As Scleroderma Awareness Month spotlights a little-known autoimmune disease, researchers are working to understand why women develop scleroderma far more often than men.
The chronic condition takes its name from the Greek words for “hard skin.” Scleroderma causes the immune system to produce excess collagen, leading to the hardening and thickening of the skin. In some cases, it can also damage vital organs, including the lungs, heart, and kidneys.
Scientists believe part of the answer may lie in genetics. Women have two X chromosomes, and research suggests genes linked to scleroderma may be located on the X chromosome — which could increase the likelihood of developing the disease and explain why about 80% of people diagnosed with scleroderma are women, making it one of the autoimmune diseases that affects women at the highest rates.
Why women are affected more often
Raai Mahmood, MD, a rheumatologist in the Division of Rheumatology in the Department of Internal Medicine at The University of Texas Medical Branch (UTMB), said scleroderma most often affects women between the ages of 35 and 60. Diagnosis can be delayed, as patients often see multiple specialists before reaching a rheumatologist.
“It’s a difficult disease to diagnose because it can resemble symptoms of other conditions,” Mahmood said. “Patients may first see a primary care physician or dermatologist for skin concerns. Others may have shortness of breath and see a specialist who identifies lung fibrosis or interstitial lung disease.”
Once an autoimmune condition is suspected, patients are typically referred to a rheumatologist.
A complex disease with a range of symptoms
“Symptoms involving the skin can be mild or even deforming,” Mahmood said. “Some patients may lose mobility in their fingers or elbows. In other cases, symptoms are less visible but affect the esophagus or gastrointestinal tract.”
Scleroderma can affect multiple body systems. Early symptoms often include fingers turning blue in response to cold, tightening of the skin on the face, and acid reflux. As collagen builds up, it can narrow blood vessels, lead to ulcers on the fingertips, cause high blood pressure, create difficulty swallowing, and result in joint stiffness.
“We begin by screening for scleroderma-specific antibodies in the blood and then evaluate for complications,” Mahmood said. “Testing may include an echocardiogram, CT scan, or urine test. We start with the patient’s signs and symptoms and proceed from there.”
Risk factors for scleroderma
The exact cause of scleroderma is unknown, but both genetic and environmental factors are believed to play a role. Exposure to silica dust, often found in mining, construction, and sandblasting, has been strongly associated with the disease. Certain industrial chemicals, air pollution, infections, and severe physical trauma or stress may also increase risk.
What women should know about scleroderma and reproductive health
Because the disease disproportionately affects women, many patients ask about its impact on reproductive health.
“Scleroderma does not directly affect a woman’s reproductive system,” Mahmood said. “However, many treatments involve immunosuppressive medications, and women are advised not to become pregnant while taking them. The disease can also affect the heart and increase the risk of pulmonary hypertension, which makes pregnancy detrimental to a woman’s health.”
Skin involvement may extend to the external genitalia, she added, which can indirectly affect reproductive health, but it does not directly affect the ovaries.
The importance of self-advocacy
Mahmood emphasizes the importance of self-advocacy, especially for women who may dismiss or delay addressing symptoms.
“If you notice your skin tightening or see bluish discoloration in your fingers, ask your doctor to investigate,” she said. “Women often put their own health concerns aside. I hear that all the time.”
Some women may attribute symptoms to perimenopause or other conditions.
“It is always better to be evaluated,” she said. “There are effective treatments available, and newer therapies are being studied, including chimeric antigen receptor T-cell, or CAR-T, therapy.”
New treatments, reasons for hope
Originally developed to treat certain blood cancers, CAR-T therapy is now being studied for autoimmune diseases such as scleroderma. The approach targets B cells, a type of immune cell that can drive autoimmune activity, with the goal of resetting the immune system.
“There are many effective medications already available,” Mahmood said. “With regular monitoring, patients can stabilize. Long-term survival rates are improving, although the disease can still progress in some cases.”
Despite the challenges of diagnosis and management, Mahmood said there is reason for optimism.
“Skin symptoms can improve with treatment and monitoring,” she said. “Most patients are able to manage their condition, stabilize, and lead close to normal lives. The most important thing is to have frequent visits with the specialist, report symptoms, and advocate for yourself.”
If you are experiencing scleroderma symptoms, see a primary care provider to see what treatment options may be right for you.