Skin Sclerosis Research Articles

Platelet indices as markers of inflammation in systemic sclerosis patients: Relation to vascular endothelial growth factor and flow mediated dilatation

Aim of the workTo evaluate platelet indices in systemic sclerosis (SSc) patients and identify their clinical significance as novel inflammatory biomarkers in correlation to markers of endothelial dysfunction: vascular endothelial growth factor (VEGF) and flow mediated dilatation (FMD). Patients and methodsThirty-five SSc patients were enrolled in addition to 35 age and sex matched healthy volunteers as controls. All patients and controls underwent full medical history taking, thorough clinical examination, assessment of severity extent of skin sclerosis using the modified Rodnan skin score (mRss), erythrocyte sedimentation rate (ESR), C- reactive protein (CRP), complete blood count with special consideration to mean platelet volume (MPV), platelet distribution width and platelets count, assay for serum VEGF concentration, and brachial FMD assessment by color duplex sonography. ResultsThere was a highly significant decrease in the mean MPV in SSc patients compared to the controls (8.65 ± 0.6 fl vs. 9.55 ± 0.52 fl). There was a significant increase in the mean platelet count in SSc patients compared to controls (331.63 ± 64.66 × 103/ml vs. 297.80 ± 44.48 × 103/ml). In SSc patients, a significant negative correlation was found between the mean MPV and each of ESR, CRP and VEGF (r = −0.42, r = −0.37 and r = −0.55 respectively, p < .05); and a significant positive correlation was found between the mean MPV and mean FMD (r = 0.38, p < .05). Linear regression test, showed an association between mean MPV and each of ESR and CRP (t = −3.31, −2.92 respectively, p < .05). ConclusionMPV levels could be an easily measurable parameter to reflect the inflammatory condition in systemic sclerosis patients.

Measurement of Skin Induration Size Using Smartphone Images and Photogrammetric Reconstruction: Pilot Study

Background: The tuberculin skin test (TST) is the most common method for detecting latent tuberculosis infection (LTBI). The test requires that a patient return to the health facility or be visited by a health care worker 48 to 72 hours after the intradermal placement of tuberculin so that the size of the resulting skin induration, if any, can be measured. Objective: This study aimed to propose and evaluate an image-based method for measuring induration size from images captured using a smartphone camera. Methods: We imaged simulated skin indurations, ranging from 4.0 to 19 mm, in 10 subjects using a handheld smartphone, and performed three-dimensional reconstruction of the induration sites using photogrammetry software. An experienced TST reader measured the size of each induration using the standard clinical method. The experienced reader and an inexperienced observer both measured the size of each induration using the software. The agreement between measurements generated by the standard clinical and image-based methods was assessed using the intraclass correlation coefficient (ICC). Inter- and intraobserver agreement for the image-based method was similarly evaluated. Results: Results showed excellent agreement between the standard and image-based measurements performed by the experienced reader with an ICC value of .965. Inter- and intraobserver agreements were also excellent, indicating that experience in reading TSTs is not required with our proposed method. Conclusions: We conclude that the proposed smartphone image-based method is a potential alternative to standard induration size measurement and would enable remote data collection for LTBI screening.

Role of vasculopathy in the pathogenesis of systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder characterized by skin sclerosis and internal organ fibrosis. Although its etiology and pathogenesis are unclear, the main pathological features of SSc are vasculopathy, aberrant immune activation and tissue fibrosis. Increasing studies have indicated that vasculopathy may be an initial event in the occurrence of SSc, including small vessel spasm, intimal thickening, reduction of vessel number and so on. This review summarizes recent research progress in SSc-related vasculopathy, including the disarrangement of pro-angiogenic factors (e.g. vascular endothelial growth factor and stromal cell-derived factor-1) , angiostatic factors (e.g. endostatin and pentraxin 3) and their receptors (e.g. vascular endothelial growth factor receptor and urokinase-type plasminogen activator receptor) , aberrant number and function of vascular endothelial progenitor cells and vascular endothelial cells, imbalance in the regulation of vascular tone, and dysfunction of platelets and their releasers in SSc. Key words: Scleroderma, systemic; Peripheral vascular diseases; Endothelial cells; Stem cells; Blood platelets

Phototherapy in systemic sclerosis: Review.

