Atlas of pathophysiology, 2 Edition

Part II - Disorders

Immunologic Disorders

Scleroderma

Scleroderma (also known as systemic sclerosis) is an uncommon disease of diffuse connective tissue. Degenerative and fibrotic changes in the skin, blood vessels, synovial membranes, skeletal muscles, and internal organs (especially the esophagus, intestinal tract, thyroid, heart, lungs, and kidneys) follow the initial inflammation. The seven forms of scleroderma are diffuse systemic sclerosis, localized, linear, chemically induced localized, eosinophilia myalgia syndrome, toxic oil syndrome, and graft-versus-host disease.

Age Alert

Scleroderma affects women 3 to 4 times more often than it does men, especially between ages 30 and 50. The peak incidence is in people ages 50 to 60.

Causes

Unknown

Possible causes

·   Systemic exposure to silica dust or polyvinyl chloride

·   Anticancer agents such as bleomycin; nonnarcotic analgesics such as pentazocine hydrochloride

·   Abnormal immune response

·   Underlying vascular cause with tissue changes initiated by persistent perfusion defect

Pathophysiology

Scleroderma usually begins in the fingers and extends proximally to the upper arms, shoulders, neck, and face. The skin atrophies, edema and infiltrates containing CD4+ T cells surround the blood vessels, and inflamed collagen fibers become edematous and degenerative, losing strength and elasticity. The dermis becomes tightly bound to the underlying structures, resulting in atrophy of the affected appendages and destruction of the distal phalanges by osteoporosis. As the disease progresses, the fibrosis and atrophy can affect other areas, including muscles and joints.

Signs and symptoms

·   Skin thickening, commonly limited to the distal extremities and face, but possibly involving internal organs

·   CREST syndrome (a benign subtype of limited systemic sclerosis): calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia

·   Patchy skin changes with a teardrop-like appearance known as morphea (localized scleroderma)

·   Band of thickened skin on the face or extremities that severely damages underlying tissues, causing atrophy and deformity (linear scleroderma)

·   Raynaud's phenomenon (blanching, cyanosis, and erythema of the fingers and toes); progressive phalangeal resorption that may shorten the fingers (early symptoms)

·   Taut, shiny skin over the entire hand and forearm due to skin thickening

·   Tight and inelastic facial skin, causing a masklike appearance and “pinching” of the mouth

·   Thickened skin over proximal limbs and trunk (diffuse systemic sclerosis)

·   Abdominal distention

·   Pain, stiffness, and swelling of fingers and joints (later symptoms)

·   Frequent reflux, heartburn, dysphagia, and bloating after meals due to GI dysfunction

·   Diarrhea, constipation, and malodorous floating stool

Diagnostic test results

·   Laboratory analysis reveals slightly elevated erythrocyte sedimentation rate, positive rheumatoid factor in 25% to 35% of patients, and positive antinuclear antibody.

·   Urinalysis shows proteinuria, microscopic hematuria, and casts.

·   Hand X-rays show terminal phalangeal tuft resorption, subcutaneous calcification, and joint space narrowing and erosion.

·   Chest X-rays show bilateral basilar pulmonary fibrosis.

·   GI X-rays show distal esophageal hypomotility and stricture, duodenal loop dilation, small-bowel malabsorption pattern, and large diverticula.

·   Pulmonary function studies show decreased diffusion and vital capacity.

·   Electrocardiogram reveals nonspecific abnormalities related to myocardial fibrosis and possible arrhythmias.

·   Skin biopsy shows changes consistent with disease progression, such as marked thickening of the dermis and occlusive vessel changes.

Treatment

No cure

To preserve normal body functions and minimize complications

·   Immunosuppressants, vasodilators, antihypertensives

·   Digital sympathectomy, cervical sympathetic blockade

·   Possible surgical debridement

·   Antacids, soft, bland diet

·   Angiotensin-converting enzyme inhibitors

·   Physical therapy, heat therapy

·   Broad-spectrum antibiotics

P.271

SCLERODACTYLY

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