What is Scleroderma?

Scleroderma is a connective tissue disease characterized by skin inflammation, degeneration, thickening and fibrosis, and then sclerosis and atrophy. This disease can cause multiple systemic damage. In addition to systemic sclerosis, in addition to degenerative lesions on the skin, synovium, and finger (toe) arteries, internal organs such as the digestive tract, lungs, heart, and kidneys can also be affected.

Basic Information

nickname

Systemic sclerosis

English name

scleroderma

Visiting department

Division of Rheumatology

Common causes

Etiology unknown, may be related to heredity, environmental factors, female hormones, immune abnormalities, etc.

Common symptoms

Raynaud's phenomenon, fatigue, musculoskeletal pain, etc.

Causes of scleroderma

The cause of scleroderma is still unclear. It may be caused by genetic, environmental factors (viral infections, chemicals such as silicon), female hormones, cellular and humoral immune abnormalities, and fibroblasts synthesize and secrete collagen. And visceral fibrosis. Chemical or viral infections are environmental factors that affect susceptibility to disease. People who are often exposed to silica at work have a relatively high risk of developing the disease.

Clinical manifestations of scleroderma

Systemic sclerosis is a chronic multisystem disease. Onset symptoms are often non-specific, including Raynaud's phenomenon, fatigue, and musculoskeletal pain, which persist for weeks or months before other indications appear. The early clinical manifestations of specific scleroderma are swelling and thickening of the skin, which starts in the fingers and hands. A variety of manifestations follow, mainly in the skin, lungs, heart, digestive tract, or kidneys. In patients without Raynaud's, the risk of kidney involvement is increased.
According to the degree of skin invasion, scleroderma can be divided into several subtypes: Patients with localized scleroderma only thicken the skin of the distal limbs and the trunk is not invaded. CREST syndrome includes: calcium deposits, Raynaud's phenomenon, esophageal dysfunction, finger sclerosis, and capillary dilatation, which belong to the category of localized scleroderma. Patients with diffuse scleroderma show thickening of the skin at the distal and proximal extremities and / or the trunk.

Raynaud phenomenon

Suffering from cold or nervousness, the patient suddenly became cold in hands and feet, pale in color on the fingers (toes), and then turned purple. 10 to 15 minutes after the end of external stimulation, vasospasm is restored, and the color of the finger (toe) end becomes normal with red or spot-like variegations. This change is called paroxysmal vasospasm (Raynaud's phenomenon). Cold-induced paleness may also occur at the tip of the nose, tip of tongue, lips and earlobe.

Skin

In the early stage of the disease (edema phase), the skin shows mild redness. Some patients have erythema, pruritus, and edema. The early finger edema period can last for a long time. The skin changes stop at the distal end of the upper limbs and can also spread to the forearms, forearms, Belly, back and face. In diffuse scleroderma, the skin is extensively hardened with deepening or decreasing pigmentation, leaving the skin like salt and pepper.

With the progress of the disease, the skin became tight and shiny, the normal wrinkles and skin wrinkles disappeared, the facial skin was thin and dull and expressionless. Lips are thin and tight, mouth opening is limited, systemic melanin appears at the same time, and some cases are even earlier. Finger, face, lips, tongue, and forearms can appear patchy capillary dilatation and subcutaneous calcification. The fingertips are most common, ranging from small spots to large clumps, ranging in size from the knee, elbow, or other prominent areas. Parts. In patients with CREST syndrome, calcium deposits and telangiectasias are often more pronounced.
When the scleroderma progresses to the sclerosis phase, the skin becomes thicker and the skin becomes dry, causing itching. This phase develops progressively, lasting for 1 to 3 years or longer, and finally the inflammation and fibrosis stop and enter the atrophic phase. The skin is atrophied and thinner, and the fibrotic tissue is closely attached to the subcutaneous tissue, which is not easy to pinch by hand. Bone ulcers may appear at the site of the flexion contracture, such as near the knuckle (toe) joint. In the later stage of atrophy, the skin in some areas gradually softens, and can return to normal skin, especially the skin of the trunk and proximal limbs.

