Scleroderma is a rare autoimmune disease that is a type of systemic connective tissue disease (systemic sclerosis). Scleroderma is characterized by progressive skin and connective tissue tightening and hardening. It may also affect subcutaneous tissue, muscles, and internal organs.
There are five stages of scleroderma symptom development and progression.
- Stage 1: Immune system malfunction
- Something such as environmental toxins or infections triggers changes to the immune system
- Stage 2: Circulating pathogenic factors
- The altered immune system regularly produces destructive autoantibodies or other disease-causing molecules
- Stage 3: Microvascular endothelial damage
- Stage 4: Fibrosis (thickening/scarring)
- Repeated trauma to the endothelium triggers the process of scarring
- Stage 5: Organ damage
- Scarring affects multiple organ systems, including the skin and internal organs
Five-year survival rates
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 five-year survival rate (that is, patients who are still alive 5 years following diagnosis) among patients with diffuse cutaneous systemic sclerosis is about 84%.
- Five-year survival among patients with limited skin (cutaneous) systemic sclerosis is high — over 90%.
What Are Symptoms of Scleroderma?
Generalized symptoms of scleroderma include:
- Fatigue
- Weight loss
- Loss of appetite
Symptoms of systemic sclerosis may affect many parts of the body, such as:
- Skin
- Tightening of the skin on the face is an early symptom
- Skin hardening first affects the fingers (sclerodactyly) and extends inward
- Progressive skin tightness and hardening (induration), often preceded by swelling
- Pigment changes (lightening and darkening of skin)
- Widespread itching
- Vascular
- Raynaud’s phenomenon
- A condition in which the fingers and toes often feel cold
- Visible small blood vessels just under the skin (telangiectasias)
- Pitting ulcers in fingertips which may lead to finger amputation
- Can also affect larger blood vessels and lead to heart attack
- Raynaud’s phenomenon
- Gastrointestinal (GI)
- Gastroesophageal reflux disease (GERD)
- Indigestion, bloating, and feeling of fullness
- Decreased or absent digestive tract muscle movements in the lower two thirds of the esophagus (can cause hoarseness, difficulty swallowing, and aspiration pneumonia)
- Intestinal pseudo-obstruction
- Constipation alternating with diarrhea from bacterial overgrowth
- Fecal incontinence
- Malnutrition
- Chronic iron deficiency anemia
- Musculoskeletal
- Muscle pain and weakness
- Joint pain and loss of range of motion in joints
- Symptoms of carpal tunnel syndrome
- Respiratory
- Shortness of breath
- Dry and persistent cough
- Chest pain due to pulmonary artery hypertension (PAH)
- Cardiac (heart)
- Palpitations, irregular heartbeats, and lightheadedness/fainting
- Shortness of breath due to congestive heart failure or heart tissue scarring
- Symptoms of congestive heart failure or right sided heart failure
- Renal (kidneys)
- High blood pressure (hypertension)
- Renal crisis
- Chronic renal insufficiency
- Genitourinary
- Erectile dysfunction
- Bladder scarring
- Vaginal narrowing, dryness, and pain caused by vaginal scarring
- Painful sexual intercourse
- Eyes, ears, nose, and throat
- Loosening teeth
- Sicca syndrome and poor tooth development secondary to sicca syndrome
- Hoarseness due to acid reflux
- Increased risk for tongue cancer
- Decreased mouth opening
- Blindness
- Endocrine
- Neurologic/psychiatric
- Facial pain and decreased sensation due to trigeminal neuralgia
- Numbness, tingling, pain, and weakness in the hands
- Depression and anxiety
- Headache and stroke during hypertensive crisis
How Is Scleroderma Diagnosed?
Scleroderma is diagnosed with a patient history and physical examination.
Tests used to help with the initial diagnosis or to rule out other conditions may include:
- Laboratory testing
- Complete blood cell count (CBC)
- Erythrocyte sedimentation rate (ESR)
- Serum muscle enzyme levels
- Serum CXCL4 level
- N-terminal pro-brain natriuretic peptide
- Autoantibody assays
- Testing for gastrointestinal symptoms
- X-rays of the gastrointestinal tract
- Gastric emptying study
- Colonoscopy
- Esophagogastroduodenoscopy with appropriate biopsies
- Esophageal manometry assessment
- Testing for heart and lung (cardiopulmonary) symptoms
- Chest X-rays
- Pulmonary function testing
- High-resolution computerized tomography (HRCT)
- Electrocardiograms (ECGs)
- Bronchoscopy with bronchoalveolar lavage
- Transthoracic echocardiography
- Right-heart catheterization
- Other studies
- X-rays of extremities
- Nail-fold capillary microscopy
What Is the Treatment for Scleroderma?
There is currently no cure for scleroderma. The goal of treatment is relief of symptoms and management if complications. Patients should be re-evaluated every 3-6 months, depending on disease activity and progression.
Treatment approaches for scleroderma depend on the stage of the disease.
Stage 1 treatment may include:
- Hematopoietic stem cell transplants (HSCT)
- Immune system regulation
- Hydroxychloroquine (Plaquenil)
- Intravenous immunoglobulin (IVIG)
- Extracorporeal photopheresis
- A procedure in which blood is removed from the body, treated with ultraviolet light and drugs that become active when exposed to light, and then returned to the body
Stage 2 treatment may include:
- Immunosuppressants
- Prednisone
- Methotrexate
- Mycophenolate mofetil (Cellcept)
- Cyclophosphamide (Cytoxan)
- Rituximab (Rituxan)
Stage 3 treatment may include:
- Therapeutic plasma exchange (TPE)
- May reduce or prevent endothelial damage and the later fibrotic disease stages
Stage 4 treatment may include:
- Anti-fibrotic drugs (currently in early testing stages)
- Pirfenidone (Esbriet)
- Imatinib mesylate (Gleevec)
- Connective tissue growth factor inhibitors (CCG-203971)
Stage 5 treatment may include targeted treatments such as:
- Raynaud’s/digital ulcers
- Calcium channel blockers such as nifedipine (Procardia XL, Adalat CC, Afeditab CR)
- PDE5 inhibitors such as sildenafil (Viagra, Revatio)
- Dual endothelin receptor antagonists such as bosentan (Tracleer, Safebo)
- Gastroesophageal reflux disease (GERD)
- Omeprazole (Prilosec OTC, Zegerid OTC, OmePPi) or lansoprazole (Prevacid 24Hr, Prevacid SoluTab, Prevacid)
- Gastroparesis
- Metoclopramide (Reglan)
- Scleroderma renal crisis
- Angiotensin-converting enzyme (ACE) inhibitors
From 
Autoimmune Disease Resources
Reviewed on 1/9/2023
References
Image source: iStock Images
http://emedicine.medscape.com/article/331864-overview
https://sclerodermainfo.org/research/systemic-sclerosis-disease-staging/
http://emedicine.medscape.com/article/331864-overview
https://sclerodermainfo.org/research/systemic-sclerosis-disease-staging/