⚡ Quick Start — If You Read Nothing Else

The 8 most important things to know right now.

Systemic sclerosis is a chronic autoimmune disease, not just skin hardening. It can affect the lungs, heart, kidneys, GI tract, and blood vessels. The term “scleroderma” means hard skin, but the disease goes far beyond the skin.
There are two main subtypes: limited and diffuse. Limited cutaneous SSc (lcSSc) tends to progress more slowly and is associated with anti-centromere antibodies and pulmonary arterial hypertension. Diffuse cutaneous SSc (dcSSc) progresses more rapidly with broader organ involvement and is associated with anti-Scl-70 (anti-topoisomerase I) antibodies.
Lung disease is the leading cause of death. Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) together account for the majority of SSc-related deaths. Early screening and treatment are critical.
Nintedanib (Ofev) is FDA-approved for SSc-ILD. The SENSCIS trial demonstrated that nintedanib slows the decline in lung function in SSc-associated ILD. This was a landmark achievement for the field.
Tocilizumab (Actemra) is FDA-approved for SSc-ILD. The focuSSced trial showed tocilizumab preserved lung function in early diffuse SSc with ILD, leading to FDA approval in 2021.
Stem cell transplant can be transformative for severe diffuse SSc. The ASTIS and SCOT trials showed that autologous HSCT can improve long-term survival and reverse skin and lung fibrosis in severe dcSSc, though it carries significant upfront risk.
Scleroderma renal crisis is a medical emergency. Sudden hypertension and kidney failure require immediate ACE inhibitor treatment. Corticosteroids increase the risk — avoid high-dose steroids in diffuse SSc.
Get to a scleroderma center. SSc is rare and complex. Care at a center with SSc expertise dramatically changes outcomes. A rheumatologist experienced in scleroderma, with access to a multidisciplinary team, is essential.

▼ Collapse

Understanding Systemic Sclerosis

Systemic sclerosis (SSc), commonly called scleroderma, is a chronic autoimmune disease characterized by three core processes: immune system dysregulation, vasculopathy (blood vessel damage), and fibrosis (excess scar tissue formation). These three processes interact to cause progressive hardening and thickening of the skin and potentially damage to internal organs including the lungs, heart, kidneys, and gastrointestinal tract.

SSc is not just a skin disease. While visible skin changes are often the first sign, the disease can silently affect internal organs long before symptoms appear. Early detection and proactive organ screening are critical for preserving function and quality of life.

SSc is a rare disease — there is no cure, but there are now effective treatments for many of its manifestations. The goal of treatment is to slow or stop disease progression, manage symptoms, prevent organ damage, and maintain quality of life.

Approximately 100,000 people in the United States live with systemic sclerosis
Incidence is approximately 20 per million per year in the US
Women are affected approximately 4 times more often than men
Average age of onset is 30–50 years, but SSc can occur at any age
African Americans tend to develop SSc at a younger age and have more severe disease
SSc is more common in certain occupational groups exposed to silica dust, solvents, and certain chemicals

Autoimmunity: The immune system attacks the body’s own tissues, producing specific autoantibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III) and activating inflammatory pathways
Vasculopathy: Small blood vessels are damaged, causing Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis
Fibrosis: Excessive collagen production leads to thickening and hardening of the skin and internal organs, particularly the lungs (interstitial lung disease), heart (cardiac fibrosis), and GI tract

The most important concept in this guide: SSc is a multi-organ disease that requires a team approach. Your rheumatologist should coordinate with pulmonologists (for lungs), cardiologists (for PAH and cardiac disease), gastroenterologists (for GI involvement), nephrologists (for renal crisis), and hand therapists (for contractures). Insist on regular organ screening even when you feel well.

Key Breakthroughs in Systemic Sclerosis

SSc has historically had very few effective treatments. Several important advances have changed the landscape:

FDA-APPROVED Nintedanib is a triple tyrosine kinase inhibitor originally developed for idiopathic pulmonary fibrosis (IPF). The SENSCIS trial demonstrated that nintedanib slowed the annual rate of decline in forced vital capacity (FVC) by approximately 44% compared to placebo in patients with SSc-ILD. This was the first drug to receive FDA approval specifically for SSc-ILD (September 2019). Common side effects include diarrhea and nausea.

FDA-APPROVED Tocilizumab is an IL-6 receptor inhibitor. The focuSSced trial enrolled patients with early diffuse cutaneous SSc. While the primary endpoint (skin score improvement) was not met, a key secondary endpoint showed significant preservation of lung function (FVC). Based on these lung findings, the FDA approved tocilizumab for slowing FVC decline in SSc-ILD in March 2021. Tocilizumab is given as a subcutaneous injection weekly.

GUIDELINE-SUPPORTED Two landmark randomized trials (ASTIS in Europe, SCOT in North America) demonstrated that autologous hematopoietic stem cell transplant (HSCT) provides superior long-term event-free survival compared to intravenous cyclophosphamide for severe, rapidly progressive diffuse SSc. The SCOT trial showed 79% event-free survival at 54 months with HSCT vs. 50% with cyclophosphamide (and 86% overall survival at 72 months vs. 51%). However, HSCT carries significant treatment-related mortality (approximately 6–10% in early trials, now lower at experienced centers). This is reserved for carefully selected patients with severe, early dcSSc at risk of progressive organ failure.

OFF-LABEL Rituximab, a B-cell depleting antibody, has shown promising results in observational studies and the DESIRES randomized controlled trial for improving skin fibrosis and stabilizing lung function in SSc. While not FDA-approved for SSc, rituximab is increasingly used off-label at scleroderma centers, particularly for patients with progressive skin or lung disease who do not respond to mycophenolate or cyclophosphamide. The RECITAL trial showed rituximab was non-inferior to cyclophosphamide for connective tissue disease-associated ILD.

