Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

Regional vitamin C in Bier block reduces the incidence of CRPS-1 following distal radius fracture surgery.

BACKGROUND: Systemic vitamin C supplementation after wrist fracture has been suggested to reduce the incidence of complex regional pain syndrome (CRPS). This study aimed to evaluate the effect of regional vitamin C in Bier block in the early phase of fracture on CRPS occurrence following surgery for distal radius fractures. METHODS: Seventy-four patients with isolated extra-articular distal radius fracture with the plan of fixation under Bier block were enrolled. Patients were assigned randomly into two groups: receiving either 500 mg vitamin C or sterile water as a Bier block adjuvant. Both groups received 500 mg of oral vitamin C for six weeks. The patients were evaluated for CRPS signs and symptoms at 2, 4, 6, and 12 weeks post-surgery. RESULTS: The overall incidence of CRPS 12 weeks after surgery in the vitamin C group was significantly less than the controls (22.9% vs 45.5%, p = 0.04). Logistic regression analysis showed that the only significant contribution in predicting the incidence of CRPS came from the intervention variable (OR 0.26, CI95% 0.08-0.85; P = 0.027). CONCLUSIONS: The findings suggest that adding vitamin C 500 mg to the local anesthetic in Bier block significantly reduces the incidence of CRPS following distal radius fractures.

Proximal myofascial pain in patients with distal complex regional pain syndrome of the upper limb.

BACKGROUND: Patients suffering from complex regional pain syndrome (CRPS) endure myofascial-related pain in at least 50% of cases. AIMS: To evaluate the association of upper limb CRPS with myofascial pain in muscles that might influence arm or hand pain, and to evaluate whether the paraspinal skin and subcutaneous layers' tenderness and allodynia are associated with CRPS. METHODS: A case-control study comprising 20 patients presenting with upper limb CRPS, and 20 healthy controls matched for sex and age, were evaluated in the thoracic paraspinal area and myofascial trigger points (MTrPs) (infraspinatus, rhomboids, subclavius, serratus posterior superior and pectoralis minor) via a skin rolling test. RESULTS: The prevalence of MTrPs in the affected extremity of the subjects was significantly higher than in the right limb of the controls: 45% exhibited active and latent MTrPs in the infraspinatus muscle (χ2 = 11.613, p = 0.001); 60% in active and latent MTrPs in the subclavius muscle (χ2 = 17.143, p < 0.001); and in the pectoralis minor muscle (χ2 = 13.786, p < 0.001). In addition, 55% of the cases exhibited active and latent MTrPs in the serratus posterior superior muscle (χ2 = 15.172, p < 0.001). Significant differences between the groups in skin texture and pain levels (p = 0.01, p < 0.001, respectively) demonstrated that CRPS patients felt more pain, and their skin and subcutaneous layers were much tighter than in the healthy controls. CONCLUSION: There is a high prevalence of MTrPs in the shoulder and upper thoracic area muscles in subjects who suffer from CRPS. We recommend adding an MTrPs evaluation to the standardized examination of these patients.

Complex Regional Pain Syndrome Type I, a Debilitating and Poorly Understood Syndrome. Possible Role for Pulsed Electromagnetic Fields: A Narrative Review.

BACKGROUND: Complex regional pain syndrome type I (CRPS-I), also called algodystrophy, is a complex syndrome characterized by limb pain, edema, allodynia, hyperalgesia and functional impairment of bone with a similar clinical picture of osteoporosis, including an increased release of various pro-inflammatory neuropeptides and cytokines. Several treatments have been proposed for CRPS-I, but due to the poor outcome of conventional drugs and the invasiveness of some techniques, expectations are now directed towards new resources that could be more effective and less invasive. OBJECTIVE: In the light of preclinical evidence, which underlined pulsed electromagnetic fields' (PEMFs) properties on osteoblasts (OBs), osteoclasts (OCs), and pathologies with an inflammatory profile, the present review aims to investigate whether there is a rationale for the use of PEMFs, as a combined approach, in CRPS-I. STUDY DESIGN: This review analyzed the 44 in vitro and in vivo studies published in the last decade that focused on 2 main aspects of CRPS-I: local osteoporosis (OP) and inflammation. SETTING: Not applicable. METHODS: This review includes in vitro and in vivo studies found with a PubMed and Web of Knowledge database search by 2 independent authors. The limits of the search were the publication date between January 1, 2006, and January 1, 2016, and English language. In detail, the search strategy was based on: 1) CRPS-I or algodystrophy; 2) OP, OCs, and OBs; and 3) inflammatory aspects. RESULTS: The included studies looked at the relationship between PEMFs and OCs (2 in vitro studies), osteoporotic animal models (8 in vivo studies), OBs (20 in vitro studies), inflammatory cytokines, and reactive oxygen species. They also tried to define the molecular cell pathways involved (5 in vivo and 9 in vitro studies on inflammatory models). It was observed that PEMFs increased OC apoptosis, OB viability, bone protein and matrix calcification, antioxidant protein, and the levels of adenosine receptors, while it decreased the levels of pro-inflammatory cytokines. LIMITATIONS: Data from clinical trials are scarce; moreover, experimental conditions and PEMF parameters are not standardized. CONCLUSIONS: The present review underlined the rationale for the use of PEMFs in the complex contest of CRPS-I syndrome, in combination with conventional drugs. Key words: Complex regional pain syndrome type I, algodystrophy, pulsed electromagnetic field stimulation, osteoporosis, inflammation, osteoclasts, osteoblasts, pain.

