Systemic Sclerosis

1. Overview

Systemic sclerosis (SSc), commonly known as scleroderma, is a chronic, multisystem autoimmune connective tissue disease defined by three interrelated and self-reinforcing pathological processes: immune dysregulation, widespread vasculopathy, and progressive fibrosis of the skin and internal organs. The name derives from the Greek skleros (hard) and derma (skin), reflecting the most visible manifestation — abnormal thickening and hardening of the skin — but systemic sclerosis extends far beyond the skin to affect the lungs, gastrointestinal tract, heart, kidneys, and musculoskeletal system, with potentially life-threatening consequences.

Systemic sclerosis is classified into two major subtypes based on the extent of skin involvement and the pattern of visceral disease:

• Limited cutaneous SSc (lcSSc) — skin thickening confined to the face and distal extremities (hands, forearms, feet). Formerly called CREST syndrome, an acronym for its defining features: Calcinosis cutis (calcium deposits in subcutaneous tissue), Raynaud's phenomenon (episodic digital vasospasm), Esophageal dysmotility (impaired peristalsis and reflux), Sclerodactyly (tight skin of the fingers), and Telangiectasia (dilated superficial vessels visible on face, hands, and mucous membranes). lcSSc follows a more indolent early course but carries significant long-term risk of pulmonary arterial hypertension (PAH) emerging years to decades after onset. Anti-centromere antibodies (ACA) are the serological hallmark, present in 60–80% of lcSSc patients.
• Diffuse cutaneous SSc (dcSSc) — skin thickening extends proximal to the elbows and knees and involves the trunk and face. Characterized by rapid early skin progression and earlier, more severe visceral involvement affecting the lungs, kidneys, heart, and gastrointestinal tract. Associated with anti-topoisomerase I (anti-Scl-70) antibodies (predicting interstitial lung disease) and anti-RNA polymerase III antibodies (specifically linked to scleroderma renal crisis and cancer-associated SSc).

A third subset — SSc sine scleroderma — presents with internal organ involvement and SSc-specific serology without clinically apparent skin thickening, underscoring that fibrosis is not confined to the skin. There is no cure for SSc. Management is organ-targeted, aimed at early detection and treatment of complications, and outcomes have improved substantially with the introduction of ACE inhibitors for renal crisis and targeted vasodilator therapies for PAH.

2. Epidemiology

Systemic sclerosis is a rare disease with an estimated prevalence of 150–300 cases per million population in the United States, equating to approximately 75,000–100,000 affected Americans. Incidence is approximately 9–19 new cases per million per year. Prevalence and incidence vary by geographic region; the United States and Australia report among the highest rates worldwide.

The disease shows a striking female predominance with a female-to-male ratio of approximately 4:1 overall, rising to 7–12:1 during the reproductive years (ages 30–55). This sex disparity narrows after menopause, implicating hormonal factors. Peak onset is between 30 and 50 years of age, though SSc can present at any age; pediatric SSc (juvenile SSc) accounts for fewer than 5% of all cases and tends to follow a more favorable course.

Notable racial and ethnic disparities exist. African Americans are diagnosed at a younger age, have higher rates of dcSSc and anti-Scl-70 positivity, more severe ILD and cardiac involvement, and worse overall survival compared to White Americans. The Choctaw Nation of Oklahoma has reported extraordinarily high prevalence — up to 469 per 100,000 — with evidence of strong shared genetic susceptibility. Family history confers modestly elevated risk; first-degree relatives of SSc patients have an approximately 1.6% lifetime risk compared to 0.026% in the general population. SSc clusters with other autoimmune diseases within families.

The 5- and 10-year survival rates have improved substantially since the introduction of ACE inhibitors for scleroderma renal crisis in the 1980s and targeted PAH therapies in the 2000s, though SSc still significantly shortens life expectancy in a substantial proportion of affected patients. The standardized mortality ratio remains approximately 3- to 5-fold elevated compared to age- and sex-matched controls.