FDA-APPROVED Upfront combination therapy for PAH (including SSc-PAH) with ambrisentan + tadalafil (AMBITION trial) is now standard of care. More recently, sotatercept (Winrevair), an activin signaling inhibitor, was FDA-approved in March 2024 for PAH based on the STELLAR trial, representing a novel mechanism of action that may benefit SSc-PAH patients. Selexipag (Uptravi) adds a third pathway. Triple or even quadruple combination therapy is now standard at expert centers.

Diagnosis: The Tests You Need

SSc diagnosis is based on clinical features, specific autoantibodies, and the ACR/EULAR 2013 classification criteria. Early diagnosis is critical because organ damage can begin before symptoms are obvious.

The ACR/EULAR 2013 criteria use a scoring system. A score of 9 or more (out of possible items) classifies a patient as having SSc:

Skin thickening of fingers extending proximal to the metacarpophalangeal joints (9 points): This single finding is sufficient for classification
Skin thickening of fingers (puffy fingers = 2, sclerodactyly = 4)
Fingertip lesions (digital tip ulcers = 2, pitting scars = 3)
Telangiectasia (2 points)
Abnormal nailfold capillaries (2 points)
Pulmonary arterial hypertension and/or ILD (2 points)
Raynaud’s phenomenon (3 points)
SSc-related autoantibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III — 3 points)

Specific autoantibodies are essential for diagnosis, subtype classification, and predicting which organs are at risk:

Anti-centromere antibody (ACA): Associated with limited cutaneous SSc, lower risk of ILD, higher risk of PAH, generally better prognosis
Anti-topoisomerase I (anti-Scl-70): Associated with diffuse cutaneous SSc, high risk of ILD, skin fibrosis progression
Anti-RNA polymerase III: Associated with diffuse cutaneous SSc, rapidly progressive skin disease, high risk of scleroderma renal crisis, and an association with concurrent malignancy
Anti-U1 RNP: Associated with overlap syndromes (SSc + myositis, lupus features)
Anti-PM/Scl: Associated with SSc-myositis overlap
Anti-Th/To, anti-U3 RNP (fibrillarin): Less common, associated with specific organ involvement patterns

At diagnosis, every SSc patient should have a comprehensive baseline organ assessment:

Pulmonary function tests (PFTs): FVC and DLCO — baseline and every 3–6 months for the first 3–5 years
High-resolution CT of the chest (HRCT): To detect ILD, even if PFTs are normal
Echocardiogram: To screen for PAH (estimated right ventricular systolic pressure), cardiac involvement
Nailfold capillaroscopy: To assess microvascular damage (giant capillaries, hemorrhages, avascular areas)
Modified Rodnan skin score (mRSS): To quantify extent and severity of skin thickening
Blood pressure monitoring: For early detection of scleroderma renal crisis
NT-proBNP: Screening marker for PAH and cardiac involvement
Complete blood count, renal function, urinalysis
GI symptom assessment: Dysphagia, reflux, motility symptoms

What type of systemic sclerosis do I have — limited or diffuse?
What are my specific autoantibodies, and what do they predict about my disease course?
Has an HRCT of my chest been done to check for interstitial lung disease?
What are my baseline pulmonary function tests, and how often should they be repeated?
Has an echocardiogram been done to screen for pulmonary arterial hypertension?
Should I be monitored for scleroderma renal crisis?
Are there any organ-specific treatments I should be starting now?
Is there a scleroderma specialist or center I should be referred to?

Subtypes & Antibody Profiles

SSc is divided into subtypes based on the extent of skin involvement. The subtype and antibody profile together help predict disease course and organ risks.

Feature	Limited Cutaneous SSc (lcSSc)	Diffuse Cutaneous SSc (dcSSc)
Skin involvement	Distal to elbows and knees; face	Proximal limbs, trunk, face; widespread
Typical antibody	Anti-centromere	Anti-Scl-70 or anti-RNA polymerase III
Raynaud’s onset	Often years before skin changes	Close to or with skin changes
Major organ risks	PAH (isolated), GI dysmotility, limited ILD	ILD, scleroderma renal crisis, cardiac, extensive GI
Progression	Generally slower; can be stable for years	Most progression in first 3–5 years
Previously called	CREST syndrome (calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, telangiectasia)	Diffuse scleroderma

Important: Limited cutaneous SSc is not “mild.” Patients with lcSSc can develop life-threatening PAH and severe GI involvement. The term “limited” refers to the distribution of skin involvement, not the severity of the disease. Both subtypes require regular organ screening.

Skin Disease

Skin thickening and hardening is the hallmark of SSc. In diffuse disease, skin involvement can be severe, restricting joint movement and causing significant disability. There is no single highly effective therapy for SSc skin disease, but several approaches can help.

GUIDELINE-SUPPORTED Mycophenolate mofetil (MMF) is the most widely used first-line immunosuppressive for SSc. The Scleroderma Lung Study II (SLS-II) showed MMF was equivalent to oral cyclophosphamide for improving FVC and was better tolerated. MMF also appears to improve skin scores in early diffuse disease. Typical dose: 2–3 g/day in divided doses.

GUIDELINE-SUPPORTED Low-dose methotrexate (15–25 mg/week) has shown modest benefit for early diffuse SSc skin disease in two small randomized trials. It is recommended by EULAR 2017 for the treatment of SSc skin disease, particularly early dcSSc. Often used when skin is the dominant problem and ILD is not present or mild.

Hand therapy and stretching exercises are essential for preventing joint contractures and maintaining function. Paraffin wax baths, gentle stretching, and splinting can help preserve hand mobility. Physical therapy should be started early and maintained throughout the disease course.

