Systemic Sclerosis

📋 Key Information Summary

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Systemic sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease characterised by fibrosis, vasculopathy, and immune dysregulation.
Classified as limited cutaneous SSc (lcSSc) or diffuse cutaneous SSc (dcSSc) based on extent of skin involvement; dcSSc carries higher risk of internal organ disease.
Anti-centromere antibodies (ACA) associate with lcSSc and PAH; anti-Scl-70 (topoisomerase I) and RNA polymerase III associate with dcSSc and ILD/scleroderma renal crisis respectively.
Raynaud phenomenon is present in >95% of patients; secondary Raynaud with nailfold capillaroscopy abnormalities predicts internal organ involvement.
Digital ulcers occur in 30–50% of patients; treat with vasodilators (CCBs, bosentan, iloprost) and wound care.
Interstitial lung disease (ILD) is the leading cause of death in SSc; screen with PFTs and HRCT; treat with immunosuppression (mycophenolate preferred) ± nintedanib.
Scleroderma renal crisis (SRC) — acute hypertension + renal impairment — is an emergency. ACE inhibitors (captopril) are first-line; avoid corticosteroids >15 mg/day prednisolone.
Pulmonary arterial hypertension (PAH) affects 10–15% of SSc patients; screen annually with echocardiography and PFTs; confirm with right heart catheterisation.
GI dysmotility affects >90% of patients; treat symptomatically with prokinetics, PPI, antibiotics for bacterial overgrowth, and nutritional support.
Aboriginal and Torres Strait Islander patients may have reduced access to specialist rheumatology and pulmonary services; telehealth and outreach clinics are essential.

Introduction & Australian Epidemiology

Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease characterised by immune activation, obliterative vasculopathy, and progressive fibrosis of skin and internal organs. It remains one of the most lethal rheumatic diseases, with standardised mortality ratios of 3–5× the general population.

Parameter	Data
Australian prevalence	~20 per 100,000 adults
Annual incidence	~2 per 100,000
Female : male ratio	4 : 1
Peak onset	30–50 years
Leading causes of death	ILD/fibrosis, PAH, cardiac involvement

Australian data from the Scleroderma Australia Registry show that dcSSc accounts for ~40% of cases, with higher mortality compared to lcSSc. The disease carries substantial morbidity from vascular, pulmonary, and gastrointestinal complications.

Limited vs Diffuse Cutaneous SSc

Classification by LeRoy criteria determines prognosis and organ risk stratification.

Feature	lcSSc	dcSSc
Skin fibrosis	Distal to elbows/knees, face	Proximal (trunk, upper arms, thighs)
Antibodies	ACA (70–80%)	Scl-70 (30%), RNA Pol III (20%)
PAH risk	Higher	Lower
ILD risk	Moderate	High (~80%)
SRC risk	Low (~2%)	Higher (~15%)
Natural history	Slowly progressive	Rapid skin progression (peak 3–5 yr), then plateau
10-year survival	~75%	~55–65%

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RNA polymerase III positive patients: Higher risk of scleroderma renal crisis and cancer (particularly within 3 years of SSc onset). Cancer screening is recommended.

Raynaud Phenomenon & Digital Ulcers

Raynaud phenomenon (RP) is present in >95% of SSc patients and is often the earliest manifestation. Secondary RP is distinguished by nailfold capillary abnormalities, specific autoantibodies, and tissue injury.

Management of Raynaud Phenomenon

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Nifedidine XR

Adalat® · CCB — first-line vasodilator

Adult dose 30–60 mg PO daily (XR formulation)

Paediatric 0.25–0.5 mg/kg/day (limited data)

Renal adj. Start low, titrate cautiously

PBS status ✔ PBS General Benefit

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Bosentan

Tracleer® · Endothelin receptor antagonist

Adult dose 62.5 mg PO BD for 4 weeks → 125 mg PO BD

Indication Prevention of new digital ulcers (2+ ulcers)

Monitoring LFTs monthly; teratogenic — contraception required

PBS status ⚠ Authority Required — PAH/digital ulcer specialist script

Digital Ulcer Management — Step-Up Approach

1

Conservative

Wound care, avoid cold, smoking cessation, CCBs

2

Add vasodilator

PDE-5 inhibitor (sildenafil 20 mg PO TDS) or iloprost IV infusion

3

Prevention

Bosentan for recurrent ulcers; botulinum toxin injection for refractory cases

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Acute digital ischaemia: IV iloprost (2 ng/kg/min, escalate to max 6 ng/kg/min over 6 hours × 3–5 days), heparin if thrombosis suspected, surgical consult for critical gangrene. Avoid cold exposure.

