Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n
"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"690",leadTitle:null,fullTitle:"Gamma Knife Radiosurgery",title:"Gamma Knife Radiosurgery",subtitle:null,reviewType:"peer-reviewed",abstract:"Gamma knife radiosurgery is a minimally-invasive treatment alternative for intracranial disorders, including tumors, vascular malformations, facial pain and epilepsy. 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\r\n\tThe recent emergence of a novel, pathogenic coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, officially COVID-19) and its subsequent rapid spread across the world has put the global health at risk. The ongoing efforts are focused on gaining insights into the epidemiology along with the discovered genome structure and important viral factors of SARS-CoV-2. Biotechnology-based innovative solutions are being sought to develop new rapid methods including point-of-care diagnostics and surveillance technologies to detect SARS-CoV-2 early in order to control the disease and mitigate it in a timely fashion. These efforts have also focused on investigating therapeutics including significant breakthroughs in clinical trials on antiviral drugs and vaccines to alleviate the challenges of COVID-19.
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1. Introduction
Over the last decades, renewable energy sources have witnessed major (annual) growth rates, mainly the solar energy ones, which offer competitive, environmental friendly, low-cost solutions, accessible at a mass production level. The renewable energy producing units located close to energy loads are advantageous as the transportation energy losses are practically eliminated. The energy needed for a typical residential home is relatively small and can be covered mainly from renewable sources.
Considering the two major renewable energy sources, such as the wind and sun, the efficient energy harvesting from these sources is one major target of the energy industry. Although these energies seem to be free, with low negative impact, only the way these energies are extracted and used can state if the system is a sustainable system or not. In view of this, one can state that a system is efficiently harvesting the energy from these sources in a sustainable way if the overall efficiency of the system is high and if the energy produced is managed in such a way that these systems have minimum negative effect on the power grid. In other words, it is more efficient to use or store locally the energy produced from renewable sources instead of injecting the energy into the grid. In this way, the power grid is not perturbed by a small production facility with high dynamic behavior. Moreover, if the system is designed in an overall cost-efficient way, the number of PV panels, the wind turbine power, and battery storage capacity can all be minimized in order to obtain an optimized solution in which the power grid can be used only as an energy buffer supply.
The renewable systems of the future will have to integrate all the energy-dependent applications into a system that can be centrally controlled to obtain the best cost-performance balance. In view of this, one interesting way is to combine the electric car and the home electric systems. Concepts like vehicle-to-grid are recently being introduced [1], imposing that the energy storage of the electric vehicle can be integrated into the home electric system to maximize the overall system performance. An overview on solar heat pump systems is presented in Ref. [2]. Garcia et al. [3] present an optimal energy management system for standalone wind turbine/photovoltaic/hydrogen/battery hybrid based on fuzzy logic. Also, Ben Salah et al. [4] and Athari and Ardehali [5] are using fuzzy logic to facilitate the integration of renewable energy into residential or decentralized small power grid applications. Several papers, written by the same research group, present optimal control of different combinations of power sources that feed a heat pump and other loads. A wind/PV + power grid combination is used in Ref. [6], whereas a PV/diesel/battery + power grid combination and a fuel cell/wind/PV + power grid combination are used in Refs. [7] and [8], respectively. These three papers present cost savings derived from optimal control strategies.
The following sections present the power system under study, the presentation of the fuzzy logic energy management, the simulation results, and a conclusion.
2. Power system under study
This chapter proposes a concept in which two power systems interact by means of two interchangeable small batteries: a lightweight electric vehicle and a household partially powered from renewable energy sources. The overall schematic of the studied system is represented in Figure 1. The power generation system is composed of renewable energy conversion equipment: PV panels and a wind generator, both components being connected at the outputs on a DC-Link by means of MPPT-based converters. This DC-Link can be considered the main power line of the system on which also all the DC house loads are connected. This power system is also connected to the grid with a bidirectional DC-AC converter. The storage element is a battery from a lightweight electric vehicle. This small capacity battery is exchangeable with a second battery that is installed in the vehicle. The heat pump load is a key element in the proposed system, mainly because it will be the main electric load in balancing the energy from the renewable sources. Also, a key element of the proposed system is that the battery storage capacity is kept to a minimum; the two batteries are alternately used by the vehicle and are recharged mainly from the renewable sources. The battery can be used by the home electric system only when the power grid is unavailable. It must be stated that, to obtain a feasible approach, the battery has to be as light as possible in order to be easily exchanged.
Figure 1.
Schematic of the power system.
The main objective of this study is to develop an energy management control system, based on fuzzy logic, which performs in such way that all the energy from the renewable sources is used, with minimum or no energy injection into the power grid and with a small energy storage capacity. The electrical energy can also be obtained from the power grid. In this way, the best cost-performance tradeoff with minimum storage capacity and maximum utilization of the renewable energy can be obtained.
3. Fuzzy logic energy management
The fuzzy logic energy management is developed with the aim of splitting the renewable energy power to be either stored into the battery or transformed into thermal energy, with a multiplication factor by a heat pump. The fuzzy algorithm is using as inputs the battery state of charge (SoC) and the required heat energy (hot water and heating during cold periods). The output is the battery power (Pbatt), the heat pump power (Php) being calculated with the simple Eq. (1):
Php=1−PbattE1
Figure 2 presents the two inputs and one output of the fuzzy logic supervisor.
Figure 2.
Fuzzy logic energy management inputs and output.
Figures 3–5 present the membership functions (MFs) of the two inputs and output. The implementation of the fuzzy logic supervisor is done using Fuzzy logic toolbox and Matlab/Simulink® software from Mathworks®. It should be noted that those membership functions are built considering that the sum of them is on the entire interval 1 and the variation on both axes is expressed in per unit.
Figure 3.
MFs for the first input of the fuzzy logic management system.
Figure 4.
MFs for the second input of the fuzzy logic management system.
Figure 5.
The output of the fuzzy logic management system.
The rule base of the fuzzy algorithm is presented in Table 1. It contains nine rules according to the fact that each input has three MFs, all of them being considered in the rule-editing phase. These rules were established considering the next principle: the thermal energy level and the battery SoC should increase similarly if they have a similar level (in per unit), but if one is lower than the other, it will be favored in order to reach a similar level (in per unit).
Battery power
Battery SoC
Small
Moderate
High
Thermal energy level
Small
Moderate
Small
Small
Moderate
Big
Moderate
Small
High
Big
Big
Small
Table 1.
Rule base of the fuzzy logic power management.
The defuzzification method used is centroid, which returns the center of area under the response surface. Figure 6 presents the response surface generated for this fuzzy logic supervisor. As it can be seen from this figure, the output variation does not reach the full range between 0 and 1 (its range is between 0.163 and 0.837). Thus, in order to extend the output range, the output result is subtracted with 0.163 and then multiplied with 1.485.
Figure 6.
Response surface for the fuzzy logic supervisor.
4. Simulation results
The following figures present the simulation results for a power system with the following assumptions:
Wind turbine and PV panels have an installed power of 1 kW each.
The electric vehicle battery has a capacity of 1 kWh with an SoC of 40% when the charge process starts.
It is considered that the vehicle is an ultralight version having two interchangeable batteries: one that equips the vehicle and the other left at home for charging.
The heat pump has a coefficient of performance (COP) of 3, thus it consumes one-third electrical energy and generates three times more heat energy.
The necessary heat energy considered is 30 kWh, thus a 10 kWh of electrical energy is required for the heat pump.
The heat pump has the possibility to adjust power according to renewable energy production.
Simulations are made for 1 day (24 h).
Figures 7 and 8 present the power and energy produced by the wind/PV hybrid system. The PV power curve has similar variations with some classic production curves for a sunny day, and the wind power has approximate variations according to a wind measurement from Brasov area (Romania).
Figure 7.
Renewable sources power curves.
Figure 8.
Renewable energy production.
The necessary electrical and thermal powers required are presented in Figure 9. The electrical power consumption is taken from a figure presented in Ref. [9] and the thermal power is estimated considering 30 kWh of needed energy (for a cold period) and no energy consumption during workhours.
Figure 9.
Estimated consumption of thermal and electrical powers.
Figure 10 presents the power grid failures. Even if it is unlikely to have two grid voltage drops during 1 day, it was considered in the simulation for demonstration purposes. Each voltage drop has a period of 15 min, first, from 14h30 to 14h45 and second from 21h30 to 21h45.