Is my skin score getting better or worse?
Should I be on mycophenolate or another immunosuppressive for my skin?
Would methotrexate help my skin disease?
Should I be referred to hand therapy?
Is my skin disease severe enough to consider more aggressive treatment?

Interstitial Lung Disease (ILD)

ILD is the leading cause of death in SSc. Approximately 40–60% of SSc patients develop some degree of ILD, and about 25% develop clinically significant progressive disease. ILD is characterized by inflammation and fibrosis of the lung tissue, leading to progressive shortness of breath and declining lung function.

FDA-APPROVED The SENSCIS trial (N=576) showed nintedanib reduced the annual rate of FVC decline by 44% vs. placebo (−52.4 mL/year vs. −93.3 mL/year). Nintedanib is taken as 150 mg twice daily with food. The most common side effect is diarrhea (76% vs. 32% placebo), which is usually manageable with loperamide and dose adjustments.

Who should receive it: Patients with SSc-ILD who have progressive or extensive disease on HRCT. Can be used alone or in combination with mycophenolate.

FDA-APPROVED The focuSSced trial studied tocilizumab in early diffuse SSc (within 5 years of onset). While the primary endpoint (skin score) was not met, the key secondary finding was preservation of FVC: mean FVC change was −0.4% predicted with tocilizumab vs. −4.6% with placebo at 48 weeks. Given as 162 mg subcutaneous injection weekly. Tocilizumab was FDA-approved for SSc-ILD in March 2021.

GUIDELINE-SUPPORTED The Scleroderma Lung Study II (SLS-II) showed mycophenolate mofetil was as effective as oral cyclophosphamide for improving FVC and reducing ILD progression, with a better safety profile. MMF is now the most widely used first-line immunosuppressive for SSc-ILD. Typical dose: 2–3 g/day. Takes 3–6 months for full effect.

GUIDELINE-SUPPORTED The Scleroderma Lung Study I (SLS-I) established that oral cyclophosphamide improved FVC and dyspnea scores compared to placebo, though the benefit faded after treatment was stopped. Due to toxicity (infections, gonadal damage, bladder toxicity, malignancy risk), cyclophosphamide is now reserved for patients who fail MMF or have severe, rapidly progressive ILD. IV pulse cyclophosphamide (monthly for 6–12 months) is preferred over daily oral dosing to reduce cumulative toxicity.

Combination approach: Many SSc-ILD experts now use a combination of mycophenolate (as background immunosuppression) plus nintedanib (as antifibrotic), particularly for progressive disease. This combines anti-inflammatory and antifibrotic mechanisms. (This MMF + nintedanib combination is a pragmatic real-world approach, not yet validated in a dedicated randomized trial; the SLS-III trial tested MMF + pirfenidone, which added no significant lung-function benefit.) A newer oral antifibrotic, nerandomilast (Jascayd), was FDA-approved in December 2025 for progressive pulmonary fibrosis — a category that can include progressive scleroderma lung disease — though it is not yet specifically approved for SSc-ILD.

Do I have interstitial lung disease? How extensive is it on my CT scan?
Is my lung function declining? By how much over the past year?
Should I start nintedanib, tocilizumab, or mycophenolate?
Would a combination of mycophenolate and nintedanib be appropriate?
How often should my PFTs and chest imaging be repeated?
Should I be evaluated for lung transplant?
Are there clinical trials for SSc-ILD I should consider?

Pulmonary Arterial Hypertension (PAH)

PAH develops in approximately 8–12% of SSc patients, more commonly in limited cutaneous SSc with anti-centromere antibodies. SSc-PAH has a worse prognosis than other forms of PAH. Early detection through annual echocardiographic screening is critical.

The DETECT algorithm is a two-step screening tool designed to identify SSc patients who should undergo right heart catheterization (RHC) to confirm PAH. Step 1 uses clinical variables (FVC/DLCO ratio, NT-proBNP, uric acid, ECG); Step 2 adds echocardiographic findings. Right heart catheterization is required to confirm the diagnosis of PAH (mean pulmonary artery pressure >20 mmHg with PAWP ≤15 mmHg and PVR >2 Wood units).

PAH therapy targets three pathways: endothelin, nitric oxide, and prostacyclin. Current guidelines recommend upfront combination therapy.

Endothelin receptor antagonists (ERAs): Ambrisentan (Letairis), bosentan (Tracleer), macitentan (Opsumit)
PDE5 inhibitors: Sildenafil (Revatio), tadalafil (Adcirca)
Soluble guanylate cyclase stimulator: Riociguat (Adempas) — do NOT combine with PDE5 inhibitors
Prostacyclin pathway agents: Epoprostenol (Flolan/Veletri — IV), treprostinil (Remodulin — SC/IV/inhaled/oral), selexipag (Uptravi — oral), iloprost (Ventavis — inhaled)
Sotatercept (Winrevair): FDA-APPROVED 2024 A novel activin signaling inhibitor approved for PAH based on the STELLAR trial. Subcutaneous injection every 3 weeks. This represents the first new PAH mechanism in over a decade.

SSc-PAH is different from other PAH. Patients with SSc-PAH tend to have worse outcomes than patients with idiopathic PAH, partly because of concurrent cardiac and lung disease. Aggressive combination therapy and consideration of lung transplant should occur earlier. Annual screening with echocardiogram, PFTs (especially DLCO), and NT-proBNP is recommended for all SSc patients.

Have I been screened for pulmonary arterial hypertension?
Should I have a right heart catheterization to confirm PAH?
Am I on the appropriate combination of PAH medications?
Should sotatercept (Winrevair) be considered for my PAH?
Is prostacyclin therapy (IV or subcutaneous) appropriate for me?
Should I be evaluated for lung transplant?