Interstitial Lung Disease (SSc-ILD)

SSc-ILD is the leading cause of SSc-related death, present in up to 80% of dcSSc and 35% of lcSSc patients. NSIP is the predominant histological pattern.

Screening Protocol

Baseline HRCT + PFTs (FVC, DLCO) at diagnosis
Annual PFTs (FVC, DLCO) — more frequent if dcSSc or positive Scl-70
Repeat HRCT if FVC decline >10% or new respiratory symptoms
Consider screening with anti-Scl-70, anti-U3 RNP, and extent of skin disease

Treatment — Severity-Stratified

Mild

<10% ILD extent on HRCT

FVC >70% predicted, stable. Monitor closely with PFTs every 6–12 months.

Setting: Outpatient rheumatology

Moderate

10–20% ILD extent or declining FVC

Mycophenolate mofetil 1.5–2 g/day PO (preferred 1st-line). Cyclophosphamide IV monthly alternative.

Setting: Outpatient rheumatology + respiratory

Severe

>20% ILD extent or progressive disease

Mycophenolate or cyclophosphamide induction → consider nintedanib (antifibrotic) add-on. Lung transplant assessment if eligible.

Setting: Multidisciplinary ILD clinic

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Mycophenolate mofetil

CellCept® · Antiproliferative immunosuppressant

Adult dose 500 mg PO BD week 1 → 1 g PO BD (target 2 g/day)

Renal adj. eGFR <25: avoid or halve dose

Monitoring FBC, LFTs monthly × 3 months, then 3-monthly

PBS status ✔ PBS General Benefit

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Nintedanib

Ofev® · Antifibrotic (tyrosine kinase inhibitor)

Adult dose 150 mg PO BD with food

Indication SSc-ILD with progressive fibrosing phenotype

Side effects Diarrhoea (most common), hepatotoxicity

PBS status ⚠ Authority Required

Scleroderma Renal Crisis (SRC)

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Medical emergency. SRC occurs in ~10% of dcSSc (most within first 4 years). Characterised by acute onset hypertension (often >150/90), microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. Mortality without treatment is high.

Risk Factors

Diffuse cutaneous disease, rapidly progressive skin thickening
RNA polymerase III antibody positive
New anaemia, thrombocytopenia, or pericardial effusion
Corticosteroids >15 mg/day prednisolone — major trigger
Cyclosporine, tacrolimus use

Emergency Management

1

ACE inhibitor — immediate

Captopril 6.25–25 mg PO TDS, titrate every 24–48 hours to BP <130/80. Continue even if dialysis required — renal recovery possible over months.

2

Avoid harmful agents

No corticosteroids >15 mg, no cyclosporine, no NSAIDs. ARBs do not substitute for ACEi.

3

Renal replacement

Haemodialysis if needed; some patients recover renal function after 12–24 months on ACEi — avoid early nephrectomy.

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Captopril

Capoten® · ACE inhibitor — SRC first-line

Adult dose 6.25–25 mg PO TDS, titrate aggressively to BP target

Note Short-acting preferred in acute SRC for titration

PBS status ✔ PBS General Benefit

Monitor BP, renal function, FBC (MAHA), LDH, haptoglobin closely. Nephrology referral for all SRC patients.

Pulmonary Arterial Hypertension (PAH)

PAH (mean PAP >20 mmHg, PAWP ≤15 mmHg, PVR >3 WU on RHC) affects 10–15% of SSc patients and is the second leading cause of death. Higher risk with lcSSc, ACA positivity, longstanding disease, and digital ulcer history.

Screening Protocol

Annual echocardiography (TR velocity, RV function) + DLCO from diagnosis
Symptom assessment: dyspnoea (WHO functional class), exercise tolerance
Right heart catheterisation (RHC) if echocardiographic or functional concern
DLCO <60% predicted or declining >15% — refer for RHC

PAH Therapy — Australian Access

Drug class	Example	Route	PBS
ERA	Ambrisentan 5–10 mg daily	PO	Authority
PDE-5i	Sildenafil 20 mg TDS	PO	Authority
Prostacyclin	Treprostinil SC, epoprostenol IV	SC/IV	Authority
sGC stimulator	Riociguat 1–2.5 mg TDS	PO	Authority
Combination	ERA + PDE-5i (standard of care)	PO	Authority

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Riociguat contraindicated with PDE-5 inhibitors. ERA + PDE-5i combination is first-line dual therapy. Initiate treatment through specialised PAH centre (e.g., Royal Adelaide, St Vincent's Sydney, Alfred Melbourne).