Systemic scleroderma-also known as systemic sclerosis (SSc)-is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis-à-vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.

Incidence of peripheral trophic disorders determined by vein thrombosis of the lower limbs correlated with risk factors by age

Introduction: Venous thromboembolism (VTE), in its clinical spectrum, includes both deep venous thrombosis (DVT) and pulmonary embolism (PE). It is a disease with high incidence and morbidity in hospital and community settings. Venous thromboembolism has various risk factors and there are studies proving that the risk of increasing the incidence of the disease is proportional to the risk factors. Diagnosis, treatment and complications of lower limb deep vein thrombosis (DVT) depend on the anatomical location and extent of the process. The post-thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT) and clinically it is characterized by chronic pain, edema, enlarged veins, skin induration and other signs of the affected limb, while, in severe cases, it can develop venous ulcers. The incidence of peripheral trophic disorders by age and the prevalence of risk factors for deep vein thrombosis of the lower limbs were examined in this regard. Materials and method: A retrospective study (January 2013 - December 2015) was conducted by collecting data from medical documents available in ""Floreasca"" Emergency Hospital Bucharest, Romania. The patients diagnosed with deep vein thrombosis, on the basis of Doppler ultrasound, were divided into two groups, according to age: group A (59 patients aged ≤50 years) and group B (130 patients aged&gt; 50 years). A number of data from the medical anamnesis, along with clinical and paraclinical data were collected by us and we were interested in the incidence of peripheral trophic disorders caused by deep vein thrombosis of the lower limbs correlated with the risk factors. The study showed the incidence of deep venous thrombosis in a certain age and a certain environment of origin. The incidence of patients who have had a VTE history is half the patients with deep vein thrombosis who have had prophylactic anticoagulant therapy before hospitalization. The incidence of patients who have had prophylactic anticoagulant therapy before hospitalization is 61.1% of the patients with deep vein thrombosis and a VTE history. The incidence of trophic disorders caused by deep vein thrombosis of the lower limbs in patients who have had prophylactic anticoagulant therapy before hospitalization and in patients who also had a history of VTE is higher in those over 50 years old. The study showed the association of some risk factors for venous thrombosis with an age-related factor. Conclusions: Improving preventive strategies and an optimally efficient utilization of these strategies for patients at risk of venous thrombosis can lead to improved clinical outcomes in practice and also to the post-thrombotic syndrome prevention. Taking into consideration the risk factors by age group and a better understanding of epidemiology and the risk factors for the first or recurrent venous thrombosis can lead to optimal use of prophylactic strategies and improved quality of life. DVT affects all age groups and the incidence associated with PTS is high, therefore the prevalence of PTS in general population is considerable.

Erythema nodosum masking nephrogenic systemic fibrosis as initial skin manifestation

BackgroundNephrogenic systemic fibrosis (NSF) is a complication of the gadolinium-based contrast agent used in imaging studies. It is typically characterised by hard, erythematous and indurated skin plaques with surrounding subcutaneous oedema. Distinct papules and subcutaneous nodules can also be seen. Fibrocytes in NSF are immunohistochemically positive for CD34.Case presentationWe present a case of NSF occurred after gadolinium exposure in which the initial presentation mimics an erythema nodosum (EN)-like picture. An initial skin biopsy showed EN. Subsequently the patient developed progressive skin and joints contracture. A repeated skin biopsy done three months later confirmed the diagnosis of NSF. As far as we are aware, this is the second reported case of NSF that mimicked the presentation of EN in the early phase of the disease.ConclusionsThe appearance of EN-like disease can be one of the early manifestations of NSF. We hope that early recognition of this unusual presentation can alert the physician or nephrologist to the potential diagnosis of NSF.