Figure 10.
Power grid failure.
Figures 11 and 12 present the thermal energy level and the battery SoC, respectively, of the heat pump and battery powers, for the considered application. Both the thermal energy level and the SoC have an initial level. Due to the fact that at 18h00, the thermal power consumption restarts, and even if the heat pump is still working, the thermal energy level decreases (Figure 11). At the same time (18h00), the batteries are switched, the charged one is placed on the electric vehicle and the discharged one is put to charge. In order to use mainly the renewable energy to charge the battery and considering that the thermal energy demand is high, during the remaining hours of the day (18h00–24h00), the charging of the battery is stopped. By the end of the day, the thermal energy level and the battery SoC are lower compared with the situation at the beginning of the day. It is clear that not all required energy can be obtained from the renewable sources, thus, some has to come from the power grid to arrive to the necessary level. From Figure 12 one can observe that the first power grid drop is easily covered from renewable energy sources, just a sudden drop in the heat pump power can be observed. But the second one takes a lot of energy from the battery, which arrives to an SoC of about 5%. If the power grid loss would be longer, the feeding of all the loads would not be possible, and if considered appropriate, only the mandatory loads (pumps, lighting, etc.) should be fed. Or, if charging the discharged one is started at 18h00, the SoC would not decrease that much (Figure 13). Of course, in this case, the thermal energy level will decrease. For this situation, the heat pump and battery working powers are changed (Figure 14).
Figure 11.
Thermal energy level and the battery SoC.
Figure 12.
Heat pump power and battery power.
Figure 13.
Thermal energy level and the battery SoC for the immediate charging of the discharged battery.
Figure 14.
Heat pump and battery powers for the immediate charging of the discharged battery.
5. Conclusion
A fuzzy logic energy management algorithm has been proposed and validated by simulations, for a household application. This algorithm allows the distribution of the renewable energy to charge a battery and also to feed a heat pump that produces thermal energy. The results show that the battery charges to around 97%, and the thermal energy level from renewable sources is around 88% for the first case (discharged battery is not charged during the evening) and around 83% for the second (discharged battery is charged during the evening). The rest of the needed energy should be covered from the power grid.
\n',keywords:"fuzzy logic energy management, PVs, wind turbine, heat pump, electric vehicle, battery",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/55958.pdf",chapterXML:"https://mts.intechopen.com/source/xml/55958.xml",downloadPdfUrl:"/chapter/pdf-download/55958",previewPdfUrl:"/chapter/pdf-preview/55958",totalDownloads:1491,totalViews:441,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"November 7th 2016",dateReviewed:"April 27th 2017",datePrePublished:null,datePublished:"August 30th 2017",dateFinished:null,readingETA:"0",abstract:"A fuzzy logic energy management algorithm is proposed for a hybrid wind/photovoltaic (PV) power generation unit, an electric vehicle battery, and a heat pump for household applications. The proposed concept refers to two independent power systems—a light electric vehicle and a household that interact through light, interchangeable batteries; moreover, they are powered from a renewable energy system comprising PV panels, wind generator, and appropriate MPPT-based converters. The main features of the concept are the heat pump load that produces thermal energy, as the main electric load of the system, and the storage element that is alternately used by the vehicle, which can be recharged from renewable sources. The presented algorithm allows the implementation, by means of fuzzy tools, of an appropriate energy management control system in order to obtain maximum utilization of the renewable energy. The results show that most of the energy required to charge the battery and to feed the heat pump can be covered from renewable sources.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/55958",risUrl:"/chapter/ris/55958",book:{slug:"modern-fuzzy-control-systems-and-its-applications"},signatures:"Stefan Breban, Ioana Gros, Calin Marginean and Petre Teodosescu",authors:[{id:"178814",title:"Dr.",name:"Stefan",middleName:null,surname:"Breban",fullName:"Stefan Breban",slug:"stefan-breban",email:"stefan.breban@emd.utcluj.ro",position:null,institution:{name:"Technical University of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"195867",title:"Dr.",name:"Petre",middleName:"Dorel",surname:"Teodosescu",fullName:"Petre Teodosescu",slug:"petre-teodosescu",email:"petre.teodosescu@emd.utcluj.ro",position:null,institution:{name:"Technical University of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"200905",title:"Dr.",name:"Ioana",middleName:null,surname:"Gros",fullName:"Ioana Gros",slug:"ioana-gros",email:"Ioana.Vese@emd.utcluj.ro",position:null,institution:null},{id:"200906",title:"Dr.",name:"Calin",middleName:null,surname:"Marginean",fullName:"Calin Marginean",slug:"calin-marginean",email:"ignatc@emd.utcluj.ro",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Power system under study",level:"1"},{id:"sec_3",title:"3. Fuzzy logic energy management",level:"1"},{id:"sec_4",title:"4. Simulation results",level:"1"},{id:"sec_5",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Guille C, Gross G. A conceptual framework for the vehicle-to-grid (V2G) implementation. Energy Policy. 2009;37(11):4379-4390. ISSN: 0301-4215'},{id:"B2",body:'Sparber W, Vajen K, Herkel S, Ruschenburg J, Thür A, Fedrizzi R, D’Antoni M. Overview on solar heat pump systems and review of monitoring results. In: ISES World Solar Congress, 28 August -2 September 2011, Kessel, Germany; Published by International Solar Energy Society, Freiburg Germany:1-12'},{id:"B3",body:'Garcia P, Torreglosa JP, Fernandez LM, Jurado F. Optimal energy management system for standalone wind turbine/photovoltaic/hydrogen/battery hybrid system with supervisory control based on fuzzy logic. International Journal of Hydrogen Energy. 2013;23:14146-14158'},{id:"B4",body:'Ben Salah C, Chaabene M, Ben Ammar M. Multi-criteria fuzzy algorithm for energy management of a domestic photovoltaic panel. Renewable Energy. 2008;33(5):993-1001. ISSN: 0960-1481'},{id:"B5",body:'Athari MH, Ardehali MM. Operational performance of energy storage as function of electricity prices for on-grid hybrid renewable energy system by optimized fuzzy logic controller. Renewable Energy. 2016;85:890-902'},{id:"B6",body:'Sichilalu S, Mathaba T, Xia X. Optimal control of a wind–PV-hybrid powered heat pump water heater. Applied Energy. 2017;185:1173-1184'},{id:"B7",body:'Sichilalu S, Xia X. Optimal energy control of grid tied PV–diesel–battery hybrid system powering heat pump water heater. Solar Energy. 2015;115:243-254'},{id:"B8",body:'Sichilalu S, Tazvinga H, Xia X. Optimal control of a fuel cell/wind/PV/grid hybrid system with thermal heat pump load. Solar Energy. 2016;135:59-69'},{id:"B9",body:'Arif MT, Oo AMT, Ali ABMS. Estimation of energy storage and its feasibility analysis. In: Zobaa AF, editor. Energy Storage—Technologies and Applications. InTech, Rijeka, Croatia; 2013: 41-78. ISBN: 978-953-51-0951-8'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Stefan Breban",address:"stefan.breban@emd.utcluj.ro",affiliation:'
Technical University of Cluj-Napoca, Cluj-Napoca, Romania
Technical University of Cluj-Napoca, Cluj-Napoca, Romania
'}],corrections:null},book:{id:"5883",title:"Modern Fuzzy Control Systems and Its Applications",subtitle:null,fullTitle:"Modern Fuzzy Control Systems and Its Applications",slug:"modern-fuzzy-control-systems-and-its-applications",publishedDate:"August 30th 2017",bookSignature:"S. 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\n
1. Introduction
\n
In this chapter, we discuss the groups of disorders classified as systemic sclerosis mimics. Localized and sometimes generalized skin stiffness is typical for this group of diseases. However, quite incongruous pathogenesis, underlying disease mechanisms and distinct organ involvement are significantly different in these conditions. This chapter describes the pathogenesis, clinical manifestation, histopathology findings, and therapeutic possibilities of the most common diseases that may cause difficulties in the differential diagnosis of systemic sclerosis.
