Systemic sclerosis is a rare multisystem connective tissue disease characterized by chronic inflammation, fibrosis, and vasculopathy, primarily affecting skin and internal organs, with a higher incidence in women aged 35-50. The disease presents with various symptoms including skin changes, musculoskeletal issues, organ involvement such as pulmonary and renal complications, and can be classified into localized and diffuse scleroderma. Treatment focuses on managing vascular complications and fibrosis, though no agents currently reverse the fibrotic process, with several novel therapies under investigation.

1. Systemic Sclerosis Samar Tharwat Radwan
Lecturer of Internal Medicine
(Rheumatology & Immunology)
Mansoura University

2. Definintion
Systemic sclerosis
• A multisystem connective tissue disease
• Affect the skin and internal organs
• Chronic inflammation +fibrosis+ vasculopathy

3. Incidence and Prevalence
• A rare disease
• Incidence:18-20 cases per million population per year
• Prevalence: 100 -300 cases per million population
• Age:35 -50
• More common among women (3 to 7 : 1 female-to-male ratio)

4. General Principles
• Early, signs of classic inflammatory events
• Later, indolent subclinical fibrotic process organ damage
• Skin is the site of the most dramatic physical findings
• Multisystem disease

5. Classification

6. Classification and Clinical Subsets

7. Localized
Scleroderma

8. Localized Scleroderma
Inflammatory morpheaHyper- and hypopigmentation
on the circumscribed morphea

9. Morphea subtypes
Circumscribed
morphea
Linear
morphea
En coup de
sabre
Coalescent
plaques
Pansclerotic
morphea

10. Skin Manifestations in SSc
Raynaud’s
phenomenon
Telangiectasias Ulcer Hypopigmentation
with salt and-pepper
Spotty
hypopigmented areas
Thickened skin of the
trunk
Thickened skin of the
dorsum of the hand

11. Digital tip
infarcts

12. A) Loss of finger pad substance
(B) Subcutaneous calcinosis
(C) Telangiectasias

13. Musculoskeletal disease in SSc
Flexion
contractures
Shortening of the tip of
the left index finger
Flexion contracture,
pseudoclubbing
Synovitis,
Tenosynovitis, and
Tendon Friction Rubs

14. Ischemic Digital Ulcers
Cyanotic phase of
Raynaud’s phenomenon
Pallor phase of
Raynaud’s phenomenon
Cutaneous ulcer Deep ulcer
Gangrene Autoamputation

15. subcutaneous calcinosis

16. Pulmonary Involvement
Interstitial
Lung
Disease

17. Pulmonary Artery Hypertension

18. Cardiac Involvement
• Range from clinically silent cardiac involvement to
frank heart failure
• Involveme of the endocardium, myocardium, and
pericardium separately or concomitantly
• Pericardial effusion
• Auricular and/or ventricular arrhythmias,
• Conduction disease
• Valvular regurgitation
• Myocardial ischemia,
• Myocardial hypertrophy
• Heart failure

19. Renal Involvement
• Scleroderma renal crisis (SRC) is a life-threatening
condition
• 5% -10% of patients with scleroderma.
• Risk factors:
early diffuse skin disease
use of corticosteroids
presence of anti-RNA polymerase III antibodies.
• Early pharmacologic intervention with ACE inhibitors is
crucial

20. Renal Involvement: may be due to
• Medication adverse effects
• Comorbid conditions
• Associated heart disease
• GI disease
• Lung disease
• Pauci-immune necrotizing crescentic glomerulonephritis

21. Gastrointestinal Involvement in Systemic Sclerosis (Esophagus)

22. Stomach
Gastric antral vascular
ectasia (GAVE or
watermelon stomach)

23. Small Bowel
Intestinal pseudo-obstruction
Pneumatosis intestinalis
Pneumatosis cystoides intestinalis

24. Colon and Anorectal Disorders
Constipation
Fecal
incontinence

25. Psychosocial Aspects

26. Score
assessment of
skin by the
modified
Rodnan skin
scoring system

27. Nailfold
Capillaroscopy

28. Autoantibodies

29. Patients with a total score of ≥9 are classified as having definite SSc

30. Measuring Disease Activity and Severity

31. Overlap Syndrome
• Polyarthritis
• Myositis
• Primary biliary cirrhosis
• Autoimmune hepatitis
• Vasculitis
• Rheumatoid arthritis
• Anti-neutrophil cytoplasm antibody
(ANCA)-associated pauci-immune
glomerulonephritis
• Mixed connective tissue disease

32. Systemic Sclerosis Mimics
Eosinophilic
Fasciitis
Scleredema Scleromyxedema
Nephrogenic
Systemic Fibrosis
Diabetic
Cheiroarthropathy

33. Natural
History of
Disease
A chronic monophasic illness
Internal organ involvement can be
predicted by the extent of skin affected
Indolent in patients with limited
scleroderma
Explosive multisystem disease can emerge
rapidly over in diffuse scleroderma
Males may have a more aggressive disease
course than do females

34. Summary Of Current Practical Recommendations
For Treatment

35. Treatment of Vascular Disease
• Organ-specific: SRC,PAH, and RP
• Nonspecific vasodilators
• Novel agents :prostacyclin, endothelin antagonists,
statins, and phosphodiesterase inhibitors

36. Treatment of Fibrosis
• To date, no drugs have proved able to reverse the fibrotic disease
process in scleroderma
• D-Penicillamine:?? Not used
• A human recombinant neutralizing TGF-β antibody:under study
• Tyrosine kinase inhibitors: Imatinib, dasatinib, and nilotinib
• Halofuginone:e ncouraging results
• Rosiglitazone
• Pirfenidone: antifibrotic and antiinflammatory properties
• Anti connective tissue growth factor (anti-CTGF)

37. Immunotherapy