What is the role of IV immunoglobulin in the treatment of complex regional pain syndrome (CRPS)?

Updated: Jun 20, 2018
  • Author: Gaurav Gupta, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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A small study suggested that intravenous immunoglobulin (IVIG) can provide relief for people suffering from CRPS. Thirteen people with a CRPS duration of 6-30 months and who reported a pain intensity of at least 5 on an 11-point scale for 7 consecutive days were included in the study. One subject dropped out due to pregnancy. Of the remaining 12, half of the subjects received 1 dose of IVIG 0.5 g and the other half received a placebo (saline). Six days after infusion, when the discomfort from the injection and any other transient side effects had subsided, subjects were asked to rate their pain every day for the subsequent 2 weeks. Five subjects reported mean pain scores at least 2 points lower with IVIG than with saline, and 3 of the 5 reported pain scores at least 50% lower. [138]

Study limitations included the smaller number of subjects and the higher cost of IVIG than the alternatives that have shown similar efficacy, such as ketamine, magnesium, and tadalafil. A preliminary study of magnesium in 2009 showed promising results in CRPS. [139] However, a more complete study from 2013 showed magnesium to have no significant benefit over placebo. [140] A study investigating the effect of tadalafil on the microcirculation in patients with cold CRPS found that the drug did not reduce temperature asymmetry compared to placebo, but did significantly reduce pain. [141]

One editorial in response to the IVIG study expressed concern regarding adequate blinding of the study, since it failed to show any placebo response. [142] Moreover, the treatment response was within the range of expected placebo responses.

This study, despite its shortcomings, provides additional evidence that the immune system plays a key role in generating chronic and disproportionate pain characteristics such as those seen with CRPS. Other researchers have found antineural autoantibodies in patients with CRPS. IVIG interferes with those antibodies, downregulates proinflammatory cytokines (which are thought to play an important role in CRPS pain), and reduces hyperalgesia in both the CNS and the peripheral nervous system.

Patients with CRPS are more likely than healthy persons to show evidence of cytokines and other proinflammatory markers in tissue fluids, including cerebrospinal fluid. In his editorial, Dr. Schwartzman agreed that the immune system helps CRPS. Pain is not only dependent on the neurons that transmit it, but probably also on microglia and astrocytes, which make cytokines and stimulate pain processing. [137]

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