Background/Purpose: Raynaud’s phenomenon (RP) is an early marker of microvascular damage in systemic sclerosis (SSc) and digital ulcers (DU) are a serious complication of vascular dysfunction, occurring in about 50% of SSc patients.  DU are painful, difficult to heal, and in some cases progress to gangrene and autoamputation. Current treatments for RP and DU focus on improving distal blood flow using vasodilators, vasoconstrictor antagonists, or drugs which reduce vasospasm.  Nevertheless, many patients continue to develop DU over time, suggesting the need for alternative treatment options.

Methods: We reviewed all publications between 1978 and 2016 on the use of therapeutic plasma exchange (TPE) to treat patients with SSc. Out of the 40 papers reviewed, 13 reported effects on RP and DU.  Four studies were confounded by simultaneous use of drug therapies and were excluded from the analysis shown in the table.

Results: A commonly reported finding was that a single course of a small number of weekly TPE treatments (typically four) had significant effects on both RP and DU as well as blood flow, microvessel patency, and blood rheology.  In many patients, RP disappeared or was significantly improved, and even long-standing digital ulcers began to heal. Several studies documented abnormal blood rheology pre-treatment (elevated whole blood viscosity (WBV) and RBC aggregation) that was significantly reduced after four weekly TPE treatments.  The improvements in symptoms and blood rheology were surprisingly long lasting: at least six months and in one study no reoccurrence of DU was observed at three-year follow-up.

Conclusion: In patients diagnosed with SSc, a limited course of TPE treatments appears to lead to significant improvements in RP and DU symptoms as well as objective improvements in blood flow, microvessel patency, and blood rheology that persist for several months.  Since TPE treatments have no known direct effects on blood vessels, these results suggest that TPE may have an entirely different mechanism of action.  Volkov (2006) noted that WBV is highest in patients with active DU, raising the possibility that the long-lasting normalization of whole blood viscosity and significant reduction of RBC aggregation may directly lead to enhanced microvascular blood flow and thus to improved microvessel patency and SSc symptoms.  We recommend that a randomized, double blind, placebo-control study of TPE that includes measurements of blood rheology be conducted to better understand these effects.