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1 J KMA Special Issue Diagnosis and Treatment of Complex Regional Pain Syndrome Dong Eon Moon, MD Department of Anesthesiology and Pain Medicine, Catholic University College of Medicine demoon@catholic.ac.kr J Korean Med Assoc 2006; 49(8): Abstract The complex regional pain syndromes (CRPS I and CRPS II), also known as reflex sympathetic dystrophy and causalgia, have been recognized for the past 2,500 years. Despite its long history, the diagnosis and treatment of CRPS are still challenging. These syndromes can be characterized by discrete sensory, motor, and autonomic findings, but many patients with CRPS continue to suffer for years without the diagnosis. Although much progress has been made in the understanding of CRPS, many questions still remain unanswered. CRPS is probably a disease of the central nervous system. Yet, peripheral inflammatory processes, abnormal sympatheticafferent coupling, and adrenoreceptor pathology may also be part of the picture. A close multidisciplinary approach amongst the pain medicine consultants, psychologist, physical and occupational therapists, and neurologist is necessary to achieve the maximum treatment outcomes. If conventional treatment (e.g. pharmacotherapy) fails to show a significant response within 12 weeks, an interventional technique such as spinal cord stimulation (SCS) needs to be tried. The current concepts of CRPS could be replaced by a new mechanismbased term or group of terms in the near future leading to improved clinical guidelines. This article reviews the different aspects of CRPS including its definition, classification, epidemiology and natural history, clinical presentation, pathophysiology and management. Keywords : Complex regional pain syndrome; Reflex sympathetic dystrophy; Causalgia; Multidisciplinary approach; Spinal cord stimulation 688

2 Diagnosis and Treatment of Complex Regional Pain Syndrome International Association for the Study of Pain (IASP) Diagnostic Criteria for CRPS and CRPS CRPS (Reflex Sympathetic Dystrophy) 1. The presence of an initiating noxious event, or a cause of immobilization. 2. Continuous pain, allodynia, or hyperalgesia with which the pain is disproportionate to any inciting event. 3. Evidence at some time of oedema, changes in skin blood flow, or abnormal sudomotor activity in the region of the pain. 4. The diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction. Note : Criteria 24 must be satisfied CRPS (Causalgia) 1. The presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily limited to the distribution of the injured nerve. 2. Evidence at some time of oedema, changes in skin blood flow, or abnormal sudomotor activity in the region of the pain. 3. This diagnosis is excluded by the existence of a condition that would otherwise account for the degree of pain and dysfunction. Note : All three criteria must be satisfied 689

3 Moon DE Proposed Experimental Revision of CRPS Diagnostic Criteria 1. Continuing pain which is disproportionate to inciting event 2. Must report at least one symptom in each of the four following categories Sensory : reports of hyperesthesia Vasomotor : reports of temperature asymmetry and / or skin color changes and / or skin color asymmetry Sudomotor / edema : reports of edema and / or sweating changes and / or sweating asymmetry Motor / trophic : reports of decreased range of motion and / or motor dysfunction(weakness, tremor, dystonia) and / or trophic changes (hair, nail, skin) 3. Must display at least one sign in two or more of the follwing categories: Sensory : evidence of hyperalgesia (to pinprick) and / or allodynia (to light touch) Vasomotor : evidence of temperature asymmetry and / or skin color changes and / or asymmetry Sudomotor / edema : evidence of edema and / or sweating changes and / or sweating asymmetry Motor / trophic : evidence of decreased range of motion and / or motor dysfunction (weakness, tremor, dystonia) and / or trophic changes (hair, nail, skin) 690

4 Diagnosis and Treatment of Complex Regional Pain Syndrome Revised Diagnostic Criteria for CRPS Categories of clinical signs or symptoms Positive sensory abnormalities : Oedema, sweating abnormalities Spontaneous pain Swelling Mechanical hyperalgesia Hyperhidrosis Thermal hyperalgesia Hyporhidrosis Deep somatic hyperalgesia Motor (M) or trophic (T) changes Vascular abnormalities Motor weakness (M) Vesodilation Tremor (M) Vasoconstriction Dystonia (M) Skintemperature asymmetries Coordination deficits (M) Skincolour changes Nail or hair chages (T) Skin atrophy (T) Joint stiffness (T) Softtissue changes (T) Interpretation Clinical use 1 symptoms of 3 categories each AND 1 signs of 2 categories each Sensitivity 0.85, specifcity 0.60 Research use 1 symptoms in each of the 4 categories AND 1 signs of 2 categories each Sensitivity 0.70, specifidity

5 Moon DE Differential diagnosis of CRPS and CRPS Etiology Localization Spreading of Sx Spontaneous pain Mechanical allodynia Autonomic Sx Motor Sx Sensory Sx Sxsymptom CRPS (RSD) Any kind of lesion Distal part of extremity Independent from site of lesion Obligatory Common Mostly deep & superficial Orthostatic component Most of patients with spreading tendency Distally generalized with spreading tendency Distally generalized with spreading tendency Distally generalized with spreading tendency CRPS (Causalgia) Partial nerve lesion Mostly confined to the territory of affected nerve Rare Obligatory Predominately superficial No orthostatic component Obligatory in nerve territory Related to nerve lesion Related to nerve lesion Related to nerve lesion 692

6 Diagnosis and Treatment of Complex Regional Pain Syndrome TCA, tricyclic antidepressants; noradrenaline reuptake inhibitors. *Pain relieving effect of topical lidocaine has been shown in patients with allodynia. Treatment algorithm. Proposed algorithm for the treatment of peripheral neuropathic pain 693