\n
\n
\n
2. Localized scleroderma, morphea
\n
\n
2.1 Introduction
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Localized scleroderma is a clinically distinct inflammatory disease, primarily of the dermis and also subcutaneous fat [1]. The inflammation leads to scar-like sclerosis. Inflammatory infiltrates and changes of small vessels are similar in morphea and systemic sclerosis (SSc), but morphea has more asymmetric or linear skin localization and distribution than SSc, which has symmetrical distribution. Generalized morphea can prevent and mimic diffuse cutaneous SSc, but this clinical variant does not have Raynaud’s phenomenon, digital sclerosis and lung, and gastrointestinal tract manifestation of the disease. Morphea is responsible for the morbidity of the patient such as skin tightness, joint mobility reduction leading to contractures, growth retardation, and pain [1, 2, 3].
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2.2 Epidemiology
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Morphea typically develops in adults, although morphea can occur at any age. The incidence of morphea is 3 per 100,000 people, and the prevalence of morphea increases with age. The mean age of disease onset is 45 years. Morphea is more prevalent in women than in men (2.6:1), except linear morphea, which has no gender preference [2, 3, 4].
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2.3 Pathogenesis
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The cause of the disease is unknown. Coexistence of various forms of scleroderma and the rare possibility of progression of localized scleroderma into SSc indicate that both types represent different manifestations of the same pathological process. Pathogenesis may be due to participation of environmental influences, immunological disorders, and infections, e.g., association with Borrelia burgdorferi [3]. Sclerosis of the skin is induced by vascular damage, activated T cells, and accented connective tissue production by dermal fibroblasts. Vascular changes represent a reduction in the number of capillaries. Enhanced production of collagen and other extracellular matrix proteins and components is induced by T-cell-derived cytokines, interleukin 4 (IL-4), IL-13, and transforming growth factor beta (TGF-β) [3, 5, 6].
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2.4 Clinical features
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Morphea can be divided into several clinical groups: plaque-type morphea, linear morphea, generalized morphea, deep morphea, nodular morphea, and guttate morphea. Patient with morphea does not have involvement of internal organs and Raynaud’s phenomenon. Some patients may have involvement of muscles, tendons, and joints or neurological or ophthalmological symptoms which depend more likely on anatomical site, e.g., in a patient with linear morphea [2].
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2.5 Plaque-type morphea, circumscribed morphea
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Plaque-type morphea is the most common variant, characterized by a slightly elevated, edematous, erythematous, or violaceous and livid plaque with oval to round or centrifugal distribution (Figure 1). The developmental stage of the disease may influence the clinical features: (i) inflammatory, (ii) sclerotic, and (iii) atrophic [1, 2].
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Figure 1.
Plaque-type morphea, lesion on the right side of the trunk. Plaques are surrounded by a dark red rim on the periphery with a yellowish white color center of the lesion as a result of the increasing deposition of connective tissue.
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In the inflammatory phase, these are delimited striated skin plaques with the accentuated surface by skin pores, which resemble “orange peel” due to the edema of the corium expanding the follicular orifice. Plaques are surrounded by a violaceous rim on the periphery, indicating the active inflammatory stage of the disease. A yellowish-white color develops in the center of the lesion as a result of the increasing deposit of connective tissue [3]. In the sclerotic phase, the inflammatory border is absent. The skin of the lesion is smooth, shiny, and difficult or unable to be shaken. In the final (atrophic) phase, induration disappears; the plaques are soft, slightly sloping for skin and subcutaneous atrophy, and mostly gray-brown pigmented. Circumscribed morphea usually presents as single or multiple skin lesions. It is generally asymptomatic, but the central portion of the progressing lesion starts to get rigid and may be slightly painful [2, 3].
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A different manifestation of morphea can be present. Guttate morphea presents as multiple rather superficial and nummular plaques (Figure 2).
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Figure 2.
Guttate morphea, multiple nummular lesions on the right thigh.
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Deep morphea represents sclerosis that affects the primarily deep parts of the dermis and subcutaneous fat (Figure 3).
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Figure 3.
Deep morphea, the affection of the front of the right thigh, mapping distribution of erythematous and whitish parts with visible scarring.
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2.6 Linear morphea
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Linear morphea is similar in the clinical feature to circumscribed morphea but with a linear distribution. Linear morphea initially starts as a linear erythematous streak or harmless lesion that later forms a scar-like band (Figure 4).
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Figure 4.
Linear morphea, linear distribution of plaques, leading to atrophic changes in the affected limb.
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This scar-like band significantly impairs the mobility of the affected limb. Linear morphea can affect the underlying fascia, the muscle, and tendons. Linear morphea that transcends joints can significantly reduce movement and lead to developmental limb defects in children. Rarely, it can form bizarre configurations when copying Blaschko’s lines [1, 3, 7].
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2.7 “En coup de sabre”
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The “en coup de sabre” represents a linear type of morphea of the head. This morphea is unilateral and extends from the forehead into the frontal scalp (Figure 5).
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Figure 5.
“En coup de sabre” as linear morphea of the head. Linear scarring lesion on the forehead with an erythematous rim spreading to the scalp.
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It usually starts as a small plaque with the surrounding inflammatory erythematous rim. Parry-Romberg syndrome is a rare variant of linear morphea of the forehead and scalp, with progressive loss of subcutaneous fat, with a smaller share of sclerosis [3, 8, 9].
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2.8 Generalized morphea
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Generalized morphea begins as multiple plaque-type morphea on the trunk. This clinical variant is defined by the presence of ≥4 plaques involving at least two different anatomic sites (Figure 6).
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Figure 6.
Generalized morphea begins as multiple-plaque-type morphea on the abdomen, circularly affecting breasts and the neck. In the margins, lesions are with a rim of erythema, indicating the inflammatory stage of the disease.
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In contrast to systemic sclerosis, generalized morphea does not present with sclerosis primarily involving acral skin or sclerodactyly, but this anatomical site can also be affected [10]. Apart from the skin, generalized morphea can also affect the subcutis and fascia, and be accompanied by slight changes in internal organs (especially the gastrointestinal tract and lungs) and the formation of joint contractures with mostly secondary joint involvement and movement limitation [11, 12]. Carapace-like tightening of the chest, can reduce breathing and cause swallowing difficulties.
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2.9 Laboratory findings
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Laboratory abnormalities are typically associated with generalized and linear morphea, but some patients with morphea have elevated antinuclear antibody (ANA). Reported rates of ANA positivity among patients with morphea range from 18 to 68%. Other autoantibodies that are detected less frequently than ANA in patients with morphea include anti-single-stranded DNA (ssDNA), anti-double-stranded DNA (dsDNA), antihistone, anti-topoisomerase IIα, antiphospholipid, and rheumatoid factor [1, 13].
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2.10 Histopathology
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The histopathological findings depend on the stage of the disease and area where the biopsy was taken (inflammatory border or central sclerotic lesion). Biopsy specimens for histology must include subcutaneous fat (Figure 7).
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Figure 7.
Deep skin biopsy to subcutaneous fat after formaldehyde fixation.
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Biopsies performed from inflammatory lesions demonstrate an interstitial and perivascular inflammatory cell infiltrate composed primarily of CD4+ T cells, eosinophils, plasma cells, and mast cells. Inflammation may extend into the subcutaneous tissues. Furthermore, tissue edema, enlarged tortuous vessels, and thickened collagen bundles may be observed. Biopsy from a sclerotic lesion demonstrates homogenization of the papillary dermis and thickened collagen bundles extending into the reticular dermis or beyond (Figure 8). In biopsy from deep morphea, the deep reticular dermis, subcutis, and fascia show sclerotic changes [14].
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Figure 8.
Biopsy from a sclerotic lesion demonstrates homogenization of the papillary dermis and thickened collagen bundles extending into the reticular dermis.
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2.11 Differential diagnosis
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A number of other disorders can present with clinical features that resemble morphea. Generalized morphea is necessary to distinguish from systemic sclerosis or scleredema diabeticorum. In addition to the skin sclerosis, systemic sclerosis generally begins with the Raynaud’s phenomenon, and patients commonly exhibit initial puffiness and eventual sclerosis in the fingertips (sclerodactyly), usually accompanied by nail fold capillary changes. These changes are absent in patients with morphea. The differential diagnosis of plaque-type morphea includes lichen sclerosus, morpheaform basal cell carcinoma, and postirradiation morphea. Furthermore, we need to think of lipodermatosclerosis as fibrosing panniculitis with typical localization on the lower extremities or eosinophilic fasciitis. In some cases of limb involvement, pretibial myxedema or Lyme disease (acrodermatitis atrophicans) must be excluded [1, 13, 14].
