Scleroderma is an autoimmune disease in which the body produces too much collagen, the protein that normally gives skin and connective tissue their structure. This excess collagen causes hardening and tightening of the skin and, in some forms, damages internal organs like the lungs, heart, and digestive tract. It affects roughly 18 per 100,000 people, with women outnumbering men about five to one.
Localized vs. Systemic Scleroderma
Scleroderma falls into two broad categories that behave quite differently. Localized scleroderma (also called morphea) affects the skin and the tissue just beneath it. It shows up as patches or bands of thickened, hardened skin. Plaque morphea, the most common form in adults, produces oval patches on the trunk or limbs. Linear morphea is more common in children and can extend deeper, sometimes affecting muscle and bone underneath the skin. Localized scleroderma does not involve internal organs, and people with it typically don’t develop the blood vessel changes or organ complications seen in the systemic form.
Systemic sclerosis is the more serious type. It causes skin thickening that can spread across large areas of the body and, critically, involves internal organs. It’s further divided into two subtypes. Limited cutaneous systemic sclerosis affects skin mainly on the hands, forearms, and face, and tends to progress more slowly. Diffuse cutaneous systemic sclerosis spreads skin thickening to the trunk and upper arms and carries a higher risk of organ damage early in the disease.
Under a microscope, the two forms look identical: swollen blood vessel walls, dense collagen bundles replacing normal tissue, and loss of sweat glands and small blood vessels. The key differences are clinical. Systemic sclerosis involves Raynaud’s phenomenon (color changes in the fingers from blood vessel spasms), specific autoantibodies in the blood, and internal organ complications. Localized scleroderma generally lacks all three.
What Causes It
The underlying problem is a chain reaction involving three types of cells: the cells lining blood vessels, immune cells, and fibroblasts (the cells that produce collagen). It starts with damage to blood vessel walls, which triggers repeated cycles of constriction and reopening that starve tissues of oxygen. The immune system responds by sending lymphocytes and other inflammatory cells to the area, and those cells release chemical signals that activate fibroblasts.
Once activated, fibroblasts shift into overdrive. They transform into a more aggressive cell type called a myofibroblast, which pumps out not just collagen but a whole suite of structural proteins: fibronectin, laminin, and others that make up the scaffolding between cells. A growth factor called TGF-beta, produced by both fibroblasts and blood vessel cells, keeps this cycle running. The result is progressive fibrosis, where normal, flexible tissue is gradually replaced by dense, stiff scar-like material.
Most people with systemic sclerosis also have autoantibodies, immune proteins that mistakenly target the body’s own cells. The specific autoantibody a person carries helps predict which subtype they have and which organs are most at risk. One hypothesis suggests that the disease may be triggered by an immune reaction related to fetal cells that remain in the mother’s body after pregnancy, which could partly explain why scleroderma is so much more common in women.
Early Signs and Symptoms
For most people with systemic sclerosis, Raynaud’s phenomenon is the first clue. Roughly 95% of people with scleroderma experience it. During an episode, fingers (and sometimes toes) turn white or blue in response to cold or stress as small blood vessels clamp shut, then flush red as blood flow returns. These episodes can precede other symptoms by months or even years.
Other early signs include puffy, swollen fingers that feel stiff in the morning, skin that gradually becomes tight and shiny, and fatigue that doesn’t improve with rest. Some people notice small red spots on the face or hands (telangiectasias), which are clusters of widened blood vessels visible through the skin. Joint pain and muscle aches are common even in the early stages.
In the diffuse form, skin thickening can progress rapidly over the first one to three years, sometimes extending from the fingers up to the forearms, face, and trunk. In the limited form, skin changes tend to stay below the elbows and below the knees, plus the face, and develop much more gradually.
How It Affects Internal Organs
Lungs
Lung involvement is the most serious complication and the leading cause of scleroderma-related death. More than 40% of patients show evidence of interstitial lung disease, where fibrosis stiffens the lung tissue and makes it harder to exchange oxygen. On autopsy studies, evidence of lung scarring has been found in over 90% of patients, suggesting that some degree of lung involvement is nearly universal even when it doesn’t cause noticeable symptoms early on. Risk factors for developing significant lung disease include older age at diagnosis, having the diffuse subtype, being African American, and carrying a specific autoantibody called anti-topoisomerase I (also known as anti-Scl-70).
Pulmonary arterial hypertension, where blood pressure in the arteries feeding the lungs becomes dangerously high, is another lung complication. It’s more common in the limited subtype and can develop years after diagnosis, which is why regular screening with lung function tests and echocardiograms is standard practice.
