Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD)


Article Author:
Kevin Guthmiller


Article Editor:
Matthew Varacallo


Editors In Chief:
Michael Labanowski


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/4/2019 6:46:22 PM

Introduction

Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder defined by the presence of distinct clinical features including allodynia, hyperalgesia, sudomotor and vasomotor abnormalities, and trophic changes. The pain experienced is disproportionate to the degree of tissue injury and persists beyond the normal expected time for tissue healing. The pathophysiology is multifactorial and involves pain dysregulation in both the sympathetic and central nervous systems, with likely genetic, inflammatory and psychological contributions.  

There are two subtypes: type I, formerly known as reflex sympathetic dystrophy, and type II, formerly known as causalgia. Type I occurs in the absence of nerve trauma, while type II occurs in the setting of known nerve trauma. Clinically they are indistinguishable and follow a regional rather than a dermatomal or peripheral nerve distribution and favor the distal extremities, though spread outside of the initially affected area commonly occurs to the proximal or contralateral limb.  CRPS is further subdivided into "warm" versus "cold," and sympathetically-maintained (SMP) versus sympathetically-independent (SIP), which may affect prognosis and treatment options.[1]

Etiology

CRPS occurs as a result of varying degrees or types of tissue trauma but has even been documented in the absence of injury or due to periods of prolonged immobilization. The most common injury associated with developing CRPS is a fracture which occurs in > 40% of CRPS cases. Other common inciting injuries or insults include sprains, contusions, crush injuries, and surgery. CPRS even has been reported to arise after seemingly innocuous interventions such as intravenous line placement. Increased psychological distress experienced during the physical injury associated with the onset of CRPS may affect its severity and prognosis.  

Epidemiology

Using the 1994 International Association for the Study of Pain (IASP) diagnostic criteria, the incidence of CRPS in the United States was noted to be 5.46 per 100,000 person-years for CRPS type I and 0.82 per 100,000 person-years for CRPS type II, with CRPS to be three to four times more common in women than in men, more common in the upper limbs, and with a peak incidence at 50-70 years of age. Of note, the modification of the IASP diagnostic criteria for CRPS in 2012 has been shown to reduce diagnostic rates by 50%.[1]  

Pathophysiology

The underlying mechanism is multifactorial and involves at least abnormal neuronal transmission, autonomic dysregulation, and central sensitization. This contributes to the variation in clinical presentation. At the site of injury, there is a proinflammatory and immunological response which includes B-cell activation and increased production of interleukins, bradykinin, substance P, and osteoprotegerin (an osteoclastogenesis inhibitory factor). Peripheral sensitization ensues which results in persistent noxious primary afferent traffic into the dorsal horn leading to “wind up” and central sensitization. This, in turn, may result in eventual remodeling in the spinal cord and somatosensory cortex.  There is an alteration of the sympathetic nervous system; sympatho-afferent coupling occurs, and there is an increased expression of adrenergic receptors on nociceptive fibers, which during times of sympathetic activation may explain the presence of autonomic features. The genetic and immune-related factors are subjects of ongoing research.

History and Physical

Patients may endorse allodynia, hyperalgesia, vasomotor dysfunction, and sudomotor dysfunction. The vasomotor and sudomotor dysfunctions manifest as alterations in sweating, skin color, and temperature and trophic changes in the skin, hair, or nails. There may also be weakness or decreased range of motion in the affected extremity. A systematic review by Lohnberg et al examined psychosocial factors associated with CRPS and concluded there is no support in the literature for specific personality or psychopathology predictors of CRPS.[2]  However, patients with a significant comorbid psychological burden and/or poor coping mechanisms may demonstrate pain-related behavior and catastrophic thinking.  CRPS has been associated with systemic medical issues as well as described by Schwartzman (Schwartzman RJ. Systemic complications of complex regional pain syndrome. Neurosci Med. 2012;3:225-242). Systemic complications of complex regional pain syndrome. Neurosci Med. 2012;3:225-242 -- PMID not available), including neuropsychological deficits (executive functioning, memory, word retrieval), constitutional symptoms (lethargy, weakness, disruptions in sleep architecture), cardiopulmonary involvement (neurocardiogenic syncope, atypical chest pain, chest wall muscle dystonia leading to shortness of breath), endocrinopathies (impaired hypothalamo-pituitary-adrenal axis with low serum cortisol, hypothyroidism), urologic dysfunction (increased urinary frequency and urgency, urinary incontinence), and gastrointestinal dysmotility (nausea, vomiting, diarrhea, constipation, indigestion). 