Mini Hydrocelectomy – Outcome of A Short Term Study And Comparison With Conventional Jaboulays Technique

Background: Hydrocele is among the commonest benign conditions of scrotum. Its incidence is around 1% in adult male population with a predilection for males above 40 years of age. Conventional surgical procedures like Jaboulays Eversion of Sac (EOS) and Lords plication of redundant tunica vaginalis remain the most commonly used procedures used in the treatment of idiopathic adult hydrocele. Both procedures are invasive and are associated with durable success and low incidence of recurrence. These procedures are however associated with many post-operative complications like pain, hematoma, infection, persistent swelling and induration of scrotal skin, wound related complications, chronic pain and reduced fertility. All these translate into high morbidity, loss of work hours and increased surgical expenses. To avoid / minimize these complications associated with plication or excision of the redundant hydrocele sac fenestration has been proposed as a minimal access procedure. Fenestration exposes the secretory surface of the tunica vaginalis sac to the lymphatic-rich subcutaneous tissues, from where the hydrocele fluid is cleared off the scrotal cavity. Methods: The present study was carried out in the Department of General Surgery, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard during the time period of June 2014 - December 2015. 120 patients of primary vaginal type hydrocele with ASA grade 1 were randomly allocated into two groups of 60 patients each – one group for the Mini-Hydroceletomy MiH-(Group A) and the other group for routine Jaboulays EOS (Group B). All the patients were followed up for a period ranging from 6-18 months. Results: Mean age of patients was 42 years for jabouleys and 45 for mini hydrocelectomy group. Mean hydrocele volume for Group A was 240 ml and for group B was 252 ml. Average time for the procedure in group A was 10-12 min (mean 11min) and for group B was 25 -30min (mean 27min). In Group A, Average incision length was 2.1 cm whereas in Group B it was 5.4 cm. Conclusions: We hereby present our experience that mini-hydrocelectomy (MiH) technique to be the procedure of choice for medium sized uncomplicated hydroceles.

Serum LL-37 levels correlate with the efficacy of i.v. cyclophosphamide pulse for skin sclerosis and interstitial lung disease in systemic sclerosis.

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Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.

Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Chronic lymphocytic leukemia skin infiltration mimicking an ICD pocket infection: a case report

BackgroundWe are presenting a case report on an unreported and unusual cutaneous manifestation of chronic lymphocytic leukemia in a patient with an implantable cardioverter-defibrillator (ICD).Case presentationA 65-year-old man with a history of chronic lymphocytic leukemia (CLL), previously treated with chlorambucil, was referred in October 2013 for extraction of a single chamber ICD due to a suspected device-related infection in the pulse generator area (left-hand side of Fig. 1). The ICD system (Current VR, St. Jude Medical, USA) had been implanted in November 2009. The patient complained of painless erythema with pruritus in the pocket area. Inflammatory blood parameters were C-reactive protein 17.3 mg/L and leucocytes 29.0 × 109/L. Due to the atypical appearance of the pocket area we did not extract the device. Instead, we created an exploratory excision in the skin induration, which had been present for approximately 6 weeks, and conducted a microbiological and histological examination. All cultivation examinations were negative. However, we did histologically show skin infiltration by CD-5 positive low-grade B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL). Re-initiation of chemotherapy was not necessary and the skin induration completely disappeared within 2 months (right-hand side of Fig. 1).ConclusionsComplete removal of an ICD system carries considerable risk. In patients with a history of hematological disease, it is crucial to exclude cutaneous manifestations of the disease prior to device removal.

Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013.

In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired.

Peripheral kynurenine/tryptophan ratio is not a reliable marker of systemic indoleamine 2,3-dioxygenase: A lesson drawn from patients on hemodialysis

Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry. In 228 patients from two hemodialysis centers, the two IDO markers were higher in patients than in healthy controls but were not correlated with each other. In vitro experiments demonstrated that peripheral blood mononuclear cells could not metabolize tryptophan into kynurenine, indicating that the increased Kyn/Trp ratio was IDO-independent. Skin induration diameters of tuberculin skin testing were correlated with the IDO MFI (negatively), but not the Kyn/Trp ratio. Further, in a 24-month prospective cohort, the Kyn/Trp ratio was not correlated with clinical infection. Alternatively, patients with a higher IDO MFI had a lower accumulative infection-free survival rate. Using a Cox proportional hazard model, it was also revealed that a higher IDO MFI was significantly associated with new bacterial infection. Taken together, these results indicate that the Kyn/Trp ratio is not a reliable circulating IDO marker in hemodialysis patients. However, the IDO MFI reflects an immunocompromised state and thus might be a potential clinical marker of bacterial infection.

