The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

Background Recent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the infl ammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders. Objective To study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population. Methods NLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin. Results Conditional analyses revealed a signifi cant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fi brosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA. Conclusions Our results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fi brosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.Several lines of evidence have recently raised the paradigm of the contribution of innate immune mechanisms to autoimmunity. The concept of innate immunity as a primitive system, being nonspecifi c in most aspects of both recognition and response, has been transformed by the identifi cation of the membrane-associated Toll-like receptors and the cytosol-expressed Nod-like receptors (NLR). 1 2 The NLR family, pyrin domain containing 1 (NLRP1), is a member of the NLR family, which are cytoplasmic proteins that sense endogenous microbial products and metabolic stresses, thereby stimulating innate immunity. NLR associated with other proteins form multiprotein cytoplasmic complexes, the so-called infl ammasomes. NLRP1 provides a scaffold for the assembly of the infl ammasome that activates caspases 1 and 5, which subsequently promote the processing and maturation of the infl ammatory cytokines, pro-interleukin 1β (IL-1β), Some studies have highlighted a potential role of IL-1β in fi brotic disorders. 5 6 In systemic sclerosis (SSc), the prototypic fi brotic connective tissue disorder, IL-1β has been reported to induce the fi brogenic phenotype of SSc fi broblasts and to increase strikingly in vitro the production of extracellular matrix by these cells. 7 8 SSc is a chronic autoimmune disease with a complex pathogenesis driven by a combination of genetic risk factors and environmental events that ...

SSc is a multisystem disease characterized by an unpredictable course, high mortality and resistance to therapy. The complexity and severity of SSc is a growing burden on the health-care systems. As a result, researchers are seeking new therapeutic strategies for effectively managing these patients. Disease registries are used to support care management efforts for groups of patients with chronic diseases and are meaningful to capture and track key patient information to assist the physicians in managing patients. For these reasons, SSc surveys, research associations and consortiums are pivotal to conduct ongoing research and data collection to enhance disease knowledge and support research projects. Currently, there are several national SSc registries in the UK, Germany, USA, Canada, Brazil and Australia. There is also an international registry established by the European League Against Rheumatism scleroderma trial and research (EUSTAR) called minimal essential data set (MEDS) Online, which collects data from over 8000 patients from 92 centres worldwide, including 21 European centres and 9 centres outside Europe. By collecting, analysing and disseminating data on disease progression and patient responses to long-term disease management strategies, registries help to improve understanding of the disease and keep medical professionals up to date on the latest advances.