Diagnostic Considerations

The International Association for the Study of Pain (IASP) has developed criteria (also known as the Budapest criteria) for the clinical diagnosis of complex regional pain syndrome and continues to update these criteria.^[11]Current IASP criteria are presented below.

A clinical diagnosis can be made when four criteria are met. The first is continuing pain that is disproportionate to any inciting event.

Second, the patient must report at least one symptom in at least three of the following categories:

Sensory: Hyperalgesia, allodynia
Vasomotor: Temperature asymmetry, skin color changes, skin color asymmetry
Sudomotor/edema: Edema, sweating changes, sweating asymmetry
Motor/trophic: Decreased range of motion, motor dysfunction (eg, weakness, tremor, dystonia), trophic changes (eg, hair, nail, skin)

Third, at time of evaluation the clinician must observe at least one sign in at least two of the following categories:

Sensory: Evidence of hyperalgesia (to pinprick), allodynia (to light touch, temperature sensation, deep somatic pressure, joint movement)
Vasomotor: Evidence of temperature asymmetry (> 1° C), skin color changes or asymmetry
Sudomotor/edema: Evidence of edema, sweating changes, or sweating asymmetry
Motor/trophic: Evidence of decreased range of motion, motor dysfunction (eg, weakness, tremor, dystonia), trophic changes (eg, hair, nail, skin)

Fourth, there must be no other diagnosis that better explains the signs and symptoms

Differential diagnosis

Differential diagnostic considerations include the following^[12]:

Infection (of bone, soft tissue, joint, or skin)
Orthopedic malfixation
Joint instability
Arthritis or arthrosis
Bone or soft tissue injury (eg, stress fracture, instability, ligament damage)
Compartment syndrome
Neural injury (peripheral nerve damage, including compression or entrapment, or central nervous system or spinal lesions), or neuropathy (such as from diabetes mellitus or alcohol misuse)
Thoracic outlet syndrome (due to nerve or vascular compression)
Arterial insufficiency (usually after preceding trauma, atherosclerosis in older people, or thrombangiitis obliterans [Burger disease])
Raynaud syndrome
Lymphatic or venous obstruction
Gardner–Diamond syndrome
Brachial neuritis or plexitis (Parsonage-Turner syndrome or neuralgic amyotrophy)
Erythromelalgia (may include all limbs)
Self-harm

