Scleroderma

Published on 02/04/2015 by admin

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149 Scleroderma

Instruction

Look at these hands.

Salient features

History

• Tight skin over face and joints

• Raynaud’s phenomenon (Case 161, p. 587)

• Puffy hands and feet

• Fatigue

• Shortness of breath (lung involvement, cardiac fibrosis), dry cough

• GI symptoms: dysphagia, diarrhoea, bloating and indigestion

• Dry eyes

• History of renal failure.

Examination

• Thickening and tightening of the skin over fingers, sclerodactyly (finger pulp atrophy) (Fig. 149.1), beaking of nails (pseudoclubbing), atrophic nails, telangiectasia (nailfold capillaries) (Fig. 149.2)

• Raynaud’s phenomenon (see Fig. 161.1)

• Subcutaneous calcification (fingers, elbows and extensor aspect of the forearms)

• Vitiligo or pigmentation.

image

Fig. 149.1 Hands in scleroderma.

image

Fig. 149.2 Digital ulcers.

(With permission from Charles et al. 2006.)

Proceed as follows:

• Assess hand function: pincer movements, handgrip, unbuttoning of clothes, abduction of thumb and writing.

• Examine:

• the joints for arthalgia or arthritis
• the face for microstomia, difficulty in opening the mouth, beak-like or pinched appearance of the nose, blotchy telangiectasia
• the abdomen for liver (primary biliary cirrhosis).

Diagnosis

This patient has sclerodactyly, tightening of the skin over hands and face (lesion) caused by scleroderma (aetiology). He has difficulty in buttoning his clothes and has marked dysphagia as a result of oesophageal involvement (functional status).

Questions

What other organ systems are involved?

Skin. Raynaud’s phenomenon, localized morphea, local or generalized oedema, hyperpigmentation, telangiectasia, subcutaneous calcification, ulceration, particularly at the fingertips. Ten-year survival rate is 71% with skin tightness limited to fingers but 21% with diffuse truncal skin involvement. Ilioprost, a prostacyclin analogue, helps to heal digital ulceration. Penicillamine improves the skin and prolongs survival in patients with early, rapidly progressive, systemic sclerosis.

Musculoskeletal system. Arthritis, myositis, myopathy, bone ischaemia with resorption of the phalanges.

GI tract. Dysphagia, reflux oesophagitis, large or small bowel obstruction.

Lung. Fibrosis, atelectasis, pulmonary hypertension; pneumonia.

Kidney. Glomerulonephritis, malignant hypertension (poorest prognosis with renal involvement). ACE inhibitors dramatically improve renal crisis.

Heart. Myocardial fibrosis.

Remember: The prognosis is worse in those with renal disease and in males. Patients with skin and/or gut involvement without other organ disease have the best prognosis. Severely debilitating oesophageal dysfunction is the most common visceral complication, and lung involvement is the leading cause of death.

What are the variants of scleroderma?

CREST syndrome (see below), eosinophilic fasciitis, Thibierge–Weissenbach syndrome.

What is ‘CREST’ syndrome?

Calcinosis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia. It has a more favourable prognosis than systemic sclerosis and is associated with the anti-centromere antibody.

Advanced-level questions

What are the criteria for diagnosis of scleroderma?

• Major criterion is proximal scleroderma (affecting metacarpophalangeals and metatarsophalangeals) (Arthritis Rheum 1980;23:581–90).

• Minor criteria are:

• sclerodactyly
• digital tip pitting or loss of substance of distal finger pads
• bi-basal pulmonary fibrosis.

At least the sole criterion or two or more minor criteria are required. These proposed criteria had a 97% sensitivity for definite systemic sclerosis and 98% specificity.

What are the subsets of scleroderma?

• Limited cutaneous scleroderma: where the skin is affected only at the extremities

• Diffuse cutaneous scleroderma: skin of trunk and extremities affected

• Scleroderma sine scleroderma: skin not affected, patients present with pulmonary fibrosis, scleroderma renal crisis, cardiac failure or malabsorption and pseudo-obstruction. The presence of anti-centromere, scleroderma-70 and anti-nuclear antibodies can be helpful.

What are the causes of anaemia in such a patient?

• Iron deficiency from chronic oesophagitis

• Folate and vitamin B deficiency from malabsorption

• Anaemia of chronic disease

• Microangiopathic haemolytic anaemia.

What are the phases of skin changes in scleroderma?

• An early oedematous phase (with pitting oedema of hands and possibly forearms, legs and face)

• The dermal phase

• An atrophic phase, followed by contracture

• Other skin changes, e.g. depigmentation.

What do you know about the pathogenesis of these skin changes?

• Endothelial damage caused by a circulatory protein factor has been implicated as an early component of the ‘inflammatory’ phase; this endothelial damage may result in the capillary and arteriolar abnormalities seen as well as affecting local access of circulating proteins acting on fibroblast-enhancing collagen secretion.

• The profibrotic phenotype of fibroblasts in scleroderma is maintained by at least three factors:

• Abnormal signalling by transforming growth factor-β (TGF-β) results in an increased level of platelet-derived growth factor receptor (PDGFR) (TGF-β1 mediates fibrosis)
• Amplification of the Ras–ERK1/2–ROS signalling loop, perhaps as a result of the upregulation of PDGFR.
• Stimulation of autoantibodies against PDGFR that initiate and maintain the Ras–ERK1/2–ROS cascade.

How would you manage a patient with scleroderma?

• Educational and psychological support

• Treat vascular abnormalities such as Raynaud’s phenomenon

• Symptomatic treatment, e.g. omeprazole for oesophagitis

• Early phase of diffuse form: immunosuppressive drugs (cyclophosphamide, methotrexate, anti-thymocyte immunoglobulin)

• Later stages: antifibrotic drugs (penicillamine, interferon).

What is the role of prednisone in the treatment of scleroderma?

Prednisone has little or no role in the treatment of scleroderma.

What are the common fatal events in this disease?

In most cases, death results from cardiac, renal or respiratory failure.

The first reports of scleroderma were by WD Chowne in 1842 and James Startin, both from London, in 1846. The term sclerodermie was suggested by E Gintrac (1791–1877) of Bordeaux; Italian physician GB Fantonetti introduced the term skleroderma in 1836.

Maurice Raynaud commented on the presence of Raynaud’s phenomenon in scleroderma in 1863.

Heirich Auspitz (1835–1886) reported, in 1863, on death from renal failure in scleroderma; this was proved to be a more than chance association by H Moore and H Sheehan of Liverpool in 1952.

David A Isenberg is Professor of Rheumatology, University College London.

Carol Black is Professor of Rheumatology, Royal Free Hospital.

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