Systemic scleroderma

PSS, Progressive Systemic Scleroderma, Systemic Sclerosis, Ssc, Diffuse Scleroderma.

An autoimmune disease belonging to the collagenoses, characterised by fibrosclerosis of the skin, subcutis and internal organs (vessels, lungs, intestine, skeleton, kidney, heart, liver).

• Incidence: 0.6 -122/1000000/year (depending on study).
• Prevalence: 10-15/100.000/Jahr.
• Regional variation in prevalence (USA & Australia > Japan & Europe, Aficans > Caucasians).
• Peak in age: 30-70 yrs.
• F: M = 5-15:1

• Divisions
• Type I: Acral type
  • Hands and acras
  • Most common form
  • Vascular symptomatology very pronounced
• Type II: Proximal ascending type
  • Migrating distally (the acras) to proximally
  • Frequent involvement of the GI tract, lungs, and kidneys and liver.
• Type III: truncal sclerosis type
  • The sclerosis starts at the trunk and spreads centrifugally.
  • Vascular symptomatology may be absent (no Raynaud's phenomenon)
  • Frequent involvement of heart, GI tract and kidney.

• Often onset with complaints lasting for years
• Prodomi
  • ↓ AZ.
  • Cold hands/feet or acrocyanosis
  • Joint stiffness.
  • Livedo racemosa
  • Sensitivity to cold
  • Loss of weight
• Cutaneous manifestation
  • Raynaud's phenomenon/ Raynaud's syndrome in about 90% the first symptom
  • Reversible arterial vasoconstriction
  • In chronic vascular damage, episodes may last longer and occur more often
  • Clinical:
    • Colour changes of the fingers (Tricolore phenomenon)
      • White (pallor)
      • Blue (cyanosis)
      • Red (hyperaemia)
  • Trigger:
  • Cold or temperature changes
  • Stress
• Note
  • Primary Raynaud's syndrome: cause unknown.
  • Secondary Raynaud's syndrome: symptoms can be attributed to a disease.

• "Skin gets tighter"
  • swelling
  • hardening
  • atrophy
• Sclerosis
• Calcinosis: painful, cutaneous calcification (Thibierge-Weissenbach syndrome)
• Hyper-/hypopigmentation
• Poikiloderma (rare)

• Hands:
  • Flexion contractures (claw hand)
  • Sclerodactyly
  • Sausage fingers (oedematous fingers)
  • Madonna fingers (finger end links become narrow)
  • Sclerosed, pain-sensitive cuticle with pinpoint bleeding
  • Rat bite necrosis (digital ulcers, fingertip necrosis)
  • Nail dystrophies

• Face:
  • Tobacco bag mouth
  • Mask face (amimia, atrophic gloss)
  • Radial folding of the mouth
  • Microstomia
  • Microcheilia
  • Frenulum sclerosis

• Capillitium:
  • Atrophy of the skin
  • If applicable, diffuse alopecia

Systemic manifestation

• Skeletal system
  • Arthralgias
  • Muscle stiffness
  • Myalgias
  • Muscle strength ↓
  • Myositis
  • Osteolysis
  • Osteoporosis
  • Tendovaginitis
• GI tract affected in 90%, only approx. 50% develop symptoms
  • Dysphagia
  • Globar sensation
  • Hypomotility of the oesophagus
  • Gastrooesophageal reflux
    • →Reflux oesophagitis
    • →Barrett's oesophagus
    • Meteorism
    • Diarrhoea
• Liver
  • Primary biliary cirrhosis (in about 10%)
    • Pos. antimichondrial antibodies.
• Cardiopulmonary
  • Dizziness
  • Syncope
  • Myocarditis
  • Myocardial fibrosis
  • Pericardial effusion
  • Tachycardia
• Lung
  • Interstitial pulmonary fibrosis with restrictive ventilatory dysfunction
  • Pulmonary hypertension
  • Triad:
    • Dyspnoea (exertional and/or resting dyspnoea)
    • Unremarkable chest X-ray
    • Normal lung function
  • Dry cough
  • Thoracic pain
• Kidney
  • Malignant hypertension due to vascular fibrosis
  • Renal insufficiency
  • Proteinuria
• Eyes
  • Cataract
• Salivary glands
  • Xerophthalmia
  • Xerostomia
• Nervous system
  • Carpal tunnel syndrome
  • Trigeminal neuralgia
  • Peripheral neuropathy
• Vocal cords
  • Harsh or raspy voice.

