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COMPLEX REGIONAL PAIN SYNDROME (CRPS)

Introduction

Complex regional pain syndrome (CRPS) is a disabling, often chronic neurological condition that usually affects a single limb. It encompasses a diverse collection of signs and symptoms involving the sensory, motor, and autonomic nervous systems; cognitive deficits; changes in mood and anxiety; bone demineralization, skin growth changes, and vascular dysfunction. Historically, CRPS has been called reflex sympathetic dystrophy (RSD), causalgia, allodynia, sympathetically maintained pain.  Recently Matzon and Lutsky described CRPS as disproportionate pain and disability.7  CRPS is also labeled Type 1 in the absence of a nerve lesion and Type II when a nerve lesion is present.8  CRPS can occur spontaneously or emerge after surgery, trauma, or a minor injury, and CRPS can have a varying course that ranges drastically from mild to chronic. The upper limb is affected more in adults and the lower limb in children, and the pain from it can be conceptually described as an exaggeration or abnormal prolongation of expected sequelae after injury or surgery. There is no known cure for CRPS, but a combination of pharmacological, physical, and psychological interventions may effectively address symptoms, especially if treatment starts within one year. Surgery is reserved for cases that are unresponsive to conservative strategies and may include intrinsic muscular release, osteotomy, or sympathectomy.1-4

Pathophysiology

  • The pathophysiologic cause of CRPS is not well defined, but the syndrome has a complex and evolving origin that deviates from the predictable response of an extremity to a traumatic or surgical insult.
  • In affected patients, there is an abnormal prolongation of the transient dystrophic response to the offending insult, and they become unable to modulate or control the pain cycle, which may be followed by a cascade of reversible and irreversible events2
    • The five cardinal signs of inflammation (redness, increased heat, swelling, pain and loss of function) have been observed during the acute phase of CRPS.  This suggests an exaggerated inflammatory response to trauma in CRPS patients.3
    • The most frequent causes of CRPS involve surgery—especially hand surgery—and trauma
    • While there is evidence suggesting sympathetic nervous system (SNS) involvement, a causal relationship has not been established4
    • Several CRPS manifestations suggest functional changes within the central nervous system (CNS), as motor symptoms, including exaggerated tendon reflexes, dystonia, myoclonus, paresis, and tremor, have been observed in up to 97% of patients4
    • Family studies suggest a genetic predisposition toward developing CRPS, but there is a lack of consensus regarding the influence of genetic factors3
    • Owing to the prevalence of anxiety and depression and the unusual nature of symptoms, psychological factors also are thought to play an etiologic role3

Related Anatomy

  • Peripheral nerves
  • Distal radius
  • Carpal tunnel
  • CRPS is typically classified by its signs and symptoms and/or by disease severity and duration (Table).
Classification by type
Type 1
  • More common that Type 2
  • Also known as classic reflex sympathetic dystrophy (CRSD)
  • Chronic pain without identifiable nerve involvement
  • Usually develops after a noxious event
  • Not limited to the distribution of a single peripheral nerve and disproportionate to the inciting event
  • Associated with edema, changes in skin blood flow, abnormal sudomotor activity, allodynia, and hyperalgesia
  • Commonly involves the distal aspect of the affected extremity or with a distal-to-proximal gradient
Type 2
  • Also known as causalgia
  • Defined as a burning pain, allodynia, and hyperpathia that occurs in a region of the limb after partial injury of a nerve or one of its major branches3,5
Classification by severity
Acute
  • Lasting 0-3 months
  • Symptoms include pain, swelling, warmth, redness, decreased range of motion, and hyperhidrosis
  • X-rays are normal; three-phase bone scan is positive
Subacute
  • Lasting 3-12 months
  • Pain typically increases and is accompanied by cyanosis, dry skin, stiffness, and skin atrophy
  • Osteopenia found on x-ray
Chronic
  • Lasting >12 months
  • Pain typically diminishes, but fibrosis, glossy skin, and joint contractures develop
  • Extreme osteopenia found on x-ray

Incidence and Related Conditions

  • CRPS has a reported incidence of 5.5-26.2/100,000 person-years and a prevalence of 20.7/100,000 person-years6,8
  • ~50,000 new cases of CRPS are reported in the U.S. each year6
  • Women are affected more than men (3:1 and 4:1); the upper extremity is involved more frequently than the lower extremity (3:2)6
  • CRPS occurs most frequently in individuals aged 61-70 years3
  • Risk factors include menopause and history of migraine, osteoporosis, asthma, and angiotensin converting enzyme inhibitor therapy3
  • CRPS occurs in 5-40% of patients after fasciotomy for Dupuytren’s contracture, 28% after carpal tunnel surgery, and 1% to 37% after distal radius fracture4,9
  • The likelihood of developing CRPS is not proportional to the extent of injury or complexity of surgery4
  • Related conditions include double-crush syndrome and chronic neuropathic pain

