What Triggers Scleroderma?

Skin hardening first affects the fingers in people with scleroderma.

Scleroderma is a rare autoimmune disease characterized by progressive skin and connective tissue tightening and hardening. Scleroderma is a type of systemic connective tissue disease (systemic sclerosis) that may also affect subcutaneous tissue, muscles, and internal organs.

Generalized symptoms and signs of scleroderma include

• fatigue,
• weight loss, and
• loss of appetite.

Symptoms and signs of systemic sclerosis may affect many parts of the body:

• Skin
  • Progressive skin tightness and hardening (induration), often preceded by swelling
  • Skin hardening first affects the fingers (sclerodactyly) and extends inward
  • Tightening of facial skin is an early symptom
  • Pigment changes (lightening and darkening of skin)
  • Widespread itching
• Vascular
  • Raynaud's phenomenon
  • Pitting ulcers in fingertips which may lead to finger amputation
  • Visible small blood vessels just under the skin (telangiectasias)
  • Affects larger blood vessels and can lead to heart attack
• Gastrointestinal (GI)
  • GERD
  • Decreased or absent digestive tract muscle movements in the lower two-thirds of the esophagus (may lead to hoarseness, trouble swallowing, and aspiration pneumonia)
  • Indigestion, bloating, and feeling of fullness
  • Intestinal pseudo-obstruction
  • Constipation alternating with diarrhea from bacterial overgrowth
  • Fecal incontinence
  • Malnutrition
  • Chronic iron deficiency anemia
• Respiratory
  • Shortness of breath
  • Chest pain due to pulmonary artery hypertension (PAH)
  • Dry and persistent cough
• Musculoskeletal
  • Joint pain and loss of range of motion in joints
  • Muscle pain and weakness
  • Carpal tunnel syndrome symptoms
• Cardiac
  • Shortness of breath due to congestive heart failure or heart tissue scarring
  • Palpitations, irregular heartbeats, and lightheadedness/fainting
  • Symptoms of congestive heart failure or right-sided heart failure
• Renal (affecting the kidneys)
  • High blood pressure (hypertension)
  • Renal crisis
  • Chronic renal insufficiency
• Genitourinary
  • Erectile dysfunction
  • Bladder scarring
  • Painful sexual intercourse
  • Vaginal narrowing, dryness, and pain caused by vaginal scarring
• Eyes, ears, nose, and throat
  • Sicca syndrome and poor tooth development secondary to sicca syndrome
  • Loosening teeth
  • Hoarseness due to acid reflux
  • Increased risk for tongue cancer
  • Decreased mouth opening
  • Blindness
• Endocrine
  • Hypothyroidism
• Neurologic/psychiatric
  • Facial pain and decreased sensation due to trigeminal neuralgia
  • Numbness, tingling, pain, and weakness in the hands
  • Headache and stroke during hypertensive crisis
  • Depression and anxiety

The exact cause of scleroderma is unknown.

Risk factors for development of the disease include the following:

• Genetic predisposition
• Environmental factors (for example, triggers) such as
  • Silica exposure
  • Solvent exposure (vinyl chloride, trichloroethylene, epoxy resins, benzene, carbon tetrachloride)
  • Radiation exposure or radiotherapy
• Past treatment with the immune checkpoint inhibitor pembrolizumab for metastatic melanoma

The diagnosis of scleroderma is based on a physical examination. Your doctor may order tests to help with the initial diagnosis or to rule out other conditions.

Laboratory testing may include the following:

• Complete blood cell count (CBC)
• Serum muscle enzyme levels
• Erythrocyte sedimentation rate
• Serum CXCL4 level
• N-terminal pro-brain natriuretic peptide
• Autoantibody assays

Other testing may include the following:

• For gastrointestinal symptoms:
  • X-rays of the gastrointestinal tract
  • Esophagogastroduodenoscopy with appropriate biopsies
  • Esophageal manometry assessment
  • Gastric emptying study
  • Colonoscopy
• For cardiopulmonary symptoms:
  • Chest X-rays
  • High-resolution computerized tomography (HRCT)
  • Pulmonary function testing
  • Bronchoscopy with bronchoalveolar lavage
  • Electrocardiogram (ECG)
  • Transthoracic echocardiography
  • Right-heart catheterization
• Other studies:
  • X-rays of extremities
  • Nail-fold capillary microscopy

Treatment of scleroderma aims to relieve symptoms and signs and manage complications. Doctors should reevaluate patients should be every 3-6 months, depending on the disease activity and progression.

Treatment of skin hardening and scarring may include the following:

• D-penicillamine
• Bovine collagen
• Methotrexate
• Mycophenolate mofetil
• Allogeneic bone marrow transplantation

Treatment for itching may include

• moisturizers,
• antihistamines -- histamine 1 (H1) and histamine 2 (H2) blockers,
• tricyclic antidepressants, and
• trazodone.

Treatment for Raynaud phenomenon may include the following:

• Calcium channel blockers
• Prazosin
• Prostaglandin derivatives (for example, prostaglandin E1)
• Dipyridamole
• Aspirin
• Topical nitrates
• In serious cases, a tissue plasminogen activator, heparin, and urokinase may be necessary. In very severe cases, intravenous iloprost or related prostanoids may be indicated.

Treatment for digital ulcers (ulcers on the fingers or toes) may include

• bosentan,
• combination therapy with iloprost and bosentan, and
• ambrisentan and other endothelin receptor antagonists.

Treatment for gastrointestinal symptoms may include

• antacids, histamine 2 (H2) blockers, proton pump inhibitors;
• reflux and aspiration precautions;
• prokinetic agents;
• octreotide;
• stool softeners; and
• laxatives.

Treatment for pulmonary fibrosis (lung scarring) may include

• cyclophosphamide, either orally or intravenously, and
• mycophenolate mofetil.

Treatment for pulmonary arterial hypertension (PAH) in scleroderma may include the following:

• Prostaglandin derivatives such as epoprostenol, treprostinil, beraprost, and iloprost
• Phosphodiesterase type 5 (PDE-5) inhibitors such as sildenafil and tadalafil
• Endothelin receptor antagonists such as bosentan, ambrisentan, and macitentan

Other treatments...

• Carpal tunnel entrapment symptoms may be treated with local corticosteroid injections.
• Muscle inflammation (myositis) may be treated with steroids (first choice), methotrexate, or azathioprine.
• Joint pain may be treated with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).

Surgery for scleroderma symptoms may include the following:

• Digital (involves fingers and/or toes) sympathectomy and botulinum toxin injections for patients with severe Raynaud's phenomenon
• Digital debridement or amputation for severe ischemic or infected digital lesions
• Hand surgery to correct severe flexion contractures
• Removal of severely painful, draining, or infected calcinotic deposits
• Fundoplication to treat severe esophageal reflux with complicating aspiration pneumonitis

Renal crisis occurs in about 10% of all patients with systemic sclerosis. If this condition is not treated promptly and aggressively, it leads to leads to renal failure requiring dialysis, kidney transplantation, or death.

Other complications of systemic sclerosis include

• tissue death in the fingers or toes (digital infarctions),
• pulmonary hypertension,
• muscle inflammation (myositis),
• kidney failure, and
• wound infections.

Systemic sclerosis has the highest mortality rate among systemic autoimmune diseases due to pulmonary hypertension, pulmonary fibrosis (interstitial lung disease), and scleroderma renal crisis.

The 5-year survival rate (patients are still alive 5 years following diagnosis) among patients with diffuse cutaneous systemic sclerosis is about 84%. The 5-year survival among the patients with limited skin (cutaneous) systemic sclerosis is high, over 90%.