Effect of Perioperative Vitamin C Supplementation on Postoperative Pain and the Incidence of Chronic Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Postoperative pain can contribute to increased risk for complications and lengthened hospital stays. The objective was to analyze the effects of perioperative vitamin C supplementation on postoperative pain and the development of complex regional pain syndrome I (CRPS I) in patients undergoing surgical procedures. MATERIALS AND METHODS: A systematic review of published literature was performed through April 2014. References from relevant studies were scanned for additional studies. Results were screened for relevance independently, and full-text studies were assessed for eligibility. Reporting quality was assessed using a modified Newcastle-Ottawa Scale. RESULTS: The search strategy yielded 710 studies, of which 13 were included: 7 on postoperative pain and 6 on CRPS I. In the final analysis, 1 relevant study found a reduction in postoperative morphine utilization after preoperative vitamin C consumption, whereas another showed no difference in postoperative pain outcomes between the vitamin C and control groups. A meta-analysis of 3 applicable CRPS I studies showed a decrease in postoperative CRPS I after perioperative vitamin C supplementation (relative risk=2.25; τ²=0). DISCUSSION: There is moderate-level evidence supporting the use of a 2 g preoperative dose of vitamin C as an adjunct for reducing postoperative morphine consumption, and high-level evidence supporting perioperative vitamin C supplementation of 1 g/d for 50 days for CRPS I prevention after extremity surgery. Additional studies are necessary to increase the level of evidence to determine the overall effectiveness and optimum dosage of vitamin C.

Síndrome doloroso regional complejo tipo i. Análisis de una casuística infantil / Complex regional pain syndrome type i. An analysis of 7 cases in children

Introducción: El síndrome doloroso regional complejo (SDRC) se caracteriza por la presencia de dolor acompañado de síntomas sensoriales, autonómicos y motores. Es precedido habitualmente por una lesión o inmovilización. Su curso clínico es desproporcionado con respecto a la lesión inicial tanto en su intensidad como en su duración. Su distribución es regional, predominando en las extremidades. Se clasifica en tipo I y tipo II según ausencia o presencia de lesión nerviosa. Casos clínicos: Se presentan 7 casos clínicos, 6 niñas y un varón con SDRC tipo I, con edades comprendidas entre 7-15 años. Tres tenían antecedente de traumatismo previo. En 5 casos los síntomas se localizaron en miembros inferiores. La demora diagnóstica fue entre 4-90 días. Tres pacientes presentaron elementos de ansiedad y depresión. En todos se realizaron pruebas complementarias de imagen e inmunológicas para descartar diagnósticos diferenciales. Se realizó tratamiento interdisciplinario no farmacológico (fisioterapia y psicoterapia) y farmacológico con analgésicos mayores, gabapentina o pregabalina. Todos presentaron buena evolución, sin recidivas en el seguimiento que fue entre 4 meses y 2,5 años. Conclusiones: El poco reconocimiento de este síndrome en niños, la ansiedad familiar que genera y los costos en paraclínica innecesaria, resaltan la importancia de su difusión entre pediatras y neuropediatras para favorecer su reconocimiento, evitar estudios innecesarios y múltiples consultas a especialistas que retrasan el diagnóstico y el inicio de un tratamiento efectivo

Introduction: Complex regional pain syndrome (CRPS) is characterised by the presence of pain accompanied by sensory, autonomic and motor symptoms, usually preceded by a lesion or immobilisation. The clinical course is disproportionate to the initial injury in intensity and in duration. Its distribution is regional, predominantly in limbs. It is classified as type I and type II according to the absence or presence of nerve injury. Cases: We present the cases of seven children, 6 girls and 1 boy, aged 7 to 15 years. Three had a history of previous trauma. In 5 cases, the symptoms were located in the lower limbs. Time to diagnosis was between 4 and 90 days. Three patients had clinical features of anxiety and depression. Imaging and immunological studies were performed to rule out differential diagnoses in all the children. Interdisciplinary treatment was performed with physiotherapy, psychotherapy, and gabapentin or pregabalin. All patients had a good clinical outcome, with no relapses in the follow-up period (between 4 and 30 months). Conclusions: CRPS is frequently unrecognised in children, leading to family anxiety and unnecessary para-clinical costs. Paediatricians and paediatric neurologists should be aware of this syndrome in order to avoid delay in diagnosis, unnecessary studies, and multiple visits to specialists, with a view to providing effective treatment

Demographic characteristics of patients with severe neuropathic pain secondary to failed back surgery syndrome.

