Diagnosis and Treatment Options of RSD/CRPS Srinivasa N. Raja, MD Director of Pain Research Johns Hopkins University School of Medicine

Introduction RSD/CRPS is a chronic neurologic syndrome characterized by pain of varying intensity Early diagnosis and appropriate treatment are essential to avoid disabling pain RSD/CRPS is often under-diagnosed and under-treated by the medical community The Reflex Sympathetic Dystrophy Association of America (RSDSA) statistic show the average patient visits 4.8 physicians before being correctly diagnosed with RSD/CRPS. Because many physicians are unaware of the clinical signs of RSD/CRPS, patients are frequently told their symptoms are phycosomatic. Dr. Robert J. Schwartzman states that early diagnosis and treatment (within 6 months of onset) is vital for any hope of remissions.

What Is Reflex Sympathetic Dystrophy Syndrome? Reflex sympathetic dystrophy syndrome (RSD) is a debilitating neurologic syndrome characterized by Pain and hypersensitivity Vasomotor skin changes Functional impairment Various degrees of trophic change RSD generally follows a musculoskeletal trauma RSD reflects the prevailing belief that conditions [characterized by pain associated with sensitivity to touchy, together with color, temperature and trophic changes] involved abnormal reflex activity in the sympathetic nervous system. Causalgia is reserved for those conditions caused by an injury to a major peripheral nerve. 1 1 Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546 Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546.

Challenges Natural course and pathophysiology remain elusive1 Diagnosis made by exclusion of other causes2 Therapies remain controversial3 Underdiagnosed and undertreated Significant morbidity and loss of quality of life Lack of consensus and confusion re RSD and causalgia have retarded clinical research Complex regional pain syndromes are difficult problems in treatment and diagnosis. 1 Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546 2.Raja SN and Grabow TS. Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). Anesthesiology. 2002.96:1254-1260. 1. Jänig W. In: Harden , Baron Janig, eds. Complex regional Pain Syndrome, Progress in Pain Research and Management. 2001: 3-15. 2. Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546. 3. Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Terminology: RSD vs CRPS RSD = traditional term Complex regional pain syndrome (CRPS) = more comprehensive term Includes disorders not related to sympathetic nervous system dysfunction CRPS I = RSD CRPS II = causalgia (involves nerve injury) Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001: 388-411.

Name Change to CRPS Goals: standardized, reliable diagnostic criteria and decision rules Allow generalization Make appropriate treatment selection Identify reproducible research samples 1 Galer et al. 388-411. Term RSD changed to CRPS I because the lack of consensus and the confusion with regard to RSD and causalgia diagnostic criteria have retarded clinical research. Little agreement existed among those from different medial fields and parts of the worked as to the diagnositic criteria and appropriate therapies for RSD and causalgia. Medical folklore exists re RSD and causalgia based on anecdotal personal physician experiences that hove not been proven scientifically or are inconsistent with more extensive worldwide clinical experience Many patients do not demonstrate the classically described dystrophic signs (atrophy and changes in skin, nails, and hair). Bonica’s Management of Pain. 3rd edition, Ed. John D. Loesser, a chapter by Galer BS, Schwartz L, Allen R. Complex Regional Pain Syndromes—type I: Reflex Sympathetic Dystrophy, and Type II: Causalgia.P 389 Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001:388-411.

Epidemiology Age – common in younger adults Mean 41.8 years Mean age at time of injury 37.7 years Mean duration of symptoms before pain center evaluation = 30 months 2.3 to 3 times more frequent in females than males1 Usually involves a single limb in the early stage 2 1. Raja SN et al. Anesthesiology. 2002;96:1254-1260. 2. Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001, 388-411.

Clinical Features Presence of an initiating noxious event or a cause of immobilization Continuing pain Allodynia: pain from a stimulus that does not normally provoke pain Hyperalgesia: excessive sensitivity to pain Pain disproportionate to any inciting event Notes: A US study from a chronic pain clinical reported only 77% of patients had a known event that resulted in the development of CRPS (strain or sprain, post surgical, contusion or crash injury)1 CRPS type II has the same clinical features as CRPS type I except for the present of clinical signs and history consistent with a nerve injury. 2 1. Bonica’s Management of Pain. 3rd edition, Ed. John D. Loesser, a chapter by Galer BS, Schwartz L, Allen R. Complex Regional Pain Syndromes—type I: Reflex Sympathetic Dystrophy, and Type II: Causalgia.P 389 2.Raja SC and Grabow TS. Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). Anesthesiology. 2002.96:1254-1260. Stanton-Hicks M et al. Pain. 1995;63:127-133. Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001; 388-411.

