Sign Up for a Free Account
  • Updated 04.24.2021
  • Released 04.01.1997
  • Expires For CME 04.24.2024

Systemic sclerosis

Introduction

Overview

In 1945 Goetz, emphasizing the widespread and generally worsening visceral involvement seen in some individuals with scleroderma, proposed the term “progressive systemic sclerosis.” Today we recognize that progressive systemic sclerosis, a whole body disease, can have both diffuse cutaneous involvement and limited cutaneous involvement. Either form has the potential to cause major morbidity. Progressive systemic sclerosis occurs more frequently in females, especially during the peak incidence years of 30 to 55, where the female-to-male ratio may be as high as 12 to 1. Major mechanisms accounting for the pathological changes in progressive systemic sclerosis include generalized fibrosis, systemic microangiopathy, and immunoregulatory abnormalities. Pain symptoms are common in patients with systemic sclerosis and are independently associated with more frequent episodes of Raynaud phenomenon, active ulcers, and worsening synovitis. Among the various concepts entertained for the pathophysiology of scleroderma, the role of hypoxia, cellular stress, and a concert of interacting cytokines has been highlighted. Tyrosine kinases are involved in transforming growth factor-beta and platelet-derived growth factor, which play a central role in the pathophysiology of systemic sclerosis. Clear understanding of these mechanisms might pave the way for novel therapies for systemic sclerosis.

Key points

• The development of new Raynaud phenomenon should always raise concern for incipient scleroderma.

• Pulmonary artery hypertension is a complication of scleroderma and may be seen in both limited and diffuse cutaneous disease.

• Scleroderma renal crisis can be seen in up to 10% of scleroderma patients and should be immediately managed with an ACE inhibitor.

• Antinuclear antibodies are seen in excess of 95% of scleroderma patients.

• Bone marrow transplant is increasingly a treatment option, but careful patient selection is paramount.

Historical note and terminology

The earliest description of scleroderma (skleros, hard; derma, skin) may have been made by Hippocrates around 400 BCE (Aphorism V:71). He noted, "In those persons in whom the skin is stretched, parched, and hard, the disease terminates without sweats." More definitive, early descriptions are attributed to Curzio (1753) (119), Chowne (1842), Startin (1846), and Gintrac (1847), who suggested the descriptive term sclerodermie (11). In 1863 Raynaud commented on the occurrence of peripheral vasospastic events in an individual with scleroderma. Reports of occasional visceral (lung, kidney, gastrointestinal, and cardiac) involvement in some cases of scleroderma were made in the late 1800s and early 1900s. In 1942 Thomas noted the association of calcinosis, Raynaud phenomenon, esophageal dysfunction, and telangiectasias in an individual with scleroderma. Later, in 1964 Winterbauer applied the CRST (CREST) acronym to this limited cutaneous syndrome. After it became clear that patients with CRST also had esophageal dysmotility, Velayos and colleagues added the “E,” thus, coining the term CREST (127). CREST is an acronym for calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias. Recognized subsets of scleroderma include: diffuse systemic sclerosis, limited cutaneous systemic sclerosis (CREST), localized (morphea and linear scleroderma), overlap syndromes, and undefined connective tissue disease (144; 88). Formal classification criteria for systemic sclerosis were put forth by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) in 2013. The classification system is based on a scoring system with different weight given to various clinical features and the presence of antibodies associated with scleroderma. Important exclusion criteria include patients who have scleroderma-like disorders or patients with skin thickening that spares the fingers. Skin thickening of the fingers of both hands extending proximally to the metacarpal phalangeal joints carries the most weight in the classification criteria. Other clinical criteria include skin thickening of the fingers only, fingertip lesions, telangiectasia, abnormal nailfold capillaries, pulmonary arterial hypertension or interstitial lung disease, and Raynaud phenomenon. Serologic antibodies account for only 1 numerical score given for anti-centromere, anti-topoisomerase I (anti-Scl 70), and anti-RNA polymerase III (141).

Table 1. ACR/EULAR Criteria for the Classification of Systemic Sclerosis

Item

Sub-item

Weight/Score

Skin thickening of the fingers of both hands extending proximal to the metacarpal phalangeal joints


9

Skin thickening of the fingers (only count the higher score)

• Puffy fingers
• Sclerodactyly of the fingers (distal to the MCP joints but proximal to the PIP joints)

2
4

Fingertip lesions (only count the higher score)

• Distal tip ulcers
• Fingertip pitting ulcers

2
3

Telangiectasia


2

Abnormal nailfold capillaries


2

Pulmonary arterial hypertension and/or ILD (maximum score 2)

• Pulmonary arterial hypertension
• ILD

2

2

Raynaud’s phenomenon


3

SSc-related autoantibodies (anti-centromere, anti-topoisomerase I (anti-Scl-70), anti-RNA polymerase III (maximum score 3)

• Anticentromere
• Anti-topoisomerase I
• Anti-RNA polymerase III

3


Patients with a total score of 9 or higher are classified as having definite systemic sclerosis.


This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, 
including video clips of 
neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of 
neurology in 1,200 
comprehensive articles.

Questions or Comment?

MedLink, LLC

10393 San Diego Mission Rd, Suite 120

San Diego, CA 92108-2134

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com