Limited Scleroderma Research Articles

1854 Conservative Management of Pneumatosis Cystoides Intestinalis With Pneumoperitoneum in a Scleroderma-Related Illness

INTRODUCTION: Pneumatosis Cystoidea Intestinalis with pneumoperitoneum in scleroderma-related illness could mimic an acute abdomen, presenting with pseudo-obstruction and gas within and outside the intestinal wall in the absence of a true perforation of the intestinal wall. The recognition of the clinical presentation of pseudoobstruction with pneumoperitoneum, due to Pneumatosis Cystoidea Intestinalis is paramount for the clinical decision to manage conservatively and avoid a surgical intervention. CASE DESCRIPTION/METHODS: A 30-year-old female with a 3-year history of limited scleroderma and myositis overlap presented with worsening nausea, vomiting, abdominal pain and bloating for about a week. She had a similar episode about a month prior to presentation, with abdominal imaging showing intestinal wall blebs with pneumoperitoneum, and had undergone an exploratory laparotomy. There was no bowel perforation on exploratory laparotomy and biopsy results showed fibrous tissues lined by reactive mesothelial cells and chronic inflammation. On examination, her abdomen was distended with epigastric tenderness, without guarding or rebound tenderness. An abdominal x-ray and CT scan revealed small bowel obstruction with pneumoperitoneum, features characteristic of Pneumatosis Cystoidea Intestinalis. She was evaluated by gastroenterology, surgery and the rheumatology team, and managed conservatively with intravenous fluids, nasogastric tube decompression, and administration of proton pump inhibitor. Her vital signs were normal and abdominal distension subsided with a resolution of her symptoms after 24 hours of conservative management. She was subsequently able to tolerate diet and was discharged on day 2 of admission with a plan for outpatient follow up. DISCUSSION: The presence of pneumoperitoneum portends a sinister finding in a patient with intestinal obstruction, often requiring surgical intervention. Pneumatosis Cystoides Intestinalis is characterized by micro-perforations of intestinal wall blebs which give rise to pneumoperitoneum, without a true perforation of the intestinal wall. The bacterial overgrowth and mechanical theory are both highlighted as mechanisms for the loss of integrity of the intestinal intimal layer, resulting in leakage and formation of gas within the intestinal wall. However, in the absence of acute peritonitis, abdominal abscess, and a worsening clinical status, Pneumatosis Cysotiodea Intestinalis can be managed conservatively in spite of a pseudo-obstruction with pneumoperitoneum.

Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms

To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

SCLEROATROPHIC LICHEN - CURRENT DATA ON THE ETIOLOGY, PATHOGENESIS, CLINICAL FEATURES AND TREATMENT

Scleroatrophic lichen (SL) - chronic autoimmune dermatosis, is one of the clinical variants of limited scleroderma, characterized by multifactorial genesis of development against the background of immunological changes, vascular and metabolic disorders in the connective tissue, which is characterized by severe focal atrophy of the skin and mucous membranes of the external genitals. SL is a debilitating disease causing itching, pain, dysuria and impaired urination, dyspareunia and significant sexual dysfunction in women and men. This article presents a review of current literature data on the etiology and pathogenesis, clinical picture, classification, differential diagnosis of the disease, as well as methods of treatment of patients. This review is based on the analysis of 64 articles, which were obtained from eLibrary, PubMed, NCBI, Embase.

Pulmonary hypertension in Spanish patients with systemic sclerosis. Data from the RESCLE registry.

