Systemic sclerosis

_ERN Re-CONNET  

Versione in italiano

WHAT IS IT
Systemic sclerosis (SSc), or Scleroderma, is a rare autoimmune disease of unknown etiology potentially able to affect any organ or tissue and thus variably expressed among distinct persons. SSc is a chronic disorder, characterized by early vascular abnormalities, activation of immune system with inflammation and autoantibody production, and finally fibrosis of the skin and various internal organs. Skin fibrosis (“skin thickness”) represents the hallmark of the disease and, together with digital ulcers and musculoskeletal involvement, deeply affects the overall quality of life. SSc is a severe disease: SSc patients have a 1.5-7 times higher risk of mortality. The prognosis is related to presence and extent of organ involvement, with lung and heart involvement as major determinant of mortality.

WHAT ARE THE MANIFESTATIONS of IgG4-RD AND HOW IS IT RECOGNIZED
The most frequent manifestations of SLE are:

• Raynaud’s phenomenon, i.e. discoloration of body’s extremities (mainly hands and feet) in response to cold exposure or emotional stress; fingers became white, then blue end eventually red;
• Puffy fingers;
• Articular pain; Raynaud’s phenomenon represents in all cases the first manifestation of the disease.

Raynaud’s phenomenon is a common manifestation, especially in young women, being present in 5 to 15% of females between 15 and 40 years. In most cases, it represents a benign response to cold exposure or emotional stress and is not associated with underlying diseases.
Recognizing those patients with Raynaud phenomenon possibly related to SSc or other connective tissue disease is of cardinal importance; to do so, two simple exams are needed: capillaroscopy and detection of anti-nuclear antibodies. SSc, indeed, is associated with ANA positivity and presence of specific antibodies, as anti-centromere or anti-topoisomerase I, anti-RNA polymerase III or other rare antibodies.
Skin fibrosis and organ involvement usually follow the early vascular manifestations, and their early recognition allow to improve patient’s outcome.

WHO IS AFFECTED
SSc can present at any age, although young women are more frequently affected.

HOW DO WE TREAT IT 
Milder cases are usually treated with vasoactive drugs (such as nifedipine and other calcium-channel blockers) and immunomodulant as hydroxychloroquine.
Patients with severe Raynaud or digital ulcers or pulmonary arterial hypertension will receive vasoactive therapy beside nifedipine, as intravenous iloprost, bosentan, ambrisentan or macitentan, sildenafil, riociguat or selexipag. Immunosuppressive therapy (mycophenolate, methotrexate, cyclophosphamide and other) is needed for skin fibrosis and organ involvement, including lung, heart, kidney and gastrointestinal tract.
For refractory or resistant patients, therapy with biologic therapy with anti-CD20 rituximab, intravenous or subcutaneous immunoglobulins, or anti-IL6 tocilizumab could be considered; this latest has been recently approved for treatment of SSc-related interstitial lung disease (ILD).
Recently, the anti-fibrotic drug nintedanib has been approved for treatment of SSc-related ILD, leading to stabilization of lung function. For selected severe cases, haematopoietic stem cell transplantation could also be offered.

SPECIFIC SERVICES OFFERED TO PATIENTS AT SAN RAFFAELE HOSPITAL
All patients with SSc are followed up in a dedicated Scleroderma Clinic (Systemic Sclerosis and Cardiovascular Immunopathology Clinic), which integrates the skills of rheumatologists and immunologists expert in the management of this disease with the contribution of a dedicated team which includes: cardiologist, arrhythmologist, dermatologist, pneumologist, gastroenterologist and haemagologist; a great contribution derives from an integrated team for the diagnosis and management of pulmonary arterial hypertensions and from a dedicated Woud Care Clinic, dedicated to the advanced management of digital ulcers by specialized personell who completed a II degree Master in Wound Care.
The Systemic Sclerosis and Cardiovascular Immunopathology Clinic allows a great reduction of waiting list (30-45 days of a non-complicated first evaluation), and the availability of weekly access dedicated to emergency. All patients with SSc are followed-up by the same multidisciplinary team guided by two expert physician (rheumatologist and immunologist), allowing the strengthen of a fruitful physician-patient relationship.
Patients followed-up at Scleroderma Clinic receive all needed support by the Italian patient’s association GILS (Gruppo Italiano Lotta alla Sclerodermia), whose volunteers are weekly present with a help desk during the Scleroderma Clinic. Pregnant patients with SSc are also followed up in the Hospital Pregnancy Clinic, which consists in a team of gynecologists/obstetricians visiting in synergy with an immunologist. Each patient case is regularly discussed at the end of the clinic sessions and further review at least on a weekly basis.
For the treatment of most severe cases, participation in interventional clinical trials with new drugs is offered. In selected and severe cases, access to innovative, off-label treatments are also offered.
Finally, the strict collaboration with the Haematology and Bone Marrow Transplant Unit allows to systematically evaluate eligibility for stem cell transplantation in selected severe and rapidly progressive cases. co All SSc patients, finally, have direct contact of physicians dedicated to Scleroderma Clinic. Besides patient care, the Sclerdoerma clinic also has a strong commitment to clinical and translational research and with both Italian and European network dedicated to SSc, as Italinan Society of Rheumatology (SIR), the EULAR scleroderma trials and research group (EUSTAR) and the World Scleroderma Foundation (WSF).

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REFERRING DOCTORS for this desease
at Ospedale San Raffaele