Systemic sclerosis

Notes

## Basic introduction

  • Systemic sclerosis (SS) is an autoimmune disease of unknown etiology which is characterized by vasculopathy, thickening of the skin, internal organ involvement especially gastrointestinal system, lungs, kidney and heart as well as development of autoantibodies[a][b][c][f]
  • SS is also known as scleroderma (a word that is derived from a Greek word for hard skin)
  • The disease is characterized by the abnormal build-up of fibrous tissue in the skin that can cause it to tighten and affect other body functions[c]

## Etiology of SS[d][h]

  • The exact etiology of SS is unknown
  • Possible triggers include the following:
  • Genetic predisposition
  • Infections

|||Parvovirus B19

|||Human cytomegalovirus

|||Hepatitis B virus

|||Retroviruses

|||Helicobacter pylori

|||Chlamydia

  • Environmental factors such as:

|||Silica

|||Industrial fumes

  • Gadolinium contrast agent
  • Cytotoxics
  • Vitamin D deficiency

## Classification of scleroderma[a],[b],[c]

  • Scleroderma is classified into;
  • Systemic sclerosis (scleroderma)
  • Localized scleroderma
  • Localized scleroderma is subdivided into;
  • Morphea

|||This is a rare skin condition that causes reddish or purplish patches on the skin

  • Generalized/panscrelotic morphea
  • Progressive hemifacial atrophy
  • Linear scleroderma
  • Systemic sclerosis (SS) is subdivided into
  • Limited cutaneous scleroderma

|||Generally, it has good prognosis

|||It affects distal extremities, face and neck

  • Diffuse cutaneous scleroderma

|||Generally, it has poor prognosis

|||Visceral involvement at fairly an early stage of the disease

|||Skin changes tend to develop rapidly

  • Systemic sclerosis sine scleroderma

## Pathophysiology

  • The production of fibrosis in SS is thought to be mediated though the two major mechanisms: immunologic and ischemic mechanisms
  • Immunologic mechanism involves;
  • Excitation of immune response by external stimulus, end organ damage and genetic factors, that leads to;
  • Production of cytokine and cell recruitment , that leads to;
  • Production of growth factor, that leads to;
  • Fibrosis

NB: Auto-antibody production is occasionally involved

  • Ischemic mechanism involves;
  • Chronic endothelial cell injury by stimulus such as Raynaud’s Phenomenon, that leads to;
  • Chronic tissue injury, that leads to;
  • Chronic tissue repair (with fibroblast proliferation), that leads to;
  • Fibrosis
  • Fibrosis is characterized by:
  • Abnormal regulation of the growth of fibroblasts
  • Elevated production of;

||| Collagen

||| Fibronectin

||| Glycosaminoglycan

  • Thickening of the skin
  • Fibrosis of internal organs

## Statistics[b],[e]

  • Global prevalence: 0.019 to 0.075%
  • The disease onset is 30 -50 yrs.
  • Women to men ratio - 3-5: 1
  • Antinuclear antibodies are present in more than 95% cases of SS
  • In Kenya, a retrospective descriptive study by Illovi and Oyoo (2013) established the following:

 

Findings

Prevalence

Diffuse cutaneous SS

82%

Overlap syndromes

8%

Skin manifestations

100%

Raynaud’s phenomenon

64%

Pulmonary disease

56%

Esophageal disease

54%

Antinuclear antibodies +ve

67%

Anti- SCL-70 autoantibodies +ve

28%

Cases on immunosuppresants Rx

80%

Cases on proton pump inhibitors/prokinetics Rx

54%

Symptoms
  • Calcinosis
  • Calcium crystal deposits in tissues
  • Mainly in fingers
  • Raynaud’s phenomenon;
  • It affects hands and feet
  • It is characterized by reversible skin color change (white-blue-red)
  • It is induced by cold or emotional stress
  • Its global prevalence is 4-15%
  • Esophageal dysfunction;
  • Acid reflux
  • Barrett’s esophagus
  • Dysphagia
  • Erosive esophagitis with bleeding
  • Lower esophageal stricture
  • Reduced motility of esophagus
  • Sclerodactyly
  • Thickening and tightening of the skin of the fingers and hands
  • Telangiectasia;
  • Red marks on the surface of the skin that is caused by dilation of the capillaries 

NB: Mnemonic - CREST

  • Other symptoms and signs include the following:
  • Acro-osteolysis
  • Cardiac disorders

|||They affect about 10% of cases of SS

|||They are caused by myocardial fibrosis, pericarditis, arrhythmias and eventually heart failure

