya D; Pasichna, Iryna A

2016-09-01

Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi-the agent of Lyme disease-is suggested to be one of the possible etiological factors of localized scleroderma. However, among scientists, this hypothesis is quite controversial. We have conducted investigations of the level of IgM and IgG class antibodies to B. burgdorferi in the serum of patients with localized scleroderma. To rationally substantiate the role of B. burgdorferi in the occurrence of localized scleroderma, thirty-two patients with localized scleroderma treated at an in-patient department were examined. The level of anti-Borrelia antibodies was determined in ELISA. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p < 0.01). Positive levels of anti-Borrelia antibodies in patients with localized scleroderma confirm the borreliosis nature of the disease, requiring conduction of complex antimicrobial treatment.

Neurological abnormalities in localized scleroderma of the face and head: a case series study for evaluation of imaging findings and clinical course.

PubMed

Lis-Święty, Anna; Brzezińska-Wcisło, Ligia; Arasiewicz, Hubert

2017-09-01

Localized scleroderma (LoS) of the face and head is often associated with neurological manifestations and/or imaging abnormalities in the central nervous system (CNS). We present an analysis of 20 cases of LoS affecting the face and head. The CNS symptoms and/or abnormalities in high-resolution computed tomography (HRCT) and/or magnetic resonance imaging (MRI) were observed in 12 patients (60%). In addition to the mild and unspecific disorders (e.g. headaches), serious neurological complications probably in the course of vasculitis were revealed: epilepsy (in two patients), epilepsy and pyramidal sings (in one patient). Neurological disorders and LoS occurred at the same time (in three patients) or at the course of the disease (nine patients) and no later than 29 years since the onset of the disease. No link between neurological disorders and the LoS clinical morphology, immunological and other laboratory parameters has been established. CNS involvement is not correlated with the clinical course of the facial and head LoS and may occur years after the disease initial symptomatology. Imaging follow-up is not required if there is not any emerging neurological symptom. In some cases, however, both HRCT and MRI are useful for monitoring disease evolution and addressing therapeutic choices.

Increased expression of latent TGF-β-binding protein 4 affects the fibrotic process in scleroderma by TGF-β/SMAD signaling.

PubMed

Lu, Jiaying; Liu, Qingmei; Wang, Lei; Tu, Wenzhen; Chu, Haiyan; Ding, Weifeng; Jiang, Shuai; Ma, Yanyun; Shi, Xiangguang; Pu, Weilin; Zhou, Xiaodong; Jin, Li; Wang, Jiucun; Wu, Wenyu

2017-05-01

Scleroderma is a fibrosis-related disorder characterized by cutaneous and internal organ fibrosis, and excessive collagen deposition in extracellular matrix (ECM) is a major cause of fibrosis. Transforming growth factor-β (TGF-β)/SMAD signaling has a central role in the pathogenesis of fibrosis by inducing abnormal collagen accumulation in ECM, and latent TGF-β-binding protein 4 (LTBP-4) affects the secretion of latent TGF-β to ECM. A previous study indicated that bleomycin (BLM) treatment increased LTBP-4 expression in lung fibroblasts of Thy-1 knockout mice with lung fibrosis, and LTBP-4 further promoted TGF-β bioavailability as well as SMAD3 phosphorylation. However, the expression and function of LTBP-4 in human scleroderma remain unclear. We aimed to investigate the potential role of LTBP-4 in scleroderma through clinical, in vivo and in vitro studies. LTBP-4 and TGF-β expressions were significantly upregulated in systemic scleroderma (SSc) patients' plasma compared with normal controls (LTBP-4, 1,215±100.2 vs 542.8±41.7 ng/ml, P<0.0001; TGF-β, 1.5±0.2 vs 0.7±0.1 ng/ml, P=0.0031), while no significant difference was found between localized scleroderma (LSc) and normal controls. The plasma concentrations of LTBP-4 and TGF-β were even higher in SSc patients with lung fibrosis (LTBP-4, 1462± 137.3 vs 892.8±113.4 ng/ml, P=0.0037; TGF-β, 2.0±0.4 vs 0.9±0.2 ng/ml, P=0.0212) and esophagus involvement (1390±134.4 vs 940.7±127.0 ng/ml, P=0.0269; TGF-β, 1.9±0.3 vs 0.9±0.2 ng/ml, P=0.0426). The area under receiver operating characteristics (ROC) curve of LTBP-4 was 0.86. Immunohistochemistry measurement also demonstrated a higher LTBP-4 expression in sclerotic skin tissue of LSc and SSc compared with normal controls. More positive fibroblasts were also found in BLM-induced scleroderma mouse model than the saline-treated group. In in vitro studies, knockdown of LTBP-4 in SSc skin fibroblasts prominently reduced downstream COL1A1, COL1A2, and COL3A1 mRNA level by 84%, 82%, and 43%, respectively, and other fibrosis-related genes' expression were also decreased. Furthermore, extracellular TGF-β level and the SMAD2/3 phosphorylation were inhibited through LTBP-4 knockdown treatment, suggesting that the knockdown of LTBP-4 reduced the collagen expression through TGF-β/SMAD signaling pathway. Taken together, these data suggest that LTBP-4 affects fibrotic process in scleroderma, and the high expression of LTBP-4 in SSc plasma may serve as a clinical biomarker in diagnosing this disease. In addition, this study also lays the theoretical foundation for targeting LTBP-4 as treatment of scleroderma.

Evaluation of heart rhythm variability and arrhythmia in children with systemic and localized scleroderma.

PubMed

Wozniak, Jacek; Dabrowski, Rafal; Luczak, Dariusz; Kwiatkowska, Malgorzata; Musiej-Nowakowska, Elzbieta; Kowalik, Ilona; Szwed, Hanna

2009-01-01

To evaluate possible disturbances in autonomic regulation and cardiac arrhythmias in children with localized and systemic scleroderma. There were 40 children included in the study: 20 with systemic and 20 with localized scleroderma. The control group comprised 20 healthy children. In 24-hour Holter recording, the average rate of sinus rhythm was significantly higher in the groups with systemic and localized scleroderma than in the control group, but there was no significant difference between them. The variability of heart rhythm in both groups was significantly decreased. In the group with systemic scleroderma, single supraventricular ectopic beats were observed in 20% and runs were seen in 40% of patients. In the group with localized scleroderma, supraventricular single ectopic beats occurred in 35% of patients and runs in 45% of those studied. Ventricular arrhythmia occurred in 2 children with systemic scleroderma, but in 1 child, it was complex. The most frequent cardiac arrhythmias in both types of scleroderma in children were of supraventricular origin, whereas ventricular arrhythmias did not occur very often. There were no significant differences in autonomic disturbances manifesting as a higher heart rate and decreased heart rate variability between localized and systemic scleroderma.

BILATERAL CHOROIDAL EXCAVATION IN JUVENILE LOCALIZED SCLERODERMA.

PubMed

Franklin, Mackenzie L; Day, Shelley

2018-01-01

To describe a case of bilateral choroidal excavation in a patient with juvenile localized scleroderma. Case report. An asymptomatic 12-year-old boy with localized scleroderma presented for examination and was found to have bilateral areas of choroidal excavation temporal to the fovea. Previous reports of ocular complications of localized scleroderma have primarily described adnexal and anterior segment changes. This is the second report of choroidal changes in a patient with localized scleroderma, and the first in a pediatric patient.

Localized scleroderma and systemic sclerosis: is there a connection?

PubMed

Gupta, Rajnish A; Fiorentino, David

2007-12-01

Excess fibrosis of the skin is a clinical hallmark of both localized scleroderma and systemic sclerosis. Localized scleroderma is generally thought to be a skin-limited disease whereas systemic sclerosis can have a wide range of internal organ involvement. Recent data suggest that a subset of patients with juvenile localized scleroderma can go on to develop systemic involvement of their disease. This raises the question of what the connection is, if any, between localized scleroderma and systemic sclerosis.

Morphea "en coup de sabre": An unusual oral presentation.

PubMed

Niklander, Sven; Marín, Constanza; Martínez, René; Esguep, Alfredo

2017-02-01

Morphea, or localized scleroderma, is an inflammatory disease that leads to sclerosis of the skin and underlying tissues due to excessive collagen deposition. Oral involvement is unusual and it may produce white linear fibrotic areas with a scar-like appearance, atrophy of tongue papillae, gingival recession and alveolar bone resorption. We report a case of a 13-year-old girl who consulted for progressive recession on the attached gingiva of her upper left incisors. She also presented a hypopigmented line on the left side skin of her upper lip, which continued through the vermilion and the lip mucosa, including the gingiva of the affected teeth. Clinical examination, blood tests, computerized axial tomography, echo-Doppler ultrasound and histopathological evaluation confirmed the diagnosis of morphea. Treatment with methotrexate and systemic corticosteroids was conducted. After 24 months, no other lesions appeared. No adverse side effects have been reported so far. Key words: Localized scleroderma, oral morphea, linear scleroderma, oral involvement, intraoral lesions.

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge*

PubMed Central

Mulinari-Brenner, Fabiane Andrade; Guilherme, Marina Riedi; Peretti, Murilo Calvo; Werner, Betina

2017-01-01

Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation. PMID:29267454

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge.

PubMed

Mulinari-Brenner, Fabiane Andrade; Guilherme, Marina Riedi; Peretti, Murilo Calvo; Werner, Betina

2017-01-01

Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

Computed tomographic features of idiopathic fibrosing interstitial pneumonia: comparison with pulmonary fibrosis related to collagen vascular disease.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Sahin, Hakan; Brown, Kevin K; Newell, John D; Lynch, David A

2009-01-01

To compare the computed tomographic (CT) features of idiopathic fibrosing interstitial pneumonia with those of pulmonary fibrosis related to collagen vascular disease (CVD). We reviewed the CT scans of 177 patients with diffuse interstitial pulmonary fibrosis, of which 97 had idiopathic fibrosing interstitial pneumonia and 80 had CVD. The CT images were systematically scored for the presence and extent of pulmonary and extrapulmonary abnormalities. Computed tomographic diagnosis of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was assigned. A CT pattern of UIP was identified in 59 (60.8%) of patients with idiopathic fibrosing interstitial pneumonia compared with 15 (18.7%) of those patients with CVD; conversely, the CT diagnosis of NSIP was made in 51 (64%) of patients with CVD compared with 36 (37%) of patients with idiopathic disease (P < 0.01). In 113 patients who had lung biopsy, the CT diagnoses of UIP and NSIP were concordant with the histologic diagnoses in 36 of 50 patients and 34 of 41 patients, respectively. Pleural effusions, esophageal dilation, and pericardial abnormalities were more frequent in patients with CVD than in patients with idiopathic fibrosing interstitial pneumonia. Compared with patients with CVD, those patients with an idiopathic fibrosing interstitial pneumonia showed a higher prevalence of a UIP pattern and lower prevalence of an NSIP pattern as determined by CT. Identification of coexisting extrapulmonary abnormalities on CT can support a diagnosis of CVD.

Supportive Use of Adipose-Derived Stem Cells in Cell-Assisted Lipotransfer for Localized Scleroderma.

PubMed

Chen, Bo; Wang, Xiaojun; Long, Xiao; Zhang, Mingzi; Huang, Jiuzuo; Yu, Nanze; Xu, Jing

2018-06-01

The authors aimed to analyze factors related to lipotransfer for localized scleroderma, and to explore the feasibility of cell-assisted lipotransfer for localized scleroderma treatment. Abdominal fat samples were taken from six scleroderma patients without corticosteroid therapy, five scleroderma patients with corticosteroid therapy, and 10 normal liposuction patients. Their quantity, morphology, and proliferation ability were measured. Blood flow was measured by laser speckle contrast imaging in localized scleroderma lesions and normal contralateral regions for eight localized scleroderma patients. Bleomycin-induced skin fibrosis nude mice were also used to investigate differences between lipotransfer and cell-assisted lipotransfer. Fat weight was measured, and expression of transforming growth factor (TGF)-β1 and type III collagen in the injected skin was determined by immunohistochemistry. The number of stem cells from scleroderma patients with corticosteroid treatment was significantly reduced. Mean blood perfusion in localized scleroderma lesions was not significantly different than in the contralateral normal regions. In normal nude mice, there were no significant changes in TGF-β1 and type III collagen between the control, lipotransfer, and cell-assisted lipotransfer groups, whereas in bleomycin-induced skin fibrosis nude mice, lipotransfer and cell-assisted lipotransfer reduced TGF-β1 and type III collagen expression. For scleroderma patients, fewer adipose-derived stem cells, because of a history of corticosteroid therapy and a local inflammatory microenvironment, are more important factors, whereas blood supply showed no significant change. Therefore, cell-assisted lipotransfer not only improves the survival rate of transplanted fat but also improves skin texture in bleomycin-induced skin fibrosis nude mice.

Frontal fibrosing alopecia in postmenopausal women.

PubMed

Tosti, Antonella; Piraccini, Bianca Maria; Iorizzo, Matilde; Misciali, Cosimo

2005-01-01

Frontal fibrosing alopecia is a variety of cicatricial alopecia characterized by a band of frontal/frontoparietal hair recession and marked decrease or a complete loss of the eyebrows, typically observed in women who are postmenopausal. The purpose of this study was to report clinical and histopathologic findings and results of treatment in a group of women affected by the disease. A total of 14 women with alopecia of the frontal hairline were evaluated from June 2000 through July 2003 in our outpatient consultation for hair disorders. Clinical examination revealed a band of symmetric recession of the frontoparietal hairline extending to the preauricular areas associated with loss of follicular orifices, mild skin atrophy, and perifollicular erythema at the scalp margin. In all, 9 patients also had partial or total loss of the eyebrows. The histologic features of the scalp specimens were similar in all our patients with a reduction of the number of hair follicles, and a high number of intermediate and velluslike follicles. Intemediate and velluslike follicles were more commonly affected than terminal follicles by the lymphocytic inflammatory infiltrate and perifollicular fibrosis. Frontal fibrosing alopecia is a cicatricial alopecia that follows destruction of hair follicles by an inflammatory lymphocytic infiltrate that is localized around the upper portion of the hair follicle. It differs from lichen planopilaris because the lymphocytic infiltrate and fibrosis affect selectively the intermediate and the velluslike follicles of the frontal margin and eyebrows. The reason for this selective involvement is still unknown. Frontal fibrosing alopecia may represent a variety of lichen planopilaris with selective involvement of certain androgen-dependent areas. The affected follicles may have typical biologic markers that could explain the clinical and histologic features found in the disease. It is interesting to note that some of the patients treated with finasteride (2.5 mg/d) showed an arrest in the progression of the disease. Even if there is no proof for a hormonal basis of the disease, the effectiveness of finasteride in some patients may indicate that androgens might be partially responsible of the pathogenesis of the disease.

Paraneoplastic Scleroderma: Are There Any Clues?

PubMed

Jedlickova, Hana; Durčanská, Veronika; Vašků, Vladimír

2016-04-01

Dear Editor, Scleroderma associated with neoplasia is rare, with only a small number of cases reported. We describe 4 patients with paraneoplastic scleroderma who were treated at the I. Department of Dermatovenereology, St. Anna Hospital, during the period between 2004 and 2014. The patients were diagnosed with cholangiogenic carcinoma, endometrial carcinoma, prostatic adenocarcinoma, and adenoma of the suprarenal gland. In the case of concurrent scleroderma and tumor, four situations may occur: they can develop independently of each other; scleroderma may be induced by the tumor; the tumor can develop in the scleroderma; or the tumor can be induced by immunosuppressive therapy. Sclerotization of the skin was described in association with lung cancer, carcinoid, plasma cell dyscrasia, cancer of the ovary, cervix, breast, esophagus, stomach, nasopharynx, melanoma, and sarcoma (1,2,5,7,10). Symptoms may be induced by substances secreted by the tumor (hormones, cytokines, etc.) (9). Tumorous cells further induce cytotoxic and autoantibody response. Scleroderma is characterized by immunological dysregulation, vasculopathy, and hyperproduction of the extracellular matrix by activated fibroblasts. Endothelial, inflammatory, and mesenchymal cells produce cytokines, chemokines, and growth factors e.g. Interleukin-1 (IL1), Interleukin-6 (IL6), tumor necrosis factor alpha (TNF α), collagen alpha 1, connective tissue growth factor (CTGF) (3), and basic fibroblast growth factor (bFGF). This factor is also produced by lung cancer cells (4). The clinical picture of scleroderma and paraneoplastic scleroderma is similar. Diffuse thickening of the skin and/or sclerodermatous plaques can be seen. The histological picture is consistent with scleroderma. Capillaroscopy changes, antinuclear antibodies (ANA), sclerodactyly, and Raynaud phenomenon suggest the diagnosis of systemic scleroderma (SS) (4). Our patients did not fulfill enough of the criteria for SS. Both diffuse and localized scleroderma was seen in 3 patients and generalized localized scleroderma in one case. All patients had a histological picture consistent with scleroderma, negative ANA and ENA antibodies (Table 1, Figure 1). A 66-year-old woman presented with a 10 months history of sclerodermatous plaques on her neck, trunk, and upper and lower extremities. The skin on her breasts and cheeks was diffusely indurated. Examination showed thrombocytopenia, elevated transaminases, Cancer antigen 19-9 (Ca 19-9), thyroid stimulating hormone (TSH), and anti-thyroid peroxidase antibodies, dysmotility of the lower part of esophagus, hepatosplenomegaly, cholecystolithiasis, and benign polyps of colon. She was given prednisone 40 mg/day but did not return for follow up. After 6 months she was diagnosed with cholangiogenic carcinoma with metastatic disease and died shortly afterwards. A 74-year-old woman had localized scleroderma on the trunk for three years. She was treated with procaine penicillin for positive borrelia Immunoglobulin M (IgM) antibodies. Her condition worsened suddenly with confluent scleroderma plaques on her trunk, extremities, and genital region, and vasoneurosis on her lower extremities; she was started on prednisone 35 mg/day. Examination revealed endometrial cancer. The patient underwent a hysterectomy, adnexectomy, and radiotherapy with curative effect. Scleroderma patches softened with residual hyperpigmentation, and prednisone was stopped two years later. A 80-year-old man had a month-long history of diffuse thickening and toughening of the skin on the forearms and lower legs and scleroderma patches on the thighs and shins. Examination revealed prostate adenocarcinoma, and therapy with antiandrogen bicalutamide and prednisone 15 mg/day was started. Two years after the diagnosis he continues with bicalutamide treatment, prednisone 5 mg q.a.d. and has residual toughening of the skin on his lower legs. A 62-year-old woman with seronegative rheumatoid arthritis presented with diffusely tough skin on her extremities and trunk, present for 2 months. Examination revealed cervicitis with a benign endometric polyp, cholecystolithiasis, borderline pulmonary hypertension, and a hormonally inactive suprarenal adenoma. She was given prednisone 40 mg/day and penicillamine with effect. In the 3rd year of therapy she has residual induration of her lower legs and a scleroderma plaque in the lumbar region. She is monitored for her suprarenal adenoma. Two patients had scleroderma at the same time as a malignant tumor; in one patient the localized scleroderma worsened rapidly at the time of the tumor diagnosis, and in one patient a clinically silent adenoma was found. Adrenal tissue can secrete molecules such as serotonine or bFGF involved in fibroplasia (3,6). One patient died of a metastatic disease, two patients after the successful treatment of the tumor, and the patient with suprarenal adenoma experienced softening of the skin and regression of scleroderma. Although paraneoplastic scleroderma is often classified as a pseudoscleroderma, we regard neoplasia as a distinct triggering impulse for scleroderma. Recently, an association between RNA polymerase I/III antibodies in systemic scleroderma and cancer was suggested (8). Such studies may confirm the true link between scleroderma and malignancy. These patients are characterized by older age, sudden onset, diffuse thickening of the skin, and/or generalized morphea with a concurrent neoplastic process. In the case of a successful tumor treatment, skin changes regress.

Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

DTIC Science & Technology

2010-06-01

SITE-SPECIFIC DIFFERENTIATION OF FIBROBLASTS IN NORMAL AND SCLERODERMA SKIN PRINCIPAL INVESTIGATOR: Howard Y. Chang, M.D., Ph.D...2010 4. TITLE AND SUBTITLE Site-Specific Differentiation of Fibroblasts in Normal and 5a. CONTRACT NUMBER Scleroderma Skin 5b. GRANT NUMBER...activated fibroblasts from SSc. 15. SUBJECT TERMS Scleroderma , fibroblasts, gene expression 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF

Cancer and systemic sclerosis: novel insights into pathogenesis and clinical implications

PubMed Central

Shah, Ami A.; Rosen, Antony

2012-01-01

Purpose of review Most epidemiologic studies have demonstrated an increased risk of cancer in scleroderma patients. Reasons for this risk increase have been poorly understood and often attributed to cytotoxic therapies or damage from scleroderma. Recognition that some patients have a close temporal relationship between cancer diagnosis and scleroderma clinical onset has focused attention on the possibility that scleroderma may be a paraneoplastic syndrome in a subset of patients. This review will discuss the latest epidemiologic data linking cancer and scleroderma and explore a model for the development of paraneoplastic scleroderma. Recent findings New investigations have demonstrated an association between RNA polymerase III autoantibodies and a close temporal relationship between cancer diagnosis and the development of clinical scleroderma. A unique nucleolar RNA polymerase III expression pattern has been identified in malignant tissue from these scleroderma patients suggesting that autoantigen expression in the cancer and the autoantibody response are associated. Similar data in inflammatory myositis have illustrated that disease-specific autoantigens may be expressed in cancers and damaged target tissues (muscle) undergoing regeneration. Summary These data suggest a model of paraneoplastic autoimmunity in which cross-reactive immune responses may target autoantigens that are expressed in both cancers and diseased autoimmune target tissues. PMID:21825998

Localized scleroderma and regional inflammatory myopathy.

PubMed

Zivković, Saša A; Freiberg, William; Lacomis, David; Domsic, Robyn T; Medsger, Thomas A

2014-05-01

Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of regional inflammatory myopathy associated with localized scleroderma and review 10 reported cases of localized scleroderma associated with an inflammatory myopathy with regional muscle involvement, more often in the upper extremities. Serum creatine kinase was mildly elevated or normal. Histopathology often showed perimysial inflammation and plasma cell infiltration. These cases demonstrate that inflammatory myopathy should be considered in patients with localized scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can confirm the diagnosis of myositis, which if identified, will require anti-inflammatory and/or immunosuppressive therapy. Published by Elsevier B.V.

The Modulation of Fibrosis in Scleroderma by 3-deoxyglucosone

DTIC Science & Technology

2009-06-01

TITLE: The modulation of fibrosis in scleroderma by 3-deoxyglucosone PRINCIPAL INVESTIGATOR: Carol M. Artlett, PhD...5a. CONTRACT NUMBER The modulation of fibrosis in scleroderma by 3-deoxyglucosone 5b. GRANT NUMBER W81XWH-07-1-0450 5c. PROGRAM ELEMENT...Approved for public release: distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Scleroderma is a disease where excess collagen is

Prospective study to evaluate the clinical and radiological outcome of patients with scleroderma of the face.

PubMed

Careta, Mariana Figueiroa; Leite, Claudia da Costa; Cresta, Fernando; Albino, Jose; Tsunami, Mirian; Romiti, Ricardo

2013-09-01

Scleroderma featuring rare connective tissue disease that manifests as skin sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement and localized scleroderma or morphea which classically presents benign evolution and self-limited, confined to the skin and/or underlying tissue. Recent studies show that the localized form may possibly course with involvement of internal organs and variable morbidity. This study aimed to determine the demographic characteristics, the prevalence of systemic manifestations and laboratory findings, as well as the association with autoimmune diseases, and the evolution of neurological findings, both clinical as brain MRI in patients with scleroderma of the face and its relation with the activity skin. Patients with localized scleroderma with facial involvement were evaluated and underwent neurological examination, magnetic resonance imaging and ophthalmology evaluation. After 3years, the patients were subjected again to MRI. We studied 12 patients with localized scleroderma of the face. Of this total, headache being the most frequent complaint found in 66.7% of patients, 33.3% had neurological changes possibly associated with scleroderma. As for ophthalmologic evaluation, 25% of patients showed abnormalities. The most frequent parenchymal finding was the presence of lesions with hyperintense or hypointense signal in 75% of patients, followed by ventricular asymmetry at 16.7%. Of the patients who had neurological deficits, 75% also had a change to MRI. In all patients, imaging findings after 3years were unchanged. During this interval of 3years, 25% of patients showed signs of activity of scleroderma. Patients with localized scleroderma of the face have a high prevalence of neurological and ophthalmological changes. Based on these findings, we suggest that all cases of localized scleroderma of the face should be thoroughly examined for the presence of systemic changes. Copyright © 2013 Elsevier B.V. All rights reserved.

Scleroderma Research Foundation

MedlinePlus

... with suspected lung hypertension. Scleroderma Patients Needed for Research Study to Evaluate Internet Self-Management Program January-2017 ... year before a standard clinical test could. Clinical Research Study for Scleroderma with Interstitial Lung Disease (lung scarring) ...

Parry-romberg syndrome with en coup de sabre.

PubMed

Jun, Jae Hun; Kim, Ho Youn; Jung, Han Jin; Lee, Weon Ju; Lee, Seok-Jong; Kim, Do Won; Kim, Moon Bum; Kim, Byung Soo

2011-08-01

Parry-Romberg syndrome (PRS) is a relatively rare degenerative disorder that is poorly understood. PRS is characterized by slowly progressing atrophy affecting one side of the face, and is frequently associated with localized scleroderma, especially linear scleroderma, which is known as en coup de sabre. This is a report of the author's experiences with PRS accompanying en coup de sabre, and a review of the ongoing considerable debate associated with these two entities. Case 1 was a 37-year-old woman who had right hemifacial atrophy with unilateral en coup de sabre for seven years. Fat grafting to her atrophic lip had been conducted, and steroid injection had been performed on the indurated plaque of the forehead. Case 2 was a 29-year-old woman who had suffered from right hemifacial atrophy and bilateral en coup de sabre for 18 years. Surgical corrections such as scapular osteocutaneous flap and mandible/maxilla distraction showed unsatisfying results.

Scleroderma and Sexuality

MedlinePlus

Scleroderma and Sexuality INTRODUCTION If you or your partner have been diagnosed with scleroderma, you may be wondering how this will ... will continue to find satisfaction and enjoyment through sexuality. If you are single, you may wonder how ...

International Team Identifies Biomarker for Scleroderma

MedlinePlus

... Identifies Biomarker for Scleroderma Spotlight on Research International Team Identifies Biomarker for Scleroderma By Kirstie Saltsman, Ph. ... suggests it stems from immune system malfunction. The team chose to focus on immune cells called plasmacytoid ...

Systemic and localized scleroderma.

PubMed

Chung, Lorinda; Lin, Jan; Furst, Daniel E; Fiorentino, David

2006-01-01

Sclerosing conditions of the skin are manifested by a full spectrum of presentations that includes skin-limited forms as well as those which can involve internal organs and result in death. At this point, we are just beginning to understand the mechanisms of tissue fibrosis, and it is likely that the fibrotic processes are a heterogeneous group of disorders in which perturbation of multiple molecular pathways, including vascular and immunologically mediated pathways, can lead to fibrosis. We now have some moderately effective therapies for vascular aspects of systemic sclerosis (eg, bosentan for pulmonary arterial hypertension, calcium-channel blockers for Raynaud's, or angiotensin-converting enzyme inhibitors for renal crisis). We also are beginning to find treatments interrupting the immunologic pathways that manifest as systemic sclerosis (eg, methotrexate for the skin or cyclophosphamide for the lungs). The basic process of fibrosis, however, awaits proven, effective therapy.

Scleroderma in hospital settings in Lomé: 50 cases.

PubMed

Akakpo, A S; Teclessou, J N; Mouhari-Touré, A; Saka, B; Matakloe, H; Kakpovi, K; Kombate, K; Pitché, P

2017-11-01

The aim of this study was to document the epidemiological and clinical profile, treatment used, and outcome of patients with scleroderma in hospital settings in Lomé. This descriptive study examined the records of all patients seen as outpatients or admitted for scleroderma in hospital dermatology and rheumatology departments in Lomé during the 20-year period of 1993-2012. During the study period, 50 (0.04%) of the 121,021 patients seen in these departments had scleroderma. There were 29 cases of localized scleroderma and 21 systemic cases, predominantly women (sex-ratio=0.2). The patients' mean age was 36 years. All patients with systemic scleroderma had speckled achromia (100%), and most (90.48%) had cutaneous sclerosis. After a mean follow-up period of 43.5 days, 71.43% of the patients had been lost to follow-up. All of the patients with localized scleroderma had cutaneous sclerosis, and the rate of loss to follow-up (after a mean of 17 days) was 96.55%. The results of this study confirm the extreme rarity of scleroderma in the teaching hospitals in Lomé and a clear female predominance. It points out the difficulty of management, which both influences and is aggravated by the high rate of loss to follow-up.

A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide.

PubMed

Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

2015-01-01

Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.

Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study.

PubMed

Arif, Tasleem; Masood, Qazi; Singh, Jaswinder; Hassan, Iffat

2015-02-15

Systemic sclerosis (SSc) is a generalized disorder of unknown etiology affecting the connective tissue of the body. It affects the skin and various internal organs. Gastrointestinal tract involvement is seen in almost 90% of the patients. Esophagus is the most frequently affected part of the gastrointestinal tract. Esophageal motility disturbance classically manifests as a reduced lower esophageal sphincter pressure (LESP) and loss of distal esophageal body peristalsis. Consequently, SSc patients may be complicated by erosive esophagitis and eventually by Barrett's esophagus and esophageal adenocarcinoma. Morphea, also known as localized scleroderma, is characterized by predominant skin involvement, with occasional involvement of subjacent muscles and usually sparing the internal organs. The involvement of esophagus in morphea has been studied very scarcely. The proposed study will investigate the esophageal involvement in the two forms of scleroderma (systemic and localized), compare the same and address any need of upper gastrointestinal evaluation in morphea (localized scleroderma) patients. 56 and 31 newly and already diagnosed cases of SSc and morphea respectively were taken up for the study. All the patients were inquired about the dyspeptic symptoms (heartburn and/or acid regurgitation and/or dysphagia). Upper gastrointestinal endoscopy, esophageal manometry and 24-hour pH monitoring were done in 52, 47 and 41 patients of SSc; and 28, 25 and 20 patients of morphea respectively. Esophageal symptoms were present in 39 cases (69.6%) of SSc which were mild in 22 (39.3%), moderate in 14 (25%), severe in three (5.3%); while only four cases (7.1%) of morphea had esophageal symptoms all of which were mild in severity. Reflux esophagitis was seen in 17 cases (32.7%) of SSc and only two cases (7.14%) of morphea. Manometric abnormalities were seen in 32 cases (68.1%) of SSc and none in morphea. Ambulatory 24-hour esophageal pH monitoring documented abnormal reflux in 33 cases (80.5%) of SSc and no such abnormality in morphea. While the esophageal involvement is frequent in SSc, no such motility disorder is seen in morphea. Meticulous upper gastrointestinal tract evaluation is justified only in SSc and not in morphea.

Lung Transplant in Patients with Scleroderma Compared with Pulmonary Fibrosis. Short- and Long-Term Outcomes.

PubMed

Crespo, Maria M; Bermudez, Christian A; Dew, Mary Amanda; Johnson, Bruce A; George, M Patricia; Bhama, Jay; Morrell, Matthew; D'Cunha, Jonathan; Shigemura, Norihisa; Richards, Thomas J; Pilewski, Joseph M

2016-06-01

Patients with advanced lung disease due to systemic sclerosis have long been considered suboptimal and often unacceptable candidates for lung transplant. To examine post-lung transplant survival of patients with systemic sclerosis compared with patients with pulmonary fibrosis and to identify risk factors for 1-year mortality. In a retrospective cohort study, we compared post-lung transplant outcomes of 72 patients with scleroderma with those of 311 patients with pulmonary fibrosis between June 2005 and September 2013 at our institution. Actuarial survival estimates were calculated using Kaplan-Meier curves. In Cox regression models, we determined risk factors for post-transplant mortality, controlling for whether patients had scleroderma or pulmonary fibrosis. Post-transplant survival did not differ significantly between scleroderma and pulmonary fibrosis at year 1 (81% scleroderma vs. 79% pulmonary fibrosis; P = 0.743), at year 5 conditional on 1-year survival (66% vs. 58%; P = 0.249), or overall (P = 0.385). In multivariate analysis, body mass index greater than or equal to 35 kg/m(2) predicted poor 1-year survival in pulmonary fibrosis (hazard ratio, 2.76; P = 0.003). Acute cellular rejection-free survival did not differ significantly between the scleroderma and pulmonary fibrosis cohorts. Patients with scleroderma had significantly better bronchiolitis obliterans syndrome stage 1 or higher-free survival than did patients with pulmonary fibrosis. Our findings that 1- and 5-year survival rates of patients with scleroderma were similar to those of patients with pulmonary fibrosis indicate that lung transplant is a reasonable treatment option in selected patients with scleroderma.

Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells

PubMed Central

Yang, Jiayue; Waldron, Richard T.; Su, Hsin-Yuan; Moro, Aune; Chang, Hui-Hua; Eibl, Guido; Ferreri, Kevin; Kandeel, Fouad R.; Lugea, Aurelia; Li, Ling

2016-01-01

Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and hyperinsulinemia, the latter due to increased insulin secretion by pancreatic beta-cells. We reported that high-fat diet-induced PDAC progression in mice is associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic stellate cells (PaSC). We investigated here the effects of high concentrations of insulin and glucose on mouse and human PaSC growth and fibrosing responses. We found that compared with normal, pancreata from T2DM patients displayed extensive collagen deposition and activated PaSC in islet and peri-islet exocrine pancreas. Mice fed a high-fat diet for up to 12 mo similarly displayed increasing peri-islet fibrosis compared with mice fed control diet. Both quiescent and activated PaSC coexpress insulin (IR; mainly A type) and IGF (IGF-1R) receptors, and both insulin and glucose modulate receptor expression. In cultured PaSC, insulin induced rapid tyrosine autophosphorylation of IR/IGF-1R at specific kinase domain activation loop sites, activated Akt/mTOR/p70S6K signaling, and inactivated FoxO1, a transcription factor that restrains cell growth. Insulin did not promote activation of quiescent PaSC in either 5 mM or 25 mM glucose containing media. However, in activated PaSC, insulin enhanced cell proliferation and augmented production of extracellular matrix proteins, and these effects were abolished by specific inhibition of mTORC1 and mTORC2. In conclusion, our data support the concept that increased local glucose and insulin concentrations associated with obesity and T2DM promote PaSC growth and fibrosing responses. PMID:27609771

Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies

MedlinePlus

... Novel Insights Into Causes of Scleroderma Offer Potential New Treatment Strategies By Kirstie Saltsman, Ph.D. | December ... address the immune system’s role thanks to a new mouse model of scleroderma, which mirrors many aspects ...

Scleroderma renal crisis and ovarian hyperstimulation syndrome related to the use of clomiphene in a patient with scleroderma.

PubMed

Kobak, Senol; Hacivelioglu, Servet; Gungor, Selen

2014-01-01

This paper presented a 28-year-old female with systemic sclerosis who developed scleroderma renal crisis and ovarian hyperstimulation syndrome following clomiphene administration. Urgent therapy including angiotensin-converting enzyme (ACE) inhibitors and supportive care resulted in regression and eventually resolution of all the clinical and laboratory symptoms. Although scleroderma renal crisis is a fatal complication of high-dose corticosteroids, rarely is this seen with the use of ACE inhibitors. This case report aimed to investigate the potential capacity of the selective oestrogen receptor modulator clomiphene to induce scleroderma renal crisis as well as corticosteroids. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

PubMed

Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

2007-02-01

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

Antibodies against human cytomegalovirus late protein UL94 in the pathogenesis of scleroderma-like skin lesions in chronic graft-versus-host disease.

PubMed

Pastano, Rocco; Dell'Agnola, Chiara; Bason, Caterina; Gigli, Federica; Rabascio, Cristina; Puccetti, Antonio; Tinazzi, Elisa; Cetto, Gianluigi; Peccatori, Fedro; Martinelli, Giovanni; Lunardi, Claudio

2012-09-01

Human cytomegalovirus (hCMV) infection and its reactivation correlate both with the increased risk and with the worsening of graft-versus-host disease (GVHD). Because scleroderma-like skin lesions can occur in chronic GVHD (cGVHD) in allogeneic stem-cell transplant (HCT) patients and hCMV is relevant in the pathogenesis of systemic sclerosis (SSc), we evaluated the possible pathogenetic link between hCMV and skin cGVHD. Plasma from 18 HCT patients was tested for anti-UL94 and/or anti-NAG-2 antibodies, identified in SSc patients, by direct ELISA assays. Both donors and recipients were anti-hCMV IgG positive, without autoimmune diseases. Patients' purified anti-UL94 and anti-NAG-2 IgG binding to human umbilical endothelial cells (HUVECs) and fibroblasts was performed by FACS analysis and ELISA test. HUVECs apoptosis and fibroblasts proliferation induced by patients' anti-NAG-2 antibodies were measured by DNA fragmentation and cell viability, respectively. About 11/18 patients developed cGVHD and all of them showed skin involvement, ranging from diffuse SSc-like lesions to limited erythema. Eight of eleven cGVHD patients were positive for anti-UL94 and/or anti-NAG-2 antibodies. Remarkably, 4/5 patients who developed diffuse or limited SSc-like lesions had antibodies directed against both UL94 and NAG-2; their anti-NAG-2 IgG-bound HUVECs and fibroblasts induce both endothelial cell apoptosis and fibroblasts proliferation, similar to that induced by purified anti-UL94 and anti-NAG-2 antibodies obtained from SSc patients. In conclusion, our data suggest a pathogenetic link between hCMV infection and scleroderma-like skin cGVHD in HCT patients through a mechanism of molecular mimicry between UL94 viral protein and NAG-2 molecule, as observed in patients with SSc.

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

PubMed

Rosenkranz, Margalit E; Agle, Lucila M A; Efthimiou, Petros; Lehman, Thomas J A

2006-01-01

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.

Alopecia with perineural lymphocytes: a clue to linear scleroderma en coup de sabre.

PubMed

Goh, Carolyn; Biswas, Asok; Goldberg, Lynne J

2012-05-01

Linear scleroderma en coup de sabre ('the stroke of the sword') is an uncommon form of morphea with onset typically in childhood or adolescence. Involvement is usually located on the paramedian forehead and is associated with alopecia. It is microscopically indistinguishable from other forms of scleroderma. We present a 51-year-old woman who presented with alopecia and subsequently developed linear scleroderma en coup de sabre on her adjacent forehead. Histopathology revealed a strikingly perineural lymphocytic and plasmacytic infiltrate, extending deeply into the subcutis and fascia. To our knowledge, this is the first report of alopecia with perineural lymphocytic inflammation as a presenting sign of linear scleroderma en coup de sabre. Copyright © 2012 John Wiley & Sons A/S.

Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports.

PubMed

Fain, Emily T; Mannion, Melissa; Pope, Elena; Young, Daniel W; Laxer, Ronald M; Cron, Randy Q

2011-07-29

Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition.

Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports

PubMed Central

2011-01-01

Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition. PMID:21801349

Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

MedlinePlus

... which scar tissue forms in the lungs . Pulmonary fibrosis eventually causes difficulty breathing and can be life-threatening within ... Keavney B, Bézieau S, Mayosi BM. Mutations in FAM111B cause hereditary fibrosing ... myopathy, and pulmonary fibrosis. Am J Hum Genet. 2013 Dec 5;93( ...

A neoteric multidrug combination: novel approach to limited cutaneous systemic scleroderma involving the face

PubMed Central

Kumar, M Hari; Kumar, M Siva; Kumar, Sabitha Hari; Kumar, Kingsly Selva

2016-01-01

Limited cutaneous scleroderma is a subtype of scleroderma limited to the skin of the face, hands, feet and forearms. We present a case of a 45-year-old woman affected by limited cutaneous systemic scleroderma involving the orofacial region and causing restricted mouth opening. The patient showed noteworthy improvement of the skin lesion by use of a combination of intralesional corticosteroid with hyaluronidase and various multiantioxidants, resulting in amelioration of her mouth opening problem. The patient gave her full informed written consent to this report being published. PMID:27033280

Orofacial manifestations of scleroderma. A literature review.

PubMed

Hadj Said, M; Foletti, J M; Graillon, N; Guyot, L; Chossegros, C

2016-11-01

Scleroderma is a rare disease of the connective tissue (50 to 200 patients/1 million people; 60,000 patients in France). We conducted a literature review about the orofacial manifestations of scleroderma that have been little studied. The 45 articles found in 6 different databases by using the keywords "scleroderma", "systemic sclerosis", "oral medicine", "face" and published between 1944 and 2016 were selected, for a total of 328 patients. A total of 1187 orofacial manifestations of scleroderma were identified, occurring mainly in women (84.5%) with a mean age of 40.2 years, 10 years on average after the first manifestation of the disease. The main ones were limitation of mouth opening (69.8%), widening of the periodontal ligament (67.3%), xerostomia (63.4%), telangiectasia (36.2%) and bone lesions (34.5%). Dental root resorptions, pulp and nose calcifications were also reported but with no evident link with scleroderma. Orofacial manifestations of scleroderma are probably more common than reported. They mostly affect women with a mean age of 40. The most common oral manifestations are limitation of mouth opening, widening of the periodontal ligament and xerostomia. Because of the handicap they may be responsible for, these manifestations must be detected early in order to prevent from functional impairments and from dental and periodontal lesions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Surgical Management of Localized Scleroderma.

PubMed

Lee, Jae Hyun; Lim, Soo Yeon; Lee, Jang Hyun; Ahn, Hee Chang

2017-09-01

Localized scleroderma is characterized by a thickening of the skin from excessive collagen deposits. It is not a fatal disease, but quality of life can be adversely affected due to changes in skin appearance, joint contractures, and, rarely, serious deformities of the face and extremities. We present six cases of localized scleroderma in face from our surgical practice. We reviewed six localized scleroderma cases that were initially treated with medication and then received follow-up surgery between April 2003 and February 2015. Six patients had facial lesions. These cases presented with linear dermal sclerosis on the forehead, oval subcutaneous and dermal depression in the cheek. En coup de sabre (n=4), and oval-shaped lesion of the face (n=2) were successfully treated. Surgical methods included resection with or without Z-plasty (n=3), fat graft (n=1), dermofat graft (n=1), and adipofascial free flap (n=1). Deformities of the affected parts were surgically corrected without reoccurrence. We retrospectively reviewed six cases of localized scleroderma that were successfully treated with surgery. And we propose an algorithm for selecting the best surgical approach for individual localized scleroderma cases. Although our cases were limited in number and long-term follow-up will be necessary, we suggest that surgical management should be considered as an option for treating scleroderma patients.

"Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma "en coup de sabre" with CNS tumor

PubMed Central

Bergler-Czop, Beata; Lis-Święty, Anna; Brzezińska-Wcisło, Ligia

2009-01-01

Background Hemifacial atrophy (Parry-Romberg syndrome) is a relatively rare disease. The etiology of the disease is not clear. Some authors postulate its relation with limited scleroderma linearis. Linear scleroderma "en coup de sabre" is characterized by clinical presence of most commonly one-sided linear syndrome. In a number of patients, neurological affection is the medium of the disease. The treatment of both scleroderma varieties is similar to the treatment of limited systemic sclerosis. Case presentation We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an "en coup de sabre" scleroderma and with CNS tumor. Conclusion We described typical cases of a rare diseases, hemifacial atrophy and "en coup de sabre" scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor. PMID:19635150

Reasons for attending support groups and organizational preferences: the European scleroderma support group members survey.

PubMed

Gumuchian, Stephanie T; Delisle, Vanessa C; Kwakkenbos, Linda; Pépin, Mia; Carrier, Marie-Eve; Malcarne, Vanessa L; Peláez, Sandra; El-Baalbaki, Ghassan; Thombs, Brett D

2017-12-19

The objectives were to identify reasons why patients attend scleroderma support groups and to ascertain preferences for how meetings are best organized. The survey included 30-items on reasons for attending and nine items on organizational preferences. Patients were recruited through European patient organizations. Exploratory factor analysis was used to group reasons for attendance thematically. About 213 scleroderma patients (192 women) completed the survey. A three-factor model best described reasons for attending [χ 2 (348) = 586.1, p < 0.001; Comparative Fit Index = 0.98; Tucker Lewis Index = 0.97; Root Mean Square Error of Approximation = 0.06] with themes that included: (1) obtaining interpersonal and social support, (2) learning about treatment and symptom management strategies, and (3) discussing other aspects of scleroderma. Among organizational preferences, respondents emphasized that meetings should include educational aspects and the opportunity to share information and support. People with scleroderma attend support groups to give and obtain social support and for education about managing their disease and other aspects of living with scleroderma. Support groups should be structured to facilitate both educational and informational aspects and to provide opportunities for sharing and support between members. Implications for rehabilitation Local peer-led support groups are an important support and informational resource for patients living with scleroderma. People with scleroderma attend support groups in order to: (1) obtain interpersonal and social support, (2) learn about disease treatment and symptom management strategies, and (3) discuss other aspects of living with scleroderma outside of symptom management. Most support group members prefer groups with a trained facilitator, that include family members or loved ones in the groups, that include between 11and 20 members, that last between 1 and 2 h, and that meet once every 1-3 months. Rehabilitation professionals can support the formation and management of local support groups or can refer patients to national scleroderma patient organizations for information on support groups that they may be able to access.

