Plasma Exchange Therapy in Patients with
Complex Regional Pain Syndrome
Authors: Alexander Guillermo M. 
Published: February 2021

Background: Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most
often develops following trauma. Some investigators have postulated CRPS to be a post-traumatic
neuralgia associated with distal degeneration of small-diameter peripheral axons. Intravenous
immunoglobulin treatment (IVIG) has been shown to be efficacious in the treatment of painful
polyneuropathies. Some CRPS patients have been reported to respond to IVIG. Based on a recent
hypothesis proposing an autoimmune etiology for CRPS, we decided to offer plasma exchange
therapy (PE) to CRPS patients with a clinical presentation suggestive of a small fiber neuropathy.
Objectives: To evaluate the efficacy of PE in a group of CRPS patients with a clinical presentation
suggestive of a small fiber neuropathy that were either non-responders or poor responders to their
current treatment.
Study Design: This is a retrospective case series study of CRPS patients that met the Budapest
diagnostic criteria for CRPS and received PE as treatment for their illness between September 2012 and
June 2014. Approval for this review was granted by the Drexel University Institutional Review Board.
Setting: Drexel University College of Medicine pain clinic
Methods: Thirty-three CRPS patients that received PE treatment were retrospectively studied. The
workup for these patients consisted of a complete medical and pain evaluation, the completion of
the short-form McGill questionnaire, quantitative sensory testing (QST), and skin punch biopsy. The
PE protocol was as follows: all patients had a series of PE therapies (range 5 to 11 with a mean of
7.2) performed over a 2 to 3 week period. Following the PE series, the patients had a pain evaluation
and completed the short-form McGill questionnaire. Patients that responded to PE were offered
maintenance therapy consisting of either weekly PE or other immune modulating agents. In these
patients, their pain was evaluated during the maintenance phase.
Results: Thirty of the 33 patients demonstrated significant (P < 0.01) median pain reduction of 64%
following the initial series of PE. Three patients demonstrated no improvement. Twenty-four patients
are receiving maintenance therapy, the pain reduction in these patients following the initial PE series
has been maintained with either weekly PE (n = 15), oral immune modulating agents (n = 8), or IVIG
(n = 1). The remaining 6 patients are not receiving maintenance therapy and their pain has returned
to pre-treatment levels. In addition, this study suggests that patients with the greatest loss of small
fibers and the greatest temperature sensory deficits are most likey to benefit from PE therapy.
Limitations: The major limitation of this study is its retrospective nature which includes nonrandomization, non-blinding, and an uncontrolled design.
Conclusions: This study shows that PE is effective in a subset of patients with severe long-standing
CRPS and that the reduction in pain following the initial series of PE treatments can be maintained
on a weekly PE schedule, IVIG, or with other immune modulating drugs. Large, randomized, placebo
controlled studies may be required to confirm and expand these results. Such studies may lead to
new therapies for this severe life-altering condition.
Key words: Complex regional pain syndrome, small fiber neuropathy, plasma exchange, skin punch
biopsies, immune modulating therapies