Topical anaesthetics for pain control during repair of dermal laceration.

Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017. To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application of the ester anaesthetic, cocaine. For this updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), Cumulative Index to Nursing and Allied Health Literature (CINAHL; 2010 to December 2016), Embase (2010 to December 2016) and MEDLINE (2010 to December 2016). We did not limit this search by language or format of publication. We contacted manufacturers, international scientific societies and researchers in the field. Weemailed selected journalsand reviewed meta-registers of ongoing trials. For the previous version of this review, we searched these databases to November 2010. We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of dermal laceration in adult and paediatric participants. Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information when needed. We collected adverse event information from trial reports. We assessed methodological risk of bias for each included study and employed the GRADE approach to assess the overall quality of the evidence. The present updated review included 25 RCTs involving 3278 participants. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data for all but one outcome: pain intensity. In two pooled studies, the mean self-reported visual analogue scale (VAS; 0 to 100 mm) score for topical prilocaine-phenylephrine (PP) was higher than the mean self-reported VAS (0 to 100 mm) score for topical tetracaine-epinephrine-cocaine (TAC) by 5.59 points (95% confidence interval (CI) 2.16 to 13.35). Most trials that compared infiltrated and topical anaesthetics were at high risk of bias, which is likely to have affected their results. Researchers found that several cocaine-free topical anaesthetics provided effective analgesic efficacy. However, data regarding the efficacy of each topical agent are based mostly on single comparisons in trials with unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one of 1042 participants who had undergone application of TAC. Investigators reported no serious complications among any of the participants treated with cocaine-based or cocaine-free topical anaesthetics. The overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached. We have found two new studies published since the last version of this review was prepared. We have added these studies to those previously included and have conducted an updated analysis, which resulted in the same review conclusions as were presented previously.Mostly descriptive analysis indicates that topical anaesthetics may offer an efficacious, non-invasive means of providing analgesia before suturing of dermal lacerations. Use of cocaine-based topical anaesthetics might be hard to justify, given the availability of other effective topical anaesthetics without cocaine. However, the overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached.

Systemic sclerosis and the gastrointestinal tract.

Systemic sclerosis (SSc) is an autoimmunological disease of unknown origin with complex pathogenesis and multiple organ involvement. It is characterised by vascular and immunological abnormalities leading to fibrosis of the skin and internal organs. It is a rather rare disease with a prevalence of around 20 per 100,000. The disease results in heterogeneous clinical findings and different courses. Systemic sclerosis usually begins with the onset of Raynaud’s phenomenon (RP), followed by skin sclerosis and internal organ involvement, although it may appear synchronously with RP. Gastrointestinal involvement is a serious and prevalent complication of SSc, and the oesophagus is the most frequently affected organ. Both limited and diffuse cutaneous SSc involve internal organs, with the involvement of the gastrointestinal tract as a leading cause of morbidity. At present, treatment is mainly symptomatic with no disease-modifying drugs.

Recognizing systemic sclerosis: comparative analysis of various sets of classification criteria.

Systemic sclerosis is a complex disease characterized by autoimmunity, vasculopathy and tissue fibrosis. Although most patients present with some degree of skin sclerosis, which is a distinguishing hallmark, the clinical presentation vary greatly complicating the diagnosis. In this regard, new classification criteria were jointly published in 2013 by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). A recent major development in the classification criteria is improved sensitivity, particularly for detecting early disease. The new criteria allow more cases to be classified as having systemic sclerosis (SSc), which leads to earlier treatment. Moreover it is clinically beneficial in preventing the disease progression with its irreversible fibrosis and organ damage. The aim of this review is to give insight into new classification criteria and current trends in the diagnosis of systemic sclerosis.