3. Muscle and bone

Non-specific muscle and bone symptoms such as arthralgia and myalgia are the earliest manifestations of scleroderma. Sometimes arthritic symptoms can be noticeable, but pain and stiffness at the joints are always more severe than objective signs of inflammation. The patient's muscle atrophy is caused by apraxia, which is the result of limited joint movement due to the involvement of skin, joints and muscle keys.

4. Lungs

Impaired lung function is common in scleroderma, but clinical symptoms are often not very significant. Until the late stage of the disease, lung involvement can be the cause of death. Common clinical symptoms are shortness of breath after exertion (dyspnea on exercise), dry cough after exertion, and generally do not cause chest pain. Chest pain in patients with scleroderma is often caused by muscle inflammation, reflux esophagitis, pleurisy, or pericarditis. The progression of fibrotic alveolitis to pulmonary interstitial fibrosis or vascular intimal fibrosis, and pulmonary vascular disease caused by smooth muscle hyperplasia can impair the ventilation function of the lung.

5. Gastrointestinal tract

Patients may experience narrowing of the cleft lip, dryness of the mucous membranes, periodontal disease causing chewing difficulties, tooth loss and malnutrition. Acid reflux, heartburn, and sternal burning are the most common symptoms of scleroderma. Reflux esophagitis can lead to bleeding, ulcers, stenosis, and Barrett's esophagus, which can easily turn into esophageal cancer. The cause of concurrent reflux esophagitis is related to factors such as excessive esophageal peristaltic dysfunction caused by deposition and fibrosis of subesophageal mucosa and muscular layer, lower esophageal sphincter pressure, and decreased gastric emptying capacity. After the gastric emptying time is prolonged, in addition to exacerbating gastroesophageal reflux, it can also cause patients to experience symptoms of indigestion such as abdominal distension and belching.

The weakened small bowel motility may be asymptomatic, or it may cause severe chronic pseudo-intestinal obstruction with severe abdominal distension, abdominal pain, and vomiting. Scleroderma can also affect the large intestine and rectum. Large intestinal wall muscle atrophy often causes asymptomatic wide-mouth diverticulum in the transverse and descending colons, which is specific to scleroderma. Reduced colonic motion can cause refractory constipation. Fibrosis of the rectal sphincter can cause intractable fecal incontinence and rectal prolapse.

6. Heart

It was only discovered late in the course of the disease that most patients showed signs of left ventricular insufficiency, with difficulty breathing, palpitations, and occasional chest pain after exertion. The pathological examination of the heart and the diagnostic test of sensitivity indicate that the myocardium, myocardial blood vessels, and pericardium can be involved. The manifestations of cardiomyopathy include refractory congestive heart failure, and various atrial and ventricular arrhythmias. Any symptom of heart disease is an indication of a poor prognosis. Transmural patchy myocardial fibrosis is a feature of SSc, which determines the nature and severity of heart disease. 30% to 40% of patients with SSc can detect pericardial effusion through echocardiography, but obvious pericardial effusion is not common. A large amount of pericardial effusion is an indication of poor prognosis, but pericardial tamponade rarely occurs. ECG damage and asymptomatic arrhythmias are common on ECG.

7. Kidney

Scleroderma is often accompanied by kidney involvement. Scleroderma renal crisis is a major cause of death in diffuse scleroderma. Nephrotic hypertension and / or aggressive renal failure are more common. 80% of renal crisis occurs in the first 4 to 5 years of the disease, often in patients with diffuse scleroderma with a blood pressure higher than 150 / 90mmHg, malignant hypertension can occur without warning, and hypertensive encephalopathy.

8. Other performance

50% of SSc patients often have depression, mainly because of depression in response to treatment. Sexual dysfunction is also common, and organic neurovascular diseases can often cause impotence in male patients. Most patients have neuropathy caused by Sjogren's syndrome and carpal tunnel syndrome. Hypothyroidism secondary to thyroid fibrosis or autoimmune thyroiditis (Hashimoto's thyroiditis) is also commonly encountered in scleroderma. Clinical issues. Complicated liver disease and primary biliary cirrhosis, especially in women with CREST syndrome.

Scleroderma test

The auxiliary examination of scleroderma mainly includes laboratory examination and imaging examination.

1. Hemoglobin can be reduced, and proteinuria indicates kidney damage. ESR increased, serum globulin increased, and rheumatoid factor could be positive at low titers.

