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Scleroderma

Scleroderma or progressive systemic sclerosis is a clinically diagnosed by classical  features of skin thickening, Raynaud’s phenomenon and organ involvement. It is characterised as a chronic multisystem connective tissue disorder, with a pathophysiological triad of vasculopathy, fibrosis due to excess deposition of collagen and extracellular matrix components, and autoimmunity. It has an incidence of approximately 20 cases per million per year. Women are more commonly affected than men (4.6 to 1).

The most common initial sign of scleroderma is Raynaud phenomenon (RP), a clinical problem of cold- and stress-induced vasospasm of the digital arteries (primarily affecting the fingers) and cutaneous arterioles involved in body thermoregulation, leading to fingers going very cold or very hot. It is most often benign and is not necessarily associated with scleroderma.

The classic diagnostic criteria of using CREST (at least 3 of 5) has been found to be inadequate for those with early disease.

The prevalence of scleroderma is higher among those of African origin and varies across regions, appearing higher in North America and Australia than in Europe and Japan.

Classification of scleroderma

  • Localised (morphea)
  • Pseudo-scleroderma
  • Systemic sclerosis
    • Limited systemic sclerosis
      • Generally milder disease, with less skin involvement, insidious onset and slow progression
      • The insidious onset may result in relatively unnoticed symptoms until internal complications occur.
    • Diffuse systemic sclerosis
      • Usually more rapid onset, with skin thickening and Raynaud’s phenomenon existing together or within a short period of time. Skin changes may spread rapidly, within months of disease onset.
      • Skin changes can subside after several years, with skin softening of and significant mobility improvement.
      • Symptoms tend to be worst in the first 3 – 5 years of the disease, after which there is a stable phase and further deterioration is unlikely. The disease may then reverse to some extent, with softening of the skin and improved mobility.
      • Internal organ involvement is more common.

Clinical Features

  • Tendon friction rubs: palpable, and sometimes audible rub on movement of the ankle, wrist, knee, shoulder, or elbow, which indicate a poor prognosis
  • Synovitis: joint tenderness on squeezing can be present
  • Subcutaneous calcinosis: present as small, localised, finger hard masses, forearms, or other pressure points such as the elbows
  • Telangiectasias: can be numerous and are usually located on the face, mucous membranes, and hands
  • Increased pulmonary component of the second heart sound indicating pulmonary hypertension
  • Features suggestive of interstitial lung disease.
  • Inflammatory arthritis
  • Active Raynaud’s phenomenon
  • Skin changes: differs in limited and diffuse disease.
    • Limited cutaneous disease is actually defined with skin thickening distal to the elbows and knees.
    • Involvement of the face is present in both diffuse and limited disease.
    • In diffuse disease demonstrate skin changes proximal to the elbows and/or involving the anterior chest and abdomen.
    • Sclerodactyly is seen in both types.

Diagnosis

  • Major criteria
    • proximal diffuse sclerosis
      • skin tightness and thickening
      • non pitting induration
  • Minor criteria
    • sclerodactyly (fingers and/or toes only)
    • digital pitting scars of loss of digital finger pad substance loss
    • pulmonary fibrosis

Investigations

Blood Tests:

  • Full blood count, renal function liver function, erythrocyte sedimentation rate (ESR) and C-reactive protein
  • Anti-nuclear antibody (positive in 90% of patients)
    • Associated with pulmonary hypertension and interstitial lung disease

To classify the sub-types

  • Anti-topoisomerase I (Scl 70) antibody (around  20%) and associated with an increased risk of interstitial lung disease
    • Associated with rapidly progressive skin thickening, renal crises and pulmonary fibrosis
  • Anti-RNA polymerase III antibody (about 20% of cases) and associated with renal crises and disease
  • Anti-centromere antibodies (20% – 25% of cases) and associated with limited skin involvement and generally a better prognosis
  • The remaining 40% have no specific antibody

Skin biopsy is usually not required.

Evaluation of pulmonary disease

  • Plain chest radiograph
  • Pulmonary function tests
  • High resolution computer tomography

All the above should be done for all confirmed scleroderma patients annually for monitoring

Evaluation of cardiac disease:

  • 12 Lead electrocardiogram
  • Trans-thoracic echocardiogram
    • If right ventricular systolic pressure (RVSP) is elevated, right heart catheterisation will be required

Evaluation of gastro-intestinal disease

  • Barium swallow for dysmotility and reflux
  • Anaemia
    • If present, investigate appropriately with e.g. upper GI endoscopy

Evaluation of muscle involvement

  • Serum creatine kinase if muscle weakness present as a possible sign of inflammatory myositis
  • If positive, nerve conduction studies +/- nerve biopsy

Differential Diagnosis

  • Amyloidosis
  • Chronic graft-versus-host disease
  • Diffuse fasciitis with eosinophilia
  • Lichen sclerosis et atrophicus
  • Eosinophilia-myalgia syndrome
  • Nephrogenic fibrosing dermopathy
  • Paraneoplastic syndromes
  • Scleromyxedema (papular mucinosis)
  • Toxic oil syndrome

Treatment

Has to be tailored to the patient due to the different manifestations and sub-types of disease.

Raynaud’s phenomenon

  • α-adrenoreceptor inhibitors
  • Angiotensin-II receptor inhibitors
    • Also aids treatment of hypertension and renal disease
  • Long acting calcium channel inhibitors
  • Pentoxifylline
  • Digital sympathectomy

Skin Fibrosis

  • Immunotherapy medications:
    • α-penicillamine, mycophenolate mofetil or cyclophosphamide

Gastroesophageal reflux disease (GORD)

  • Antacids
  • Histamine H2 inhibitors, for example ranitidine
  • Proton pump inhibitors, for example lansoprazole

Intestinal dysmotility or bacterial overgrowth

  • Antibiotics
  • Correct nutritional deficiencies
  • Promotility agents

Interstitial lung disease (see interstitial lung disease)

Pulmonary hypertension (see pulmonary hypertension)

Prognosis

Prognosis is always improving, but depends upon early diagnosis and initiation of treatment for the complications to ensure a good prognosis.