Our objective was to evaluate the pulmonary hypertension (PH) data for Spanish patients with systemic sclerosis (SSc), define the PH types and determine the associated factors. Descriptive study of PH-related data from the multicentre RESCLE registry. Estimated systolic pulmonary artery pressure (esPAP), measured via echocardiogram was considered elevated if ≥ 35mmHg. Left heart disease (LHD) and interstitial lung disease (ILD) were identified. When performed, data from right heart catheterisation (RHC) were collected. esPAP was elevated in 350 of 808 patients (43.3%). One hundred and forty-four patients (17.8%) were considered to have PH (88 via RHC and the rest due to elevated esPAP along with evidence of significant LHD or ILD): PAH 3.7%, secondary to ILD 8.3%, secondary to LHD 2.8% and unclassified 3%. Prevalence of elevated esPAP was greater in diffuse SSc (dSSc) than in limited scleroderma (lSSc) (50.5 vs. 42.2%, p 0.046). In the group with elevated esPAP, a lower prevalence of anti-centromere antibodies (41.9% vs. 52.3%, p 0.006) and a greater prevalence of anti-topoisomerase-1 antibodies (ATA) (25.1% vs. 18.6%, p 0.04) were observed compared to the group with normal esPAP. Patients with elevated esPAP had a lower rate of digital ulcers (50.6% vs. 60.2%, p 0.007) and esophageal involvement (83.6% vs. 88.7%, p 0.07) and higher rate of renal crisis (4.6% vs. 1.8%, p 0.066). Prevalence of PAH was lower than expected (3.7%). Probability of having elevated esPAP was higher among patients with dSSc and among those with ATA.

PULMONARY FUNCTION TEST PARAMETERS IN DIFFUSE AND LIMITED SCLERODERMA

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Scleroderma is characterized by varying degrees of organ fibrosis and obliterative vasculopathy. Lung involvement is the leading cause of morbidity in Scleroderma. The spectrum of Pulmonary Function Test (PFT) abnormalities in Scleroderma has been reported to be variable, with a recent study revealing that PFTs have a low sensitivity in detecting Scleroderma-related interstitial lung disease, with false negative cases more common in diffuse Scleroderma. The objectives of this study are to determine the spectrum of PFT abnormalities in Scleroderma and to compare PFTs in limited and diffuse Scleroderma. METHODS: We reviewed the records of 174 Scleroderma patients followed at the rheumatology clinic in our institution. Patient demographics and PFT parameters [FEV1, FVC, FEV1/FVC, TLC and DLCO percent predicted (%)] were noted in patients with limited (Scl-Ltd) and diffuse (Scl-Diffuse) disease. Obstruction was defined as FEV1/FVC < 70%; restriction as TLC < 80% and impaired diffusion as DLCO < 80%. Severity of restriction was defined per ATS criteria. PFT parameters in the two groups were compared by Student’s t-test. p < 0.05 was deemed statistically significant. RESULTS: Mean age: 65 +/- 12.2 years; 91% were females; 76.4% had Scl-Ltd. Mean FEV1 was: 92 +/- 22%; mean FVC: 88.5 +/- 21.3%; mean TLC: 91.5 +/- 18%; mean DLCO:70.5 +/- 23%. Twenty-eight % patients had normal PFTs; 12 % had obstruction, 32% had restriction and 28% patients had isolated reduction in DLCO. Thirty-five % patients with Scl-Ltd and 24.4% patients with Scl-Diffuse had a normal DLCO. In patients with restriction, 40% had mild, 51% moderate and 9% had severe restriction. PFT abnormalities were seen in 37.6% Scl-Ltd, and 56% Scl-Diffuse. PFT parameters in the 2 groups are shown below. PFT parameters in 2 groups (Table) CONCLUSIONS: Majority of Scleroderma-patients have abnormal PFTs. Restriction and impairment in diffusion were the most common abnormalities. Over 1/3rd patients with limited disease had PFT abnormalities. CLINICAL IMPLICATIONS: Whether restriction defined by TLC corelates with fibrosis on imaging need to be studied. DISCLOSURES: No relevant relationships by Debapriya Datta, source=Web Response No relevant relationships by Carol Halasan, source=Web Response No relevant relationships by Sophie Korzan, source=Web Response

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Assessing the response of morphea and limited scleroderma to tranilast: a small prospective study comparing topical corticosteroids to a combination of topical corticosteroids and tranilast.

