Associated pain, ulceration and critical ischaemia can impose a major burden on affected patients, and require careful management both in the acute context and in the outpatient setting.

Disease spectrum and clinical issues

Digital ischaemia is a complication of Raynaud’s phenomenon which may be primary (Raynaud’s disease) or secondary (Raynaud’s syndrome). The prevalence of Raynaud’s phenomenon varies depending on climate, ranging from 5.7-20.1% in women.¹ Raynaud’s syndrome is associated with a number of rheumatological diseases including systemic sclerosis, systemic lupus erythematosus, dermatomyositis,  polymyositis, rheumatoid arthritis (RA) and Buerger’s disease.²

Raynaud’s syndrome imposes a major clinical burden on affected patients. The Pittsburgh scleroderma database, focusing on a group of over 2,000 patients, determined that almost 60% had experienced at least one digital ulcer over the course of their illness.³ The detrimental effect of such ulceration on patients’ quality of life should not be underestimated, due to associated pain and functional impairment.⁴

Clinical evaluation

In the patient with known connective tissue disease presenting with digital ischaemia, an appropriate physical examination is vital. Signs of ischaemia should be sought, namely discolouration, ulceration, tenderness/pain and frank gangrene. Pulses should be palpated and Doppler ultrasound utilised as necessary.

Angiography has a valuable role, its main indication being the identification of proximal lesions amenable to surgical intervention in cases of severe ischaemia.⁵ The choice of angiographic technique may be dictated by the resources an individual clinician has at their disposal. Prompt referral to a surgical service is essential in cases of severe ischaemia, particularly considering the positive outcomes associated with surgical intervention as shall be detailed later in this article.

Management of digital ischaemia

The management of affected patients primarily comprises the appropriate utilisation of various supportive and vasodilatory pharmacological agents. Avoidance of factors precipitating ischaemia plays a valuable role. Exposure to cold should be avoided and patients should avoid vasoconstrictive medications such as beta-blockers.⁶

Smoking cessation should be strongly advocated in individuals with systemic sclerosis as it appears beneficial in reducing the severity of Raynaud’s phenomenon in this population.⁷

Vasodilatory medications

Calcium channel blockers (CCBs) are the mainstay of treatment of both secondary and (when necessitated by severity) primary Raynaud’s phenomenon. 

The European League Against Rheumatism (EULAR) recommends that dihydropyridine calcium channel blockers, usually nifedipine, should be considered as first-line therapy of systemic sclerosis-associated Raynaud’s syndrome.⁸ CCBs reduce the severity of attacks in this population by 35%.⁹

Prostacyclin analogues are potent vasodilators. Most benefit is derived from their intravenous administration and thus their use is restricted to the inpatient setting. Studies have shown that intravenous iloprost is effective in decreasing the frequency and severity of attacks and in preventing or healing digital ulcers.¹⁰

Typically, a six-hour infusion of iloprost is given daily for a three-to-five-day period with the dose being titrated upward according to tolerance. Side-effects such as flushing, headaches and hypotension are common and thus attentive nursing care is vital.

Endothelin-1 receptor antagonists have attracted considerable research interest in recent years. EULAR recommends their use in diffuse systemic sclerosis with multiple ulcers after failure of the therapies outlined above.⁸

Endothelin-1 is a potent vasoconstrictor and blocking it with oral agents such as bosentan reduces the number of digital ulcers by 30% but does not increase the healing of existing ulcers.¹¹

Phosphodiesterase-5 (PDE-5) inhibitors and nitrates are widely used but the evidence for these therapies is lacking. A number of recent studies have reported a benefit for short-term PDE-5 inhibition^12,13,14 but further studies are necessary.

Supportive measures

Adequate analgesia is essential and the use of opioids is frequently necessary. Swabs should be taken and antibiotics prescribed if there is a possibility of superimposed infection. Additional therapies intended to modify vascular risk factors, such as aspirin and statins, are often prescribed intuitively. Surprisingly, evidence for the former is somewhat lacking but atorvastatin has been shown to improve Raynaud’s severity.¹⁵ 

Surgical options

In the event of failure of medical therapy, surgery is indicated. Options include microsurgical revascularisation, digital arterial reconstruction and peripheral sympathectomy. These measures may improve digital vascular perfusion, heal ulcers and reduce pain.¹⁶

Conclusion

Digital ischaemia is a common manifestation of a variety of rheumatological diseases and represents a debilitating, burdensome phenomenon. 

Patient education regarding simple lifestyle adjustments can greatly reduce risk of ischaemia and its complications. Management is largely with vasodilatory agents, namely calcium channel blockers, prostacyclin analogues and, in selected cases, endothelin-1 antagonists. 

References

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13. Herrick AL, van den Hoogen F, Gabrielli A et al. Modified-release sildenafil reduces Raynaud’sphenomenon attack frequency in limited cutaneous systemic sclerosis. Arthritis Rheum 2011; 63(3): 775-782 
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