For several years now, June 29th has been marked as World Scleroderma Day. The observance was established by FESCA (Federation of European Scleroderma Associations) during a meeting in 2008, originating as a European-level event. By 2010, participants at the first Systemic Sclerosis World Congress decided to expand Scleroderma Day into a global phenomenon. Since then, associations from around the world have coordinated annual initiatives and awareness campaigns aimed at increasing knowledge about the symptoms, manifestations, and implications—both physical and psychological—of scleroderma. The ultimate goal is to raise public awareness regarding the challenges faced by those living with scleroderma and to promote the early diagnosis of a condition for which there is no cure, though timely, highly specialized treatment is available.

Pathophysiology of Scleroderma

Scleroderma—also known as "systemic sclerosis"—is a rare autoimmune disease that is estimated to affect approximately 25,000 individuals in Italy. The condition primarily impacts connective tissue in its various forms—a type of tissue characterized by cells embedded within an extracellular matrix of varying density, which serves the fundamental role of supporting and connecting surrounding tissues and organs. In this disease, the mechanisms responsible for regulating both the quantity and quality of the extracellular matrix fail, leading to a pathological process known as "fibrosis"—an excessive accumulation of extracellular matrix, specifically collagen—which can affect the skin, eyes, blood vessels, and various internal organs.

The range and severity of clinical manifestations vary significantly, making the diagnosis of scleroderma a delicate assessment—yet one that is critically important for initiating an appropriate, personalized therapeutic pathway as early as possible. Nevertheless, the most common signs characterizing scleroderma include the hardening of the skin—medically termed "sclerosis"—which appears shiny, taut, and hyperpigmented. Another hallmark is Raynaud’s phenomenon, in which the hands and/or feet change color—shifting from pale to purplish and subsequently to red—due to the sudden, intense constriction of small and medium-sized peripheral blood vessels. When associated with scleroderma, Raynaud’s phenomenon is often accompanied by edema (swelling) of the fingers, joint inflammation and stiffness, patches of hyperkeratosis, calcinosis (the formation of calcium salt deposits within the skin and underlying tissues), and a susceptibility to ulceration in the extremities—particularly on the fingertips, the skin folds between the fingers, and the skin overlying the extensor surfaces of the joints. These complications are extremely debilitating, painful, and can sometimes lead to a loss of function.

Regarding the ulcerative aspect in particular, experts recommend taking special care of the hands and feet by using gloves and socks made of natural fibers, wearing comfortable, wide-fitting shoes, and employing insoles to alleviate discomfort caused by calcinosis. They also advise using gentle, non-stripping cleansers—which help preserve the skin’s natural moisture—and applying emollient and exfoliating creams, such as those containing urea.

Scleroderma is further subdivided into “localized scleroderma” or “diffuse scleroderma,” based on the extent of skin involvement and whether other organs are affected. In the former case, the disease is limited to the skin—specifically the hands and the more distal portions of the upper limbs. In the latter case, skin thickening affects the entire body, and other areas—such as the esophagus, the gastrointestinal tract, the lungs, the kidneys, and the heart—may also be compromised to varying degrees. The cumulative, deleterious effects of fibrosis and vasculopathy (the progressive occlusion of blood vessels) can, in extreme cases, lead to the development of pulmonary arterial hypertension, interstitial lung disease, or renal or cardiac failure.

The etiology of scleroderma remains unknown; however, its distinct and complex clinical presentation can be traced back to alterations in three separate functions: the immune response, the regulation of blood vessel wall homeostasis, and the production of collagen and other components of the extracellular matrix. While the extent to which these three aspects overlap and influence one another in the pathogenesis of scleroderma is not fully understood, it is widely recognized that their consequences have a systemic impact, intersecting with the precise cellular regulation of energy processes—collectively known as "metabolism." A state of chronic inflammation and a susceptibility to thrombotic events—the formation of fibrotic vascular obstructions—are hallmark features not only of scleroderma but also of "metabolic syndrome." The latter is a cluster of metabolic dysfunctions rooted in insulin resistance, which places affected individuals at an increased risk of developing cardiovascular disease. Studies have shown that a significant number of patients with scleroderma also exhibit insulin resistance. This underscores the importance of targeted diagnostic efforts to identify—and subsequently treat—these individuals early and comprehensively, particularly those whose cardiovascular risk, stemming from scleroderma-related complications, is further amplified by the risks inherent to metabolic syndrome.