Angiostatic and Angiogenic Chemokines in Systemic Sclerosis: An Overview

In systemic sclerosis (SSc), the dysregulation of several molecular pathways seem to have a role in the disease pathogenesis. Either angiogenesis and vasculogenesis are disturbed and impaired, and an imbalance between angiogenic and angiostatic factors may be involved in the genesis and maintenance of vasculopathy. Aberrant immune system activation and function involves both B and T cells, as well as many different chemokines and cytokines. Particularly, chemokines are central to the initiation and maintenance of inflammatory responses as well as angiogenesis and fibrosis. Increased expression of several chemokines as CXCL4 (platelet factor 4), CXCL8 (IL8), CXCL5 (ENA-78), CCL5 (RANTS), CXCL9 (MIG), CCL24, CXCL10 IP-10), CXCL12, CXCL16 (SRPSDX), CCL2 (MCP-1), CCL19 (MIP-3β/ELC), CCL24 (Eotaxin 2), suggests a complex mechanism by which many immune cell types, including T cells, macrophages and neutrophils are recruited to the skin in SSc patients. Many of these chemokines have redundant roles, possibly to ensure recruitment of specific cell types. Several studies have shown a synergistic effect of combinations of these chemokines in cell recruitment, emphasizing the importance of understanding global chemokine expressions. urthermore, chemokines can be detected in peripheral blood compared with cytokines or growth factors. The utility of cytokines as biomarkers has been investigated but longitudinal studies are necessary to clarify their clinical utility for the evaluation of disease activity, therapeutic effects on skin sclerosis or interstitial lung disease and risk stratification of SSc patients. An effective therapeutic agent, able to interfere with complex chemokine networks, is warranted to attenuate perivascular inflammation, dysregulated angiogenesis and the evolution of skin and internal organ fibrosis, is the most ambitious goal for the scientific research of the future.

Chronic radiation-induced dermatitis: challenges and solutions

Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical trials are strongly needed to provide more efficacious therapies.

Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study.

ObjectiveSystemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc.MethodsIn the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.ResultsOf the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.ConclusionIn SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

Clinical significance of serum soluble T-cell immunoglobulin and mucin domain 3 levels in systemic sclerosis: Association with disease severity.

T-cell immunoglobulin and mucin domain 3 (TIM-3) has been thought to play a crucial role in the negative regulation of immune responses. Here, we examined the levels of serum soluble TIM-3 (sTIM-3) in patients with systemic sclerosis (SSc) and evaluated the results with respect to the clinical features of the disease. Patients with diffuse cutaneous SSc (dcSSc) had higher levels of sTIM-3 than those with limited cutaneous SSc and healthy individuals. Serum sTIM-3 levels were positively correlated with the severity of skin sclerosis in early phase dcSSc. Moreover, serum sTIM-3 levels were increased more often in patients with renal crisis and cardiac involvement than in those with normal sTIM-3 levels. These results suggest that serum sTIM-3 levels may be increased in patients with early phase dcSSc and associated with cardiac involvement and renal crisis. Measurement of serum sTIM-3 may be useful for risk stratification in the early stage of the disease.

Ways of Improvement of Safety and Efficiency of Endovenous Laser Coagulation in Treatment of Lower Limb Varicose Vein Disease

Nowadays endovenous laser coagulation is the priority method of treatment of lower limb varicose vein disease. However, there are a number of specific complications that reduce efficiency of its usage.The objective of the research was to decrease specific postoperative complications after endovenous laser coagulation due to the introduction of its mathematical design.Materials and methods. The study included 168 patients with lower limb varicose vein disease. Prior to surgery the mathematical calculation of the basic parameters of laser coagulation such as density of laser irradiation and rate of reverse movement of the light pipe depending on the diameter of varicose veins was made. The control group consisted of 146 patients with varicose vein disease; the aforementioned parameters were established according to the instruction of using a laser device.Results. The analysis of complications such as induration of skin over coagulase great or small saphenous vein, phlebitis in the projection of the great or small saphenous vein, ecchymosis or dermatomelasma in the early postoperative period, pain syndrome showed the reduction in the number of complications while applying the mathematical model of calculation of linear density of laser radiation and the speed of reverse traction of the light pipe with its transfer to the graphic image.Conclusions. The application of the mathematical model of calculation of linear density of laser radiation and the speed of reverse traction of the light pipe with its transfer to the graphic image allows us to improve the results of endovenous laser coagulation for varicose veins due to the reduction in specific complications.