What are the types of systemic sclerosis?

Types of Systemic Sclerosis

Systemic sclerosis is classified into three main types based on the extent and distribution of skin involvement: limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc), and SSc sine scleroderma. 1, 2, 3

Primary Classification System

Limited Cutaneous Systemic Sclerosis (lcSSc)

• Skin involvement is restricted to areas distal to the elbows and/or knees, without truncal involvement, although skin thickening may occur on the face and neck 1, 3
• Patients typically have a long history of Raynaud phenomenon before other symptoms develop 4
• This subset was formerly known as CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia) 4
• Digital ulcers and esophageal dysmotility are frequent complications 4
• Life-threatening complications can include small intestine hypomotility and pulmonary hypertension, despite generally being a milder form than dcSSc 4
• Anti-centromere antibodies are commonly associated with this subset 3

Diffuse Cutaneous Systemic Sclerosis (dcSSc)

• Skin involvement extends both distal and proximal to the knees and/or elbows and includes the trunk 1, 3
• Disease onset is much more acute compared to lcSSc, with constitutional symptoms, arthritis, carpal tunnel syndrome, and marked swelling of hands and legs 4
• Skin thickening progresses from fingers to trunk and typically increases over the first 4 years of disease, potentially regressing somewhat thereafter 3
• Internal organ involvement is common, including gastrointestinal and pulmonary fibrosis 4
• Severe life-threatening involvement of the heart and kidneys can occur, particularly scleroderma renal crisis which occurs predominantly in early dcSSc 3, 4
• Anti-topoisomerase I (Scl-70) antibodies are associated with higher frequency of interstitial lung disease 3
• Anti-RNA polymerase III antibodies indicate high risk for scleroderma renal crisis 3

SSc Sine Scleroderma

• This rare subset (1.5-8% of cases) lacks definite skin involvement but develops major internal organ-based complications 1, 3
• Patients often have a similar disease trajectory to the lcSSc subset 1
• Three subtypes have been proposed 5:
  • Type I (complete): Complete absence of any cutaneous changes typical for the disease until systemic sclerosis-related organ insufficiency occurs
  • Type II (incomplete): Absence of sclerodactyly, but other cutaneous manifestations (calcifications, telangiectasias, pitting scars) may be present
  • Type III (delayed): Clinical internal organ involvement appears before skin changes develop
• Diagnosis remains challenging and should be considered in all cases of unexplained fibrotic involvement of internal organs 5

Prescleroderma (Very Early Systemic Sclerosis)

• A potential precursor subset characterized by isolated Raynaud phenomenon, puffy fingers, specific autoantibodies, or SSc-associated capillaroscopic changes 1, 3
• Up to half of these patients develop a defined connective tissue disease (including SSc) during long-term follow-up 1

Clinical Implications of Classification

The distinction between these types is critical because:

• dcSSc has a more aggressive pace with rapid progression and higher risk of severe organ involvement 4
• lcSSc generally follows a more indolent course but can still develop life-threatening complications, particularly pulmonary hypertension 4
• Autoantibody profiles help predict disease subtype and organ involvement patterns, guiding screening and treatment strategies 2, 3
• Nearly all patients (>95%) across all subtypes present with Raynaud phenomenon, and approximately 50% develop digital ulcers 2, 3
• Gastrointestinal involvement affects nearly 90% of patients regardless of subtype 1, 2