  • Chronic constipation
  • Delayed emptying of the stomach
  • Digital necrosis
  • Digital resorption
  • Digital pitting scars
  • Digital ulcers
  • Discoloration of the affected part of the skin (light or dark discoloration)
  • Diverticular
  • Gangrene
  • Fatigue
  • Fecal impaction
  • Ease of satiety
  • Inability to open the mouth
  • Joint pain and swelling
  • Loss of facial expression
  • Loss of hair and sweat gland
  • Lung disorders

|||They are caused by interstitial fibrosis and intimal thickening of pulmonary arterioles (that end up causing pulmonary hypertension)

|||These are the major cause of morbidity and mortality in later stage of SS

|||2/3 of patients with SS will be affected by these disorders in one way or another

|||They are manifested by non-productive cough, dyspnea, coarse basal crackles and limited tolerance to effort

  • Malabsorption
  • Myalgia
  • Mouth ulcers
  • Muscle atrophy (due to skin sclerosis)
  • Paralytic ileus
  • Pinched nose
  • Polyarthropathy
  • Pseudo-obstruction of GIT
  • Pursed lips (microstomia)
  • Reduced range of motion of limbs
  • Renal failure
  • Salt and pepper appearance on nose and ear
  • Sjongren’s syndrome

|||Dry eyes and mouth

  • Shortening of digits
  • Ulcers at various stages that include;

|||Edematous

|||Indurative

|||Atrophic (thick skin becomes thinner) 

  • Weight loss
Diagnosis
  • Clinical review
  • Imaging (depending on the suspected underlying cause) e.g. CXR, ECG etc.
  • Anti-Scl antibodies
  • Detected in 70% of all cases
  • Associated with diffuse cutaneous scleroderma
  • Anti-centromere antibodies
  • Detected in 40% of all cases
  • Associated with limited cutaneous scleroderma
  • VEDOSS initiative;
  • This initiative stand for: Very Early Diagnosis of SS
  • The following features are key to diagnosing SS at an very early stage;

||| Puffy fingers in Raynaud's syndrome patients

||| Antinuclear antibodies

||| Scleroderma-specific antibodies

||| SS pattern on nailfold capillaroscopy

Differential
  • Primary Raynaud's phenomenon
  • Acrodermatitis chronicum atrophicans
  • Eosinophilia-Myalgia Syndrome
  • Eosinophilic fasciitis
  • Graft-Versus-Host Disease
  • Medicines such as bleomycin and pentazocine
  • Nephrogenic systemic fibrosis
  • Polymyositis
  • Porphyria cutanea tarda
  • Radiation exposure
  • Reflex Sympathetic Dystrophy
  • Sclerodermiform genodermatoses such as progeria and Werner disease
  • Scleredema adultorum of Buschke
  • Scleredema diabeticorum
  • Scleroderma-like lesions in malignancies
  • Scleromyxoedema
  • Systemic lupus erythematosus (SLE)
Prevention
  • Not much can be done to prevent SS
  • Smoking cessation
  • Exercise
  • Protective clothing against cold
  • Correction and prevention of malnutrition
Reference
  1. Fabri, M., & Hunzelmann, N. (2007). Differential diagnosis of scleroderma and pseudoscleroderma. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 5(11), 977-983
  2. Illovi, C. S., & Oyoo, G. O. (2013). Characteristics of systemic sclerosis patients in Nairobi, Kenya: a retrospective study. African Journal of Rheumatology, 1(1), 23-27
  3. Gabrielli, A., Avvedimento, E. V., & Krieg, T. (2009). Scleroderma. New England Journal of Medicine, 360(19), 1989-2003.
  4. Nietert, P. J., & Silver, R. M. (2000). Systemic sclerosis: environmental and occupational risk factors. Current opinion in rheumatology, 12(6), 520-526.
  5. Chifflot H, Fautzi B, Sordet C. et al. Incidence and prevalence of systemic sclerosis: a systematic literature review
  6. Gilliland, B. C. (2005). Systemic sclerosis (scleroderma) and related disorders. HARRISONS PRINCIPLES OF INTERNAL MEDICINE, 16(2), 1979.
  7. Khanna, D. (2010). Diagnosis and management of systemic sclerosis. Indian Journal of Rheumatology, 5(2), 69-75
  8. Systemic Sclerosis: Current Concepts in Pathogenesis and Therapeutic Aspects of Dermatological Manifestations.
Management
  • The treatment of SS is not specific for the disease.
  • Treatment of the underlying causes such as;
  • Raynaud’s syndrome

||| Avoid cold or trauma

||| Calcium channel blockers

||| Sildenafil to relieve pulmonary arterial hypertension (PAH): Tabs 0.25 mg TID

||| Pentoxifylline

  • GIT involvement

||| Proton pump inhibitors

||| Gastro prokinetic agent such as mozapride

  • Cardiac involvement
  • Immune stimulation

||| Immunosuppressants such as corticosteroids, cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, and methotrexate   

  • Early detection and treatment of complications of SS
  • Prompt treatment of ulcers

||| Antibiotics

||| Proper dressings

||| Surgery for tight skin, nodules, and others

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