Clinical Features (cont’d) History of edema, changes in skin blood flow, or abnormal sweating in the region of pain Exclusion of medical conditions that would otherwise account for the degree of pain and dysfunction   Stanton-Hicks M et al. Pain. 1995;63:127-133. Galer BS et al. In: Loeser, ed. Bonica’s Management of Pain. 2001: 388-411.

Checklist for the Diagnosis of RSD: History Burning pain Skin, sensitivity to touch Skin, sensitivity to cold Abnormal swelling Abnormal hair growth Abnormal nail growth Abnormal sweating Abnormal skin color changes Abnormal skin temperature changes Limited movement Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546.

Checklist for the Diagnosis of RSD/CRPS: Examination Mechanical allodynia Hyperalgia to single pinprick Summation to multiple pinprick Cold allodynia Abnormal swelling Abnormal hair growth Abnormal skin color changes Abnormal skin temperature (> or < 1ْ C) Limited range of movement Motor neglect Bogduk N. Current Opinions in Anesthesiology. 2000;14:541-546.

Revised Diagnostic Criteria Clinical Presentation Pain and sensory changes disproportionate to the injury in magnitude or duration Patients should have at least one symptom in each of these categories and one sign in 2 or more categories Sensory (hyperesthesia = increased sensitivity to a sensory stimulation) Vasomotor (temperature or skin abnormalities) Sudomotor (edema or sweating abnormalities) Motor (decreased range of movement, weakness, tremor, or neglect) 1. Bruehl et al. Pain. 1999;81:147-154. 2. Harden et al. Pain. 1999;83:211-219. .

Swelling and Color Changes

Abnormal Sweating in RSD

Differential Diagnoses Diabetic and small-fiber peripheral neuropathies Entrapment neuropathies Thoracic outlet syndrome Discogenic disease Deep vein thrombosis Cellulitis Vascular insufficiency Lymphedema Erythromelalgia Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Psychological Aspects Pain can cause symptoms of psychologic distress including Anxiety Depression Fear Anger Notes: Most patients with RSD/CRPS suffer some form of psychologic distress. The symptoms listed above are deemed to be the result of the pain associated with RSD/CRPS, not the cause of it. The signs and symptoms of RSD/CRPS may get worse because of illness behaviors, such as disuse and immobilization, or by maladaptive coping skills. Raja SC and Grabow TS. Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). Anesthesiology. 2002.96:1254-1260. Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Treatment Goals Multidisciplinary Rehabilitation Pain management Psychological treatment Multidisciplinary Physiotherapy Medical Psychological Notes: No scientifically established treatments exist for RSD/CRPS. A few treatments have some controlled trial data suggesting efficacy, no treatment cures RSD/CRPS. Many treatments for RSD/CRPS have been reported or recommended, but the majority are descriptive and anecdotal, not based on the results of controlled clinical trials. Galer et al. pg 400 Stanton-Hicks M et al. Pain Practice. 2002;2:1-16.

Rehabilitation: Clinical Pathway Physiotherapy + pain management + psychological therapies = sequential progression through the rehabilitation pathway PT + OT crucial to patient’s progression Therapist assesses patient’s motivation and helps set goals Adequate analgesia, encouragement, and education of disease process Stanton-Hicks M et al. Pain Practice. 2002;2:1-16.

Rehabilitation: General Steps Desensitization of the affected region Mobilization, edema control, and isometric strengthening Stress loading, isotonic strengthening, range of motion, postural normalization and aerobic conditioning Vocational and functional rehabilitation Stanton-Hicks M et al. Clin J Pain. 1998;14:155-166.