Evaluation

The diagnosis of CRPS is largely clinical and one of exclusion.  The differential diagnosis includes small or large fiber sensorimotor neuropathy, cellulitis, erythromelalgia, vasculitis, vascular insufficiency, lymphedema, deep vein thrombosis, and Reynaud’s phenomenon.  

The  Budapest consensus panel implemented a set of decision rules for proposed clinical criteria (sensitivity 0.85, specificity 0.7). In addition to continuing pain which is disproportionate to the inciting event, they must demonstrate the following symptoms and signs.

They should report at least one symptom in three of the four following categories:

  1. Sensory: Reports of hyperalgesia and/or allodynia,
  2. Vasomotor: Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry,
  3. Sudomotor/edema: Reports of edema and/or sweating changes and/or sweating asymmetry,
  4. Motor/trophic: Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, skin, nails).  

Additionally, they must display at least one sign at the time of evaluation in two or more of the following categories:

  1. Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch or deep somatic pressure),
  2. Vasomotor: Evidence of temperature asymmetry and/or skin color changes and/or asymmetry,
  3. Sudomotor/edema: Edema and/or sweating changes and/or sweating asymmetry,
  4.  Motor/trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, skin, nails).  

Finally, there is no other diagnosis that better explains the signs and symptoms.

Various objective testing measures have been utilized to include thermography, triple phase bone scan, and the quantitative sudomotor axon reflex test. While these studies provide further data, they are not necessary to make the diagnosis of CRPS.

Treatment / Management

Although there is a possibility that patients with CRPS may spontaneously improve, considering the debilitating nature of this syndrome, it is prudent to institute aggressive management as soon as possible as a delay may result in an unfavorable outcome. Comprehensive treatment involves a multidisciplinary strategy with a rehabilitation program at the forefront, so referral to a pain management clinic with these capabilities is ideal.[3]

Physical and occupational therapy including mirror therapy is imperative in the treatment of CRPS.  

Drug treatments considered standard therapeutic options include oral corticosteroids (for warm CRPS), anticonvulsants (ie, gabapentin), analgesic antidepressants (ie, duloxetine), transdermal lidocaine, and opioids. A multimodal pharmacologic regimen that combines several different classes may be superior.  

The 2013 Cochrane Review of Interventions for CRPS concluded that although a broad range of therapeutic approaches have been proposed for the treatment of CRPS pain and disability, there is a critical lack of high-quality evidence evaluating the effectiveness of most of these therapies.[4] Despite this, procedural interventions may be helpful when timed correctly and utilized in a multidisciplinary setting. Serial sympathetic ganglion blocks, either with local anesthetic or chemical/thermal neurolysis, are often utilized to provide relief; yet, despite their widespread use and several case reports and series touting their benefit, when reviewed systematically they have not been shown to provide significant long-term improvement.  Still, when timed very early on in the course of CPRS they might convey substantial benefit, such as demonstrated by Gungor et al.[5]  Sympathetic and perineural blockade with or without a catheter may enable patients to tolerate PT and OT if administered beforehand. Neuromodulation usually is considered after sympathetic nerve blockade has been attempted. While the literature overall reflects positively on spinal cord stimulation (SCS) for CRPS, especially in CRPS with an SMP component, an RCT comparing SCS to physical therapy found that the SCS group performed no better than physical therapy alone 5 years after implantation. Intrathecal drug delivery systems are typically considered salvage therapy. Intravenous regional sympatholytic blocks with guanethidine and reserpine have not been supported by RCTs, and there is moderate quality evidence that intravenous regional blockade with guanethidine is not effective.  With respect to intravenous infusions in particular, a 2016 review concluded that while there is evidence to support infusions of ketamine, lidocaine, bisphosphonates, and immunoglobulin as being efficacious, the authors noted that most of the included studies were pre- Budapest Criteria and several were not of high quality.[6]

Because of the association with comorbid psychiatric disorders such as depression and anxiety, cognitive behavioral therapy is considered a necessary component in treating CRPS, although there are no available studies to provide evidence to support the use of this treatment approach. Still, the treating clinician should appreciate that suboptimal management of psychological comorbidities serves as a barrier to improvement for any chronic pain condition. 

