CRPS
Treatment of long-standing CRPS is empirical and often of limited efficacy [33]. Preliminary data suggest that the immune system is involved in sustaining this condition [34], perhaps through an autoimmune mechanism [7,35], and that treatment with low-dose IVIg may substantially reduce pain in some patients. An open trial of repeated low-dose treatment (usually 36 g equal approximately to 0.5 g/kg) in 11 patients was first performed, where 3/11 patients experienced >70% pain relief after repeated treat- ments and 6/11 patients had no benefit [30]. A subse- quent crossover RCT in 13 CRPS patients, who were treated with IVIg (0.25 g/kg/day for 2 days) and saline [36] was positive. The average pain intensity 4–19 days after IVIg treatment was 1.55 units lower than after saline, and in three patients, pain intensity after IVIg was reduced by >50% more than after saline. Median onset of pain reduc- tion and median time to maximal effect were 2 and 5 days, respectively (Table 1). The duration of the effect was vari- able, but pain returned to baseline by 3 months in all patients. No serious adverse reactions were reported. A larger RCT is currently being conducted aiming to confirm these findings [37]. In a follow-on study, three patients (disease duration >5 years) with >30% pain relief in the RCT received openly first a single dose of either 1 or 0.5 g/kg IVIg, and if they had >30% pain relief, they con- tinued receiving SCIg in weekly home applications through a small pump. Two of these three participants experienced profound and sustained pain reduction during their 3–12 months of maintenance SCIg treatment; the 1 g/kg doses were not more effective than the 0.5 g/kg doses in the earlier RCT. Both patients remained in remission at 12 months after treatment stop [38]. It should be noted that induction of long-lasting remission was unexpected and had not previously been observed. In earlier studies, patients had been scheduled for repeat treatment only when their pain had became unbearable, usually every 6–12 weeks, and plasma-IgG levels would be assumed to have repeatedly returned to baseline, although this was not measured; in contrast, in this latter study, a higher IVIg trough concentration may have been maintained. It is possible that maintenance of higher IgG-plasma levels over several months induces disease remission in CRPS, as is known in some other IVIg-responsive conditions [39]; however, studies in larger groups would be required both to confidently confirm these clinical results and to clarify trough levels. There is currently no published evidence suggesting a better efficacy for high-dose as compared with low-dose IgG treatment. Use of a Liverpool protocol for future treatments is suggested: patients should first be treated with an intravenous loading dose of 0.5 g/kg; if >40% pain relief is achieved, patients should— commencing 2 weeks after the loading dose—be offered a trial of 6–12 months of low-dose maintenance treat- ment; this could be either 0.5 g/kg/month divided into weekly portions (or even smaller portions if a “push- technique” is used instead of a pump) for subcutaneous therapy, or 0.5 g/kg every 3 weeks intravenously; after 3–6 months an attempt should be made to halve these doses, and after 6–12 months to stop treatment.