Differential Diagnoses

Workup

Guthmiller KB, Varacallo M. Complex Regional Pain Syndrome. 2021 Jan. [Medline]. [Full Text].
Stanton-Hicks M, Janig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995 Oct. 63(1):127-33. [Medline].
Kemler MA, van de Vusse AC, van den Berg-Loonen EM, et al. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology. 1999 Oct 12. 53(6):1350-1. [Medline].
Sebastin SJ. Complex regional pain syndrome. Indian J Plast Surg. 2011 May. 44(2):298-307. [Medline]. [Full Text].
Coderre TJ, Bennett GJ. A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): pain due to deep-tissue microvascular pathology. Pain Med. 2010 Aug. 11(8):1224-38. [Medline].
Pleger B, Draganski B, Schwenkreis P, Lenz M, Nicolas V, Maier C, et al. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex. PLoS One. 2014. 9(1):e85372. [Medline]. [Full Text].
Barad MJ, Ueno T, Younger J, Chatterjee N, Mackey S. Complex regional pain syndrome is associated with structural abnormalities in pain-related regions of the human brain. J Pain. 2014 Feb. 15(2):197-203. [Medline].
Lee DH, Lee KJ, Cho KI, Noh EC, Jang JH, Kim YC, et al. Brain alterations and neurocognitive dysfunction in patients with complex regional pain syndrome. J Pain. 2015 Jun. 16 (6):580-6. [Medline].
Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford). 2011 Oct. 50(10):1739-50. [Medline].
Abu-Arafeh H, Abu-Arafeh I. Complex regional pain syndrome in children: incidence and clinical characteristics. Arch Dis Child. 2016 Aug. 101 (8):719-23. [Medline].
Harden RN, Oaklander AL, Burton AW, Perez RS, Richardson K, Swan M, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition. Pain Med. 2013 Feb. 14 (2):180-229. [Medline]. [Full Text].
[Guideline] Royal College of Physicians. Complex regional pain syndrome in adults (2nd edition). Available at https://www.rcplondon.ac.uk/guidelines-policy/complex-regional-pain-syndrome-adults. 2018; Accessed: December 28. 2020.
Won AS, Tataru CA, Cojocaru CM, Krane EJ, Bailenson JN, Niswonger S, et al. Two Virtual Reality Pilot Studies for the Treatment of Pediatric CRPS. Pain Med. 2015 Aug. 16 (8):1644-7. [Medline].
Solcà M, Ronchi R, Bello-Ruiz J, Schmidlin T, Herbelin B, Luthi F, et al. Heartbeat-enhanced immersive virtual reality to treat complex regional pain syndrome. Neurology. 2018 Jul 31. 91 (5):e479-e489. [Medline].
Roy C, Chatterjee N. Radiofrequency ablation of stellate ganglion in a patient with complex regional pain syndrome. Saudi J Anaesth. 2014 Jul. 8 (3):408-11. [Medline].
Akkoc Y, Uyar M, Oncu J, Ozcan Z, Durmaz B. Complex regional pain syndrome in a patient with spinal cord injury: management with pulsed radiofrequency lumbar sympatholysis. Spinal Cord. 2008 Jan. 46 (1):82-4. [Medline].
Wie C, Gupta R, Maloney J, Pew S, Freeman J, Strand N. Interventional Modalities to Treat Complex Regional Pain Syndrome. Curr Pain Headache Rep. 2021 Feb 3. 25 (2):10. [Medline].
O'Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30. 4:CD009416. [Medline].
Stanton TR, Wand BM, Carr DB, Birklein F, Wasner GL, O'Connell NE. Local anaesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Aug 19. 8:CD004598. [Medline].
van Hilten BJ, van de Beek WJ, Hoff JI, et al. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med. 2000 Aug 31. 343(9):625-30. [Medline].
Javed S, Abdi S. Use of anticonvulsants and antidepressants for treatment of complex regional pain syndrome: a literature review. Pain Manag. 2021 Mar. 11 (2):189-199. [Medline].
Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain. 1992 Feb. 48(2):171-5. [Medline].
Littlejohn G. Therapy: Bisphosphonates for early complex regional pain syndrome. Nat Rev Rheumatol. 2013 Apr. 9(4):199-200. [Medline].
Varenna M, Adami S, Rossini M, Gatti D, Idolazzi L, Zucchi F, et al. Treatment of complex regional pain syndrome type I with neridronate: a randomized, double-blind, placebo-controlled study. Rheumatology (Oxford). 2013 Mar. 52(3):534-42. [Medline].
[Guideline] Netherlands Society of Anaesthesiologists, Netherlands Society of Rehabilitation Specialists. Updated Guidelines for Complex Regional Pain Syndrome type 1. Available at https://www.crps-vereniging.nl/pdf/Executive_summary_guideline_CRPS_I_2014_docx.pdf. November 2014; Accessed: December 28, 2020.
Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012 Mar 1. 26(3):215-28. [Medline].
Orhurhu VJ, Roberts JS, Ly N, Cohen SP. Ketamine In Acute and Chronic Pain Management. 2021 Jan. [Medline]. [Full Text].
Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006 Feb. 10(2):91-101. [Medline].
Kemler MA, Barendse GA, van Kleef M, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000 Aug 31. 343(9):618-24. [Medline].
[Guideline] National Institute for Health and Care Excellence. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. NICE. Available at http://www.nice.org.uk/guidance/ta159. Accessed: December 28, 2020.
Deer TR, Levy RM, Kramer J, et al. Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial. Pain. 2017 Apr. 158 (4):669-681. [Medline]. [Full Text].
Ghosh P, Gungor S. Utilization of Concurrent Dorsal Root Ganglion Stimulation and Dorsal Column Spinal Cord Stimulation in Complex Regional Pain Syndrome. Neuromodulation. 2020 Mar 11. [Medline].
[Guideline] Perez RS, Zollinger PE, Dijkstra PU, Thomassen-Hilgersom IL, Zuurmond WW, Rosenbrand KC, et al. Evidence based guidelines for complex regional pain syndrome type 1. BMC Neurol. 2010 Mar 31. 10:20. [Medline]. [Full Text].
Midbari A, Suzan E, Adler T, Melamed E, Norman D, Vulfsons S, et al. Amputation in patients with complex regional pain syndrome: a comparative study between amputees and non-amputees with intractable disease. Bone Joint J. 2016 Apr. 98-B (4):548-54. [Medline].
Laumonerie P, Martel M, Tibbo ME, Azoulay V, Mansat P, Bonnevialle N. Influence of vitamin C on the incidence of CRPS-I after subacromial shoulder surgery. Eur J Orthop Surg Traumatol. 2020 Feb. 30 (2):221-226. [Medline].
Cimaz R, Matucci-Cerinic M, Zulian F, Falcini F. Reflex sympathetic dystrophy in children. J Child Neurol. 1999 Jun. 14(6):363-7. [Medline].
Badri T, Ben Jennet S, Fenniche S, Benmously R, Mokhtar I, Hammami H. Reflex sympathetic dystrophy syndrome in a child. Acta Dermatovenerol Alp Panonica Adriat. 2011 Jun. 20(2):77-9. [Medline].
Bean DJ, Johnson MH, Heiss-Dunlop W, Lee AC, Kydd RR. Do psychological factors influence recovery from Complex Regional Pain Syndrome Type-1? A Prospective Study. Pain. 2015 Jul 1. [Medline].

Media Gallery

of 0

Author

T P Sudha Rao, MD Associate Professor of Medicine, Virginia Commonwealth University School of Medicine; Chief, Rheumatology Fellowship Coordinator, Department of Rheumatology, McGuire VA Medical Center

T P Sudha Rao, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Stock ownership for: Johnson & Johnson.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Don R Revis, Jr, MD Consulting Staff, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Florida College of Medicine

Don R Revis, Jr, MD is a member of the following medical societies: American College of Surgeons, American Society for Aesthetic Plastic Surgery, American Society of Plastic Surgeons, American Medical Association

Disclosure: Nothing to disclose.

Robert E Wolf, MD, PhD Professor Emeritus, Department of Medicine, Louisiana State University School of Medicine in Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Affairs Medical Center

Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, Society for Leukocyte Biology

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Lewis Katz School of Medicine at Temple University

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Sections Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy)
Overview
Presentation
DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
References

Complex Regional Pain Syndrome Type 1 (Reflex Sympathetic Dystrophy) Differential Diagnoses

Diagnostic Considerations

Differential diagnosis

Differential Diagnoses

References

Tables

Contributor Information and Disclosures

What would you like to print?