The spectrum of muscle histopathologic findings in 42 weak scleroderma patients

PubMed Central

Paik, Julie J.; Wigley, Fredrick M.; Lloyd, Thomas E.; Corse, Andrea M.; Casciola-Rosen, Livia; Shah, Ami A.; Boin, Francesco; Hummers, Laura K.; Mammen, Andrew L.

2015-01-01

Objective To determine if distinct muscle pathological features exist in scleroderma subjects with weakness. Methods This retrospective study included weak scleroderma subjects with muscle biopsies available for review. Biopsies were systematically assessed for individual pathologic features including inflammation, necrosis, fibrosis, and acute neurogenic atrophy. Based on the aggregate individual features, biopsies were assigned a histopathologic category of polymyositis, dermatomyositis, necrotizing myopathy, non-specific myositis, “acute denervation”, “fibrosis only”, or “other”. Clinical data analyzed included autoantibody profiles, scleroderma subtype and disease duration, Medsger muscle severity scores, creatine kinase (CK), electromyography (EMG), and muscle magnetic resonance imaging (MRI). Results 42 subjects (79% female and 64% diffuse scleroderma) were included in this study. Necrosis (67%), inflammation (48%), acute neurogenic atrophy (48%), and fibrosis (33%) were the most prevalent pathologic features. The presence of fibrosis was strongly associated with anti-PM-Scl antibodies. Histopathologic categories included non-specific myositis (36%), necrotizing myopathy (21%), dermatomyositis (7%), “acute denervation” (7%), “fibrosis only” (7%), and polymyositis (5%). Disease duration of scleroderma at the time of muscle biopsy was shorter in polymyositis than other histopathologic categories. Patients with anti-PM-Scl and Scl-70 antibodies also had a shorter disease duration than those with other auto-antibody profiles. Conclusion Non-specific myositis and necrotizing myopathy were the most common histopathologic categories in weak scleroderma subjects. Surprisingly, nearly half of the subjects studied had histological evidence of acute motor denervation (acute neurogenic atrophy); this has not been previously reported. Taken together, these observations suggest that a variety of pathologic mechanisms may underlie the development of myopathy in scleroderma. PMID:25989455

Overlapping gene expression profiles indicative of antigen processing and the interferon pathway characterize inflammatory fibrotic skin diseases.

PubMed

Limpers, Annelies; van Royen-Kerkhof, Annet; van Roon, Joel A G; Radstake, Timothy R D J; Broen, Jasper C A

2014-02-01

Inflammatory fibrotic disorders have been of high interest both for dermatologists and rheumatologists. Although the phenotypic end stage of this group of diseases is ultimately the same, namely fibrosis, patients present with different clinical features and are often treated with distinct therapeutic modalities. This review addresses whether there is evidence for different underlying molecular pathways in the various inflammatory fibrotic diseases such as localized scleroderma, pediatric lichen sclerosus, adult lichen sclerosus, eosinophilic fasciitis and systemic sclerosis. To investigate this, a large number of gene expression microarray studies performed on skin or fibroblasts from patients with these aforementioned diseases were described, (re-)analysed, and compared. As suspected by the heterogeneous phenotype, most diseases showed unique gene expression features. Intriguingly, a clear overlap was observed between adult and pediatric lichen sclerosus and localized scleroderma, in antigen processing and the interferon pathway. Delineating the cause and consequence of these pathways may generate novel tools to better characterize and more effectively treat these patients.

Abnormal exhaled ethane concentrations in scleroderma.

PubMed

Cope, K A; Solga, S F; Hummers, L K; Wigley, F M; Diehl, A M; Risby, T H

2006-01-01

Scleroderma (systemic sclerosis) is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. Therefore, it was postulated that patients with scleroderma would have abnormally high breath ethane concentrations, which is a volatile product of free-radical-mediated lipid peroxidation, compared with a group of controls. There was a significant difference (p<0.05) between the mean exhaled ethane concentration of 5.27 pmol ml(-1) CO(2) (SEM=0.76) in the scleroderma patients (n=36) versus the mean exhaled concentration of 2.72 pmol ml(-1) CO(2) (SEM=0.71) in a group of healthy controls (n=21). Within the scleroderma group, those subjects taking a calcium channel blocker had lower ethane concentrations compared with patients who were not taking these drugs (p=0.05). There was a significant inverse association between lung diffusion capacity for carbon monoxide (per cent of predicted) and ethane concentration (b=-2.8, p=0.026, CI=-5.2 to -0.35). These data support the presence of increased oxidative stress among patients with scleroderma that is detected by measuring breath ethane concentrations.

Treatment of Linear Scleroderma (en Coup de Sabre) With Dermal Fat Grafting.

PubMed

Barin, Ensar Zafer; Cinal, Hakan; Cakmak, Mehmet Akif; Tan, Onder

2016-05-01

Linear scleroderma, also known as "en coup de sabre," is a subtype of localized scleroderma that warrants aesthetic correction because it appears on the forehead region in children. To report dermal fat grafting as a novel and effective surgical treatment option in linear scleroderma. Under local anesthesia, a dermal fat graft was successfully placed into a subcutaneous pocket that was prepared underneath the depressed scar. The donor site was closed primarily. No early or late complications developed postoperatively. After 1-year follow-up, the dermal fat graft was viable, the depressed scar was adequately augmented, and a good aesthetic result and patient satisfaction were obtained. We believe that dermal fat grafting is a cost-effective option and provides a long-lasting aesthetic outcome in the management of linear scleroderma. © The Author(s) 2015.

A neoteric multidrug combination: novel approach to limited cutaneous systemic scleroderma involving the face.

PubMed

Kumar, M Hari; Kumar, M Siva; Kumar, Sabitha Hari; Kumar, Kingsly Selva

2016-03-31

Limited cutaneous scleroderma is a subtype of scleroderma limited to the skin of the face, hands, feet and forearms. We present a case of a 45-year-old woman affected by limited cutaneous systemic scleroderma involving the orofacial region and causing restricted mouth opening. The patient showed noteworthy improvement of the skin lesion by use of a combination of intralesional corticosteroid with hyaluronidase and various multiantioxidants, resulting in amelioration of her mouth opening problem. The patient gave her full informed written consent to this report being published. 2016 BMJ Publishing Group Ltd.

Mechanistic and clinical insights at the scleroderma-cancer interface

PubMed Central

Shah, Ami A.; Casciola-Rosen, Livia

2017-01-01

Emerging data suggest tantalizing links between cancer and systemic inflammatory rheumatic syndromes. In scleroderma, patients may have an increased risk of cancer secondary to chronic inflammation and damage from the disease, malignant transformation promoted by immunosuppressive therapies, a shared susceptibility to both cancer and autoimmunity, or a common inciting exposure. However, it is increasingly recognized that a subset of patients develop cancer around the time that scleroderma clinically manifests, raising the question of cancer-induced autoimmunity. In this review, we discuss data suggesting a mechanistic link between cancer and the development of scleroderma, and the clinical implications of these findings. PMID:29264402

Clinical Investigation Program Annual Progress Report.

DTIC Science & Technology

1985-09-30

027 78/114 In Vitro Effect of Minoxidil on Collagen Produc- tion by Normal and Scleroderma Fibroblasts (C) (PR...effect of minoxidil on collagen production Dy normal and scleroderma fibroblasts. Previously titled: The use of minoxidil in treating progressive...Svc: (tO) Assoc Investigators: (11) Key Words: scleroderma, minoxidil Thomas P. O’Barr PhD, DAC fibroblasts, collagen Ellen Swanson MS, DAC Don

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-1-0452 TITLE: Predicting Disease Progression in Scleroderma with Skin...Annual 3. DATES COVERED 23Sep 2013 – 22 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Predicting Disease Progression in...Scleroderma (Systemic Sclerosis, SSc) is a chronic, incurable autoimmune disease associated with high morbidity and mortality primarily due to SSc-lung

Scleroderma Related Lung Disease: Is There a Pathogenic Role for Adipokines?

PubMed Central

Haley, Shannon; Shah, Dilip; Romero, Freddy; Summer, Ross

2013-01-01

Scleroderma is a systemic autoimmune disease of unknown etiology whose hallmark features include endothelial cell dysfunction, fibroblast proliferation and immune dysregulation. Although virtually any organ can be pathologically involved in scleroderma, lung complications including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading cause of death in patients with this condition. Currently, the molecular mechanisms leading to development of scleroderma-related lung disease are poorly understood; however, the systemic nature of this condition has led many to implicate circulating factors in the pathogenesis of some of its organ impairment. In this article, we focus on a new class of circulating factors derived from adipose-tissue called adipokines, which are known to be altered in scleroderma. Recently, the adipokines adiponectin and leptin have been found to regulate biological activities in endothelial, fibroblast and immune cell types in lung and in many other tissues. The pleiotropic nature of these circulating factors and their functional activity on many cell types implicated in the pathogenesis of ILD and PAH suggest these hormones may play a mechanistic role in the onset and/or progression of scleroderma-related lung diseases. PMID:24173692

Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma.

PubMed

Paik, Julie J; Mammen, Andrew L; Wigley, Fredrick M; Shah, Ami A; Hummers, Laura K; Polydefkis, Michael

2016-08-01

To determine the prevalence of peripheral neuropathy in scleroderma. The prevalence of length-dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy. A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti-U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy. While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma-related conditions. © 2016, American College of Rheumatology.

Periostin in Mature Stage Localized Scleroderma.

PubMed

Kim, Min-Woo; Park, Jung Tae; Kim, Jung Ho; Koh, Seong-Joon; Yoon, Hyun-Sun; Cho, Soyun; Park, Hyun-Sun

2017-06-01

Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. To investigate the expression of periostin and other molecules in localized scleroderma. A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p =0.013), diffuse periostin positivity (42.9% vs. 0%, p =0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p =0.001) in patients than in the controls. Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma.

Influence of childhood scleroderma on physical function and quality of life.

PubMed

Baildam, Eileen M; Ennis, Holly; Foster, Helen E; Shaw, Lindsay; Chieng, Alice S E; Kelly, Jane; Herrick, Ariane L; Richards, Helen L

2011-01-01

there have been few studies of quality of life in childhood scleroderma and these focused predominantly on self-perception and the influence of skin lesions. Our cross-sectional study aimed to describe the influence of childhood scleroderma on physical function and quality of life in relation to clinical and demographic measures. children with either localized scleroderma or systemic sclerosis (SSc) attending pediatric rheumatology clinics, together with their parents or guardians, were asked to complete a set of 4 validated measures. Clinical and demographic data were provided by consultant pediatric rheumatologists. in total, 28 children and their parents/guardians participated in the study (68% female, median age 13 yrs; 86% localized scleroderma, 14% SSc). The median Child Health Assessment Questionnaire (CHAQ) score was 0.1 (range 0-3, 0 indicating no impairment), the median Child Dermatology Life Quality Index (CDLQI) score was 5 (range 0-30, 0 indicating no impairment), and the median Child Quality of Life Questionnaire (CQOL) function score was 26 (range 0-105, 0 indicating no impairment). Family activity, measured by the Child Health Questionnaire (CHQ-PF50), was also moderately impaired by scleroderma, with a median score of 83 (0-100, 100 indicating no impairment). scleroderma had only a moderate effect on quality of life and physical function as measured by the 4 validated instruments. Although a small number of children reported greater impairment, this is an encouraging finding, given its potential disfiguring and debilitating effects.

Update on diagnosis and treatment of idiopathic pulmonary fibrosis

PubMed Central

Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

2015-01-01

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

Is seborrhoeic dermatitis associated with a diffuse, low-grade folliculitis and progressive cicatricial alopecia?

PubMed

Pitney, Lucy; Weedon, David; Pitney, Michael

2016-08-01

An association between adult scalp seborrhoeic dermatitis and cicatricial hair loss has not previously been convincingly established. This study seeks to demonstrate a unique relationship between a clinically identifiable chronic scalp dermatitis-folliculitis with the characteristic histological features of low-grade inflammatory fibrosing alopecia, resulting in a distinctive progressive cicatricial alopecia which we believe is prevalent and hitherto unrecognised, and befits the description of seborrhoeic folliculitis. The clinical, epidemiological and histopathological features of seborrhoeic folliculitis are demonstrated to establish its unique status among the disorders of adult diffuse cicatricial alopecia. © 2015 The Australasian College of Dermatologists.

[Comprehensive characteristics of the pulmonary syndrome in chronic liver diseases].

PubMed

Pashchenko, I G; Romanov, A A; Zhumanbaeva, R M; Osmolovskiĭ, V S; Faliushina, N V

1988-01-01

Combined investigations have shown that the pulmonary syndrome in chronic liver diseases is a group of changes (heterogeneous in their structure and origin), most of which are of intercurrent nature (chronic bronchitis and its complications, chronic pneumonia), the lesser part of them is related directly to an inflammatory liver process and constitutes the true pulmonary syndrome (interstitial pneumonitis, fibrosing alveolitis). In view of the fact that chronic liver pathology is attended by concomitant disorders of pulmonary ventilation, hemodynamics and immunologic homestasis, the authors propose that they should be regarded as a risk factor contributing to the development of respiratory diseases.

Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris.

PubMed

Kossard, S; Lee, M S; Wilkinson, B

1997-01-01

Lichen planopilaris usually produces multifocal areas of scarring alopecia. Recently, a condition in postmenopausal women characterized by progressive frontal hairline recession associated with scarring has been described. Our purpose was to study the clinical and histopathologic features and results of treatment in a group of women with the frontal variant of lichen planopilaris and to compare the immunohistochemical profile of scalp biopsy specimens from this subset with that found in the multifocal variant of lichen planopilaris. The clinical data as well as the histopathologic findings in 16 women with frontal fibrosing alopecia were collated. The immunohistochemical profile of six scalp biopsy specimens from the frontal hairline were compared with six specimens from women with multifocal lichen planopilaris. In addition to the progressive frontal fibrosing alopecia in all 16 women, total loss or a marked decrease of the eyebrows was observed in 13. No evidence of lichen planus was observed at other sites. In one patient multifocal areas of lichen planopilaris developed in the scalp. The frontal fibrosing alopecia was slowly progressive but has stabilized in five patients. Biopsy specimens from the frontal hairline showed histologic changes identical to lichen planopilaris. Immunophenotyping failed to reveal any significant differences between the frontal and multifocal variants. No effective treatments emerged although oral steroids and antimalarials may temporarily slow the course. Hormone replacement therapy did not appear to influence the course of the alopecia. Progressive frontal fibrosing alopecia is a clinically distinct variant of lichen planopilaris that affects in particular elderly women and frequently involves the eyebrows. The basis for this lichenoid tissue reaction targeting frontal scalp follicles and eyebrows is unknown.

Gastroesophageal reflux demonstrated by hepatobiliary imaging in scleroderma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sawaf, N.W.; Orzel, J.A.; Weiland, F.L.

1987-03-01

Radionuclide hepatobiliary imaging was performed on a patient with a longstanding history of scleroderma who presented with abdominal pain suggestive of biliary disease. Cystic duct patency was documented after 10 min with tracer accumulation in the second portion of the duodenum which failed to progress consistent with the duodenal hypomotility of scleroderma. The patient was given intravenous Kinevac resulting in gastroesophageal reflux of radionuclide.

Frontal fibrosing alopecia.

PubMed

Clark-Loeser, Lesley; Latkowski, Jo-Ann

2005-12-30

A 75-year-old woman presented with a 3-year history of progressive loss of her eyebrow hair and with frontal-parietal hairline recession. Multiple biopsy specimens supported a histopathologic diagnosis of lichen planopilaris. With these histolopathologic findings, and the patient's clinical presentation, a diagnosis of frontal fibrosing alopecia was made. Treatment to date with topical glucocorticoid preparations, intralesional triamcinolone injections, and tacrolimus ointment have been unsuccessful.

Diagnostic criteria, severity classification and guidelines of localized scleroderma.

PubMed

Asano, Yoshihide; Fujimoto, Manabu; Ishikawa, Osamu; Sato, Shinichi; Jinnin, Masatoshi; Takehara, Kazuhiko; Hasegawa, Minoru; Yamamoto, Toshiyuki; Ihn, Hironobu

2018-04-23

We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma. © 2018 Japanese Dermatological Association.

Indocyanine green angiographic evidence of choroiditis in scleroderma.

PubMed

Abdellatief, Amro; Balasubramaniam, Saranya C; Grube, Thomas J; Gonzalez Santiago, Tania M; Osborn, Thomas G; Pulido, Jose S

2015-01-01

The purpose of this case report was to demonstrate evidence of indocyanine green angiography leakage consistent with choroiditis in a patient with scleroderma. In this case report, the patient underwent a variety of tests and examinations, including systemic evaluation, full ocular examination, skin biopsy, indocyanine green, and fluorescein angiography testing. A 52-year-old man had blurred vision centrally in both eyes. Vision was 20/25 and 20/20. Posterior examination showed cotton-wool spots in both eyes. The patient met European League against Rheumatism (EULAR) criteria for scleroderma. Fluorescein angiography confirmed the presence of leakage from the retinal vessels. More importantly, indocyanine green angiography revealed choroidal vessel leakage in both eyes. This provided evidence of choroiditis before vessel obliteration. Previous studies have shown evidence of choriocapillaris obliteration. Choroidal vessel leakage, however, has not been reported in patients with scleroderma. The results of this case demonstrate the usefulness of indocyanine green angiography in detecting the presence of choroiditis in scleroderma.

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

PubMed

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18 and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

Acute and regressive scleroderma concomitant to an acute CMV primary infection.

PubMed

Goulabchand, Radjiv; Khellaf, Lakhdar; Forestier, Amandine; Costes, Valerie; Foulongne, Vincent; le Quellec, Alain; Guilpain, Philippe

2014-12-01

To describe the pathophysiological mechanisms involving cytomegalovirus (CMV) primary infection and natural killer (NK) cell expansion in the development of localized scleroderma. A 43-year-old woman presented acute erythematous discoloration and skin thickening concerning face, neck, trunk, abdomen, and the four limbs, predominantly in proximal areas. Our case did not respond to systemic sclerosis criteria diagnosis. However, skin and muscle biopsy revealed early scleroderma associated with capillary thrombi, and tissue infiltration with NK cells (CD56+/Granzyme B). Scleroderma was attributed to CMV primary infection responsible for cytolytic hepatitis (7-fold over the limit) and circulating NK cell excess. After 6 months of prednisone and a 2-year follow-up, a complete resolution of symptoms was observed. Our observation suggests a potential triggering role of CMV primary infection in the development of scleroderma. Histological features from our observation addresses the role of CMV and NK cells in the development of endothelial damage and fibrotic process. Copyright © 2014 Elsevier B.V. All rights reserved.

[Localized scleroderma (morphea) in childhood].

PubMed

Weibel, L

2012-02-01

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0452 TITLE: Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers PRINCIPAL INVESTIGATOR: Dr...Predicting Disease Progression in Scleroderma with Skin and Blood 5a. CONTRACT NUMBER Biomarkers 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...autoimmune disease associated with high morbidity and mortality primarily due to lung disease . There is a large variability in individual patients’ courses

Periostin in Mature Stage Localized Scleroderma

PubMed Central

Kim, Min-Woo; Park, Jung Tae; Kim, Jung Ho; Koh, Seong-Joon; Yoon, Hyun-Sun; Cho, Soyun

2017-01-01

Background Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. Objective To investigate the expression of periostin and other molecules in localized scleroderma. Methods A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. Results Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p=0.013), diffuse periostin positivity (42.9% vs. 0%, p=0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p=0.001) in patients than in the controls. Conclusion Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma. PMID:28566901

Musculoskeletal MRI findings of juvenile localized scleroderma.

PubMed

Eutsler, Eric P; Horton, Daniel B; Epelman, Monica; Finkel, Terri; Averill, Lauren W

2017-04-01

Juvenile localized scleroderma comprises a group of autoimmune conditions often characterized clinically by an area of skin hardening. In addition to superficial changes in the skin and subcutaneous tissues, juvenile localized scleroderma may involve the deep soft tissues, bones and joints, possibly resulting in functional impairment and pain in addition to cosmetic changes. There is literature documenting the spectrum of findings for deep involvement of localized scleroderma (fascia, muscles, tendons, bones and joints) in adults, but there is limited literature for the condition in children. We aimed to document the spectrum of musculoskeletal magnetic resonance imaging (MRI) findings of both superficial and deep juvenile localized scleroderma involvement in children and to evaluate the utility of various MRI sequences for detecting those findings. Two radiologists retrospectively evaluated 20 MRI studies of the extremities in 14 children with juvenile localized scleroderma. Each imaging sequence was also given a subjective score of 0 (not useful), 1 (somewhat useful) or 2 (most useful for detecting the findings). Deep tissue involvement was detected in 65% of the imaged extremities. Fascial thickening and enhancement were seen in 50% of imaged extremities. Axial T1, axial T1 fat-suppressed (FS) contrast-enhanced and axial fluid-sensitive sequences were rated most useful. Fascial thickening and enhancement were the most commonly encountered deep tissue findings in extremity MRIs of children with juvenile localized scleroderma. Because abnormalities of the skin, subcutaneous tissues and fascia tend to run longitudinally in an affected limb, axial T1, axial fluid-sensitive and axial T1-FS contrast-enhanced sequences should be included in the imaging protocol.

Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-09-01

Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patientsmore » with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease.« less

Bilateral Breast Enlargement: An Unusual Presentation of Superior Vena Cava Obstruction in a Hemodialysis Patient with Fibrosing Mediastinitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goo, Dong Erk, E-mail: degoo@hosp.sch.ac.kr; Kim, Yong Jae; Choi, Deuk Lin

2011-02-15

A 67-year-old woman with end-stage renal disease presented with profound edema of both breasts. The presence of a patent hemodialysis basilic transposition fistula and superior vena cava obstruction (SVC), due to fibrosing mediastinitis, was demonstrated by the use of fistulography. Endovascular treatment with a balloon and stent caused immediate resolution of the breast edema.

Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS.

PubMed

Whyte, Michael P; Griffith, Malachi; Trani, Lee; Mumm, Steven; Gottesman, Gary S; McAlister, William H; Krysiak, Kilannin; Lesurf, Robert; Skidmore, Zachary L; Campbell, Katie M; Rosman, Ilana S; Bayliss, Susan; Bijanki, Vinieth N; Nenninger, Angela; Van Tine, Brian A; Griffith, Obi L; Mardis, Elaine R

2017-08-01

Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient's mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using four algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS, perhaps facilitated by germline LEMD3 haploinsufficiency, causing his MEL. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased expression of p53 and p21 (Waf1/Cip1) in the lesional skin of bleomycin-induced scleroderma.

PubMed

Yamamoto, Toshiyuki; Nishioka, Kiyoshi

2005-05-01

Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive deposition of extracellular matrix in the affected skin as well as various internal organs, vascular injury and immune abnormality; however, the etiology of SSc remains still unknown. We previously established an experimental mouse model for scleroderma by repeated local injections of bleomycin, a DNA damaging agent. In this study, we examined the induction of apoptosis and the expression of p53, p21 (Waf1/Cip1), and proliferating cell nuclear antigen (PCNA) in the lesional skin following bleomycin exposure in this model. Dermal sclerosis was induced by alternate day's injections of bleomycin for 4 weeks. TUNEL assay showed that apoptotic cells began to appear at 1 week after bleomycin exposure, and were prominently detected at 3-4 weeks. Immunohistochemical examination showed increased expression of p53 and p21 mainly in the infiltrating mononuclear cells at 2 weeks after bleomycin treatment. Bleomycin treatment markedly enhanced PCNA expression at 1-2 weeks, mainly in mesenchyme, as compared with control phosphate buffered saline treatment. Reverse transcriptase-polymerase chain reaction analysis showed that the expression of p53 and p21 mRNA was concurrently upregulated at 1-2 weeks after bleomycin treatment. Taken together, coordinate increased levels of p53 and p21 preceded the maximal induction of apoptosis and dermal sclerosis. Our findings suggest that apoptotic processes are involved in the pathophysiology of bleomycin-induced scleroderma, which may be mediated, in part, by the upregulation of p53 and p21.

Scleroderma en coup de sabre treated with polymethylmethacrylate - Case report.

PubMed

Franco, Joanna Pimenta de Araujo; Serra, Márcio Soares; Lima, Ricardo Barbosa; D'Acri, Antônio Macedo; Martins, Carlos José

2016-04-01

The scleroderma en coup de sabre is a variant of localized scleroderma that occurs preferentially in children. The disease progresses with a proliferative and inflammatory phase and later atrophy and residual deformity, which are treated with surgical techniques such as injectable fillers, transplanted or autologous fat grafting and resection of the lesion. Among the most widely used fillers is hyaluronic acid. However, there are limitations that motivate the search for alternatives, such as polymethylmethacrylate, a permanent filler that is biocompatible, non-toxic, non-mutagenic and immunologically inert. In order to illustrate its application, a case of scleroderma en coup de sabre in a 17-year-old patient, who was treated with polymethylmethacrylate with excellent aesthetic results, is reported.

Systemic sclerosis and localized scleroderma in childhood.

PubMed

Zulian, Francesco

2008-02-01

Juvenile scleroderma syndromes, including the systemic and the localized varieties, represent the third most frequent chronic rheumatic conditions in pediatric rheumatology practice. In children, systemic sclerosis shows a significantly less frequent involvement of all organs, a higher prevalence of arthritis and myositis, and a better outcome than in adults. Recently, new classification criteria were proposed, which help improve patient care by enabling earlier, more definite diagnoses and by standardizing the conduct of clinical trials. Localized scleroderma is the more frequent subtype of scleroderma in childhood. It comprises a group of distinct conditions that involve mainly the skin and subcutaneous tissues. They range from small plaques of fibrosis involving only the skin to diseases causing significant functional deformity with various extracutaneous features.

Work Productivity in Scleroderma – Analysis from the UCLA Scleroderma Quality of Life Study

PubMed Central

Singh, Manjit K.; Clements, Philip J.; Furst, Daniel E.; Maranian, Paul; Khanna, Dinesh

2011-01-01

Objective To examine the productivity of patients with scleroderma (SSc) both outside and within the home in a large observational cohort. Methods 162 patients completed the Work Productivity Survey. Patients indicated whether or not they were employed outside of the home, how many days/month they missed work (employment or household work) due to SSc and how many days/month productivity was decreased ≥ 50%. Patients also completed other patient-reported outcome measures. We developed binomial regression models to assess the predictors of days missed from work (paid employment or household activities). The covariates included: type of SSc, education, physician and patient global assessments, HAQ-DI, FACIT-Fatigue, and Center of Epidemiologic Studies Depression Scale – Short Form (CESD). Results The average age of patients was 51.8 years and 51% had limited SSc. Of 37% patients employed outside of the home, patients reported missing 2.6 days/month of work and had 2.5 days per month productivity reduced by half. Of the 102 patients who were not employed, 39.4% were unable to work due to their SSc. When we assessed patients for household activities (N = 162), patients missed an average of 8 days of housework/month and had productivity reduced by average of 6 days/month. In the regression models, patients with lower education and poor assessment of overall health by physician were more likely to miss work outside the home. Patients with limited SSc and high HAQ-DI were more likely to miss work at home. Conclusion SSc has a major impact on productivity at home and at work. Nearly 40% of patients reported disability due to their SSc. PMID:22012885

Connective tissue ulcers.

PubMed

Dabiri, Ganary; Falanga, Vincent

2013-11-01

Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren's syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

Non-achalasic motor disorders of the oesophagus.

PubMed

Sifrim, Daniel; Fornari, Fernando

2007-01-01

Motor abnormalities of the oesophagus are characterised by a chronic impairment of the neuromuscular structures that co-ordinate oesophageal function. The best-defined entity is achalasia, which is discussed in a separate chapter. Other motor disorders with clinical relevance include diffuse oesophageal spasm, oesophageal dysmotility associated with scleroderma, and ineffective oesophageal motility. These non-achalasic motor disorders have variable prevalence but they could be associated with invalidating symptoms such as dysphagia, chest pain and gastro-oesophageal reflux disease. New oesophageal diagnostic techniques, including high-resolution manometry, high-frequency intraluminal ultrasound and intraluminal impedance, allow (1) better definition of peristalsis and sphincter function, (2) assessment of changes in oesophageal wall thickness, and (3) evaluation of pressure gradients within the oesophagus and across the sphincters that can produce normal or abnormal patterns of bolus transport. This chapter discusses recent advances in physiology, pathophysiology, diagnosis and treatment of non-achalasic oesophageal motor disorders.

Scleroderma

MedlinePlus

... Scleroderma causes the body to produce too much collagen. Collagen is a protein that makes up connective tissues, such as the skin. Too much collagen can make the skin stretch, harden and thicken, ...

LUMBAR SYMPATHECTOMY BY ELECTROCOAGULATION—Its Use in the Management of Certain Vascular and Visceral Disorders

PubMed Central

Raney, R. B.; Raney, Aidan A.; Silver, Harrison E.

1954-01-01

Although normally the sympathetic nerves aid vascular dilatation during effort, in certain diseases of the vascular system they have a reverse effect. Abolition of sympathetic vasoconstrictive impulses by sympathectomy is the most effective treatment in some chronic peripheral vascular conditions. The authors have used electrocoagulation for a number of years and found it quick, effective and more likely to prevent regeneration of the affected nerves. Improvement was obtained by sympathectomy in arteriosclerotic vascular insufficiency, thromboangiitis obliterans, Raynaud's disease, reflex sympathetic dystrophy following thrombophlebitis or trauma, scleroderma, spinal sympathetic dystrophy and acquired megacolon. A case of causalgia was aggravated by the operation. Abstention from the use of tobacco appears to be sufficient for control of symptoms in many cases. Since vasospasm is manifested in many conditions long before a thrombotic catastrophe occurs, not only relief of symptoms but prevention of irreversible changes may be achieved by early operation. ImagesFigure 1.Figure 2. PMID:13116029

Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells

PubMed Central

2013-01-01

Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury. Fibroblasts are the resident cells of connective tissue that become activated at sites of damage and are likely to be important effector cells in SSc. Differentiation into myofibroblasts is a hallmark process, although the mechanisms and cellular origins of this important fibroblastic cell are still unclear. This article reviews fibroblast biology in the context of SSc and highlights the potentially important place of fibroblast effector cells in fibrosis. Moreover, the heterogeneity of fibroblast properties, multiplicity of regulatory pathways and diversity of origin for myofibroblasts may underpin clinical diversity in SSc, and provide novel avenues for targeted therapy. PMID:23796020

Health-related quality of life, optimism, and coping strategies in persons suffering from localized scleroderma.

PubMed

Szramka-Pawlak, B; Dańczak-Pazdrowska, A; Rzepa, T; Szewczyk, A; Sadowska-Przytocka, A; Żaba, R

2013-01-01

The clinical course of localized scleroderma may consist of bodily deformations, and bodily functions may also be affected. Additionally, the secondary lesions, such as discoloration, contractures, and atrophy, are unlikely to regress. The aforementioned symptoms and functional disturbances may decrease one's quality of life (QoL). Although much has been mentioned in the medical literature regarding QoL in persons suffering from dermatologic diseases, no data specifically describing patients with localized scleroderma exist. The aim of the study was to explore QoL in localized scleroderma patients and to examine their coping strategies in regard to optimism and QoL. The study included 41 patients with localized scleroderma. QoL was evaluated using the SKINDEX questionnaire, and levels of dispositional optimism were assessed using the Life Orientation Test-Revised. In addition, individual coping strategy was determined using the Mini-MAC scale and physical condition was assessed using the Localized Scleroderma Severity Index. The mean QoL score amounted to 51.10 points, with mean scores for individual components as follows: symptoms = 13.49 points, emotions = 21.29 points, and functioning = 16.32 points. A relationship was detected between QoL and the level of dispositional optimism as well as with coping strategies known as anxious preoccupation and helplessness-hopelessness. Higher levels of optimism predicted a higher general QoL. In turn, greater intensity of anxious preoccupied and helpless-hopeless behaviors predicted a lower QoL. Based on these results, it may be stated that localized scleroderma patients have a relatively high QoL, which is accompanied by optimism as well as a lower frequency of behaviors typical of emotion-focused coping strategies.

Caveolin-1 Regulates Leukocyte Behaviour in Fibrotic Lung Disease

PubMed Central

Tourkina, Elena; Richard, Mathieu; Oates, James; Hofbauer, Ann; Bonner, Michael; Gööz, Pal; Visconti, Richard; Zhang, Jing; Znoyko, Sergei; Hatfield, Corey M.; Silver, Richard M.; Hoffman, Stanley

2010-01-01

Objectives Reduced caveolin-1 levels in scleroderma lung fibroblasts and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. We now evaluate whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and scleroderma patients and examine the consequences of this deficiency and its reversal. Methods Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, we examined caveolin-1 levels in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue. To validate our results in human disease and identify caveolin-1-regulated molecular mechanisms, we isolated monocytes and neutrophils from scleroderma patients and control subjects and evaluated caveolin-1, ERK, JNK, p38, CXCR4, and MMP-9 expression/activation. We also studied these parameters in monocytes treated with cytokines or CSD peptide. Results Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression is diminished in monocytes and CSD peptide inhibits leucocyte recruitment into the lungs. These observations are relevant to human disease. Scleroderma monocytes and neutrophils contain less caveolin-1 and more activated ERK, JNK, and p38 than their normal counterparts. CSD peptide treatment reverses ERK, JNK, and p38 hyperactivation. Scleroderma monocytes also overexpress CXCR4 and MMP-9. The overexpression of CXCR4 and MMP-9 is inhibited by the CSD peptide. Cytokine treatment of normal monocytes causes adoption of the scleroderma phenotype: low caveolin-1, high CXCR4 and MMP-9, and signaling molecule hyperactivation. Conclusions Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as a promising therapeutic target in scleroderma. PMID:20410070

Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life.

PubMed

Crowell, Michael D; Umar, Sarah B; Griffing, W Leroy; DiBaise, John K; Lacy, Brian E; Vela, Marcelo F

2017-02-01

Systemic scleroderma (SSc) is associated with esophageal aperistalsis and hypotensive esophagogastric junction pressure, although there could be a gradation in esophageal motor dysfunction. We characterized esophageal motor function by high-resolution esophageal manometry (HRM) and assessed associations between SSc severity, health-related quality of life (HRQOL), and HRM findings in patients. We performed a prospective study of 200 patients with SSc and 102 patients without SSc (controls) who underwent HRM at Mayo Clinic Arizona from May 2006 through January 2015. We used data on integrated relaxation pressure, distal contractile integral, and distal latency to classify esophageal motility disorders according to the Chicago Classification v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were compared among diffuse SSc, limited SSc, and control subjects. Categorical variables were compared by using the χ 2 or Fisher exact test; continuous variables were compared by using Mann-Whitney or Kruskal-Wallis test. Multivariable logistic regression was used to assess the association between severity of esophageal dysmotility and baseline clinical factors. Among patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%). Absent contractility was more frequent in patients with SSc than in controls (56% vs 13%; P < .001). HRM findings varied among the patients; absent contractility (56%) was the most frequent diagnosis, followed by normal motility (26%) and ineffective esophageal motility (10%). Classic scleroderma esophagus (esophagogastric junction pressure with absent contractility) was only observed in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe esophageal dysmotility was associated with disease duration, interstitial lung disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was decreased in patients with SSc and severe esophageal dysmotility. Although severe dysmotility is more common in patients with SSc than in controls, we observed the so-called scleroderma esophagus in only one-third of patients with SSc. Esophageal motor function appears to be heterogeneous in SSc. Esophageal dysmotility reduces HRQOL in patients with SSc. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Frequency of motor alterations detected through manometry in patients with esophageal symptoms and scleroderma.

PubMed

Pérez Y López, N; Lugo-Zamudio, G; Barbosa-Cobos, R E; Wong-Lam, A; Torres-López, E

Scleroderma can present with esophageal involvement causing important morbidity. To describe the manometric findings and clinical characteristics of patients with scleroderma and esophageal symptoms. Patients with scleroderma and esophageal symptoms were evaluated through esophageal manometry within the time frame of one year. Descriptive statistics were carried out and the continuous variables were expressed as means and standard deviation. Frequencies were expressed as percentages. The study included 24 female patients with a mean age of 53.5 years and mean disease progression of 7.84 years. The most frequent findings were short and hypotonic lower esophageal sphincter (mean length 1.58cm and mean tone 9.49mmHg) and ineffective esophageal motility (mean non-transmitted waves 92.91%, mean effective primary peristalsis 40.05%, and mean amplitude 13.11mmHg). The most frequent symptom was dysphagia. Scleroderma is associated with lower esophageal sphincter alterations and symptomatic ineffective esophageal motility. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Localized severe scleroderma: a retrospective study of 26 pediatric patients.

PubMed

Beltramelli, Matilde; Vercellesi, Paolo; Frasin, Adina; Gelmetti, Carlo; Corona, Fabrizia

2010-01-01

Juvenile localized scleroderma includes different conditions characterized by skin hardening with increased collagen deposition. Although juvenile localized scleroderma is considered a relatively benign disease, lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Furthermore, extracutaneous manifestations are described. We retrospectively analyzed a cohort of 26 patients with severe Juvenile localized scleroderma with particular attention to clinical features, therapy, and long-term outcome. A subgroup of three patients has been further evaluated with infrared thermography. Our findings were consistent with the current literature for demographic, laboratory, and clinical characteristics at disease onset, but, with our patients, the prevalence of extracutaneous manifestations was higher, thus confirming the potential for severe juvenile localized scleroderma to affect organs other than the skin, without increased risk of development toward systemic sclerosis. Correlation between various treatments and clinical endpoint showed that systemic therapy lead to a better outcome: in particular, methotrexate appeared the most effective drug, capable in halting the progression of the disease and sometimes inducing its regression. © 2010 Wiley Periodicals, Inc.

Localized scleroderma.

PubMed

Kreuter, Alexander

2012-01-01

Localized scleroderma (also called morphea) is a term encompassing a spectrum of sclerotic autoimmune diseases that primarily affect the skin, but also might involve underlying structures such as the fat, fascia, muscle, and bones. Its exact pathogenesis is still unknown, but several trigger factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis. To date, there are no specific serological markers available for localized scleroderma. Within the last years, several validated clinical scores have been introduced as potential outcome measures for the disease. Given the rarity of localized scleroderma, only few evidence-based therapeutical treatment options exist. So far, the most robust data is available for ultraviolet A1 phototherapy in disease that is restricted to the skin, and methotrexate alone or in combination with systemic corticosteroids in more severe disease that additionally affects extracutaneous structures. This practical review summarizes relevant information on the epidemiology, pathogenesis, clinical subtypes and classifications, differential diagnoses, clinical scores and outcome measures, and current treatment strategies of localized scleroderma. © 2012 Wiley Periodicals, Inc.

Nailfold capillaroscopy in children and adolescents with rheumatic diseases.

PubMed

Piotto, Daniela Gerent Petry; Len, Cláudio Arnaldo; Hilário, Maria Odete Esteves; Terreri, Maria Teresa Ramos Ascensão

2012-10-01

To assess nailfold capillaroscopy in children and adolescents with autoimmune rheumatic diseases (juvenile idiopathic arthritis, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma and mixed connective tissue disease) and relate it to clinical and laboratory findings and disease activity. Cross-sectional study assessing 147 patients by use of nailfold capillaroscopy as follows: 60 with juvenile idiopathic arthritis; 30 with systemic lupus erythematosus; 30 with juvenile dermatomyositis; 20 with localized scleroderma; four with systemic sclerosis; and three with mixed connective tissue disease. Clinical and laboratory tests and nailfold capillaroscopy were performed in all patients. The nailfold capillaroscopy was performed with an optical microscope (at 10- and 16-time magnifications) by the same observer. Most patients (76.2%) had normal nailfold capillaroscopy. The major changes in nailfold capillaroscopy, characterizing the scleroderma pattern, were observed in patients with juvenile dermatomyositis, systemic scleroderma and mixed connective tissue disease. There was no association between nailfold capillaroscopy and disease activity in patients with juvenile idiopathic arthritis, systemic lupus erythematosus and localized scleroderma. Disease activity and capillaroscopy were associated in patients with juvenile dermatomyositis. Nailfold capillaroscopy is a useful method to diagnose autoimmune rheumatic diseases and monitor disease activity.

Localized Scleroderma

MedlinePlus

... diagnosis of localized scleroderma is mainly by visual recognition, though a biopsy often may be done to ... sclerodactyly), and thickening of the skin on the face (without color changes).There are other clues that ...

Stretching the boundaries of extracellular matrix research.

PubMed

Hynes, Richard O

2014-12-01

Extracellular matrix (ECM) proteins constitute >1% of the proteome and interact with many modifiers and growth factors to affect most aspects of cellular behaviour during development and normal physiology, as well as in diseases such as fibroses, cancer and many genetic disorders. In addition to biochemical signals provided to cells by ECM proteins, important cell–ECM interactions involve bidirectional mechanotransduction influences, which are dependent on the physical structure and organization of the ECM. These are beginning to be understood using twenty-first-century approaches, including biophysics, nanotechnology, biological engineering and modern microscopy. Articles in this issue of Nature Reviews Molecular Cell Biology review progress in our understanding of the ECM.

[Normotensive scleroderma renal crisis].

PubMed

Villaverde, Marcelo; González, Alejandra; Orellano, Pablo; Lafage, Matías

2003-01-01

A 60 year old male patient having systemic scleroderma and normotensive scleroderma renal crisis was admitted in our hospital. He presented polyarticular, esophagic, lung and skin compromise. Before admission he had been treated with high doses of corticosteroids. We believe corticosteroids led to the worsening of renal damage with renal failure, microangiopathic hemolytic anemia without high blood pressure. The 10% of these cases have normal blood pressure. The patient was treated with enalapril and hemodialysis. There was no favourable response to this treatment and he died seven days after admission.

Hyaluronic Acid is Overexpressed in Fibrotic Lung Tissue and Promotes Collagen Expression

DTIC Science & Technology

2008-04-01

cause of morbidity and mortality in scleroderma . The overexpression of collagen is accompanied by the overexpression of other extracellular matrix...7 Appendices…………………………………………………………………………… 7 3 INTRODUCTION Systemic scleroderma is a debilitating disease...excessive accumulation of extracellular matrix [ECM] proteins, particularly collagen I) is the major cause of morbidity and mortality in scleroderma . The

[Frontal fibrosing alopecia: case series and literature review].

PubMed

Tinoco-Fragoso, Fátima; Domínguez-Cherit, Judith; Méndez-Flores, Silvia

2017-01-01

Frontal fibrosing alopecia is a disease characterized by a symmetric and progressive loss of hair in the fronto-temporal and fronto-parietal lines that generally affects postmenopausal women. It is considered a variant of lichen planus pilaris for its clinical and histopathological features; although, its etiopathology is still unknown. In this report, we analyzed 4 cases of this disease and we discussed its clinical and histopathological characteristics, as well as their course after initiating treatment.

Frontal fibrosing alopecia associated with generalized hair loss.

PubMed

Armenores, Paul; Shirato, Kyoko; Reid, Catherine; Sidhu, Shireen

2010-08-01

We present six cases of frontal fibrosing alopecia, in which generalized hair loss is a feature. Although this variant of lichen planopilaris has been reported clinically in a number of patients, there is very little histological evidence that the condition exists in peripheral sites. We believe this pattern of involvement may be more common than is reported, and have provided histological evidence of lichen planopilaris being present at sites beyond the scalp and eyebrows.

Expiratory lung crackles in patients with fibrosing alveolitis.

PubMed

Walshaw, M J; Nisar, M; Pearson, M G; Calverley, P M; Earis, J E

1990-02-01

Inspiratory lung crackles are a diagnostic feature of interstitial pulmonary fibrosis, but expiratory crackles are not well documented. In a phonopneumographic study of 13 patients with fibrosing alveolitis, expiratory crackles were audible with the stethoscope in 12. Phonopneumographic analysis of these 12 patients showed the crackles to be fine with the initial wave deflection of the expiratory and inspiratory crackles in opposite directions. They were few in number, occurred predominantly in mid- and late expiration, and were not affected by varying the volume history or by breath holding maneuvers. These observations support the theory that some crackles are produced by vibration of the walls of peripheral airways. In addition, this group of patients showed a significant correlation between the number of expiratory crackles and the reduction in predicted transfer factor, suggesting that expiratory crackles may be a clinical indicator of the severity of disease in fibrosing alveolitis.

Scleroderma

MedlinePlus

... of diseases that cause abnormal growth of connective tissue. Connective tissue is the material inside your body that gives ... joints. Symptoms of scleroderma include Calcium deposits in connective tissues Raynaud's phenomenon, a narrowing of blood vessels in ...

Scleroderma

MedlinePlus

... Scleroderma results from an overproduction and accumulation of collagen in body tissues. Collagen is a fibrous type of protein that makes ... Doctors aren't certain what prompts this abnormal collagen production, but the body's immune system appears to ...

Melorheostosis with scleroderma.