BackgroundScleroderma is traditionally managed with immunomodulatory agents such as methotrexate, mycophenolate mofetil and corticosteroids. There are anecdotal reports for, and theoretical reasons why, the anti-fibrotic agent tranilast may provide an additional treatment modality.ObjectiveThe objective of the current study was to demonstrate if the addition of topical tranilast to an established regime resulted in an improvement in the Localized Scleroderma Assessment Tool (LoSCAT) and modified Rodnan score.Patients and methodsA small double-blinded randomized prospective study of 11 pairs of treatment sites in four patients; three with morphea and one with limited scleroderma was performed. All patients continued with their prescribed treatment and applied 0.1% betamethasone valerate in PCCA PracaSil™ (B) to the control site with 0.1% betamethasone valerate and 1% tranilast (B/T) to the comparator site over a period of 3 months. Photographs and monthly LoSCAT scores were performed on the morphea patients and a modified Rodnan score on the limited scleroderma patient. Statistical analysis was via sign test.ResultsThe mean baseline LoScat score at the B treated sites was 6.6 which improved to 4.3 (p= 0.16). The mean baseline LoScat score at the B/T treated sites was 5.75 which improved to 2.8 following treatment. (p=0.04)LimitationsThis was a small single center study. The ideal concentration of tranilast is unknown. As all patients continued with standard management the expected response may be less than would have been anticipated in a single agent trial.ConclusionThe role of tranilast in the management in scleroderma warrants further investigation in larger trials.

Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer

ObjectivesRecent studies demonstrate autoantibodies are powerful tools to interrogate molecular events linking cancer and the development of autoimmunity in scleroderma. Investigating cancer risk in these biologically relevant subsets may provide...

Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis.

Delayed-enhancement magnetic resonance imaging (DE-MRI) is a noninvasive diagnostic tool able to identify myocardial fibrosis. In patients with scleroderma, its relationship with arrhythmias and conduction disorders has not been fully explored. The aim of this study was to evaluate the possible correlations between ventricular arrhythmias, conduction disorders, and myocardial fibrosis in patients with systemic sclerosis. Thirty-six patients with diffuse or limited cutaneous scleroderma underwent 12-lead electrocardiogram (ECG), 24-hour Holter ECG monitoring, transthoracic echocardiography, and cardiac DE-MRI, with gadolinium administration in 33 patients. High-quality DE-MRI scans were obtained in 30 patients. Myocardial fibrosis was detected in 25 patients (83.3%). Eighteen patients (60%) had ventricular arrhythmias or conduction disorders. There was no significant difference in ventricular arrhythmia burden (the total number of premature ventricular contractions [PVCs]/24 hours) (48 ± 304 vs. 69 ± 236, P = 0.97), ventricular arrhythmia severity (couplets, triplets, runs) on Holter ECG, or in the presence of conduction disorders (36% vs. 40%, P = 0.86) between patients with and without myocardial fibrosis. In univariate analysis, diffuse fibrosis was weakly associated with the number of PVCs/24 hours (R = 0.157, P = 0.03). A number of at least 597 PVCs/24 hours had a sensitivity of 60% and a specificity of 92% in predicting the presence of diffuse fibrosis on DE-MRI (area under the curve = 0.640). Delayed-enhancement magnetic resonance imaging can identify myocardial fibrosis in a high percentage of scleroderma patients. Its presence does not seem to influence the ventricular arrhythmia burden and severity or the presence of conduction disorders, with the exception of diffuse myocardial fibrosis, which modestly influences the total number of PVCs/24 hours.

Cutaneous calcinosis in a patient with limited scleroderma: CREST Syndrome.

Cutaneous calcinosis in a patient with limited scleroderma: CREST Syndrome.

The evaluation of a home-based program for hands in patients with systemic sclerosis