7 Moon DE Treatment paradigm for CRPS. A paradigm should be layered (inparallel) in a interdisciplinary approach with the goal being functional recovery. 694

8 Diagnosis and Treatment of Complex Regional Pain Syndrome 695

9 Moon DE 696

10 Diagnosis and Treatment of Complex Regional Pain Syndrome 697

11 Moon DE 1. Mitchell SW. Injuries of the Nerves and Their Consequences. Philadelphia: JB Lippincott, Evans J. Reflex sympathetic dystrophy. Surg Clin North Am. 1946; 26: StantonHicks M, Janig W, Hassenbusch S, Haddox JD, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain 1995; 63: Taylor RS. Epidemiology of refractory neuropathic pain. Pain Practice 2006; 6: Quisel A, Gill JM, Witherell P. Complex regional pain syndrome underdiagnosed. J Fam Pract 2005; 54: Harden RN, Bruehl SP. Diagnosis of complex regional pain syndrome: signs, symptoms, and new empirically derived diagnostic criteria. Clin J Pain 2006; 22: Intenzo CM, Kim SM, Capuzzi DM. The role of nuclear medicine in the evaluation of complex regional pain syndrome type I. Clin Nucl Med 2005; 30: Oaklander AL, Rissmiller JG, Gelman LB, Zheng L, Chang Y, Gott R. Evidence of focal smallfiber axonal degeneration in complex regional pain syndromei (reflex sympathetic dystrophy). Pain 2006; 120: Albrecht PJ, Hines S, Eisenberg E, Pud D, Finlay DR, Connolly MK, et al. Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome. Pain 2006; 120: Galer BS, Bruehl S, Harden RN. IASP diagnostic criteria for 698

12 Diagnosis and Treatment of Complex Regional Pain Syndrome complex regional pain syndrome: a preliminary empirical validation study. International Association for the Study of Pain. Clin J Pain 1998; 14: Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M, et al. External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Pain 1999; 81: Harden RN, Bruehl S, Galer BS, Saltz S, Bertram M, Backonja M, et al. Complex regional pain syndrome: Are the IASP diagnostic criteria valid and sufficiently comprehensive? Pain 1999; 83: Harden R, Bruehl S. Diagnostic criteria: the statistical derivation of the four criterion factors. In: Wilson PR, StantonHicks M, Harden RN, eds. CRPS: Current Diagnosis and Therapy. Seattle: IASP Press, 2005: Baron R, Janig W. Complex regional pain syndromeshow do we escape the diagnostic trap? Lancet 2004; 364: Janig W, Baron R. Complex regional pain syndrome: mystery explained? Lancet Neurol 2003; 2: Maihofner C, Handwerker HO, Birklein F. Functional imaging of allodynia in complex regional pain syndrome. Neurology 2006; 66: Raja SN, Grabow TS. Complex regional pain syndrome I (reflex sympathetic dystrophy). Anesthesiology 2002; 96: Bennett DS, Brookoff D. Complex regional pain syndromes (reflex sympathetic dystrophy and causalgia) and spinal cord stimulation. Pain Med 2006; 7: S Maleki J, LeBel AA, Bennett GJ, Schwartzman RJ. Patterns of spread in complex regional pain syndrome type I (reflex sympathetic dystrophy). Pain 2000; 88: StantonHicks MD, Burton AW, Bruehl SP, Carr DB, Harden RN, Hassenbusch SJ, et al. An updated interdisciplinary clinical pathway for CRPS: report of an expert panel. Pain Practice 2002; 2: Forouzanfar T, Koke AJ, van Kleef M, Weber WE. Treatment of complex regional pain syndrome type I. Eur J Pain 2002; 6: Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997; 73: Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clin J Pain 2006; 22: Quisel A, Gill JM, Witherell P. Complex regional pain syndrome: which treatments show promise? J Fam Pract 2005; 54: Harden RN. Pharmacotherapy of complex regional pain syndrome. Am J Phys Med Rehabil 2005; 84: S van de Vusse AC, Stompvan den Berg SG, Kessels AH, Weber WE. Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN ]. BMC Neurol 2004; 29; Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005; 118: Harden RN, Swan M, King A, Costa B, Barthel J. Treatment of complex regional pain syndrome: functional restoration. Clin J Pain 2006; 22: Bruehl S, Chung OY. Psychological and behavioral aspects of complex regional pain syndrome management. Clin J Pain 2006; 22: Bonica JJ. Causalgia and other reflex sympathetic dystrophies. In: Bonica JJ, Loeser JD, Chapman CR, et al. eds. The Mana- 699

13 Moon DE gement of Pain. 2nd ed, vol 1. Philadelphia: Lea & Febiger, 1990: Nelson DV, Stacey BR. Interventional therapies in the management of complex regional pain syndrome. Clin J Pain 2006; 22: Kemler MA, Barendse GA, van Kleef M, de Vet HC, Rijks CP, Furnee CA, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med 2000; 33. Kemler MA, De Vet HC, Barendse GA, Van Den Wildenberg FA, Van Kleef M. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years' followup of the randomized controlled trial. Ann Neurol 2004; 55: StantonHicks M. Complex regional pain syndrome: manifestations and the role of neurostimulation in its management. J Pain Symptom Manage 2006; 31: S : Peer Reviewer Commentary 700

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R