Scleroderma is categorized into localized and systemic varieties. Localized scleroderma consists of morphea and linear scleroderma, which is manifest as sclerotic lesions of the skin without visceral involvement. Systemic sclerosis, characterized by inflammation and fibrosis in the skin (see Plate 5-55), is also associated with internal organ involvement. It is classified into four major clinical subtypes: limited cutaneous scleroderma (lcSSc) (also called CREST syndrome [Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia]), diffuse cutaneous scleroderma (dcSSc), systemic sclerosis sine scleroderma, and scleroderma overlap. Limited disease is more common than diffuse disease in a ratio of 2 : 1.

In addition to the skin, systemic sclerosis involves the blood vessels, joints, skeletal muscle, and, frequently, internal organs such as the gastrointestinal tract, heart, kidney, and lungs. In the United States, the incidence of scleroderma is about 20 new cases per million adults annually, with a prevalence of 240 per million. The female-to-male incidence ratio is 4 : 1, and the peak age at onset is between 30 and 50 years. White persons develop scleroderma more commonly than black persons (4 : 1) and more often tend to have limited disease. Afflicted black individuals are more likely to have severe disease (dcSSc) and overall have a worse outcome.

ETIOLOGY AND PATHOGENESIS

The etiology of scleroderma remains unknown. An individual with a susceptible genetic background may encounter an inciting factor such as infection, organic solvents, drugs, or environmental agents.

Clinical expression of scleroderma includes vascular, fibrotic, and immunologic features. Endothelial injury is followed by inflammatory cell extravasation and fibroblast activation. The autonomous activated fibroblasts continue to produce excessive extracellular matrix, which is a self-perpetuating fibrotic process.

CLINICAL PRESENTATION

The clinical subtypes of scleroderma are distinguished from each other primarily on the basis of the extent and degree of skin involvement.

Limited Cutaneous Scleroderma (lcSSc). Skin tightening is restricted, affecting the distal extremities (beyond the elbows and knees) and face. Pulmonary arterial hypertension can be a late manifestation, whereas pulmonary fibrosis develops in about a third of such patients. Symptomatic intestinal pseudo-obstruction can lead to malabsorption. The 10-year survival is more than 70%.

Diffuse Cutaneous Scleroderma (dcSSc). Here widespread skin tightening also involves the upper arms and thighs, trunk, and face. There is rapid progression of skin thickening and early occurrence of visceral disease affecting the gastrointestinal tract, lungs, heart, and kidneys. Palpable tendon friction rubs and flexion contractors develop frequently. The 10-year survival rate is between 40% and 60%.

Scleroderma sine Sclerosis. Some patients with systemic sclerosis may have no detectable skin thickening but present with other features seen in limited scleroderma, such as Raynaud phenomenon, telangiectases, and pulmonary and gastrointestinal disease.

Overlap. Scleroderma-overlap patients concomitantly develop features of one or more of the other autoimmune rheumatic diseases, such as rheumatoid arthritis, SLE, polymyositis, or Sjögren syndrome.

Raynaud Phenomenon. Raynaud phenomenon, an episodic and reversible vasospasm affecting fingers and toes, is precipitated by cold exposure or emotional stress. It occurs in 90% to 95% of patients and is manifested by triphasic color changes: pallor (white), acrocyanosis (blue), and reperfusion hyperemia (red). Ischemic necrosis may occur, leading to ulceration or gangrene of the fingertips.

Cutaneous Manifestations. In lcSSc, skin thickening is confined to distal extremities. Calcinosis from intracutaneous or subcutaneous calcific deposition of hydroxyapatite can develop on the distal digital pads and extensor surface of the forearms, elbows, and knees. Telangiectases can appear on the fingers, face, legs, and anterior chest. On nail-fold capillaroscopy, dilated nail-fold vessels or capillary “drop outs” can be seen (see Plate 5-56).

In the early phase, patients develop puffy, edematous hands. This is followed by progressive skin thickening and tightening over subsequent weeks to months. Cutaneous hypopigmentation and hyperpigmentation may occur. Often, after 3 to 5 years, the skin starts to soften, and eventually it may revert to normal thickness or even become thin. Perioral involvement leads to thinning of the lips, puckering, and reduced oral aperture.

Musculoskeletal Manifestations. Arthralgias and joint stiffness may affect the small and large joints. Tendon friction rubs commonly palpated over the flexor or extensor tendons due to fibrinous tenosynovitis and tendinitis are specific for dcSSc. Erosive joint disease can develop in some patients. Myopathy can be a result of microvasculopathy and muscle fibrosis, but sometimes there is pathologic evidence of myositis.

Gastrointestinal Tract Manifestations. Esophageal dysmotility eventually develops in about 80% of patients. The most frequent symptoms are heartburn (from gastroesophageal reflux disease) and dysphagia. Gastric antral vascular ectasias (also known as watermelon stomach) is a result of submucosal ectatic vessels in the gastric antrum. These vessels can erode through the gastric mucosa, leading to chronic loss of blood and severe iron-deficiency anemia. Small bowel dysfunction, seen in 20% to 60% of patients, comprises reduced peristalsis, stasis, and bacterial overgrowth. This leads to malabsorption and severe malnutrition. Pneumatosis cystoides intestinales, a condition that results from submucosal or subserosal gas cysts that develop in the wall of the small intestine, can manifest as an acute abdomen, leading to unnecessary laparotomy. Fecal incontinence may develop in some patients due to fibrosis of the anal sphincter. Primary biliary cirrhosis, the liver disorder seen most frequently with lcSSc, is associated with the presence of the anti-mitochondrial antibody.