PubMed

Shivanand, G; Srivastava, D N

2004-01-01

The association of linear scleroderma with melorheostosis is very rare. Until now, only a few cases have been reported in the English literature. We describe a case of melorheostosis of a rib associated with overlying skin changes.

Clinical associations of anticentromere antibodies and antibodies to topoisomerase I. A study of 355 patients.

PubMed

Weiner, E S; Earnshaw, W C; Senécal, J L; Bordwell, B; Johnson, P; Rothfield, N F

1988-03-01

Anticentromere antibodies (ACA) and anti-topoisomerase I (anti-topo I) were assayed in serum samples from 355 patients: 89 with proximal scleroderma; 54 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), without proximal scleroderma; 154 with primary and secondary Raynaud's disease; and 58 with other rheumatic diseases, without Raynaud's disease. Sera from healthy control subjects were also assayed. Using immunoblotting techniques, anti-topo I was detected in 28% of the patients with proximal scleroderma; using immunodiffusion techniques, this antibody was found in only 20% of the same group of patients. Anti-topo I and ACA were found primarily in patients with scleroderma, CREST syndrome, and Raynaud's phenomenon. ACA identified patients with less severe disease, whereas anti-topo I identified patients with skin and cardiac involvement and patients with malignancies.

The role of nailfold capillary dropout on mortality in systemic sclerosis.

PubMed

Tieu, Joanna; Hakendorf, Paul; Woodman, Richard J; Patterson, Karen; Walker, Jenny; Roberts-Thomson, Peter

2018-05-01

Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ 2 = 8.75, P = 0.003) and antibody status (log-rank χ 2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality. © 2018 Royal Australasian College of Physicians.

Predictors of Longitudinal Quality of Life in Juvenile Localized Scleroderma.

PubMed

Ardalan, Kaveh; Zigler, Christina K; Torok, Kathryn S

2017-07-01

Localized scleroderma can negatively affect children's quality of life (QoL), but predictors of impact have not been well described. We sought to identify predictors of QoL impact in juvenile localized scleroderma patients. We analyzed longitudinal data from a single-center cohort of juvenile localized scleroderma patients, using hierarchical generalized linear modeling (HGLM) to identify predictors of QoL impact. HGLM is useful for nested data and allows for evaluation of both time-variant and time-invariant predictors. The number of extracutaneous manifestations (ECMs; e.g., joint contracture and hemifacial atrophy) and female sex predicted negative QoL impact, defined as a Children's Dermatology Life Quality Index score >1 (P = 0.019 for ECMs and P = 0.002 for female sex). As the time since the initial visit increased, the odds of reporting a negative QoL impact decreased (P < 0.001). Our results suggest that ECMs, sex, and time since initial visit are more predictive of QoL impact in localized scleroderma than cutaneous features. Further study is required to determine which ECMs have the most impact on QoL, which factors underlie sex differences in QoL in localized scleroderma, and why increasing the time since the initial visit appears to be protective. An improved understanding of predictors of QoL impact may allow for the identification of patients at risk of poorer outcomes and for the tailoring of treatment and psychosocial support. © 2016, American College of Rheumatology.

Autoantigens targeted in scleroderma patients with vascular disease are enriched in endothelial lineage cells

PubMed Central

McMahan, Zsuzsanna H.; Cottrell, Tricia R.; Wigley, Fredrick M.; Antiochos, Brendan; Zambidis, Elias T.; Park, Tea Soon; Halushka, Marc K.; Gutierrez-Alamillo, Laura; Cimbro, Raffaello; Rosen, Antony; Casciola-Rosen, Livia

2016-01-01

Objective Scleroderma patients with autoantibodies to centromere proteins (CENPs) and/or interferon-inducible protein 16 (IFI16) are at increased risk of severe vascular complications. We set out to define whether these autoantigens are enriched in cells of the vasculature. Methods Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI16 and CD31 expression were defined in skin paraffin sections from scleroderma patients and from healthy controls. IFI16 expression was determined by flow cytometry in circulating endothelial cells (CECs) and circulating progenitor cells (CPCs). Results Expression of CENP-A, IFI16 and CD31 was enriched in EBs at days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI16, CD31, CENPs A and-B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of skin paraffin sections showed enrichment of IFI16 in CD31-positive vascular endothelial cells in biopsies from scleroderma patients and normal controls. Flow cytometry analysis revealed IFI16 expression in CPCs, but minimal expression in CECs. Conclusion Expression of scleroderma autoantigens IFI16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens. PMID:27159521

Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

PubMed Central

Kondo, H; Rabin, B S; Rodnan, G P

1976-01-01

Cell-mediated immunity to skin extracts was studied by the macrophage migration inhibition test, lymphocyte transformation, and direct cytotoxicity to skin fibroblasts, in normal individuals and patients with progressive systemic sclerosis. The latter included 18 individuals with diffuse scleroderma and 12 with the CREST syndrome, a variant form of systemic sclerosis in which there is more limited involvement of the skin. Controls consisted of 13 patients with other connective tissue diseases and 16 normal individuals. Phosphate-buffered saline and 3 M KCl extracts of both normal and sclerodermatous skin were used as antigens. No evidence of lymphocyte reactivity was found by the lymphocyte transformation and direct cytotoxicity test procedures. However, the lymphocytes of patients with diffuse scleroderma did respond to extracts of both normal and sclerodermatous skin in the migration inhibition assay. 10 of 16 patients (62.5%) had migration indices below 2 SD of the normal range, 1 of 10 CREST patients and 1 of 13 patients with other connective tissue diseases showed similar reactivity. Antisera specific for immunoglobulin-bearing lymphocytes (B lymphocytes) and T lymphocytes were used to characterize the lymphocytes found in skin biopsies of patients with diffuse scleroderma. T lymphocytes made up the majority of lymphocytes in the skin infiltrates. These findings suggest that lymphocytes sensitized to skin extracts are present in patients with diffuse scleroderma. The cell-mediated immune reaction to skin antigens may be a factor in the pathogenesis of diffuse scleroderma. Images PMID:791970

Sclerotic Regressing Large Congenital Nevus.

PubMed

Patsatsi, Aikaterini; Kokolios, Miltiadis; Pikou, Olga; Lambropoulos, Vasilios; Efstratiou, Ioannis; Sotiriadis, Dimitrios

2016-11-01

Regression of congenital nevi is usually associated with loss of pigment or halo formation. In rare cases, regression is characterized by sclerosis and hair loss. We describe a rare case of a sclerotic hypopigmented large congenital melanocytic nevus in which a localized scleroderma-like reaction process of regression seemed to have started in utero and progressed throughout early childhood. © 2016 Wiley Periodicals, Inc.

Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma.

PubMed

Li, Suzanne C; Torok, Kathryn S; Pope, Elena; Dedeoglu, Fatma; Hong, Sandy; Jacobe, Heidi T; Rabinovich, C Egla; Laxer, Ronald M; Higgins, Gloria C; Ferguson, Polly J; Lasky, Andrew; Baszis, Kevin; Becker, Mara; Campillo, Sarah; Cartwright, Victoria; Cidon, Michael; Inman, Christi J; Jerath, Rita; O'Neil, Kathleen M; Vora, Sheetal; Zeft, Andrew; Wallace, Carol A; Ilowite, Norman T; Fuhlbrigge, Robert C

2012-08-01

Juvenile localized scleroderma (LS) is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies has been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment has made it difficult to compare approaches and identify optimal therapy. Our objective was to develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile LS. A core group of pediatric rheumatologists, dermatologists, and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for juvenile LS using consensus methods/nominal group techniques. Recommendations were validated in 2 face-to-face conferences with a larger group of practitioners with expertise in juvenile LS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the US and Canada. Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (66% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with juvenile LS. Using consensus methodology, we have developed standardized treatment plans and assessment methods for juvenile LS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of juvenile LS. Copyright © 2012 by the American College of Rheumatology.

Mechanism of Hepatocyte Growth Factor Inhibition of Angiotensin II-induced Apoptosis in Primary Lung Cells

DTIC Science & Technology

2010-02-19

infectious agents such as Epstein - Barr virus [53-55], hepatitis C [56-58], influenza [59-61] and cytomegalovirus [62]. Parainfluenza 1 virus [63...J.M., et al., Cryptogenic fibrosing alveolitis and Epstein - Barr virus : an association? Lancet, 1984. 2(8406): p. 768-71. 54. Egan, J.J., et al... Epstein - Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis. Thorax, 1995. 50(12): p. 1234-9. 55. Watanabe, A

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

PubMed

Magro, Cynthia M; Crowson, A Neil; Ferri, Clodoveo

2007-01-01

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Scleroderma: a case report

NASA Astrophysics Data System (ADS)

Harahap, T. A.; Marpaung, B.

2018-03-01

Scleroderma is a complex disease in which extensive fibrosis, vascular alterations, and autoantibodies against various cellular antigens are among the principal features.[1,2] The prevalenceranging from 50 to 300 cases per 1 million persons with women are at much higher risk. The average age of diagnosis is the fifth decades of life.[2] There is no cure for scleroderma, but many of its problems and complications can be treated.[3-7]A 54-year-old female patient with main complains limitation of motion and mouth, stiffness and painful joints in the hands and feet, thickening on the skin in the chest and trunk for eight years, purplish red spots on arms and legs intermittent for tenyears. On physical examination found sclerosis lesions, sclerodactyly on fingers and toes, telangiectasias in the antebrachii and cruris region. On laboratory, examination showed ANA test 10.7 and Anti DS DNA 123. The histopathological of the skin result is scleroderma. The patient was diagnosed with scleroderma and treated with methotrexate 7.5 mg/weeks, ciclosporin 2×100 mg/day, omeprazole 2×20 mg. After seven days of therapy, there is aclinical improvement, and the patient becomes anoutpatient treatment.

Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound

PubMed Central

Kleinert, Stefan; Roll, Petra; Baumgaertner, Christian; Himsel, Andrea; Mueller, Adelheid; Fleck, Martin; Feuchtenberger, Martin; Jenett, Manfred; Tony, Hans-Peter

2012-01-01

Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID:22670165

[Huge aspergilloma developed within a zone of scleroderma-related pulmonary fibrosis].

PubMed

Rakotoson, J L; Vololontiana, H M D; Raherison, R E; Andrianasolo, R L; Rakotomizao, J R; Rakotoharivelo, H; Rajaoarifetra, J; Randria, M J D; Rapelanoro, R F; Andrianarisoa, A C F; Rajaona, H R

2012-02-01

In pulmonary aspergilloma, Aspergillus colonizes and proliferates as a saprophyte in deterged cavities deprived of local defense. Although pulmonary tuberculosis constitutes the one well-know predisposing factor, other causes can create favorable conditions. We describe a first published case of a huge aspergilloma which developed within a zone of pulmonary fibrosis secondary to systemic scleroderma. The patient was a 58-year-old woman in poor general health who experienced repeated episodes of hemoptysis and dyspnea. Physical examination disclosed sclerodactyly, generalized cutaneous sclerosis and Raynaud's phenomenon. There was no clinical history of pulmonary tuberculosis or bronchectasis. Aspergillosis serology was positive. Broncho-alveolar liquid was positive for Aspergillus fumigatus at direct examination and after culture. Immunological assessment confirmed scleroderma. The chest computed tomography scan showed a huge oblong-shaped opacity in the upper left lobe which had developed within a zone of pulmonary fibrosis. Medical management was instituted. The clinical course was marked by repeating hemoptysis and the stability of pulmonary lesions after two years. Management of scleroderma-related pulmonary aspergiloma remains difficult and complicated. Prognosis depends on the course of both conditions, scleroderma and aspergillosis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maquart, F.X.; Bellon, G.; Cornillet-Stoupy, J.

1985-08-01

It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. (/sup 14/C)Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls. By contrast, the amount of collagen, expressed as percentage of total secreted protein, was far higher in scleroderma cultures than in normal ones (14.4% +/- 6.0% vs 4.6% +/- 0.9%). Addition of CTGP to the medium inducedmore » a concentration-dependent inhibition of (/sup 14/C)proline incorporation into proteins from both control and scleroderma cells. In control cultures, no significant decrease of the percentage of collagen was observed, but over 60 micrograms/ml, both cytotoxic effects and inhibition of protein synthesis occurred. In scleroderma cultures, the inhibition was twice as effective on collagen as on noncollagen protein synthesis. The inhibition of collagen secretion was not related either to changes in collagen hydroxylation or to the intracellular catabolism of newly synthesized procollagen.« less

Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nitenberg, A.; Foult, J.M.; Kahan, A.

1986-08-01

The maximum coronary vasodilator capacity after intravenous dipyridamole (0.14 mg X kg-1 X min-1 X 4 minutes) was studied in seven patients with primary scleroderma myocardial disease and compared to that of seven control subjects. Hemodynamic data and left ventricular angiographic data were not different in the two groups. The coronary flow reserve was evaluated by the dipyridamole/basal coronary sinus blood flow ratio (D/B CSBF) and the coronary resistance reserve by the dipyridamole/basal coronary resistance ratio (D/B CR). Coronary reserve was greatly impaired in the group with primary scleroderma myocardial disease: D/B CSBF was lower than in the control groupmore » (2.54 +/- 1.37 vs 4.01 +/- 0.56, respectively; p less than 0.05) and D/B CR was higher than in the control group (0.47 +/- 0.25 vs 0.23 +/- 0.04, respectively; p less than 0.05). Such a decreased coronary flow and resistance reserve in patients with primary scleroderma myocardial disease was not explained by an alteration of left ventricular function. It may be an important contributing factor in the pathogenesis of primary scleroderma myocardial disease.« less

Multifocal fibrosing thyroiditis and its association with papillary thyroid carcinoma using BRAF pyrosequencing.

PubMed

Frank, Renee; Baloch, Zubair W; Gentile, Caren; Watt, Christopher D; LiVolsi, Virginia A

2014-09-01

Multifocal fibrosing thyroiditis (MFT) is characterized by numerous foci of fibrosis in a stellate configuration with fibroelastotic and fibroblastic centers entrapping epithelial structures. MFT has been proposed as a risk factor for papillary thyroid carcinoma (PTC) development. We attempted to identify whether MFT showed such molecular changes and could possibly be related to PTC. We identified seven cases of PTC with MFT in our institutional pathology database and personal consult service of one of the authors (VAL) for the years 1999 to 2012. Areas of PTC, MFT, and normal tissue were selected for BRAF analysis. Macro-dissection, DNA extraction and PCR amplification, and pyrosequencing were performed to detect BRAF mutations in codon 600. All of the MFT lesions and normal thyroid tissue were negative for BRAF mutations. Of the seven PTCs analyzed, five (71 %) were negative for BRAF mutations, while two cases were positive. In our study, none of the MFT lesions harbored BRAF mutations, whereas 29 % (two of seven) PTCs in the same gland were positive. Hence, in this small study, we found no evidence that the MFT lesion is a direct precursor to PTC. It is likely an incidental bystander in the process and a reflection of the background thyroiditis.

Raynaud, digital ulcers and calcinosis in scleroderma.

PubMed

Nitsche, Alejandro

2012-01-01

Raynaud, digital ulcers and calcinosis are frequent manifestations of patients with systemic sclerosis. Digital ulcers are seen in more than half of the patients with scleroderma. Hospitalizations, ischemic complications and impairment of hand function are frequently observed in patients with digital ulcers, especially if treatment is delayed. Rapid and intensive treatment escalation in patients with scleroderma and refractory Raynaud's phenomenon is one of the most effective preventive action available in order to avoid the development of digital ulcers and tissue loss. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Validity, Reliability, and Feasibility of Durometer Measurements of Scleroderma Skin Disease in a Multicenter Treatment Trial

PubMed Central

MERKEL, PETER A.; SILLIMAN, NANCY P.; DENTON, CHRISTOPHER P.; FURST, DANIEL E.; KHANNA, DINESH; EMERY, PAUL; HSU, VIVIEN M.; STREISAND, JAMES B.; POLISSON, RICHARD P.; ÅKESSON, ANITA; COPPOCK, JOHN; van den HOOGEN, FRANK; HERRICK, ARIANE; MAYES, MAUREEN D.; VEALE, DOUGLAS; SEIBOLD, JAMES R.; BLACK, CAROL M.; KORN, JOSEPH H.

2013-01-01

Objective To determine the validity, reliability, and feasibility of durometer measurements of skin hardness as an outcome measure in clinical trials of scleroderma. Methods Skin hardness was measured during a multicenter treatment trial for scleroderma using handheld digital durometers with a continuous scale. Skin thickness was measured by modified Rodnan skin score (MRSS). Other outcome data collected included the Scleroderma Health Assessment Questionnaire. In a reliability exercise in advance of the trial, 9 investigators examined the same 5 scleroderma patients by MRSS and durometry. Results Forty-three patients with early diffuse cutaneous systemic sclerosis were studied at 11 international centers (mean age 49 years [range 24–76], median disease duration 6.4 months [range 0.3–23], and median baseline MRSS 22 [range 11–38]). The reliability of durometer measurements was excellent, with high interobserver intraclass correlation coefficients (ICCs) (0.82–0.92), and each result was greater than the corresponding skin site ICCs for MRSS (0.54–0.85). Baseline durometer scores correlated well with MRSS (r = 0.69, P < 0.0001), patient self-assessments of skin disease (r = 0.69, P < 0.0001), and Health Assessment Questionnaire (HAQ) disability scores (r = 0.34, P = 0.03). Change in durometer scores correlated with change in MRSS (r = 0.70, P < 0.0001), change in patient self-assessments of skin disease (r = 0.52, P = 0.003), and change in HAQ disability scores (r = 0.42, P = 0.017). The effect size was greater for durometry than for MRSS or patient self-assessment. Conclusion Durometer measurements of skin hardness in patients with scleroderma are reliable, simple, accurate, demonstrate good sensitivity to change compared with traditional skin scoring, and reflect patients' self-assessments of their disease. Durometer measurements are valid, objective, and scalable, and should be considered for use as a complementary outcome measure to skin scoring in clinical trials of scleroderma. PMID:18438905

Caveolin-1 regulates leucocyte behaviour in fibrotic lung disease.

PubMed

Tourkina, Elena; Richard, Mathieu; Oates, James; Hofbauer, Ann; Bonner, Michael; Gööz, Pal; Visconti, Richard; Zhang, Jing; Znoyko, Sergei; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

2010-06-01

Reduced caveolin-1 levels in lung fibroblasts from patients with scleroderma and the lungs of bleomycin-treated mice promote collagen overexpression and lung fibrosis. This study was undertaken to determine whether caveolin-1 is deficient in leucocytes from bleomycin-treated mice and patients with scleroderma and to examine the consequences of this deficiency and its reversal. Mice or cells received the caveolin-1 scaffolding domain (CSD) peptide to reverse the pathological effects of reduced caveolin-1 expression. In bleomycin-treated mice, the levels of caveolin-1 in leucocytes and the effect of CSD peptide on leucocyte accumulation in lung tissue were examined. To validate the results in human disease and to identify caveolin-1-regulated molecular mechanisms, monocytes and neutrophils were isolated from patients with scleroderma and control subjects and caveolin-1, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, CXC chemokine receptor 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9) expression/activation were evaluated. These parameters were also studied in monocytes treated with cytokines or CSD peptide. Leucocyte caveolin-1 is important in lung fibrosis. In bleomycin-treated mice, caveolin-1 expression was diminished in monocytes and CSD peptide inhibited leucocyte recruitment into the lungs. These observations are relevant to human disease. Monocytes and neutrophils from patients with scleroderma contained less caveolin-1 and more activated ERK, JNK and p38 than those from control subjects. Treatment with CSD peptide reversed ERK, JNK and p38 hyperactivation. Scleroderma monocytes also overexpressed CXCR4 and MMP-9, which was inhibited by the CSD peptide. Cytokine treatment of normal monocytes caused adoption of the scleroderma phenotype (low caveolin-1, high CXCR4 and MMP-9 and signalling molecule hyperactivation). Caveolin-1 downregulation in leucocytes contributes to fibrotic lung disease, highlighting caveolin-1 as a promising therapeutic target in scleroderma.

Unilateral Nevoid Telangiectasia Associated with Ipsilateral Melorheostosis

PubMed Central

Kim, Jihyun; Cho, Sung Bin; Cho, Suhyun

2012-01-01

Melorheostosis is a rare disorder characterized by irregular, flowing hyperostosis in long bones, commonly described on radiographs as wax flowing down a candle. In addition to bony sclerosis, cutaneous manifestations overlying the involved bones have been reported including linear scleroderma, neurofibromatosis, and vascular and lymphatic malformations. Unilateral nevoid telangiectasia (UNT) is a rare primarily cutaneous condition characterized by linearly arranged small dilated blood vessels in dermatomal or Blaschkoid patterns on the skin. Here, we present the case of a nine-year-old Korean male with UNT associated with ipsilateral melorheostosis. PMID:22577274

Application of cloud database in the management of clinical data of patients with skin diseases.

PubMed

Mao, Xiao-fei; Liu, Rui; DU, Wei; Fan, Xue; Chen, Dian; Zuo, Ya-gang; Sun, Qiu-ning

2015-04-01

To evaluate the needs and applications of using cloud database in the daily practice of dermatology department. The cloud database was established for systemic scleroderma and localized scleroderma. Paper forms were used to record the original data including personal information, pictures, specimens, blood biochemical indicators, skin lesions,and scores of self-rating scales. The results were input into the cloud database. The applications of the cloud database in the dermatology department were summarized and analyzed. The personal and clinical information of 215 systemic scleroderma patients and 522 localized scleroderma patients were included and analyzed using the cloud database. The disease status,quality of life, and prognosis were obtained by statistical calculations. The cloud database can efficiently and rapidly store and manage the data of patients with skin diseases. As a simple, prompt, safe, and convenient tool, it can be used in patients information management, clinical decision-making, and scientific research.

Scleroderma Autoantigens Are Uniquely Fragmented by Metal-catalyzed Oxidation Reactions: Implications for Pathogenesis

PubMed Central

Casciola-Rosen, Livia; Wigley, Fredrick; Rosen, Antony

1997-01-01

The observation that revelation of immunocryptic epitopes in self antigens may initiate the autoimmune response has prompted the search for processes which induce novel fragmentation of autoantigens as potential initiators of autoimmunity. The reversible ischemia reperfusion which characterizes scleroderma has focused attention on reactive oxygen species as molecules which might induce autoantigen fragmentation. We demonstrate that several of the autoantigens targeted in diffuse scleroderma are uniquely susceptible to cleavage by reactive oxygen species, in a metal-dependent manner. Multiple features of the fragmentation reaction and its inhibition indicate that these autoantigens possess metal-binding sites, which focus metal-catalyzed oxidation reactions (and consequent fragmentation) to specific regions of the antigens. These data suggest that the autoantibody response in scleroderma is the immune marker of unique protein fragmentation, induced by ischemia reperfusion in the presence of appropriate metals, and focus attention on abnormal metal status as a potential pathogenic principle in this disease. PMID:8996243

Corticosteroids in Myositis and Scleroderma

PubMed Central

Postolova, Anna; Chen, Jennifer K; Chung, Lorinda

2017-01-01

Synopsis Idiopathic inflammatory myopathies (IIM) involve inflammation of the muscles and are classified based on the patterns of presentation and immunohistopathologic features on skin and muscle biopsy into four categories: dermatomyositis, polymyositis, inclusion body myositis, and immune mediated necrotizing myopathy. The term “scleroderma” refers to fibrosis of the skin. Localized scleroderma (morphea) is skin-limited, while systemic sclerosis (SSc) is associated with vascular and internal organ involvement. Although there is a paucity of randomized clinical trials, treatment with systemic corticosteroids (CS) is the standard of care for IIM with muscle and organ involvement. The extra-cutaneous features of systemic sclerosis are frequently treated with CS, however high doses have been associated with scleroderma renal crisis in high-risk patients. CS monotherapy is neither recommended for the cutaneous manifestations of dermatomyositis nor scleroderma. While CS can be effective first line agents, their significant side effect profile encourages concomitant treatment with other immunosuppressive medications to enable timely tapering. PMID:26611554

Mild Cognitive Impairment as a single sign of brain hemiatrophy in patient with Localized Scleroderma and Parry-Romberg Syndrome.

PubMed

Klimiec, Elzbieta; Klimkowicz-Mrowiec, Aleksandra

2016-01-01

Neurologic involvement is well recognized in Systemic Scleroderma and increasingly reported in Localized Scleroderma. MRI brain abnormalities are often associated with symptoms such as seizures or headaches. In some cases they may be clinically silent. We describe a 23 years old female with head, trunk and limbs scleroderma who developed Parry-Romberg Syndrome. Brain MRI showed ipsilateral temporal lobe atrophy without any prominent neurologic symptoms. Neuropsychological examination revealed Mild Cognitive Impairment. During the 7 years of follow up we have noticed progression of face atrophy but no progression of brain atrophy. Cognitive functions have been stable. This case highlight that major MRI brain abnormalities in LS may occur with only subtle clinical manifestation such as Mild Cognitive Impairment. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Case report of robotic dor fundoplication for scleroderma esophagus with aperistalsis on manometry.

PubMed

Andrade, Alonso; Folstein, Matthew K; Davis, Brian R

2017-01-01

Scleroderma is a systemic disease of collagen deposition resulting in fibrosis of small arteries and arterioles. It commonly affects the skin, lungs, and gastrointestinal tract. The most common site of GI tract involvement is the esophagus. We present the case report of a 44year old female with scleroderma esophagus and severe reflux which was successfully treated with robotic dor fundoplication. Because of the wide variety of symptoms with which this problem can present, a tailored approach taking into consideration the patient's symptomatology and findings during diagnostic work-up was implemented with good results. The patient exhibited complete resolution of symptoms at short term follow up. Robotic dor fundoplication is an effective option for patients with scleroderma esophagus and no evidence of hiatal hernia or esophageal shortening. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Male frontal fibrosing alopecia with generalised hair loss.

PubMed

Chen, Wenchieh; Kigitsidou, Evanthia; Prucha, Hanna; Ring, Johannes; Andres, Christian

2014-05-01

Frontal fibrosing alopecia predominantly affects postmenopausal women and is regarded as a variant of lichen planopilaris. Male cases have rarely been reported. Here we describe a 66-year-old man with a typical receding fronto-temporal hair line in a form of scarring alopecia, which shows features of lichen planopilaris in histology. An extensive loss of body hair involving bilateral axillae, limbs and pubic area was also observed. © 2012 The Authors Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.

Pigmentation abnormalities in systemic scleroderma examined by using a colorimeter (Choromo Meter CR-200).

PubMed

Maeda, M; Kachi, H; Matubara, K; Mori, S; Kitajima, Y

1996-03-01

Cutaneous colors of the dorsum of the hands (A), the distal forearms (B; 5 cm from the wrists), the proximal forearm (C; proximal 1/3 from the elbow) and sternal skin region (D) in patients with systemic scleroderma (73 cases; M:F = 16:57) systemic lupus erythematosus (SLE) or dermatomyositis (27 cases; M:F = 7:20) and healthy controls (HC) (36 cases; M:F = 8:28) was characterized by a XYZ colorimetric system (CIE, 1931) using a colorimeter (Choromo Meter CR-200, Minolta Camera Co. Ltd., Osaka). The index Y, which means color value shows a lower value in male HC and in patients with systemic scleroderma, especially in the more severe type with hyperpigmentation (score 5-6; the system proposed by Ishikawa) than that of female HC. The values of indices x and y, which relate to reddish (erythema with hyperpigmentation) and greenish color (pale), respectively, were higher in the exposed portion of the severe type of systemic scleroderma with hyperpigmentation, especially male and older patients, and in unexposed portions of the female group without hyperpigmentation. Histopathologically, there was prominent pigmentation in the upper dermis of the forearm in the severe type of systemic scleroderma, so that melanin quantity may be closely related to the decrease in index Y. There was no statistical significance in the value of indices Y, x and y between HC, SLE and dermatomyositis. This method may contribute not only to diagnosis of systemic scleroderma and differentiation from other collagen diseases, but also studies of clinical follow-up and effects of medication.

Pirfenidone gel in patients with localized scleroderma: a phase II study.

PubMed

Rodríguez-Castellanos, Marco; Tlacuilo-Parra, Alberto; Sánchez-Enríquez, Sergio; Vélez-Gómez, Ezequiel; Guevara-Gutiérrez, Elizabeth

2015-01-28

Localized scleroderma is an inflammatory disease in its first stages and a fibrotic process in later stages, principally mediated by the transforming growth factor β. To date, there is no standard treatment. The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma. This was an open phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times daily for 6 months. Patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well with a durometer and histologically using hematoxylin and eosin stain and Masson's trichrome stain. The baseline mLoSSI average scores were 5.83 ± 4.80 vs. 0.83 ± 1.75 (P = 0.002) at 6 months. The initial durometer induration of the scleroderma plaques was 35.79 ± 9.10 vs. 32.47 ± 8.97 at 6 months (P = 0.05). We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis and annex atrophy from 12.25 ± 3.25 to 9.75 ± 4.35 (P = 0.032). The 8% pirfenidone gel application was well tolerated, and no side effects were detected. This is the first study on the therapeutic use of pirfenidone gel in localized scleroderma. It acts on both the inflammatory and the fibrotic phases. Considering its effectiveness, good safety profile and the advantage of topical application, pirfenidone is a treatment option in this condition.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

PubMed

Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

2017-12-16

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Post-tuberculous fibrosing mediastinitis: a review of the literature

PubMed Central

Wu, Zhe; Jarvis, Hannah; Howard, Luke S; Wright, Corrina; Kon, Onn Min

2017-01-01

Fibrosing mediastinitis (FM) is a rare disease where there is thickening of the fibrous tissue in the mediastinum. While histoplasmosis is the the most common recognised cause, the link with tuberculosis (TB) has been rarely documented. We review the link between TB and FM, and describe a case of probable TB-related FM.Our case is of a 74-year-old man who presented with breathlessness 3 years after fully treated TB. Scans revealed a calcified soft tissue mass within the mediastinum, and a diagnosis of fibrosing mediastinitis resulting in pulmonary hypertension was made. Tests for histoplasmosis and IgG4 staining were negative. Surgical intervention was not felt to be beneficial, and he was treated with prednisolone and mycophenolate mofetil.In the review, we highlight the two forms of mediastinitis—granulomatous versus fibrous, and how these two entities may be on a spectrum of disease progression. We also explore the prevalence, clinical presentation, pathogenesis, imaging techniques and treatment options of TB-related FM. PMID:28725444

Autologous fat transplantation for the treatment of linear scleroderma en coup de sabre.

PubMed

Ibler, Kristina S; Gramkow, Christina; Siemssen, Peter A

2015-01-01

Scleroderma en coup de sabre is a disfiguring disease for which only limited therapeutic options exist. Three cases of facial linear scleroderma treated with autologous fat transplantation with acceptable results are presented. Autologous fat transplantation was preferred to corrective surgery because of the extent of the lesions and absence of any associated facial distortion. Fat as a filler was chosen to reduce the risk of adverse effects. Adipocytes are suggested to have wider biological effects than other fillers and may offer more durable results. At least two transplantations were needed to evoke a significant effect.

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2012-07-01

Philadelphia, PA 19104 1 Jul 2011 - 30 Jun 2012Annual01-07-2012 This project is focused on an animal model of the human disease, systemic sclerosis ...earliest indicator of tight-skin in the tissue Animal model, systemic sclerosis , scleroderma, Tsk2/+, fibrosis, gene, genetics, TGFβ 35 eblanken...the  multiple  clinical parameters of fibrotic disease from birth  onward.   BODY  Milestones were assigned to this proposal, with tasks to be

The psychological impact of facial changes in scleroderma.

PubMed

Amin, Kavit; Clarke, A; Sivakumar, B; Puri, A; Fox, Z; Brough, V; Denton, C P; Peter, E M; Butler, P; Butler, M D

2011-05-01

The physical disabilities associated with scleroderma are well known but the psychological impact of the condition has received less attention. Few studies have examined appearance related issues, most notably of the face. The aim of this study is to evaluate the psychological impact of facial, aesthetic and functional changes in scleroderma. One hundred seventy-one patients with a clinical diagnosis of scleroderma were recruited into the study. Digital photographs were objectively graded into groups based on severity of disfigurement as judged by an observer. Facial movement was recorded using a modified House-Brackmann Grading Scale. Psychological evaluation comprised the Derriford Appearance Scale short-form (DAS), the Noticeability and Worry score and the Hospital Anxiety and Depression Scale (HADS). Severity of disfigurement predicted decreased mouth opening, the extent to which participants judged their appearance as noticeable to others, and the level of appearance-related concern as measured by the DAS24. There was an inverse relationship with age. Facial changes were ranked as the most worrying aspect of the condition. This study shows facial disfigurement impacts on patient with scleroderma independent of functional changes related to systemic disease. The major difficulty is with the perceived noticeably of the condition to other people and the resulting self-consciousness in social encounters. © 2011 Taylor & Francis

Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database.

PubMed

Ingegnoli, Francesca; Ardoino, Ilaria; Boracchi, Patrizia; Cutolo, Maurizio

2013-09-01

The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Lubatti, Chiara; Meani, Laura; Zahalkova, Lenka; Zeni, Silvana; Fantini, Flavio

2008-07-01

To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs). The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries). The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

PubMed

Martini, Giorgia; Fadanelli, Gloria; Agazzi, Anna; Vittadello, Fabio; Meneghel, Alessandra; Zulian, Francesco

2018-05-03

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently. Copyright © 2018 Elsevier B.V. All rights reserved.

A Patient with Localized Scleroderma Successfully Treated with Etretinate

PubMed Central

Shima, Tomoko; Yamamoto, Yuki; Ikeda, Takaharu; Furukawa, Fukumi

2014-01-01

There are several treatment methods for localized scleroderma, but treatment is difficult when the lesion is widely distributed. We encountered a case who was treated successfully with etretinate, a vitamin A derivative. The usefulness of this agent is discussed. PMID:25408646

Assessment of ventricular and left atrial mechanical functions, atrial electromechanical delay and P wave dispersion in patients with scleroderma.

PubMed

Aktoz, Meryem; Yilmaztepe, Mustafa; Tatli, Ersan; Turan, Fatma Nesrin; Umit, Elif G; Altun, Armagan

2011-01-01

The aim of this study was to investigate ventricular functions and left atrial (LA) mechanical functions, atrial electromechanical coupling, and P wave dispersion in scleroderma patients. Twenty-six patients with scleroderma and twenty-four controls were included. Left and right ventricular (LV and RV) functions were evaluated using conventional echocardiography and tissue Doppler imaging (TDI). LA volumes were measured using the biplane area- -length method and LA mechanical function parameters were calculated. Inter-intraatrial electromechanical delays were measured by TDI. P wave dispersion was calculated by 12-lead electrocardiograms. LV myocardial performance indices (MPI) and RV MPI were higher in patients with scleroderma (p = 0.000, p = 0.000, respectively) while LA passive emptying fraction was decreased and LA active emptying fraction was increased (p = 0.051, p = 0.000, respectively). P wave dispersion and inter-intraatrial electromechanical delay were significantly higher in patients with scleroderma (25 [10-60] vs 20 [0-30], p = 0.000, 16.50 [7.28-26.38] vs 9.44 [3.79-15.78] and 11.33 [4.88-16.06] vs 4.00 [0-12.90], p < 0.05, respectively). Interatrial electromechanical delay was negatively correlated with LV E wave, (p = 0.018). LV E wave was demonstrated to be a factor independent of the interatrial electromechanical delay (R² = = 0.270, b = -0.52, p = 0.013). This study showed that in scleroderma patients, global functions of LV, RV and mechanical functions of LA were impaired, intra-interatrial electromechanical delays were prolonged and P wave dispersion was higher. LV E wave was demonstrated to be a factor that is independent of the interatrial electromechanical delay. Reduced LV E wave may also give additional information on the process of risk stratification of atrial fibrillation.

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

PubMed Central

2011-01-01

Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

Immunopathologic effects of silicone breast implants.

PubMed Central

Teuber, S S; Yoshida, S H; Gershwin, M E

1995-01-01

Silicone-gel breast implants have been associated with a myriad of autoimmune and connective tissue disorders by anecdotal reports and small observational series. To date, no prospective epidemiologic studies have been done to substantiate these observations, but an increasing body of literature is being developed and older studies are being recognized that point to immunotoxic or inflammatory effects of these breast implant components. The development of disease due to implants would depend on the interaction of genetic host factors so that only a few patients would potentially be at risk. Based on the example of other chemically mediated disorders, such as scleroderma in association with silica exposure, latency periods of more than 30 years before disease develops may be possible. Herein we review studies on silicone and immunity. PMID:7785255

Nailfold Capillaroscopy - Its Role in Diagnosis and Differential Diagnosis of Microvascular Damage in Systemic Sclerosis.

PubMed

Lambova, Sevdalina; Hermann, W; Muller-Ladner, Ulf

2013-01-01

In the nailfold area, specific diagnostic microvascular abnormalities are easily recognized via capillaroscopic examination in systemic sclerosis (SSc). They are termed "scleroderma" type capillaroscopic pattern, which includes presence of dilated, giant capillaries, haemorrhages, avascular areas, and neoangiogenic capillaries and are observed in the majority of SSc patients (in more than 90%). LeRoy and Medsger (2001) proposed criteria for early diagnosis of SSc with inclusion of the abnormal capillaroscopic changes and suggested to prediagnose SSc prior to the development of other manifestations of the disease. It is a new era in the diagnosis of SSc. At present, an international multicenter project is performed. It aims validation of criteria for very early diagnosis of SSc (project VEDOSS (Very Early Diagnosis of Systemic Sclerosis) and is organized by European League Against Rheumatism (EULAR) Scleroderma Trials and Reasearch. Very recently the first results of the VEDOSS project were processed and new EULAR/ACR (American College of Rheumatology) classification criteria have been validated and published (2013), in which the characteristic capillaroscopic changes have been included. Our observations confirm the high frequency of the specific capillaroscopic changes of the fingers in SSc, which have been found in 97.2% of the cases from the studied patient population. We have performed for the first time capillaroscopic examinations of the toes in SSc. Interestingly,"scleroderma type" capillaroscopic pattern was also found at the toes in a high proportion of patients - 66.7%, but it is significantly less frequent as compared with fingers (97.2%, p<0.05). In our opinion, the examination of the toes of SSc patients should be considered as it suggests an additional opportunity for evaluation of the microvascular changes in these patients although the observed changes are in a lower proportion of cases. Thus, capillaroscopic examination is a cornerstone for the very early diagnosis of SSc. Patients with clinical symptoms of peripheral vasospasm (Raynaud's phenomenon (RP)) in association with puffy fingers and/or sclerodactyly should be carefully examined. Hence, appearance of "scleroderma" type capillaroscopic changes in RP patients should be interpreted in the clinical context, because some of the components of this pattern may be observed in several other connective tissue diseases such as mixed connective tissue disease, undifferentiated connective tissue disease that are termed "scleroderma-like" capillaroscopic changes. Capillaroscopic examination is an obligatory screening method in these cases, but the pathologic capillaroscopic changes are not specific and their interpretation is in clinical context.

Scleroderma in children: an update.

PubMed

Zulian, Francesco; Cuffaro, Giorgio; Sperotto, Francesca

2013-09-01

Scleroderma, in its localized and systemic presentation, represents the third most frequent rheumatic condition in childhood after juvenile idiopathic arthritis and systemic lupus erythematosus. Early diagnosis, appropriate assessment and effective treatment are crucial to improve the long-term outcome. Recent studies, concerning histopathology and clinical associations with other conditions, open new horizons on the etiopathogenesis of scleroderma. New developments have been also reached in the field of outcome measures. In juvenile localized scleroderma (JLS), new techniques such as Doppler and laser Doppler imaging have shown their usefulness for the daily monitoring of the patients. In juvenile systemic sclerosis (JSSc), a new severity score has been developed and needs to be validated in future trials. Finally, a randomized, double-blind controlled trial, a multicenter consensus statement and long-term follow-up studies have confirmed the important role of methotrexate (MTX) for the treatment of JLS. Studies over recent years highlighted the role of imaging as outcome measures for JLS and introduced a severity score for JSSc. New studies on MTX confirmed its important role for the treatment of JLS.

[Scleroderma cluster among type-setters].

PubMed

Magnavita, N

2007-01-01

The etiology of systemic sclerosis, probably multifactorial, is not yet well defined. Among the many endogenous and exogenous factors probably involved, occupational elements may play an essential role. Here we report a cluster of local scleroderma and systemic sclerosis, which occurred in a small group of typography workers exposed to polyvinyl-acetate glues, containing up to 1% of vinyl-acetate. Vinyl acetate exposure has been associated with acidification of the intracellular environment, which is thought to produce cytotoxic and/or mitogenic responses that are the sentinel pharmacodynamic steps toward cancer. Autoantibody production in systemic sclerosis depends upon intracellular acidification. More studies are needed to clarify the relationship between vinyl acetate exposure and scleroderma.

Pediatric scleroderma: systemic or localized forms.

PubMed

Torok, Kathryn S

2012-04-01

Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Histological features of localized scleroderma 'en coup de sabre': a study of 16 cases.

PubMed

Taniguchi, T; Asano, Y; Tamaki, Z; Akamata, K; Aozasa, N; Noda, S; Takahashi, T; Ichimura, Y; Toyama, T; Sugita, M; Sumida, H; Kuwano, Y; Miyazaki, M; Yanaba, K; Sato, S

2014-12-01

Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings in localized scleroderma. Since en coup de sabre (ECDS) is a certain subset of localized scleroderma with a relatively uniform clinical manifestation, we focused on this disease subset and evaluated its histopathological features. A total of 16 patients with ECDS were retrospectively evaluated on the basis of clinical and histological findings. Regardless of clinical manifestations, vacuolar degeneration was found in all of the ECDS patients. Importantly, keratinocyte necroses were restricted to early and active ECDS lesions. In early ECDS patients (disease duration of <3 years), moderate to severe perivascular and/or periappendageal lymphocytic infiltrate and vacuolar changes in follicular epithelium were more prominent, whereas epidermal atrophy was less frequently observed, than in late ECDS patients (disease duration of ≥6 years). Vacuolar degeneration at the dermoepidermal junction is a common histological feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degeneration of follicular epithelium are characteristic especially in early ECDS, further supporting a canonical idea that the elimination of mutated epidermal cells by immune surveillance contributes to tissue damage and resultant fibrosis in localized scleroderma. © 2013 European Academy of Dermatology and Venereology.

Evaluation of mean platelet volume in localized scleroderma.

PubMed

Bahali, Anil Gulsel; Su, Ozlem; Emiroglu, Nazan; Cengiz, Fatma Pelin; Kaya, Mehmet Onur; Onsun, Nahide

2017-01-01

Localized scleroderma is a chronic inflammatory skin disease characterized by sclerosis of the dermis and subcutaneous tissue. Platelets play an important role in inflammation. Following activation, platelets rapidly release numerous mediators and cytokines, which contribute to inflammation. To evaluate whether there was any relation between localized scleroderma and platelet parameters. Forty-one patients with localized scleroderma were enrolled in the study. The control group consisted of 30 healthy subjects. The mean platelet volume level in the patient group was 9.9 ± 1.3 fl and in the control group was 7.6 ± 1.1 fl. This difference was statistically significant (p< 0.001). The plateletcrit values are minimally higher in the patient group as compared to the control group. It was statistically significant (p<0.001). There was no significant difference in the platelet counts between the two groups (p= 0.560) In the patient group, there was no significant relation between the mean platelet volume levels and clinical signs of disease (p=0.09). However, plateletcrit values are higher in generalized than localized forms of disease (p=0.01). The limited number of patients and the retrospective nature of the study were our limitations. This study suggests that platelets might play a role in the pathogenesis of scleroderma. Platelet parameters may be used as markers for evaluating disease severity and inflammatory processes. Thus, there is a need for more detailed and prospective studies.

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study.

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Smith, Vanessa; Cutolo, Maurizio; Foeldvari, Ivan

2015-11-01

Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. Copyright © 2015 Elsevier Inc. All rights reserved.

Defining the Role of Integrin Alpha 11 in Wound Healing and Fibrosis

DTIC Science & Technology

2009-09-01

Introduction Scleroderma is characterized by fibrosis, the replacement of healthy tissue with collagenous matrix. The collagen-binding integrins are...Itga11 and determine its role in the etiology of fibrosis and scleroderma . Body The heterozygous (Het) phenotype of one intact Itga11 allele and one

Microscopic characterization of orchid mycorrhizal fungi: Scleroderma as a putative novel orchid mycorrhizal fungus of Vanilla in different crop systems.

PubMed

González-Chávez, Ma Del Carmen A; Torres-Cruz, Terry J; Sánchez, Samantha Albarrán; Carrillo-González, Rogelio; Carrillo-López, Luis Manuel; Porras-Alfaro, Andrea

2018-02-01

Vanilla is an orchid of economic importance widely cultivated in tropical regions and native to Mexico. We sampled three species of Vanilla (V. planifolia, V. pompona, and V. insignis) in different crop systems. We studied the effect of crop system on the abundance, type of fungi, and quality of pelotons found in the roots using light and electron microscopy and direct sequencing of mycorrhizal structures. Fungi were identified directly from pelotons obtained from terrestrial roots of vanilla plants in the flowering stage. Root samples were collected from plants in crop systems located in the Totonacapan area in Mexico (states of Puebla and Veracruz). DNA was extracted directly from 40 pelotons and amplified using ITS rRNA sequencing. Peloton-like structures were observed, presenting a combination of active pelotons characterized by abundant hyphal coils and pelotons in various stages of degradation. The most active pelotons were observed in crop systems throughout living tutors (host tree) in comparison with roots collected from dead or artificial tutors. Fungi identified directly from pelotons included Scleroderma areolatum, a common ectomycorrhizal fungus that has not been reported as a mycorrhizal symbiont in orchids. Direct amplification of pelotons also yielded common plant pathogens, including Fusarium and Pyrenophora seminiperda, especially in those sites with low colonization rates, and where large numbers of degraded pelotons were observed. This research reports for the first time the potential colonization of Vanilla by Scleroderma, as a putative orchid mycorrhizal symbiont in four sites in Mexico and the influence of crop system on mycorrhizal colonization on this orchid.