Gastrointestinal Involvement

GI involvement occurs in up to 90% of SSc patients and can affect the entire GI tract from the esophagus to the rectum. While rarely life-threatening, GI disease significantly impacts quality of life, nutrition, and medication absorption.

Proton pump inhibitors (PPIs): First-line for GERD and esophagitis. Omeprazole, esomeprazole, or pantoprazole. Often needed at high doses. Protects against Barrett’s esophagus and strictures.
Prokinetics: Domperidone (where available) or metoclopramide for esophageal dysmotility. Use metoclopramide cautiously (risk of tardive dyskinesia).
Lifestyle measures: Elevate head of bed 6–8 inches, avoid eating 3 hours before bedtime, small frequent meals, remain upright after eating.

Small intestinal bacterial overgrowth (SIBO): Very common in SSc due to dysmotility. Symptoms include bloating, diarrhea, and malabsorption. Treated with rotating antibiotics (rifaximin, ciprofloxacin, metronidazole).
Pseudo-obstruction: Intestinal dysmotility can mimic bowel obstruction. Treated with IV fluids, bowel rest, prokinetics, and sometimes octreotide.
Nutritional support: Monitor for micronutrient deficiencies (iron, B12, folate, vitamin D). Some patients require enteral or parenteral nutrition.

Should I be tested for SIBO?
Am I on the right dose of PPI for my reflux?
Should I be screened for Barrett’s esophagus?
Am I at risk for malnutrition, and should I see a dietitian?
Would a prokinetic medication help my symptoms?

Scleroderma Renal Crisis

Scleroderma renal crisis (SRC) is a medical emergency. It presents with sudden, severe hypertension and rapidly progressive kidney failure. Without immediate treatment, it is fatal. ACE inhibitors are life-saving and must be started immediately at full dose. Do NOT use ARBs as a substitute.

SRC occurs in approximately 5–10% of SSc patients, predominantly in early diffuse disease with anti-RNA polymerase III antibodies. Risk factors include corticosteroid use (especially >15 mg/day of prednisone), early diffuse SSc, and anti-RNA polymerase III positivity.

ACE inhibitors are the cornerstone: Captopril (short-acting, allowing rapid titration) or enalapril. Start immediately and titrate to maximum tolerated dose. ACE inhibitors have transformed SRC from a near-universally fatal condition to one where approximately 60–75% of patients survive.
Do NOT use corticosteroids in diffuse SSc: Corticosteroids (especially >15 mg/day prednisone) are a known trigger for SRC. Avoid in early diffuse SSc. If steroids are necessary, use the lowest possible dose and monitor blood pressure daily.
Dialysis may be needed temporarily: Some patients require dialysis during the acute phase but can recover kidney function over months if ACE inhibitor therapy is maintained.
Home blood pressure monitoring: All patients with early diffuse SSc should monitor blood pressure at home at least twice weekly.

Cardiac Involvement

Cardiac disease in SSc is increasingly recognized as a significant contributor to morbidity and mortality. It can include myocardial fibrosis, arrhythmias, pericardial effusion, conduction abnormalities, and diastolic dysfunction. Cardiac involvement may be clinically silent and detected only by advanced imaging.

Echocardiogram: Baseline and annually. Evaluates ventricular function, valve disease, pericardial effusion, and estimated PA pressures.
Cardiac MRI: More sensitive than echocardiography for detecting myocardial fibrosis and inflammation. Consider in patients with cardiac symptoms, arrhythmias, or elevated cardiac biomarkers.
ECG/Holter monitoring: For patients with palpitations, syncope, or suspected arrhythmias.
NT-proBNP and troponin: Elevated values warrant further cardiac workup.
Treatment: Standard heart failure therapy as indicated. Avoid calcium channel blockers that worsen GI dysmotility. Immunosuppression may help SSc-related myocarditis.

Raynaud’s Phenomenon & Digital Ulcers

Raynaud’s phenomenon is present in nearly all SSc patients. It causes episodes of vasospasm in the fingers (and sometimes toes, ears, nose) triggered by cold or stress, with color changes (white→blue→red). In SSc, Raynaud’s can be severe enough to cause digital ulcers and, rarely, gangrene.

Non-pharmacological: Keep entire body warm (not just hands), heated gloves, avoid cold exposure, stop smoking (critical), avoid vasoconstrictive drugs (beta-blockers if possible, decongestants, caffeine)
Calcium channel blockers: Nifedipine (extended-release) or amlodipine are first-line. Start low, titrate gradually. Side effects include headache, ankle edema, and hypotension.
PDE5 inhibitors: Sildenafil or tadalafil for refractory Raynaud’s or active digital ulcers.
Topical nitroglycerin: Applied to affected fingers; may help individual digits.

Bosentan (Tracleer): APPROVED (EU/EULAR) Reduces new digital ulcer formation. FDA-approved for PAH but used off-label in the US for digital ulcer prevention.
IV iloprost or epoprostenol: For acute, severe digital ischemia or refractory ulcers. Usually given as IV infusion over 5 days.
Wound care: Keep ulcers clean and moist. Debridement if needed. Infection surveillance and prompt antibiotic treatment. Referral to wound care or hand surgery when appropriate.
Sympathectomy: Digital sympathectomy (surgical or chemical with botulinum toxin injection) may be considered for refractory digital ischemia.

Am I on the right medications for my Raynaud’s?
Are my digital ulcers healing, or do I need more aggressive treatment?
Should I be on bosentan to prevent new ulcers?
Would IV prostacyclin therapy help my digital ulcers?
Should I be referred to a hand surgeon or wound care specialist?

Immunosuppressive Therapies

Immunosuppressive drugs are the backbone of SSc treatment, targeting the overactive immune system that drives inflammation and fibrosis. No single drug is FDA-approved as a disease-modifying therapy for SSc itself (as distinct from SSc-ILD), but several are supported by clinical trials and guidelines.

