On the face, SSc is characterized early on by periorbital edema and later by the development of a beaked nose, a reduction in the size of the mouth (microstomia) with radial furrowing, thinning of the lips, and telangiectasias.45,49 As the sclerosis worsens, patients are frequently left with expressionless, mask-like faces.48
Other common cutaneous manifestations of SSc include a “salt and pepper” appearance, with alternating areas of hypo- and hyperpigmented skin. Additionally, patients may suffer from a loss of hair follicles, severely dry skin, and pruritus.45,48
There are 2 major subsets of SSc—limited cutaneous SSc and diffuse cutaneous SSc. While they can be differentiated based on the history of symptoms, the appearance and extent of cutaneous involvement, and certain serological makers, the most important difference is the speed at which the disease progresses and its severity: Limited cutaneous SSc typically progresses slowly, while diffuse cutaneous SSc is characterized by a relatively rapid onset of disease, with skin and internal organ involvement likely to be severe.49
Scleroderma diagnosis and treatment: Vascular changes are an important clue
Skin changes seen in localized scleroderma and SSc can be clinically and histologically similar, making it difficult to arrive at a definitive diagnosis.
One clinical clue is that in localized scleroderma, vascular changes, such as RP and periungual nailfold telangiectasia, are typically absent. In addition, cutaneous changes in the hands and fingers, such as sclerodactyly, are more characteristic of systemic disease.10
SSc can be diagnosed using criteria proposed by the ACR, which have been shown to be highly sensitive (97%) and specific (98%).50 The major criterion is proximal scleroderma—symmetric thickening, tightening, and induration of the skin of the fingers and areas proximal to the metacarpophalangeal or metatarsophalangeal joints, which may include the trunk, neck, and face. Minor criteria include (1) sclerodactyly, (2) digital pitting scars of fingertips or loss of substance of the distal finger pad, and (3) bilateral basilar pulmonary fibrosis. Diagnosis is based on the presence of either the major criterion or 2 of the 3 minor criteria.50
Numerous therapies are available for localized scleroderma, including topical, intralesional, and systemic corticosteroids, topical tacrolimus, hydroxychloroquine, topical and systemic calcipotriol, penicillamine, sulfasalazine, interferon-[H9253], methotrexate, phototherapy with UV light, and imiquimod.
SSc skin manifestations, which can be severe and disabling, can be treated with a wide range of therapies. Topical or systemic corticosteroids; topical calcineurin inhibitors; systemic immunosuppressive agents such as methotrexate, cyclophosphamide, cyclosporine, and D-penicillamine; and phototherapy have all had varying success at reducing hardening of the skin.51-54 Other skin manifestations, including RP, dryness and itching, pigment changes, digital ulcerations, calcifications, and telangiectasias, should be managed as needed, with various supplemental treatment options available.45 These may include emollients, antihistamines, and topical corticosteroids for dryness and itching; laser therapy for telangiectasias; and corticosteroid injection, laser therapy, or surgery for calcifications. However, there is limited evidence of efficacy for most of these options.45
FIGURE 3
An attack of Raynaud’s phenomenon
Raynaud’s phenomenon, characterized by blanching of the distal fingertips, is shown here in a patient with systemic sclerosis.
FIGURE 4
Sclerodactyly in a patient with systemic sclerosis
Hardening and thickening of the skin can result in highly disabling sclerodactyly in patients with systemic sclerosis.
FIGURE 5
Dissolution of terminal phalanges
Bony resorption and ulceration have led to the loss of distal phalanges in this patient with systemic sclerosis.
Mixed connective tissue disease has features of several disorders
Mixed connective tissue disease (MCTD) is an apparently distinct rheumatologic condition characterized by a combination of clinical features of systemic LE, dermatomyositis, scleroderma, polymyositis, and rheumatoid arthritis. The presence of high titers of a unique autoantibody, anti-U1-RNP,54-57 aids in diagnosis.
Although precise prevalence data are lacking, MCTD is thought to occur in about 1 in 10,000 people.58 The disease is much more common in women, with a female-to-male ratio as high as 7 to 1, and generally occurs in the second or third decade of life.58-60
The clinical manifestations of MCTD typically evolve, with overlapping features of various autoimmune disorders appearing sequentially over several months to years.57 Early in the course of MCTD, patients commonly experience fatigue, polyarthritis, hand edema, and RP. In time, virtually every organ system may be involved. Pulmonary hypertension is a major cause of death.59,61