CT findings in malignant pleural mesothelioma related to nonoccupational exposure to asbestos and fibrous zeolite (erionite)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erzen, C.; Eryilmaz, M.; Kalyoncu, F.

1991-03-01

Endemic malignant pleural mesothelioma (MPM) in Turkey is related to two mineral fibers, tremolite asbestos and fibrous zeolite (erionite). Thirteen cases of MPM from the Cappadocian area, where the soil is rich in erionite, and 29 cases of MPM, from villages whose occupants have high asbestos exposure, were examined by CT. The CT findings of the two groups of MPM were compared with respect to the configuration of the pleural lesions, stage of disease, fissural involvement, pleural effusion, presence of calcified pleural plaques, and chronic fibrosing pleuritis. In erionite-related MPM the pleural lesions were flat and smooth in 69.1%; inmore » asbestos-related MPM the lesions were nodular in 55.1%. Stage IV disease, calcified pleural plaques, and chronic fibrosing pleuritis were more common in the erionite-related MPM. The rest of the findings were similar in both groups. The early radiological diagnosis of erionite-related MPM may be even more difficult because of the similarity of the pleural lesions to chronic fibrosing pleuritis.« less

Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases.

PubMed

Pascucci, Anabella; Lynch, Peter J; Fazel, Nasim

2016-05-01

Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.

Hyaluronic Acid is Overexpressed in Fibrotic Lung Tissue and Promotes Collagen Expression

DTIC Science & Technology

2009-04-01

inflammation, and fibrosis (i.e. the overexpression of collagen). Lung fibrosis is the major cause of morbidity and mortality in scleroderma and is...References……………………………………………………………………………. 8 Appendices…………………………………………………………………………… 9 INTRODUCTION Systemic scleroderma is a... scleroderma . The overexpression of collagen I in fibrotic lung tissue is accompanied by the overexpression of other ECM molecules (e.g. the proteins

South Australian Scleroderma Register: analysis of deceased patients.

PubMed

Bond, C; Pile, K D; McNeil, J D; Ahern, M J; Smith, M D; Cleland, L G; Roberts-Thomson, P J

1998-11-01

The demographic, clinical, pathological and serological features of 123 decreased patients with systemic sclerosis have been analysed. These patients consisted of all identified patients dying with this disease in South Australia between 1983 and 1996 inclusive. There were 85 females and 38 males, with the ratio of limited:diffuse:overlap disease subset being 9:5:1. Disease characteristics revealed that patients with the limited disease tended to be female with high frequencies of the centromere autoantibody, while patients with the diffuse disease had equal gender representation with the frequent presence of nucleolar, speckled or homogeneous antinuclear antibody. Mean duration of disease and mean age of death for the limited:diffuse:overlap subsets differed significantly between groups (p < 0.05) and were 16.5, 9.3 and 10.9 years and 71.9, 57.8 and 52.8 years respectively. Cumulative survival curves for the subsets differed highly significantly, with patients with the limited diseases dying more commonly from right heart failure (documented terminally in 25% of the centromere positive limited subset), cardiovascular disease or cancer, while patients with the diffuse subset died from respiratory failure, renal failure or cardiovascular disease. In conclusion, this retrospective analysis has revealed that scleroderma is a relatively common but clinically heterogeneous disorder. There are important clinical and prognostic implications in defining limited versus diffuse versus overlap disease.

Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'.

PubMed

Englert, H; Champion, D; Wu, J C; Giallussi, J; McGrath, M; Manolios, N

2011-02-01

In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration

PubMed Central

Ogawa, Rei; Hsu, Chao-Kai

2013-01-01

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers–Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases. PMID:23672502

308nm Excimer Laser in Dermatology

PubMed Central

Mehraban, Shadi

2014-01-01

308nm xenon-chloride excimer laser, a novel mode of phototherapy, is an ultraviolet B radiation system consisting of a noble gas and halide. The aim of this systematic review was to investigate the literature and summarize all the experiments, clinical trials and case reports on 308-nm excimer laser in dermatological disorders. 308-nm excimer laser has currently a verified efficacy in treating skin conditions such as vitiligo, psoriasis, atopic dermatitis, alopecia areata, allergic rhinitis, folliculitis, granuloma annulare, lichen planus, mycosis fungoides, palmoplantar pustulosis, pityriasis alba, CD30+ lympho proliferative disorder, leukoderma, prurigo nodularis, localized scleroderma and genital lichen sclerosus. Although the 308-nm excimer laser appears to act as a promising treatment modality in dermatology, further large-scale studies should be undertaken in order to fully affirm its safety profile considering the potential risk, however minimal, of malignancy, it may impose. PMID:25606333

Chronic exposure of interleukin-13 suppress the induction of matrix metalloproteinase-1 by tumour necrosis factor α in normal and scleroderma dermal fibroblasts through protein kinase B/Akt.

PubMed

Brown Lobbins, M L; Shivakumar, B R; Postlethwaite, A E; Hasty, K A

2018-01-01

Peripheral blood mononuclear cells taken from patients with scleroderma express increased levels of interleukin (IL)-13. Moreover, the expression of matrix metalloproteinase-1 (MMP-1) from involved scleroderma skin fibroblasts is refractory to stimulation by tumour necrosis factor (TNF)-α. To elucidate the mechanism(s) involved, we examined the effect of IL-13 on TNF-α-induced MMP-1 expression in normal and scleroderma human dermal fibroblast lines and studied the involvement of serine/threonine kinase B/protein kinase B (Akt) in this response. Dermal fibroblast lines were stimulated with TNF-α in the presence of varying concentrations of IL-13. Total Akt and pAkt were quantitated using Western blot analyses. Fibroblasts were treated with or without Akt inhibitor VIII in the presence of IL-13 followed by TNF-α stimulation. MMP-1 expression was analysed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using analysis of variance (anova) or Student's t-test. Upon TNF-α stimulation, normal dermal fibroblasts secrete more MMP-1 than systemic sclerosis (SSc) fibroblasts. This increase in MMP-1 is lost when fibroblasts are co-incubated with IL-13 and TNF-α. IL-13 induced a significant increase in levels of pAkt in dermal fibroblasts, while Akt inhibitor VIII reversed the suppressive effects of IL-13 on the response of cultured fibroblasts to TNF-α, increasing their expression of MMP-1. We show that IL-13 suppresses MMP-1 in TNF-α-stimulated normal and scleroderma dermal fibroblast. Akt inhibitor VIII is able to reverse the suppressive effect of IL-13 on MMP-1 expression and protein synthesis. Our data suggest that IL-13 regulates MMP-1 expression in response to TNF-α through an Akt-mediated pathway and may play a role in fibrotic diseases such as scleroderma. © 2017 British Society for Immunology.

[Pathogenesis of skin scleroderma--literature review].

PubMed

Wojas-Pelc, Anna; Lipko-Godlewska, Sylwia

2005-01-01

The pathogenesis of skin scleroderma (LS) is still unknown. Disturbances of vessels system, connective tissue metabolism and humoral and cellular immunological response is observed. Antinuclear antibodies are detected in 30-80% of patients with different types of skin scleroderma. They are present more often in patients with disseminated lesions and linear type of LS compared to morphoea au plaque. In our own analysis 28.5% of patients had also antibodies directed against Borrelia burgdorferi. It is believed that the injury of endothelial cells and proliferation in medial part of small vessels - which both lead to chronic ischemia - are the earliest disturbances observed in histopathological examination of the skin taken from systemic as well as from skin scleroderma patients. During last few years, there were some interesting reports concerning functional changes of endothelial cells which led to disturbances in tension of vessels smooth muscles. Free radicals - in genetically predispose people--can also provoke scleroderma lesions through their injury action on endothelial cells and stimulation of fibroblasts. In morphoea, the process of fibrosis begins around vessels. Deposition of connective tissue matrix is observed, especially collagen type I and III. This stimulation of fibroblasts as well as accumulation of connective tissue matrix are secondary to some stimulatory factors. These are: PDF, bFGF, TGFbeta and some cytokines. In morphoea patients serum levels of IL-1, IL-2, IL-4, IL-6 and IL-8 were elevated. In literature, levels and production of collagenases were decreased, although more authors say that tissue inhibitors of metalloproteinases are the main factor in fibrosis. The analysis of data tends to suspicion that enormous fibrosis observed in different types of scleroderma can be the result of increased production of collagen and other components of connective tissue as well as their incomplete degradation. Presented clinical and laboratory data show how many different factors influence etiopathogenesis of morphoea.

Immunochemical characterization of the anti-RNA antibodies found in scleroderma and systemic lupus erythematosus. II. Reactivity with hsa-coupled, uridine-containing, monophosphoric ribodinucleotides.

PubMed Central

Alarcón-Segovia, D; Fishbein, E; Estrada-Parra, S; García-Ortigoza, E

1976-01-01

Sera from patients with scleroderma have been found to have anti-RNA antibodies which react with human serum albumin (HSA)-coupled uridine and uridine monophosphate (UMP) and are inhibited by uracil, uridine and UMP. Scleroderma sera react uniformly with 5'-polyuridylic acid (poly(U)) and fail to react with polyadenylic, polyuridylic acid poly(A) - poly(U)) which is also indicative of their uracil specificity. Anti-RNA antibodies found in systemic lupus erythematosus (SLE) are immunochemically different from those found in scleroderma in that, instead of being uniformly specific to uracil, they are markedly heterogeneous and may react with uracil, uridine and/or UMP. SLE sera frequently react with poly(A) - poly(U), indicating also their ability to recognize the double helical structure of double-stranded RNA. Thirty-seven scleroderma and thirty-four SLE sera from as many patients with either of these conditions were tested against HSA-coupled, uridine-containing monophosphoric dinucleotides in an attempt to characterize further their anti-RNA antibodies. Scleroderma sera were found to react primarily with dinucleotides in which uridine was the base proximal to the carrier protein and, except for sera that also contained antibodies to adenosine which reacted with UpA, they failed to react with dinucleotides in which uridine was in a terminal position only. Reaction with dinucleotides in which uridine was proximal to the carrier protein could be inhibited by uracil but not by the corresponding terminal base. Some lupus sera were found to react with both dinucleotides that contain the same bases in opposite sequence, e.g. ApU and UpA, while others were found to react with only one of the sequences. They were also found to react more frequently with dinucleotides in which HSA was coupled to a base other than uridine, suggesting that the reaction is primarily due to anti-DNA antibodies. Because immunization with dinucleotides coupled to protein prepared by the same method we have used, yields higher specificity to the base attached to the carrier protein, our findings suggest that, in scleroderma, a single event, akin to that of immunization with a purified antigen, gives rise to the anti-RNA antibodies, whereas in systemic lupus erythematosus there is a considerably wider immunological aberration. PMID:1082854

Localized Scleroderma: A Clinical Review.

PubMed

Tratenberg, Mark; Gutwein, Farrah; Rao, Varuni; Sperber, Kirk; Wasserrman, Amy; Ash, Julia

2017-01-01

Localized scleroderma (LS) is characterized by excessive collagen deposition leading to thickening of the dermis, subcutaneous tissue or both. The outcome for most patients with localized scleroderma is directly related to the type and stage of the affected tissue. The major challenge for untreated patients is not increased mortality risk, rather deformity and growth defects from skin, muscle and bone abnormalities. Treatment is individualized to type and stage of the lesion and may include pharmacologic and non-pharmacologic therapies. Among the pharmacologic modalities, methotrexate with systemic glucocorticoids is currently the mainstay of treatment. More controlled trials are needed to determine the length of treatment and the maintenance dose of this combination therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens.

PubMed

Ek, Weronica; Sahlqvist, Anna-Stina; Crooks, Lucy; Sgonc, Roswitha; Dietrich, Hermann; Wick, Georg; Ekwall, Olov; Andersson, Leif; Carlborg, Örjan; Kämpe, Olle; Kerje, Susanne

2012-10-01

Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21 days of age) and late (175 days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nailfold Capillaroscopy Within and Beyond the Scope of Connective Tissue Diseases.

PubMed

Lambova, Sevdalina Nikolova; Muller-Ladner, Ulf

2018-04-20

Nailfold capillaroscopy is a noninvasive instrumental method for morphological analysis of the nutritive capillaries in the nailfold area. In rheumatology, it is a method of choice among instrumental modalities for differential diagnosis between primary and secondary Raynaud's phenomenon (RP) in systemic rheumatic diseases. RP is a common diagnostic problem in rheumatology. Defining the proper diagnosis is a prerequisite for administration of the appropriate treatment. Thus, nailfold capillaroscopic examination is of crucial importance for the every-day practice of the rheumatologists and is currently gaining increasing attention. The most specific capillaroscopic changes are observed in Systemic Sclerosis (SSc). Due to the high prevalence of the capillaroscopic changes in this clinical entity and their early appearance, they could be used for early and very early diagnosis of the disease. More recently, "scleroderma" type capillaroscopic changes have been defined as diagnostic criterion in the new EULAR/ACR classification criteria for SSc together with the presence of scleroderma-related autoantibodies, RP, telangiectasia and other clinical signs. Capillaroscopic changes in other connective tissue diseases and in different rheumatic-like conditions like those in diabetes mellitus (e.g., diabetic stiff-hand syndrome) and paraneoplastic syndromes associated with microvascular pathology should be interpreted properly in order to obtain precise diagnosis in the shortest possible differential diagnostic process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Bidirectional cell traffic between mother and fetus: new insights in pediatric and adult disorders].

PubMed

Guillemin, M; Reinert, P

2002-02-01

There is a heavy traffic of cells and DNA through the placenta during pregnancy. The rate of fetal cells in the maternal blood is correlated with abnormalities, such as aneuploidy and pre-eclampsia. Studying and quantifying these cells could improve antenatal diagnosis techniques, especially for Down syndrome. Maternal-fetal microchimerism is frequently observed in several auto-immune diseases in adulthood, such as systemic scleroderma. Studies suggest a rather allo-immune pathophysiology, involving maternal-fetal HLA compatibility. Microchimerism is also found in auto-immune diseases in children. Thus, the cells traffic offers new insights for antenatal diagnosis techniques and pathophysiology of auto-immune diseases.

Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

PubMed Central

Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

2014-01-01

Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

Predicting Treatment Outcomes and Responder Subsets in Scleroderma-related Interstitial Lung Disease

PubMed Central

Roth, Michael D.; Tseng, Chi-Hong; Clements, Philip J.; Furst, Daniel E.; Tashkin, Donald P.; Goldin, Jonathan G.; Khanna, Dinesh; Kleerup, Eric C.; Li, Ning; Elashoff, David; Elashoff, Robert E.

2014-01-01

Objectives To identify baseline characteristics of patients with Scleroderma-Related Interstitial Lung Disease (SSc-ILD) which predict the most favorable response to a 12-month treatment with oral cyclophosphamide (CYC). Methods Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in %-predicted Forced Vital Capacity (FVC) and the placebo-adjusted change in %-predicted FVC over time (the CYC treatment effect). Results Completion of the CYC arm of the Scleroderma Lung Study was associated with a placebo-adjusted improvement in %-predicted FVC of 2.11% at 12 months which increased to 4.16% when patients were followed for another 6 months (p=0.014). Multivariate regression analyses identified the maximal severity of reticular infiltrates on baseline high-resolution computerized tomography (HRCT), the modified Rodnan Skin Score (mRSS), and Mahler's Baseline Dyspnea Index (BDI) as independent correlates of treatment response. When patients were stratified based on whether 50% or more of any lung zone was involved by reticular infiltrates on HRCT and/or the presence of a mRSS of at least 23, a subgroup emerged with an average CYC treatment effect of 4.73% at 12 months and 9.81% at 18 months (p<0.001). Conversely, there was no treatment effect (−0.58%) in patients with less severe HRCT findings and a lower mRSS. Conclusions A retrospective analysis of the Scleroderma Lung Study identified the severity of reticular infiltrates on baseline HRCT and the baseline mRSS as patient features that might predict responsiveness to CYC therapy. PMID:21547897

Mechanical properties of the gastro-esophageal junction in health, achalasia, and scleroderma.

PubMed

Mearin, F; Fonollosa, V; Vilardell, M; Malagelada, J R

2000-07-01

Manometric assessment of the gastro-esophageal junction (GEJ) is deceptive in that ignores key dynamic properties of the junction, such as resistance to flow and compliance. Our aim was to investigate the mechanical properties of the GEJ comprising intraluminal pressure (measured by manometry), resistance to flow and compliance (measured by resistometry). We studied 8 healthy subjects, 11 patients with achalasia and 11 patients with scleroderma. We used a pneumatic resistometer, previously developed and validated in our laboratory. The resistometer consists of a flaccid polyurethane 5-cm cylinder connected to an electronically regulated nitrogen-injection system; the instrument records nitrogen flow through the cylinder while maintaining a constant pressure gradient between its proximal and distal ends. By placing the cylinder successively in the proximal stomach and along the GEJ we measured the GEJ-gastric resistance gradient (GEJ resistance minus gastric resistance) and were able to calculate the cumulative resistance (sum of resistance exerted at each pressure level), peak resistance (at any injection pressure), nil resistance point (injection pressure in mmHg at which GEJ resistance equals gastric resistance), and compliance slope (flow/pressure relationship). We found that GEJ resistance to flow (cumulative resistance, peak resistance, and nil resistance point) is significantly increased in achalasia and decreased in scleroderma (P < 0.05 versus health) while GEJ compliance is diminished in achalasia (P < 0.05 versus health) and normal in scleroderma. Achalasia is a disease characterized by increased GEJ resistance and rigidity. By contrast, although scleroderma is characterized by decreased GEJ resistance, GEJ compliance may be normal.

Detecting Subclinical Biventricular Impairment in Scleroderma Patients by Use of Pulsed-Wave Tissue Doppler Imaging

PubMed Central

Can, Ilknur; Onat, Ahmet Mesut; Aytemir, Kudret; Akdogan, Ali; Ureten, Kemal; Kiraz, Sedat; Ertenli, Ihsan; Tokgozoglu, Lale; Oto, Ali

2009-01-01

Systemic scleroderma is a disease that is characterized by excessive fibroblastic activity and collagen deposition in various organs, including the heart. We sought to evaluate the limits of biventricular function as derived noninvasively from pulsed-wave tissue Doppler imaging (TDI) of tricuspid and mitral annular motion in patients who had scleroderma. We enrolled 24 patients with scleroderma (study group; mean age, 49 ± 11 yr; 20 women) and 24 healthy participants (control group; mean age, 51 ± 9 yr; 19 women). Persons with cardiovascular risk factors were excluded. We obtained images by conventional echocardiography and by pulsed-wave TDI, measuring the respective peak systolic velocities (S, Sm) and peak early (E, Em) and late (A, Am) diastolic velocities. Mean Sm, mean Em, and mean Am were averages of the 4 measured sites (anterior, inferior, lateral, and septal). We calculated noninvasive estimates of left ventricular (LV) filling pressure by dividing E velocities (from the mitral inflow) by Em velocities (E/Em ratios). Biventricular regional Sm, regional LV myocardial Em, and ratios of myocardial Em/atrial component velocity (Em/Am) for the LV, and mean Sm, mean Em, and mean Em/mean Am ratios for the LV were significantly lower in the study group. The E/Em ratio was higher in the study group (7.3 ± 2.6 vs 5.2 ± 1.0, P = 0.01). Global LV systolic and diastolic function did not differ between the groups. Tissue Doppler imaging complements conventional echocardiography in detecting subclinical biventricular impairment in patients with scleroderma who have normal global measurements. PMID:19436783

A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia

PubMed Central

Kobayashi, Takehiko; Kitaichi, Masanori; Tachibana, Kazunobu; Kishimoto, Yutaro; Inoue, Yasushi; Kagawa, Tomoko; Maekura, Toshiya; Sugimoto, Chikatoshi; Arai, Toru; Akira, Masanori; Inoue, Yoshikazu

2017-01-01

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. Rare cases of organizing pneumonia are rapidly progressive. Yousem et al. studied pathologic predictors of idiopathic bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis. Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74-year-old female non-smoker presented with a 2-week history of dry cough followed by dyspnea and a fever. The clinical course was fulminant, but we successfully performed bronchoscopy. After the diagnosis of FOP, we treated the patient with mechanical ventilation and high-doses of steroids/immunosuppressants, which improved the disease. PMID:28502934

Aberrant Recapitulation of Developmental Program: Novel Target in Scleroderma

DTIC Science & Technology

2015-12-01

promoter hypermethylation in systemic sclerosis. Annals of the rheumatic diseases . 2014;73:1232-1239) ...can prevent or attenuate fibrosis in scleroderma, and to ascertain whether markers of -catenin signaling can be used as biomarkers of disease activity...and disease subtype, FVC, DLCO and PAP will be analyzed by linear regression. (Months 1-12) We have successfully measured Wnt activity using LSL

Scanning laser Doppler imaging may predict disease progression of localized scleroderma in children and young adults.

PubMed

Shaw, L J; Shipley, J; Newell, E L; Harris, N; Clinch, J G; Lovell, C R

2013-07-01

Localized scleroderma is a rare but potentially disfiguring and disabling condition. Systemic treatment should be started early in those with active disease in key functional and cosmetic sites, but disease activity is difficult to determine clinically. Superficial blood flow has been shown to correlate with disease activity in localized scleroderma. To examine whether superficial blood flow measured by laser Doppler imaging (LDI) has the potential to predict disease progression and therefore select patients for early systemic treatment. A group of 20 individuals had clinical assessment and scanning LDI blood-flow measurements of 32 affected body sites. After a mean follow-up of 8.7 months their clinical outcome was compared with the results of the initial LDI assessment. Eleven out of 15 patients with an assessment of active LDI had progressed clinically, and 16 out of the 17 scans with inactive LDI assessment had not progressed, giving a positive predictive value of 73% and a negative predictive value of 94%. We believe that LDI can be a useful tool in predicting disease progression in localized scleroderma, and it may help clinicians to decide which patients to treat early. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

PubMed

Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

2014-01-01

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

PubMed

Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

2014-01-01

A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

[Lower incidence of severe damage to target organs in mexican patients with systemic sclerosis and diffuse skin affection].

PubMed

Rojas-Serrano, Jorge; Codina-Velásquez, Helga; Medrano-Ramírez, Gabriel; Abraham Simón, J; Vera-Lastra, Olga; Vázquez-Mellado, Janitzia

2008-01-01

To determine the cumulative incidence of severe organ involvement in Mexican patients with systemic sclerosis (SS) and diffuse scleroderma at 3 years from the onset of SS symptoms, and to compare itwith the cumulative incidence observed in a cohort of white patients with SS. Patients with SS and diffuse scleroderma were evaluated within the first 2 years from the onset of SS symptoms and were included. An estimation of the cumulative incidence of severe involvement to the skin, kidney, heart, lungs, and gastrointestinal track at 3 years from the onset of SS symptoms was carried out. This cumulative incidence was compared with that of white SS patients with diffuse scleroderma, using the one sample test for a binomial proportion. Sixty-three patients were included. The cumulative incidence of severe involvement to the skin was 3.17% (2/63) (95% CI, 0.04%-11); kidney involvement in 4.17% (3/63) (95% CI, 0.99%-13.29%); heart involvement in 1.6% (1/63) (95% CI, 0.04%-8.5%); lung involvement in 11.11% (7/63) (95% IC, 4.5%-21.5%); and gastrointestinal involvement in 4.7% (3/63) (95% IC, 0.99%-13.3%). Mexican patients had a lower Reumatol Clin. 2008;4(1):3-7 3 02 ORIG 2582 (3-7).qxp 23/1/08 11:09 Página 4 Rojas-Serrano J et al. Incidencia de daño grave en pacientes mexicanos con esclerosis sistémica incidence of severe skin involvement (P=.0001), kidney involvement (P=.03) and heart involvement (P=.03) compared to white SS patients with diffuse scleroderma. The cumulative incidence of severe organ involvement in SS Mexican patients with diffuse scleroderma was determined. The incidence of severe skin, kidney and heart involvement is lower than in white SS patients with diffuse scleroderma. Copyright © 2008 Elsevier España. Reumatología Clínica ® Sociedad Española de Reumatología and ® Colegio Mexicano de Reumatología. Published by Elsevier Espana. All rights reserved.

Correlation of Glomerular Filtration Rate Between Renal Scan and Estimation Equation for Patients With Scleroderma.

PubMed

Suebmee, Patcharawan; Foocharoen, Chingching; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Theerakulpisut, Daris; Nanagara, Ratanavadee

2016-08-01

Renal involvement in scleroderma is life-threatening. Early detection of a deterioration of the glomerular filtration rate (GFR) is needed to preserve kidney function. To (A) determine the correlation between (1) estimated GFR (eGFR) using 4 different formulae and (2) measured GFR (mGFR) using isotopic renal scan in Thai patients with scleroderma with normal serum creatinine and (B) to define the factors influencing eGFR. A cross-sectional study was performed in adult Thai patients with scleroderma at Srinagarind Hospital, Khon Kaen University, between December 2013 and April 2015. GFR was measured using the gold standard Tc-99m DTPA (Tc-99m diethylenetriaminepentaacetic acid) renal scan. We compared the latter with the eGFR, calculated using the Cockroft-Gault formula, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and creatinine clearance equation. A total of 76 patients with scleroderma (50 women and 26 men) with median age 54.8 years (interquartile range: 47.4 to 58.9) were enrolled. Mean disease duration was 5.6 ± 4.5 years. Median value of mGFR was 100.1 ± 27.6mL/minute/1.73m². There was a correlation between mGFR from the Tc-99m DTPA renal scan and the eGFR using the Cockroft-Gault formula, MDRD and CKD-EPI equation (P = 0.01, <0.001 and <0.001, respectively), but no correlation with eGFR using the creatinine clearance equation (P = 0.27). Body weight, prednisolone use and systolic blood pressure (SBP) had a negative association with mGFR (P = 0.01, 0.01 and 0.007, respectively). After multivariate analysis, SBP was the only clinical parameter that influenced mGFR (P = 0.03). The Cockroft-Gault formula, MDRD study equation and CKD-EPI were useful formulae for assessing GFR in Thai patients with scleroderma. Higher SBP was associated with a lower GFR. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Generalized morphea in a child with harlequin ichthyosis: a rare association.

PubMed

Giacomin, Maria F A; França, Camila M P; Oliveira, Zilda N P; Machado, Maria C R; Sallum, Adriana M E; Silva, Clovis A

2016-01-01

Harlequin ichthyosis (HI) is a severe and rare hereditary congenital skin disorder characterized by excessive dryness, ectropion and eclabion. The association of ichthyosis with systemic sclerosis has been described in only three children. No patient with generalized morphea (GM) associated with harlequin ichthyosis was described. A 4-years and 6-months girl, diagnosed with harlequin ichthyosis based on diffuse cutaneous thickening, scaling, erythema, ectropion and eclabium since the first hours of birth was described. She was treated with acitretin (1.0mg/kg/day) and emollient cream. At 3 years and 9 months, she developed muscle contractures with pain on motion and limitation in elbows and knees, and diffuse sclerodermic plaques on the abdomen, back, suprapubic area and lower limbs. Skin biopsy showed rectified epidermis and mild hyperorthokeratosis, reticular dermis with perivascular and periadnexal infiltrates of lymphocytes and mononuclear cells, and reticular dermis and sweat gland sclerosis surrounded by a dense collagen tissue, compatible with scleroderma. The patient fulfilled the GM subtype criteria. Methotrexate and prednisone were introduced. At 4 years and 3 months, new scleroderma lesions occurred and azathioprine was associated with previous therapy, with no apparent changes after two months. A case of harlequin ichthyosis associated with a GM was reported. The treatment of these two conditions is a challenge and requires a multidisciplinary team. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study.

PubMed

Khanna, Dinesh; Yan, Xiaohong; Tashkin, Donald P; Furst, Daniel E; Elashoff, Robert; Roth, Michael D; Silver, Richard; Strange, Charlie; Bolster, Marcy; Seibold, James R; Riley, David J; Hsu, Vivien M; Varga, John; Schraufnagel, Dean E; Theodore, Arthur; Simms, Robert; Wise, Robert; Wigley, Fredrick; White, Barbara; Steen, Virginia; Read, Charles; Mayes, Maureen; Parsley, Ed; Mubarak, Kamal; Connolly, M Kari; Golden, Jeffrey; Olman, Mitchell; Fessler, Barri; Rothfield, Naomi; Metersky, Mark; Clements, Philip J

2007-05-01

To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment. One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed. After adjustment for baseline scores, differences in the HAQ DI, SF-36 role physical, general health, vitality, role emotional, mental health scales, and SF-36 mental component summary (MCS) score were statistically significant for CYC versus placebo (P < 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF-36, HAQ DI, and SF-6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF-36 MCS score (33.3% versus 18.5%), and SF-6D score (21.3% versus 3.8%). One year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.

Induction of Scleroderma Fibrosis in Skin-Humanized Mice by Administration of Anti-Platelet-Derived Growth Factor Receptor Agonistic Autoantibodies.

PubMed

Luchetti, Michele M; Moroncini, Gianluca; Jose Escamez, Maria; Svegliati Baroni, Silvia; Spadoni, Tatiana; Grieco, Antonella; Paolini, Chiara; Funaro, Ada; Avvedimento, Enrico V; Larcher, Fernando; Del Rio, Marcela; Gabrielli, Armando

2016-09-01

To describe a skin-SCID mouse chimeric model of systemic sclerosis (SSc; scleroderma) fibrosis based on engraftment of ex vivo-bioengineered skin using skin cells derived either from scleroderma patients or from healthy donors. Three-dimensional bioengineered skin containing human keratinocytes and fibroblasts isolated from skin biopsy specimens from healthy donors or SSc patients was generated ex vivo and then grafted onto the backs of SCID mice. The features of the skin grafts were analyzed by immunohistochemistry, and the functional profile of the graft fibroblasts was defined before and after treatment with IgG from healthy controls or SSc patients. Two procedures were used to investigate the involvement of platelet-derived growth factor receptor (PDGFR): 1) nilotinib, a tyrosine kinase inhibitor, was administered to mice before injection of IgG from SSc patient sera (SSc IgG) into the grafts, and 2) human anti-PDGFR monoclonal antibodies were injected into the grafts. Depending on the type of bioengineered skin grafted, the regenerated human skin exhibited either the typical scleroderma phenotype or the healthy human skin architecture. Treatment of animals carrying healthy donor skin grafts with SSc IgG resulted in the appearance of a bona fide scleroderma phenotype, as confirmed by increased collagen deposition and fibroblast activation markers. Results of the experiments involving administration of nilotinib or monoclonal antibodies confirmed the involvement of PDGFR. Our results provide the first in vivo demonstration of the fibrotic properties of anti-PDGFR agonistic antibodies. This bioengineered skin-humanized mouse model can be used to test in vivo the progression of the disease and to monitor response to antifibrotic drugs. © 2016, American College of Rheumatology.

Cardiovascular assessment of asymptomatic patients with juvenile-onset localized and systemic scleroderma: 10 years prospective observation.

PubMed

Borowiec, A; Dabrowski, R; Wozniak, J; Jasek, S; Chwyczko, T; Kowalik, I; Musiej-Nowakowska, E; Szwed, H

2012-02-01

The aim of the present study was non-invasive evaluation of the cardiovascular system in asymptomatic young adult patients with juvenile localized scleroderma (JLS) and juvenile systemic sclerosis (JSS). A group of 34 consecutive children with scleroderma were prospectively observed in the study. The control group (CG) consisted of 20 healthy subjects. In each subject 12-lead electrocardiographic, echocardiographic, ECG Holter, and ambulatory blood pressure monitoring examinations were performed at the baseline visit and after 10 years. Additionally, B-type natriuretic peptide (BNP) concentrations were measured after 10 years. Examinations were performed in 13 patients with JLS and 15 with JSS at the final visit. Two children had died (one from each group). Four patients were alive but refused the final visit. After 10 years, a higher prevalence of ventricular extrasystoles (p = 0.01) and an elevated pulmonary arterial pressure (JLS: p = 0.04, JSS: p = 0.03) were observed in both groups, but in comparison with the controls there was no significant difference at the final visit. In JLS patients more cases of left ventricle diastolic dysfunction, hypertension, and sinus tachycardia were diagnosed at the final visit (p ≤ 0.05). More atrioventricular block episodes in both groups of scleroderma patients were observed. Over the 10 years, arterial hypertension was diagnosed in three patients from the JLS group and in two with JSS. There were no significant differences in BNP concentrations at the final visit. The results of the present study show that juvenile scleroderma seems to be more benign than adult-onset disease. This observational study shows subclinical, not severe, cardiac abnormalities in adult patients with juvenile-onset disease.

Non-malignant Fibrosing Tumors in the Pediatric Hand: A Clinicopathologic Case Review

PubMed Central

Baumholtz, Michael A.; Popek, Edwina; Schneider, Adam M.

2008-01-01

Non-malignant fibrosing tumors in the pediatric hand or juvenile fibromatoses are clinically challenging because of their relatively infrequent occurrence and because of the variety of names associated with these diseases. We conducted a review of a personal case series of pediatric patients with these tumors and discuss here the more common histologic types and clinical characteristics of the disease spectrum in the context of the available published literature. All histologic samples were reviewed by a single pathologist. Infantile myofibromatosis, fibrous hamartoma of infancy, juvenile aponeurotic fibromatosis, palmar fibromatosis (Dupuytren’s type), infantile digital fibromatosis (Reye’s tumor), fibroma of the tendon sheath, and melorheostosis represent the encountered lesions. PMID:19048350

Discovery or Extinction of New Scleroderma Species in Amazonia?

PubMed

Baseia, Iuri G; Silva, Bianca D B; Ishikawa, Noemia K; Soares, João V C; França, Isadora F; Ushijima, Shuji; Maekawa, Nitaro; Martín, María P

2016-01-01

The Amazon Forest is a hotspot of biodiversity harboring an unknown number of undescribed taxa. Inventory studies are urgent, mainly in the areas most endangered by human activities such as extensive dam construction, where species could be in risk of extinction before being described and named. In 2015, intensive studies performed in a few locations in the Brazilian Amazon rainforest revealed three new species of the genus Scleroderma: S. anomalosporum, S. camassuense and S. duckei. The two first species were located in one of the many areas flooded by construction of hydroelectric dams throughout the Amazon; and the third in the Reserva Florestal Adolpho Ducke, a protected reverse by the INPA. The species were identified through morphology and molecular analyses of barcoding sequences (Internal Transcribed Spacer nrDNA). Scleroderma anomalosporum is characterized mainly by the smooth spores under LM in mature basidiomata (under SEM with small, unevenly distributed granules, a characteristic not observed in other species of the genus), the large size of the basidiomata, up to 120 mm diameter, and the stelliform dehiscence; S. camassuense mainly by the irregular to stellate dehiscence, the subreticulated spores and the bright sulfur-yellow colour, and Scleroderma duckei mainly by the verrucose exoperidium, stelliform dehiscence, and verrucose spores. Description, illustration and affinities with other species of the genus are provided.

Scleroderma in the Caribbean: characteristics in a Dominican case series.

PubMed

Gottschalk, Paola; Vásquez, Ricardo; López, Persio David; Then, Jossiell; Tineo, Carmen; Loyo, Esthela

2014-01-01

Scleroderma is a rare disease with limited data in Latin America. Preliminary genetic studies suggest a strong African ascendance in the Dominican Republic, which could modulate the expression of the disease. The objective of this study is to describe the clinical and demographic characteristics of scleroderma in a series of 26 Dominican patients. Patients who fulfilled the EULAR/ACR criteria for scleroderma were selected from the Rheumatology Department of a tertiary health center; systemic sclerosis subtypes were defined according to the EULAR classification. Clinical and demographic information was obtained retrospectively from clinical records. Mean age at time of onset was 32.6±15 years; 68% of patients had 40 years of age or less. 73% of patients was feminine, with a female:male ratio of 2.7:1. The most affected systems were pulmonary and gastrointestinal; renal affection was scarce. Anti-Scl-70 antibodies were positive in 64% of patients, sometimes in coexistence with anti-centromere antibodies. The prevalence of systemic sclerosis is lower in the Dominican population than the reported elsewhere. The age of onset of the disease seems to be lower in the Dominican population than that reported in literature. A different pattern of autoantibodies is observed in this population. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Cytokine profiles in localized scleroderma and relationship to clinical features.

PubMed

Kurzinski, Katherine; Torok, Kathryn S

2011-08-01

Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future. Published by Elsevier Ltd.

Discovery or Extinction of New Scleroderma Species in Amazonia?

PubMed Central

Baseia, Iuri G.; Silva, Bianca D. B.; Ishikawa, Noemia K.; Soares, João V. C.; França, Isadora F.; Ushijima, Shuji; Maekawa, Nitaro

2016-01-01

The Amazon Forest is a hotspot of biodiversity harboring an unknown number of undescribed taxa. Inventory studies are urgent, mainly in the areas most endangered by human activities such as extensive dam construction, where species could be in risk of extinction before being described and named. In 2015, intensive studies performed in a few locations in the Brazilian Amazon rainforest revealed three new species of the genus Scleroderma: S. anomalosporum, S. camassuense and S. duckei. The two first species were located in one of the many areas flooded by construction of hydroelectric dams throughout the Amazon; and the third in the Reserva Florestal Adolpho Ducke, a protected reverse by the INPA. The species were identified through morphology and molecular analyses of barcoding sequences (Internal Transcribed Spacer nrDNA). Scleroderma anomalosporum is characterized mainly by the smooth spores under LM in mature basidiomata (under SEM with small, unevenly distributed granules, a characteristic not observed in other species of the genus), the large size of the basidiomata, up to 120 mm diameter, and the stelliform dehiscence; S. camassuense mainly by the irregular to stellate dehiscence, the subreticulated spores and the bright sulfur-yellow colour, and Scleroderma duckei mainly by the verrucose exoperidium, stelliform dehiscence, and verrucose spores. Description, illustration and affinities with other species of the genus are provided. PMID:28002414

Parasitization by Scleroderma guani influences protein expression in Tenebrio molitor pupae.

PubMed

Zhu, Jia-Ying; Wu, Guo-Xing; Ze, Sang-Zi; Stanley, David W; Yang, Bin

2014-07-01

Ectoparasitoid wasps deposit their eggs onto the surface and inject venom into their hosts. Venoms are chemically complex and they exert substantial impact on hosts, including permanent or temporary paralysis and developmental arrest. These visible venom effects are due to changes in expression of genes encoding physiologically relevant proteins. While the influence of parasitization on gene expression in several lepidopterans has been reported, the molecular details of parasitoid/beetle relationships remain mostly unknown. This shortcoming led us to pose the hypothesis that envenomation by the ectoparasitic ant-like bethylid wasp Scleroderma guani leads to changes in protein expression in the yellow mealworm beetle Tenebrio molitor. We tested our hypothesis by comparing the proteomes of non-parasitized and parasitized host pupae using iTRAQ-based proteomics. We identified 41 proteins that were differentially expressed (32↑- and 9↓-regulated) in parasitized pupae. We assigned these proteins to functional categories, including immunity, stress and detoxification, energy metabolism, development, cytoskeleton, signaling and others. We recorded parallel changes in mRNA levels and protein abundance in 14 selected proteins following parasitization. Our findings support our hypothesis by documenting changes in protein expression in parasitized hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review

PubMed Central

Breuckmann, Frank; Gambichler, Thilo; Altmeyer, Peter; Kreuter, Alexander

2004-01-01

Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications. PMID:15380024

Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses.

PubMed

Guyard, Alice; Danel, Claire; Théou-Anton, Nathalie; Debray, Marie-Pierre; Gibault, Laure; Mordant, Pierre; Castier, Yves; Crestani, Bruno; Zalcman, Gérard; Blons, Hélène; Cazes, Aurélie

2017-06-15

Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry. Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%. This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

Deciphering the main venom components of the ectoparasitic ant-like bethylid wasp, Scleroderma guani.

PubMed

Zhu, Jia-Ying

2016-04-01

Similar to venom found in most venomous animals, parasitoid venoms contain a complex cocktail of proteins with potential agrichemical and pharmaceutical use. Even though parasitoids are one of the largest group of venomous animals, little is known about their venom composition. Recent few studies revealed high variated venom composition existing not only in different species but also between closely related strains, impling that increasing information on the venom proteins from more greater diversity of species of different taxa is key to comprehensively uncover the complete picture of parasitoid venom. Here, we explored the major protein components of the venom of ectoparasitic ant-like bethylid wasp, Scleroderma guani by an integrative transcriptomic-proteomic approach. Illumina deep sequencing of venom apparatus cDNA produced 49,873 transcripts. By mapping the peptide spectral data derived from venom reservoir against these transcripts, mass spectrometry analysis revealed ten main venom proteins, including serine proteinase, metalloprotease, dipeptidyl peptidase IV, esterase, antithrombin-III, acid phosphatase, neural/ectodermal development factor IMP-L2 like protein, venom allergen 3, and unknown protein. Interestingly, one serine proteinase was firstly identified with rarely high molecular weight about 200 kDa in parasitoid venom. The occurrence of abundant acid phosphatase, antithrombin-III and venom allergen 3 demonstrated that S. guani venom composition is similar to that of social wasp venoms. All identified venom genes showed abundantly biased expression in venom apparatus, indicating their virulent functions involved in parasitization. This study shed light on the more better understanding of parasitoid venom evolution across species and will facilitate the further elucidation of function and toxicity of these venom proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

Examination of the association of sex and race/ethnicity with appearance concerns: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort study.

PubMed

Jewett, Lisa R; Kwakkenbos, Linda; Carrier, Marie-Eve; Malcarne, Vanessa L; Bartlett, Susan J; Furst, Daniel E; Gottesman, Karen; Mayes, Maureen D; Assassi, Shervin; Harcourt, Diana; Williamson, Heidi; Johnson, Sindhu R; Körner, Annett; Steen, Virginia; Fox, Rina S; Gholizadeh, Shadi; Mills, Sarah D; Molnar, Jacqueline C; Rice, Danielle B; Thombs, Brett D

2016-01-01

Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95, p<.001). Black patients had significantly greater odds of appearance concerns than White patients in unadjusted (OR=2.64, 95% CI=1.01-6.34, p=.030), but not multivariate analysis (OR=1.76, 95% CI=0.67-4.60, p=.250). Compared to a general population sample, appearance concerns were substantially more common in SSc, particularly for men across all age groups and for younger women. The most commonly reported features of concern were related to the face and head, followed by the hands and fingers; this did not differ by sex or race/ethnicity. Appearance concerns were common in SSc. Women were substantially more likely than men to have appearance concerns. Although non-significant in multivariate analysis, Black patients were more likely to have concerns than White patients, likely due to more severe changes in appearance.

Biomarker-Based Prediction Models for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease

DTIC Science & Technology

2017-10-01

in the baseline samples of the Scleroderma Lung Study II (SLS II). We are currently analyzing whether these serum proteins have predictive...In this project, we use the valuable samples collected in the Scleroderma Lung Study II (SLSII) clinical trial and the observational cohort, GENISOS...determine key serum protein levels and transcript signatures in whole blood and skin samples collected in the SLSII study . The identified candidate

Gadolinium-Induced Fibrosis.

PubMed

Todd, Derrick J; Kay, Jonathan

2016-01-01

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

Occipital neuralgia: anatomic considerations.

PubMed

Cesmebasi, Alper; Muhleman, Mitchel A; Hulsberg, Paul; Gielecki, Jerzy; Matusz, Petru; Tubbs, R Shane; Loukas, Marios

2015-01-01

Occipital neuralgia is a debilitating disorder first described in 1821 as recurrent headaches localized in the occipital region. Other symptoms that have been associated with this condition include paroxysmal burning and aching pain in the distribution of the greater, lesser, or third occipital nerves. Several etiologies have been identified in the cause of occipital neuralgia and include, but are not limited to, trauma, fibrositis, myositis, fracture of the atlas, and compression of the C-2 nerve root, C1-2 arthrosis syndrome, atlantoaxial lateral mass osteoarthritis, hypertrophic cervical pachymeningitis, cervical cord tumor, Chiari malformation, and neurosyphilis. The management of occipital neuralgia can include conservative approaches and/or surgical interventions. Occipital neuralgia is a multifactorial problem where multiple anatomic areas/structures may be involved with this pathology. A review of these etiologies may provide guidance in better understanding occipital neuralgia. © 2014 Wiley Periodicals, Inc.

