Chronic Regional Pain Syndrome

Introduction

Chronic Regional Pain Syndrome (CRPS) is an umbrella term to describe a wide variety of post-traumatic neuropathic pain conditions of limbs. The hallmark of CRPS is pain that is disproportionate in magnitude and / or duration to the anticipated course after a noxious event or period of immobilisation. The incidence varies to between 0.3% and 4.3% when the Budapest criteria is used within foot and ankle literature.

 

Classification

The classication is based upon whether nerve damage is presnent or not.

Type 1 = no nerve injury (90% of cases). Synonyms include Sudeck’s atrophy/dystrophy, reflex sympathetic dystrophy (RSD), reflex neurovascular dystrophy (RND), algoneurodystrophy.

Type 2 = distinct nerve injury. Synonym includes causalgia.

 

Staging of disease

Stage 1 = acute; pain / sensory symptoms predominate; typically < 3 months.

Stage 2 = dystrophic; usually lasting 3 – 6 months.

Stage 3 = atrophic; usually >1 year of onset.

 

Pathophysiology

Probably a mix of several different mechanisms:

  • Genetic - HLA-B62 and HLA-DQ8 alleles have been implicated
  • Psychological - anxiety and depression have been postulated but the exact relationship is unclear; it may be that the pain experienced influences the psychological symptoms which, in turn, exacerbate pain symptoms
  • Neurological - injury to type C and A(alpha) nerve fibres cause nociceptors to become overly sensitive, resulting in peripheral sensitisation; central sensitisation results in an exaggerated response to innocuous stimuli 
  • Inflammatory - activation of nociceptors results in release of inflammatory mediators

 

Presentation

A variety of symptoms may be present in CRPS including:

  • Pain
  • Allodynia - pain felt from something that would not normally cause pain
  • Hyperalgesia - excessive pain felt from something that would normally cause pain
  • Dysaesthesia - abnormal sensation
  • Vasomotor - skin colour and temperature changes
  • Sudomotor - abnormal sweating and swelling
  • Motor dysfunction - reduced range of motion, weakness
  • Bone density alterations - osteopenia
  • Trophic changes - brittle and fast-growing nails, abnormal hair growth

 

Diagnosis

CRPS is defined as continuing pain disproportionate to any inciting event. There should be no other diagnosis that can explain the signs and symptoms; i.e. it is a diagnosis of exclusion so infection, DVT, self-harm, joint instability etc. need to be ruled out. The Orlando criteria was previously used, but now the Budapest criteria is used which is approved by the International Association for the Study of Pain. A patient must have at least 1 symptom in 3 of the 4 following categories:

  • Sensory: hyperaesthesia and/or allodynia
  • Vasomotor: temperature asymmetry and/or skin colour changes and/or skin colour asymmetry
  • Sudomotor: oedema and/or sweating changes and/or sweating asymmetry
  • Motor/trophic: decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

At least 1 sign must be present at the time of evaluation in 2 or more of the following categories:

  • Sensory: hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement)
  • Vasomotor: temperature asymmetry and/or skin colour changes and/or asymmetry
  • Sudomotor: oedema and/or sweating changes and/or sweating asymmetry
  • Motor/trophic: decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

A subgroup of patients with CRPS do not fulfill the Budapest criteria can be considered to have CRPS-NOS (not otherwise stated).

 

Prognosis

Partial recovery over the next 12 months is typical. Most significant improvements in symptoms are generally within the first 6 months. Only a small proportion of patients are completely symptom-free after 12 months. 7% of patients with CRPS will develop it in another limb during their lifetime. 

 

Management

  • Avoid prolonged immobilisation – “hurting not harming”
  • Prophylactic vitamin C for 50 days was observed to have a protective role after wrist fractures in a large multicentred RCT but this is controversial and data within foot and ankle conditions is lacking.
  • Physical therapies
    • 1) pacing – activity management
    • 2) desensitisation
    • 3) graded motor imagery e.g. mirror therapy
  • Medical – gabapentin, topical lidocaine, calcitonin, bisphosphonates, steroids
  • Surgical – sympathectomy, amputation
  • Psychological – CBT 

The evidence for management of CRPS is generally poor although some guideless exist.

  • Medical treatment - insufficient evidence for many drug treatments. Patients should be offered one of either amitriptyline, duloxetine, gabapentin or pregabalin as per the NICE guidelines for neuropathic pain management. Sub-anaesthetic doses of IV ketamine, steroids / bisphosphonates may have a positive effect but dose, timing and duration is unknown. No drugs in the UK are licenced for the treatment of CRPS.
  • Surgical treatment - insufficient evidence to support sympathectomy or amputation. Moreover amputation may worsen the situation (e.g. reports of CRPS onset in opposite limb).
  • Spinal cord stimulation may have a role.
  • Psychological treament - insufficient evidence.
  • Physical therapy - physiotherapy (graded motor imagery, mirror therapy) seems to have a positive impact on outcomes, but few studies clarify their regimen and most use physiotherapy as an adjuvant treatment.

 

MCQs

Which of the following is not a hallmark sign or symptom of CRPS?

  1. Hyperaesthesia
  2. Temperature asymmetry and/or skin colour changes and/or skin colour asymmetry
  3. Sweating changes and/or sweating asymmetry
  4. Absent sensation
  5. Nail trophic changes

Answer 4. Allofthe others are hallmark features of CRPS

 

Which of the following is true regarding CRPS in the foot and ankle?

  1. It is a common occurrence
  2. Its pathophysiology is multifactorial
  3. Most cases will be accompanied with a significant nerve injury
  4. Osteopenic changes of x-ray confirms the diagnosis
  5. Most patients can expect a quick and complete resolution of their symptoms

Answer 2. CRPS is an uncommon occurrence but can be life-changing if it occurs. Most occur without a nerve injury (Type 1). Osteopenia may be seen on x-ray but this isnot diagnostic. Most patients experience a lengthy recovery with incomplete resolution of symptoms.

 

References

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  • Rewhorn MJ, Leung AH, Gillespie A, Moir JS, Miller R. Incidence of complex regional pain syndrome after foot and ankle surgery. J Foot Ankle Surg. 2014. 53(3):256-8
  • Royal College of Physicians. 2018. Complex regional pain syndrome in adults UK guidelines for diagnosis, referral and management in primary and secondary care. https://www.rcplondon.ac.uk/guidelines-policy/complex-regional-pain-syndrome-adults
  • Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007. 89(7): 1424-31