The complex regional pain syndrome (CRPS) is a painful disorder that can occur in an extremity after any type of injury, or even spontaneously. Data on the incidence of CRPS are scarce and mostly hospital based. Therefore the size of the problem and its burden on health care and society are unknown. The objective of the present study was to estimate the incidence of CRPS in the general population. A retrospective cohort study was conducted during 1996–2005 in the Integrated Primary Care Information (IPCI) project, a general practice research database with electronic patient record data from 600,000 patients throughout the Netherlands. Potential CRPS cases were identified by a sensitive search algorithm including synonyms and abbreviations for CRPS. Subsequently, cases were validated by electronic record review, supplemented with original specialist letters and information from an enquiry of general practitioners. The estimated overall incidence rate of CRPS was 26.2 per 100,000 person years (95% CI: 23.0–29.7). Females were affected at least three times more often than males (ratio: 3.4). The highest incidence occurred in females in the age category of 61–70 years. The upper extremity was affected more frequently than the lower extremity and a fracture was the most common precipitating event (44%). The observed incidence rate of CRPS is more as four times higher than the incidence rate observed in the only other population-based study, performed in Olmsted County, USA. Postmenopausal woman appeared to be at the highest risk for the development of CRPS. 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

http://rsds.org/wp-content/uploads/2015/02/deMos_incidence_crps_pain_2006.pdf

The incidence of complex regional pain syndrome: a population-based study.

The purpose of this evidence summary is to provide the best available information on the effect of anti-oxidants on mortality in patients with various diseases.

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Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Since the early musings in the mid-1800s of Claude Bernard and his French neurological colleagues on the association of pain with the sympathetic nervous system, complex regional pain syndrome (CRPS) has both fascinated and perplexed practitioners. Some of the clearest and most interesting descriptions of ‘causalgia’ come from the American Civil War by one of Bernard’s students, Silas Weir-Mitchell. The low-velocity, high-mass missiles used in this confrontation (the ‘Minnie ball’) seemed to be particularly effective in inducing neuropathic pain associated with intense autonomic dysregulation. Weir-Mitchell’s depictions are clear and elegant, and as good as any clinical description that can be found in this century. 64 Many great minds have struggled with the pathophysiology of what came to be called ‘reflex sympathetic dystrophy’ in the later part of the 1900s and what has, since the Orlando consensus-based workshop of 1999, come to be called complex regional pain syndrome (CRPS) (Table 1). 37 63 85 From Leriche 46 and his vicious circles we have progressed through Livingston 47 and Sunderland 88 with the turbulence theory, and finally to the solid physiological information generated by the various animal models of causalgia, especially the chronic constriction injury model of Bennett and Xie. 5 Recently, the effort to understand the syndrome has turned towards consensus symposia. The first of these concerned taxonomy, as above. 37 85 A second Dahlem-type conference was conducted in regard to the guidelines for therapy, 84 and recently the International Association for the Study of Pain (IASP) sponsored a symposium in Cardiff, Wales in 2000 to discuss issues of pathophysiology and to amend the diagnostic considerations. 83 The epidemiology of the syndrome is very unclear. Although the syndrome has traditionally been considered rare, its ‘discovery’ by personal injury lawyers in the United States has caused a radical increase in the reporting of the syndrome (at least in the USA). The current diagnostic criteria, as set forth by the Committee of Classification of Chronic Pain of the IASP, have contributed to the liberalization of the diagnosis (Table 1). 63 This effort was extremely important in providing standardized diagnostic criteria, and caused a vast improvement in clinical communication and research homogeneity. It provided the hope that results could be generalized across studies, and in fact widespread use of these standardized criteria has helped all these things considerably. These criteria, while being very sensitive, greatly lack specificity. 92 1 31 The intent of the Orlando conference in 1994 was that these criteria should evolve on the basis of experience and empirical testing, and that they should be subject to systematic validation research over time. 37 62 85 This has been accomplished to some extent, and through a process of internal and external validation the opportunity to improve the specificity of the bedside diagnostic criteria is available. 92 1 31 Although the original IASP criteria required only subjective and potentially only historical signs and symptoms, the suggestions for improving these criteria are that some objectification and observed evidence be included. It is recommended that the diagnostic criteria be modified to include at least one symptom in each of the four diagnostic categories derived by factor analysis: sensory

Complex Regional Pain Syndrome

https://www.anesthesiology.theclinics.com/article/S0889-8537(04)00127-0/pdf

Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain.