Differential Diagnosis

  • Posttraumatic neuralgia
  • Peripheral neuropathy
  • Bone or soft tissue injury
  • Arthritis
  • Infection
  • Compartment syndrome
  • Arterial insufficiency
  • Raynaud’s Disease
  • Lymphatic or venous obstruction
  • Thoracic outlet syndrome
  • Gardner-Diamond Syndrome
  • Erythromelalgia
  • Cellulitis
  • Undiagnostic fracture
  • Deep vein thrombosis
  • Plexopathy
  • Radiculopathy
  • Fictitious disorder or malingering
  • Acute carpal tunnel syndrome
ICD-10 Codes

  • COMPLEX REGIONAL PAIN SYNDROME (CRPS)

    Diagnostic Guide Name

    COMPLEX REGIONAL PAIN SYNDROME (CRPS)

    ICD 10 Diagnosis, Single Code, Left Code, Right Code and Bilateral Code

    DIAGNOSISSINGLE CODE ONLYLEFTRIGHTBILATERAL (If Available)
    COMPLEX REGIONAL PAIN SYNDROME, UPPER LIMB G90.512G90.511 

    ICD-10 Reference

    Reproduced from the International statistical classification of diseases and related health problems, 10th revision, Fifth edition, 2016. Geneva, World Health Organization, 2016 https://apps.who.int/iris/handle/10665/246208

Clinical Presentation Photos and Related Diagrams
Complex Regional Pain Syndrome Clinical Presentation
  • Complex Regional Pain Syndrome Type II in a 46 y.o. male after a bicycle accident and a closed injury to the ulnar nerve at the elbow. Note the intrinsic atrophy (arrow), swollen and stiff hand.
    Complex Regional Pain Syndrome Type II in a 46 y.o. male after a bicycle accident and a closed injury to the ulnar nerve at the elbow. Note the intrinsic atrophy (arrow), swollen and stiff hand.
  • Note the marked lack of active finger flexion and redness (arrows).
    Note the marked lack of active finger flexion and redness (arrows).
Symptoms
Pain, numbness, swelling, joint stiffness and cold intolerance
Hyperalgesia, allodynia, hyperpathia, hyperhidrosis, and dystonia
Skin changes, hand posturing, tremors , restricted range of motion (ROM)
Intrinsic muscle contractures, atrophy and contracture
Osteoporosis
Typical History

A 64-year-old woman recently underwent surgery to repair a distal radius fracture in her left wrist. Several days after the procedure, the pain in her repaired wrist returned.  She reported that even minor stimuli were resulting in extremely painful responses. This primary complaint was accompanied by numbness, swelling, and stiffness, and continual changes in the skin color, texture, and temperature surrounding her left wrist.

Positive Tests, Exams or Signs
Work-up Options
Treatment Options
Conservative
  • Physical treatments, medication, and psychological support can help manage symptoms; treatment decisions should be guided by the patients’ symptoms and whether they have sympathetically maintained pain (SMP)
  • There are no FDA-approved therapies for CRPS, and only a few for chronic neuropathic pain; however, several drug classes with a sympatholytic component are recommended for CRPS, including antidepressants (eg, amitriptyline, fluoxetine), anticonvulsants (eg, phenytoin, gabapentin, pregabalin), membrane-stabilizing agents, and adrenergic agents (eg, phenoxybenzamine, clonidine)
    • Corticosteroids stabilize membranes and to decrease inflammatory pain
    • Calcium channel blockers (eg, nifedepine, amlodipine)
    • GABA agonists like Gabapentin
    • Parenteral agents (eg, guanethidine, cortisone, reserpine, lidocaine, bretylium)
    • Physical therapy is commonly recommended as the first-line treatment and considered a key component of the rehabilitation process8
      • Aim is to help patients overcome kinesophobia and enable them to gain the best functional use of their affected limb(s)
      • Elevation
      • Massage
      • Hydrotherapy/contrast baths
      • Transcutaneous electrical nerve stimulation
      • Gentle ROM exercises and/or isometric strengthening exercises
      • Stress loading of the affected limb
      • Sensory reeducation1
      • Occupational therapy encourages use of the affected limb in activities of daily living
        • Specialized garments or wrappings may be used to reduce edema and sensory overload
        • Mirror box therapy may be effective for reducing neuropathic pain and improving two-point sensation in the affected limb3
        • Psychological counseling may be helpful for addressing the emotional and psychological components of CRPS and their impact on quality of life; may be followed up with cognitive behavioral therapy, learning relaxation skills, and biofeedback3
        • Neurolysis may occasionally be indicated for perineural fibrosis
        • Chemical sympathectomy  is considered as another option if physical therapy and other conservative treatments fail
        • Spinal cord stimulation
Operative
  • Any surgical treatment should be considered very carefully before recommending operative intervention7
  • If symptoms are not completely resolved after conservative interventions, surgery may be considered, especially when refractory SMP is present5
  • Intrinsic muscle release: may be indicated for patients who develop proximal interphalangeal joint contractures
  • Osteotomy: may be indicated for bony malunion or nonunion due to CRPS-induced osteopenia5
  • Surgical sympathectomy: can be performed as an extension of temporary sympathetic blockade in patients who have good but transient relief from the blockade3
  • Surgical decompression: may be indicated for some cases of CRPS type 2
  • Amputation: extreme option that is rarely used, since there is a significant risk that CRPS will subsequently develop in the stump
Complications
  • Persistent or worsening pain
  • Neuralgia
  • Anhydrosis
  • Horner’s syndrome
Outcomes
  • The natural history of CRPS varies, with some patients’ symptoms resolving spontaneously in weeks or months and others having persistent pain and symptoms after undergoing both conservative and surgical treatments
  • Aggressive treatment at the acute stage is generally associated with the best possible outcomes
    • ~80% of patients treated within one year of symptom onset report considerable improvements; ~50% of those treated after one year improve markedly
    • Despite early and appropriate treatment, some patients continue to have long-term functional impairments, chronic pain, or deformity2
    • The prognosis is also better for children, as more patients achieve a full recovery, but relapses are possible1
  • CRPS that develops after a distal radius fracture is associated with a poorer prognosis, and there is a correlation between patients who continue to have stiffness and impaired finger function after three months and morbidity after 10 years6
  • One study found that spinal cord stimulation and physical therapy were significantly more effective at relieving pain than physical therapy alone at six months and two years, but this effectiveness diminished after five years3
  • Epidural clonidine and corticosteroids have elicited successful outcomes in patients with refractory CRPS symptoms5
  • Chronic ketamine infusions were efficacious when administered in the chronic phase4
  • The prognosis of CRPS is poorer in smokers compared to non-smokers3
Key Educational Points
  • The lack of satisfactory treatments for CRPS is primarily due to phenotypic heterogeneity, the evolving nature of the syndrome, and the overall lack of understanding of its pathophysiology4
  • Although early diagnosis and treatment seem to improve outcomes, beginning management within 6-12 weeks of the onset of symptoms is not typical in most patients, and delays are especially common in patients with milder variants of CRPS5
  • FDA recently classified CRPS an official disease, which researchers consider to be a catalyst for new advances in appropriate drug development3
  • The American Academy of Orthopaedic Surgeons has recommended the use of vitamin C to prevent CRPS after distal radius fracture based on level II data but Malay and Chung suggest level I studies and vitamin C dose control would make this recommendation stronger
References

