A 32-year-old woman with a diagnosis of systemic sclerosis (scleroderma) undergoes serology. Her anti-centromere antibodies (ACA) are positive, and anti-Scl-70 (anti-topoisomerase I) antibodies are negative. Which clinical feature best distinguishes limited cutaneous systemic sclerosis (lcSSc) from diffuse cutaneous systemic sclerosis (dcSSc)?

Question

Accepted Answer

B. Presence of anti-centromere antibodies and limited skin involvement distal to elbows and knees. ## Distinguishing Limited vs. Diffuse Cutaneous Systemic Sclerosis

### Serological and Clinical Phenotypes

**Key Point:** Anti-centromere antibodies (ACA) are strongly associated with limited cutaneous SSc (lcSSc), occurring in 70–80% of lcSSc cases. Anti-Scl-70 antibodies are associated with diffuse cutaneous SSc (dcSSc) and predict worse prognosis.

### Comparison Table

| Feature | Limited Cutaneous SSc (lcSSc) | Diffuse Cutaneous SSc (dcSSc) |
| --- | --- | --- |
| **Skin involvement** | Distal to elbows/knees; face | Proximal; trunk; early face involvement |
| **Anti-centromere antibodies (ACA)** | 70–80% | 5–10% |
| **Anti-Scl-70 antibodies** | 5–10% | 40–60% |
| **Onset of internal organ involvement** | Late (5–10 years) | Early (within 1–3 years) |
| **Pulmonary fibrosis** | Rare | Common (50%) |
| **Scleroderma renal crisis** | Rare (<2%) | Common (10–15%) |
| **Prognosis** | Better; longer survival | Worse; higher mortality |
| **CREST syndrome** | Classic presentation | Uncommon |

### High-Yield Mnemonic

**Mnemonic:** **CREST** — **C**alcinosis, **R**aynaud phenomenon, **E**sophageal dysmotility, **S**clerodactyly, **T**elangiectasia. This syndrome is the hallmark of lcSSc and is associated with ACA positivity.

### Clinical Pearl

**Clinical Pearl:** ACA-positive patients have a favorable long-term prognosis with slow progression and late-onset internal organ involvement. PAH (pulmonary arterial hypertension) is the most common internal organ manifestation in ACA-positive lcSSc, but it typically appears 5–10 years after disease onset, not within 1 year.

### Pathophysiology

Anti-centromere antibodies target kinetochore proteins and are associated with a more indolent, limited form of disease. Anti-Scl-70 antibodies target topoisomerase I and correlate with aggressive fibrosis and early internal organ involvement.

Answer

A. Early onset of pulmonary arterial hypertension (PAH) within 1 year of symptom onset

Answer

C. Rapid progression to renal crisis and malignant hypertension within 6 months

Answer

D. Presence of anti-Scl-70 antibodies with proximal skin involvement including trunk and face

Explanation

Distinguishing Limited vs. Diffuse Cutaneous Systemic Sclerosis

Serological and Clinical Phenotypes

Comparison Table

High-Yield Mnemonic

Clinical Pearl

Pathophysiology

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Feature	Limited Cutaneous SSc (lcSSc)	Diffuse Cutaneous SSc (dcSSc)
Skin involvement	Distal to elbows/knees; face	Proximal; trunk; early face involvement
Anti-centromere antibodies (ACA)	70–80%	5–10%
Anti-Scl-70 antibodies	5–10%	40–60%
Onset of internal organ involvement	Late (5–10 years)	Early (within 1–3 years)
Pulmonary fibrosis	Rare	Common (50%)
Scleroderma renal crisis	Rare (<2%)	Common (10–15%)
Prognosis	Better; longer survival	Worse; higher mortality
CREST syndrome	Classic presentation	Uncommon