Being able to identify the hallmark signs of disease is not always enough. Clinicians may recognize the taut and contracted, statue-like skin that characterizes scleroderma, but failure to identify the systemic manifestations of the disease can have deadly results. Scleroderma can affect multiple systems and virtually every body organ. Earlier diagnosis of the disease’s systemic form can help improve prognosis and ultimately increase survival rates for affected patients.
Systemic scleroderma (SSc), also known as systemic sclerosis, is a chronic connective tissue disease that is characterized by vasculopathy, autoimmunity, and inflammation.1,2 As SSc develops, the body’s fibroblasts produce too much collagen, leading to fibrosis of the skin and the internal organs.1,3 It was not until the 20th century that scleroderma was shown to affect the internal organs—resulting in the devastating outcomes that are now associated with SSc.
SSc is more prevalent than many clinicians realize. About 300,000 people in the United States have a form of scleroderma, and nearly one-third of these (perhaps 75,000 to 100,000) are believed to be affected by its systemic variant.1,4,5
When SSc invades the major internal organs, especially the lungs, kidneys, and heart, the prognosis is poor. SSc carries a survival rate of only 55% at 10 years postdiagnosis—the highest risk of fatality among connective tissue diseases.1 Therefore, when any form of scleroderma is suspected, it is imperative that the patient be examined for multisystem involvement.
Patient presentation varies, depending on the form of scleroderma. To recognize the symptoms, the clinician must first understand the various classifications of the disease. Scleroderma is often seen as a spectrum of illness, ranging from mild to life-threatening. The two major variants are localized scleroderma (with fibrosis restricted to the skin) and systemic scleroderma (in which fibrosis affects the internal organs).6
Localized scleroderma may manifest as linear scleroderma, with band-like thickened skin lesions that begin to develop during childhood and usually affect one area, such as an arm or a leg; involvement of the forehead, face, or scalp is referred to as en coup de sabre (“cut of the sword”). By contrast, morphia (which can be limited or generalized) appears as circumscribed sclerotic patches or plaques on the skin and can be intermittent. These lesions vary in size but are usually round or oval, with purple edges and a waxy appearance6 (see Figure 1).
Systemic scleroderma comprises both cutaneous and noncutaneous involvement (although scleroderma sine sclerosis, fibrosis of the internal organs with no skin lesions, is rare). Typically, limited systemic scleroderma affects only the hands, the face, and the distal extremities (see Figure 2). It was originally referred to as CREST syndrome, an acronym for calcinosis of the digits, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias.6 The lungs may eventually be affected.7
Diffuse systemic scleroderma usually begins with Raynaud’s phenomenon, followed by sclerosis of the proximal extremities, the trunk, and the face, and progresses to dysfunction of the lungs, kidneys, heart, and gastrointestinal (GI) system.1,8 For the purposes of this review, further mentions of “SSc” will refer to the diffuse form.
Although presentation varies in patients with SSc, vascular changes are among its earliest presenting signs (see Table 16,8,9 for a list of clinical manifestations). Raynaud’s phenomenon accounts for 70% of SSc patients’ first reported symptoms, and it occurs in 90% to 99% of patients with systemic disease.10,11
Raynaud’s phenomenon is the episodic constriction of blood vessels in response to environmental factors such as cold, stress, or emotional changes. This circulation disturbance is evidenced by color changes in the digits and the development of digital ulcers resulting from ischemia (found in almost half of all patients).11,12 It manifests as a series of changes in appearance: white or pale as a result of vasospasm, cyanotic from ischemia, then red or flushed as the blood flow returns.10,11
Raynaud’s phenomenon may be present for many years before any other clinically significant symptoms or systemic manifestations occur. Even among patients who do not experience all of the skin changes associated with Raynaud’s phenomenon, most report digital pallor11 (see Figure 3). Care of digital ulcers is required to prevent potentially serious sequelae, including osteomyelitis and soft-tissue necrosis12,13 (see Figure 4).
Once patients with SSc have begun to experience circulation problems and blood vessel damage, cutaneous changes result. Skin edema occurs, manifesting in swollen, pruritic hands and digits.14 Over time, the skin hardens and thickens over the digits, extremities, face, and trunk—all resulting from vascular dysfunction and oxidative stress, followed by immunologic activation and inflammation.1,3,15 The tight, fibrotic skin that results is the hallmark of SSc1,3 (see Figure 5).