Systemic sclerosis – dermatological aspects. Part 1: Pathogenesis, epidemiology, clinical findings

Authors


  • Section Editor 
    Prof. Dr. Jan C. Simon, Leipzig

  • Sclerosis is a uniform reaction of the skin and the connective tissue framework of numerous internal organs to different triggers. Dermatologically, circumscript scleroderma can be differentiated from systemic scleroderma with an inflammatory background and from skin sclerosis of other cause.

  • Pathogenetically, the vasculature, connective tissue and immune system are involved; the temporal sequence and relative significance of the different components is unclear.

  • Animal models are available only to a limited extent. Cutaneous chronic graft-versus-host disease reflects only partial aspects of PSS.

  • A genetic predisposition to systemic scleroderma is probable. Various triggers can in face of a predisposing immunogenetic and inflammatory background lead to manifestation or maintenance of the disease.

  • Systemic scleroderma is characterized by an antiendothelial environment that leads to reduced neovascularization and the clinical signs and symptoms of a vasculopathy.

  • Fibrosis is due to an increased deposition and reduced degradation of components of the extracellular matrix. Cellular (fibroblasts) as well as extracellular components (matrix metalloproteinases and their inhibitors) are involved.

  • Elements of cellular and humoral immunity are centrally involved in the pathogenesis of systemic scleroderma. Cytokines, adhesion molecules as well as specific autoantibodies are associated with disturbances of the vascular system and connective tissue in a not yet clearly defined relationship.

  • The diagnosis of systemic scleroderma is based on the presence of proximal diffuse sclerosis, basal lung fibrosis, sclerodactyly and acral necrotic areas. Additional criteria are currently being discussed and will lead to an adjustment of diagnostic criteria.

  • Clinically and immunoserologically two forms of systemic scleroderma can be differentiated, the limited and diffuse form.

  • The Raynaud phenomenon is positive in over 90 % of all patients with systemic scleroderma. It describes an attack-like reduced perfusion, blood stasis and reactive hyperperfusion with the colors white-blue-red. Two phases including the reduced perfusion (white) are required for the diagnosis.

  • Digital ulcers are clinical signs of the underlying vasculopathy and result in a severe impairment of quality of life of those affected. They therefore represent a central therapeutic goal in the management of scleroderma patients.

  • Important clinical signs and symptoms of skin sclerosis are loss of facial expression (mask face), microstomia and perioral folds.

  • Internal organs are affected to an individually variable degree and course. Important for the prognosis of the affected is particularly the involvement of heart, lungs and kidneys. A great discrepancy exists between post mortem findings and clinically symptomatic lesions.

  • Pulmonary arterial hypertension (PAH) is a prognostically significant complication of both subtypes of scleroderma. Its early recognition and therapy is important for the survival of the patient.

  • Renal crises are important complications of renal involvement. They are particularly seen in diffuse scleroderma of an early stage in the first two years and correlate with administration of systemic corticosteroids. These should therefore only be employed on a short-term basis.

  • Sicca symptoms of eyes, mouth and genital mucosa should be specifically sought and documented. Men should be asked if symptoms of erectile dysfunction are present.

Prof. Dr. Michael Sticherling, Department of Dermatology, University of Erlangen, Ulmenweg 18, D-91054 Erlangen, Germany. Tel.: +49-9131-85-33851, Fax: +49-9131-85-36175, E-mail: michael.sticherling@uk-erlangen.de

Summary

Systemic sclerosis is a chronic inflammatory multiorgan disease belonging to the group of collagen-vascular disorders. With a prevalence of 10/100,000 inhabitants it may be regarded a rather rare disease. Its etiology and pathogenesis have still not been elucidated in detail, especially with regard to the differential involvement of skin and the cause of the clinically heterogeneous disease courses. Various components of the vasculature, connective tissue as well as the immune system are involved in a yet unknown sequence and significance. Patients need to be cared for in an interdisciplinary fashion depending on the individual organ involvement. Apart from the skin, the heart, kidneys and lungs are mainly affected in addition to frequent gastrointestinal and musculoskeletal symptoms. Clinically two distinct subsets may be separated, acral (also termed limited) and diffuse scleroderma, which are characterized by anti-centromere and anti-Scl-70/topoisomerase-1 antibodies, respectively. Recent data demonstrate a poor prognosis even in limited disease when pulmonary arterial hypertension develops at an early stage. In diffuse disease sudden and rapid onset will result in a sclerosis of major internal organs and early death in many cases.

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