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2.12 Treatment
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A variety of treatment options are available for patients with active lesions of morphea; however, evidence in support and success of these therapeutics modalities is limited. The expected outcome of successful therapy for morphea is not a complete healing or normal skin texture. In patients with progressive disease, successful treatment presents stopping the formation of new lesions and limiting the spreading of the disease [1, 15].
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2.13 Topical and intralesional treatment
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Topical therapies are unlikely to be effective for the disease involving the subcutis or deeper tissues and are not useful for preventing the development of new lesions in patients with rapidly progressive disease. Topical tacrolimus as tacrolimus 0.1% ointment may be effective for active, inflammatory morphea [16]. High potency topical and intralesional corticosteroids are widely used for the treatment of morphea; however, no formal studies have documented their efficacy. Topical vitamin D—vitamin D as topical calcipotriene 0.005% ointment—may inhibit effects on fibroblast proliferation, collagen synthesis, and T-cell activation. In some clinical studies, an improvement on this therapy was noted in limited numbers of patients [15, 17].
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Imiquimod is a topical immunomodulator that induces interferon-gamma, a cytokine that inhibits TGF-beta and the production of extracellular matrix proteins. Imiquimod also downregulates the profibrotic cytokine IL-4. Limited data suggest that imiquimod is effective in some patients with plaque-type morphea [18].
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It is possible to use phototherapy in patients with sclerotic diseases like morphea. Longer wavelengths of light as ultraviolet A (UVA) (320–400 nm) are capable of greater depth of penetration into the skin, and most studies of UV phototherapy in sclerotic skin disease have focused on the use of UVA light (320–400 nm). Fewer data are available on the use of PUVA therapy (a combination of UVA and topical or oral use of psoralens) and ultraviolet B (UVB) light (290–320 nm). Phototherapy is unlikely to be effective for morphea with deep involvement (subcutis, fascia, or muscle) and should not be considered as primary therapy alone [19].
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2.14 Systemic treatment
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Patients with the progressive disease require systemic therapy with methotrexate or corticosteroids. Methotrexate is the most appropriate systemic therapy for morphea. In patients with acute generalized or rapidly progressive disease, we combine treatment with systemic corticosteroids. Methotrexate is typically given for at least 6–12 months with a weekly dose of 15–25 mg. The systemic corticosteroids are usually tapered and discontinued after 3–4 months or pulse intravenous therapy is used instead (500–1000 mg of intravenous methylprednisolone sodium succinate for 3 consecutive days/month) [15, 20].
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3. Morpheaform inflammatory syndromes/conditions
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Some diseases and disorders with acrosclerosis and Raynaud’s phenomenon have a clinical presentation similar to localized scleroderma. The etiology of these disorders is diverse and includes, e.g., secondary sclerosis after exposition to bleomycin, vinyl chloride, L-tryptophan, or toxic oils. Sclerosis can also be induced by endogenous metabolites, by x-irradiation, or during chronic graft-versus-host disease (GVHD) (Figure 9). Morphea-like lesion, eosinophilic fasciitis, and lichen sclerosus can also be observed in these patients [21].
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Figure 9.
Morphea-like lesion in a patient with GVHD. Post-inflammatory hyperpigmentation with whitish areas of sclerotic skin affecting the left thigh.
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3.1 Lipodermatosclerosis
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3.1.1 Introduction
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Typical changes associated with chronic venous insufficiency include erythema, induration, and hemosiderin pigmentary changes. But a variety of clinical appearances and histopathologic findings also include sclerosis, or sclerosing panniculitis. The various manifestations of this panniculitis have been consolidated under the heading of lipodermatosclerosis or sclerosing panniculitis [22].
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Lipodermatosclerosis typically manifests in patients, usually in women over the age of 40 years with chronic venous insufficiency as a result of chronic hypoxia. Venous hypertension leads to a compromised ability to reduce foot vein pressure during exercise. This change results in increased capillary permeability, with leakage of fibrinogen, with subsequent polymerization leading to formation of fibrin plaques around vessels. There may also be an abnormal regulation of angiogenesis in a patient with lipodermatosclerosis. For example, increased expression of vascular endothelial growth factor receptor 1 (VEGFR-1) can be a result of VEGF-mediated angiogenesis. Another factors may include local stimulation of collagen and obesity [23, 24].
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3.1.2 Clinical features
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Sclerosis affects the acral parts of the lower limbs symmetrically. The acute and progressive phase of lipodermatosclerosis presents with pain, erythema, and the formation of induration on the affected area of lower limbs. In the chronic phase, sclerosis of the dermis and subcutis is typically present, and sclerosis results in induration that is more sharply demarcated from the adjacent normal skin (Figure 10). Other gravity dependent sites such as the lower aspect of the abdominal pannus can also develop lipodermatosclerosis. At this point, the changes are relatively diffuse. Hyperpigmentation due to hemosiderin deposition or chronic ulceration of the lower limbs may also be present [22].
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Figure 10.
Lipodermatosclerosis in a patient with chronic venous insufficiency. In this case erythema and sclerotic whitish induration on the medial part of the shank with the border of hemosiderin pigmentary changes are present.
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3.1.3 Histopathology
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Early lesions show mid-lobular panniculitis, a lymphocytic infiltrate in the septa, variable degrees of capillary congestion, and extravasation of erythrocytes with hemosiderin deposition. Chronic lesions show septal sclerosis and membranocytic change with a marked reduction in inflammation or lymphocytic infiltrate [25, 26].
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3.1.4 Differential diagnosis
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In differential diagnosis, it is necessary to distinguish inflammatory changes such as cellulitis and erysipelas but also erythema nodosum or erythema induratum. As induration develops and progresses, differentiation from morphea and scleromyxedema may be necessary. In morphea, subcutaneous involvement is predominantly septal, and lipophagic and lipodystrophic changes are not typically present [22, 25].
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3.1.5 Treatment
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Leg elevation and consistent compression therapy are crucial for the treatment of lipodermatosclerosis. Traditional anti-inflammatory therapies are usually ineffective, but topical or intralesional corticosteroids (e.g., triamcinolone 5–10 mg/cc) may bring relief and improvement with compression therapy [27].
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3.2 Injection of vitamin K
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Oil-soluble injection of vitamin K may be responsible for the eosinophilic reaction of the deep part of the dermis and subcutaneous fat, which may resemble localized eosinophilic fasciitis with similar clinical manifestation as deep morphea. This inflammation can result in dermal and subcutaneous atrophy [28].
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3.3 Vaccination-associated morphea
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Circumscribed morphea and deep morphea have been described after intramuscular injections of different types of vaccines. The etiology and antigens responsible for this type of inflammation have not been reliably elucidated [29].
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3.4 Paraffin and silicone injections or silicone implants
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The leak of silicone from implants and silicone or paraffin injection after reconstructive or plastic surgery induce chronic inflammation that results in localized morphea-like lesion. The contribution to the induction of SSc, eosinophilic fasciitis, or mixed connective tissue disease has also been discussed [30].
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3.5 Porphyrias
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Porphyria cutanea tarda can lead to a morphea-like lesion and scarring in the chronic sun (UV)-exposed sites, such as the face, scalp, dorsal part of the hands, and upper part of the chest [31].
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3.6 Radiation-induced morphea
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X-irradiation can induce sclerotic, chronic erythematous, and secondary pigmented lesions typically in a patient after irradiation of the chest and axillary region for breast carcinoma (Figure 11). The morphea-like lesions can start several years after radiation [32].
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Figure 11.
Morphea-like lesion in a patient after x-irradiation for breast carcinoma. The erythematous and sclerodermic lesion on the right breast.
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3.7 Differential diagnosis
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The differential diagnosis is summarized in this paragraph, but the most important entity in the differential diagnosis of SSc or localized scleroderma is lichen sclerosus et atrophicus and scleromyxedema. Absence of overall symptoms and organ involvement is crucial [21].
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4. Lichen sclerosus
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Lichen sclerosus et atrophicus is an inflammatory disease, primarily of the superficial dermis or mucosa, which leads to white scar-like atrophy. Extragenital lichen sclerosus may itch and be cosmetically annoying. Genital lichen sclerosus causes dryness and persistent pruritus. Genital lichen leads to progressive atrophy, and functional impairment, which significantly reduces the quality of life.
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4.1 Epidemiology
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Prevalence of lichen sclerosus is unknown. This chronic disease occurs at all ages with a similar incidence in all races. The ratio of occurrence in men and women varies considerably, but in both sexes, the most affected area is the anogenital region (about 85% of patients, in women usually as a vulvar disease) [33, 34].
