Systemic scleroderma

Last Updated: 2021-11-19

Author(s): Anzengruber, Navarini

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

- Protection from the cold (gloves, hat, heated socks).

- Physiotherapy (no isometric exercises)/ massages/respiratory training.

- Stop smoking (vasoconstriction).

- Psychotherapy.

 

Topical therapy

- Re-greasing

  • Urea-containing topical preparations
  • Excipial U Hydrolotio®
  • Excipial U Lipolotio® without perfume
  • Excipial U Lipolotio®

     

    - Light therapy

  • UVA1 whole body irradiation

     

    - Systemic therapy

  • Glucocorticoids
  • Taper off prednisolone (Spiricort®) i.v. 75-100 mg 1x t.d. and remain at 5-20 mg 1x t.d. p.o

     

    - Combined with

     

    - Azathioprine (Imurek®) p.o. 1x tgl.

  • Initial: 1-2 mg/kg bw
  • Progression: Reduction by approx. 0.5 mg/kg bw to the lowest still effective dosage.
  • CAVE: In case of concomitant administration of allopurinol, a reduction of the azathioprine dose to ¼ is indicated

     

    - or with

     

  • Ciclosporin (Sandimmun®) p.o. 3-5 mg/kg bw daily
  • Take independently of meals

     

  • Methotrexate (MTX) s.c. 15 mg 1x weekly
  • Start with 10 mg 1x weekly
  • Increase by 2.5 mg weekly until 15 mg is reached.
  • Folic acid p.o. 5 mg 1-0-0 the following day to reduce side effects

     

    - If therapy fails:

  • Cyclophosphamide (Endoxan®) 50 mg 1-4 tbl. daily
  • Combination with systemic glucocorticoids possible

     

    - Extracorporeal photopheresis

  • For circulating immune complexes or high-titer antibodies
  • One treatment at a time for 2 consecutive days
  • Low side effects
  • Although limited data exist, very positive results are reported

     

    - Intravenous immunoglobulins (IVIG)

  • Particularly to be used in arthritis, myositis and GI symptoms
  • Fibrosis of the skin ↓

     

    Symptomatic treatment

    - Reflux oesophagitis:

  • Pantoprazole p.o. 40 mg 1x tgl

    - Vessels

  • Pentoxifylline (Pentoxi® 400 mg, 100 pcs) p.o. 600 mg daily.
  • Alprostadil i.v. 10 μg 1-2x tgl.
  • Not on the market in Switzerland
  • Available in Germany under the name Prostavasin®

     

    - Lung:

  • Pulmonary hypertension
  • Bosentan (Tracleer®) (32, 62.5, 125 mg) p.o. 62.5 mg 2x daily for 4 weeks, then 2x 125 mg daily
  • Pulmonary fibrosis:
    • Cyclophosphamide (Endoxan®) 50 mg 1-4 tbl. tgl.
    • Combination with systemic glucocorticoids is possible
  • For respiratory symptoms
    • Inhaled glucocorticoids
    • Symbicort®
    • Pulmicort®

       

Therapy of 1st choice according to Lebwohl

Evidence level

Nifedipine

A

Iloprost

A

ACE inhibitor

B

   

Therapy of the 2nd choice after Lebwohl

 

Methotrexate

A

Cyclophosphamide

B

Prednisolone

B

Losartan

B

Acitretin

C

Colchicine (not commercially available in Switzerland)

C

UVA

C

Mycophenolate

C

 

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