Study DesignThis study used a quasi-experimental design where patients were evaluated before and after participation in the self-management program. IntroductionHands are commonly affected in systemic sclerosis (SSc). Strategies to maintain or improve hand function are indicated upon diagnosis and throughout the course of the disease. Purpose of the StudyThe purpose of this study was to develop and evaluate a home-based program for hands in patients with SSc. MethodsA home-based self-management program that consisted of concise instructions about SSc and hand exercises was developed and evaluated in a group of patients with SSc during 8 weeks. Primary outcome measures were hand pain (Visual Analogue Scale) and hand function (Cochin Hand Function Scale). Secondary outcome measures were disability (Scleroderma Health Assessment Questionnaire), finger motion (delta finger-to-palm), grip strength, tip and key pinch strength, Raynaud phenomenon and digital ulcers impact, quality of life (Short Form Health Survey). For comparisons between different times analysis of variance for repeated measures was used. To calculate the effect size (ES), the Cohen's test was performed. To evaluate skin moisturizing and warming habits before and after intervention, the McNemar test was used. Statistical significance was set at P ≤ .05. ResultsTwenty-two SSc patients (19 women: 3 men; 16 limited scleroderma: 6 diffuse scleroderma) completed the program. Significant improvements were noted for hand pain (3.97 vs 2.21, ES: 0.69), Cochin Hand Function Scale (19.24 vs 12.48, ES: 0.48), Scleroderma Health Assessment Questionnaire (0.95 vs 0.48, ES: 1.01), delta finger-to-palm (92.86 vs 106.33, ES: 0.40), grip strength (14.43 vs 19, ES: 0.58), tip pinch strength (2.49 vs 4.18, ES: 1.15), key pinch strength (4.01 vs 5.22, ES: 0.76), Raynaud phenomenon impact (0.94 vs 0.47, ES: 0.75), Short Form Health Survey–role physical (47.38 vs 60.14, ES: 0.61), physical functioning (34.62 vs 61.9, ES: 0.18), social functioning (60.71 vs 75.6, ES: 0.64), bodily pain (50.55 vs 63.38, ES: 0.58), vitality (45.95 vs 62, ES: 2.22), mental health (56.62 vs 72.38, ES: 0.84) moisturizing, and cold avoidance habits. Patients considered the program easy to follow with no adverse effects related to exercises. DiscussionWe developed a home based hand care program to be offered to SSc patients. Improvements in hand function, strength, disability, motion, and overall quality of life were independent of age, income, education level, disease duration, and skin score. Our findings support those of other studies that reported the benefits of hand exercises in SSc. Some study limitations include the lack of a control group, the small number of subjects and the short-time follow up. ConclusionsThis home-based program for patients with SSc improved hand pain, function, mobility, and strength at the end of 8 weeks. Patient adherence and sustained efficacy is still to be determined.

Choroidal and central foveal thickness in patients with scleroderma and its systemic associations

BackgroundThe aim was to investigate the morphological changes in the fovea and choroid in patients with scleroderma and its systemic associations.MethodsThirty‐four scleroderma patients and 31 healthy controls were enrolled. Choroidal thickness (CT) at five defined points (subfoveal [sfCT] and 1.0 [N1.0] and 3.0 µm nasal [N3.0] and 1.0 [T1.0] and 3.0 µm temporal [T3.0] from the centre of the fovea) and central foveal thickness were measured.ResultsThe mean central foveal thickness (right eye 229.3 ± 28.6 versus 232.6 ± 29.7 and left eye 219.8 ± 21.4 versus 223.3 ± 21.9 µm) and sfCT (right eye 326.4 ± 56.5 versus 327.3 ± 62.1 and left eye 316.7 ± 53.4 versus 317.6 ± 51.6 µm) values were not different in patients with scleroderma compared with the controls (p > 0.05). The mean CT at N1.0, N3.0, T1.0 and T3.0 did not differ among these groups in both eyes (p > 0.05). There was no difference in the mean central foveal thickness and CT of both eyes in diffuse and limited scleroderma (p > 0.05). A negative correlation was found between anti‐nuclear antibody positivity and CT at T3 and N3 (respectively, r = −0.439 and r = −0.383, p < 0.05).ConclusionChoroidal thickness at five points and central foveal thickness in both eyes did not significantly differ in scleroderma patients compared with healthy controls. Choroidal thickness at the T3 and N3 points showed a negative correlation with anti‐nuclear antibody positivity.