Drug	Primary Use in SSc	Key Evidence	Common Side Effects
Mycophenolate mofetil (CellCept)	ILD, skin disease; first-line	SLS-II (non-inferior to cyclophosphamide for FVC)	GI symptoms, cytopenias, infection risk
Cyclophosphamide	Severe ILD, second-line	SLS-I (improved FVC vs. placebo)	Infections, gonadal toxicity, bladder toxicity, malignancy risk
Rituximab	Skin, ILD (off-label)	DESIRES trial, RECITAL, observational data	Infusion reactions, infections, hypogammaglobulinemia
Methotrexate	Skin disease (early dcSSc)	Two small RCTs; EULAR recommended	Liver toxicity, mucositis, cytopenias; avoid in ILD (concern for MTX pneumonitis)
Tocilizumab (Actemra)	SSc-ILD (FDA-approved)	focuSSced trial (preserved FVC)	Infections, liver enzyme elevation, lipid changes

Autologous Stem Cell Transplant (HSCT)

Autologous HSCT is the most aggressive and potentially most effective treatment for severe, early diffuse SSc. It works by using high-dose chemotherapy to destroy the overactive immune system, then reconstituting it from the patient’s own stored stem cells — essentially “rebooting” the immune system.

ASTIS Trial (2014): European randomized trial (N=156). HSCT vs. 12 monthly IV cyclophosphamide pulses. In the first year, more deaths in the HSCT group (8 treatment-related deaths, about 10%). But at long-term follow-up, HSCT showed significantly better event-free survival and overall survival. Most HSCT deaths occurred in the first year.

SCOT Trial (2018): North American randomized trial (N=75). HSCT (with total body irradiation) vs. 12 monthly IV cyclophosphamide pulses. At 54 months, event-free survival was 79% with HSCT vs. 50% with cyclophosphamide. HSCT patients had significant improvement in skin scores, lung function, and quality of life. Treatment-related mortality was approximately 3% in the HSCT arm (lower than ASTIS, reflecting better patient selection and center experience).

Diffuse cutaneous SSc within the first 4–5 years of skin onset
Progressive skin or organ involvement despite conventional immunosuppression
Adequate organ function: No severe PAH (mean PAP >25–30 mmHg), no severe cardiac disease (LVEF <45%), adequate renal function
No active SRC or severe GI disease
Age typically <65 years (varies by center)

HSCT is not appropriate for: Limited cutaneous SSc, very late-stage disease with irreversible organ damage, severe PAH, severe cardiac disease, active infections.

Important reality check: HSCT for SSc is a serious procedure with significant risks, including treatment-related mortality (3–6% at experienced centers). But for carefully selected patients with severe, progressive dcSSc, it offers the best chance of halting disease progression and potentially reversing damage. It should only be performed at centers with extensive SSc-HSCT experience.

Is my disease severe enough to consider stem cell transplant?
Do I meet the inclusion criteria based on the ASTIS and SCOT trial designs?
What is the treatment-related mortality rate at the center performing the transplant?
What alternatives to HSCT should I try first?
How long is the recovery period after transplant?

class="content-section" data-stage="advanced">

Clinical Trials — Finding and Enrolling

Clinical trials are vital in SSc because approved therapies remain limited, and many organ manifestations lack effective treatments. Trials offer access to promising therapies not yet commercially available.

Trial / Program	Agent(s)	Population	NCT Number
SLS-III	MMF + pirfenidone vs. MMF + placebo	SSc-ILD	NCT03221257
RECITAL	Rituximab vs. cyclophosphamide	CTD-ILD (includes SSc-ILD)	NCT01862926
DESIRES	Rituximab vs. placebo	SSc (skin and lung endpoints)	JPRN-jRCTs031180036 (Japanese registry — jRCTs031180036)
STELLAR (completed)	Sotatercept	PAH (includes SSc-PAH subgroup)	NCT04576988
Various HSCT registries	Autologous HSCT	Severe dcSSc	Search ClinicalTrials.gov for “HSCT scleroderma”
Various anti-fibrotic trials	Novel anti-fibrotic agents	SSc skin and lung	Search ClinicalTrials.gov for “systemic sclerosis fibrosis”

ClinicalTrials.gov (clinicaltrials.gov): Search for “systemic sclerosis” or “scleroderma” and filter by status (recruiting), location, and condition.
Scleroderma Research Foundation (SRF): srfcure.org
National Scleroderma Foundation: scleroderma.org — Patient education and clinical trial listings
Your scleroderma center: Academic centers often have trials not widely advertised. Ask your rheumatologist.

International Access & Regulatory Landscape

Drug approvals and availability for SSc vary by country. Some therapies approved in one region may not be available in another.

Drug	US FDA	EMA (Europe)	PMDA (Japan)	Notes
Nintedanib (Ofev)	2019 (SSc-ILD)	2020 (progressive fibrosing ILD)	2019	EMA approved for broader progressive fibrosing ILD indication
Tocilizumab (Actemra)	2021 (SSc-ILD)	Not approved for SSc-ILD	Not approved for SSc-ILD	US-specific SSc-ILD approval; EMA did not grant indication
Bosentan (Tracleer)	PAH only	PAH + digital ulcer prevention	PAH	EU approved for digital ulcer prevention (not US)
Sotatercept (Winrevair)	2024 (PAH)	2024 (PAH)	Under review	Novel activin signaling inhibitor for PAH
Mycophenolate, cyclophosphamide, rituximab	Off-label for SSc	Off-label for SSc	Off-label for SSc	Guideline-supported but no SSc-specific regulatory approval

EULAR (European Alliance of Associations for Rheumatology): Published 2017 recommendations for SSc treatment (Kowal-Bielecka et al., Ann Rheum Dis 2017)
ACR/EULAR 2013: Classification criteria for SSc (van den Hoogen et al., Ann Rheum Dis 2013)
BSR/BHPR (UK): 2016 guidelines for management of SSc
NICE (UK): Technology appraisals for specific SSc therapies
Health Canada / CADTH: Canadian drug access pathway
EUSTAR (EULAR Scleroderma Trials and Research): Major European SSc research network and registry

Failed & De-Adopted Therapies

Understanding what has been tried and did not work helps evaluate new options and avoid ineffective treatments.