La fibrose rétropéritonéale: à propos de 12 cas

PubMed Central

Majdoub, Aziz El; Khallouk, Abdelhak; Farih, Moulay Hassan

2017-01-01

La fibrose rétropéritonéale (FRP) est une maladie rare. Elle se caractérise par la transformation progressive du tissu adipeux rétopéritonéal en une masse fibreuse qui enserre l'aorte, la veine cave inférieure et les voies urinaires responsable d'une altération progressive de la fonction rénale. Le mode habituel de présentation de cette maladie comporte l'association de douleurs lombaires, d'une insuffisance rénale, et d'un syndrome inflammatoire biologique. Nous rapportons 12 cas de fibrose rétropéritonéale dont nous précisons les particularités cliniques, radiologiques et thérapeutiques. Il s'agit d'une étude rétrospective portant sur douze cas de fibrose rétropéritonéale colligés au service d'urologie au CHU Hassan II de Fès durant une période de 9 ans (2005-2013). Il s'agissait de dix hommes et deux femmes. La symptomatologie clinique était très variable, dominée par la douleur lombaire qui était présente chez tous les malades et une hydrocèle chez un patient. Les explorations biologiques avaient montré une insuffisance rénale chez tous les malades et un syndrome inflammatoire chez dix patients. Le diagnostic de la maladie était suspecté dans tous les cas sur les données de l'échographie qui a montré une obstruction de la voie excrétrice supérieure sans obstacle visible chez tous les malades, et confirmé par la TDM abdominale sans injection du produit de contraste qui objectivait une lésion tissulaire rétropéritonéale engainant les vaisseaux et les voies urinaires. Dans notre série, la fibrose rétropéritonéale était idiopathique dans neuf cas. Elle était péri anévrysmale chez deux malades, et post radiothérapie chez un malade. Tous nos patients avaient bénéficié d'un drainage urinaire par sonde urétérale double J. Sept malades avaient reçu une corticothérapie. Une amélioration clinique et biologique, avec disparition de la douleur et amélioration de l'état général, a été observée chez 6 patients. A travers cette étude nous avons confirmé la rareté de la fibrose rétropéritonéale, la difficulté de son diagnostic, la fréquence de la douleur, du syndrome inflammatoire et de l'insuffisance rénale. La TDM abdominale sans injection du produit de contraste confirme le diagnostic. Le drainage urinaire est indispensable dans la plupart des cas et le suivi régulier des malades est nécessaire. PMID:29610632

Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature.

PubMed

Gelber, Allan C; Manno, Rebecca L; Shah, Ami A; Woods, Adrianne; Le, Elizabeth N; Boin, Francesco; Hummers, Laura K; Wigley, Fredrick M

2013-07-01

Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-2.2), renal (OR, 1.6; 95% CI, 1.2-2.1), digital ischemia (OR, 1.5; 95% CI, 1.4-2.2), muscle (OR, 1.7; 95% CI, 1.3-2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1-9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4-2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0-1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings.

Scleroderma and dentistry: Two case reports.

PubMed

Dixit, Shantanu; Kalkur, Chaithra; Sattur, Atul P; Bornstein, Michael M; Melton, Fred

2016-10-24

Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues causing vascular disturbances which can result in tissue hypoxia. These changes are manifested as atrophy of the skin and/or mucosa, subcutaneous tissue, muscles, and internal organs. Such changes can be classified into two types, namely, morphea (localized) and diffuse (systemic). Morphea can manifest itself as hemifacial atrophy (Parry-Romberg syndrome) although this remains debatable. Hence, we present a case of morphea, associated with Parry-Romberg syndrome, and a second case with the classical signs of progressive systemic sclerosis. Case one: A 20-year-old man of Dravidian origin presented to our out-patient department with a complaint of facial asymmetry, difficulty in speech, and loss of taste sensation over the last 2 years. There was no history of facial trauma. After physical and radiological investigations, we found gross asymmetry of the left side of his face, a scar on his chin, tongue atrophy, relative microdontia, thinning of the ramus/body of his mandible, and sclerotic lesions on his trunk. Serological investigations were positive for antinuclear antibody for double-stranded deoxyribonucleic acid and mitochondria. A biopsy was suggestive of morphea. Hence, our final diagnosis was mixed morphea with Parry-Romberg syndrome. Case two: A 53-year-old woman of Dravidian origin presented to our out-patient department with a complaint of gradually decreasing mouth opening over the past 7 years. Her medical history was noncontributory. On clinical examination, we found her perioral, neck, and hand skin to be sclerotic. Also, her fingers exhibited bilateral telangiectasia. An oral examination revealed completely edentulous arches as well as xerostomia and candidiasis. Her serological reports were positive for antinuclear antibodies against centromere B, Scl-70, and Ro-52. A hand and wrist radiograph revealed acro-osteolysis of the middle finger on her right hand. Hence, our final diagnosis was progressive systemic sclerosis. Through this article, we have tried to emphasize the importance of a general examination when diagnosing rare systemic diseases such as scleroderma and the role of the general dentist when caring for such patients, even though they can be quite rare in general practice.

[Two cases of frontal fibrosing alopecia in postmenopausal women].

PubMed

Herrmann, Anke; Bormann, Gisela; Marsch, Wolfgang Christian; Wohlrab, Johannes

2004-08-01

Frontal fibrosing alopecia (FFA) is an uncommon, slowly progressive, cicatricial alopecia which mainly affects postmenopausal women. It is considered to be a variant of lichen planopilaris. We describe two postmenopausal women who developed over 11 and 24 months an asymptomatic atrophic alopecia, restricted to the frontal hairline. The diagnosis of FFA was confirmed by biopsy showing a perifollicular lymphocytic infiltrate with fibrosis. Topical corticosteroids, in one case combined with minoxidil, administered for 3 months arrested the hair loss. The treatment of FFA is often difficult. In most cases, the disease resolves spontaneously after several years. Immunomodulators such as corticosteroids and calcineurin antagonists should be tried in the early stage of FFA (frontal effluvium with perifollicular erythema) in order to arrest the disease in its inflammatory phase.

[Rheumatic features of Grave's disease in children].

PubMed

Chávez-Legaspi, M; Ocampo-Campos, R; García-Velarde, E; Ríos-González, J

1992-01-01

We report three cases from girls with Graves disease who developed serious rheumatic manifestations. One patient had systemic lupus erythematosus with articular, renal, neurological and cardiac afectation with fatal outcome. Other patient presented clinical features of scleroderma with skin thickness, myopathy, arthritis, Raynaud's phenomenon and findings of pulmonary fibrosis. A lupus-like syndrome associated to methimazole therapy (polyarthritis, rash and hemolytic anemia) with positive Cel-LE preparations but negative antinuclear-antibodies was observed in a third patient. A careful history and the recognition of these manifestations will help in the identification of these syndromes.

Clinical Investigation Program. Annual Research Progress Report.

DTIC Science & Technology

1980-09-30

1 Derma, Voi O, No. I, Spriny 1980. Thompson, P.B., Aeling, J.L., Chalet, M.D.; Collagen : Basic Science and Related Diseases, J of the Assoc of Mil...Oxidation in Rat Skeletal Muscle M LLb,.,dria. (0) (P) (PR) .......... ... 080 78/114 Treatment of Systemic Scleroderma with Minoxidil (U-1858) (0...D- .. . i. . tut Il Sumilrc, ry )tluc I) ~ (T~ProtNo.: 78/114 77 > Treatment of Systemic Scleroderma with Minoxidil (U-1858) .,, r- L-. Jun 79 L

Mercuric chloride induces autoantibodies against U3 small nuclear ribonucleoprotein in susceptible mice.

PubMed Central

Reuter, R; Tessars, G; Vohr, H W; Gleichmann, E; Lührmann, R

1989-01-01

Autoantibodies to nucleolar components are a common serological feature of patients suffering from scleroderma, a collagen vascular autoimmune disease. While animal models, which spontaneously develop abundant anti-nucleolar antibodies, have not yet been described, high titers of such antibodies may be induced by treating susceptible strains of mice with mercuric chloride. We have identified the nucleolar autoantigen against which the HgCl2-induced IgG autoantibodies from mice of strain B10.S are directed. It is a protein with an apparent molecular mass of 36 kDa and a pI value of approximately 8.6, which is associated with the nucleolar small nuclear RNA U3, and by these criteria must be identical with a polypeptide called fibrillarin. It is striking that scleroderma patients spontaneously produce autoantibodies against the same U3 ribonucleoprotein (RNP). The HgCl2-induced murine and the scleroderma-specific human anti-U3 RNP autoantibodies were indistinguishable in their reactivities toward fibrillarin. They further resemble each other insofar as both recognize epitopes on the 36-kDa protein, which have been highly conserved throughout evolution. Our results provide a basis to investigate at the molecular level whether similar immunoregulatory dysfunctions may lead to the preferential anti-U3 RNP autoantibody production in the animal model and in scleroderma patients. Images PMID:2521387

Histomorphometric Analysis of Cutaneous Remodeling in the Early Stage of the Scleroderma Model

PubMed Central

de Oliveira, Cristiane Carla; Velosa, Ana Paula Pereira; Parra, Edwin Roger; Capelozzi, Vera Luiza; Teodoro, Walcy Rosolia; Yoshinari, Natalino Hajime

2009-01-01

INTRODUCTION/OBJECTIVES Systemic sclerosis, or scleroderma, is a rheumatic disease characterized by autoimmunity, vasculopathy, and fibrosis of the skin and several internal organs. In the present study, our aim was to assess the skin alterations in animals with scleroderma during the first stages of disease induction. METHODS: To induce scleroderma, female New Zealand rabbits (n = 12) were subcutaneously immunized with 1 mg/ml of collagen V (Col V) in complete Freund’s adjuvant, twice with a thirty-day interval. Fifteen days later, the animals received an intramuscular booster with type V collagen in incomplete Freund’s adjuvant, twice with a fifteen-day interval. The control group was inoculated with 1 ml of 10 mM acetic acid solution diluted with an equal amount of Freund’s adjuvant. Serial dorsal skin biopsies were performed at 7, 15, and 30 days and stained with H&E, Masson’s trichrome and Picrosírius for morphological and morphometric analyses. RESULTS: Immunized rabbits presented a significant increase in collagen in skin collected seven days after the first immunization (p=0.05). CONCLUSION: The results from this experimental model may be very important to a better understanding of the pathogenic mechanisms involved in the beginning of human SSc. Therapeutic protocols to avoid early remodeling of the skin may lead to promising treatments for SSc in the future. PMID:19578663

Outcomes of lung transplantation in patients with scleroderma.

PubMed

Massad, Malek G; Powell, Charles R; Kpodonu, Jacques; Tshibaka, Cimenga; Hanhan, Ziad; Snow, Norman J; Geha, Alexander S

2005-11-01

Patients with pulmonary insufficiency due to scleroderma have long been considered suboptimal candidates for lung transplantation. This has been supported by small single-center experiences that did not reflect the entire U.S. experience. We sought to evaluate the outcome of patients with scleroderma who underwent lung transplantation. We conducted a retrospective review of 47 patients with scleroderma who underwent lung transplantation at 23 U.S. centers between 1987 and 2004 and were reported to the United Network for Organ Sharing. Women constituted 57% of the patients. The mean age was 46 years. Twenty-seven patients received single lung transplants (57%), and the remaining received double lung transplants. The mean cold ischemia time was 4.1 hours. There were 7 early deaths (< or =30 days) and 17 late deaths (> 30 days). The causes of early death were primary graft failure and a cardiac event in two patients each and bacterial infection and stroke in one patient each. Late mortality was due to infection in seven patients, respiratory failure in three, malignancy in two, and multisystem organ failure, rejection, pulmonary hypertension, and a cardiac event in one patient each. The causes of early and late death were not recorded for two patients. One patient received a second transplant owing to graft failure of the first. Twenty-three patients (49%) were alive at a mean follow-up of 24 months. The Kaplan-Meier 1- and 3-year survival rates were 67.6% and 45.9% respectively, which are not significantly different from those of 10,070 patients given transplants for other lung conditions during the same period (75.5% and 58.8% respectively, P = 0.25). Donor gender, recipient's age, and type of transplant did not affect survival. In carefully selected patients with scleroderma who have end-stage lung disease, lung transplantation is a valid life-saving therapeutic option. Available data suggest acceptable short-term morbidity and mortality and a long-term survival similar to that of patients given transplants for other lung conditions.

Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.

PubMed

Badea, I; Taylor, M; Rosenberg, A; Foldvari, M

2009-03-01

SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.

Fertility and pregnancy outcome in women with systemic sclerosis.

PubMed

Steen, V D; Medsger, T A

1999-04-01

To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants. However, a well-timed pregnancy with careful obstetric monitoring will maximize the likelihood of a successful outcome.

Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

PubMed

Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

2018-05-02

We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

New developments in juvenile systemic and localized scleroderma.

PubMed

Foeldvari, Ivan

2013-11-01

Juvenile localized scleroderma (jLS) and juvenile systemic sclerosis (jSS) are both orphan diseases, with jLS around 10 times more frequent than jSS. In recent years the time gap between the appearance of symptoms and diagnosis has become significantly shorter. This review focuses on the new classifications of jSS and jLS, and on the developments and adaptations of the outcome measures for certain organ involvements whereby progress has been made regarding pediatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Recent Developments in the Classification, Evaluation, Pathophysiology, and Management of Scleroderma Renal Crisis.

PubMed

Ghossein, Cybele; Varga, John; Fenves, Andrew Z

2016-01-01

Scleroderma renal crisis (SRC) is an uncommon complication of systemic sclerosis. Despite the advent of angiotensin-converting inhibitor therapy, SRC remains a life-threatening complication. Recent studies have contributed to a better understanding of SRC, but much remains unknown regarding its pathophysiology, risk factors, and optimal management. Genetic studies provide evidence that immune dysregulation might be a contributing factor, providing hope that further research in this direction might illuminate pathogenesis and provide novel predictors for this complication.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2014-10-01

fibrosis, interstitial lung diseases 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...cadherin-11 in scleroderma patients with interstitial lung disease . We have been working with our collaborators at UTHSC to identify and sera that...83% female, avg age 49, avg disease duration 2.5 years, 59% with diffuse SSc, 28% with ILD and avg skin score of 16 at enrollment). Since there is

Frontal fibrosing alopecia treatment options.

PubMed

Fertig, Raymond; Tosti, Antonella

2016-11-01

Frontal fibrosing alopecia (FFA) is a rare dermatologic disease that causes scarring and hair loss and is increasing in prevalence worldwide. FFA patients typically present with hair loss in the frontal scalp region and eyebrows which may be associated with sensations of itching or burning. FFA is a clinically distinct variant of lichen planopilaris (LPP) that affects predominantly postmenopausal women, although men and premenopausal women may also be affected. Early diagnosis and prompt treatment are necessary to prevent definitive scarring and permanent hair loss. Data from retrospective studies indicate that 5-alpha-reductase inhibitors (5aRIs) are effective in stabilizing the disease. In our clinical experience, we have seen optimal results treating FFA patients with oral finasteride in conjunction with hydroxychloroquine, topical calcineurin inhibitors (tacrolimus) and excimer laser in patients with signs of active inflammation.

Uterine prolapse with endometrial eversion in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis in a cat.

PubMed

Valentine, Matthew J; Porter, Susan; Chapwanya, Aspinas; Callanan, John J

2016-01-01

This case describes a young non-pregnant cat that presented with uterine prolapse in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis. Following ovariohysterectomy the cat recovered fully. No intra-abdominal complications were seen on ultrasound examination 3 months postsurgery. At the time of writing, the cat remains healthy. Uterine prolapse in the cat is relatively rare and usually associated with the periparturient period. Inflammatory polypoid perimetritis and parametritis have not previously been documented in cats, and in dogs have only been reported in association with the administration of oestrogenic compounds. The polypoid inflammation affecting the uterus and parametrium may have contributed to increased laxity of the uterine ligaments and predisposed to the development of uterine prolapse.

CT in the diagnosis of interstitial lung disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergin, C.J.; Mueller, N.L.

1985-09-01

The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT changemore » in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.« less

Raynaud’s phenomenon and digital ischemia: a practical approach to risk stratification, diagnosis and management

PubMed Central

McMahan, Zsuzsanna H.; Wigley, Fredrick M.

2015-01-01

Digital ischemia is a painful and often disfiguring event. Such an ischemic event often leads to tissue loss and can significantly affect the patient’s quality of life. Digital ischemia can be secondary to a vasculopathy, vasculitis, embolic disease, trauma, or extrinsic vascular compression. It is an especially serious complication in patients with scleroderma. Risk stratification of patients with scleroderma at risk for digital ischemia is now possible with clinical assessment and autoantibody profiles. Because there are a variety of conditions that lead to digital ischemia, it is important to understand the pathophysiology underlying each ischemic presentation in order to target therapy appropriately. Significant progress has been made in the last two decades in defining the pathophysiological processes leading to digital ischemia in rheumatic diseases. In this article we review the risk stratification, diagnosis, and management of patients with digital ischemia and provide a practical approach to therapy, particularly in scleroderma. PMID:26523153

[Morphea or juvenile localised scleroderma: Case report].

PubMed

Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

2016-01-01

Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Melorheostosis of Leri: report of a case in a young African.

PubMed

Adeyomoye, A A O; Awosanya, G O G; Arogundade, R A

2004-09-01

Melorheostosis of Leri is a non-familial condition of hyperostosis of the cortical bone that usually presents unilaterally in long bones of the upper and lower limbs, but may also present in vertebra, ribs, skull and jaw. The incidence of this disease is quite rare, only about 300 cases have been reported worldwide. We present a case, which may be the first documented case in sub-Saharan Africa. S.K. is a 14 year old male student who presented to the hospital with an 18 month history of persistent pain in the joints of the right upper limb and a limb length discrepancy since birth which has worsened with growth. Examination revealed generalised hypoplasia of the right upper limb with shortening of the limb and atrophy of the muscles, also hypoplasia and contracture of the thumb was observed. The radiographs of the limb showed multiple areas of dense hyperostosis and scleroderma, which showed a linear distribution along the radial half of the bones. In children presentation of melorheostosis, is more likely be as limb length discrepancy, deformity or joint contractures which may be seen before radiographic evidence of any bony changes. Improvement in imaging techniques will therefore result in early diagnosis and greater success with conservative management. Also the increased frequency of tumours necessitates long-term follow up. melorheostosis, scleroderma.

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implicationsfor Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2013-07-01

www.le.ac.uk/ge/collagen/), in addition to mutations on COL1A1 and COL5A2. These mutations result in amino acid substitutions, RNA splicing...fibrillogenesis of type I collagen resulting in thinner collagen fibrils [29]. In the absence of PIIINP, Romanic and colleagues demonstrate that COL1A1 is...larger, shorter, and apparently stiffer; whereas in the presence of PIIINP/ COL1A1 copolymer, the type I collagen was longer, thinner, and more

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and subset Distinctions

DTIC Science & Technology

2014-07-01

onto an 8% SDS gel. Proteins were transferred to a polyvinylidene fluoride membrane, blocked in 5% nonfat milk in Tris-buffered saline, probed with...a)marker)of)fibrosis)[3,)4]),)we)assessed)both) protein )and)mRNA)levels)in)fibroblasts)that)received)DNA)from)a) plasmid)containing)a)single)allele...of)a)single)Col3a1%gene.)In)three)independent)experiments,)COL1A1) protein ) was)significantly)elevated)after)48)hours)of)transfection)with)Col3a1Tsk2

Uterine prolapse with endometrial eversion in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis in a cat

PubMed Central

Valentine, Matthew J; Porter, Susan; Chapwanya, Aspinas; Callanan, John J

2016-01-01

Case summary This case describes a young non-pregnant cat that presented with uterine prolapse in association with an unusual diffuse, polypoid, fibrosing perimetritis and parametritis. Following ovariohysterectomy the cat recovered fully. No intra-abdominal complications were seen on ultrasound examination 3 months postsurgery. At the time of writing, the cat remains healthy. Relevance and novel information Uterine prolapse in the cat is relatively rare and usually associated with the periparturient period. Inflammatory polypoid perimetritis and parametritis have not previously been documented in cats, and in dogs have only been reported in association with the administration of oestrogenic compounds. The polypoid inflammation affecting the uterus and parametrium may have contributed to increased laxity of the uterine ligaments and predisposed to the development of uterine prolapse. PMID:28491407

Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

PubMed

Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L; Lam, TuKiet T; Kanyo, Jean E; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H; Bai, Hanwen; Feghali-Bostwick, Carol A; Gan, Ye; Peng, Xueyan; Moore, Meagan W; White, Eric S; Sava, Parid; Gonzalez, Anjelica L; Cheng, Yuwei; Niklason, Laura E; Herzog, Erica L

2016-05-01

Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored. The aim of this study was to use a novel translational platform based on decellularized human lungs to determine whether the lung ECM of patients with scleroderma controls the development of fibrocytes from peripheral blood mononuclear cells. We performed biomechanical evaluation of decellularized scaffolds prepared from lung explants from healthy control subjects and patients with scleroderma, using tensile testing and biochemical and proteomic analysis. Cells obtained from healthy controls and patients with SSc-related ILD were cultured on these scaffolds, and CD45+pro-ColIα1+ cells meeting the criteria for fibrocytes were quantified. The contribution of the neuromolecule netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and by administering bleomycin via inhalation to netrin-1(+/-) mice. Compared with control lung scaffolds, lung scaffolds from patients with SSc-related ILD showed aberrant anatomy, enhanced stiffness, and abnormal ECM composition. Culture of control cells in lung scaffolds from patients with SSc-related ILD increased production of pro-ColIα1+ cells, which was stimulated by enhanced stiffness and abnormal ECM composition. Cells from patients with SSc-related ILD demonstrated increased pro-ColIα1 responsiveness to lung scaffolds from scleroderma patients but not enhanced stiffness. Enhanced detection of netrin-1-expressing CD14(low) cells in patients with SSc-related ILD was observed, and antibody-mediated netrin-1 neutralization attenuated detection of CD45+pro-ColIα1+ cells in all settings. Netrin-1(+/-) mice were protected against bleomycin-induced lung fibrosis and fibrocyte accumulation. Factors present in the lung matrices of patients with scleroderma regulate fibrocyte accumulation via a netrin-1-dependent pathway. Netrin-1 regulates bleomycin-induced pulmonary fibrosis in mice. Netrin-1 might be a novel therapeutic target in SSc-related ILD. © 2016, American College of Rheumatology.

The frequency of pulmonary hypertension in patients with juvenile scleroderma.

PubMed

Adrovic, Amra; Oztunc, Funda; Barut, Kenan; Koka, Aida; Gojak, Refet; Sahin, Sezgin; Demir, Tuncalp; Kasapcopur, Ozgur

2015-08-22

Juvenile scleroderma (JS) represents a rarely seen group of connective tissue diseases with multiple organ involvement. Cardiac involvement in JSS is well known and, although rare in children, it may be an important cause of mortality and morbidity. Therefore, an early determination of cardio-vascular and pulmonary involvement is of the most relevance to reduce the mortality in patients with juvenile scleroderma. The aim of the study was to explore the non-invasive methods (Doppler echocardiography, pulmonary function tests), Forced vital capacity (FVC) and Carbon monoxide diffusion capacity (DLCO) in the assessment of the cardiopulmonary involvement in patients with JS. The assessment of pulmonary arterial pressure (PAP) and risk factors for pulmonary arterial hypertension (PAH) were made by the measurement of maximum tricuspid insufficiency (TI), end-diastolic pulmonary insufficiency (PI), ratio of acceleration time (AT) to ejection time (ET) (AT/ET), right atrial pressure (RAP) and contraction of vena cava inferior during inspiration. Thirty-five patients with confirmed JS were included in the study. The mean age of onset of the disease was 9.57 years (median 10 years, range 2-18 years). The mean disease duration and follow-up time was 2 years (median 1 year, range 0.5-8 years) and 3.57 years (median 2 years, range 0.5-14.5 years), respectively.The values of all the analyzed parameters including TI, PI, AT/ET, PAP, FVC and DLCO were found to be within normal ranges in all the patients tested, confirming an uncommonness of cardiopulmonary involvement in patients with juvenile scleroderma.

Development of Consensus Treatment Plans for Juvenile Localized Scleroderma

PubMed Central

Li, Suzanne C.; Torok, Kathryn S.; Pope, Elena; Dedeoglu, Fatma; Hong, Sandy; Jacobe, Heidi T.; Rabinovich, C. Egla; Laxer, Ronald M.; Higgins, Gloria C.; Ferguson, Polly J.; Lasky, Andrew; Baszis, Kevin; Becker, Mara; Campillo, Sarah; Cartwright, Victoria; Cidon, Michael; Inman, Christi J; Jerath, Rita; O'Neil, Kathleen M.; Vora, Sheetal; Zeft, Andrew; Wallace, Carol A.; Ilowite, Norman T.; Fuhlbrigge, Robert C

2013-01-01

Objective To develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile localized scleroderma (jLS). Background jLS is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies have been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment of have made it difficult to compare approaches and identify optimal therapy. Methods A core group of pediatric rheumatologists, dermatologists and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for jLS using consensus methods/nominal group techniques. Recommendations were validated in two face-to-face conferences with a larger group of practitioners with expertise in jLS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the U.S and Canada. Results Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (67% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with jLS. Conclusions Using consensus methodology, we have developed standardized treatment plans and assessment methods for jLS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of jLS. PMID:22505322

microRNA-7 down-regulation mediates excessive collagen expression in localized scleroderma.

PubMed

Etoh, Mitsuhiko; Jinnin, Masatoshi; Makino, Katsunari; Yamane, Keitaro; Nakayama, Wakana; Aoi, Jun; Honda, Noritoshi; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu

2013-01-01

Localized scleroderma (LSc), a connective tissue disorder restricted to the skin and subcutaneous tissue, is characterized by skin fibrosis due to an excessive deposition of types I collagen. The mechanism of such fibrosis is still unknown, but epigenetics may play some roles in the excessive collagen expression. In the present study, we investigated the mechanism of fibrosis seen in LSc, focusing on microRNA (miRNA). miRNA expression was determined by PCR array, real-time PCR, and in situ hybridization. The function of miRNA was evaluated using specific inhibitor. Immunoblotting was performed to detect α2(I) collagen protein. PCR array analysis using tissue miRNA demonstrated miR-7 level was significantly decreased in LSc skin as well as keloid tissue compared to normal skin in vivo. In situ hybridization also showed miR-7 expression in dermal fibroblasts was decreased in LSc dermis. The transfection of specific inhibitor for miR-7 into cultured normal dermal fibroblasts resulted in the up-regulation of α2(I) collagen protein in vitro. Also, the serum levels of miR-7 were significantly decreased in LSc patients compared with healthy controls, but serum miR-29a levels not. Systemic or local down-regulation of miR-7 may contribute to the pathogenesis of LSc via the overexpression of α2(I) collagen, and serum miR-7 may be useful as a disease marker. Investigation of the regulatory mechanisms of LSc by miRNA may lead to new treatments by the transfection into the lesional skin of this disease.

[Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension].

PubMed

Navarro, Carmen

2006-11-01

Pulmonary involvement in systemic sclerosis. Alveolitis, fibrosis and pulmonar arterial hypertension Lung disease is present in most of the patients with systemic sclerosis and is now the most important cause of mortality. Interstitial lung disease and pulmonary hypertension are, so far, the main disorders found and both are difficult to detect at the earliest stages. However, diagnostic tools such as immunological test, lung function test, high resolution CT, bronchoalveolar lavage, echocardiography, right-side cardiac catheterization, or lung biopsy are necessary to accurately evaluate the clinical status and allow to improve the management organ-specific ad hoc. Progress in immunological and vascular therapies as well as other emergence drugs offer new expectations to scleroderma patients. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

Imaging findings in systemic childhood diseases presenting with dermatologic manifestations.

PubMed

Fink, Adam Z; Gittler, Julia K; Nakrani, Radhika N; Alis, Jonathan; Blumfield, Einat; Levin, Terry L

Many childhood diseases often present with skin abnormalities with which radiologists are largely unfamiliar. Knowledge of associated dermatologic manifestations may aid the radiologist in confirming the diagnosis and recommending targeted imaging of affected organs. We review the imaging findings in childhood diseases associated with dermatologic manifestations. Diseases include dermatologic findings which herald underlying malignancy (Neuroblastoma, leukemia/lymphoma, Langerhans cell histiocytosis),are associated with risk of malignancy (Epidermolysis Bullosa, basal cell nevus syndrome, Cowden's syndrome, Tuberous Sclerosis),or indicate a systemic inflammatory/immune disorder (Kawasaki's disease, Henoch Schonlein Purpura, systemic lupus erythematosus, scleroderma, sarcoidosis, dermatomyositis and immune thrombocytopenic purpura). Familiarity with pertinent findings in childhood diseases presenting with dermatologic manifestations in childhood diseases aids the radiologist in confirming the diagnosis and guiding imaging workup. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidative stress parameters in localized scleroderma patients.

PubMed

Kilinc, F; Sener, S; Akbaş, A; Metin, A; Kirbaş, S; Neselioglu, S; Erel, O

2016-11-01

Localized scleroderma (LS) (morphea) is a chronic, inflammatory skin disease with unknown cause that progresses with sclerosis in the skin and/or subcutaneous tissues. Its pathogenesis is not completely understood. Oxidative stress is suggested to have a role in the pathogenesis of localized scleroderma. We have aimed to determine the relationship of morphea lesions with oxidative stress. The total oxidant capacity (TOC), total antioxidant capacity (TAC), paroxonase (PON) and arylesterase (ARES) activity parameters of PON 1 enzyme levels in the serum were investigated in 13 LS patients (generalized and plaque type) and 13 healthy controls. TOC values of the patient group were found higher than the TOC values of the control group (p < 0.01). ARES values of the patient group was found to be higher than the control group (p < 0.0001). OSI was significantly higher in the patient group when compared to the control (p < 0.005). Oxidative stress seems to be effective in the pathogenesis. ARES levels have increased in morphea patients regarding to the oxidative stress and its reduction. Further controlled studies are required in wider series.

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.

1984-01-19

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thalliummore » defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.« less

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2013-07-01

in addition to mutations on  COL1A1  and  COL5A2. These mutations result in amino acid substitutions, RNA splicing alterations, deletions, or null...Romanic and colleagues demonstrate  that  COL1A1   is  larger,  shorter,  and  apparently  stiffer; whereas  in  the  presence  of  PIIINP/ COL1A1

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2015-09-01

skin)and)used)as) a)marker)of)fibrosis)[3,)4]),)we)assessed)both) protein )and)mRNA)levels)in)fibroblasts)that)received)DNA)from)a) plasmid...containing)a)single)allele)of)a)single)Col3a1%gene.)In)three)independent)experiments,)COL1A1) protein ) was)significantly)elevated)after)48)hours)of)transfection...Mouse& Col3a1eKO& fibroblasts& transfected& with& a& plasmid& bearing&the&mutant&Col3a1Tsk2&express&34%&more&COL1A1& protein &than& Col3a1WT

Scleroderma "en coup de sabre" With Epilepsy and Uveitis Successfully Treated With Tocilizumab.

PubMed

Osminina, Maria; Geppe, Nathalia; Afonina, Elena

2018-06-18

Case history of a small girl outlet with epilepsy, followed by scleroderma skin damage and uveitis, neurovasculitis with white matter foci in brain on the side of skin lesion in two months, immunologic disease activity. Resistance to conventional immunosuppressive therapy forced us to initiate the treatment with tocilizumab. It was well tolerated and led to significant improvement of brain, ocular and skin manifestations. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Race and Association With Disease Manifestations and Mortality in Scleroderma

PubMed Central

Manno, Rebecca L.; Shah, Ami A.; Woods, Adrianne; Le, Elizabeth N.; Boin, Francesco; Hummers, Laura K.; Wigley, Fredrick M.

2013-01-01

Abstract Experience suggests that African Americans may express autoimmune disease differently than other racial groups. In the context of systemic sclerosis (scleroderma), we sought to determine whether race was related to a more adverse expression of disease. Between January 1, 1990, and December 31, 2009, a total of 409 African American and 1808 white patients with scleroderma were evaluated at a single university medical center. While the distribution by sex was virtually identical in both groups, at 82% female, African American patients presented to the center at a younger mean age than white patients (47 vs. 53 yr; p < 0.001). Two-thirds of white patients manifested the limited cutaneous subset of disease, whereas the majority of African American patients manifested the diffuse cutaneous subset (p < 0.001). The proportion seropositive for anticentromere antibody was nearly 3-fold greater among white patients, at 34%, compared to African American patients (12%; p < 0.001). Nearly a third of African American (31%) patients had autoantibodies to topoisomerase, compared to 19% of white patients (p = 0.001). Notably, African American patients experienced an increase in prevalence of cardiac (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3–2.2), renal (OR, 1.6; 95% CI, 1.2–2.1), digital ischemia (OR, 1.5; 95% CI, 1.4–2.2), muscle (OR, 1.7; 95% CI, 1.3–2.3), and restrictive lung (OR, 6.9; 95% CI, 5.1–9.4) disease. Overall, 700 (32%) patients died (159 African American; 541 white). The cumulative incidence of mortality at 10 years was 43% among African American patients compared to 35% among white patients (log-rank p = 0.0011). Compared to white patients, African American patients experienced an 80% increase in risk of mortality (relative risk [RR], 1.8; 95% CI, 1.4–2.2), after adjustment for age at disease onset and disease duration. Further adjustment by sex, disease subtype, and scleroderma-specific autoantibody status, and for the socioeconomic measures of educational attainment and health insurance status, diminished these risk estimates (RR, 1.3; 95% CI, 1.0–1.6). The heightened risk of mortality persisted in strata defined by age at disease onset, diffuse cutaneous disease, anticentromere seropositivity, decade of care at the center, and among women. These findings support the notion that race is related to a distinct phenotypic profile in scleroderma, and a more unfavorable prognosis among African Americans, warranting heightened diagnostic evaluation and vigilant care of these patients. Further, we provide a chronologic review of the literature regarding race, organ system involvement, and mortality in scleroderma; we furnish synopses of relevant reports, and summarize findings. PMID:23793108

Lung Transplantation in a Patient with Fibrosing Alveolitis

PubMed Central

Hugh-Jones, P.; Macarthur, A. M.; Cullum, P. A.; Mason, S. A.; Crosbie, W. A.; Hutchison, D. C. S.; Winterton, M. C.; Smith, A. P.; Mason, B.; Smith, L. A.

1971-01-01

The transplantation of the right lung into a man aged 40 who was suffering from cryptogenic fibrosing alveolitis is described. Before transplantation he had been dependent on oxygen, even at rest, for 24 hours a day for almost two years. The donor was a boy of 16 years who had had a fatal cerebral haemorrhage. The transplanted lung functioned perfectly from the time of operation until the patient's sudden death two months later from an overwhelming haemoptysis apparently from a small peribronchial abscess rupturing into the pulmonary artery. By the third postoperative week the patient had been able to walk unaided and without distress outdoors. The problem of differentiating infection from incipient rejection is discussed. We conclude that clinically successful lung transplantation can be achieved, but only if the problems of lung function, infection, and immunosuppression can all be overcome. ImagesFIG 1FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4105315

Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome.

PubMed

Kosmidis, Chris; Newton, Pippa; Muldoon, Eavan G; Denning, David W

2017-04-01

Chronic pulmonary aspergillosis (CPA) has substantial impact on quality of life. A subset of patients develops significant pulmonary fibrosis, identified either on biopsy or radiologically. The term chronic fibrosing pulmonary aspergillosis (CFPA) has been suggested. We describe 11 patients with CFPA referred to our centre. Mean age was 58.5 years and five were male. In nine, fibrosis was already evident on presentation, while in two it developed 3 and 6 years later. The predominant radiological feature was extensive or complete involvement of the entire lung, with minimal contralateral involvement. All patients received prolonged antifungal treatment. Two patients had surgical treatment; both developed post-operative complications. The contralateral lung remained free of significant disease in all but three patients. CFPA is a rare complication of CPA that is usually evident on presentation, but may develop after years in patients not on antifungals. Fibrosis resembles the 'destroyed lung' syndrome described after treated tuberculosis.

Health status measurement in Toxic Oil Syndrome.

PubMed

Gómez de la Cámara, A; Posada de la Paz, M; Abaitua Borda, I; Barainca Oyagüe, M T; Abraira Santos, V; Ruiz-Navarro, M D; Terracini, B

1998-10-01

Toxic Oil Syndrome (TOS) is a previously unreported condition which affected more than 20,000 people in Spain in 1981 and whose natural history is unknown. In 1993-94, a stratified random sample of 1400 survivors was drawn to measure their health status through clinical examination and their self-perception of well-being through the Nottingham Health Profile Questionnaire (NHPQ). Two-thirds of the sample population responded; indirect estimates suggest that selection bias was limited. Clear and intermediate signs of neuropathy were found in one-fifth and one-half of the patients, respectively. One-fourth and one-sixth showed some degree of scleroderma and contractures. All conditions were more frequent in women than in men and in age >50 than in younger ages. Although no concurrent control group was included in the study, prevalences of these conditions are well above expectations and are largely attributable to TOS. NHPQ scores increased with age in both sexes up to age 50, after which they reached a plateau (with values around 48 in men and 62 in women). Scores were associated to the occurrence of peripheral neurological changes, contractures, and scleroderma-like conditions. A multivariate analysis indicated age, sex, and severity of neurological conditions as major determinants of the NHPQ scores. This overall pattern of findings is peculiar to TOS and differs from the typical post-disaster nonspecific syndrome.

Epstein-Barr virus infection induces aberrant TLR activation pathway and fibroblast-myofibroblast conversion in scleroderma.

PubMed

Farina, Antonella; Cirone, Mara; York, Michael; Lenna, Stefania; Padilla, Cristina; Mclaughlin, Sarah; Faggioni, Alberto; Lafyatis, Robert; Trojanowska, Maria; Farina, Giuseppina A

2014-04-01

Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV-Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation.

Scurfy mice: A model for autoimmune disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godfrey, V.L.

1993-01-01

Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work somore » well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.« less

Exercise habits and factors associated with exercise in systemic sclerosis: a Scleroderma Patient-centered Intervention Network (SPIN) cohort study.

PubMed

Azar, Marleine; Rice, Danielle B; Kwakkenbos, Linda; Carrier, Marie-Eve; Shrier, Ian; Bartlett, Susan J; Hudson, Marie; Mouthon, Luc; Poiraudeau, Serge; van den Ende, Cornelia H M; Johnson, Sindhu R; Rodriguez Reyna, Tatiana Sofia; Schouffoer, Anne A; Welling, Joep; Thombs, Brett D

2018-08-01

Exercise is associated with improved health in many medical conditions. Little is known about the exercise habits of people with systemic sclerosis (SSc, or scleroderma). This study assessed the proportion of individuals with SSc who exercise and associations of demographic and disease variables with exercise. Additionally, the weekly amount of time spent exercising and the types of exercise performed were assessed among patients exercising. The sample consisted of adult participants with SSc enrolled in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort who completed baseline questionnaires from March 2014 through August 2015. Baseline questionnaires included questions on exercise habits, physician-reported medical characteristics, self-report demographic characteristics, the Health Assessment Questionnaire-Disability Index, Patient Health Questionnaire-9, and Patient-Reported Outcomes Measurement Information System-29. Of 752 patients, 389 (51.7%) reported presently engaging in exercise, and these patients exercised on average 4.7 h [standard deviation (SD) = 2.8] per week. Among patients who reported exercising, walking was most commonly reported (n = 295, 75.8%). In bivariate analyses, present exercise was associated with more education, lower body mass index, some (versus no) alcohol consumption, non-smoking, limited/sine disease subtype, absence of skin thickening, lower disability, higher physical function, lower symptoms of anxiety and depression, less fatigue, lower sleep disturbance, higher ability to participate in social roles and activities, and less pain. Approximately half of SSc patients reported that they are currently exercising with walking being the most common form of exercise. Understanding exercise patterns and factors associated with exercise will help better inform intervention programs to support exercise for patients with SSc. Implications for rehabilitation Systemic sclerosis is a rare autoimmune rheumatic disease associated with great morbidity and highly diverse presentation. Approximately half of people with both limited and diffuse systemic sclerosis report exercising. Most exercisers walk, but patients engage in a wide variety of exercise-related activities. Individually designed exercise programs are most likely to support and encourage exercise in patients with diverse disease manifestations.

[Differences between Chicago and traditional classifications in the diagnosis of esophageal motor disorders with high-resolution manometry and topography of esophageal pressure].

PubMed

Abreu-Y Abreu, A T; González Sánchez, C B; Villanueva Sáenz, E; Valdovinos Díaz, M A

2010-01-01

With the introduction of high resolution manometry (HRM) and esophageal topography a novel classification (Chicago Classification) has been proposed for the diagnosis of esophageal motor disorders (EMD). Clinical differences with the traditional classification are currently under evaluation. To investigate differences between the Chicago (CC) and traditional (TC) classifications in the diagnosis of EMD. Consecutive patients with indication for esophageal manometry were studied. HRM was performed with a 36 sensors solid-state catheter and Manoview software (V2.0).Conventional manometric tracings were analyzed by an investigator blinded to the results of HRM. Diagnosis by CC and CT were compared. Two hundred patients were studied, 106 (53%) of them women (53%) with a mean patient age of 43.4 (range 16 - 84) years. Preoperative evaluation for GERD 152 (76%) was the most frequent indication. Achalasia (8), scleroderma (2) and peristaltic dysfunction (60 vs. 59) were similarly diagnosed by CC and CT. Spastic disorders were more frequently identified by CC: nutcracker esophagus (NC) in 3, spastic NC in3 and segmental NC in 11 patients versus TC: NC 5. Three patients had spasm with CC and 1 with TC. Non specific motor disorder was diagnosed by TC and 2 patients had functional obstruction with CC. Hypotensive lower esophageal sphincter was identified in 63 patients with CC vs.57 with TC. Spastic disorders and functional obstruction were the EMD better identified by HRM and CC.

Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma.

PubMed

Li, S C; Liebling, M S; Haines, K A; Weiss, J E; Prann, A

2011-05-01

To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool. Copyright © 2011 by the American College of Rheumatology.

Oligosaccharide modification by N-acetylglucosaminyltransferase-V in macrophages are involved in pathogenesis of bleomycin-induced scleroderma.

PubMed

Kato, Arisa; Yutani, Mizuki; Terao, Mika; Kimura, Akihiro; Itoi, Saori; Murota, Hiroyuki; Miyoshi, Eiji; Katayama, Ichiro

2015-08-01

Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), which catalyses the formation of β1,6 GlcNAc (N-acetylglucosamine) branches on N-glycans, is associated with various pathologies, such as cancer metastasis, multiple sclerosis and liver fibrosis. In this study, we demonstrated the involvement of GnT-V in the pathophysiology of scleroderma. High expression of GnT-V was observed in infiltrating cells in skin section samples from systemic and localized patients with scleroderma. Most of the infiltrating cells were T cells and macrophages, most of which were CD163(+) M2 macrophages. To determine the role of GnT-V in scleroderma, we next investigated skin sclerosis in GnT-V knockout (MGAT5(-/-) ) mice. Expression of GnT-V was also elevated in bleomycin (BLM)-injected sclerotic skin, and MGAT5(-/-) mice were resistant to BLM-induced skin sclerosis with reduced collagen type 1 α1 content, suggesting the biological significance of GnT-V in skin sclerosis. Furthermore, the number of CD163(+) M2 macrophages and CD3-positive T cells in BLM-induced skin sclerosis was significantly fewer in MGAT5(-/-) mice. In bone marrow-derived macrophages (BMDMs), IL-4-induced expressions of Fizz1 and Ym1 were significantly reduced in MGAT5(-/-) mice-derived BMDMs. Taken together, these results suggest the induction of GnT-V in skin sclerosis progression is possibly dependent on increased numbers of M2 macrophages in the skin, which are important for tissue fibrosis and remodelling. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

PubMed

Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

2017-12-01

In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

Expanding the spectrum of frontal fibrosing alopecia: a unifying concept.

PubMed

Chew, Ai-Lean; Bashir, Saqib J; Wain, E Mary; Fenton, David A; Stefanato, Catherine M

2010-10-01

In frontal fibrosing alopecia (FFA), scalp alopecia dominates the clinical picture. However, eyebrow loss and hair loss in other body sites may also occur; this has been documented clinically, but rarely histopathologically. We describe the clinicopathological findings of 13 cases of FFA, with histopathologic data from the scalp, eyebrow, and body hair. Thirteen patients with a diagnosis of FFA, seen between 2006 and 2008, were included. Scalp biopsies were performed in all patients for histology and direct immunofluorescence (DIF). Biopsy specimens for histology were taken from the eyebrow in 6 patients and from the upper limb in 5 patients. All 13 patients were female, 11 of whom were postmenopausal. The median age at onset of alopecia was 57 years. Clinical examination revealed a band of frontal hairline recession in all patients. Eyebrow loss was present clinically in all patients, with loss of body hair in 10 of 13. Histopathologic examination of the scalp, eyebrow, and upper limb skin biopsy specimens showed similar features, including a marked reduction in the number of hair follicles and a perifollicular lymphoid cell infiltrate with perifollicular fibrosis. Direct immunofluorescence was negative in all cases. Not all patients consented to biopsies of the eyebrows or upper limbs. Eyebrow and peripheral body hair loss is not uncommon in FFA-a finding that is likely underreported. We have demonstrated that alopecia of the upper limbs in FFA is indeed common and, histopathologically, shows features of lichen planopilaris and scarring, similar to findings in the scalp and eyebrows. Consequently, the process of lichen planopilaris with scarring alopecia is generalized rather than localized only to the frontal scalp and eyebrows.