3. Pathophysiology

SSc pathogenesis involves three cardinal, interlocking processes that reinforce one another in a self-sustaining cycle.

Vasculopathy

Vascular injury is the earliest pathological event. Raynaud's phenomenon — episodic vasospasm of digital arteries triggered by cold or emotional stress — is the initial symptom in the vast majority of patients, often preceding other manifestations by years. Underlying structural vascular disease involves endothelial cell activation and apoptosis, intimal hyperplasia, adventitial fibrosis, and ultimately obliterative vasculopathy of small arteries and arterioles. The resulting tissue ischemia promotes fibrosis through hypoxia-inducible pathways. Nailfold capillaroscopy directly visualizes this microvascular pathology, showing a characteristic progression from enlarged "giant" capillaries and hemorrhages (early pattern) through capillary dropout and architectural disorganization (active pattern) to avascular areas and neoangiogenesis with bizarre capillary forms (late pattern).

Immune Activation

Both innate and adaptive immune arms are activated. Plasmacytoid dendritic cells in SSc skin and lungs generate a strong type I interferon signature, similar to but distinct from lupus. CD4+ T helper cells polarize toward Th2 and Th17 phenotypes, driving profibrotic cytokine production. Regulatory T cells are functionally deficient, allowing unchecked immune activation. B cells contribute through cytokine secretion and production of disease-specific autoantibodies. Key profibrotic cytokines include:

• TGF-β (transforming growth factor beta) — the master profibrotic mediator; activates resident fibroblasts to become collagen-secreting myofibroblasts; creates an autocrine activation loop
• IL-4 and IL-13 — Th2 cytokines directly stimulating collagen synthesis and fibroblast activation
• PDGF (platelet-derived growth factor) — promotes fibroblast proliferation; agonistic autoantibodies against PDGF receptor are found in SSc
• IL-6 — pleiotropic cytokine contributing to B-cell activation, T-cell differentiation, and fibroblast stimulation
• CTGF/CCN2 (connective tissue growth factor) — amplifies TGF-β-driven collagen deposition downstream

SSc autoantibodies define clinically distinct subsets and are generally mutually exclusive (present in approximately 95% of patients):

• Anti-centromere antibodies (ACA) — 20–30% of SSc patients; strongly associated with lcSSc; predict PAH risk; relative protection from ILD and renal crisis
• Anti-topoisomerase I (anti-Scl-70) — 20–40% of dcSSc patients; strongly predict ILD and diffuse skin involvement; high specificity for SSc
• Anti-RNA polymerase III (anti-RNAP III) — 5–20% of SSc patients, predominantly dcSSc; specifically associated with scleroderma renal crisis, rapid skin progression, and cancer-coincident SSc onset
• Anti-U3 RNP (anti-fibrillarin) — approximately 5%; associated with African American race, diffuse disease, and cardiac and pulmonary involvement
• Anti-Th/To — lcSSc; associated with PAH and ILD in the absence of anti-centromere or anti-Scl-70

Fibrosis

The end result of chronic vascular injury and immune activation is progressive fibrosis mediated by myofibroblast activation. Myofibroblasts — derived from resident fibroblasts, pericytes, and circulating fibrocytes — produce excessive extracellular matrix dominated by types I and III collagen. In SSc, myofibroblasts develop a constitutive autocrine TGF-β activation loop that renders them active even in the absence of ongoing immune stimulation, explaining in part why SSc fibrosis can continue to progress despite apparent control of systemic inflammation. Fibrosis replaces normal parenchyma throughout the skin, lung, GI tract, heart, and kidney, producing the irreversible structural changes and organ dysfunction that define advanced disease.