All SSc-PAH patients require referral to a designated PAH centre for RHC confirmation, treatment initiation, and ongoing monitoring. Anticoagulation is not routinely recommended in SSc-PAH (unlike idiopathic PAH).

GI Dysmotility

GI involvement affects >90% of SSc patients and significantly impairs quality of life. Fibrosis and vasculopathy cause smooth muscle atrophy and dysmotility from mouth to anus.

Site-Specific Manifestations & Treatment

Site	Manifestation	Treatment
Oesophagus	GORD, dysphagia, Barrett's	PPI (omeprazole 20–40 mg daily), elevation of HOB, prokinetics
Stomach	Gastroparesis, early satiety	Metoclopramide 10 mg TDS or domperidone 10 mg TDS pre-meals
Small bowel	Bacterial overgrowth, pseudo-obstruction	Rotating antibiotics (ciprofloxacin, doxycycline, amoxicillin-clavulanate 1 week/month)
Colon	Constipation, pseudo-obstruction	Osmotic laxatives, fibre, prucalopride
Anorectal	Faecal incontinence	Biofeedback, sacral nerve stimulation if severe

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Prucalopride

Resotrans® · 5-HT4 agonist prokinetic

Adult dose 2 mg PO daily (1 mg if eGFR <30)

PBS status ✔ PBS General Benefit (chronic constipation)

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Nutritional screening: Weight loss >10%, BMI <18.5, or severe dysphagia → dietitian referral. Consider nasojejunal or gastrostomy feeding if oral intake insufficient. Parenteral nutrition as last resort (risk of hepatic complications).

Special Populations

🤰 Pregnancy

Mycophenolate

Teratogenic — stop ≥6 weeks before conception. Switch to azathioprine or tacrolimus.

Methotrexate

Teratogenic — stop ≥3 months before conception.

Bosentan

Teratogenic — switch to sildenafil or IV epoprostenol for PAH.

ACE inhibitors

Contraindicated in pregnancy — switch to labetalol or nifedipine for hypertension.

SRC in pregnancy

Risk of SRC persists — monitor BP closely; ACEi may be used if life-threatening SRC postpartum.

👴 Elderly

General

Late-onset SSc (>65) often dcSSc with worse prognosis. Dose-adjust for renal function. Falls risk with vasodilators.

Immunosuppression

Higher infection risk — monitor closely, consider dose reduction.

🫘 Renal Impairment

Mycophenolate

Reduce dose if eGFR <25; avoid if severe impairment.

NSAIDs

Avoid — risk of worsening renal function and triggering SRC.

Cyclophosphamide

Dose reduce by 25–50% if eGFR <30.

🛡️ Immunocompromised

Vaccination

Influenza, pneumococcal (Prevenar 13 + Pneumovax 23), COVID-19, shingles (≥50 yr) — vaccinate before starting immunosuppression where possible.

Infection risk

Monitor for PCP (consider TMP-SMX prophylaxis if on high-dose immunosuppression), TB screening before biologics.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Epidemiology

Limited Australian data on SSc prevalence in ATSI populations. Connective tissue diseases may be underdiagnosed due to reduced access to rheumatology services in remote and regional areas.

Geographic barriers

Rheumatology and PAH specialist centres are concentrated in major cities. ATSI patients in remote NT, QLD, WA face significant travel burden for RHC, HRCT, and specialist review.

Telehealth

Telehealth rheumatology consultations (MBS items 91822, 91823) should be used for follow-up. Local health workers can facilitate nailfold capillaroscopy images and BP monitoring.

Medication access

Ensure PBS Authority applications for bosentan, ambrisentan, sildenafil (PAH), and nintedanib are processed through Aboriginal Medical Services (AMS) pharmacies where possible. Closing the Gap PBS co-payment reduces out-of-pocket costs.

Cultural safety

Use Aboriginal Health Workers and Liaison Officers in care planning. Respect kinship obligations and ensure culturally appropriate discussions about prognosis, dialysis, and end-of-life care in SRC.

Comorbidities

Higher rates of renal disease, diabetes, and cardiovascular disease in ATSI populations may complicate SRC management and PAH therapy. Coordinate with local GP and AMS for chronic disease management.

📚 References

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