Pharmacalogic Pain Management Most drugs used for neuropathic pain are used to treat RSD/CRPS IV bretylium IV ketanserin IV phentolamine IV lidocaine Intranasal calcitonin IV alendronate (bisphosphonate) Topic dimethyl sulfoxide Topical clonidine Notes: Few placebo-controlled trials have shown therapeutic efficacy of analgesics for patients with CRPS regardless of route of injection or drug delivery technique. Raja SN et al. Anesthesiology. 2002;96:1254-1260. Kingery WS. Pain.1997;73:123-139

Minimally Invasive Therapies Sympathetic, IV regional, and somatic nerve blocks Patients with a sympathetic component to their pain (SMP) should receive nerve blocks For patients without SMP, a somatic block or epidural infusion may be indicated to optimize analgesia for PT Notes Nerve blocks can reduce pain and aid physiotherapy and functional rehabilitation. Historically, interventions that interrupt sympathetic nervous system or adrenergic receptor function have been used to treat RSD/CRPS. However, there is little evidence-based information regarding timing, number, necessity, or appropriateness of nerve blocks for RSD/CRPS Raja SC and Grabow TS. Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy). Anesthesiology. 2002.96:1254-1260. Stanton-Hicks M et al. Pain Practice. 2002;2:1-16.

More Invasive Therapies Neuroaugmentation Spinal cord stimulation Intrathecal drug delivery Notes: Neuroaugmentation includes neurostimulation. Spinal cord stimulation has produced analgesic results Stanton-Hicks M et al. Pain Practice. 2002;2:1-16.

Surgical Therapies: Sympathectomy Controversial procedure In carefully selected patients, may result in reduction in pain severity and disability Patients with SMP who respond to selectivesympathetic blockade Radiofrequency and neurolytic techniques are alternatives to a surgical sympathectomy Notes: The sympathectomy is very controversial but may be used in patients with SMP who respond to sympathetic blockade Stanton-Hicks M et al. Pain Practice. 2002;2:1-16. Bandyk DF et al. J Vasc Surg. 2002;35:269-277.

Other Therapies Behavioral modification Psychiatric consultation Complimentary and Alternative therapies Acupuncture Few placebo-controlled trials have shown therapeutic efficacy of analgesics for patients with CRPS regardless of route of injection or drug delivery technique. Raja SN et al. Anesthesiology. 2002; 96:1254-1260.

Prognosis Difficult to predict Earlier intervention may be more likely to be successful Some patients experience reduced symptoms or apparently full recovery Some patients continue to experience significant disability Raja SN et al. Anesthesiology. 2002;96:1254-1260.

Conclusions RSD/CRPS is a chronic neurologic syndrome Not all patients have the same set of symptoms Early diagnosis and appropriate treatment is essential Ideal treatment should be multidisciplinary

Bibliography Bandyk DF, Johnson BL, Kirkpatrick AF, Novotney ML, Back MR, Schmacht DC. Surgical sympathectomy for reflex sympathetic dystrophy syndromes. J Vasc Surg. 2002;35:269-277. Bogduk N. Complex regional pain syndrome. Current Opinions in Anesthesiology. 2000;14:541-546. Bruehl SP, Harden RN, Galer BS, et al. External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Internal Association for the Study of Pain. Pain. 1999;81:147-154. Galer BS, Schwartz L, Allen RJ. In: Loeser, ed. Bonica’s Management of Pain. 2001: 388-411. Harden RN, Bruehl SP, Galer BS, et al. Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive? Pain. 1999;83:211-219.

Bibliography (continued) Jänig W. CRPS-I and CRPS-II: A strategic view, In: Harden , Baron Jänig, eds. Complex regional Pain Syndrome, Progress in Pain Research and Management. 2001: 3-15. Kingery WS. Pain. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. 1997;73:123-139. Raja SN , Grabow TS. Complex regional pain syndrome I (Reflex Sympathetic Dystrophy) Anesthesiology. 2002;96:1254-1260. Stanton-Hicks M, Burton AW, Bruehl SP, et al. An updated interdisciplinary clinical pathway for CRPS: Report of an expert panel. Pain Practice. 2002;2:1-16. Stanton-Hicks M, Jänig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain. 1995;63:127-133 Stanton-Hicks M, Baron R, Boas R, et al. Complex Regional Pain Syndrome: guidelines for therapy. Clin J Pain. 1998;14:155-166.