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.

References:^[1][2]

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:

• Trauma (> 60% of cases)
  • Iatrogenic (e.g., amputation or carpal tunnel surgery)
• Medical conditions
  • Carpal tunnel syndrome
  • Acute MI
  • Malignancy: e.g., lung cancer, breast cancer, ovarian cancer, brain tumors
  • CNS disorders: e.g., traumatic brain injury, stroke, tumor
• Idiopathic (∼ 10% of cases)

References:^[1]

• 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).
References:^[1]

• CRPS is a clinical diagnosis
  • All four of the following criteria must be met:
    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

References:^[1]

• Infection (e.g., tenosynovitis, osteomyelitis)
• Compartment syndrome
• Peripheral vascular disease
• Deep vein thrombosis
• Peripheral neuropathy
• Thoracic outlet syndrome
• Rheumatoid arthritis
• Raynaud phenomenon
• Conversion disorder
• Factitious disorder

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
  • Desensitization techniques
  • Lymph drainage for the treatment of edema
  • Hot/cold contrast therapy
• Medical therapy
  • Indicated for pain management, which facilitates movement of the affected limb
  • NSAIDs and glucocorticoids
  • Anticonvulsants or low-dose tricyclic antidepressants: may help if the pain is neuropathic in nature
  • Topical lidocaine or capsaicin cream
  • Medications that slow bone resorption
    • Calcitonin
    • Bisphosphonates
• Interventional procedures
  • Indicated in patients who do not improve with noninvasive therapy
  • Trigger point injections, regional sympathetic nerve block, spinal cord stimulation (a neuromodulation technique to relieve chronic neuropathic pain by using a mild electric current that is administered percutaneously or through electrodes implanted in the epidural space)

References:^[3]

• Vitamin C supplementation following fractures
• Early mobilization after injury

References:^[3]