title: The molecular pathogenesis of morphoea: from genetics to future treatment targets.
abstract: A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches.
authors.affiliation: The Royal Free London NHS Foundation Trust, Department of Dermatology, London, U.K.|University College London, Centre for Rheumatology and Connective Tissue Diseases, Division of Medicine, London, U.K.
authors.forename: A M
authors.initials: AM
authors.lastname: Saracino
authors.affiliation: University College London, Centre for Rheumatology and Connective Tissue Diseases, Division of Medicine, London, U.K.|The Royal Free London NHS Foundation Trust, Department of Rheumatology, London, U.K.
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: The Royal Free London NHS Foundation Trust, Department of Dermatology, London, U.K.
authors.forename: C H
authors.initials: CH
authors.lastname: Orteu
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004817:Epidermis / Q000502:physiology; D044127:Epigenesis, Genetic / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology; D005544:Forecasting; D015870:Gene Expression / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D010375:Pedigree; D012594:Scleroderma, Localized / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016207:Cytokines; D006680:HLA Antigens