Digestive Tract
The gastrointestinal tract is affected in the vast majority of patients, and the esophagus bears the brunt. Up to 90% of people with systemic sclerosis develop esophageal problems. The same fibrosis that hardens the skin replaces the smooth muscle of the esophagus, weakening its ability to push food downward and loosening the valve at the bottom that keeps stomach acid out.
This creates two overlapping problems. The first is acid reflux, often severe, with chronic heartburn and regurgitation. The second is difficulty swallowing, because the esophagus can no longer contract effectively to move food along. About 55% of patients develop what’s called “classic scleroderma esophagus,” where the lower esophagus has essentially no useful muscle contractions and the valve at the stomach is too weak to close properly. Left unmanaged, chronic reflux can lead to yeast infections in the esophagus or narrowing from scar tissue.
Kidneys and Heart
Scleroderma renal crisis, a sudden spike in blood pressure that can rapidly damage the kidneys, occurs in a smaller percentage of patients but is a medical emergency. Heart involvement can include inflammation of the heart muscle, irregular rhythms, or fluid buildup around the heart. Both complications are more common in the diffuse subtype.
How It’s Diagnosed
If skin thickening extends past the knuckles and up the fingers, that alone is considered strong enough evidence to classify someone as having systemic sclerosis. When skin changes are less extensive, doctors use a weighted scoring system developed jointly by the American College of Rheumatology and the European League Against Rheumatism. Points are assigned for features like Raynaud’s phenomenon, fingertip ulcers or pitting scars, abnormal nail-fold capillaries (tiny blood vessels at the base of the fingernail that look distorted under magnification), lung involvement, and the presence of specific autoantibodies.
Three autoantibodies are particularly useful for diagnosis and prognosis. Anti-centromere antibodies are linked to the limited subtype and a lower risk of lung fibrosis. Anti-topoisomerase I antibodies are associated with the diffuse subtype and a higher risk of interstitial lung disease. Anti-RNA polymerase III antibodies are connected to rapid skin progression and kidney crisis. A blood test positive for any of these carries significant weight in the diagnostic scoring.
Treatment Options
There is no cure for scleroderma, but treatments can slow organ damage and manage symptoms. For lung involvement, two medications have established roles. Nintedanib, an antifibrotic drug, slowed the rate of lung function decline by about 41 milliliters per year compared to placebo in a major clinical trial, and follow-up studies confirmed its benefit across different types of lung fibrosis. Tocilizumab, which blocks an inflammatory signal called IL-6, preserved lung function with a measurable benefit in breathing capacity, earning FDA approval for scleroderma-related lung disease. Neither drug reverses existing scarring, but both can meaningfully slow the progression.
For digestive symptoms, acid-suppressing medications are a mainstay, and drugs that help the esophagus and stomach contract more effectively can reduce swallowing difficulties. Raynaud’s episodes are managed with medications that relax blood vessels and by keeping the hands and body warm. Skin tightness and joint stiffness often benefit from physical therapy to maintain range of motion.
For severe, treatment-resistant cases, early results from a small case series using CAR-T cell therapy (a technique originally developed for blood cancers, where a patient’s own immune cells are engineered to eliminate specific immune cells driving the disease) have been striking. Six patients with severe diffuse scleroderma who hadn’t responded to at least two prior treatments received the therapy, and all showed improvement within six months with no serious adverse events. This approach remains experimental, but it represents a fundamentally different strategy: resetting the immune system rather than simply dampening it.
Long-Term Outlook
Survival statistics vary significantly by subtype. Five-year survival is approximately 87% for limited cutaneous disease and 86% for diffuse cutaneous disease. At ten years, those numbers diverge more: about 79% for limited and 70% for diffuse. The gap widens further at fifteen years, with limited at roughly 60% and diffuse at 55%. These numbers reflect all causes of death, not just scleroderma itself, and outcomes have been improving as lung screening and organ-protective treatments have become more routine.
African American women face a disproportionate burden. They develop scleroderma at nearly twice the rate of white women (2.25 vs. 1.28 per 100,000 person-years) and are more likely to develop the diffuse subtype, which carries worse outcomes. The reasons for this disparity are not fully understood but likely involve both genetic susceptibility and differences in access to early, specialized care.
The most important factor in long-term outcomes is early detection of organ involvement, particularly in the lungs and kidneys. People diagnosed with systemic sclerosis typically undergo regular lung function testing, heart imaging, and blood pressure monitoring so that complications can be caught and treated before they cause irreversible damage.