Cited

  1. Palmer G. Complex regional pain syndrome. Aust Prescr 2015;38(3):82-6. PMID: 26648626
  2. Patterson RW, Li Z, Smith BP, et al. Complex regional pain syndrome of the upper extremity. J Hand Surg Am 2011;36(9):1553-62. PMID: 21872098
  3. Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns Trauma 2017;5:2. PMID: 28127572
  4. Tajerian M, Clark JD. New Concepts in Complex Regional Pain Syndrome. Hand Clin 2016;32(1):41-9. PMID: 26611388
  5. Li Z, Smith BP, Tuohy C, et al. Complex regional pain syndrome after hand surgery. Hand Clin. 2010;26(2):281-9. PMID: 20494753
  6. de Mos M, de Bruijn AG, Huygen FJ, et al. The incidence of complex regional pain syndrome: a population-based study. Pain 2007;129(1-2):12-20. PMID: 17084977
  7. Matzon J, Lutsky K. Hand surgery after an episode of disproportionate pain and disability.  J Hand Surg Am 2013; 38:2454-2456. PMID: 23890393
  8. Zimmerman RM, Astifidis RP, Katz RD. Modalities for complex regional pain syndrome.  J Hand Surg Am 2015; 40:1469-1472. PMID: 25910590
  9. Malay S, Chung KC. Testing the validity of preventing complex regional pain syndrome with vitamin C after distal radius fracture.  J Hand Surg Am 2014; 39(11):2251-2257. PMID: 25239047
  10. Yang A, Hunter CW. Dorsal root ganglion stimulation as a salvage treatment for complex regional pain syndrome refractory to dorsal column spinal cord stimulation; a case series. Neuromodulation 2017; 20(7):703-707. PMID: 28621025

New Articles

  1. Bussa M, Mascaro A, Cuffaro L, Rinaldi S. Adult Complex Regional Pain Syndrome Type I: A Narrative Review. PM R 2017;9(7):707-719. PMID: 27890578
  2. Weissmann R, Uziel Y. Pediatric complex regional pain syndrome: a review. Pediatr Rheumatol Online J 2016;14(1):29. PMID: 27130211

Reviews

  1. Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: a recent update. Burns Trauma 2017;5:2. PMID: 28127572
  2. Zyluk A. Complex regional pain syndrome type I. Risk factors, prevention and risk of recurrence. J Hand Surg Br 2004;29(4):334-7. PMID: 15234496

Classics

  1. Noble JA. Reflex sympathetic dystrophy. Can Med Assoc J 1949;60(2):135-40. PMID: 18123143
  2. Bayles TB, Judson WE, Potter TA. Reflex sympathetic dystrophy of the upper extremity (hand-shoulder syndrome). J Am Med Assoc 1950;144(7):537-42. PMID: 14774132
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