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4.2 Pathogenesis
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Association with the MHC class II antigen HLA-DQ7 was observed, but the specific genetic predisposition is unknown. Unspecific inflammation seems to be essential for the initiation and also the progression of lichen sclerosus. Autoantibodies such as those against the extracellular matrix protein 1 (ECM-1) were found in 80% of patients with lichen sclerosus. Moreover, in female patients with lichen sclerosus, there is a higher prevalence of autoimmune diseases (especially autoimmune thyroid disease) and ANA positivity than in male patients with lichen sclerosus [34, 35, 36].
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4.3 Clinical features
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Lichen sclerosus manifests by polygonal, bluish-white, shiny, slightly elevated maculopapules with a pointed follicular bounds of hyperkeratoses, which may be solitary or in groups. This skin lesion can be bounded with an area of erythema. The solitary lesion enlarges to plaques and to the scar-like lesion with a rough surface and skin atrophy (Figure 12).
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Figure 12.
Extragenital lichen sclerosus, slightly elevated plaque with scar-like presentation, with a whitish erythematous rim and skin atrophy.
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More rarely, blistering with possible hemorrhagic content can be present (Figure 13). Extragenital predilection sites include supraclavicular localization, under the breasts, cubit, groin, loose wrist, and cross. Symptoms of extragenital lichen sclerosus are dryness and pruritus.
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Figure 13.
Extragenital lichen sclerosus, whitish plaque with blisters and crusts. Blisters resemble hemorrhagic-like content.
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However, lichen sclerosus most frequently affects the anogenital region. In women, it typically affects the vulva and the perianal localization in figure-of-eight configuration (Figure 14). Genital lichen sclerosus begins as slightly elevated lesion of erythema, sometimes with erosions. During the chronic stage of the disease, the skin becomes shiny, sclerotic, and also hypopigmented. The scarring may affect the clitoris and labia, and disability may be significant or even make the sexual intercourse impossible. Although the disease may be symptom-free, it frequently causes severe pruritus and pain is a typical symptom. Another symptom may be dysuria or pain upon defecation [34, 37].
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Figure 14.
Genital lichen sclerosus affects the labia minora, clitoris, and vulval vestibule. Whitish and erythematous plaques are also present in the labia majora, the perineum, and the perianal region.
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4.4 Histopathology
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Lichen sclerosus has a specific histopathological pattern. Initially, superficial dermal edema is associated with a band-like lymphocytic infiltrate. The epidermis is thinned and atrophic, with orthohyperkeratosis and vacuolar degeneration of the basal layer. Hyperkeratosis is especially pronounced at follicular openings and may lead to plugging. Vacuolar degeneration of the basal layer and flattening of the rete ridges predispose to the development of blisters, which may become hemorrhagic. The most important changes are found in the superficial dermis with the presence of homogenized collagen (Figure 15). Loss of elastic fibers is typical for lichen sclerosus and is not observed in morphea [38, 39, 40].
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Figure 15.
Skin biopsy of extragenital lichen sclerosus where atrophic thinned epidermis and mild vacuolar degeneration of the basal layer are present. In the superficial dermis, homogenized collagen with perivascular lymphocytic infiltrates can be found.
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4.5 Differential diagnosis
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The differential diagnosis of extragenital lichen sclerosus includes morphea, vitiligo, tinea versicolor, anetoderma, or cutaneous lymphoma. In the case of genital lichen sclerosus, erosive lichen planus and erythroplasia of Queyrat must be considered.
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Sometimes it is not possible to distinguish morphea from lichen because clinical and especially histopathological findings of both diseases can also be present in one patient or one biopsy [34].
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4.6 Treatment
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Topical medications, phototherapy, and systemic therapy have been used for the treatment of lichen sclerosus. The effect of topical corticosteroids was reported especially in genital lichen sclerosus, but mitigation has also been demonstrated in extragenital lichen. Effect of topical corticosteroid therapy has been reported in randomized treatment and retrospective studies. Phototherapy is preferred second-line treatment for patients with limited disease that cannot be effectively treated with topical corticosteroids. An alternative to topical corticosteroids is the use of calcineurin inhibitors pimecrolimus and tacrolimus despite concerns of possible increase of development of squamous cell carcinoma or reactivation of HPV [15, 37, 41].
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The use of systemic therapy is limited to a small group of patients with progressive worsening of extragenital lichen sclerosus that failed to respond to a potent topical corticosteroid and phototherapy. For systemic therapy, methotrexate (15–20 mg/week) and systemic corticosteroids (1 g of intravenous methylprednisolone sodium succinate for 3 consecutive days/month) can be used [42].
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5. Eosinophilic fasciitis
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Eosinophilic fasciitis is a relatively recently described disease, characterized by fibrosing induration of the extremities and peripheral eosinophilia. In many patients strenuous physical activity precedes the development of this condition.
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5.1 Clinical feature
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Initial clinical manifestation includes painful edema of the extremities, which progresses to fibrosis and pseudo-inflammatory appearance (Figure 16). The manifestation of the disease is typically symmetrical on extremities without involvement of the hands, feet, and face [43].
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Figure 16.
Eosinophilic fasciitis with initial clinical manifestation of progressive fibrotic changes with pseudo-inflammatory appearance.
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Laboratory findings include elevation of ESR, hypergammaglobulinemia and peripheral eosinophilia which can be present in the early phase of the disease. ANA titer and complement level are usually normal. Pancytopenia, anemia, thrombocytopenia, myeloproliferative disorders, and monoclonal gammopathy have been reported in association with eosinophilic fasciitis. The diagnosis of eosinophilic fasciitis is established via fascial biopsy and/or by MRI [44].
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5.2 Histopathology
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Histologically eosinophils and mast cells are present, and dermal fibrosis with patchy infiltrates composed of lymphocytes and plasma cells are also present. In deep biopsy thickening of the fascia is typical, which may be 10–50 times the normal width [44].
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5.3 Treatment
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Once the diagnosis of eosinophilic fasciitis is established via fascial biopsy and/or MRI, prompt treatment is essential to preserve mobility and function and prevent joint contractures. Prompt therapy with oral corticosteroids (e.g., prednisone 1–2 mg/kg daily) is usually necessary for reduction or cessation of rapid disease progression and as prevention of mobility reduction and development of joint contractures. The response is typically noted within the first few weeks, and clinical improvement may be seen over several months. Alternatively, hydroxychloroquine, cyclosporine, dapsone, methotrexate, PUVA, or infliximab may be used alone or in combination with prednisone. Phototherapy as UVA1 can also be beneficial [45].
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6. Nephrogenic systemic fibrosis
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Nephrogenic systemic fibrosis is most often observed in middle-aged adults but has also been described in children and elderly patients. There is no gender or race predilection. Renal dysfunction and exposure to gadolinium-based contrast medium play a crucial role in the pathogenesis. Although the context use of the gadolinium in a patient with renal dysfunction is irrefutable, the mechanisms of fibrosis are still unknown [46, 47].
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6.1 Clinical features
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This disorder presents with large and thick, indurated plaques distributed symmetrically on the extremities and trunk. The skin lesions are irregular and erythematous with a tendency to develop hyperpigmentation. The manifestation on the extremities often results in joint contractures. The condition is frequently associated with considerable pain and loss of mobility. Extracutaneous manifestations include yellow scleral plaques and systemic fibrosis with involvement of the heart, lungs, and also skeletal muscles [48, 49].
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6.2 Histopathology
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A deep biopsy is necessary for diagnosis. Histologic features include increased dermal fibroblast-like cells with positivity for CD34 and procollagen I. Haphazard arrangement of thickened collagen bundles is also present. Furthermore, vascular proliferation and mucin deposition may also be present.
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6.3 Treatment
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Nephrogenic systemic fibrosis is refractory to treatment with corticosteroids and other immunosuppressive drugs. There have only been case reports of improvement with imatinib, rapamycin, phototherapy UVA1, PUVA, or plasmapheresis. Improvement in renal function after renal transplantation may improve this type of fibrosis [49].
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7. Stiff skin syndrome
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This dysfunction may be hereditary as a congenital disorder or acquired during early childhood. Familiar hereditary subtype is caused by heterozygosity for a mutation in the gene that encodes fibrillin-1 (FBN1). Dysfunction of this gene results in the production of giant collagen fibrils in the affected fascia [50].