4. Clinical Presentation

Raynaud's Phenomenon

Raynaud's phenomenon is present in approximately 95–99% of SSc patients and is typically the first symptom, often preceding formal diagnosis by months to years. The classic triphasic color change in the fingers (white → blue → red, representing vasospasm → ischemic deoxygenation → reperfusion hyperemia) occurs in response to cold or emotional stress. SSc-associated Raynaud's differs from primary Raynaud's phenomenon (which affects 3–5% of the general population) by being more severe, being associated with nailfold capillaroscopic abnormalities, and progressing to digital ulcers in 30–50% of patients. In severe cases, digital gangrene requiring amputation can occur.

Skin Involvement

The extent of skin fibrosis is quantified using the modified Rodnan skin score (mRSS), which grades skin thickening at 17 body areas on a 0–3 scale (maximum score 51). An mRSS above 15–20 is associated with greater visceral involvement and worse prognosis. Skin involvement evolves through three phases: an early edematous/puffy phase (puffy fingers and hands), an indurative phase with progressive thickening and tightening, and an atrophic phase with skin thinning and telangiectasias. SSc-specific features include:

• Sclerodactyly — tight, shiny skin of the fingers limiting flexion; can cause fixed flexion contractures
• Facial changes — taut perioral skin reducing mouth opening (microstomia), beak-like nose, beaking of the philtrum, and loss of facial expression lines
• Calcinosis cutis — subcutaneous calcium deposits at fingertips, elbows, and extensor surfaces; more common in lcSSc; can ulcerate, discharge chalky material, and become infected
• Telangiectasias — dilated capillaries visible on the face, hands, lips, and mucous membranes; prominent in lcSSc
• Pigmentary changes — hyperpigmentation and hypopigmentation in a "salt and pepper" pattern; pruritus in inflammatory early disease

Gastrointestinal Involvement

The GI tract is the most commonly affected internal organ, involved in approximately 90% of SSc patients. Any portion from mouth to anorectum can be affected:

• Esophageal dysmotility — the most common GI manifestation; smooth muscle atrophy and fibrosis cause reduced lower esophageal sphincter pressure and impaired peristalsis; symptoms include heartburn, regurgitation, and dysphagia; Barrett's esophagus is a long-term complication
• Gastroparesis — delayed gastric emptying produces early satiety, nausea, vomiting, and bloating; "watermelon stomach" (gastric antral vascular ectasia) causes occult GI bleeding in some patients
• Small intestinal hypomotility — leads to small intestinal bacterial overgrowth (SIBO) in 30–60% of patients, causing bloating, diarrhea, malabsorption, and weight loss; vitamin B12 and fat-soluble vitamin deficiencies are common sequelae
• Colonic involvement — pathognomonic wide-mouthed diverticula (large-mouthed pseudodiverticula of the antimesenteric border on barium enema), constipation, fecal incontinence from anal sphincter fibrosis, and pseudo-obstruction
• Malnutrition — a significant complication of combined GI dysfunction; protein-calorie malnutrition develops in up to 40% of patients with advanced GI disease

Pulmonary Involvement

Pulmonary complications are the leading cause of SSc-related mortality. Two distinct pulmonary complications predominate:

• Interstitial lung disease (ILD) — present radiographically in 40–75% of SSc patients; clinically significant ILD in 25–40%; nonspecific interstitial pneumonia (NSIP) is the most common histological pattern, unlike idiopathic pulmonary fibrosis where UIP predominates; associated with anti-Scl-70 antibodies; symptoms include progressive exertional dyspnea and non-productive cough; HRCT shows ground-glass opacification and reticulation in a basal-predominant, subpleural distribution
• Pulmonary arterial hypertension (PAH) — develops in 8–12% of SSc patients, with highest risk in lcSSc; arises from obliterative pulmonary vasculopathy (not fibrosis); associated with anti-centromere antibodies; presents insidiously with exertional dyspnea, fatigue, and reduced exercise tolerance; right heart catheterization (RHC) is the gold standard for diagnosis (mean pulmonary artery pressure ≥20 mmHg at rest with pulmonary vascular resistance ≥3 Wood units in the absence of left heart or significant lung disease)