DE-ADOPTED D-penicillamine was widely used for SSc skin disease for decades. A randomized controlled trial (high dose vs. low dose) showed no difference in skin scores, and subsequent analyses confirmed no benefit over placebo. It is no longer recommended. Significant toxicity including nephrotic syndrome and cytopenias.

FAILED Recombinant human relaxin was investigated for SSc based on the hypothesis that it could reduce fibrosis. Phase 2 trials did not demonstrate significant improvement in skin scores or lung function. Development was discontinued.

FAILED Imatinib, a tyrosine kinase inhibitor, was hypothesized to have anti-fibrotic effects through TGF-beta and PDGF inhibition. Clinical trials showed no significant benefit for SSc skin or lung disease, with poor tolerability (edema, GI side effects).

INCONCLUSIVE The ASSET trial of abatacept for diffuse SSc showed a trend toward skin improvement but did not meet its primary endpoint. The drug is not currently recommended for SSc skin disease but remains under investigation in specific subpopulations.

INCONCLUSIVE While FDA-approved for idiopathic pulmonary fibrosis, pirfenidone has not been proven effective specifically for SSc-ILD. The SLS-III trial tested mycophenolate + pirfenidone versus mycophenolate + placebo and found that adding pirfenidone produced no significant lung-function benefit. Nintedanib is the preferred antifibrotic for SSc-ILD based on SENSCIS data.

Why this matters: If someone suggests one of these therapies, you now know its history. Always ask your rheumatologist about the evidence supporting any proposed treatment.

Is my disease severe enough to consider stem cell transplant?
Are there clinical trials available for my specific situation?
What new treatments are on the horizon for SSc?
Should I be evaluated for lung transplant?
Is rituximab an option for my skin or lung disease?

class="content-section" data-stage="resources">

Specialty Centers

SSc outcomes are measurably better at centers with dedicated scleroderma programs, multidisciplinary teams, and access to clinical trials. A referral to a scleroderma center is strongly recommended, even if you plan to receive most of your care locally.

No endorsement. Listing a center here does not constitute an endorsement or recommendation. Trouvera has no financial relationship with any medical center listed unless explicitly disclosed. Patients should evaluate centers based on their own needs and in consultation with their medical team.

University of Utah — Division of Rheumatology

Academic rheumatology program with scleroderma expertise and multidisciplinary ILD program

Location: 30 N 1900 E, Salt Lake City, UT 84132
Phone: 801-581-2121
Programs: Division of Rheumatology with scleroderma expertise. University of Utah ILD Program for SSc-ILD management. Huntsman Cancer Institute (801-585-0303) for HSCT evaluation. Collaboration with pulmonology, cardiology, and nephrology for multidisciplinary care.

Why it matters. The University of Utah offers comprehensive SSc care with a dedicated ILD program experienced in SSc-ILD. Huntsman Cancer Institute provides HSCT capability. The Division of Rheumatology participates in multicenter SSc clinical trials.

Intermountain Health

Phone: 801-442-2000
Programs: Rheumatology and pulmonology services across the Intermountain West. ILD expertise. Broad geographic coverage with telemedicine options for rural patients.

Primary Children’s Hospital

Location: 100 N Mario Capecchi Dr, Salt Lake City, UT 84113
Phone: 801-662-1000
Programs: Pediatric rheumatology for juvenile-onset scleroderma and related conditions.

University of Colorado — Scleroderma Program

Location: Anschutz Medical Campus, Aurora, CO 80045
Phone: 720-848-0000
Programs: Dedicated scleroderma clinic. ILD program. Clinical trial participation. HSCT evaluation.

How to choose. University of Utah = Academic rheumatology with dedicated ILD program, HSCT through HCI, clinical trial access. Intermountain Health = Broad community coverage, rheumatology and pulmonology, often in-network.

Information verified May 2026. Availability changes — confirm with each institution directly.

Johns Hopkins Scleroderma Center

Location: Baltimore, MD · Phone: 410-550-7715
One of the largest and most experienced scleroderma programs in the world. Multidisciplinary clinic with rheumatology, pulmonology, cardiology, GI, and dermatology. Extensive clinical trial portfolio. Major HSCT program for SSc.

University of Pittsburgh — Scleroderma Center of Excellence

Location: Pittsburgh, PA · Phone: 412-647-6700
Major scleroderma research center. PAH program. Clinical trials. Nailfold capillaroscopy expertise.

Georgetown University — Scleroderma Program

Location: Washington, DC · Phone: 202-444-6200
Dedicated scleroderma program with multidisciplinary care.

University of Michigan — Scleroderma Program

Location: Ann Arbor, MI · Phone: 734-936-5560
Multidisciplinary scleroderma clinic. ILD program. Clinical trial participation. HSCT available.

UCLA — Scleroderma Program

Location: Los Angeles, CA · Phone: 310-825-5510
SLS-I and SLS-II trial site. Lung transplant program experienced with SSc-ILD patients.

Hospital for Special Surgery (HSS)

Location: New York, NY · Phone: 212-606-1000
Scleroderma research and clinical program. Multidisciplinary care.

VA Rheumatology & Scleroderma Care

The VA system provides rheumatology care through its network of medical centers. For SSc requiring specialized multidisciplinary management, the VA can arrange referrals to academic scleroderma centers through community care.