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7.1 Clinical features
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Stiff skin syndrome is characterized by “rock hard” induration and thickening of the skin and subcutaneous tissues. Typical manifestation is on the buttocks and thighs with mild hypertrichosis without affecting the inguinal folds. This disorder does not affect the hands and feet. The condition is stable or slowly progressive, and abnormalities of internal organs are not typically observed. In differential diagnosis the disease may resemble scleredema, deep morphea, or linear scleroderma [51].
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7.2 Histopathology
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Histologically, significant thickness of fascia with deposition of hyaline without an associated inflammatory infiltrate can be found. Thickened collagen bundles and mucin deposition may be present in the dermis. The epidermis and papillary dermis are mostly without any pathologies [52].
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7.3 Treatment
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Treatment of stiff skin syndrome is very difficult, and no effective treatments have been reported. Physical therapy and regimen measures for the patient can help to prevent progressive joint contractures and immobility [51, 52].
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8. Scleromyxedema
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Scleromyxedema is a chronic idiopathic disorder characterized by papules and lesion of induration with dermal mucin deposition and with an increase of dermal collagen resulting in skin sclerosis. Many patients with scleromyxedema have monoclonal gammopathy, with systemic or lethal manifestations. Scleromyxedema represents a generalized variant that needs to be distinguished from localized lichen myxedematosus (variant without sclerosis and paraproteinemia) [53].
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8.1 Pathogenesis
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The exact pathogenesis of scleromyxedema is unknown, typically affecting middle-aged adults of both sexes equally. The role of the associated monoclonal gammopathy remains a matter of debate, because, for example, paraprotein levels do not correlate with progression of the disease. But clinical remission of scleromyxedema, during the reduction of paraprotein, that follows after autologous hematopoietic stem cell transplantation was described [53, 54].
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8.2 Clinical features
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In the clinical manifestation of scleromyxedema, typically widespread and symmetrically firm, waxy, and closely aligned papules are present (Figure 17).
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Figure 17.
Scleromyxedema. Numerous skin-colored papules of the neck.
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Predilection localizations include the head and neck, upper trunk, forearms, and thighs and the proximal parts of fingers. The surrounding skin is shiny with sclerodermoid appearance. Deep longitudinal furrowing is typically involved on the glabella. Strong and rigid infiltrates of the face can result in the face of a lionlike face. As the condition progresses, erythematous and infiltrated plaques may be present with skin stiffening, sclerodactyly, and decreased motility of the mouth and joints.
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Scleromyxedema is almost always associated with paraproteinemia. The monoclonal gammopathy is usually IgG and the light chains are more commonly lambda. Patients with scleromyxedema can have a number of internal manifestations, such as dysphagia, proximal muscle weakness due to myositis, peripheral neuropathy, arthropathies, carpal tunnel syndrome, restrictive or obstructive lung disease, and also scleroderma-like renal disease [54].
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8.3 Histopathology
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Scleromyxedema is characterized by diffuse deposits of mucin in the upper and middle part of the reticular dermis, increase in collagen deposition in the reticular dermis, and significant proliferation of irregularly distributed fibroblasts. Mucin may fill the walls of myocardial blood vessels as well as vessels of the kidney, the pancreas, adrenal glands, nerves, or lymph nodes [55].
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8.4 Differential diagnosis
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The primary differential diagnosis of scleromyxedema includes systemic sclerosis and scleredema. Other conditions in differential diagnosis with possible presence of mucin in the biopsy include nephrogenic systemic sclerosis. Differential diagnosis of leonine facies includes, for example, lepromatous changes, leishmaniasis, cutaneous lymphoma (T cell, rarely B cell), an actinic reticuloid as chronic actinic dermatitis, systemic amyloidosis, nodular mastocytosis, or sarcoidosis [53].
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8.5 Treatment
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Recommendations are still based on case reports and open-label small case series. Many chemotherapeutics, primarily melphalan, cyclophosphamide, methotrexate, or chlorambucil, have been tried, with no better results but with the risk of significant side effects. IVIg, alone or in combination with systemic medications such as thalidomide or systemic corticosteroids, may be administered as first-line therapy for cutaneous involvement and also systemic manifestations, including the dermatoneurological syndrome. Additional therapies include PUVA, UVA1, systemic retinoids, cyclosporine, electron beam radiation, plasmapheresis, and extracorporeal photochemotherapy with variable and unpredictable results [56].
\n
\n
\n
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9. Scleredema adultorum of Buschke
\n
Scleredema is typically symmetrical diffuse induration and sclerosis of the upper part of the body especially of the trunk due to thickened dermis with mucin deposition and with relationship to diabetes mellitus.
\n
\n
9.1 Pathogenesis
\n
Scleredema is a relatively unusual and rare disease that affects patients of all races. The typical form that is associated with diabetes mellitus is more prevalent in men, while other forms are seen more commonly in women. Irreversible glycosylation of collagen and resistance to degradation lead to an accumulation of collagen deposition. Furthermore, stimulation by insulin, microvascular changes and damage, and hypoxia during diabetes mellitus may increase the synthesis of collagen and mucin which result in a dermal deposition of collagen [57].
\n
\n
\n
9.2 Clinical features
\n
Scleredema adultorum may be divided into three clinical types of scleredema. The first type affects primarily children and middle-aged women. It is preceded by fever, malaise, and an infection (usually streptococcal) of the upper or lower respiratory tract. The localization of this type is the cervicofacial region with extension to the trunk and proximal upper limbs. The cervicofacial region typically affects the perioral localization with difficult opening of the mouth and hindered swallowing. This type usually resolves spontaneously. The second type shares the same clinical features as the first but with very slow manifestation and is more commonly associated with a monoclonal gammopathy [58].
\n
The third type typically affects obese middle-aged men with insulin-dependent diabetes (scleredema diabeticorum). Sclerosis usually starts very slowly and the involvement is persistent. Affected skin is usually erythematous and indurated with typical localization of the posterior region of the neck and the back (Figure 18). The affected skin has peau d’orange appearance. In all three forms, systemic manifestations such as serositis, myositis, dysarthria, dysphagia, parotitis, and ocular and cardiac abnormalities may be present [57, 58, 59].
\n
Figure 18.
Scleredema adultorum with typical localization of the posterior region of the neck and the back with affected erythematous and indurated skin.
\n
\n
\n
9.3 Histopathology
\n
The main histopathological feature is the thickening of the reticular dermis, with atypical large collagen bundles. Mucin deposition is also present among separated collagen bundles. There is no increase in the number of fibroblasts, but the elastic fibers are significantly reduced in number. Mucin is also accumulated in the skeletal muscle and in the heart.
\n
\n
\n
9.4 Treatment
\n
Scleredema which is associated with streptococcal infections is self-limited, thus no therapy is needed. Therapy of scleredema associated with diabetes or a monoclonal gammopathy is more difficult, and no specific treatment is available. Phototherapy as UVA1 or PUVA is the first-line therapy. Systemic and intralesional corticosteroids, intralesional hyaluronidase, antibiotics, methotrexate, cyclosporine, pulse therapy with cyclophosphamide plus oral corticosteroids, tamoxifen, and allopurinol have all been tried, with variable results [58, 59].
\n
\n
\n
\n
10. Endocrine disorders
\n
Some endocrine disorders like diabetes mellitus and hypothyroidism can be accompanied with skin induration and sclerotic changes and may thus be a diagnostic problem for both systemic sclerosis and its localized forms. Endocrine disorders include sclerodactyly as “diabetic cheiroarthropathy” and myxedema in hypothyroidism.
\n
\n
10.1 Diabetic cheiroarthropathy
\n
Diabetes mellitus is associated with a wide variety of rheumatologic manifestations which can significantly affect a patient’s quality of life. One of these manifestations includes diabetic cheiroarthropathy which is associated with type I diabetes. Diabetic cheiroarthropathy affects typically the hands. It is postulated to result from increased glycosylation of collagen in the skin and is associated with retinopathy, nephropathy, and duration of the diabetes [60, 61].
\n
\n
10.1.1 Clinical features
\n
Clinical features include thickened skin and limited joint mobility of the hands and fingers, leading to flexion contractures and an inability to approximate the palmar surfaces of the hands and fingers. Sometimes ischemic ulceration and calcinosis cutis can be present.