Scleroderma Renal Crisis

Scleroderma renal crisis (SRC) is an acute, potentially life-threatening complication occurring in 5–10% of SSc patients, almost exclusively in dcSSc. It presents with abrupt-onset severe hypertension (systolic BP often exceeding 150–180 mmHg acutely), microangiopathic hemolytic anemia (MAHA), acute kidney injury (AKI), and thrombocytopenia — a clinical triad resembling thrombotic thrombocytopenic purpura. Risk factors include: rapidly rising mRSS, anti-RNA polymerase III antibodies, dcSSc of less than 4 years' duration, and high-dose corticosteroid use (≥15 mg/day prednisone equivalent). ACE inhibitors — specifically captopril — are the treatment of choice and have transformed SRC from near-universally fatal to survivable in approximately 60–70% of patients. ARBs do not provide equivalent benefit and should not be substituted. Despite optimal therapy, 30–40% of SRC patients require long-term renal replacement.

Cardiac Involvement

Cardiac involvement may be primary (SSc vasculopathy and fibrosis of the myocardium and conduction system) or secondary (from PAH causing right heart strain, or systemic hypertension). Primary cardiac manifestations include pericarditis, pericardial effusion, myocardial fibrosis leading to cardiomyopathy and arrhythmias, and conduction abnormalities. Clinically significant primary cardiac involvement affects approximately 15–20% of patients and is associated with poor prognosis. Ventricular arrhythmias and sudden cardiac death can occur.

5. Diagnosis

2013 ACR/EULAR Classification Criteria

The 2013 ACR/EULAR classification criteria for SSc use a weighted additive scoring system with a threshold score of 9 or greater:

• Skin thickening of both hands extending proximal to the MCPs — 9 points (sufficient alone for classification)
• Puffy fingers — 2 points; sclerodactyly of fingers only — 4 points (higher score applies)
• Fingertip lesions — digital tip ulcers: 2 points; pitting scars: 3 points (higher score applies)
• Telangiectasia — 2 points
• Abnormal nailfold capillaries — 2 points
• Pulmonary arterial hypertension and/or ILD — 2 points
• Raynaud's phenomenon — 3 points
• SSc-related antibodies (anti-centromere, anti-Scl-70, or anti-RNA polymerase III) — 3 points

These criteria have sensitivity of 91% and specificity of 92%. They do not apply to SSc sine scleroderma or when skin thickening spares the fingers.

Autoantibody Testing

• Antinuclear antibody (ANA) — positive in 90–95% of SSc patients; nucleolar or centromere pattern on IIF raises clinical suspicion
• Anti-centromere (ACA) — associated with lcSSc; predicts PAH risk and relative protection from ILD and renal crisis
• Anti-topoisomerase I (anti-Scl-70) — associated with dcSSc and ILD; high specificity for SSc
• Anti-RNA polymerase III — associated with dcSSc, rapid skin progression, scleroderma renal crisis, and concurrent cancer; warrants cancer screening at diagnosis
• Anti-U1 RNP — seen in overlap syndromes including mixed connective tissue disease (MCTD)

Nailfold Capillaroscopy

A non-invasive, inexpensive technique providing direct visualization of microvascular pathology. The Cutolo classification describes three progressive SSc capillaroscopic patterns:

• Early — few enlarged/giant capillaries, few hemorrhages, relatively preserved capillary distribution and density
• Active — frequent giant capillaries and hemorrhages, moderate capillary loss, mild architectural disorganization
• Late — severe capillary loss, extensive avascular areas, bizarre ramified and bushy neoangiogenic capillaries