BACKGROUND: Neuropathic pain commonly affects the back and legs and is associated with severe disability and psychological illness. It is unclear how patients with predominantly neuropathic pain due to failed back surgery syndrome (FBSS) compare with patients with other chronic pain conditions. AIMS: To present data on characteristics associated with FBSS patients compared with those with complex regional pain syndrome, rheumatoid and osteoarthritis, and fibromyalgia. METHODS: The PROCESS (Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation, ISRCTN 77527324) trial randomized 100 patients to spinal cord stimulation (n = 52) plus conventional medical management (CMM) or CMM alone (n = 48). Baseline patient parameters included age, sex, time since last surgery, employment status, pain location and severity (visual analogue scale), health-related quality of life (HRQoL), level of disability, medication, and nondrug therapies. Reference population data was drawn from the literature. RESULTS: At baseline, patients in the PROCESS study had a similar age and gender profile compared with other conditions. PROCESS patients suffered from greater leg pain and had lower HRQoL. PROCESS patients treatment cost was higher and they commonly took opioids, while antidepressants and nonsteroidal anti-inflammatory drugs were more often used for other conditions. Prior to baseline, 87% of patients had tried at least 4 different treatment modalities. CONCLUSIONS: Patients suffering from chronic pain of neuropathic origin following FBSS often fail to obtain adequate relief with conventional therapies (eg, medication, nondrug therapies) and suffer greater pain and lower HRQoL compared with patients with other chronic pain conditions. Neuropathic FBSS patients may require alternative and possibly more (cost-) effective treatments, which should be considered earlier in their therapeutic management.

Spinal cord stimulation for complex regional pain syndrome: an evidence-based medicine review of the literature.

OBJECTIVES: The purpose of this investigation is to assess the evidence for efficacy of SCS in the management of pain in patients with CRPS. SEARCH STRATEGY: Electronic databases such as Medline and Cochrane Library were queried using key words such as "spinal cord stimulation," "reflex sympathetic dystrophy (RSD)," and "complex regional pain syndrome (CRPS)." SELECTION CRITERIA: Relevant published randomized controlled trials (RCT), cohort studies, case-control studies, case series, and case reports that described SCS as the primary treatment modality for patients with CRPS were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Data extracted from qualified studies were summarized in sections of methodology, demographics, SCS equipment, primary and secondary outcomes, and complications. RESULTS: Thirteen studies using the primary search strategy and 7 studies from their reference lists were considered. Five of these 20 studies were discarded. One RCT, 2 prospective observational, and 12 retrospective observational studies were eventually considered. The methodological quality of all studies was poor except for the single RCT study. DISCUSSION: Although limited in quality and quantity, available evidence from the examined literature suggests that SCS is effective in the management of pain in patients with CRPS (grade B/C). Clinically useful information extracted from the available studies is very limited in guiding clinicians in the rational use of SCS for pain management in CRPS patients. Future attempts to investigate the efficacy of SCS in CRPS patients should involve methodologically robust designs such as randomized studies that have sufficient power.

Does a viral infection cause complex regional pain syndrome?

In 1990 Omura, Y. reported that Herpes Simplex Virus Type 1 as the major cause of chronic intractable pain and its effective treatment using mixture of EPA & DHA with Selective Drug Uptake Enhancement Method. Subsequently among the other causes of pain, he included Chlamydia Trachomatis, Borrelia Burgdorferi, Mycobacterium Tuberculosis, human Herpes Virus type 6, and Circulatory Disturbances. In order to test possible involvement of viral infection in Complex Regional Pain Syndrome (CRPS), a disease which usually occurs in the extremities, we did a study of 17 patients with CRPS. They were examined for Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) by measuring IgG and IgM antibody titers, and 14 of these patients were also examined for Cytomegalo-Virus (CMV). As a control group 100 healthy Japanese employees at SRL, Inc. were also studied. In CRPS group, HSV IgG was positive in 12 of the 17 patients with an average antibody titer of 90.0 EIA value. VZV IgG was positive in all 17 patients with an average antibody titer of 26.8 EIA value. CMV IgG was positive in all 14 patients with an average antibody titer of 66.6 UA/ml. In control group, HSV IgG was positive in 54 subjects with an average antibody titer of 42.3 EIA value. VZV IgG was positive in 97 subjects with an average antibody titer of 26.2 EIA value. CMV IgG was positive in 82 subjects. There were no significant differences of positive rate of IgG antibody for the three viruses between patient and control groups. Although the difference was not significant, the average antibody titers of HSV in CRPS group were more than twice of those in healthy group. Antibody titers were almost equal in both groups for VZV. Possibly, some people in the control group who had latent virus, were also asymptomatic. In 2000, Takasaki, I. et al. in a separate animal study, inoculated with HSV Type-I the shin of the mouse causing allodynia and hyperalgesia (which are some of the characteristic findings seen in CRPS in humans). Also, VZV, which causes shingles which is sometimes followed by Post-Herpetic Neuralgia (PHN), is in the same family of HSV. As PHN resembles CRPS in symptoms, it is possible that HSV contributes to CRPS. Therefore, virus infection theory is an attractive hypothesis that accounts for many enigmas of CRPS.