George E. Wahlen VA Medical Center, Salt Lake City, UT: (801) 582-1565
VA Community Care for referral to academic scleroderma centers: 1-877-881-7618

VA Cancer Care (for HSCT evaluation): cancer.va.gov

Toronto Scleroderma Program — Mount Sinai Hospital / UHN

Location: Toronto, ON
Phone: 416-603-5800
Programs: One of the largest scleroderma programs in Canada. EUSTAR center. Clinical trial participation. HSCT evaluation available at affiliated centers.

McGill University Health Centre — Montreal

Location: Montréal, QC
Phone: 514-934-1934
Programs: Canadian Scleroderma Research Group (CSRG) participation. Clinical trials. Multidisciplinary SSc care.

University of Western Ontario — London, ON

Location: London, ON
Phone: 519-685-8500
Programs: CSRG participation. SSc-ILD program.

Scleroderma Canada: scleroderma.ca
Canadian Scleroderma Research Group: Multi-center registry and research network

International Centers of Excellence for SSc

Royal Free Hospital, London, UK: Major EUSTAR center. Pioneering SSc HSCT program (Prof. Chris Denton). UK SSc study group.
Universitätsspital Zürich, Switzerland: EUSTAR center. SSc-PAH program. Clinical trial participation.
Charité — Universitätsmedizin Berlin, Germany: Major EUSTAR center. SSc research and clinical trials.
Hôpital Cochin, Paris, France: French SSc reference center. EUSTAR center.
University of Florence, Italy: EUSTAR center. Nailfold capillaroscopy expertise.
Keio University Hospital, Tokyo, Japan: Japanese SSc research center.

Caregiver Guidance

Caring for someone with SSc requires patience, adaptability, and understanding of a disease that affects nearly every aspect of daily life. SSc is chronic, unpredictable, and often invisible to outsiders.

Cold protection: Help maintain warmth in the home. Battery-heated gloves and hand warmers for outings. Pre-warm the car before travel.
Skin care: Regular moisturizing is essential for tight skin. Avoid harsh soaps. Help with application when hand function is limited.
Meal modifications: Small, frequent meals for GI dysmotility. Soft textures if swallowing is difficult. Elevate head of bed for nighttime reflux.
Adaptive equipment: Button hooks, jar openers, electric can openers, easy-grip utensils. Occupational therapy referral for home modifications.

Acknowledge the impact. SSc changes appearance, function, and independence. Grief and frustration are normal responses.
Connect with support groups. The Scleroderma Foundation (1-800-722-4673) offers peer support, local chapter meetings, and online communities.
Watch for depression. Chronic pain, disability, and body image changes increase depression risk. Professional counseling can help.
Take care of yourself. Caregiver burnout is real. Use respite care, accept help, and maintain your own health.

Pregnancy & Scleroderma

⚠ Systemic sclerosis pregnancy is HIGH RISK and requires specialized care. Women with SSc face increased risks of preterm birth, low birth weight, preeclampsia, and — most critically — scleroderma renal crisis (SRC). Do not attempt pregnancy without pre-conception planning with a rheumatologist and maternal-fetal medicine specialist.

Key points for pregnancy with SSc

Best timing — early disease (first 5 years) carries the highest renal crisis risk; pregnancy outcomes are generally better in limited SSc and in stable, more established disease. Discuss timing with your rheumatologist before conceiving.
Scleroderma renal crisis in pregnancy — the most feared complication. Symptoms: sudden severe headache, very high blood pressure, visual changes, decreased urine output. This is an emergency. ACE inhibitors (captopril, enalapril), though normally contraindicated in pregnancy, may be life-saving for SRC; the fetal risk is weighed against maternal survival. Know these warning signs.
Medications that must be stopped before pregnancy — bosentan (Tracleer), ambrisentan, macitentan, and other endothelin receptor antagonists are severely teratogenic (Category X); must be stopped at least 1 month before conception. Mycophenolate and cyclophosphamide are contraindicated in pregnancy. Methotrexate must be stopped at least 3 months before conception.
Medications that may continue — hydroxychloroquine (Plaquenil) is generally safe in pregnancy and may actually reduce preterm birth risk in autoimmune disease; do not stop. Low-dose prednisone (10 mg/day or less) is generally acceptable with monitoring. Nifedipine or other calcium channel blockers for Raynaud disease are generally acceptable. Aspirin 81 mg is typically recommended to reduce preeclampsia risk.
Pulmonary hypertension in SSc — SSc-PAH makes pregnancy extremely high risk (maternal mortality up to 30-50%). Pregnancy is generally discouraged if you have PAH; discuss very carefully with your pulmonologist and maternal-fetal medicine specialist.
Breastfeeding — hydroxychloroquine is considered acceptable; low-dose prednisone is acceptable; most immunosuppressants should be avoided. Review all medications with your rheumatologist before breastfeeding.

Pre-pregnancy checklist for SSc patients: stabilize disease activity, optimize lung/heart/kidney function, stop teratogenic medications, plan with rheumatology and maternal-fetal medicine, and have a monitoring plan for monthly blood pressure and renal function checks throughout pregnancy.