Medical comorbidities in patients with lichen planopilaris, a retrospective case-control study.

PubMed

Fertig, Raymond M; Hu, Shasa; Maddy, Austin J; Balaban, Alexandra; Aleid, Nouf; Aldahan, Adam; Tosti, Antonella

2018-04-16

Lichen planopilaris (LPP) is a rare inflammatory lymphocyte-mediated disease of the scalp considered to have an autoimmune pathogenesis. To identify the prevalence of medical comorbidities in patients with classic LPP (CLPP) and frontal fibrosing alopecia (FFA). The medical records of 206 LPP patients and 323 control patients were retrospectively reviewed for existing comorbidities. The control group consisted of 257 patients with androgenetic alopecia (ICD 9 = 704.0 or ICD 10 = L64.9) and 66 patients with actinic keratosis (ICD 9 = 702.0 or ICD 10 = L57.0). Systemic lupus erythematosus (SLE) was found in 4.37% of all patients with LPP (including CLPP and the FFA subtype) and in 0.31% of controls. Female patients with the FFA subtype were more likely to have SLE than controls (OR 31.034, 95% CI 2.405-400.382, P = 0.0085). This study is limited in that it is a retrospective chart review. Female patients with FFA are significantly more likely to have SLE. Patients with LPP (including CLPP and the FFA subtype) are less likely to have diabetes. Patients with CLPP excluding FFA are less likely to have hypertension, heart disease, and hypothyroidism. © 2018 The International Society of Dermatology.

Corticosteroids in Myositis and Scleroderma.

PubMed

Postolova, Anna; Chen, Jennifer K; Chung, Lorinda

2016-02-01

Idiopathic inflammatory myopathies (IIMs) involve inflammation of the muscles and are classified by the patterns of presentation and immunohistopathologic features on skin and muscle biopsy into 4 categories: dermatomyositis, polymyositis, inclusion body myositis, and immune-mediated necrotizing myopathy. Systemic corticosteroid (CS) treatment is the standard of care for IIM with muscle and organ involvement. The extracutaneous features of systemic sclerosis are frequently treated with CS; however, high doses have been associated with scleroderma renal crisis in high-risk patients. Although CS can be effective first-line agents, their significant side effect profile encourages concomitant treatment with other immunosuppressive medications to enable timely tapering. Published by Elsevier Inc.

Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.

PubMed

Barnes, Jammie; Mayes, Maureen D

2012-03-01

To identify the recent data regarding prevalence, incidence, survival, and risk factors for systemic sclerosis (SSc) and to compare these data to previously published findings. SSc disease occurrence data are now available for Argentina, Taiwan, and India and continue to show wide variation across geographic regions. The survival rate is negatively impacted by older age of onset, male sex, scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer, and antitopoisomerase and anti-U1 antibodies. It appears that silica exposure confers an increased risk for developing scleroderma, but this exposure accounts for a very small proportion of male patients. Smoking is not associated with increased SSc susceptibility. Malignancies are reported in scleroderma at an increased rate, but the magnitude of this risk and the type of cancer vary among reports. Prevalence and incidence of SSc appears to be greater in populations of European ancestry and lower in Asian groups. Exposure to silica dust appears to be an environmental trigger, but this only accounts for a small proportion of male cases. Evidence for increased risk of neoplasia is suggestive, but the magnitude of the risk and the types of malignancies vary among reports.

Quantification of differences between nailfold capillaroscopy images with a scleroderma pattern and normal pattern using measures of geometric and algorithmic complexity.

PubMed

Urwin, Samuel George; Griffiths, Bridget; Allen, John

2017-02-01

This study aimed to quantify and investigate differences in the geometric and algorithmic complexity of the microvasculature in nailfold capillaroscopy (NFC) images displaying a scleroderma pattern and those displaying a 'normal' pattern. 11 NFC images were qualitatively classified by a capillary specialist as indicative of 'clear microangiopathy' (CM), i.e. a scleroderma pattern, and 11 as 'not clear microangiopathy' (NCM), i.e. a 'normal' pattern. Pre-processing was performed, and fractal dimension (FD) and Kolmogorov complexity (KC) were calculated following image binarisation. FD and KC were compared between groups, and a k-means cluster analysis (n  =  2) on all images was performed, without prior knowledge of the group assigned to them (i.e. CM or NCM), using FD and KC as inputs. CM images had significantly reduced FD and KC compared to NCM images, and the cluster analysis displayed promising results that the quantitative classification of images into CM and NCM groups is possible using the mathematical measures of FD and KC. The analysis techniques used show promise for quantitative microvascular investigation in patients with systemic sclerosis.

Calcium channel blockers and esophageal sclerosis: should we expect exacerbation of interstitial lung disease?

PubMed

Seretis, Charalampos; Seretis, Fotios; Gemenetzis, George; Liakos, Nikolaos; Pappas, Apostolos; Gourgiotis, Stavros; Lagoudianakis, Emmanuel; Keramidaris, Dimitrios; Salemis, Nikolaos

2012-01-01

Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings].

PubMed

Ritter, G; Rittmeyer, K; Hopf, H C

1975-02-21

A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis.

PubMed

Bektas, Mehmet; Seven, Gulseren; Idilman, Ramazan; Yakut, Mustafa; Doğanay, Beyza; Kabacam, Gökhan; Ustun, Yusuf; Korkut, Esin; Kalkan, Çağdaş; Sahin, Günay; Cetinkaya, Hulya; Bozkaya, Hakan; Yurdaydin, Cihan; Bahar, Kadir; Cinar, Kubilay; Soykan, Irfan

2014-03-01

Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma.

PubMed

Makino, Katsunari; Jinnin, Masatoshi; Hirano, Ayaka; Yamane, Keitaro; Eto, Mitsuhiko; Kusano, Takamitsu; Honda, Noritoshi; Kajihara, Ikko; Makino, Takamitsu; Sakai, Keisuke; Masuguchi, Shinichi; Fukushima, Satoshi; Ihn, Hironobu

2013-04-15

Systemic and localized scleroderma (SSc and LSc) is characterized by excessive deposition of collagen and tissue fibrosis in the skin. Although they have fundamental common characteristics including autoimmunity, little is known about the exact mechanism that mediates the excessive collagen expression in these disorders. In the current study, we tried to evaluate the possibility that microRNAs (miRNAs) play some roles in the pathogenesis of fibrosis seen in these diseases. miRNA expression patterns were evaluated by miRNA array analysis, real-time PCR, and in situ hybridization. The function of miRNAs in dermal fibroblasts was assessed using miRNA inhibitors, precursors, or protectors. In the mouse model of bleomycin-induced dermal sclerosis, the overexpression of miRNAs was performed by i.p. miRNA injection. We demonstrated let-7a expression was downregulated in SSc and LSc skin both in vivo and in vitro, compared with normal or keloid skin. The inhibition or overexpression of let-7a in human or mouse skin fibroblasts affected the protein expression of type I collagen or luciferase activity of collagen 3'-untranslated region. Also, we found let-7a was detectable and quantitative in the serum and investigated serum let-7a levels in patients with SSc or LSc. let-7a concentration was significantly decreased in these patients, especially in LSc patients. Moreover, we revealed that the intermittent overexpression of let-7a in the skin by i.p. miRNA injection improved the skin fibrosis induced by bleomycin in mice. Investigation of more detailed mechanisms of miRNA-mediated regulation of collagen expression may lead to new therapeutic approaches against SSc and LSc.

Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis

PubMed Central

Manetti, Mirko; Guiducci, Serena; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

2010-01-01

Abstract Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem connective tissue disorder affecting the skin and various internal organs. Although the disease is characterized by a triad of widespread microangiopathy, fibrosis and autoimmunity, increasing evidence indicates that vascular damage is a primary event in the pathogenesis of SSc. The progressive vascular injury includes persistent endothelial cell activation/damage and apoptosis, intimal thickening, delamination, vessel narrowing and obliteration. These profound vascular changes lead to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and severe clinical manifestations, such as digital ulceration or amputation, pulmonary arterial hypertension and scleroderma renal crisis. The resulting tissue hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell function and tissue perfusion. Nevertheless, in SSc patients there is no evidence of significant angiogenesis and the disease evolves towards chronic tissue ischemia, with progressive and irreversible structural changes in multiple vascular beds culminating in the loss of capillaries. A severe imbalance between pro-angiogenic and angiostatic factors may also lead to impaired angiogenic response during SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers and functional defects of bone marrow-derived endothelial progenitor cells may contribute to the vascular pathogenesis of SSc. The purpose of this article is to review the contribution of recent studies to the understanding of the complex mechanisms of impaired vascular repair in SSc. Indeed, understanding the pathophysiology of SSc-associated vascular disease may be the key in dissecting the disease pathogenesis and developing novel therapies. Either angiogenic or vasculogenic mechanisms may potentially become in the future the target of therapeutic strategies to promote capillary regeneration in SSc. PMID:20132409

Cryptogenic fibrosing alveolitis and lung cancer: the BTS study.

PubMed

Harris, J M; Johnston, I D A; Rudd, R; Taylor, A J Newman; Cullinan, P

2010-01-01

The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02). These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up

PubMed Central

Springer, Chaim; Wasser, Oren; Avital, Avraham; Koplewitz, Benjamin Z.

2018-01-01

A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy. PMID:29744231

Reversal of CD8 T-Cell–Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib

PubMed Central

Okiyama, Naoko; Furumoto, Yasuko; Villarroel, Vadim A; Linton, Jay T; Tsai, Wanxia L; Gutermuth, Jan; Ghoreschi, Kamran; Gadina, Massimo; O'Shea, John J; Katz, Stephen I

2014-01-01

The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-γ-inducible chemoattractants by keratinocytes, and IFN-γ-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell–mediated mucocutaneous diseases in patients with GVHD. PMID:24213371

Avian models with spontaneous autoimmune diseases

PubMed Central

Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

2012-01-01

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry.

PubMed

Denton, Christopher P; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco

2012-05-01

The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies.

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

PubMed

Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

Fibrose kystique atypique

PubMed Central

Schram, Carrie A.

2012-01-01

Résumé Objectif Passer en revue le diagnostic des patients atteints de fibrose kystique (FK) atypique. Sources des données On a procédé à une recension exhaustive dans MEDLINE (de 1950 à la troisième semaine de mai 2009), dans MEDLINE In-Process and Other Non-Indexed Citations and Cases (de 1950 à la troisième semaine de 2009) et dans EMBASE (de 1980 à la quatrième semaine de mars 2009). On a aussi passé en revue le site web de Fibrose kystique Canada et on a consulté son plus récent rapport des inscriptions de données sur les patients. Message principal La FK atypique est une forme moins intense du trouble de la FK, qui est associée à des mutations du gène régulateur de la conductance transmembranaire de la fibrose kystique. Au lieu d’avoir les symptômes classiques, les personnes atteintes d’une FK atypique pourraient avoir une légère dysfonction d’un seul système organique et avoir ou non des concentrations de chlorure élevées dans la sueur. La FK atypique est un trouble très diversifié affectant différents systèmes organiques à divers degrés. Les symptômes du patient peuvent aussi fluctuer avec le temps; par ailleurs, certains signes et symptômes cliniques touchant les systèmes respiratoire, gastro-intestinal, endocrinien et métabolique et génito-urinaire devraient signaler aux médecins la possibilité d’une FK. Les patients atteints d’une FK atypique ont moins d’hospitalisations durant l’enfance que ceux qui ont une FK classique et le diagnostic peut passer inaperçu pendant de nombreuses années, parfois même jusqu’à l’âge adulte. Conclusion Même si les patients atteints d’une FK atypique ont une espérance de vie plus longue que les personnes atteintes de la forme classique, les issues à long terme pour de nombreuses personnes qui ont la forme atypique sont inconnues. Il est important de conseiller les patients à propos de la possibilité d’une manifestation future de la maladie. Renseigner les patients à propos de la FK peut les aider à comprendre leurs symptômes, à modifier leur mode de vie pour optimiser leur santé, à réduire l’incidence des complications et à recevoir au besoin du counseling sur la planification familiale.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

PubMed

Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

Pediatric morphea (localized scleroderma): review of 136 patients.

PubMed

Christen-Zaech, Stéphanie; Hakim, Miriam D; Afsar, F Sule; Paller, Amy S

2008-09-01

Morphea is an autoimmune inflammatory sclerosing disorder that may cause permanent functional disability and disfigurement. We sought to determine the clinical features of morphea in a large pediatric cohort. We conducted a retrospective chart review of 136 pediatric patients with morphea from one center, 1989 to 2006. Most children showed linear morphea, with a disproportionately high number of Caucasian and female patients. Two patients with rapidly progressing generalized or extensive linear morphea and arthralgias developed restrictive pulmonary disease. Initial oral corticosteroid treatment and long-term methotrexate administration stabilized and/or led to disease improvement in most patients with aggressive disease. Retrospective analysis, relatively small sample size, and risk of a selected referral population to the single site are limitations. These data suggest an increased prevalence of morphea in Caucasian girls, and support methotrexate as treatment for problematic forms. Visceral manifestations rarely occur; the presence of progressive problematic cutaneous disease and arthralgias should trigger closer patient monitoring.

Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II.

PubMed

Tashkin, Donald P; Volkmann, Elizabeth R; Tseng, Chi-Hong; Roth, Michael D; Khanna, Dinesh; Furst, Daniel E; Clements, Philip J; Theodore, Arthur; Kafaja, Suzanne; Kim, Grace Hyun; Goldin, Jonathan; Ariolla, Edgar; Elashoff, Robert M

2017-04-01

Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied. We investigated frequent cough (FC) in patients with SSc-ILD (N = 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial. Study participants who reported FC at baseline (61.3%) reported significantly more dyspnea, exhibited more extensive ILD on high-resolution CT, had a lower diffusing capacity for carbon monoxide, and reported more GERD symptoms than did those without FC. Cough-specific QoL was modestly impaired in patients with FC (total LCQ score, 15.4 ± 3.7; normal range, 3-21 [higher scores indicate worse QoL]). The proportion of patients with FC at baseline declined by 44% and 41% over 2 years in the CYC and MMF treatment arms, respectively, and this decline was significantly related to changes in GERD and ILD severity. FC occurs commonly in SSc-ILD, correlates with both the presence and severity of GERD and ILD at baseline, and declines in parallel with improvements in both ILD and GERD over a 2-year course of therapy. Frequent cough might serve as a useful surrogate marker of treatment response in SSc-ILD trials. ClinicalTrials.gov; No.: NCT00883129; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Endothelin-1, α-Klotho, 25(OH) Vit D levels and severity of disease in scleroderma patients.

PubMed

Hajialilo, Mehrzad; Noorabadi, Parisa; Tahsini Tekantapeh, Sepideh; Malek Mahdavi, Aida

2017-10-01

Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and Medsger severity scale was assessed. Serum ET-1, soluble α-Klotho and 25(OH)D 3 levels were measured using ELISA kits. The mean ± SD age of patients and controls was 46.2 ± 9.6 and 47.2 ± 7.0 years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p = 0.001); whilst serum α-Klotho and 25(OH)D 3 were significantly lower in patients (p = 0.001). The most common organs involved in patients were skin, lung, peripheral vascular and gastrointestinal system and the severity of involvement was mainly mild and/or moderate. There were no significant differences in serum ET-1 and α-Klotho levels according to the severity of different organ involvement (p > 0.05). There was no significant correlation between presence or absence of calcinosis and negative or positivity of auto-antibodies with ET-1, α-Klotho and 25(OH)D 3 levels. Although our study revealed higher serum ET-1 and lower serum α-Klotho levels in SSc patients compared to healthy controls, there were not any significant correlations between their serum levels with severity of organ involvement.

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

PubMed Central

Haak, Andrew J.; Tsou, Pei-Suen; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip; Fox, David A.; Khanna, Dinesh; Larsen, Scott D.

2014-01-01

Systemic sclerosis (SSc), or scleroderma, similar to many fibrotic disorders, lacks effective therapies. Current trials focus on anti-inflammatory drugs or targeted approaches aimed at one of the many receptor mechanisms initiating fibrosis. In light of evidence that a myocardin-related transcription factor (MRTF)–and serum response factor (SRF)–regulated gene transcriptional program induced by Rho GTPases is essential for myofibroblast activation, we explored the hypothesis that inhibitors of this pathway may represent novel antifibrotics. MRTF/SRF-regulated genes show spontaneously increased expression in primary dermal fibroblasts from patients with diffuse cutaneous SSc. A novel small-molecule inhibitor of MRTF/SRF-regulated transcription (CCG-203971) inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)–and transforming growth factor β (TGFβ)–stimulated fibroblasts. In vivo treatment with CCG-203971 also prevented bleomycin-induced skin thickening and collagen deposition. Thus, targeting the MRTF/SRF gene transcription pathway could provide an efficacious new approach to therapy for SSc and other fibrotic disorders. PMID:24706986

Deficient Adipogenesis of Scleroderma Patient and Healthy African American Monocytes

PubMed Central

Lee, Rebecca; Reese, Charles; Carmen-Lopez, Gustavo; Perry, Beth; Bonner, Michael; Zemskova, Marina; Wilson, Carole L.; Helke, Kristi L.; Silver, Richard M.; Hoffman, Stanley; Tourkina, Elena

2017-01-01

Monocytes from systemic sclerosis (SSc, scleroderma) patients and healthy African Americans (AA) are deficient in the regulatory protein caveolin-1 leading to enhanced migration toward chemokines and fibrogenic differentiation. While dermal fibrosis is the hallmark of SSc, loss of subcutaneous adipose tissue is a lesser-known feature. To better understand the etiology of SSc and the predisposition of AA to SSc, we studied the adipogenic potential of SSc and healthy AA monocytes. The ability of SSc and healthy AA monocytes to differentiate into adipocyte-like cells (ALC) is inhibited compared to healthy Caucasian (C) monocytes. We validated that monocyte-derived ALCs are distinct from macrophages by flow cytometry and immunocytochemistry. Like their enhanced fibrogenic differentiation, their inhibited adipogenic differentiation is reversed by the caveolin-1 scaffolding domain peptide (CSD, a surrogate for caveolin-1). The altered differentiation of SSc and healthy AA monocytes is additionally regulated by peroxisome proliferator-activated receptor γ (PPARγ) which is also present at reduced levels in these cells. In vivo studies further support the importance of caveolin-1 and PPARγ in fibrogenesis and adipogenesis. In SSc patients, healthy AA, and mice treated systemically with bleomycin, adipocytes lose caveolin-1 and PPARγ and the subcutaneous adipose layer is diminished. CSD treatment of these mice leads to a reappearance of the caveolin-1+/PPARγ+/FABP4+ subcutaneous adipose layer. Moreover, many of these adipocytes are CD45+, suggesting they are monocyte derived. Tracing experiments with injected EGFP+ monocytes confirm that monocytes contribute to the repair of the adipose layer when it is damaged by bleomycin treatment. Our observations strongly suggest that caveolin-1 and PPARγ work together to maintain a balance between the fibrogenic and adipogenic differentiation of monocytes, that this balance is altered in SSc and in healthy AA, and that monocytes make a major contribution to the repair of the adipose layer. PMID:28420992

The CARRA Registry

ClinicalTrials.gov

2015-11-16

Juvenile Idiopathic Arthritis; Systemic Lupus Erythematosus; Mixed Connective Tissue Disease; Juvenile Ankylosing Spondylitis; Juvenile Dermatomyositis; Localized Scleroderma; Systemic Sclerosis; Vasculitis; Sarcoid; Fibromyalgia, Primary; Auto-inflammatory Disease; Idiopathic Uveitis Idiopathic

Pregnancy and Medically Assisted Conception in Rare Diseases

ClinicalTrials.gov

2016-06-23

Rheumatoid Arthritis; Spondyloarthritis; Psoriatic Arthritis; Systemic Lupus Erythematosus; Antiphospholipid Syndrome; Sjogren Syndrome; Scleroderma; Myositis; Vasculitis; Mastocytosis; Various Autoimmune and/or Systemic and/or Rare Diseases

[Ultrasound diagnostics of muscle and tendon injuries].

PubMed

Stević, Ruza; Masulović, Dragan

2009-01-01

Sonography is a useful technique for the investigation of a number of musculoskeletal disorders. The most common indication for ultrasonography of muscles and tendons is the diagnosis of traumatic lesions, distinguishing them from other disorders and follow- up of healing process. The purpose of this paper is to show the importance of ultrasound in the diagnosis of muscle and tendon injuries. The study included 170 patients (148 male and 22 female), mean age 29.6 years (range 14-60 years). All examinations were performed by linear transducer of 7.5-10 MHz, with longitudinal and transverse scanning. Ultrasound examination followed physical examination. Traumatic lesions of muscles were diagnosed in 113 patients (66.7%) and tendon injuries in 57 cases (33.2%). The muscle changes detected by ultrasonography were the following: 70 (61.9%) partial and two (1.76%) complete ruptures, 22 (19.46%) haematoma, 9 (7.96%) strains grade I, 4 fibroses and 4 ossifying myositis 4 (3.5%, respectively). Complications of muscle injuries were diagnosed in two cases, a muscular hernia and an arteriovenous fistula. Among tendon injuries, 21 (33.8%) ruptures and 36 (66.1%) tendinitis were diagnosed. Accompanying effusion in the bursa of patients with tendon injuries was found in 9 cases. Ultrasonography allowed visualization and objective assessment of the type and the extent of traumatic pathomorphological changes of muscles and tendons. Such diagnostic possibilities of ultrasonography are especially important in the choice of appropriate therapy.

Limited Scleroderma (CREST Syndrome)

MedlinePlus

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Systemic sclerosis in Sarawak: a profile of patients treated in the Sarawak General Hospital.

PubMed

Teh, C L; Kuan, Y C; Wong, J S

2009-08-01

We performed a cross-sectional study of the demography, clinical and laboratory features of patients with systemic sclerosis patients followed up in our centre from 1984 to 2007. There were 23 cases with the majority of them (96%) being female. They have a mean age of 50.3 years and a mean disease duration of 6.02 (SD 5.82) years. Our patients comprised of multi-ethnic groups with predominantly Chinese (52%), Sarawak natives (35%) and Malays (13%). They have a mean lag time to diagnosis of 24.8 (SD 34.8) months. All the patients have sclerodermatous skin changes with 16(70%) having diffuse scleroderma and 7(30%) having limited scleroderma. The common clinical manifestations found in our patients were Raynaud's phenomenon (91%), sclerodactyly (65%), digital ulcers (52%) and pulmonary fibrosis (52%). There was low incidence of pulmonary hypertension (13%) and renal involvement (4%). The majority of our patients (67%) have positive ANA with 33% positive Scl-70. The majority received calcium channel blockers (87%), aspirin (48%) and low-dose prednisolone (48%). One patient developed adenocarcinoma of the lung on follow-up. This study demonstrated the rarity of systemic sclerosis in our centre with considerable lag time to diagnosis in our patients. Diffuse cutaneous systemic scleroderma is more common in our centre with rare pulmonary hypertension and renal involvement.

Automatic segmentation of lung parenchyma based on curvature of ribs using HRCT images in scleroderma studies

NASA Astrophysics Data System (ADS)

Prasad, M. N.; Brown, M. S.; Ahmad, S.; Abtin, F.; Allen, J.; da Costa, I.; Kim, H. J.; McNitt-Gray, M. F.; Goldin, J. G.

2008-03-01

Segmentation of lungs in the setting of scleroderma is a major challenge in medical image analysis. Threshold based techniques tend to leave out lung regions that have increased attenuation, for example in the presence of interstitial lung disease or in noisy low dose CT scans. The purpose of this work is to perform segmentation of the lungs using a technique that selects an optimal threshold for a given scleroderma patient by comparing the curvature of the lung boundary to that of the ribs. Our approach is based on adaptive thresholding and it tries to exploit the fact that the curvature of the ribs and the curvature of the lung boundary are closely matched. At first, the ribs are segmented and a polynomial is used to represent the ribs' curvature. A threshold value to segment the lungs is selected iteratively such that the deviation of the lung boundary from the polynomial is minimized. A Naive Bayes classifier is used to build the model for selection of the best fitting lung boundary. The performance of the new technique was compared against a standard approach using a simple fixed threshold of -400HU followed by regiongrowing. The two techniques were evaluated against manual reference segmentations using a volumetric overlap fraction (VOF) and the adaptive threshold technique was found to be significantly better than the fixed threshold technique.

Measurement of transepidermal water loss in localized scleroderma.

PubMed

Ďurčanská, Veronika; Jedličková, Hana; Vašků, Vladimír

2016-05-01

Localized scleroderma (LS) is a disease characterized by fibrotic changes in the dermis. Connective tissue growth factor and transforming growth factor β2 are the main mediators of fibrogenesis; this, along with excessive connective tissue production, affects epidermal keratinocytes, and thereby contributes to the changed quality of skin barrier. The objective of this article was to study the objective measurement of the skin barrier quality in LS with transepidermal water loss (TEWL) meter. The measurements of TEWL were performed on LS plaques in all three stages of various body locations. Control measurements were made on the contralateral side of healthy skin. The difference between TEWL in LS area and the contralateral side of the healthy skin was evaluated. A higher average TEWL 7.86 g/m(2) /h (SD 5.29) was observed on LS plaques compared with the control measurements on healthy skin 6.39 g/m(2) /h (SD 2.77). TEWL average values decreased from the inflammatory stage, through the sclerotic and to the atrophic stage. The mean difference 1.301 g/m(2) /h (SD 5.16) was found between TEWL on LS plaques and on the contralateral healthy skin in 82 measurements, i.e., a higher TEWL was observed in LS. The difference was statistically significant with p = 0.0250. Although fibrogenesis in scleroderma is localized in dermis, the skin barrier changes can be detected. © 2016 Wiley Periodicals, Inc.

A CLINICAL AND SEROLOGIC COMPARISON OF AFRICAN-AMERICAN AND CAUCASIAN PATIENTS WITH SYSTEMIC SCLEROSIS

PubMed Central

Steen, Virginia; Domsic, Robyn T.; Lucas, Mary; Fertig, Noreen; Medsger, Thomas A.

2013-01-01

Objective Epidemiology studies suggest that Systemic Sclerosis is more common, occurs at a younger age and is more severe in African-Americans than Caucasians. However, the scleroderma autoantibody profile is very different between these two ethnic subgroups. This study examines the demographic and disease features, frequency and severity of internal organ system involvement and survival in African-American and Caucasian SSc patients with particular attention to their serum autoantibody profiles. Methods Demographic, clinical, autoantibody, natural history of organ involvement and survival were studied in consecutive African-American and Caucasian patients seen between 1972 and 2007 as part of the Pittsburgh Scleroderma Database. The Medsger Disease Severity Scale was used to determine severe disease. Results African-American patients were more likely to have anti topoisomerase, anti U1RNP and U3 RNP auto-antibodies. Comparing African-American and Caucasians with these antibodies, African-American patients with anti topoisomerase antibody had more frequent and more severe pulmonary fibrosis than Caucasians and an associated decreased survival. Pulmonary fibrosis was also more severe in the U1 RNP patients but was not associated with a difference in survival between African Americans and Caucasians. Anti U3 RNP was associated with more severe gastrointestinal involvement in African-American’s compared to Caucasians. Conclusions African Americans with systemic sclerosis have more severe disease complications than Caucasians both because of the type of autoantibody they have and because they have more severe interstitial lung disease even within the antibody subset. Early aggressive intervention in all African Americans with interstitial lung disease should be a priority. PMID:22576620

Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium.

PubMed

Larson, Krista N; Gagnon, Amy L; Darling, Melissa D; Patterson, James W; Cropley, Thomas G

2015-10-01

Nephrogenic systemic fibrosis (NSF) is a fibrosing skin disorder that develops in patients with kidney failure and has been linked to exposure to gadolinium-containing contrast agents. The time between exposure to gadolinium and the initial presentation of NSF is typically weeks to months but has been documented to be as long as 3½ years. We report a case of NSF developing 10 years after exposure to gadolinium. A long-term hemodialysis patient was exposed to gadolinium several times between 1998 and 2004 during magnetic resonance angiography of his abdominal vessels and arteriovenous fistula. In 2014, he was seen at our clinic with new dermal papules and plaques. Biopsy of affected skin showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis, supporting the diagnosis of NSF. The clinical history and histopathological features of this case support the diagnosis of NSF 10 years after exposure to gadolinium. Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease.

Co-Infection With Intestinal Helminths Markedly Reduces Proinflammatory Cytokines And Disease Severity In Natural And Induced High-Pathology Schistosomiasis

USDA-ARS?s Scientific Manuscript database

Infection with the trematode helminth Schistosoma mansoni results in a parasite egg-induced, CD4 T cell-mediated, hepato-intestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typical in endemic areas. One possible explanation is...

Scleroderma

MedlinePlus

... to treat arthritis. Blood pressure medicines, such as ACE inhibitors for high blood pressure -- Blood pressure should be ... 27941129 . Mendoza FA, Nagle SJ, Lee JB, Jimenez SA. A prospective observational study of mycophenolate mofetil treatment ...

Systemic Sclerosis Sine Scleroderma in Mexican Patients. Case Reports.

PubMed

Vera-Lastra, Olga; Sauceda-Casas, Christian Alexis; Domínguez, María Del Pilar Cruz; Alvarez, Sergio Alberto Mendoza; Sepulceda-Delgado, Jesús

2017-01-03

Systemic sclerosis sine scleroderma (ssSSc) is a form of systemic sclerosis that is characterized by Raynaud's phenomenon (RP), visceral involvement without thickening of skin and anticentromere antibodies (ACA). We studied 10 ssSsc patients with a prevalence of 2%. The clinical signs were: RP 9/10, esophageal manifestations 8/10, pulmonary arterial hypertension 4/10, interstitial lung disease 4/10, cardiac signs 3/10 and ACA 8/10. In patients with RP, esophageal dysmotility, interstitial lung disease and pulmonary arterial hypertension should be tested for ACA in order to establish a prompt diagnosis and treatment of ssSSc. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Multifocal fibrosing thyroiditis: report of 55 cases of a poorly recognized entity.

PubMed

Fellegara, Giovanni; Rosai, Juan

2015-03-01

During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

PubMed

Kumar, Akash; Dougherty, Max; Findlay, Gregory M; Geisheker, Madeleine; Klein, Jason; Lazar, John; Machkovech, Heather; Resnick, Jesse; Resnick, Rebecca; Salter, Alexander I; Talebi-Liasi, Faezeh; Arakawa, Christopher; Baudin, Jacob; Bogaard, Andrew; Salesky, Rebecca; Zhou, Qian; Smith, Kelly; Clark, John I; Shendure, Jay; Horwitz, Marshall S

2014-01-01

Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

Scleroderma Foundation

MedlinePlus

... the fullest extent of the law. Our federal tax identification number is 52-1375827. All donations are ... under 501(c)(3) status. The foundation’s federal tax identification number is 52-1375827. Our primary goal ...

Scleroderma

MedlinePlus

... Utility Nav Community Outreach Publications in Asian Languages Portal en español Main navigation Menu Close Health Topics ... Trials News Room About NIAMS Asian Language Publications Portal en espanol Community Outreach Initiative Menu Menu Close ...

The impact of high-dose narrowband ultraviolet A1 on dermal thickness, collagen and matrix-metalloproteinases in animal model of scleroderma.

PubMed

Karpec, Diana; Rudys, Romualdas; Leonaviciene, Laima; Mackiewicz, Zygmunt; Bradunaite, Ruta; Kirdaite, Gailute; Venalis, Algirdas

2017-08-01

The main purpose of the present study was to define the impact of high-dose of 365±5nm ultraviolet A1 (UVA1) on dermal fibrosis in the pre-established, bleomycin-induced mouse model of scleroderma. DBA/2 strain mice with the pre-established, bleomycin-induced scleroderma were irradiated with cumulative UVA1 dose of 1200J/cm 2 and in parallel were challenged with prolonged administration of bleomycin. Non-treated groups served as the control. Light source emitting a narrow band UVA1 light of 365±5nm and 21mW/cm 2 power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The expressions of matrix-metalloproteinase-1 (MMP-1), matrix-metalloproteinase-3 (MMP-3), collagen types I and III were evaluated by immunohistochemical analyses. The Mann - Whitney U test was used for statistical analysis. Dermal thickness in mice injected with bleomycin during all the experiment (8weeks) and irradiated with UVA1 for the last 5weeks was significantly lower than that in mice challenged only with bleomycin for 8weeks (253.96±31.83μm and 497.43±57.83μm, respectively; P=0.002). The dermal thickness after phototherapy was lower as compared with the pre-existing fibrotic changes observed after 3weeks of bleomycin injections (253.96±31.83μm and 443.87±41.76μm, respectively; P=0.002). High-dose of UVA1 induced the 5.8- and 5.2-fold increase in MMP-1 and MMP-3 expressions, respectively, and the 1.2- and 1.4-fold decrease in collagen type I and collagen type III expressions in the pre-established, bleomycin-induced scleroderma model as compared to that in the control non-irradiated mice (P=0.002). Our study has demonstrated that a cumulative 365±5nm UVA1 radiation dosage of 1200J/cm 2 not only prevents the progression of dermal fibrosis, but also induces a regression of pre-existing fibrotic changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort.

PubMed

Nevskaya, Tatiana; Baron, Murray; Pope, Janet E

2017-07-01

To estimate the effect of disease activity, as measured by the European Scleroderma Research Group Activity Index (EScSG-AI), on the risk of subsequent organ damage in a large systemic sclerosis (SSc) cohort. Of 421 SSc patients from the Canadian Scleroderma Research Group database with disease duration of ⩽ 3 years, 197 who had no evidence of end-stage organ damage initially and available 3 year follow-up were included. Disease activity was assessed by the EScSG-AI with two variability measures: the adjusted mean EScSG-AI (the area under the curve of the EScSG-AI over the observation period) and persistently active disease/flare. Outcomes were based on the Medsger severity scale and included accrual of a new severity score (Δ ⩾ 1) overall and within organ systems or reaching a significant level of deterioration in health status. After adjustment for covariates, the adjusted mean EScSG-AI was the most consistent predictor of risk across the study outcomes over 3 years in dcSSc: disease progression defined as Δ ⩾ 1 in any major internal organ, significant decline in forced vital capacity and diffusing capacity of carbon monoxide, severity of visceral disease and HAQ Disability Index worsening. In multivariate analysis, progression of lung disease was predicted solely by adjusted mean EScSG-AI, while the severity of lung disease was predicted the adjusted mean EScSG-AI, older age, modified Rodnan skin score (mRSS) and initial severity. The EScSG-AI was associated with patient- and physician-assessed measures of health status and overpowered the mRSS in predicting disease outcomes. Disease activity burden quantified with the adjusted mean EScSG-AI predicted the risk of deterioration in health status and severe organ involvement in dcSSc. The EScSG-AI is more responsive when done repeatedly and averaged. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Decreased Interleukin-20 Expression in Scleroderma Skin Contributes to Cutaneous Fibrosis

PubMed Central

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-01-01

Objective To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Methods Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. Results PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). Conclusion IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. PMID:24470401

Decreased interleukin-20 expression in scleroderma skin contributes to cutaneous fibrosis.

PubMed

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-06-01

To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. Copyright © 2014 by the American College of Rheumatology.

Scleroderma Research and Awareness Act

THOMAS, 111th Congress

Sen. Gillibrand, Kirsten E. [D-NY

2009-07-30

Senate - 07/30/2009 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Optical Biopsy of Human Skin in Conjunction With Laser Treatment

ClinicalTrials.gov

2017-02-08

Malignant Melanoma; Merkel Cell Carcinoma; Basal Cell Carcinoma; Squamous Cell Carcinoma; Atypical Nevi; Congenital Nevi; Seborrheic Keratosis; Paget's Disease; Dermatofibroma; Kaposi's Sarcoma; Port Wine Stain; Hemangioma; Tattoos; Scleroderma; Burns

Scleroderma Research and Awareness Act

THOMAS, 113th Congress

Sen. Gillibrand, Kirsten E. [D-NY

2013-06-27

Senate - 06/27/2013 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Scleroderma Research and Awareness Act

THOMAS, 112th Congress

Sen. Gillibrand, Kirsten E. [D-NY

2011-03-17

Senate - 03/17/2011 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Coping with Scleroderma

MedlinePlus

... it much easier to adjust. THE EMOTIONS Denial, Anger and Depression Once testing has occurred and a diagnosis is ... attached on the reverse side of this panel. Anger and Depression After you’ve had time to understand the ...

Genetics Home Reference: systemic scleroderma

MedlinePlus

... 1016/j.patbio.2015.03.003. Epub 2015 Mar 25. Review. Citation on PubMed Ito I, Kawaguchi ... biological and clinical significance. Curr Rheumatol Rep. 2015 Mar;17(3):21. doi: 10.1007/s11926-014- ...

Current Treatments Available for Scleroderma Patients

MedlinePlus

... from infection from bacteria at the site of infusion, the most common include edema (swelling); accumulation of ... irritated skin and/or hardening of skin at infusion site; flushing, faintness, dizziness or lightheadedness. Less common ...

Tips for Living with Scleroderma

MedlinePlus

... raw foods – about 50% of your diet – especially dark, leafy greens to provide chlorophyll and other nutrients. ... normal levels to dangerously high levels in a matter of days. If it continues without treatment, the ...

Identification of the Gene for Scleroderma in the Tsk/2 Mouse Strain: Implications for Human Scleroderma Pathogenesis and Subset Distinctions

DTIC Science & Technology

2014-09-01

onto an 8% SDS gel. Proteins were transferred to a polyvinylidene fluoride membrane, blocked in 5% nonfat milk in Tris-buffered saline, probed with...fibrosis (shown to be expressed at high levels in Tsk2/+ skin and used as  a marker of fibrosis [3, 4]), we assessed both  protein  and mRNA levels in...fibroblasts that received DNA from a  plasmid containing a single allele of a single Col3a1 gene. In three independent experiments, COL1A1  protein   was

The EULAR Scleroderma Trials and Research Group (EUSTAR): an international framework for accelerating scleroderma research.

PubMed

Tyndall, Alan; Ladner, Ulf M; Matucci-Cerinic, Marco

2008-11-01

Systemic sclerosis has a complex pathogenesis and a multifaceted clinical spectrum without a specific treatment. Under the auspices of the European League Against Rheumatism, the European League Against Rheumatism Scleroderma Trials And Research group (EUSTAR) has been founded in Europe to foster the study of systemic sclerosis with the aim of achieving equality of assessment and care of systemic sclerosis patients throughout the world according to evidence-based principles. EUSTAR created the minimal essential data set, a simple two-page form with basic demographics and mostly yes/no answers to clinical and laboratory parameters, to track patients throughout Europe. Currently, over 7000 patients are registered from 150 centres in four continents, and several articles have been published with the data generated by the minimal essential data set. A commitment of EUSTAR is also to teaching and educating, and for this reason there are two teaching courses and a third is planned for early in 2009. These courses have built international networks among young investigators improving the quality of multicentre clinical trials. EUSTAR has organized several rounds of 'teach the teachers' to further standardize the skin scoring. EUSTAR activities have extended beyond European borders, and EUSTAR now includes experts from several nations. The growth of data and biomaterial might ensure many further fruitful multicentre studies, but the financial sustainability of EUSTAR remains an issue that may jeopardize the existence of this group as well as that of other organizations in the world.

Systematic review of systemic sclerosis-specific instruments for the EULAR Outcome Measures Library: An evolutional database model of validated patient-reported outcomes.

PubMed

Ingegnoli, Francesca; Carmona, Loreto; Castrejon, Isabel

2017-04-01

The EULAR Outcome Measures Library (OML) is a freely available database of validated patient-reported outcomes (PROs). The aim of this study was to provide a comprehensive review of validated PROs specifically developed for systemic sclerosis (SSc) to feed the EULAR OML. A sensitive search was developed in Medline and Embase to identify all validation studies, cohort studies, reviews, or meta-analyses in which the objective were the development or validation of specific PROs evaluating organ involvement, disease activity or damage in SSc. A reviewer screened title and abstracts, selected the studies, and collected data concerning validation using ad hoc forms based on the COSMIN checklist. From 13,140 articles captured, 74 met the predefined criteria. After excluding two instruments as they were unavailable in English the selected 23 studies provided information on seven SSc-specific PROs on different SSc domains: burden of illness (symptom burden index), functional status (Scleroderma Assessment Questionnaire), functional ability (scleroderma Functional Score), Raynaud's phenomenon (Raynaud's condition score), mouth involvement (Mouth Handicap in SSc), gastro-intestinal involvement (University of California Los Angeles-Scleroderma Clinical Trial Consortium Gastro-Intestinal tract 2.0), and skin involvement (skin self-assessment). Each of them is partially validated and has different psychometric requirements. Seven SSc-specific PROs have a minimum validation and were included in the EULAR OML. Further development in the area of disease-specific PROs in SSc is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Nailfold capillaroscopy in 430 patients with rheumatoid arthritis.

PubMed

Rajaei, Alireza; Dehghan, Pooneh; Amiri, Ali

2017-01-01

Microvascular changes are one of the first obvious steps in numerous inflammatory diseases such as rheumatoid arthritis (RA). Nailfold video capillaroscopy (NFC) is an easy, reliable and safe method for evaluating peripheral microangiopathy. The objective of this study was to examine nailfold microcirculation in RA patients, assess morphological and structural changes quantitatively and qualitatively, and recognize useful changes. A total of 430 patients diagnosed with RA were examined in a period of 4 years. NFC was performed on all fingers of both hands in each patient. Different parameters indicating microvascular changes were detected and analyzed; such as microvascular architecture, capillary distribution disturbances, capillary morphology, capillary density, efferent/afferent limb ratio, subpapillary venular plexus and morphological abnormalities. The obtained results were categorized into normal pattern, nonspecific morphological abnormality and scleroderma pattern. The mean age of participants was 51.03±14.54 (19-87 years) that consisted of 359 females and 71 males. Based on the findings, angiogenesis (74.7%) was the most pathological condition observed after tortuosity (99.5%). 7.2% and 20.9% of patients were categorized into normal and scleroderma pattern group, respectively. Among morphological abnormalities, angiogenesis, isolated enlarged loop, irregular enlarged loop and architectural derangement were significantly more frequent in scleroderma than normal pattern (p<0.001). NFC may play an important role in monitoring RA disease and patients' follow-up. Therefore, in our opinion it could be considered in the course and follow-up of rheumatoid arthritis.

Nailfold capillaroscopy in 430 patients with rheumatoid arthritis

PubMed Central

Rajaei, Alireza; Dehghan, Pooneh; Amiri, Ali

2017-01-01

Background: Microvascular changes are one of the first obvious steps in numerous inflammatory diseases such as rheumatoid arthritis (RA). Nailfold video capillaroscopy (NFC) is an easy, reliable and safe method for evaluating peripheral microangiopathy. The objective of this study was to examine nailfold microcirculation in RA patients, assess morphological and structural changes quantitatively and qualitatively, and recognize useful changes. Methods: A total of 430 patients diagnosed with RA were examined in a period of 4 years. NFC was performed on all fingers of both hands in each patient. Different parameters indicating microvascular changes were detected and analyzed; such as microvascular architecture, capillary distribution disturbances, capillary morphology, capillary density, efferent/afferent limb ratio, subpapillary venular plexus and morphological abnormalities. The obtained results were categorized into normal pattern, nonspecific morphological abnormality and scleroderma pattern. Results: The mean age of participants was 51.03±14.54 (19-87 years) that consisted of 359 females and 71 males. Based on the findings, angiogenesis (74.7%) was the most pathological condition observed after tortuosity (99.5%). 7.2% and 20.9% of patients were categorized into normal and scleroderma pattern group, respectively. Among morphological abnormalities, angiogenesis, isolated enlarged loop, irregular enlarged loop and architectural derangement were significantly more frequent in scleroderma than normal pattern (p<0.001). Conclusion: NFC may play an important role in monitoring RA disease and patients’ follow-up. Therefore, in our opinion it could be considered in the course and follow-up of rheumatoid arthritis. PMID:29201317

Dermal delivery of HSP47 siRNA with NOX4-modulating mesoporous silica-based nanoparticles for treating fibrosis

PubMed Central

Morry, Jingga; Ngamcherdtrakul, Worapol; Gu, Shenda; Goodyear, Shaun M.; Castro, David J.; Reda, Moataz M.; Sangvanich, Thanapon; Yantasee, Wassana

2015-01-01

Fibrotic diseases such as scleroderma have been linked to increased oxidative stress and upregulation of pro-fibrotic genes. Recent work suggests a role of NADPH oxidase 4 (NOX4) and heat shock protein 47 (HSP47) in inducing excessive collagen synthesis, leading to fibrotic diseases. Herein, we elucidate the relationship between NOX4 and HSP47 in fibrogenesis and propose to modulate them altogether as a new strategy to treat fibrosis. We developed a nanoparticle platform consisting of polyethylenimine (PEI) and polyethylene glycol (PEG) coating on a 50-nm mesoporous silica nanoparticle (MSNP) core. The nanoparticles effectively delivered small interfering RNA (siRNA) targeting HSP47 (siHSP47) in an in vitro model of fibrosis based on TGF-β stimulated fibroblasts. The MSNP core also imparted an antioxidant property by scavenging reactive oxygen species (ROS) and subsequently reducing NOX4 levels in the in vitro fibrogenesis model. The nanoparticle was far superior to n-acetyl cysteine (NAC) at modulating pro-fibrotic markers. In vivo evaluation was performed in a bleomycin-induced scleroderma mouse model, which shares many similarities to human scleroderma disease. Intradermal administration of siHSP47-nanoparticles effectively reduced HSP47 protein expression in skin to normal level. In addition, the antioxidant MSNP also played a prominent role in reducing the pro-fibrotic markers, NOX4, alpha smooth muscle actin (α-SMA), and collagen type I (COL I), as well as skin thickness of the mice. PMID:26196532

Nailfold capillaroscopy in Buerger's disease: A useful tool?