Organ-Specific Assessment

• Pulmonary: HRCT chest — most sensitive for early ILD; NSIP pattern shows ground-glass opacification with traction bronchiectasis; baseline and as indicated by PFT decline
• Pulmonary: PFTs annually — FVC and DLCO; FVC decline >10% over 12 months indicates progressive ILD; disproportionately low DLCO relative to FVC raises suspicion for PAH
• PAH screening: echocardiography annually in all SSc patients; RHC required for definitive PAH diagnosis
• Renal: blood pressure and urinalysis — frequent BP monitoring in dcSSc especially in first 4 years; serum creatinine and urine protein
• Modified Rodnan skin score — trained examiner assessment at diagnosis and follow-up; primary endpoint in dcSSc clinical trials
• GI evaluation — barium swallow, esophageal manometry, gastric emptying study, breath testing for SIBO as symptoms indicate

6. Treatment

Raynaud's Phenomenon and Digital Ulcers

• Calcium channel blockers (CCBs) — extended-release nifedipine (30–120 mg/day) or amlodipine; first-line pharmacological treatment; reduce frequency and severity of Raynaud's attacks
• PDE5 inhibitors — sildenafil (20–100 mg/day) or tadalafil; effective for Raynaud's and digital ulcer healing; add-on to or alternative to CCBs
• IV prostacyclin analogues — iloprost IV infusions for severe Raynaud's, active digital ulcers, or critical digital ischemia; most potent vasodilator option
• Endothelin receptor antagonists — bosentan specifically reduces the number of new digital ulcers (RAPIDS-1 and RAPIDS-2 trials); does not accelerate healing of existing ulcers
• Digital sympathectomy — for refractory critical ischemia unresponsive to maximal medical therapy

Interstitial Lung Disease

• Mycophenolate mofetil (MMF) — 1.5–3 g/day; established as first-line therapy based on the Scleroderma Lung Study II (SLS II) trial, which demonstrated non-inferiority to oral cyclophosphamide with better tolerability and safety; continued for 2+ years in stable responders
• Nintedanib — a tyrosine kinase inhibitor (PDGFR, VEGFR, FGFR); approved for SSc-ILD based on the SENSCIS trial demonstrating approximately 44% reduction in annual FVC decline versus placebo; can be combined with MMF
• Cyclophosphamide — IV or oral; demonstrated FVC benefit in SLS I; now second-line due to toxicity (hemorrhagic cystitis, bone marrow suppression, gonadal toxicity); used as induction in severe rapidly progressive ILD
• Tocilizumab (anti-IL-6 receptor) — FDA-approved specifically for SSc-ILD based on FVC preservation data from the focuSSced trial, despite not meeting the primary skin endpoint
• Autologous HSCT — shown superior to IV cyclophosphamide for event-free survival in early dcSSc with ILD in ASTIS and SCOT trials; reserved for carefully selected patients (<50 years, early severe progressive disease, no major organ failure)

Pulmonary Arterial Hypertension

SSc-PAH is treated with the same targeted vasodilator classes used in idiopathic PAH, though SSc-PAH carries a worse prognosis than idiopathic PAH. Initial combination therapy is preferred for most moderate-to-severe cases:

• Endothelin receptor antagonists (ERAs) — ambrisentan (selective ERA) or macitentan (dual ERA); reduce pulmonary vascular resistance; monthly liver function monitoring required
• PDE5 inhibitors — sildenafil (20 mg three times daily) or tadalafil (40 mg once daily); act synergistically with ERAs; ERA + PDE5i combination (AMBITION trial) is standard of care for WHO functional class II–III
• Prostacyclin pathway agents — epoprostenol IV (continuous infusion; gold standard for WHO functional class IV), treprostinil (IV/SC/inhaled), iloprost (inhaled), selexipag (oral prostacyclin receptor agonist)
• Riociguat — soluble guanylate cyclase stimulator; alternative to PDE5 inhibitors; do not combine with PDE5 inhibitors (risk of severe hypotension)

