Limited and Diffuse Systemic Sclerosis

Systemic sclerosis, also called systemic scleroderma, is a systemic autoimmune connective tissue disease that is categorized according to degree of skin involvement into the following:
- Limited systemic sclerosis, includes CREST syndrome (defined below) and is associated with delayed appearance of visceral involvement.
- Diffuse systemic sclerosis (DSS) (formerly referred to as progressive systemic sclerosis) which has more extensive skin involvement and often affects the internal organs and has a very poor prognosis.
Limited systemic sclerosis accounts for 90% of the cases of systemic sclerosis.
In DSS the female-to-male ratio is 4:1.

Pathogenesis ⬆ ⬇

The exact etiology of scleroderma is unknown.
Vascular inflammation and infiltration of activated T4 cells results in an increase in number and activity of fibroblasts and excess collagen. Induration, thickening and sclerosis of the skin, and subcutaneous tissues result.

Clinical Manifestations ⬆ ⬇

Thickening and fibrotic skin changes present symmetrically on the hands and fingers. These changes are termed acrosclerosis.
Initially patients may report a tightening sensation of the fingers.
In limited systemic sclerosis the sclerosis is restricted to the fingers, hands, and face.
In diffuse systemic sclerosis the fibrotic skin changes start on the fingers but then become generalized to involve the arms, trunk, face, and legs.
Raynaud phenomenon, often an early symptom, occurs in both limited and diffuse systemic sclerosis.
Raynaud phenomenon consists of pain and a characteristic sequence of color changes of the distal fingers from white to purple to red in response to cold exposure (Fig. 34.33).
Sclerodactyly, the result of long-standing disease, appears as thickened, sausage-shaped digits with a shiny, waxy atrophic look to the skin (Figs. 34.34 and 34.35).
Other skin findings include the following:
- Dyspigmentation characterized by either diffuse hyperpigmentation or depigmentation with perifollicular sparing (“leukoderma of scleroderma”).
- Dystrophic calcinosis cutis.
- Matted telangiectasias of face, lips, or palms.
- Capillary abnormalities of the proximal nail fold.

CREST syndrome is considered a clinical subset of limited systemic sclerosis and consists of the following:

Calcinosis cutis, most commonly occurring on the palms, fingertips, and bony prominences.
Raynaud phenomenon.
Esophageal dysfunction.
Sclerodactyly (“claw deformity”).
Telangiectasia (macular lesions) on the face, lips, palms, back of hands, and trunk.

Diagnosis ⬆ ⬇

Based on clinical findings and laboratory abnormalities.
Positive anticentromere antibody is seen in 70% of patients with CREST syndrome.
The Scl-70 antibody is present in approximately 30% of patients with diffuse systemic sclerosis.
Antihistone antibodies can be observed in the course of systemic sclerosis.

Differential Diagnosis

Scleredema

Generalized Morphea

Plaques of morphea may coalesce resulting in a diffuse appearance of skin hardening.
Rarely systemic associations.

Mixed Connective Tissue Disease

Has signs and symptoms that tend to occur in sequence over a number of years and consist of a combination of disorders—primarily of lupus, scleroderma, and polymyositis; sometimes referred to as an overlap syndrome.

Management

Treatment regimens are diverse, difficult to treat, and remain a great challenge. Currently, no standard therapy is available for skin sclerosis. Raynaud phenomenon often responds to calcium channel blockers such as nifedipine and scleroderma kidney disease often responds to angiotensin-converting enzyme and angiotensin II inhibitors.
The following are just some of the drugs and measures that have been tried or are currently under investigation: systemic steroids, minocycline, prostaglandins, aspirin, immunosuppressive agents, tacrolimus, thalidomide, D-penicillamine, colchicine, alpha and gamma interferon, and relaxin.
Psoralen and UVA light, photopheresis, lung transplantation, autologous stem cell transplantation, and etanercept.

Helpful Hints

Therapy of systemic scleroderma should include full range-of-motion exercises.
When Raynaud phenomenon is present, the most effective nonpharmacologic method of preventing episodes is avoiding exposure to cold temperature and wearing layers of warm, loose-fitting clothing, including socks and gloves. Also, smoking cessation is advised.

Point to Remember

CREST syndrome has a more favorable prognosis than progressive systemic sclerosis, although visceral involvement may occur late in the course of the disease.

Other Information ⬆

Diffuse Systemic Sclerosis

Diffuse involvement and symptoms secondary to the tightening of the skin, with difficulty in opening the mouth, masklike facies, “pinched” nose, numerous telangiectasias, and retraction of the lips (Fig. 34.36).
Loss of manual dexterity; later, contractures of the hands, painful fingertip ulcers resulting from vasculitis, and shortening of fingers resulting from distal bone resorption (see Fig. 34.34 above).
Esophageal dysfunction, dysphagia, bloating, and diarrhea.
Systemic symptoms may include shortness of breath, difficulty in swallowing, and arthralgia.
Possibly, rapid progression of kidney disease, reduced breathing capacity, cardiac disease, and renal failure.