• Clinical science

Complex regional pain syndrome


Complex regional pain syndrome (CRPS) is characterized by pain, typically in a limb, that is more prolonged and/or severe than would be expected given the initial injury. The pain may be accompanied by sensory abnormalities (e..g, hyperesthesia, allodynia), signs of vegetative dysfunction (e.g., changes in the temperature and color of the skin), and/or loss of motor function. The pathogenesis of CRPS is unclear. On physical examination, patients present with pain and multiple accompanying signs of vegetative and motor dysfunction on the affected side. Although osseous changes may occur in CRPS, diagnosis is based on clinical findings rather than imaging. Multimodal treatment initiated in the early stages of the condition can result in remission and consists of physical and medical therapy (e.g., NSAIDs, anticonvulsants, low-dose tricyclic antidepressants).


  • Sex: >
  • Peak incidence: 40–50 years
  • The upper limbs are affected more often than the lower limbs.

Epidemiological data refers to the US, unless otherwise specified.


The pathogenesis of CRPS is unknown. However, it can often be linked to an inciting event:


Traditionally, CRPS was classified into two different subtypes. However, the clinical utility of this classification has been questioned.

  • CRPS type I (∼ 90% of cases)
    • formerly known as reflex sympathetic dystrophy (RSD), Sudeck atrophy, or algoneurodystrophy
    • Characteristic clinical features with no evidence of peripheral nerve lesion
  • CRPS type II
    • formerly known as causalgia
    • Characteristic clinical features with evidence of peripheral nerve lesion

Clinical features

  • Symptoms usually develop within 4–6 weeks following a trauma
    • Pain excessive in duration or severity given the inciting event
    • Sensory: hyperesthesia and/or allodynia
    • Vasomotor: hypo-/hyperthermia and/or hypo-/hyperpigmentation of the skin
    • Sudomotor/edema: hypo-/hyperhidrosis and/or edema
    • Motor/trophic: range of motion and/or strength, tremors, and/or changes in nail and hair growth

Symptoms of CRPS may progress through several stages: “acute/traumatic” within weeks of injury (redness, swelling, burning) → “dystrophic” within months of injury (cold skin, increase in pain) → “atrophic” for years after injury (skin and muscle atrophy, constant pain).


Although several sources delineate the stages of CRPS, this progression is rarely observed in clinical settings.

Stage I

Acute/traumatic stage

(initial 3 months)

  • Initial pain (burning, throbbing, aching)
  • Edema
  • Hyperhidrosis
  • Hair and nail growth in the area
Stage II

Dystrophic stage

(3–6 months)

  • Increase in pain
  • Onset of joint stiffness
  • Muscle atrophy
  • Cold, pale skin
Stage III

Atrophic stage

(> 6 months)


  • CRPS is a clinical diagnosis based on the presence of several factors:
    1. Persistent pain disproportionate to the original injury
    2. At least one symptom in three of the following four categories, as reported by the patient: sensory, vasomotor, sudomotor/edema, motor/trophic
    3. At least one sign in two of the following four categories, as assessed by the physician during examination: sensory, vasomotor, sudomotor/edema, motor/trophic
    4. Exclusion of other possible etiologies (e.g., infection, radiculopathy, neuropathy, vascular disorder)
  • Additional diagnostics
    • Indication: confirmation of the diagnosis in unclear cases
      • X-ray (low sensitivity)
        • Generalized, patchy demineralization in the periarticular region, which increases over time
        • Subperiosteal bone resorption with preservation of joint space
      • Triple-phase bone scintigraphy (high sensitivity and specificity only during first year of the condition): evaluation of increased radiotracer uptake during the mineralization (i.e., third) phase on the affected side compared with the contralateral side
      • MRI (low specificity): joint effusions and changes to soft tissue
      • Autonomic testing (impractical as a routine test because monitoring is required over several hours): serial measurements of sweat output, skin temperature, and sudomotor reflexes showing differences between the affected side and the contralateral side

Differential diagnoses

The differential diagnoses listed here are not exhaustive.


  • Patient education: Explain that the condition, although painful, is not a result of ongoing tissue damage in the region.
  • Psychological interventions: identification and treatment of psychological factors that contribute to pain; treatment of comorbid anxiety or depression; relaxation techniques
  • Physical and occupational therapy: first-line therapy
    • Ensuring daily function and motion of the affected limb
    • Lymph drainage for the treatment of edema
    • Hot/cold contrast therapy
    • Desensitization techniques
    • Proprioceptive neuromuscular facilitation (PNF) stretching
  • Medical therapy
  • Interventional procedures
    • Indicated in patients who do not improve with noninvasive therapy
    • Trigger point injections, regional sympathetic nerve block, spinal cord stimulation