PubMed

Guidelli, Giacomo Maria; Bardelli, Marco; Fioravanti, Antonella; Selvi, Enrico

2014-06-01

Thromboangiitis obliterans (TAO, or Buerger's disease) is a rare inflammatory vasculitis that commonly involves small and medium-sized arteries of the extremities of tobacco smokers between the ages of 25 and 50 years. Although the diagnosis is based on the clinical picture and angiographic findings, we studied the microvascular involvement by nailfold capillaroscopy. We evaluated by nailfold capillaroscopy 2 patients with Buerger's disease, at baseline and after 6 months of tobacco discontinuation and therapy with prostanoids. Both patients presented similar capillaroscopic abnormalities, resembling a scleroderma-like pattern. The microvascular rearrangement was significantly reduced after 6 months of evaluation. The capillaroscopic abnormalities shown in the two patients could be related to thromboangiitis obliterans, and nailfold capillaroscopy could be a useful tool to evaluate disease progression and the response to treatment.

Nailfold capillaroscopy in Buerger’s disease: A useful tool?

PubMed Central

Guidelli, Giacomo Maria; Bardelli, Marco; Fioravanti, Antonella; Selvi, Enrico

2014-01-01

Thromboangiitis obliterans (TAO, or Buerger’s disease) is a rare inflammatory vasculitis that commonly involves small and medium-sized arteries of the extremities of tobacco smokers between the ages of 25 and 50 years. Although the diagnosis is based on the clinical picture and angiographic findings, we studied the microvascular involvement by nailfold capillaroscopy. We evaluated by nailfold capillaroscopy 2 patients with Buerger’s disease, at baseline and after 6 months of tobacco discontinuation and therapy with prostanoids. Both patients presented similar capillaroscopic abnormalities, resembling a scleroderma-like pattern. The microvascular rearrangement was significantly reduced after 6 months of evaluation. The capillaroscopic abnormalities shown in the two patients could be related to thromboangiitis obliterans, and nailfold capillaroscopy could be a useful tool to evaluate disease progression and the response to treatment. PMID:27708881

Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not?

PubMed

Alper, G; Sreedher, G; Zuccoli, G

2013-01-01

Isolated brain stem lesions presenting with acute neurologic findings create a major diagnostic dilemma in children. Although the brain stem is frequently involved in ADEM, solitary brain stem lesions are unusual. We performed a retrospective review in 6 children who presented with an inflammatory lesion confined to the brain stem. Two children were diagnosed with connective tissue disorder, CNS lupus, and localized scleroderma. The etiology could not be determined in 1, and clinical features suggested monophasic demyelination in 3. In these 3 children, initial lesions demonstrated vasogenic edema; all showed dramatic response to high-dose corticosteroids and made a full clinical recovery. Follow-up MRI showed complete resolution of lesions, and none had relapses at >2 years of follow-up. In retrospect, these cases are best regarded as a localized form of ADEM. We conclude that though ADEM is typically a disseminated disease with multifocal lesions, it rarely presents with monofocal demyelination confined to the brain stem.

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Preparation and Characterization of UV Emitting Fluoride Phosphors for Phototherapy Lamps

NASA Astrophysics Data System (ADS)

Belsare, P. D.; Moharil, S. V.; Joshi, C. P.; Omanwar, S. K.

2011-10-01

The use of ultraviolet radiation for the treatment of various skin diseases is well known for long time. Phototherapy employs ultraviolet-blue radiation to cure skin diseases. The basis of phototherapy is believed to be the direct interaction of light of certain frequencies with tissue to cause a change in immune response. Currently dermatologists use UV lamps having specific emissions in UV region for treating various skin diseases. The treatment of skin diseases using artificial sources of UV radiation is now well established and more than 50 types of skin diseases are treated by phototherapy. This is an effective treatment for many skin disorders, such as psoriasis, vitiligo, ofujis disease, morphea , scleroderma, cutaneous T-cell lymphoma, lupus erythematosus, hyperbilirubinemia commonly known as infant jaundice, acne vulgaris, This paper reports photoluminescence properties of UV emitting fluoride phosphors prepared by wet chemical method. Emission characteristics of these phosphors are found similar to those of commercial UV lamp phosphors with comparable intensities. The usefulness of UV emitting fluoride phosphor is discussed in the paper.

Eating Well with Scleroderma

MedlinePlus

... smoothies using fruit, yogurt, 2-percent milk, Carnation ® Instant Breakfast and/or whey protein powder. • Include soft, ... to three tea- spoons of canola oil, Carnation ® Instant Breakfast and/or whey protein powder. • Include a ...

Frontal fibrosing alopecia: a multicenter review of 355 patients.

PubMed

Vañó-Galván, Sergio; Molina-Ruiz, Ana M; Serrano-Falcón, Cristina; Arias-Santiago, Salvador; Rodrigues-Barata, Ana R; Garnacho-Saucedo, Gloria; Martorell-Calatayud, Antonio; Fernández-Crehuet, Pablo; Grimalt, Ramón; Aranegui, Beatriz; Grillo, Emiliano; Diaz-Ley, Blanca; Salido, Rafael; Pérez-Gala, Sivia; Serrano, Salvio; Moreno, Jose Carlos; Jaén, Pedro; Camacho, Francisco M

2014-04-01

To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). The retrospective design is a limitation. Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Use of dimethyl sulfoxide (DMSO) in radiation therapy (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glaser, F.H.

1973-01-01

The present clinical examinstion deals with the possible use of DMSO in rsdiation therapy. DMSO was applied to 30 patients, 8 times in radiogenic subcutaneous fibroses, 13 times in contracted scars and keloids, 3 times in cases of induratio penis plastica, and 6 times as vehicle substsnce for tamor cell sensitization with vitamin A in the radiation therapy of skin metastases sfter mamma carcinoma. The results confirm the value of a DMSO treatment of subcutaneous fibroses following highly dosed percutaneous radiation therapy, especially in cases with a radiological ulcer. In keloids of scars a clear effect could be achieved withoutmore » exceptions also in those csses showing only insufficient regression tendency to a preceded rsdiation therapy. The results of irradiation in cases with I.p.p., however, did not show any convincing improvement by a DMSO treatment. A new field of application is opened for the indiation therapy of recurrences and metastases in the area of the skin by sensitization of these cutaneous tumor infiltrates by vitamin A in connection with DMSO as vehicle substance so that a curative regression can be locally obtained by relatively low radiation doses. (auth)« less

Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes.

PubMed

Farina, Antonella; Peruzzi, Giovanna; Lacconi, Valentina; Lenna, Stefania; Quarta, Silvia; Rosato, Edoardo; Vestri, Anna Rita; York, Michael; Dreyfus, David H; Faggioni, Alberto; Morrone, Stefania; Trojanowska, Maria; Farina, G Alessandra

2017-02-28

Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells.

The management of rheumatic diseases in pregnancy

PubMed Central

Mitchell, K; Kaul, M; Clowse, MEB

2013-01-01

Pregnancy can create a challenge for physicians caring for women with rheumatic diseases. For many women with rheumatoid arthritis (RA), pregnancy can provide a reprieve from long-term joint pain and inflammation, but others will not experience remission and will continue to need medication. Systemic lupus erythematosus (SLE) may remain quiet in some women, but in others may become more aggressive during pregnancy, putting both mother and foetus at risk. Women with limited scleroderma can do remarkably well, but scleroderma renal crises can be difficult to manage. A third of pregnancies in women with antiphospholipid syndrome (APS) may be refractory to our best therapy. In general, active inflammation from rheumatic diseases poses a stronger threat to the well-being of both mother and foetus than many immunosuppressant medications. Therefore, continued immunosuppression with the least risky medications will allow for the most optimal pregnancy outcomes. PMID:20337545

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

PubMed

Knobler, R; Moinzadeh, P; Hunzelmann, N; Kreuter, A; Cozzio, A; Mouthon, L; Cutolo, M; Rongioletti, F; Denton, C P; Rudnicka, L; Frasin, L A; Smith, V; Gabrielli, A; Aberer, E; Bagot, M; Bali, G; Bouaziz, J; Braae Olesen, A; Foeldvari, I; Frances, C; Jalili, A; Just, U; Kähäri, V; Kárpáti, S; Kofoed, K; Krasowska, D; Olszewska, M; Orteu, C; Panelius, J; Parodi, A; Petit, A; Quaglino, P; Ranki, A; Sanchez Schmidt, J M; Seneschal, J; Skrok, A; Sticherling, M; Sunderkötter, C; Taieb, A; Tanew, A; Wolf, P; Worm, M; Wutte, N J; Krieg, T

2017-09-01

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum. © 2017 European Academy of Dermatology and Venereology.

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

PubMed

Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

2018-01-01

Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group.

PubMed

Foocharoen, Chingching; Tyndall, Alan; Hachulla, Eric; Rosato, Edoardo; Allanore, Yannick; Farge-Bancel, Dominique; Caramaschi, Paola; Airó, Paolo; Nikolaevna, Starovojtova M; Pereira da Silva, José António; Stamenkovic, Bojana; Riemekasten, Gabriela; Rednic, Simona; Sibilia, Jean; Wiland, Piotr; Tarner, Ingo; Smith, Vanessa; Onken, Anna T; Abdel Atty Mohamed, Walid Ahmed; Distler, Oliver; Morović-Vergles, Jadranka; Himsel, Andrea; de la Peña Lefebvre, Paloma Garcia; Hügle, Thomas; Walker, Ulrich A

2012-02-20

Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

[Non-identified antinuclear antibodies in systemic sclerosis].

PubMed

Margot, A; Smet, J; Soyfoo, S

Systemic sclerosis is a rare auto immune disease characterized by a local or diffuse skin condition and a variable visceral impairment. Anti nuclear antibodies (ANA) can be found in 95 % of patients. The most frequent are the anti topoisomerase 1 or anti Scl 70 and the anti-centromeres. Other antibodies have been reported but they are not conventionally sought in clinical practice. They are referred to as " non identified " ANA. To seek the " non identified " antibodies in patients with scleroderma at Erasme Hospital, to assess their prevalence in this cohort and to correlate their presence with the clinical characteristics. 89 patients out of the cohort of Erasme hospital patients with scleroderma have been looked at. Their clinical and biological data have been identified and a detection of antibodies have been performed by first an immonudot technique and second an EliA technique. 17 out of the 89 patients of our cohort had " non identified " ANA. Among them, antibodies in 11 patients have been identified by the immunodot, among which 7 anti-PmScl 75 and/or 100,3 RNA polymerase III and 1 antifibrillarin. The EliA technique identif ied antibodies in 10 patients among which 5 anti- PmScl, 2 anti RNA polymerase, 2 anti-fibrillarin and 1 anti-centromere. Auto antibodies other than the antitopoisomerase and anti-centromere have been found in patients with scleroderma in our cohort. Certain links exist between the presence of a given antibody and clinical features. We still have to define whether there exist other auto antibodies of which we still are unaware since in some patient no antibodies were detected.

Juvenile onset systemic sclerosis: a single center experience of 23 cases from Asia.

PubMed

Misra, Ramnath; Singh, Gurmeet; Aggarwal, Parshant; Aggarwal, Amita

2007-08-01

The aim of this paper was to study the spectrum of juvenile scleroderma (JSSc) seen at a tertiary care referral center in Asia. Retrospective analysis of case records of patients with systemic sclerosis, having age of onset less than 16 years and seen at our hospital from 1988 to 2004, was done. Patients with linear scleroderma and morphea were excluded. There were 23 patients (19 girls, 4 boys) with median age of onset of 12 years (range 5-16 years). The median age at presentation was 17 years (range 10-34 years). The median time from first symptoms to presentation was 4 years (range 0.2-26 years). Among these, 14 had diffuse systemic sclerosis (DSSc), while 9 had limited scleroderma (LSSc). The clinical features seen at presentation in patients were: Raynaud's phenomenon in 19, digital ulcers in 14, loss of finger tip pulp in 12, reflux in 8, dysphagia in 7, arthritis in 8, digital gangrene in 2, and pulmonary artery hypertension in 1. Antinuclear antibody was positive in 15 out of 18 patients tested. Interstitial lung disease was seen in 15 patients, 6 of whom had diffuse disease. The median skin score was 22 (range 7-48) . One patient died of primary pulmonary hypertension within 1 year of onset of symptoms. At a mean follow-up of 34 months, 14 patients were stable or had improvement in skin score or dyspnea on exertion. DSSc and LSSc in childhood have a clinical presentation similar to adult patients, with cardiopulmonary involvement being the major predictor of outcome. The short-term prognosis of JSSc is good.

Pulmonary Hypertension in Scleroderma

MedlinePlus

... the study was not designed to detect a difference in survival. Common side effects of epoprostenol therapy include headache, flushing, jaw pain with initial chewing, diarrhea, and bone pain. Other side effects include the potential for serious infection associated with the catheter. Chronic ...

Scleroderma Research and Awareness Act of 2010

THOMAS, 111th Congress

Rep. Capps, Lois [D-CA-23

2009-05-14

Senate - 11/15/2010 Received in the Senate and Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

Frontal fibrosing alopecia in a postmenopausal woman.

PubMed

Lee, W S; Hwang, S M; Ahn, S K

1997-12-01

A case is presented of a 52-year-old woman in whom clinical and histopathologic findings suggested cicatricial alopecia. Our patient had an uncommon, but distinctive, clinical presentation. It was characterized by bandlike frontal hair loss. This was recently described as patterned cicatricial alopecia, presented in a recent study as postmenopausal frontal hairline recession with scarring. Our patient's case should be differentiated from recognized forms of scarring alopecia.

Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

PubMed

Vukotic, R; Conti, F; Fagiuoli, S; Morelli, M C; Pasulo, L; Colpani, M; Foschi, F G; Berardi, S; Pianta, P; Mangano, M; Donato, M F; Malinverno, F; Monico, S; Tamè, M; Mazzella, G; Belli, L S; Viganò, R; Carrai, P; Burra, P; Russo, F P; Lenci, I; Toniutto, P; Merli, M; Loiacono, L; Iemmolo, R; Degli Antoni, A M; Romano, A; Picciotto, A; Rendina, M; Andreone, P

2017-10-01

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments. © 2017 John Wiley & Sons Ltd.

Juvenile, insulin-dependent diabetes mellitus, type 1-related dermatoses.

PubMed

Sehgal, V N; Bhattacharya, S N; Verma, P

2011-06-01

Juvenile insulin-dependent diabetes mellitus type 1 (IDDM) is a well-recognized worldwide entity, the significance of which has increased because of its recent upsurging trends, warranting attention on variety of its clinical expressions, in particular, pertaining to skin, an aspect seldom taken cognizance of. Hence an endeavour to recap the related dermatoses, such as limited joint mobility syndrome including sclerodermoid (scleroderma-like) changes, xerosis, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic foot syndrome, has been made. Complexities relating to the recently explored issues of atopic dermatitis and drug hypersensitivity syndrome have also been covered adequately. In addition, the current concepts of the physiopathology of type 1 diabetes-related dermatoses are briefly recapitulated for clarity. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease

PubMed Central

Loomis-King, Hillary; Moore, Bethany B.

2016-01-01

Fibrocytes were initially described in 1999 and since that time there has been a growing body of literature to suggest their importance in a number of chronic lung diseases. It is now well established that fibrocytes derive from the bone marrow and circulate within the peripheral blood. However, when injury occurs, fibrocytes can travel to the site of damage via chemokine-mediated recruitment. Recent studies suggest that fibrocyte numbers increase within the lung or circulation during numerous disease processes. Although fibrocytes readily differentiate into fibroblasts in vitro, whether they do so in vivo is still unknown. The variety of pro-fibrotic mediators that are secreted by fibrocytes makes it likely that they act via paracrine functions to influence the behavior of resident lung cells. This review summarizes recent insights regarding fibrocytes in asthma, scleroderma and IPF. PMID:27512347

[Cicatricial pemphigoid, mucous membrane pemphigoid].

PubMed

Doffoel-Hantz, Valérie; Robert, Pierre-Yves; Bédane, Christophe

2010-10-01

Mucous membrane pemphigoid belongs to the family of sub-epidermal bullous diseases and is clinically characterized by mucosal involvement leading to fibrosis and scarring. Cutaneous involvement is unfrequent and oral mucosa and conjunctivas are the most frequently involves mucosa. Treatment relies on anti-inflammatory and immunosuppressive drugs. The main goal is the limitation of the fibrosing potential of the autoimmune deposits within various mucous membranes. Copyright © 2010. Published by Elsevier Masson SAS.

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist.

PubMed

Sverzellati, Nicola; Odone, Anna; Silva, Mario; Polverosi, Roberta; Florio, Carlo; Cardinale, Luciano; Cortese, Giancarlo; Addonisio, Giancarlo; Zompatori, Maurizio; Dalpiaz, Giorgia; Piciucchi, Sara; Larici, Anna Rita

2018-04-01

To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). The writing committee selected the HRCT criteria-the Delphi items-for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as "essential", "optional", or "not relevant". The items rated "essential" by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated "essential" by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated "essential" by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists.

A computer system for timing and acoustical analysis of crackles: a study in cryptogenic fibrosing alveolitis.

PubMed

Dalmasso, F; Guarene, M M; Spagnolo, R; Benedetto, G; Righini, G

1984-01-01

A system for recording and processing lung crackles is described. These are detected by a microphone on the chest wall and recorded simultaneously with flow rate, tidal volume and oesophageal pressure on a four-channel tape recorder. The sound signal is subsequently digitized by an analog-to-digital converter and processed by a minicomputer, using the Time Series Language and the fast Fourier transform algorithm. A preliminary study on seven patients with cryptogenic fibrosing alveolitis (CFA) confirms that crackles typically occur at the end of inspiration; timing seems to be well related to inspired volume and esophageal pressure. Inspiratory crackles of CFA have a well-defined waveform: it consists of a starting component and a damped oscillation, which probably depends on the resonant frequency of the lung. The crackle energy content is mainly concentrated in the frequency range between 100 and 2 000 Hz, the spectrum shape being determined by the energy distribution between the two components of the waveform. This recording and processing system gives more complete information about crackles than auscultation does, allowing their quantification and reproducibility. It may be used to compare crackles in different diseases, and may be simplified and standardized for routine clinical use as an additional noninvasive diagnostic technique.

A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses.

PubMed

Wei, Jun; Zhu, Hongyan; Komura, Kazuhiro; Lord, Gabriel; Tomcik, Michal; Wang, Wenxia; Doniparthi, Sruthi; Tamaki, Zenshiro; Hinchcliff, Monique; Distler, Joerg H W; Varga, John

2014-02-01

Persistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. The synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), is a PPAR-γ agonist with potential effects on TGF-β signalling and dermal fibrosis. To examine the modulation of fibrogenesis by CDDO in explanted fibroblasts, skin organ cultures and murine models of scleroderma. The effects of CDDO on experimental fibrosis induced by bleomycin injection or by overexpression of constitutively active type I TGF-β receptor (TgfbR1ca) were evaluated. Modulation of fibrotic gene expression was examined in human skin organ cultures. To delineate the mechanisms underlying the antifibrotic effects of CDDO, explanted skin fibroblasts cultured in two-dimensional monolayers or in three-dimensional full-thickness human skin equivalents were studied. CDDO significantly ameliorated dermal fibrosis in two complementary mouse models of scleroderma, as well as in human skin organ cultures and in three-dimensional human skin equivalents. In two-dimensional monolayer cultures of explanted normal fibroblasts, CDDO abrogated fibrogenic responses induced by TGF-β. These CDDO effects occurred via disruption of Smad-dependent transcription and were associated with inhibition of Akt activation. In scleroderma fibroblasts, CDDO attenuated the elevated synthesis of collagen. Remarkably, the in vitro antifibrotic effects of CDDO were independent of PPAR-γ. The PPAR-γ agonist triterpenoid CDDO attenuates fibrogenesis by antagonistically targeting canonical TGF-β/Smad and Akt signalling in a PPAR-γ-independent manner. These findings identify this synthetic triterpenoid as a potential new therapy for the control of fibrosis.

Separate Influences of Birth Order and Gravidity/Parity on the Development of Systemic Sclerosis

PubMed Central

COCKRILL, TONYA; del JUNCO, DEBORAH J.; ARNETT, FRANK C.; ASSASSI, SHERVIN; TAN, FILEMON K.; McNEARNEY, TERRY; FISCHBACH, MICHAEL; PERRY, MARILYN; MAYES, MAUREEN D.

2010-01-01

Objective Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Methods Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Results Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Conclusion Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility. PMID:20391489

The involvement of galectin-3 in skin injury in systemic lupus erythematosus patients.

PubMed

Shi, Z; Meng, Z; Han, Y; Cao, C; Tan, G; Wang, L

2018-04-01

Objective Our previous research suggested that anti-galectin-3 antibody was highly associated with the development of lupus skin lesions in systemic lupus erythematosus (SLE). In this study we aimed to investigate the involvement of galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy controls. Galectin-3 was examined by ELISA and immunohistochemical staining in serum and skin, respectively. Results Serum galectin-3 was significantly higher in patients with SLE than in those with dermatomyositis ( P < 0.01), systemic scleroderma ( P < 0.001) and healthy controls ( P < 0.001); however, it was comparable between SLE patients with and without skin lesions ( P = 0.2010 and was not correlated with cutaneous disease activity ( r = -0.020, P = 0.93) or damage score ( r = -0.380, P = 0.09). Galectin-3 expression was reduced in epidermis in lesional skin from patients with SLE, dermatomyositis and systemic scleroderma compared to healthy controls ( P = 0.0055), whereas it was comparable among diseases ( P > 0.05). As for subtypes of skin lesions in SLE, galectin-3 expression was lower in chronic cutaneous lupus erythematosus than in acute cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is unlikely to play a role in the pathogenesis of lupus skin damage, but can be a potential biomarker for the measurement of SLE disease activity. Galectin-3 is greatly reduced in patients with lupus lesions compared with healthy controls, which may contribute to the recruitment of inflammatory cells in the skin.

Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

PubMed

Klein, S; Kretz, C C; Ruland, V; Stumpf, C; Haust, M; Hartschuh, W; Hartmann, M; Enk, A; Suri-Payer, E; Oberle, N; Krammer, P H; Kuhn, A

2011-08-01

To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

A cross-sectional electromyography assessment in linear scleroderma patients

PubMed Central

2014-01-01

Background Muscle atrophy and asymmetric extremity growth is a common feature of linear scleroderma (LS). Extra-cutaneous features are also common and primary neurologic involvement, with sympathetic dysfunction, may have a pathogenic role in subcutaneous and muscle atrophy. The aim was investigate nerve conduction and muscle involvement by electromyography in pediatric patients with LS. Methods We conducted a retrospective review of LS pediatric patients who had regular follow up at a single pediatric center from 1997–2013. We selected participants if they had consistently good follow up and enrolled consecutive patients in the study. We examined LS photos as well as clinical, serological and imaging findings. Electromyograms (EMG) were performed with bilateral symmetric technique, using surface and needle electrodes, comparing the affected side with the contralateral side. Abnormal muscle activity was categorized as a myopathic or neurogenic pattern. Results Nine LS subjects were selected for EMG, 2 with Parry-Romberg/Hemifacial Atrophy Syndrome, 7 linear scleroderma of an extremity and 2 with mixed forms (linear and morphea). Electromyogram analysis indicated that all but one had asymmetric myopathic pattern in muscles underlying the linear streaks. Motor and sensory nerve conduction was also evaluated in upper and lower limbs and one presented a neurogenic pattern. Masticatory muscle testing showed a myopathic pattern in the atrophic face of 2 cases with head and face involvement. Conclusion In our small series of LS patients, we found a surprising amount of muscle dysfunction by EMG. The muscle involvement may be possibly related to a secondary peripheral nerve involvement due to LS inflammation and fibrosis. Further collaborative studies to confirm these findings are needed. PMID:25053924

2013 American College of Rheumatology/European League against rheumatism classification criteria for systemic sclerosis outperform the 1980 criteria: data from the Canadian Scleroderma Research Group.

PubMed

Alhajeri, Hebah; Hudson, Marie; Fritzler, Marvin; Pope, Janet; Tatibouet, Solène; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Baron, Murray

2015-04-01

The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity. SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion. A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%. The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity. Copyright © 2015 by the American College of Rheumatology.

[Clinical, endoscopic and morphological manifestations of oesophageal lesion in systemic scleroderma].

PubMed

Karateev, A E; Movsiian, A E; Anan'eva, M M; Radenska-Lopovok, S G

2014-01-01

Oesophageal lesion is the commonest visceral manifestation of systemic scleroderma (SSD) affecting the quality of life and fraught with serious complications. The aim of this study was to evaluate clinical, endoscopic andmorphological manifestations of oesophageal lesion in systemic scleroderma and its relationships with other clinical symptoms and pharmacotherapy of the disease. 479 patients with SSD (93.7% women, 6.3% men, mean age 48.7 +/- 19.2 yr). All of them underwent EGDS in 2005-2010. 123 patients were examined for the detection of Barrett's oesophagus (BO), total screening regardless of complaints was conducted in 2010. Control group included 1018 age and sex-matched patients with RA who underwent EGDS in 2008-2009. Oesophageal lesions occurred much more frequently in SSD than in RA. Oesophageal symptoms were documented in 70.0 and 29.9% cases, non-erosive oesopahgitis in 28.8 and 1.5%, erosive esophagitis in 22.5 and 2.2% ulcers in 0.8 and 0% (p < 0.001). BO manifested as intestinal metaplasia (histological study of mucosal biopsy) was found in 30 SSD patients (4.2%). Screening revealed BO in 8.9% of the patients. The development of erosive oesophagitis was unrelated to the age of the patients, duration of the disease and its form (localized or diffusive), lung pathology or Sjogren's syndrome. Cytotoxic medicines significantly increased the frequency of erosive oesophagitis, it tended to increase under effect of NSAID and low doses of aspirin. Long-term intake of PPI did not reduce the risk of oesophagitis and BO. Half of the patients with SSD have oesophagitis. Over 20% of them suffer its complications (erosion and ulcers) and 9% have BO. All such patients need endoscopic study ofoesophagus regardless of clinical symptoms.

Social/economic costs and health-related quality of life in patients with scleroderma in Europe.

PubMed

López-Bastida, Julio; Linertová, Renata; Oliva-Moreno, Juan; Serrano-Aguilar, Pedro; Posada-de-la-Paz, Manuel; Kanavos, Panos; Taruscio, Domenica; Schieppati, Arrigo; Iskrov, Georgi; Péntek, Márta; Delgado, Claudia; von der Schulenburg, Johann Mathias; Persson, Ulf; Chevreul, Karine; Fattore, Giovanni

2016-04-01

The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with systemic sclerosis (SSc; scleroderma) in Europe. We conducted a cross-sectional study of patients with SSc (involving both localised and systemic sclerosis) from Germany, Italy, Spain, France, the UK, Hungary and Sweden. Data on demographic characteristics, healthcare resource utilisation, informal care, labour productivity losses and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. A total of 589 patients completed the questionnaire. The rate of patients with localised scleroderma, limited cutan and diffuse cutan SSc were 28, 68 and 4 %, respectively. Average annual costs varied from country to country and ranged from € 4607 to € 30,797 (reference year: 2012). Estimated direct healthcare costs ranged from € 1413 to € 17,300; direct non-healthcare costs ranged from € 1875 to € 4684 and labour productivity losses ranged from € 1701 to € 14,444. The mean EQ-5D index score for adult SSc patients varied from 0.49 to 0.75 and the mean EQ-5D visual analogue scale score was between 58.72 and 65.86. The main strengths of this study lie in our bottom-up approach to costing and our evaluation of SSs patients from a broad societal perspective. This type of analysis is very unusual in the international literature on rare diseases in comparison with other illnesses. We concluded that SSc patients incur considerable societal costs and experience substantial deterioration in HRQOL.

Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis.

PubMed

Doré, Adam; Lucas, Mary; Ivanco, Dana; Medsger, Thomas A; Domsic, Robyn T

2013-08-01

Palpable tendon friction rubs (TFRs) in systemic sclerosis (SSc; scleroderma) have been associated with diffuse skin thickening, increased disability, and poor survival. Our objective was to quantify the prognostic implications of palpable TFRs on the development of disease complications and longer-term mortality in an incident cohort of early diffuse cutaneous SSc (dcSSc) patients. We identified early dcSSc patients (disease duration <2 years from the first SSc symptom) first evaluated at the University of Pittsburgh Scleroderma Center between 1980 and 2006 and found to have palpable TFRs. These patients were matched 1:1 with the next consecutive early dcSSc patient without TFRs as a control. All had ≥2 clinic visits and 5 years of followup from the first visit. A total of 287 early dcSSc patients with TFR were identified and matched to 287 controls. The median disease duration was 0.83 years in TFR patients and 1.04 years in controls. The median followup was 10.1 years in TFR patients and 7.9 years in controls. Over the course of their illness, patients with TFRs had a >2-fold risk of developing renal crisis and cardiac and gastrointestinal disease complications, even after adjustment for other known risk factors. Patients with TFRs had poorer 5- and 10-year survival rates. Patients with early dcSSc having ≥1 TFRs are at an increased risk of developing renal, cardiac, and gastrointestinal involvement before and after their first Scleroderma Center visit and have reduced survival. Patients presenting with TFRs should be carefully monitored for serious internal organ involvement. Copyright © 2013 by the American College of Rheumatology.

Assessment of nailfold capillaroscopy in systemic sclerosis by different optical magnification methods.

PubMed

Mazzotti, N G; Bredemeier, M; Brenol, C V; Xavier, R M; Cestari, T F

2014-03-01

Systemic sclerosis (SSc) is characterized by target-organ fibrosis and microvascular dysfunction, which can be assessed using nailfold capillaroscopy. Dermoscopy is a useful and easily performed method for diagnosing skin lesions. To compare conventional capillaroscopy, using the gold-standard method (conventional stereomicroscope nailfold capillaroscopy; SNFC), with polarized light noncontact dermoscopy (PNCD) and nonpolarized light contact dermoscopy (NPCD), and to evaluate their accuracy in diagnosing characteristic SSc-related alterations. The study enrolled 45 patients with SSc. Capillaroscopy images and photographs were taken with three devices, SNFC, NPCD and PNCD, and these images were randomly analysed by a blinded observer. The scleroderma pattern was found in 83% of patients. PNCD and NPCD were highly sensitive in identifying the presence of focal capillary loss (96.4% and 100%, respectively), haemorrhage (96.2% and 92%, respectively), and scleroderma (91.9%, 94.6%), and showed high specificity for haemorrhage and enlarged loops. The intra-observer kappa values for detection of the scleroderma pattern by SNFC images, NPCD and PNCD were moderate to good: (κ = 0.71 (95% CI 0.44-0.95), κ = 0.60 (95% CI 0.35-0.83) and κ = 0.60 (95% CI 0.32-0.86), respectively. Evaluation of haemorrhage presence gave high kappa values for all methods: κ = 0.77 (95% CI 0.57-0.95), κ = 0.90 (95% CI 0.76-1.00) and κ = 0.95 (95% CI 0.85-1.00), respectively. Both polarized and nonpolarized dermoscopy are reliable methods for valuation of nailfold capillaroscopy in patients with SSc. They are easy to perform, with good rates of accuracy and results that are comparable with traditional capillaroscopy. © 2013 British Association of Dermatologists.

Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.

PubMed

Cockrill, Tonya; del Junco, Deborah J; Arnett, Frank C; Assassi, Shervin; Tan, Filemon K; McNearney, Terry; Fischbach, Michael; Perry, Marilyn; Mayes, Maureen D

2010-03-01

Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06-1.50 for birth order 2-5; OR 2.22, 95% CI 1.57-3.15 for birth order 6-9; and OR 3.53, 95% CI 1.68-7.45 for birth order 10-15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.

Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

PubMed

Takahashi, Takehiro; Asano, Yoshihide; Oka, Tomonori; Miyagaki, Tomomitsu; Tamaki, Zenshiro; Nonaka, Senshu; Sato, Shinichi

2016-02-01

We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled. However, in the course of our follow up, he had another episode of brain hemorrhage, again without any evidence of cerebral vascular abnormalities. Organic intracranial abnormalities in this disease are well-documented, but there have been few reports on comorbid recurrent brain hemorrhages. We herein discuss the possible relationship of the skin lesions with the brain hemorrhages in our case, taking notice of the implication of developmental abnormalities behind these apparently independent phenomena inside and outside the cranium. © 2015 Japanese Dermatological Association.

Points to consider in renal involvement in systemic sclerosis.

PubMed

Galluccio, Felice; Müller-Ladner, Ulf; Furst, Daniel E; Khanna, Dinesh; Matucci-Cerinic, Marco

2017-09-01

This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution

PubMed Central

Emanuele, Cocchiara; Amelia, Spinella; Clodoveo, Ferri

2018-01-01

Background Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset. PMID:29666638

Juvenile-onset localized scleroderma activity detection by infrared thermography.

PubMed

Martini, G; Murray, K J; Howell, K J; Harper, J; Atherton, D; Woo, P; Zulian, F; Black, C M

2002-10-01

The aim of this study was to define the clinical utility of infrared thermography in disease activity detection in localized scleroderma (LS). We retrospectively reviewed 130 thermal images of 40 children with LS and calculated the sensitivity and specificity of thermography, comparing clinical descriptions of the lesions and contemporary thermographs. The reproducibility of thermography was calculated by using the weighted kappa coefficient to determine the level of agreement between two clinicians who reviewed the thermographs independently. The sensitivity of thermography was 92% and specificity was 68%. Full concordance between the two clinicians was observed in 91% of lesions, with a kappa score of 0.82, implying very high reproducibility of this technique. Our results demonstrate that thermography is a promising diagnostic tool when associated with clinical examination in discriminating disease activity, as long as it is applied to lesions without severe atrophy of the skin and subcutaneous fat. Further evaluation is needed to determine whether thermography can predict the future progression of lesions.

Nailfold video-capillaroscopy in systemic sclerosis.

PubMed

Cutolo, M; Pizzorni, C; Sulli, A

2004-12-01

The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.

Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

PubMed

Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

2015-08-06

Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

Mild clinical phenotype of Kindler syndrome associated with late diagnosis and skin cancer.

PubMed

Has, C; Burger, B; Volz, A; Kohlhase, J; Bruckner-Tuderman, L; Itin, P

2010-01-01

Kindler syndrome (KS) is a heritable skin disorder with a complex phenotype consisting of congenital skin blistering, photosensitivity, progressive generalized poikiloderma and extensive skin atrophy. Here we describe 2 siblings with KS, who are, to the best of our knowledge, the oldest patients reported so far in the literature. The diagnosis was established in their seventh and eighth decades of life, and confirmed by mutation analysis. Both patients were homozygous for the recurrent FERMT1 mutation, c.328C→T, p.R110X. Because of a relatively mild course of the disease, mucosal membranes in the eyes and oesophagus being predominantly affected in recent years, they had been treated under other diagnoses, such as scleroderma. Cutaneous precancerous lesions and epithelial skin cancer arose in both siblings after the age of 50 years and were treated in an early stage. Taken together, we describe the natural course of KS, the morphological abnormalities occurring in the skin of older KS patients, we discuss the differential diagnosis and the association between KS and squamous cell carcinoma. Copyright © 2010 S. Karger AG, Basel.

[Pregnancy in pulmonary arterial hypertension patients].

PubMed

Rosengarten, Dror; Kramer, Mordechai R

2013-09-01

Pulmonary arterial hypertension (PAH) is a disorder defined by elevated mean pulmonary arterial pressure. PAH can be idiopathic or associated with a variety of medical conditions such as scleroderma, congenital heart disease, left heart failure, lung disease or chronic pulmonary thromboembolism. This progressive disease can cause severe right heart failure and death. Normal physiologic changes that occur during pregnancy may produce fatal consequences in PAH patients. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. During the past decade, new advanced therapies for PAH have emerged gathering reports of successful pregnancies in patients with pulmonary hypertension. Substantial risk still exists and current recommendations have not changed. Nevertheless, in selected cases, if a patient insists on continuing the pregnancy, being fully aware of the risks involved, an intensive treatment approach should be implemented in experienced centers. This is necessary in order to control pulmonary hypertension during pregnancy and reduce the risk so as to improve outcomes. This review will focus on the pathophysiology of PAH in pregnancy and appropriate management during pregnancy, delivery and the post-partum period.

[Therapeutic administration of immunoglobulins].

PubMed

Witte, T

2016-12-01

Intravenously administered immunoglobulins have multiple modes of action that are anti-inflammatory. They can therefore be beneficial in a number of autoimmune disorders. The aim of this article is to analyze and summarize studies on the administration of intravenous immunoglobulins in rheumatological diseases. A selective search and analysis of the literature was carried out related to the mode of action and efficacy of intravenous immunoglobulins in rheumatological diseases. Intravenous immunoglobulins have a broad mode of action and can therefore be beneficial in almost all autoimmune diseases. Conditions in which they are of special benefit include immunothrombopenia (ITP), Kawasaki disease and idiopathic inflammatory myopathies. In rare situations, they may also be indicated in systemic lupus erythematosus (SLE), Sjögren's syndrome and neuropathies, catastrophic antiphospholipid syndrome (APS), scleroderma, antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, pyoderma gangrenosum and scleromyxedema. Severe adverse events are rare. In view of the high costs of the therapy, intravenous immunoglobulins are mostly applied in emergency situations, as salvage therapy when other standard therapies have failed or when severe infections are a contraindication to the administration of immunosuppressants.

Targeting the Nociceptin/Orphanin FQ Receptor for Scleroderma Therapy

DTIC Science & Technology

2016-08-01

quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small- vessel...ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small-vessel myograph. Vasodilation will be determined by

Parasitization by Scleroderma guani influences protein expression in Tenebrio molitor pupae

USDA-ARS?s Scientific Manuscript database

Ectoparasitoid wasps deposit their eggs on the surface and inject venom into the host. Venoms are chemically complex and they exert substantial impact on hosts, including permanent or temporary paralysis and developmental arrest. These visible venom effects emerge from changes in expression of genes...

Gadolinium-based compounds induce NLRP3-dependent IL-1β production and peritoneal inflammation.

PubMed

Schmidt-Lauber, Christian; Bossaller, Lukas; Abujudeh, Hani H; Vladimer, Gregory I; Christ, Anette; Fitzgerald, Katherine A; Latz, Eicke; Gravallese, Ellen M; Marshak-Rothstein, Ann; Kay, Jonathan

2015-11-01

Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1β release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. Bone marrow derived macrophages from C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing compounds and IL-1β activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)γ-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/-)mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1β secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFNγ-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic presentation of NSF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Targeting the Nociceptin/Orphanin FQ Receptor for Scleroderma Therapy

DTIC Science & Technology

2015-12-01

bottom well; the number of migrating cells is quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will...quantified by flow cytometry. In the aortic ring assay, freshly isolated thoracic aorta rings will be harvested and mounted in a small-vessel myograph. KO

Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

DTIC Science & Technology

2009-06-01

fibro- blasts, we were able to identify the genes involved in 6 out of 10 types of Ehlers – Danlos syndrome , a congenital disease characterized by skin...hand–- foot–genital syndrome , a disease char- acterized by syndactyly, hypospadias, and malformations of the urogenital system. These results indicate

Occupational and environmental scleroderma. Systematic review and meta-analysis.

PubMed

Rubio-Rivas, Manuel; Moreno, Rafael; Corbella, Xavier

2017-03-01

The etiology of systemic sclerosis (SSc) remains unknown; however, several occupational and environmental factors have been implicated. Our objective was to perform a meta-analysis of all studies published on SSc associated with occupational and environmental exposure. The review was undertaken by means of MEDLINE and SCOPUS from 1960 to 2014 and using the terms: "systemic," "scleroderma," or "systemic sclerosis/chemically induced" [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment. The inverse variance-weighted method was performed. The meta-analysis of silica exposure included 15 case-control studies [overall OR 2.81 (95%CI 1.86-4.23; p < 0.001)] and 4 cohort studies [overall RR 17.52 (95%CI 5.98-51.37; p < 0.001)]; the meta-analysis of solvents exposure included 13 case-control studies (overall OR 2.00 [95%CI 1.32-3.02; p = 0.001); the meta-analysis of breast implants exposure included 4 case-control studies (overall OR 1.68 (95%CI 1.65-1.71; p < 0.001)) and 6 cohort studies (overall RR 2.13 (95%CI 0.86-5.27; p = 0.10)); the meta-analysis of epoxy resins exposure included 4 case-control studies (overall OR 2.97 (95%CI 2.31-3.83; p < 0.001)), the meta-analysis of pesticides exposure included 3 case-control studies (overall OR 1.02 (95%CI 0.78-1.32; p = 0.90)) and, finally, the meta-analysis of welding fumes exposure included 4 studies (overall OR 1.29 (95%CI 0.44-3.74; p = 0.64)). Not enough studies citing risks related to hair dyes have been published to perform an accurate meta-analysis. Silica and solvents were the two most likely substances related to the pathogenesis of SSc. While silica is involved in particular jobs, solvents are widespread and more people are at risk of having incidental contact with them.

Relationship Between Disease Characteristics and Orofacial Manifestations in Systemic Sclerosis: Canadian Systemic Sclerosis Oral Health Study III

PubMed Central

BARON, MURRAY; HUDSON, MARIE; TATIBOUET, SOLÈNE; STEELE, RUSSELL; LO, ERNEST; GRAVEL, SABRINA; GYGER, GENEVIÈVE; SAYEGH, TAREK EL; POPE, JANET; FONTAINE, AUDREY; MASETTO, ARIEL; MATTHEWS, DEBORA; SUTTON, EVELYN; THIE, NORMAN; JONES, NIALL; COPETE, MARIA; KOLBINSON, DEAN; MARKLAND, JANET; NOGUEIRA, GETULIO; ROBINSON, DAVID; FRITZLER, MARVIN; GORNITSKY, MERVYN

2015-01-01

Objective Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. Methods Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. Results One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren’s syndrome–related autoantibodies (β = −43.32; 95% confidence interval [95% CI] −80.89, −5.75), but not with disease severity (β = −2.51; 95% CI −8.75, 3.73). Decreased interincisal distance was related to disease severity (β = −1.02; 95% CI −1.63, −0.42) and the modified Rodnan skin thickness score (β = −0.38; 95% CI −0.53, −0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. Conclusion In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren’s syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear. PMID:25303223

Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH[S

PubMed Central

Ioannou, George N.; Subramanian, Savitha; Chait, Alan; Haigh, W. Geoffrey; Yeh, Matthew M.; Farrell, Geoffrey C.; Lee, Sum P.; Savard, Christopher

2017-01-01

We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha, NLRP3, and interleukin 1beta (IL1β) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes. PMID:28404639

Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.

PubMed

Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed

2016-01-01

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.

Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.

PubMed

Bhaskaran, Manoj; Didier, Peter J; Sivasubramani, Satheesh K; Doyle, Lara A; Holley, Jane; Roy, Chad J

2014-01-01

Ricin toxin, a type 2 ribosome-inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage, and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from group II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.

A Study of Discharge Coefficient in Bileaflet Valves

DTIC Science & Technology

2001-10-25

Granados J. Garcia MA. Luque I. Concha M. “Conservative operation for mitral stenosis with densely fibrosed or partially calcified valves. An eight...for aortic valves, whereas a lower value (around 0.7) has been proposed for valves mounted in the mitralic position, on account of the larger upstream...section; in the mitral position, then, a valve will have a smaller discharge coefficient (or Aeff/A ratio) than in the aortic position. Using dC =1

Novel disposable transnasal endoscopy for assessment of esophageal motor function.

PubMed

Lim, Chul-Hyun; Choi, Myung-Gyu; Baeg, Myong-Ki; Moon, Sung Jin; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Kyu Yong

2014-01-01

A novel disposable transnasal endoscopy (DTE) with a portable system has been developed to provide unsedated esophagoscopy by modifying capsule endoscopy. The aim of this study was to assess the feasibility of DTE to evaluate esophageal motor function. Patients with or suspected esophageal motility disorders and healthy volunteers were enrolled. Participants underwent esophageal high-resolution manometry and DTE in random order on different days. Motility was observed with DTE at 1, 8, and 16 cm above the gastroesophageal junction. Twenty healthy volunteers and 20 symptomatic subjects participated (8 achalasia, 5 scleroderma, 3 diffuse esophageal spasm, 1 hypertensive peristalsis, 1 peristaltic dysfunction, and 22 normal esophageal function). The normal findings on DTE were as follows. As the subject swallowed water, swallow-induced relaxation with elevation of the lower esophageal sphincter caused the endoscope to cross the Z-line into the gastric lumen. After the passage of water and air, complete closure of the lower esophageal sphincter occurred, with the return of the endoscope to its previous position. During the resting stage of the esophageal body, an air bubble could be seen in the center of the radially wrinkled and occluded lumen. The endoscopic diagnosis was in agreement with the clinical diagnosis in all but 2. Most of the participants reported acceptable discomfort during DTE and 62.5% of the subjects preferred DTE to manometry. DTE can accurately characterize normal esophageal motor function, allowing the diagnosis of esophageal motility disorders. DTE has potential widespread applications, especially in outpatient clinics.