\n
Treatment relies primarily on glycemic control and on nonsteroidal anti-inflammatory drugs and physical therapy with physiotherapy. With improved glycemic control, the symptoms and signs can be ameliorated and complete reversal is possible [61].
\n
\n
\n
\n
10.2 Mucinoses associated with thyroid dysfunction
\n
Pretibial myxedema is characterized by cutaneous induration of the shins due to mucin deposition. It is often associated with hyperthyroidism most commonly due to Graves’ disease. Localized myxedema with goiter, exophthalmos, and thyroid acropachy are typical signs of Graves’ disease. Pretibial myxedema is found in 1–5% of patients with Graves’ disease and in up to 25% of those with exophthalmos [62].
\n
\n
10.2.1 Localized myxedema
\n
\n
10.2.1.1 Clinical features
\n
Localized myxedema presents as erythematous, yellowish or skin-colored waxy induration in a form of a nodulus or plaques. Typical localizations include ventral or anterolateral parts of the lower legs or the feet (Figure 19). In early phases localized myxedema can also present as a diffuse non-pitting edema of the shins or feet that evolves into lymphedema. Even more rarely, localized myxedema affects the face, shoulders, upper extremities, the lower abdomen, scars, or donor graft sites. Large plaques are often painful and pruritic. When present, hypertrichosis and hyperhidrosis are confined to the pretibial myxedematous skin [63, 64].
\n
Figure 19.
Pretibial myxedema presents as erythematous waxy induration and nodulus on the ventral part of the shank.
\n
\n
\n
10.2.1.2 Treatment
\n
First-line therapy such as topical corticosteroids or their application under occlusive dressings can be used. In some cases intralesional injection of corticosteroids can be effective. In a patient with lymphedema, medical treatments including IVIg, rituximab, plasmapheresis, and their combination with surgical treatment may have some benefit [63, 65].
\n
\n
\n
\n
10.2.2 Generalized myxedema
\n
Generalized myxedema is a manifestation of hypothyroidism where mucin is deposited in the dermis, leading to waxiness of the skin. This condition is caused by a quantitative or functional deficiency of thyroxine. Impaired degradation of mucin and/or increased synthesis is suggested as the main cause.
\n
\n
10.2.2.1 Clinical features
\n
The typical skin is pale, cool, waxy, and dry. Anhidrosis as an absence of sweating may lead to ichthyosis or eczema “craquelé.” Hair and nails are dry and diffuse non-scaring alopecia is also common. A yellowish hyperkeratosis of the palms may be present. Sometimes purpura on the extremities and skin xanthomas may be observed [66].
\n
\n
\n
10.2.2.2 Treatment
\n
Early treatment of hypothyroidism is crucial for reduction or cessation of skin involvement and overall symptoms of the disease.
\n
\n
\n
\n
\n
\n
11. Amyloidosis
\n
The cutaneous amyloidosis represents a heterogeneous group of conditions in which amyloid, as a fibrillar material that can result from the pathological degradation of various proteins, is deposited in the skin. In primary cutaneous amyloidosis, the deposits are derived from keratin (macular, lichen, biphasic) or immunoglobulin light chains (nodular) [67].
\n
The specific cutaneous lesions of primary systemic amyloidosis are waxy, translucent, or purpuric papules, nodules, and plaques. Amyloid infiltration of the skin may produce thickening and stiffness. Typical localization may be on the limbs but sometimes also on the trunk. This is characteristic of AL amyloid, due to a plasma cell disorder in hematological malignancies. Primary systemic amyloidosis is due to a plasma cell dyscrasia, while secondary systemic amyloidosis arises from chronic inflammatory conditions such as rheumatoid arthritis or in the setting of chronic infections [67, 68].
\n
Skin biopsy reveals accumulation of amyloid with characteristic staining (Congo red) properties under polarizing microscopic examination. Immunofixation of serum or urine is necessary for unambiguous identification of a monoclonal component [69].
\n
Treatment of all forms of amyloidosis is challenging; although the primary cutaneous forms are not life-threatening, primary systemic amyloidosis can carry a poor prognosis for a patient [70].
\n
\n
\n
12. Conclusion
\n
Systemic sclerosis mimics include a variety of diseases that may resemble systemic connective tissue diseases such as SSc. Above all, the most common diseases are discussed in this chapter.
\n
The basis of proper diagnosis and treatment is the interdisciplinary collaboration of rheumatology and dermatology with the possibility of biopsy tissue collection and histological verification of the disease.
\n
A carefully performed clinical history and physical examination may distinguish these scleroderma mimic syndromes from systemic sclerosis (SSc, scleroderma) and from each other. The distribution and the quality/texture of skin involvement (in SSc typically: sclerodactyly, puffy fingers, ischemic defects/pitting scars/digital ulcers/gangrenes, telangiectasias, calcinosis), the presence of Raynaud’s phenomenon (typically signs of a secondary Raynaud’s phenomenon such as onset after the age of 40, asymmetry, thumb involvement, ischemic pain, history of symptoms <3 years, worsening attacks) or abnormal nail fold capillary microscopy (characteristic scleroderma patterns in SSc), the presence and type of associated systemic manifestations (typical organ involvement characteristic for SSc), and the association with particular concurrent diseases or specific laboratory parameters (SSc-specific autoantibodies such as anti-topoisomerase I, anti-centromere, anti-RNA-polymerase III) can be of substantial help in refining the diagnosis.
\n
In some cases, a full-thickness skin biopsy is helpful to confirm the clinical suspicion. Effective therapies are available for some of these conditions, whereas others are more refractory. For this reason, a prompt diagnosis is important to guide treatment decisions wisely, to spare the patients from ineffective treatments, to facilitate appropriate diagnostic evaluations, and to allow for accurate determination of prognosis [71].
\n
\n
Acknowledgments
\n
This chapter was supported by NV18-01-00161 A, MHCR 023728 and GAUK 312218.
\n
\n',keywords:"localized scleroderma, lichen sclerosus, eosinophilic fasciitis, nephrogenic systemic fibrosis, scleromyxedema, scleredema",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68564.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68564.xml",downloadPdfUrl:"/chapter/pdf-download/68564",previewPdfUrl:"/chapter/pdf-preview/68564",totalDownloads:452,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 26th 2019",dateReviewed:"July 11th 2019",datePrePublished:"August 12th 2019",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Many clinical conditions are presenting with sclerosis of the skin and with tissue fibrosis. These conditions may be confused with systemic sclerosis (SSc, scleroderma). These diseases and disabilities are generally referred to as systemic sclerosis mimics or scleroderma-like syndromes. These disorders have very different etiologies and often an unclear pathogenetic mechanism. Distinct clinical characteristics, skin histology, and disease associations may allow distinguishing these conditions from systemic sclerosis and from each other. A histopathological examination with clinicopathological correlation for diagnosis is important to spare the patients from ineffective treatments and inadequate management. In this chapter, we discussed localized scleroderma, lichen sclerosus, nephrogenic systemic fibrosis, eosinophilic fasciitis, scleromyxedema, and scleredema. These are often detected in the primary care setting and referred to rheumatologists for further evaluation. Rheumatologists, or preferably in collaboration with a dermatologist, must be able to promptly recognize them to provide valuable prognostic information and appropriate treatment options for affected patients.