scleroderma

Scleroderma
Classification and external resources
ICD-10	L94.0-L94.1, M34.
ICD-9	701.0 710.1

Scleroderma is a chronic autoimmune disease characterized by fibrosis (or hardening), vascular alterations, and autoantibodies. There are two major forms: Limited cutaneous scleroderma (or morphea)^[1] mainly affects the hands, arms and face, although pulmonary hypertension is frequent. Diffuse cutaneous scleroderma (or systemic sclerosis)^[2] is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and lungs, and can be fatal. There are no treatments for scleroderma itself, but individual organ system complications are treated.^[3][4]

Prognosis is good for limited cutaneous scleroderma, except for <10% of those who develop pulmonary arterial hypertension ≥10 to 20 years. 5-year survival is 90%, 10-year survival 75%. Prognosis is worse for diffuse cutaneous disease, particularly in older age, and for males. Death occurs most often from pulmonary, heart and kidney complications. 5-year survival is 70%, 10-year survival 55%.^[5]

The cause is unknown. Scleroderma runs in families, but the genes have not been identified. It affects the small blood vessels known as arterioles, in all organs. First, the cells on the inner lining, or endothelium, of the arteriole die off, along with smooth muscle cells, by a process of apoptosis. They are replaced by collagen and other fibrous material. Inflammatory cells, particularly CD4+ helper T cells, infiltrate the arteriole, and cause further damage. Many of the inflammatory and destructive protein signals have been identified, and they are potential targets for drugs that could interrupt the process.^[3]

Types

Scleroderma is characterized by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile, and which give the appearance of hidebound skin, a disease occurring in both localized and systemic forms:^[6]

• Localized scleroderma
  • Localized morphea
  • Morphea-lichen sclerosus et atrophicus overlap
  • Generalized morphea
  • Atrophoderma of Pasini and Pierini
  • Pansclerotic morphea
  • Morphea profunda
  • Linear scleroderma
• Systemic scleroderma
  • CREST syndrome
  • Progressive systemic sclerosis

Incidence

This disease is found among all races worldwide, but women are four times more likely to develop scleroderma than men. In the United States, approximately one person in 1,000 is affected. Children rarely suffer the systemic type, but localized scleroderma is common. Most adults are diagnosed after their 30th birthday and before age 50. The disease has high rates among the native American Choctaw tribe and African-American females.^[7]

Diagnosis

Typical scleroderma is classically defined as symmetrical skin thickening, with about 90% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes, and anti-nuclear antibodies. Patients may or may not experience systemic organ involvement. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.^[8][9] Additional symptoms of scleroderma typically present themselves within two years of Raynaud's phenomenon.^[7]

Laboratory testing can show anti-topoisomerase antibodies (causing a diffuse systemic form), or anti-centromere antibodies (causing a limited systemic form, and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.

Severe complications from Scleroderma include:

• Heart - Untreated high blood pressure strains the heart, irregular heart rhythm and enlargement of the heart lead to heart failure.
• Kidney - Blood vessel damage causes blood pressure to rise, which untreated, will result in brain swelling, headaches, retinal damage and seizures.
• Lung - Two-thirds of all patients suffer from respiratory problems such as shortness of breath, coughing, difficulty breathing, alveolitis (inflammation of lung air sacs), pneumonia and cancer.
• Digestive - Esophagus damage can make it difficult to swallow food, and acid reflux is common. A sluggish intestine may cause pain & bloating; undigested food can result in diarrhea, weight loss and anemia.
• Skin & Joints - Carpal tunnel syndrome is common, as is muscle weakness, joint pain & stiffness.^[7]

Treatment

There is no direct cure for scleroderma. Because the exact cause is unknown, any treatment is patient-specific and aimed at ameliorating symptoms of the disease. For example, patients who experience Raynaud's phenomenon may be treated with agents to increase blood flow to the fingers, including nifedipine, amlodipine, diltiazem, felodipine, or nicardipine.

Fibrosis of the skin has been treated with varying degrees of success with agents such as d-penicillamine, colchicine, PUVA, Relaxin, and cyclosporine.

Because scleroderma is an autoimmune disease, one of the major pillars of treatment involves the use of immunosuppressive agents. These drugs include methotrexate, cyclophosphamide, azathioprine, and mycophenolate.^[10][11]

Patients with lung involvement benefit from Oxygen therapy, which increases oxygen saturation in tissues damaged by the progression of scleroderma. The additional oxygen in the blood reduces the effort of the heart, decreasing shortness of breath.^[12]

Prognosis

Individuals with morphea or limited scleroderma have a relatively positive outlook. They will usually succumb to another disease, not the scleroderma. Those with very widespread skin and organ involvement (systemic) have a negative prognosis. More women have scleroderma, but the disease kills more men. Following diagnosis, two-thirds of patients live at least 11 years. The higher the patient's age at diagnosis, the more likely they are to die from the disease.

History

Cases of skin disease similar to scleroderma may be found in the writings of Hippocrates as far back as 460–370 B.C. Oribasius (325–403 A.D.) and Paulus Agineta (625–690 A.D.), also wrote on the subject. It is difficult for us to know if these were truly examples of scleroderma because the descriptions were inexact.

The first definite description of the disease was by Carlo Curzio in a monograph published in Naples in 1753. This account produced considerable interest in French and English medical circles.

The account concerns a young woman of 17 named Patrizia Galiera, who was admitted to the hospital and assigned to Dr. Curzio. Her symptoms as described by the doctor involved hardness of the skin (differing in degree from place to place), tightness around the mouth, and hardness around the neck. He noted loss of warmth in the skin but no other problem in pulse, respiration, or digestion.

Much of the report contains details of the treatment, which included warm milk and vapor baths, bleeding from the foot, and small doses of quicksilver. After 11 months, the skin became soft and flexible, and all natural functions were restored.

Curzio's observations were published in French in 1755 and aroused considerable interest. The early dermatological texts of R. William in London (1808) and his student, J. L. Alibert, in Paris (1818) referred to Curzio's observation.^[13]

Additional images

Left arm of Scleroderma patient, showing skin lesions

References