Chondrodysplasia punctata associated with maternal autoimmune diseases: expanding the spectrum from systemic lupus erythematosus (SLE) to mixed connective tissue disease (MCTD) and scleroderma report of eight cases.

PubMed

Chitayat, David; Keating, Sarah; Zand, Dina J; Costa, Teresa; Zackai, Elaine H; Silverman, Earl; Tiller, George; Unger, Sheila; Miller, Stephen; Kingdom, John; Toi, Ants; Curry, Cynthia J R

2008-12-01

Chondrodysplasia punctata (CDP) is etiologically a heterogeneous condition and has been associated with single gene disorders, chromosome abnormalities and teratogenic exposures. The first publication of the association between CDP and maternal autoimmune connective tissue disorder was by Curry et al. 1993]. Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and subsequently, other cases have been reported. We report on eight cases of maternal collagen vascular disease associated with fetal CDP and included the cases reported by Curry et al. 1993. Chondrodysplasia punctata associated with maternal collagen vascular disease. A new etiology? Presented at the David W. Smith Workshop on Morphogenesis and Malformations, Mont Tremblant, Quebec, August 1993] and Costa et al. [1993]. Maternal systemic lupus erythematosis (SLE) and chondrodysplasia punctata in two infants. Coincidence or association? 1st Meeting of Bone Dysplasia Society, Chicago, June 1993] which were reported in an abstract form. We suggest that maternal autoimmune diseases should be part of the differential diagnosis and investigation in newborns/fetuses with CDP. Thus, in addition to cardiac evaluation, fetuses/newborn to mothers with autoimmune diseases should have fetal ultrasound/newborn examination and if indicated, X-rays, looking for absent/hypoplastic nasal bone, brachydactyly, shortened long bones and epiphyseal stippling. Copyright (c) 2008 Wiley-Liss, Inc.

Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management

PubMed Central

Oldham, Justin M.; Collard, Harold R.

2017-01-01

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3–5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH), while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM) and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current state of treatment data for several key comorbidities. PMID:28824912

Parasitization by Scleroderma guani influences expression of superoxide dismutase genes in Tenebrio molitor

USDA-ARS?s Scientific Manuscript database

Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor....

Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin

DTIC Science & Technology

2008-06-01

identify the genes involved in 6 out of 10 types of Ehlers – Danlos syndrome , a congenital disease characterized by skin fragility and joint laxity...Similarly, we observed that HOXA13 is induced in toe and foreskin fibroblasts, and mutation of HOXA13 in humans leads to hand–- foot–genital syndrome , a

Inoculation of Loblolly Pine Seedlings at Planting with Basidiospores of Ectomycorrhizal Fungi in Chip Form

Treesearch

Peter R. Beckjord; Marla S. McIntosh; Edward Hacskaylo; John H. Jr. Melhuish; John H. Jr. Melhuish

1984-01-01

Basidiospores of the ectomycorrhizae-forming fungi Pisolithus tinctorius and Scleroderma auranteum incorporated into an organic hydrocolloid can be used successfully in field inoculation. Containerized loblolly pine seedlings were inoculated during outplanting by this method. This study showed that basidiospore chips were effective inocula in this investigation.

The Modulation of Fibrosis In Scleroderma by 3-Deoxyglucosone

DTIC Science & Technology

2011-06-01

24 h . . RNA was extracted and quantitative real-time PCR was performed for the GObi AI transcript. Transcript levels were normalized to !3-actin. AJI ... Red X denotes the negative effect of 3DG-collagen on that pathway. 54 55 Reference List (1) Kessler D, Dethlefsen S, Haase I, Plomann M

Pulsed versus continuous wave low-level light therapy on osteoarticular signs and symptoms in limited scleroderma (CREST syndrome): a case report

NASA Astrophysics Data System (ADS)

Barolet, Daniel

2014-11-01

Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome in reference to the associated clinical features: calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. The transforming growth factor beta has been identified as a major player in the pathogenic process, where low-level light therapy (LLLT) has been shown to modulate this cytokine superfamily. This case study was conducted to assess the efficacy of 940 nm using millisecond pulsing and continuous wave (CW) modes on osteoarticular signs and symptoms associated with lcSSc. The patient was treated two to three times a week for 13 weeks using a sequential pulsing mode on one elbow and a CW mode on the other. Efficacy assessments included inflammation, symptoms, pain, health scales, patient satisfaction, clinical global impression, and adverse effects monitoring. Considerable functional and morphologic improvements were observed after LLLT, with the best results seen with the pulsing mode. No adverse effects were noted. Pulsed LLLT represents a treatment alternative for osteoarticular signs and symptoms in limited scleroderma (CREST syndrome).

Consensus best practice pathway of the UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis.

PubMed

Hughes, Michael; Ong, Voon H; Anderson, Marina E; Hall, Frances; Moinzadeh, Pia; Griffiths, Bridget; Baildam, Eileen; Denton, Christopher P; Herrick, Ariane L

2015-11-01

Digital vasculopathy (comprising RP, digital ulceration and critical digital ischaemia) is responsible for much of the pain and disability experienced by patients with SSc. However, there is a limited evidence base to guide clinicians in the management of SSc-related digital vasculopathy. Our aim was to produce recommendations that would be helpful for clinicians, especially for those managing patients outside specialist centres. The UK Scleroderma Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including digital vasculopathy. This overview presents the background and best practice consensus pathways for SSc-related RP, digital ulceration and critical ischaemia. Examples of drug therapies, including doses, are suggested in order to inform prescribing practice. A number of treatment algorithms are provided that are intended to provide the clinician with accessible reference tools for use in daily management. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of coal ash on growth and metal uptake by some selected ectomycorrhizal fungi in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, P.; Reddy, U.G.; Lapeyrie, F.

2005-07-01

Six isolates of ectomycorrhizal fungi namely, Laccaria fraterna (EM-1083), Pisolithus tinctorius (EM-1081), Pisolithus tinctorius (EM-1290), Pisolithus tinctorius (EM-1293), Scleroderma verucosurn (EM-1283), and Scleroderma cepa (EM-1233), were grown on three variants of coal ash, namely electrostatically precipitated (ESP) ash, pond ash, and bottom ash moistened with Modified Melin-Norkans (MMN) medium in vitro. The colony diameter reflected the growth of the isolates on the coal ash. Metal accumulation in the mycelia was assayed by atomic absorption spectrophotometry. Six metals, namely aluminum, cadmium, chromium, iron, lead, and nickel were selected on the basis of their abundance in coal ash and toxicity potential formore » the present work. Growth of vegetative mycelium on fly ash variants and metal accumulation data indicated that Pisolithus tinctorius (EM-1290) was the most tolerant among the isolates tested for most of the metals. Since this isolate is known to be mycorrhizal with Eucalyptus, it could be used for the reclamation of coal ash over burdened sites.« less

Scleroderma and the temporomandibular joint: reconstruction in 2 variants.

PubMed

MacIntosh, Robert Bruce; Shivapuja, Prasanna-Kumar; Naqvi, Rabia

2015-06-01

This article reviews the pathophysiology of scleroderma (systemic sclerosis [SSc]) and its destructive effects on the mandible in general and the temporomandibular joint (TMJ) in particular. It discusses the considerations of operating on patients with devastating chronic disease and presents 2 cases of TMJ reconstruction in patients with the diagnosis. Two patients with different degrees of SSc involvement underwent TMJ reconstruction with costochondral grafts. The patients represent the surgical considerations pertinent to this disease and different outcomes as determined by the variance in severity of their afflictions. The 2 patients tolerated the surgeries well and exhibited improvement in function in the long-term. One patient thrives and continues to do well despite her SSc approximately 10 years postoperatively; the second patient died of her disease approximately 9 years after her initial surgical care. The experience with these 2 cases showed that patients with SSc can safely undergo TMJ reconstruction with anticipated good results, but that the overall severity of the disease remains paramount in determining the feasibility of corrective surgery under this diagnosis. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Type 1 neurofibromatosis and pulmonary hypertension: a report of two cases and a review

PubMed Central

Malviya, Amit; Mishra, Sundeep; Kothari, Shyam S

2012-01-01

Pulmonary hypertension in type 1 neurofibromatosis is not well known and was previously attributed to diffuse fibrosing alveolitis and parenchymal tumours. More recently, cases of severe pulmonary hypertension due to pulmonary vasculopathy have been described. Involvement of vascular beds, both large and medium calibre vessels, but not pulmonary vasculature, in type 1 neurofibromatosis is well known. The authors describe two such cases and briefly review the literature. Pulmonary arterial hypertension in neurofibromatosis warrants further studies. PMID:27326022

Skin and mucous membranes’ manifestations of dermatological diseases within the genital area in females

PubMed Central

Plagens-Rotman, Katarzyna; Przybylska, Renata; Adamski, Zygmunt; Czarnecka-Operacz, Magdalena

2018-01-01

Introduction Lichen sclerosus et atrophicus (LSA) and an inversed type of psoriasis belong to a group of benign dermatoses usually located within the region of female external genitalia. The most common subjective symptoms reported by patients are itching, pain and changes in the color and structure of the skin. Aim This paper presents 3 cases of patients suffering from selected dermatoses located within the external female genitalia treated at the Department of Dermatology, Poznan University of Medical Sciences. Case reports Case 1. A 78-year-old patient admitted to the Department of Dermatology diagnosed with l ichen sclerosus and atrophic as well as scleroderma, which had already been confirmed by histopathological examination in 2014. Laboratory tests demonstrated an increased level of glycemia, elevated ESR and lymphopenia. In the treatment of TFX (Thymus factor X) therapy (immunomodulating treatment), vitamins A + E containing cream and Protopic 0.1% ointment twice daily were recommended. Case 2. A patient aged 49 was admitted to the Department of Dermatology due to exacerbation of skin inflammation in the course of psoriasis. She presented with severe erythematous and papular lesions covered with silvery scales, with the highest intensity within the palmar surfaces of both hands, in the folds of under the breasts, groins, and therefore, the clinical picture was characteristic of inversed psoriasis (psoriasis inversa). Case 3. A 20-year-old patient admitted to the Department of Dermatology in order to proceed with the treatment of a diffuse type of scleroderma. Clinical diagnosis has been already confirmed by the skin biopsy (typical histological features of scleroderma), however exclusion of other dermatoses such as LSA was not possible. Conclusions While analyzing the available scientific reports, the physician in charge must adjust therapeutic options individually, taking into account the clinical condition of the patient in case of dermatological diseases within the female genital region. PMID:29760622

Use of a medication control officer to reduce bias in a clinical trial: lessons learned from the scleroderma lung study.

PubMed

Hsu, Vivien M; Khanna, Dinesh; Smith, Edwin; Filemon, Tan; Whelton, Sean; Lopata, Mel; Davis, John C; Polito, Albert; Heck, Louis; Molitor, Jerry; Abeles, Micha; Granda, Jose; Korn, Joseph; Clements, Philip

2010-02-01

Scleroderma Lung Study (SLS) was designed to evaluate the efficacy and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for scleroderma-associated interstitial lung disease. An independent medication control officer (MCO), usually a physician, at each center was assigned to monitor laboratory and clinical toxicity of study medication and regulate its dosing based on these results. By having an MCO who watched and managed toxicity, the study investigators were free to care for study patients and to assess study outcomes without the potential bias of knowing toxicity data (toxicity from cyclophosphamide is distinctive - cytopenias and hematuria in particular). To assess the usefulness of an MCO, whose chief role was to maintain safety while retaining the blinding in the clinical trial. Patients had safety laboratory testing every 2-4 weeks and results were sent directly to the MCO within 2 days of the test. Other clinical adverse events (AEs) were reported by the patient to a nurse coordinator who reported them to the MCO who then managed the AEs to preserve the blinding of investigators caring for the patients. The MCO was provided pre-determined algorithms for dose adjustments of test medication based on the presence and severity of laboratory abnormalities. Safety monitoring by the MCO was effective in the early detection of drug toxicity with provision of appropriate medical intervention on a timely basis. At the same time, investigator blinding appeared to be maintained. The testing of MCO effectiveness in maintaining blinding and consistency was not defined as an a priori hypothesis and thus complete data relating to the efficacy of the MCO were not collected in a prospective fashion. An MCO and pre-specified monitoring and dosing guidelines, coupled with uniform pre-specified responses to AEs, may be used effectively to preserve investigator blinding and provide consistency in response to AEs in a clinical trial setting, even when AEs of the test medication are distinctive.

Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

PubMed

McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

2017-11-01

SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Assessment of Microvascular Abnormalities by Nailfold Capillaroscopy in Juvenile Dermatomyositis After Medium- to Long-Term Followup.

PubMed

Barth, Zoltan; Witczak, Birgit N; Flatø, Berit; Koller, Akos; Sjaastad, Ivar; Sanner, Helga

2018-05-01

In juvenile dermatomyositis (DM), microvascular abnormalities, measured by nailfold capillaroscopy (NFC), are common early in the disease course. We aimed to compare the presence of NFC abnormalities in patients with medium- to long-term juvenile DM with that of controls, and to explore associations between NFC abnormalities and disease activity and other disease characteristics. Fifty-eight juvenile DM patients with a median disease duration of 16.8 (range 2-38) years were clinically examined and compared with matched controls. By NFC, we assessed nailfold capillary density (NCD), giant capillaries, scleroderma, and neovascular pattern (defined as scleroderma active or late pattern). NFC was analyzed with researchers blinded to patient/control identity and disease characteristics. We measured disease activity and damage by validated tools, and patients were categorized as having active or inactive disease according to the Paediatric Rheumatology International Trials Organisation criteria. Compared to controls, patients had decreased NCD (mean ± SD 6.4 ± 2.1/mm versus 7.6 ± 0.8/mm; P = 0.001) and showed more abnormality in all other NFC parameters; 36% of patients versus 4% of controls had NCD <6/mm (P < 0.001). Giant capillaries, scleroderma, and neovascular pattern were found in 9%, 84%, and 41% of patients, respectively. Patients with active disease (n = 30) presented more frequently with neovascular pattern than patients with inactive disease (n = 28) (P = 0.041). Decreased NCD and neovascular pattern were associated with higher levels of disease activity and impaired muscle function. After medium- to long-term followup, juvenile DM patients had decreased NCD and, often, neovascular pattern; both were associated with higher levels of disease activity and impaired muscle function. This suggests that NFC can be a biomarker for disease activity in longstanding juvenile DM too. © 2017, American College of Rheumatology.

Evaluation and management of esophageal manifestations in systemic sclerosis.

PubMed

Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

Role of platelet-derived growth factors in physiology and medicine

PubMed Central

Andrae, Johanna; Gallini, Radiosa; Betsholtz, Christer

2008-01-01

Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-α signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-β signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial–mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts. PMID:18483217

Evaluation and management of esophageal manifestations in systemic sclerosis

PubMed Central

Denaxas, Konstantinos; Ladas, Spyros D.; Karamanolis, George P.

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities. PMID:29507463

Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.

PubMed

Fillon, Sophie; Klingel, Karin; Wärntges, Simone; Sauter, Martina; Gabrysch, Sabine; Pestel, Sabine; Tanneur, Valerie; Waldegger, Siegfried; Zipfel, Annette; Viebahn, Richard; Häussinger, Dieter; Bröer, Stefan; Kandolf, Reinhard; Lang, Florian

2002-01-01

The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease. Copyright 2002 S. Karger AG, Basel

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases.

PubMed

Meng, Peng; Tan, Gan Liang; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-12-01

Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus. One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.

Pathogenesis of Systemic Sclerosis

PubMed Central

Pattanaik, Debendra; Brown, Monica; Postlethwaite, Bradley C.; Postlethwaite, Arnold E.

2015-01-01

Systemic scleroderma (SSc) is one of the most complex systemic autoimmune diseases. It targets the vasculature, connective tissue-producing cells (namely fibroblasts/myofibroblasts), and components of the innate and adaptive immune systems. Clinical and pathologic manifestations of SSc are the result of: (1) innate/adaptive immune system abnormalities leading to production of autoantibodies and cell-mediated autoimmunity, (2) microvascular endothelial cell/small vessel fibroproliferative vasculopathy, and (3) fibroblast dysfunction generating excessive accumulation of collagen and other matrix components in skin and internal organs. All three of these processes interact and affect each other. The disease is heterogeneous in its clinical presentation that likely reflects different genetic or triggering factor (i.e., infection or environmental toxin) influences on the immune system, vasculature, and connective tissue cells. The roles played by other ubiquitous molecular entities (such as lysophospholipids, endocannabinoids, and their diverse receptors and vitamin D) in influencing the immune system, vasculature, and connective tissue cells are just beginning to be realized and studied and may provide insights into new therapeutic approaches to treat SSc. PMID:26106387

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

PubMed

Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

2017-06-01

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of NASH. NEW & NOTEWORTHY This study demonstrates in a first of kind longitudinal analysis, the evolution of nonalcoholic steatohepatitis (NASH) on a fast-food diet-induced model. Key findings include 1 ) hepatic lipid composition changes in a multiphasic fashion as NASH evolves; 2 ) insulin resistance precedes hepatic inflammation and fibrosis, answering a longstanding chicken-and-egg question regarding the relationship of insulin resistance to liver histology in NASH; and 3 ) mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Copyright © 2017 the American Physiological Society.

Small intestinal bacterial overgrowth syndrome

PubMed Central

Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

2010-01-01

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

PubMed

Laique, Sobia; Singh, Tavankit; Dornblaser, David; Gadre, Abhishek; Rangan, Vikram; Fass, Ronnie; Kirby, Donald; Chatterjee, Soumya; Gabbard, Scott

2018-01-19

This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis.

PubMed

Sangiuolo, Federica; Puxeddu, Ermanno; Pezzuto, Gabriella; Cavalli, Francesco; Longo, Giuliana; Comandini, Alessia; Di Pierro, Donato; Pallante, Marco; Sergiacomi, Gianluigi; Simonetti, Giovanni; Zompatori, Maurizio; Orlandi, Augusto; Magrini, Andrea; Amicosante, Massimo; Mariani, Francesca; Losi, Monica; Fraboni, Daniela; Bisetti, Alberto; Saltini, Cesare

2015-02-01

In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage. The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation. Macrophage haemosiderin, BAL fluid MDA and BAL cell unstimulated iron-dependent oxygen radical generation were all significantly increased above controls (p<0.05). The frequency of C282Y, S65C and H63D HFE allelic variants was markedly higher in IPF compared with controls (40.4% versus 22.4%, OR 2.35, p=0.008) and was associated with higher iron-dependent oxygen radical generation (HFE variant 107.4±56.0, HFE wild type (wt) 59.4±36.4 and controls 16.7±11.8 fluorescence units per 10(5) BAL cells; p=0.028 HFE variant versus HFE wt, p=0.006 HFE wt versus controls). The data suggest iron dysregulation associated with HFE allelic variants may play an important role in increasing susceptibility to environmental exposures, leading to recurring injury and fibrosis in IPF. Copyright ©ERS 2015.

A Genome-wide Association Study of Dupuytren Disease Reveals 17 Additional Variants Implicated in Fibrosis.

PubMed

Ng, Michael; Thakkar, Dipti; Southam, Lorraine; Werker, Paul; Ophoff, Roel; Becker, Kerstin; Nothnagel, Michael; Franke, Andre; Nürnberg, Peter; Espirito-Santo, Ana Isabel; Izadi, David; Hennies, Hans Christian; Nanchahal, Jagdeep; Zeggini, Eleftheria; Furniss, Dominic

2017-09-07

Individuals with Dupuytren disease (DD) are commonly seen by physicians and surgeons across multiple specialties. It is an increasingly common and disabling fibroproliferative disorder of the palmar fascia, which leads to flexion contractures of the digits, and is associated with other tissue-specific fibroses. DD affects between 5% and 25% of people of European descent and is the most common inherited disease of connective tissue. We undertook the largest GWAS to date in individuals with a surgically validated diagnosis of DD from the UK, with replication in British, Dutch, and German individuals. We validated association at all nine previously described signals and discovered 17 additional variants with p ≤ 5 × 10 -8 . As a proof of principle, we demonstrated correlation of the high-risk genotype at the statistically most strongly associated variant with decreased secretion of the soluble WNT-antagonist SFRP4, in surgical specimen-derived DD myofibroblasts. These results highlight important pathways involved in the pathogenesis of fibrosis, including WNT signaling, extracellular matrix modulation, and inflammation. In addition, many associated loci contain genes that were hitherto unrecognized as playing a role in fibrosis, opening up new avenues of research that may lead to novel treatments for DD and fibrosis more generally. DD represents an ideal human model disease for fibrosis research. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Nephrogenic systemic fibrosis is associated with hypophosphataemia: a case-control study.

PubMed

Bernstein, Elana J; Isakova, Tamara; Sullivan, Mary E; Chibnik, Lori B; Wolf, Myles; Kay, Jonathan

2014-09-01

Nephrogenic systemic fibrosis (NSF) is an iatrogenic fibrosing disorder that primarily affects individuals with chronic kidney disease (CKD) following exposure to gadolinium-based contrast agents (GBCAs). Derangements of calcium and phosphorus have been reported in patients with NSF. The aim of this study was to investigate potential factors in addition to GBCA exposure that may be involved in the pathogenesis of NSF. We hypothesized that patients with stage 5 CKD and NSF would manifest greater alterations in calcium, phosphorus and fibroblast growth factor 23 (FGF23) levels than those who do not have NSF. Levels of phosphorus, calcium, FGF23 and 25-hydroxy-vitamin D were measured in 10 patients with stage 5 CKD and biopsy-proven NSF and in 19 patients with stage 5 CKD without NSF. Statistical analyses were performed using Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Patients with NSF had significantly lower phosphorus levels compared with controls (P = 0.01). There were no significant differences between NSF patients and controls in calcium, 25-hydroxy-vitamin D, intact parathyroid hormone or FGF23 levels. Differences in phosphorus metabolism may exist between patients with stage 5 CKD and NSF compared with patients with stage 5 CKD without NSF. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.

PubMed

Ramon, Silvia; Gleitz, Markus; Hernandez, Leonor; Romero, Luis David

2015-12-01

Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM). Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Clinical Investigation.

DTIC Science & Technology

1979-09-30

Aeling, J.L. and Chalet, M.D.: Collagen : Basic Science and Re:ated Diseases. Accepted for Publication. J. of Assoc. of Military Derm., 1979...102 Minoxidil as an Antihypertensive in Patients Refractory to Available Medications (T) (P) (PR). ...... . 037 75/107 A Comparison of the Results of...of Systemic Scleroderma with Minoxidil (U-1858) (0) .... ........................... 100 78/115 The Effect of Immunotherapy on the Tissue Threshold

A novel DNMT1 mutation associated with early onset hereditary sensory and autonomic neuropathy, cataplexy, cerebellar atrophy, scleroderma, endocrinopathy, and common variable immune deficiency.

PubMed

Fox, Robin; Ealing, John; Murphy, Helen; Gow, David P; Gosal, David

2016-09-01

DNA methyltransferase 1 (DNMT1) is an enzyme which has a role in methylation of DNA, gene regulation, and chromatin stability. Missense mutations in the DNMT1 gene have been previously associated with two neurological syndromes: hereditary sensory and autonomic neuropathy type 1 with dementia and deafness (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). We report a case showing overlap of both of these syndromes plus associated clinical features of common variable immune deficiency, scleroderma, and endocrinopathy that could also be mutation associated. Our patient was found to be heterozygous for a previously unreported frameshift mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. This case displays both the first frameshift mutation described in the literature which is associated with a phenotype with a high degree of overlap between HSAN1E and ADCA-DN and early age of onset (c. 8 years). Our case is also of interest as the patient displays a number of new non-neurological features, which could also be DNMT1 mutation related. © 2016 Peripheral Nerve Society.

Experiencing work as a daily challenge: the case of scleroderma.

PubMed

Mendelson, Cindy; Poole, Janet L; Allaire, Saralynn

2013-01-01

Little is known about the physical and discretionary aspects of work that people with scleroderma (SSc) find difficult. This article describes the findings from a study that explored the challenges and adaptations made by individuals with SSc to continue to work. Thirty-two employed individuals with SSc participated. Participants were predominantly women (82%), white (79%), and well educated (M = 16.9 years). The average age was 47.3 years, and 60.6% were married. Mean disease duration was 9.7 years, and 56.2% had diffuse SSc. Mean years on the job was 10.2 (SD ± 8.8), and 71.9% worked at least 35 hours per week. Participants engaged in a single structured interview about work-related challenges and adaptations. Content and thematic analysis was used to identify key themes across the interviews. Employees with SSc experienced Work as a daily challenge. This central theme described the general work experience for most participants. Three subthemes described their specific experiences: The work environment: Opportunities, challenges, and accommodations; Career planning; and Supportive others. The participants were anxious to find scenarios that allowed them to continue to work. Worksite accommodations and flexibility in scheduling can make the difference between working and disability.

Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guillet, G.; Guillet, J.; Sanciaume, C.

1988-04-01

We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum musclemore » enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.« less

Litter-forager termite mounds enhance the ectomycorrhizal symbiosis between Acacia holosericea A. Cunn. Ex G. Don and Scleroderma dictyosporum isolates.

PubMed

Duponnois, Robin; Assikbetse, Komi; Ramanankierana, Heriniaina; Kisa, Marija; Thioulouse, Jean; Lepage, Michel

2006-05-01

The hypothesis of the present study was that the termite mounds of Macrotermes subhyalinus (MS) (a litter-forager termite) were inhabited by a specific microflora that could enhance with the ectomycorrhizal fungal development. We tested the effect of this feeding group mound material on (i) the ectomycorrhization symbiosis between Acacia holosericea (an Australian Acacia introduced in the sahelian areas) and two ectomycorrhizal fungal isolates of Scleroderma dictyosporum (IR408 and IR412) in greenhouse conditions, (ii) the functional diversity of soil microflora and (iii) the diversity of fluorescent pseudomonads. The results showed that the termite mound amendment significantly increased the ectomycorrhizal expansion. MS mound amendment and ectomycorrhizal inoculation induced strong modifications of the soil functional microbial diversity by promoting the multiplication of carboxylic acid catabolizing microorganisms. The phylogenetic analysis showed that fluorescent pseudomonads mostly belong to the Pseudomonads monteillii species. One of these, P. monteillii isolate KR9, increased the ectomycorrhizal development between S. dictyosporum IR412 and A. holosericea. The occurrence of MS termite mounds could be involved in the expansion of ectomycorrhizal symbiosis and could be implicated in nutrient flow and local diversity.

Impact of a new simplified disability scoring system for adult patients with localized scleroderma.

PubMed

Okiyama, Naoko; Asano, Yoshihide; Hamaguchi, Yasuhito; Jinnin, Masatoshi; Motegi, Sei-Ichiro; Koizumi, Haruka; Hasegawa, Minoru; Ishikawa, Osamu; Sato, Shinichi; Takehara, Kazuhiko; Yamamoto, Toshiyuki; Fujimoto, Manabu; Ihn, Hironobu

2018-04-01

Localized scleroderma (LoS) involves dermal but not internal inflammation and fibrosis. Cosmetic changes often impact quality of life (QOL), however, impairment of activities of daily living (ADL) in LoS patients has not been investigated. To determine what factor(s) are associated with ADL in adult patients with LoS, we performed a retrospective observational study in 177 Japanese adult LoS patients using a novel LoS disability score based on Barthel's indices of ADL: feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility and stairs. LoS disability scores increased in proportion to the number of affected body parts but were not correlated to age and duration of illness. The presence of leg lesions significantly impaired ADL of LoS patients compared with lesions on other body parts. Patients treated with systemic medications, who tended to have multiple lesions, presented higher LoS disability scores than those without systemic treatments. Our study proposes that physicians evaluate ADL, not only QOL, in LoS patients. Our findings using LoS disability scoring indicate that multiple affected body parts and leg lesions are risk factors for ADL impairment. © 2018 Japanese Dermatological Association.

Improving imaging of the air-liquid interface in living mice by aberration-corrected optical coherence tomography (mOCT) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Schulz-Hildebrandt, Hinnerk; Sauer, Benjamin; Reinholz, Fred; Pieper, Mario; Mall, Markus; König, Peter; Huettmann, Gereon

2017-04-01

Failure in mucociliary clearance is responsible for severe diseases like cystic fibroses, primary ciliary dyskinesia or asthma. Visualizing the mucous transport in-vivo will help to understanding transport mechanisms as well as developing and validating new therapeutic intervention. However, in-vivo imaging is complicated by the need of high spatial and temporal resolution. Recently, we developed microscopy optical coherence tomography (mOCT) for non-invasive imaging of the liquid-air interface in intact murine trachea from its outside. Whereas axial resolution of 1.5 µm is achieved by the spectral width of supercontinuum light source, lateral resolution is limited by aberrations caused by the cylindric shape of the trachea and optical inhomogenities of the tissue. Therefore, we extended our mOCT by a deformable mirror for compensation of the probe induced aberrations. Instead of using a wavefront sensor for measuring aberrations, we harnessed optimization of the image quality to determine the correction parameter. With the aberration corrected mOCT ciliary function and mucus transport was measured in wild type and βENaC overexpressing mice, which served as a model for cystic fibrosis.

HURTLE CELLS IMMUNOHISTOCHEMICAL ACTIVITIES IN HASHIMOTO THYROIDITIS PARENCHYMA.

PubMed

Tsagareli, Z; Kvachadze, T; Melikadze, E; Metreveli, L; Nikobadze, E; Gogiashvili, L

2016-11-01

The present study was designed to evaluate the participation and utility of Hǘrtle cells morphological requirment and transformation under Hashimoto autoimmune thyroiditis versus Riedel´s struma. Several markers have been evaluated to detect induced activities of Hǘrtle cells. Study subject - specimens (tissue fragments) collected from TG surgery (thyroidectomy) for mollecular (receptor) diagnosis of Hǘrtle cells activities using routine histological and immunohistochemical samples. 89 cases were selected in Hashimoto thyroiditis diagnosis with Hǘrtle cells history (adenoma and adenomatous grouth of oncocytes). Markers as: TSH receptors, TTF-1, S-100 protein, also anti-TPO and anti-TG levels in blood plasm were detected. It was shown that solid cell claster-nests like agregation of oncocytes and adenomatous growth foci in parafollicular areas with anti-TPO and anti-TG antibodies levels arising while Riedel´s struma shown only large intra- and extra glandular inflammatory proliferative fibrosing process. Large positive expression of TTF-1 and S-100 protein and the negative reaction of TSH receptor factor suggest that Thyroid parenchyma disorganization and mollecular biological atypia with Hǘrtle cells are proceses due to hypothyreoidismus, as well as neuroectodermal cells prominent activities in 70% of Hashimoto cases.

FIB-SEM tomography of human skin telocytes and their extracellular vesicles

PubMed Central

Cretoiu, Dragos; Gherghiceanu, Mihaela; Hummel, Eric; Zimmermann, Hans; Simionescu, Olga; Popescu, Laurentiu M

2015-01-01

We have shown in 2012 the existence of telocytes (TCs) in human dermis. TCs were described by transmission electron microscopy (TEM) as interstitial cells located in non-epithelial spaces (stroma) of many organs (see www.telocytes.com). TCs have very long prolongations (tens to hundreds micrometers) named Telopodes (Tps). These Tps have a special conformation with dilated portions named podoms (containing mitochondria, endoplasmic reticulum and caveolae) and very thin segments (below resolving power of light microscopy), called podomers. To show the real 3D architecture of TC network, we used the most advanced available electron microscope technology: focused ion beam scanning electron microscopy (FIB-SEM) tomography. Generally, 3D reconstruction of dermal TCs by FIB-SEM tomography revealed the existence of Tps with various conformations: (i) long, flattened irregular veils (ribbon-like segments) with knobs, corresponding to podoms, and (ii) tubular structures (podomers) with uneven calibre because of irregular dilations (knobs) – the podoms. FIB-SEM tomography also showed numerous extracellular vesicles (diameter 438.6 ± 149.1 nm, n = 30) released by a human dermal TC. Our data might be useful for understanding the role(s) of TCs in intercellular signalling and communication, as well as for comprehension of pathologies like scleroderma, multiple sclerosis, psoriasis, etc. PMID:25823591

Review of Pharmacotherapy Options for the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD-Like Symptoms in Children and Adolescents with Developmental Disorders

ERIC Educational Resources Information Center

Rowles, Brieana M.; Findling, Robert L.

2010-01-01

Developmental disorders such as subaverage intelligence, pervasive developmental disorders, and genetic syndromes are frequently associated with comorbid attention-deficit/hyperactivity disorder (ADHD) or ADHD-like symptoms. While there are not pharmacological cures for these developmental disorders, coinciding ADHD and ADHD-like symptoms that…

Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH

PubMed Central

Ioannou, George N.; Van Rooyen, Derrick M.; Savard, Christopher; Haigh, W. Geoffrey; Yeh, Matthew M.; Teoh, Narci C.; Farrell, Geoffrey C.

2015-01-01

Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation. PMID:25520429

Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH.

PubMed

Ioannou, George N; Van Rooyen, Derrick M; Savard, Christopher; Haigh, W Geoffrey; Yeh, Matthew M; Teoh, Narci C; Farrell, Geoffrey C

2015-02-01

Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥ 3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation.

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2016-12-01

epidermal differentiation in addition to those involved in extracel- lular matrix production and myofibroblast contractility (35). In a followup study ...important manifestation of SSc are needed. Several studies have linked autoantibody production with genetics in SSc. Multiple polymorphisms in the human...longitudinal clinical data and genetic markers. GENISOS is an inception cohort that avoids survival bias inherent in studies of prevalent cases (mean disease

Study of Raynaud’s Phenomenon by Means of Infrared Functional Imaging

DTIC Science & Technology

2001-10-25

Scleroderma and 20 Primary Raynaud’s Phenomenon patients were studied subsequently to clinical evaluation and nailfold capillaroscopy . This new...severity of Raynaud�s phenomenon, Br J Rheumatol 30(3):190- 5,1991. 6. Javanetti S, et al.: Thermography and nailfold capillaroscopy as...completely exhaustive in focusing primary or secondary RP [4]. Moreover, these techniques -as nailfold capillary microscopy, cutaneous laser-Doppler

The p65 Subunit of NF-κB Inhibits COL1A1 Gene Transcription in Human Dermal and Scleroderma Fibroblasts through Its Recruitment on Promoter by Protein Interaction with Transcriptional Activators (c-Krox, Sp1, and Sp3)*

PubMed Central

Beauchef, Gallic; Bigot, Nicolas; Kypriotou, Magdalini; Renard, Emmanuelle; Porée, Benoît; Widom, Russell; Dompmartin-Blanchere, Anne; Oddos, Thierry; Maquart, François-Xavier; Demoor, Magali; Boumediene, Karim; Galera, Philippe

2012-01-01

Transcriptional mechanisms regulating type I collagen genes expression in physiopathological situations are not completely known. In this study, we have investigated the role of nuclear factor-κB (NF-κB) transcription factor on type I collagen expression in adult normal human (ANF) and scleroderma (SF) fibroblasts. We demonstrated that NF-κB, a master transcription factor playing a major role in immune response/apoptosis, down-regulates COL1A1 expression by a transcriptional control involving the −112/−61 bp sequence. This 51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1) and Sp3, acting as trans-activators of type I collagen expression in ANF and SF. Knockdown of each one of these trans factors by siRNA confirmed the trans-activating effect of Sp1/Sp3 and the p65 subunit of NF-κB trans-inhibiting effect on COL1A1 expression. Despite no existing κB consensus sequence in the COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-κB bind and/or are recruited on the proximal promoter in chromatin immunoprecipitation (ChIP) assays. Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65 are necessary to mediate the NF-κB inhibitory effect on COL1A1 in ANF and SF were carried out; in this regard, immunoprecipitation assays revealed that they interact, and this was validated by re-ChIP. Finally, the knockdown of Sp1/Sp3/c-Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF, suggesting that particular interactions are characteristic of the scleroderma phenotype. In conclusion, our findings highlight a new mechanism for COL1A1 transcriptional regulation by NF-κB, and these data could allow the development of new antifibrotic strategies. PMID:22139845

Agreement with guidelines from a large database for management of systemic sclerosis: results from the Canadian Scleroderma Research Group.

PubMed

Pope, Janet; Harding, Sarah; Khimdas, Sarit; Bonner, Ashley; Baron, Murray

2012-03-01

We determined congruence with published guidelines from the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trials and Research group, for systemic sclerosis (SSc) investigations and treatment practices within the Canadian Scleroderma Research Group (CSRG). Investigations and medication use for SSc complications were obtained from records of patients with SSc in the CSRG to determine adherence to guidelines for patients enrolled before and after the guidelines were published. The CSRG database of 1253 patients had 992 patients with SSc enrolled before publication of the guidelines and 261 after. For pulmonary arterial hypertension (PAH) treatment, there were no differences in use before and after the guidelines, yet annual echocardiograms for PAH screening were done in 95% of patients enrolled before the guidelines and in only 86% of those enrolled after (p <0.0001), and fewer followup echocardiograms were done 1 year later in the latter group (88% vs 59%). No differences were found for the frequency of PAH-specific treatment; 60% had ever used calcium channel blockers for Raynaud's phenomenon, with no differences in the groups before and after the guidelines. But the use of phosphodiesterase type 5 inhibitors (which does not have guidelines) was increased in the after-guidelines group. Proton pump inhibitors were used in > 80% with gastroesophageal reflux disease before and after the guidelines. One-quarter with gastrointestinal symptoms were taking prokinetic drugs. For those with past SSc renal crisis, use of angiotensin-converting enzyme inhibitors was not different before and after the guidelines. For early diffuse SSc < 2 years, ever-use of methotrexate was similar (one-quarter of each group); and for symptomatic interstitial lung disease, 19% had ever used cyclophosphamide before the guidelines and 9% after (p = nonsignificant). CSRG practices were generally comparable to recently published guidelines; however, use of iloprost and bosentan was low for digital ulcers because these drugs are not approved for use in Canada. There did not seem to be an increase in adherence to recommendations once the guidelines were published. For many guidelines, 25% to 40% of patients who would qualify received the recommended treatment.

The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress Toward Development of Localized Scleroderma Outcome Measures

PubMed Central

ARKACHAISRI, THASCHAWEE; VILAIYUK, SOAMARAT; LI, SUZANNE; O’NEIL, KATHLEEN M.; POPE, ELENA; HIGGINS, GLORIA C.; PUNARO, MARILYNN; RABINOVICH, EGLA C.; ROSENKRANZ, MARGALIT; KIETZ, DANIEL A.; ROSEN, PAUL; SPALDING, STEVEN J.; HENNON, TERESA R.; TOROK, KATHRYN S.; CASSIDY, ELAINE; MEDSGER, THOMAS A.

2013-01-01

Objective To develop and evaluate a Localized Scleroderma (LS) Skin Severity Index (LoSSI) and global assessments’ clinimetric property and effect on quality of life (QOL). Methods A 3-phase study was conducted. The first phase involved 15 patients with LS and 14 examiners who assessed LoSSI [surface area (SA), erythema (ER), skin thickness (ST), and new lesion/extension (N/E)] twice for inter/intrarater reliability. Patient global assessment of disease severity (PtGA-S) and Children’s Dermatology Life Quality Index (CDLQI) were collected for intrarater reliability evaluation. The second phase was aimed to develop clinical determinants for physician global assessment of disease activity (PhysGA-A) and to assess its content validity. The third phase involved 2 examiners assessing LoSSI and PhysGA-A on 27 patients. Effect of training on improving reliability/validity and sensitivity to change of the LoSSI and PhysGA-A was determined. Results Interrater reliability was excellent for ER [intraclass correlation coefficient (ICC) 0.71], ST (ICC 0.70), LoSSI (ICC 0.80), and PhysGA-A (ICC 0.90) but poor for SA (ICC 0.35); thus, LoSSI was modified to mLoSSI. Examiners’ experience did not affect the scores, but training/practice improved reliability. Intrarater reliability was excellent for ER, ST, and LoSSI (Spearman’s rho = 0.71–0.89) and moderate for SA. PtGA-S and CDLQI showed good intrarater agreement (ICC 0.63 and 0.80). mLoSSI correlated moderately with PhysGA-A and PtGA-S. Both mLoSSI and PhysGA-A were sensitive to change following therapy. Conclusion mLoSSI and PhysGA-A are reliable and valid tools for assessing LS disease severity and show high sensitivity to detect change over time. These tools are feasible for use in routine clinical practice. They should be considered for inclusion in a core set of LS outcome measures for clinical trials. PMID:19833758

Sensitivity of jarrah (Eucalyptus marginata) to phosphate, phosphite, and arsenate pulses as influenced by fungal symbiotic associations.

PubMed

Kariman, Khalil; Barker, Susan J; Jost, Ricarda; Finnegan, Patrick M; Tibbett, Mark

2016-07-01

Many plant species adapted to P-impoverished soils, including jarrah (Eucalyptus marginata), develop toxicity symptoms when exposed to high doses of phosphate (Pi) and its analogs such as phosphite (Phi) and arsenate (AsV). The present study was undertaken to investigate the effects of fungal symbionts Scutellospora calospora, Scleroderma sp., and Austroboletus occidentalis on the response of jarrah to highly toxic pulses (1.5 mmol kg(-1) soil) of Pi, Phi, and AsV. S. calospora formed an arbuscular mycorrhizal (AM) symbiosis while both Scleroderma sp. and A. occidentalis established a non-colonizing symbiosis with jarrah plants. All these interactions significantly improved jarrah growth and Pi uptake under P-limiting conditions. The AM fungal colonization naturally declines in AM-eucalypt symbioses after 2-3 months; however, in the present study, the high Pi pulse inhibited the decline of AM fungal colonization in jarrah. Four weeks after exposure to the Pi pulse, plants inoculated with S. calospora had significantly lower toxicity symptoms compared to non-mycorrhizal (NM) plants, and all fungal treatments induced tolerance against Phi toxicity in jarrah. However, no tolerance was observed for AsV-treated plants even though all inoculated plants had significantly lower shoot As concentrations than the NM plants. The transcript profile of five jarrah high-affinity phosphate transporter (PHT1 family) genes in roots was not altered in response to any of the fungal species tested. Interestingly, plants exposed to high Pi supplies for 1 day did not have reduced transcript levels for any of the five PHT1 genes in roots, and transcript abundance of four PHT1 genes actually increased. It is therefore suggested that jarrah, and perhaps other P-sensitive perennial species, respond positively to Pi available in the soil solution through increasing rather than decreasing the expression of selected PHT1 genes. Furthermore, Scleroderma sp. can be considered as a fungus with dual functional capacity capable of forming both ectomycorrhizal and non-colonizing associations, where both pathways are always accompanied by evident growth and nutritional benefits.

Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases

PubMed Central

Meng, Peng; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

2016-01-01

Background Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. Methods In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients’ final diagnoses based on multi-disciplinary consensus. Results One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24–79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Conclusions Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited. PMID:28149543

[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension].

PubMed

Popova, E N; Bolevich, S B; Litvitskiĭ, P F; Arkhipova, D V; Osipenko, V I; Kogan, E A; Kornev, B M; Mukhin, N A

2004-01-01

To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia

PubMed Central

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed. PMID:25838109

Autistic-like traits in adult patients with mood disorders and schizophrenia.

PubMed

Matsuo, Junko; Kamio, Yoko; Takahashi, Hidetoshi; Ota, Miho; Teraishi, Toshiya; Hori, Hiroaki; Nagashima, Anna; Takei, Reiko; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

2015-01-01

Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.

Melorheostosis and somatic mosaicism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fryns, J.P.

1995-08-28

Melorheostosis is a rare congenital disorder of the bone and mesenchymal tissue. The longitudinal, cortical hyperostosis in the long bones has the appearance of wax flowing down the side of a candle. The short bones appear to manifest endosteal bone deposition. Usually only one limb is affected, but bilateral involvement is possible. Also, the skull, vertebrae, pelvis, and ribs can be affected. In 1980 we reported on a 3-year-old girl with clinical and radiological findings of melorheostosis, with manifest involvement of the left lower limb and scleroderma of the overlying soft tissues. Subsequently, at age 17 years, she was admittedmore » to the Orthopedic Department for an Ilizarov operation comprising lengthening and axis correction of the left tibia. Arterial hypertension (220/130 mm Hg) was noted, and biochemical studies documented high plasma renin activity and high aldosterone concentrations. Renal studies showed a small left kidney, and angiography showed several intrarenal high-grade stenoses of the left renal artery with poor opacification, and spotted nephrogram of the middle part and upper pole. Partial nephrectomy with removal of the upper and middle poles of the left kidney was performed. Pathological examination of the small and large blood vessels showed marked intimal proliferation and splitting of the elastica. 3 refs.« less