Consequence of an Unforeseen Diagnosis of Scleroderma Esophagus in a Patient With Prior Fundoplication

In systemic sclerosis (SSc), in addition to the skin, the GI system, and in particular the esophagus, are commonly affected. The term “scleroderma esophagus” is used to describe the nature of esophageal dysfunction in patients with SSc and is characterized by esophageal aperistalsis and hypotensive esophagogastric junction pressure. First line treatment for scleroderma esophagus and GERD symptoms is pharmacotherapy with PPIs and behavioral modifications. Anti-reflux surgeries, such as fundoplication, are considered a relative contraindication as they have been associated with high rates of post-operative esophagitis and dysphagia. This case reflects the experience of a patient who received a fundoplication, initially achieved the anticipated GERD symptom improvement, and later in life developed scleroderma with esophageal manifestations. An 83 year-old woman presented with recurrent episodes of aspiration pneumonia and dysphagia for 4 yrs. An EGD revealed food in the esophagus suggestive of esophageal stasis. She had a Nissen fundoplication 20yrs prior and was without symptoms of dysphagia for 16yrs. Also, the patient was diagnosed with Raynaud's disease 10yrs after her fundoplication. On exam she had sclerodactyly and a facial telangiectasia. Barium esophagram showed a dilated and aperistaltic esophagus with retained debris. Ordered for suspicion of scleroderma, an anti-centromere antibody (ACA) was strongly positive at >1:640 (nl < 1:40), suggestive of limited type scleroderma which often presents with components of CREST syndrome. An upper endoscopy was then performed that again demonstrated dilation of the entire esophagus with food present. An intact Nissen fundoplication was clearly visualized and the wrap indentation which was 2cm distal to the esophagogastric junction was dilated to 20mm. The patient continued to have aspiration events resulting in hospitalizations for pneumonia. For this reason, and because of numerous additional co-morbidities further dilation was deemed too high risk and the patient underwent placement of a 20F PEG for feedings. It could not be predicted at the time of this patient's fundoplication that she would go on to develop scleroderma. This case demonstrates how the combination of the prior fundoplication likely contributed to development of severe dysphagia and recurrent aspiration pneumonias in the setting of her new onset scleroderma 16yrs post-operatively, ultimately necessitating placement of a PEG tube for nutrition.Figure: Intact Nissen fundoplication with dilation of entire esophagus and food in the esophagus was visualized on EGD.Figure: Esophagram demonstrating an esophagus filled with ingested debris. The esophagus was diffusely dilated with absence of peristalsis in the distal two-thirds. The gastroesophageal junction measured a maximum of 10mm in diameter.

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

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)D3 levels were measured using ELISA kits. The mean±SD age of patients and controls was 46.2±9.6 and 47.2±7.0years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p=0.001); whilst serum α-Klotho and 25(OH)D3 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)D3 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.

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Scleroderma and Related Disorders

Scleroderma spectrum diseases are a heterogeneous group of disorders that are distinguished by abnormalities of the connective tissue in the skin and, in some cases, other organs. Each disorder may be characterized by the extent of cutaneous and internal involvement, as well as histopathologic features of skin biopsy. Scleroderma spectrum diseases include systemic scleroderma, localized scleroderma, and eosinophilic fasciitis. This chapter reviews the classification, epidemiology, etiology, pathophysiology and pathogenesis, diagnosis, differential diagnosis, treatment, outcome measures, management, and clinical course of scleroderma as well as the definition and classification, etiology/genetics, differential diagnosis, and treatment of localized scleroderma. Also discussed are the definition and classification, epidemiology, etiology/genetics/pathogenesis, diagnosis, differential diagnosis, and treatment of eosinophilic fasciitis. Tables review the classification of—and antinuclear antibodies in—scleroderma as well as the key assessments and interventions in scleroderma management. Figures illustrate the disease's presentation and clinical manifestations, including several images of scleroderma of the hands; face, palmar, and buccal telangiectasias in a patient with scleroderma; a radiograph demonstrating calcinosis of the elbow; Raynaud’s phenomenon; high-resolution computed tomographic images of diffuse cutaneous scleroderma, scleroderma and severe pulmonary hypertension, and limited cutaneous scleroderma; plus an esophagram demonstrating hypomotility. This review contains 11 highly rendered figures, 3 tables, and 72 references.