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68564",risUrl:"/chapter/ris/68564",signatures:"Ondřej Kodet and Sabína Oreská",book:{id:"8269",title:"New Insights into Systemic Sclerosis",subtitle:null,fullTitle:"New Insights into Systemic Sclerosis",slug:"new-insights-into-systemic-sclerosis",publishedDate:"September 18th 2019",bookSignature:"Michal Tomcik",coverURL:"https://cdn.intechopen.com/books/images_new/8269.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"193284",title:"Dr.",name:"Michal",middleName:null,surname:"Tomcik",slug:"michal-tomcik",fullName:"Michal Tomcik"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Localized scleroderma, morphea",level:"1"},{id:"sec_2_2",title:"2.1 Introduction",level:"2"},{id:"sec_3_2",title:"2.2 Epidemiology",level:"2"},{id:"sec_4_2",title:"2.3 Pathogenesis",level:"2"},{id:"sec_5_2",title:"2.4 Clinical features",level:"2"},{id:"sec_6_2",title:"2.5 Plaque-type morphea, circumscribed morphea",level:"2"},{id:"sec_7_2",title:"2.6 Linear morphea",level:"2"},{id:"sec_8_2",title:"2.7 “En coup de sabre”",level:"2"},{id:"sec_9_2",title:"2.8 Generalized morphea",level:"2"},{id:"sec_10_2",title:"2.9 Laboratory findings",level:"2"},{id:"sec_11_2",title:"2.10 Histopathology",level:"2"},{id:"sec_12_2",title:"2.11 Differential diagnosis",level:"2"},{id:"sec_13_2",title:"2.12 Treatment",level:"2"},{id:"sec_14_2",title:"2.13 Topical and intralesional treatment",level:"2"},{id:"sec_15_2",title:"2.14 Systemic treatment",level:"2"},{id:"sec_17",title:"3. Morpheaform inflammatory syndromes/conditions",level:"1"},{id:"sec_17_2",title:"3.1 Lipodermatosclerosis",level:"2"},{id:"sec_17_3",title:"3.1.1 Introduction",level:"3"},{id:"sec_18_3",title:"3.1.2 Clinical features",level:"3"},{id:"sec_19_3",title:"3.1.3 Histopathology",level:"3"},{id:"sec_20_3",title:"3.1.4 Differential diagnosis",level:"3"},{id:"sec_21_3",title:"3.1.5 Treatment",level:"3"},{id:"sec_23_2",title:"3.2 Injection of vitamin K",level:"2"},{id:"sec_24_2",title:"3.3 Vaccination-associated morphea",level:"2"},{id:"sec_25_2",title:"3.4 Paraffin and silicone injections or silicone implants",level:"2"},{id:"sec_26_2",title:"3.5 Porphyrias",level:"2"},{id:"sec_27_2",title:"3.6 Radiation-induced morphea",level:"2"},{id:"sec_27_3",title:"3.7 Differential diagnosis",level:"3"},{id:"sec_30",title:"4. Lichen sclerosus",level:"1"},{id:"sec_30_2",title:"4.1 Epidemiology",level:"2"},{id:"sec_31_2",title:"4.2 Pathogenesis",level:"2"},{id:"sec_32_2",title:"4.3 Clinical features",level:"2"},{id:"sec_33_2",title:"4.4 Histopathology",level:"2"},{id:"sec_34_2",title:"4.5 Differential diagnosis",level:"2"},{id:"sec_35_2",title:"4.6 Treatment",level:"2"},{id:"sec_37",title:"5. Eosinophilic fasciitis",level:"1"},{id:"sec_37_2",title:"5.1 Clinical feature",level:"2"},{id:"sec_38_2",title:"5.2 Histopathology",level:"2"},{id:"sec_39_2",title:"5.3 Treatment",level:"2"},{id:"sec_41",title:"6. Nephrogenic systemic fibrosis",level:"1"},{id:"sec_41_2",title:"6.1 Clinical features",level:"2"},{id:"sec_42_2",title:"6.2 Histopathology",level:"2"},{id:"sec_43_2",title:"6.3 Treatment",level:"2"},{id:"sec_45",title:"7. Stiff skin syndrome",level:"1"},{id:"sec_45_2",title:"7.1 Clinical features",level:"2"},{id:"sec_46_2",title:"7.2 Histopathology",level:"2"},{id:"sec_47_2",title:"7.3 Treatment",level:"2"},{id:"sec_49",title:"8. Scleromyxedema",level:"1"},{id:"sec_49_2",title:"8.1 Pathogenesis",level:"2"},{id:"sec_50_2",title:"8.2 Clinical features",level:"2"},{id:"sec_51_2",title:"8.3 Histopathology",level:"2"},{id:"sec_52_2",title:"8.4 Differential diagnosis",level:"2"},{id:"sec_53_2",title:"8.5 Treatment",level:"2"},{id:"sec_55",title:"9. Scleredema adultorum of Buschke",level:"1"},{id:"sec_55_2",title:"9.1 Pathogenesis",level:"2"},{id:"sec_56_2",title:"9.2 Clinical features",level:"2"},{id:"sec_57_2",title:"9.3 Histopathology",level:"2"},{id:"sec_58_2",title:"9.4 Treatment",level:"2"},{id:"sec_60",title:"10. Endocrine disorders",level:"1"},{id:"sec_60_2",title:"10.1 Diabetic cheiroarthropathy",level:"2"},{id:"sec_60_3",title:"10.1.1 Clinical features",level:"3"},{id:"sec_62_2",title:"10.2 Mucinoses associated with thyroid dysfunction",level:"2"},{id:"sec_62_3",title:"10.2.1 Localized myxedema",level:"3"},{id:"sec_62_4",title:"10.2.1.1 Clinical features",level:"4"},{id:"sec_63_4",title:"10.2.1.2 Treatment",level:"4"},{id:"sec_65_3",title:"10.2.2 Generalized myxedema",level:"3"},{id:"sec_65_4",title:"10.2.2.1 Clinical features",level:"4"},{id:"sec_66_4",title:"10.2.2.2 Treatment",level:"4"},{id:"sec_70",title:"11. Amyloidosis",level:"1"},{id:"sec_71",title:"12. Conclusion",level:"1"},{id:"sec_72",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Sehgal VN, Srivastava G, Aggarwal AK, Behl PN, Choudhary M, Bajaj P. Localized scleroderma/morphea. International Journal of Dermatology. 2002;41(8):467-475\n'},{id:"B2",body:'Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. 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Lancet. 2003;362(9378):118-123\n'},{id:"B37",body:'Bunker CB. EDF lichen sclerosus guideline. Journal of the European Academy of Dermatology and Venereology. 2017;31(2):e97-ee8\n'},{id:"B38",body:'Wang JB, Yan H, Yang HY, Si JY, Jia LP, Li K, et al. Histopathological and ultrastructural changes of lichen sclerosus et atrophicus on the vulva. Chinese Medical Journal. 1991;104(10):868-871\n'},{id:"B39",body:'Staricco RG. Lichen striatus: A study of fifteen new cases with special emphasis on the histopathological changes and a review of the literature. A.M.A. Archives of Dermatology. 1959;79(3):311-324\n'},{id:"B40",body:'Singh L, Sengar M, Goyal S, Mansi M, Khurana N, Mohta A. Childhood phimosis secondary to lichen sclerosus: Is there a spatial pattern of histopathological changes? The American Journal of Dermatopathology. 2018;40(11):824-828\n'},{id:"B41",body:'Kai A, Lewis F. Long-term use of an ultrapotent topical steroid for the treatment of vulval lichen sclerosus is safe. Journal of Obstetrics and Gynaecology. 2016;36(2):276-277\n'},{id:"B42",body:'van der Avoort IA, Tiemes DE, van Rossum MM, van der Vleuten CJ, Massuger LF, de Hullu JA. Lichen sclerosus: Treatment and follow-up at the departments of gynaecology and dermatology. Journal of Lower Genital Tract Disease. 2010;14(2):118-123\n'},{id:"B43",body:'Lakhanpal S, Ginsburg WW, Michet CJ, Doyle JA, Moore SB. Eosinophilic fasciitis: Clinical spectrum and therapeutic response in 52 cases. Seminars in Arthritis and Rheumatism. 1988;17(4):221-231\n'},{id:"B44",body:'Onajin O, Wieland CN, Peters MS, Lohse CM, Lehman JS. Clinicopathologic and immunophenotypic features of eosinophilic fasciitis and morphea profunda: A comparative study of 27 cases. Journal of the American Academy of Dermatology. 2018;78(1):121-128\n'},{id:"B45",body:'Mazori DR, Femia AN, Vleugels RA. Eosinophilic fasciitis: An updated review on diagnosis and treatment. 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Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. The American Journal of Pathology. 2010;176(2):563-574\n'},{id:"B70",body:'Dember LM. Emerging treatment approaches for the systemic amyloidoses. Kidney International. 2005;68(3):1377-1390\n'},{id:"B71",body:'Varga J, Denton C, Wigley F, Allanore Y, Kuwana M. Scleroderma. 2nd ed. Cham: Springer International Publishing; 2017\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ondřej Kodet",address:"ondrej.kodet@vfn.cz",affiliation:'
Department of Dermatology and Venereology, First Faculty of Medicine, Charles University, Czech Republic
Institute of Anatomy, First Faculty of Medicine, Charles University, Czech Republic
BIOCEV, First Faculty of Medicine, Charles University, Czech Republic
Institute of Rheumatology, Department of Rheumatology, First Faculty of Medicine, Charles University, Czech Republic
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