Additional treatment options include topical capsaicin, free radical scavengers (topical dimethylsulfoxide, oral vitamin C), and surgical sympathectomy. 

Patients with the SIP variant may have a worse prognosis.

Enhancing Healthcare Team Outcomes

A team approach to this problem is required to maximize recovery. Social service, pharmacology nursing, and physical therapy along with early advanced pain management are key to improved outcomes. 


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD) - Questions

Take a quiz of the questions on this article.

Take Quiz
Which is not true regarding sympathectomy for complex regional pain syndrome (CRPS) patients?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is least likely to be observed in stage III complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following accounts for the difference between complex regional pain syndrome (CRPS) Type 2 and CRPS Type 1?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 33-year-old male presents with burning pain, allodynia, swelling, and intermittent blue discoloration in his left hand with all fingers and most of the forearm to the elbow. This occurred four months ago when he suffered a skateboarding accident and fell onto his left arm. Workup is negative for infection, non-union fracture, and vasculitis. He reports that instead of improving, the pain has worsened and spread proximally. A procedural intervention is considered for pain control to help the patient tolerate physical therapy. Which of the following would be most appropriate?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What differentiates complex regional pain syndrome (CRPS) type II is differentiated from CRPS type I?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is a late feature of complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a characteristic of complex regional pain syndrome (CRPS) II?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most common psychological disorder associated with complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Providers can differentiate complex regional pain syndrome (CRPS) type II from type I with which of the following features?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is the least likely presentation of complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is not a correct statement about complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which the following statements about complex regional pain syndrome I (CRPS I) treatment is incorrect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is not commonly associated with complex regional pain syndrome type I in adolescence?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is the most important intervention in complex regional pain syndrome type I?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which signs and symptoms should be assessed in a patient with suspected complex regional pain syndrome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with complex regional pain syndrome has early upper extremity involvement with hand edema, hand and shoulder pain, and fear of range of motion. What should be the treatment priority?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient sustains a crush injury to the foot and has severe pain described as fluctuating and burning. The pain is worse at night. The foot is inflamed and discolored and the metatarsophalangeal joints are stiff. What is the most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is true regarding complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is not seen in complex regional pain syndrome type I (CRPS), previously known as reflex sympathetic dystrophy (RSD)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which does not correctly describe the stages in complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is not true regarding complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD)?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient has developed complex regional pain syndrome of his right shoulder after a serious motor vehicle accident. He has been recommended many treatments and is confused as to what may be of benefit. Based on current evidence, which of the following treatments has been shown to help patients with this disorder?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a reported systemic manifestation of complex regional pain syndrome in the literature?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 25-year-old female steps off a curb and sustains a grade three inversion injury to her left ankle. The physical examination reveals a markedly swollen ankle, the neurovascular exam is intact, and radiographs are negative for a fracture. She is placed in a short leg cast and returns three weeks later complaining of cold intolerance, a swollen foot, with diffuse numbness, tingling, and pain with weight-bearing. What is the most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD) - References

References

Fukushima FB,Bezerra DM,Villas Boas PJ,Valle AP,Vidal EI, Complex regional pain syndrome. BMJ (Clinical research ed.). 2014 Jun 25     [PubMed]
Xu J,Yang J,Lin P,Rosenquist E,Cheng J, Intravenous Therapies for Complex Regional Pain Syndrome: A Systematic Review. Anesthesia and analgesia. 2016 Mar     [PubMed]
Bruehl S, Complex regional pain syndrome. BMJ (Clinical research ed.). 2015 Jul 29     [PubMed]
O'Connell NE,Wand BM,McAuley J,Marston L,Moseley GL, Interventions for treating pain and disability in adults with complex regional pain syndrome. The Cochrane database of systematic reviews. 2013 Apr 30     [PubMed]
Gungor S,Aiyer R,Baykoca B, Sympathetic blocks for the treatment of complex regional pain syndrome: A case series. Medicine. 2018 May     [PubMed]
Lohnberg JA,Altmaier EM, A review of psychosocial factors in complex regional pain syndrome. Journal of clinical psychology in medical settings. 2013 Jun     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Clinical Neurology-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Clinical Neurology-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Clinical Neurology-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Clinical Neurology-Medical Student. When it is time for the Clinical Neurology-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Clinical Neurology-Medical Student.