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature

Rituximab is a chimeric monoclonal anti-CD20 antibody approved for the treatment of some lymphoid malignancies as well as for autoimmune diseases including rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and vasculitis. Generally, rituximab is well tolerated; nevertheless, some patients develop adverse effects including infusion reactions. Albeit rare, these reactions may in some cases be life-threatening conditions. Rituximab cardiovascular side effects include more common effects such as hypertension, oedema and rare cases of arrhythmias and myocardial infarction. In this article, we report a case of a 58-year-old man with a history of overlap syndrome including RA and limited scleroderma who was treated with rituximab and developed a dramatic ST-elevation myocardial infarction (STEMI) during the drug administration. This report underlines previous published reports emphasizing the awareness of such an association. This communication also warrants the importance of screening for ischaemic heart disease in selected cases of patients treated with rituximab.

Adipose tissue-derived stem cells ameliorates dermal fibrosis in a mouse model of scleroderma.

To investigate the therapeutic potential of adipose-derived stem cells (ADSCs) for limited cutaneous scleroderma (LS) in mouse models. ADSCs were isolated from pathogen-free female C57BL/6 mice and LS was induced in wild type (WT) C57BL/6 mice via daily injection of bleomycin (0.1mL×300μg/mL) for 4 weeks; then the ADSCs were subcutaneously injected into the dorsal area in the model treatment group, and 100μL of phosphate-buffered saline (PBS) solution was injected into the same site in the model control group. Green fluorescent protein (GFP) was used to track the cells using an invivo imaging system on days 7, 14, 21, and 28 after transplantation. All mice were sacrificed and histologic analyses were performed after 4 weeks, and the skin thickness, collagen deposition and the total content of hydroxyproline were evaluated. Additionally, immunohistochemistry were performed to compare the tissue expression and distribution of TGF-β1 and VEGF between the ADSCs treatment group and the treatment control group. WT C57BL/6 LS mouse model were successfully established and GFP invivo fluorescence imaging showed that the translated ADSCs survived at the local for at least 4 weeks. Compared with the control group, the ADSCs treatment group significantly attenuated bleomycin-induced dermal fibrosis, reduced the skin thickness and the total content of hydroxyproline (P<0.05). The ADSCs treatment group displayed significantly lower levels of TGF-β1 and higher levels of VEGF than the control group (P<0.05). ADSCs may provide a feasible and practical treatment for autoimmune diseases such as LS and ameliorate dermal fibrosis.

Scleroderma overlap syndromes

Scleroderma overlap syndromes

Increased cancer incidence in SICCA syndrome patients positive for anti-centromere antibody

Objectives: The main purposes of this study were to determine the clinical significance of the presence or absence of the anti-centromere antibody in SICCA Syndrome and to diagnose the symptoms. Methods: We retrospectively investigated the prevalence of ACA in patients with SICCA syndrome between January 2006 and January 2014 in Kaohsiung Chang Gung Memorial Hospital. We compared ACA-positive patients with ACA-negative patients. Results: Clinical manifestations in ACA-positive patients are shown in table 2. Many of the clinical symptoms were primarily associated with the predominant disease, scleroderma, limited scleroderma, systemic lupus erythematosus or Sjogren's syndrome (SS). Myalgia was the most prevalent manifestation among those that were ACA-positive. There were fewer ACA-positive SICCA patients with anti-SSA or anti-SSB antibodies than ACA-negative SICCA patients (p ＜0.01, p = 0.011, respectively). Among 35 ACA-positive patients, SS was found in 21 patients (60.0 %), including 13 with primary SS and 8 with secondary SS. In the other 14 patients, 8 had cancer and 6 had other diseases. Among 36 ACA-negative patients, SS was found in 33 patients (91.6 %), including 29 with primary SS and 4 with secondary SS. In the other three patients, one had cancer and two had thyroid diseases. The incidence of cancer was significantly higher in the ACA-positive group than in the ACA-negative group [odds ratio = 10.37; 95 % confidence interval (CI), 1.22-88.02; p ＜ 0.05]. Conclusion: In our study, ACA-positive patients with SICCA syndrome had increased incidence of cancer (p ＜ 0.01; odds ratio = 10.37) and lower prevalence of anti-SSA/anti-SSB antibodies. With regard to cancer risk, anti-centromere positive SICCA syndrome patients should be carefully evaluated for early diagnosis of cancer.