2. About 90% of patients with scleroderma are positive for ANA, mostly spotted or nucleoli, and most are anti-centromere antibodies. Anti-Scl-70 antibodies are SSc-specific antibodies, but the positive rate is low (20% to 30% positive). Anti-ds-DNA antibodies are extremely rare.

3. X-ray of both hands may have irregular bone erosion and joint space narrowing. A few patients with scleroderma have terminal phalangeal resorption, often accompanied by soft tissue atrophy and subcutaneous calcium deposits, and occasionally complete dissolution of the middle phalanx.

4. Early examination of esophagus barium meal can be found in the lower part of the esophagus 1/2 or 2/3 slightly dilated, peristalsis weakened. Early chest X-ray examination showed thickening of the lower lung texture. Typically, there are a large number of linear and / or small nodules or linear nodular reticular shadows in the lower 2/3 of the lung field, and in severe cases, it is a "honeycomb lung".

Scleroderma diagnosis

Diagnostic criteria proposed by Masi et al. In 1980:

Main criteria

Proximal scleroderma, that is, symmetry thickening of the skin from the end of the finger (toe) to the metacarpophalangeal (toe) joint, tightening and hardening. Such changes can affect the entire limb, face, neck, and torso (chest and abdomen).

2. Minor criteria

(1) Finger scleroderma, the above skin lesions are limited to fingers.

(2) The scarring of the fingertips or the disappearance of the fingertip tissue.

(3) bilateral pulmonary interstitial fibrosis. The chest radiograph shows a reticular linear or nodular shadow on the base of the lungs on both sides, which can have a "honeycomb" appearance.

Those who meet the major criteria or more than two (including two) minor criteria can be diagnosed with scleroderma, and various subtypes must be subdivided. CREST syndrome can be confirmed if it meets 3 or more of the clinical manifestations of CREST syndrome and the anti-centromere antibody is positive.

Scleroderma Treatment

Quitting smoking, avoiding cold, paying attention to whole body warming, and biofeedback exercises are effective in preventing Raynaud's phenomenon; vasodilators should be used when symptoms are severe or with finger ulcers.

Treatment principle

Early diagnosis and early treatment are conducive to preventing disease progression. The principles are vasodilation, anti-fibrosis, immunosuppression and immune regulation, but there are no specific drugs.

2. Drugs that improve the condition

(1) Drugs that target blood vessels and improve microcirculation include aspirin and pansentin that alter platelet function. Ketanzerin is a histamine antagonist that can reduce the frequency and severity of Raynaud's phenomenon and improve the prognosis of fingertip ulcer , But the drug is not effective for skin thickening or improvement of internal organ damage. Nitrendipine, a calcium channel blocker, is an effective vasodilator. Angiotensin-converting enzyme inhibitors such as lyproproic acid and enalapril can effectively control hypertension and early renal insufficiency. Drugs that improve microcirculation include salvia miltiorrhiza and low-molecular dextran injection, which have certain effects on skin sclerosis, joint stiffness and pain.

(2) Glucocorticoids and immunosuppressive prednisone are reduced after one month of administration to maintain. Methotrexate and cyclosporine A (CsA) have a certain effect in the trial of a few people. Penicillamine is an immunomodulator and has a certain effect on inhibiting skin sclerosis and visceral damage. For patients with interstitial lung disease, glucocorticoids and CTX can change the condition. Triptolide and macrolides such as roxithromycin can reduce symptoms. Intravenous prostaglandin can increase survival in patients with primary pulmonary hypertension.

Renal crisis is the most terrible visceral complication of scleroderma, and the most common consequence is renal failure. ACEI or ARB antihypertensive drugs can reverse severe hypertension, renal anemia and control hypertension. Improvements in hemodialysis and renal dialysis therapy also bring hope to renal crisis, and kidney transplantation improves survival.

Scleroderma prognosis

The natural course of scleroderma varies greatly. Many patients have progressive sclerosis of their fingers, disability due to flexion contracture, and almost all patients eventually have internal organ involvement. Patients with kidney, heart, and lung involvement at the beginning of the onset, suggesting a poor prognosis. Pulmonary hypertension and intestinal malabsorption are common causes of death in patients with localized scleroderma.