Scleroderma Renal Crisis

• ACE inhibitors — captopril specifically — started immediately at low dose, titrated aggressively to control blood pressure; the treatment has transformed SRC from near-universally fatal to survivable in approximately 60–70% of patients; short half-life of captopril allows rapid titration
• ARBs are NOT equivalent and should not be substituted — clinical data indicate ARBs do not replicate ACE inhibitor benefit in SRC and may worsen outcomes
• Blood pressure reduction goal — gradual reduction; avoid precipitous drops that cause renal hypoperfusion; target approximately 10–15 mmHg reduction per 24 hours in the acute phase
• Dialysis — may be required acutely but should not prompt cessation of ACE inhibitors; renal recovery is possible up to 18–24 months after SRC onset
• Prevention — avoid corticosteroids ≥15 mg/day prednisone in dcSSc; educate patients to self-monitor BP and present immediately if acutely elevated

Gastrointestinal Management

• Proton pump inhibitors — high-dose (e.g., omeprazole 40 mg twice daily) for GERD, esophagitis, and prevention of Barrett's esophagus and aspiration pneumonia
• Prokinetics — metoclopramide, domperidone, low-dose erythromycin for gastroparesis and esophageal hypomotility; limited by side effects with chronic use
• SIBO treatment — rotating antibiotics (rifaximin, metronidazole, ciprofloxacin, tetracycline) cyclically or continuously; prevents antibiotic resistance from continuous monotherapy
• Nutritional support — oral caloric supplementation; enteral nutrition via gastrostomy or nasojejunal tube for severe dysmotility and malabsorption; parenteral nutrition as last resort for end-stage GI failure

Skin and Musculoskeletal Disease

• Methotrexate — modest evidence for reducing mRSS in early inflammatory dcSSc (two RCTs); most effective in the early inflammatory phase
• Corticosteroids — low-dose (<10 mg/day prednisone) for inflammatory arthritis or myositis; doses ≥15 mg/day avoided in dcSSc due to SRC risk
• Physical and occupational therapy — critical for maintaining hand function, preventing contractures, and preserving quality of life; range-of-motion exercises, paraffin wax baths, splinting

7. Complications

• Pulmonary fibrosis (ILD) — progressive respiratory failure; accounts for approximately 30–35% of SSc-related deaths; currently the leading cause of SSc mortality
• Pulmonary arterial hypertension — right heart failure; approximately 25–30% of SSc-related deaths; 5-year survival approximately 50% even with modern targeted therapy
• Scleroderma renal crisis — acute hypertensive crisis with MAHA and AKI; 30–40% of patients require permanent dialysis despite optimal ACE inhibitor treatment
• Digital ulcers and gangrene — affect 30–50% of patients; slow-healing, painful, prone to secondary infection (Staphylococcus, Pseudomonas); may require amputation in severe cases
• Cardiac fibrosis and arrhythmias — ventricular arrhythmias, complete heart block, cardiomyopathy, and sudden cardiac death; subclinical cardiac involvement is common on cardiac MRI
• Malnutrition and cachexia — from cumulative GI dysfunction, malabsorption, and poor oral intake; associated with markedly worsened survival
• Joint contractures and disability — progressive skin and tendon fibrosis causes fixed flexion contractures of fingers, wrists, and elbows, severely impairing hand function
• Calcinosis complications — painful calcium deposits that ulcerate, become chronically infected (occasionally with mycobacteria), and impair joint mobility
• Aspiration pneumonia — from esophageal dysmotility and reflux; contributes to ILD progression and acute respiratory illness
• Cancer risk — modestly elevated for lung cancer (from ILD background); anti-RNA polymerase III-positive patients have an associated risk of cancer-coincident SSc onset warranting thorough cancer evaluation at diagnosis
• Erectile dysfunction — from vasculopathy; affects a high proportion of men with SSc
• Hypothyroidism and thyroid fibrosis — autoimmune thyroid disease is a common comorbidity; fibrosis of the thyroid gland can produce hypothyroidism independently of autoimmune thyroiditis

8. Prognosis

Overall 10-year survival for SSc is approximately 65–70%, but this figure conceals major variation by subtype, organ involvement, and autoantibody profile. dcSSc has a worse short- and medium-term prognosis than lcSSc due to rapid early organ progression. In lcSSc, long-term risk from PAH emerging 10–20 years after onset can match or exceed that of dcSSc in the late disease phase.