• Special form:
• CREST sydrome
• Mostly anti-centromere-AK pos (in approx. 80%).
• In type I & II
  • Calcinosis cutis
  • Raynaud's syndrome
  • Esophagitis
  • Sclerodactyly
  • Teleangiectasia

• Lab
  • Blood count (anaemia)
  • Inflammatory values (ESR ↑, CRP ↑)
  • Liver values
  • Kidney values
  • U status
    • Leukocyturia, erythrocyturia or proteinuria
  • Rheuma factors
    • in up to 30% pos.
  • Protein electrophoresis
    • γ-globulins ↑
  • Cold agglutinins (in 25% pos.)
  • ANAs, ENAs
    • ANAs (in 90% pos.)
    • Scl 70 (70%), Anit-PmScl (<5%), Antinucleolar AK (30-80%).
• Deep biopsy (it is important that the subcutis is also biopsied)
• Oesophageal manometry
• PH manometry
  • Reflux oesophagitis
• X-ray of the hands and feet
  • z.A. of acroosteolyses, calcifications
• X-ray thorax
  • z.A. of pulmonary fibrosis
• Pulmonary function
• Cardioechography
• ECG
• Ultrasound
  • Upper abdomen, kidney and thyroid.
• Electromyography
• Skeletal scinitgraphy
• Capillaroscopy at the nail fold

• Avoid common mistakes:
• No isometric exercises should be done.
• Absolute abstinence from nicotine.
• Winter holidays should be taken in warm countries.
• Penicillin is not an adequate therapy for systemic scleroderma.

• Type I & II: ↓ disease activity in old age
• Type III: Death mostly within 3-5 years

1. Fleischmajer R. Alteration of Subcutaneous Tissue in Systemic Scleroderma. Arch Dermatol 1972;105:59.
2. Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis & Rheumatism 1980;23:581-90.
3. Bassett LW, Blocka KL, Furst DE, Clements PJ, Gold RH. Skeletal findings in progressive systemic sclerosis (scleroderma). American Journal of Roentgenology 1981;136:1121-6.
4. LeRoy EC. Pathogenesis of Scleroderma (Systemic Sclerosis). J Invest Dermatol 1982;79:87s-9s.
5. Arnett FC. HLA and Autoimmunity in Scleroderma (Systemic Sclerosis). International Reviews of Immunology 1995;12:107-28.
6. Hulshof MM, Bavinck JNB, Bergman W, et al. Double-blind, placebo-controlled study of oral calcitriol for the treatment of localized and systemic scleroderma. Journal of the American Academy of Dermatology 2000;43:1017-23.
7. Morita A, Kobayashi K, Isomura I, Tsuji T, Krutmann J. Ultraviolet A1 (340-400 nm) phototherapy for scleroderma in systemic sclerosis. Journal of the American Academy of Dermatology 2000;43:670-4.
8. Poormoghim H, Lucas M, Fertig N, Medsger Jr TA. Systemic sclerosis sine scleroderma: Demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis & Rheumatism 2000;43:444.
9. Arnett FC, Cho M, Chatterjee S, Aguilar MB, Reveille JD, Mayes MD. Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts. Arthritis & Rheumatism 2001;44:1359-62.
10. Seyger MMB, van den Hoogen FHJ, van Vlijmen-Willems IMJJ, van de Kerkhof PCM, J de Jong EMG. Localized and systemic scleroderma show different histological responses to methotrexate therapy. J Pathol 2001;193:511-6.
11. Agarwal SK, Tan FK, Arnett FC. Genetics and Genomic Studies in Scleroderma (Systemic Sclerosis). Rheumatic Disease Clinics of North America 2008;34:17-40.
12. Kowal-Bielecka O, Landewe R, Avouac J, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Annals of the Rheumatic Diseases 2009;68:620-8.
13. Varga, J. (2016). Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults. Uptodate.com. Retrieved 31 May 2016, from http://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-sclerosis-scleroderma-in-adults?source=search_result&search=sklerodemie+systemische&selectedTitle=1%7E150
14. Denton, C. (2016). Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults. Uptodate.com. Retrieved 31 May 2016, from http://www.uptodate.com/contents/overview-of-the-treatment-and-prognosis-of-systemic-sclerosis-scleroderma-in-adults?source=search_result&search=sklerodemie+systemische&selectedTitle=2%7E150
15. Varga, J. (2016). Diagnosis and differential diagnosis of systemic sclerosis (scleroderma) in adults. Uptodate.com. Retrieved 31 May 2016, from http://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-systemic-sclerosis-scleroderma-in-adults?source=search_result&search=sklerodemie+systemische&selectedTitle=3%7E150