Herpes zoster

https://rsds.org/wp-content/uploads/2015/02/Zollinger_VitC.pdf

Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial

Treatment of complex regional pain syndrome type I (CRPS-I) is subject to discussion. The purpose of this study was to develop multidisciplinary guidelines for treatment of CRPS-I. A multidisciplinary task force graded literature evaluating treatment effects for CRPS-I according to their strength of evidence, published between 1980 to June 2005. Treatment recommendations based on the literature findings were formulated and formally approved by all Dutch professional associations involved in CRPS-I treatment. For pain treatment, the WHO analgesic ladder is advised with the exception of strong opioids. For neuropathic pain, anticonvulsants and tricyclic antidepressants may be considered. For inflammatory symptoms, free-radical scavengers (dimethylsulphoxide or acetylcysteine) are advised. To promote peripheral blood flow, vasodilatory medication may be considered. Percutaneous sympathetic blockades may be used to increase blood flow in case vasodilatory medication has insufficient effect. To decrease functional limitations, standardised physiotherapy and occupational therapy are advised. To prevent the occurrence of CRPS-I after wrist fractures, vitamin C is recommended. Adequate perioperative analgesia, limitation of operating time, limited use of tourniquet, and use of regional anaesthetic techniques are recommended for secondary prevention of CRPS-I. Based on the literature identified and the extent of evidence found for therapeutic interventions for CRPS-I, we conclude that further research is needed into each of the therapeutic modalities discussed in the guidelines.

http://rsds.org/wp-content/uploads/2015/02/Perez_Zollinger_BMCNeurol_2010.pdf

Evidence based guidelines for complex regional pain syndrome type 1

Background: Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures. Methods: In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed. Results: Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninetynine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p = 0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42). Conclusions: Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study.

Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I

In our multicenter dose response study in which patients with distal radial fractures were randomly allocated to placebo or vitamin C in a daily dose of 200mg, 500mg or 1500mg during 50 days, an operated subgroup was analyzed

48 (of 427) fractures) were operated (112%) Twenty-nine patients (60%) were treated with external fixation, 14 patients (29%) with K-wiring according to Kapandji and five patients (10%) with internal plate fixation The 379 remaining patients were treated with a plaster

In the operated group of patients who received vitamin C no CRPS (0/37) was seen in comparison with one case of CRPS (Kapandji technique) in the operated group who received placebo (1/11 = 9%, p=23) There was no CRPS after external fixation

In the conservatively treated group 17 cases of CRPS (17/379 = 45%) occurred in comparison with one in case of CRPS in the operated group (1/48 = 21%, p=71)

External fixation doesn’t necessarily lead to a higher incidence of CRPS in distal radial fractures Vitamin C may also play a role in this This subgroup analysis in operated distal radial fractures showed no CRPS occurrence with vitamin C prophylaxis

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No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis.

Operative and conservative treatment of wrist fractures might lead to complex regional pain syndrome (CRPS) type I. In our multicenter dose response study in which patients with distal radial fractures were randomly allocated to placebo or vitamin C in a daily dose of 200mg, 500mg or 1500mg during 50 days, an operated subgroup was analyzed. 48 (of 427) fractures) were operated (11.2%). Twenty-nine patients (60%) were treated with external fixation, 14 patients (29%) with K-wiring according to Kapandji and five patients (10%) with internal plate fixation. The 379 remaining patients were treated with a plaster. In the operated group of patients who received vitamin C no CRPS (0/37) was seen in comparison with one case of CRPS (Kapandji technique) in the operated group who received placebo (1/11 = 9%, p=.23). There was no CRPS after external fixation. In the conservatively treated group 17 cases of CRPS (17/379 = 4.5%) occurred in comparison with one in case of CRPS in the operated group (1/48 = 2.1%, p=.71). External fixation doesn’t necessarily lead to a higher incidence of CRPS in distal radial fractures. Vitamin C may also play a role in this. This subgroup analysis in operated distal radial fractures showed no CRPS occurrence with vitamin C prophylaxis.

No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis § ~!2009-11-13~!2010-01-01~!2010-02-17~!

Paul E. Zollinger

Papers

Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial

Evidence based guidelines for complex regional pain syndrome type 1

Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study.

No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis.

No Higher Risk of CRPS After External Fixation of Distal Radial Fractures - Subgroup Analysis Under Randomised Vitamin C Prophylaxis § ~!2009-11-13~!2010-01-01~!2010-02-17~!