Leading causes of SSc-related death (by current estimates):

• Interstitial lung disease — approximately 30–35% of SSc-related deaths; currently the most common cause
• Pulmonary arterial hypertension — approximately 25–30%; prognosis improved but still poor relative to idiopathic PAH
• Cardiac complications — primary myocardial fibrosis and PAH-driven right heart failure
• Scleroderma renal crisis — now less common as a cause of death following ACE inhibitor introduction; still accounts for a significant minority of SSc deaths

Autoantibody profiles predict organ-specific risk and guide surveillance intensity:

• Anti-Scl-70 — associated with ILD risk; warrants HRCT and annual PFTs with low threshold for treatment
• Anti-RNA polymerase III — associated with SRC risk; requires vigilant BP monitoring and cancer screening at diagnosis
• Anti-centromere — associated with PAH and primary biliary cholangitis; requires annual echocardiography and liver function tests

Other predictors of worse prognosis include: male sex, African American race, older age at onset, high baseline mRSS, reduced baseline FVC or DLCO, elevated BNP/NT-proBNP, elevated right heart pressures on echocardiography, and evidence of primary cardiac or renal involvement. Quality of life is substantially impaired across both subtypes, with Raynaud's attacks, pain, fatigue, dyspnea, GI symptoms, and body image disturbance collectively contributing to high rates of depression, anxiety, and functional disability. Emerging disease-modifying therapies (nintedanib, tocilizumab, autologous HSCT) continue to improve outcomes for selected patients.

Table of Contents

1. Overview
2. Epidemiology
3. Pathophysiology
4. Clinical Presentation
5. Diagnosis
6. Treatment
7. Complications
8. Prognosis
9. Research Papers
10. Connections
11. Featured Videos

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Research Papers

Curated PubMed topic searches on Systemic Sclerosis. Each link opens a live PubMed query so the result set stays current as new studies are indexed.

1. PubMed topic search: Systemic sclerosis review
2. PubMed topic search: SSc ACR/EULAR 2013 classification criteria
3. PubMed topic search: SSc ILD mycophenolate SLS II trial
4. PubMed topic search: Nintedanib SSc SENSCIS trial
5. PubMed topic search: Scleroderma renal crisis captopril ACE inhibitor
6. PubMed topic search: SSc pulmonary arterial hypertension treatment
7. PubMed topic search: SSc autoantibodies Scl-70 ACA anti-RNAP III
8. PubMed topic search: SSc Raynaud digital ulcers iloprost bosentan
9. PubMed topic search: SSc gastrointestinal dysmotility SIBO malabsorption
10. PubMed topic search: SSc HSCT ASTIS SCOT trials
11. PubMed topic search: TGF-beta fibrosis scleroderma myofibroblast
12. PubMed topic search: Nailfold capillaroscopy systemic sclerosis Cutolo pattern

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Connections

• Raynaud's Disease
• Sjogren's Syndrome
• Lupus
• Rheumatoid Arthritis
• Antiphospholipid Syndrome
• Interstitial Lung Disease
• Pulmonary Hypertension
• Chronic Kidney Disease
• SIBO
• GERD
• Vasculitis
• Fibromyalgia
• Hypothyroidism
• Vitamin D3
• Magnesium
• Turmeric
• NAC (N-Acetylcysteine)
• Fatigue
• Osteoporosis
• Ehlers-Danlos Syndrome

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Featured Videos