Glossary

ACE inhibitor: Angiotensin-converting enzyme inhibitor. The critical life-saving treatment for scleroderma renal crisis. Captopril and enalapril are most commonly used.
Anti-centromere antibody (ACA): An autoantibody associated with limited cutaneous SSc, lower risk of ILD, and higher risk of PAH.
Anti-Scl-70 (anti-topoisomerase I): An autoantibody associated with diffuse cutaneous SSc and a high risk of interstitial lung disease.
Anti-RNA polymerase III: An autoantibody associated with rapidly progressive diffuse SSc, scleroderma renal crisis, and concurrent malignancy risk.
Calcinosis: Calcium deposits under the skin or in soft tissues. Common in SSc, particularly around fingers. Can cause pain and ulceration.
Diffuse cutaneous SSc (dcSSc): SSc subtype with skin thickening extending proximal to elbows and knees and on the trunk. More rapid progression and broader organ involvement.
Digital ulcers: Painful sores on the fingertips caused by impaired blood flow. Can lead to infection and tissue loss.
DLCO: Diffusing capacity of the lung for carbon monoxide. A measure of how well the lungs transfer gas. Low DLCO in SSc suggests ILD or PAH.
EUSTAR: EULAR Scleroderma Trials and Research group. Major international SSc research network and registry.
Fibrosis: Excessive formation of scar tissue. The core pathological process in SSc, affecting skin, lungs, heart, and GI tract.
FVC: Forced vital capacity. The total amount of air you can forcefully exhale. Declining FVC indicates progressive lung disease.
HRCT: High-resolution computed tomography. A type of CT scan that provides detailed images of lung tissue, used to detect and monitor ILD.
HSCT: Hematopoietic stem cell transplant. Autologous HSCT can “reboot” the immune system in severe SSc.
ILD: Interstitial lung disease. Inflammation and fibrosis of lung tissue. The leading cause of death in SSc.
Limited cutaneous SSc (lcSSc): SSc subtype with skin thickening limited to distal extremities and face. Previously called CREST syndrome.
Modified Rodnan skin score (mRSS): A standardized measure of skin thickening assessed at 17 body sites. Used to track disease progression and treatment response.
Mycophenolate mofetil (MMF): An immunosuppressive drug. First-line treatment for SSc-ILD and skin disease.
Nailfold capillaroscopy: Examination of tiny blood vessels at the base of the fingernails using a microscope. Reveals characteristic SSc vascular damage patterns.
Nintedanib (Ofev): A triple tyrosine kinase inhibitor. FDA-approved for SSc-ILD to slow FVC decline.
PAH: Pulmonary arterial hypertension. High blood pressure in the arteries of the lungs. A life-threatening complication of SSc.
Raynaud’s phenomenon: Episodes of vasospasm in fingers/toes triggered by cold or stress, causing color changes (white, blue, red). Present in nearly all SSc patients.
Scleroderma renal crisis (SRC): A medical emergency with sudden severe hypertension and kidney failure. Treated with ACE inhibitors immediately.
Telangiectasia: Dilated small blood vessels visible on the skin surface, appearing as small red spots. Common on the face, hands, and lips in SSc.
Tocilizumab (Actemra): An IL-6 receptor inhibitor. FDA-approved for SSc-ILD to slow lung function decline.
Vasculopathy: Disease of the blood vessels. One of the three core pathological processes in SSc, causing Raynaud’s, digital ulcers, PAH, and SRC.

Sources and Further Reading

This guide draws on published medical literature, clinical trial records, and the work of physicians treating SSc across multiple countries.

Primary Resources

PubMed (pubmed.ncbi.nlm.nih.gov) — Free public database of medical research
ClinicalTrials.gov (clinicaltrials.gov) — Authoritative registry of clinical trials
National Scleroderma Foundation (scleroderma.org) — Patient education and support (1-800-722-4673)
Scleroderma Research Foundation (srfcure.org) — Research funding and information
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (niams.nih.gov) — Government health information
FDA MedWatch (fda.gov/medwatch) — Report adverse events from any medication

Key Guideline and Trial References

ACR/EULAR 2013: van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis. Ann Rheum Dis. 2013;72(11):1747–1755.
EULAR 2017: Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327–1339.
BSR/BHPR 2016: Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford). 2016;55(10):1906–1910.
SENSCIS: Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019;380(26):2518–2528.
focuSSced: Khanna D, Lin CJF, Furst DE, et al. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2020;8(10):963–974.
ASTIS: van Laar JM, Farge D, Sont JK, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis. JAMA. 2014;311(24):2490–2498.
SCOT: Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;378(1):35–47.
SLS-I: Tashkin DP, Elashoff R, Clements PJ, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655–2666.
SLS-II: Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease. N Engl J Med. 2016;374(7):635–645.
STELLAR: Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478–1490.

External links notice: Links to government agencies, academic institutions, and private organizations are provided for informational convenience. Linking does not constitute endorsement by Trouvera, and we cannot attest to the accuracy of external content. You will be subject to the destination site’s privacy policy when you leave this site.

What This Guide Does Not Know

An honest guide names its own limits:

This guide cannot diagnose, subtype, or treat anyone. It does not know your autoantibodies, organ involvement, disease duration, or personal circumstances. Only your medical team can build an actual plan.
SSc treatment is evolving. New trial results and guideline updates occur regularly. Every time-sensitive fact should be re-verified with your team, on FDA.gov, and on ClinicalTrials.gov.
Drug approvals vary by country. This guide focuses primarily on FDA-approved therapies. Access differs in Europe, Asia, Canada, and other regions.
Individual outcomes cannot be predicted. Two patients with the same autoantibody can have very different disease courses. Autoantibody profiles guide monitoring but do not predict individual outcomes.
A scleroderma specialist makes a difference. SSc is rare enough that many rheumatologists see few cases. Referral to a center with SSc expertise is often the single highest-value step a patient can take.

A final word. Systemic sclerosis is a challenging diagnosis. The complexity of organ involvement, the rarity of the disease, and the limited treatment options can feel overwhelming. But the landscape is genuinely improving. Two FDA-approved therapies for SSc-ILD, proven benefit from stem cell transplant for severe disease, expanding PAH treatments, and an active clinical trial pipeline mean that more SSc patients are living longer and better than ever before. Get to a scleroderma center. Get your baseline organ screening. Ask about trials. Bring this guide to your appointments. You are not alone.