FEW presentations are more discouraging in a pain management clinic than a limb with established complex regional pain syndrome (CRPS).
The pale, wasted hand, carefully guarded by its owner, is reluctantly presented for examination. The patient grimaces before the limb is gently touched or stroked and is quick to withdraw it into a glove or boot. “I would rather you didn’t touch it” is a phrase not uncommonly heard.
CRPS is a regional pain condition, generally commencing in a distal limb after trauma or surgery. In the adult population, the most common inciting event is a fracture of the distal upper limb, but there are multiple variations on this: soft tissue injury, crush injury, surgery and spontaneous occurrence. Why some patients develop CRPS after injury, and others don’t, is unclear. Risk factors are possibly complicated fractures, intercurrent rheumatological disease and intense pain one week after trauma.
Females are more commonly affected than males at a ratio of three to one; peak incidence is at 50–70 years of age (postmenopausal women have a greater representation), and in adults, the upper limbs are more commonly affected.
A characteristic feature is evoked and spontaneous pain, which is disproportionate in intensity or longevity to usual or similar tissue trauma. Accompanying features are inflammatory and autonomic changes in the painful region, abnormal referred sensations and altered limb perception. Accompanying impairment of function and associated disability may be profound.
Over the past decade, greater medical community awareness has brought this challenging syndrome into the bright lights of evidence-based medicine. Multiple health professionals are involved in the assessment and treatment of this condition. GPs, orthopaedic surgeons and their trainees, sports physicians and physiotherapists may all be the first to encounter possible CRPS in their patients. The general consensus is that CRPS is challenging to correctly identify and even more challenging to treat.
Unrecognised CRPS and a failure to treat can have devastating long term effects for patients and their families. Persistent pain, impairment of function, mood disorders and loss of social and vocational roles are all ramifications of this condition. Comprehensive guidelines, drafted to facilitate greater index of suspicion and early referral, have been developed in the UK by a panel of representatives from every interested medical and allied health specialty.
The pathophysiology of CRPS remains hotly disputed and multiple contributing mechanisms are suggested: genetic predisposition, nerve injury, peripheral and central sensitisation, regional inflammatory and immune activation, oxidative stress and sympathetic nervous disfunction (here and here).
CRPS is classically subdivided according to the absence or presence of nerve injury. CRPS type 1, in the absence of documented nerve injury, is more common (90%) with a better prognosis. CRPS type 2, with associated major peripheral nerve injury, is less common (10%) with accompanying less favourable prognosis.
How is CRPS diagnosed?
The International Association for the Study of Pain supports a clinical diagnosis according to the Budapest criteria for CRPS. Diagnostic accuracy is approximately 80–90% if the Budapest criteria are met.
Pain is the most important symptom and, to meet the criteria, is disproportionate to the inciting event. CRPS incorporates a plethora of variable subjective descriptors and objective findings. Importantly, clinical features may be intermittent, may evolve with the duration of the presentation and may be evoked during a consultation.
To meet the Budapest criteria, subjective symptoms and objective signs in clinical categories are noted and tallied. Sensory, vasomotor, oedema/sudomotor and motor/trophic categories require the simultaneous presence of three symptoms and two signs in each of the four categories. Several clinic visits may be required for an accurate diagnosis. Allodynia (pain in response to a normally non painful stimulus) is a hallmark and CRPS is unusual in the absence of altered sensation.
Vasomotor features are colour and temperature asymmetry between unaffected and affected limbs. Intermittent limb oedema and hyperhidrosis, a characteristic sudomotor feature, may be described or photographed by the patient.
Trophic features are changes to hair growth (initial increase then later decrease) and nail health in the affected limb. Motor changes incorporate a wide range of features from tremor through to dystonia to limb neglect.
“That no other condition accounts for the presentation” is the final requirement for diagnosis and clinical suspicion for intercurrent illnesses should remain high. Differential diagnoses include infection, vascular insufficiency, limb thrombosis and neurological and musculoskeletal conditions.
Early recognition and prompt intervention
Patient education is a priority. Physiotherapists and orthopaedic practices provide patients with leaflets incorporating warning indicators, such as: “My plaster feels too tight, my hand is sweating under this”.
Functional restoration is the treatment focus. Using the affected limb in a normal fashion requires an integrated, multidisciplinary approach and early referral to a pain management clinic is considered standard practice of care.
Physiotherapists and occupational therapists in close collaboration with psychologists address maladaptive thoughts, feelings and behaviour in relation to pain and function, in particular fear avoidant behaviour and catastrophisation. A graded approach to desensitisation of the affected limb, increase in level of activity despite pain and appropriate management of pain flares are all central components to functional rehabilitation. Graded motor imagery and mirror box therapy are specific physiotherapy treatments to address altered limb perception and are incorporated into this.
Lifestyle modification and mood optimisation are critical to management. Smoking cessation is strongly encouraged, adequate sleep hygiene and nutritional intake are addressed. Depression, anxiety and post-traumatic disorder all require appropriate and regular mental health review.
The question of appropriate pharmacotherapy and interventions for CRPS requires a pragmatic approach. Good quality, highly powered studies in this area have been elusive largely due to the disparate presentations of CRPS. Suggestions below are variably incorporated into current practice in pain management clinics. By no means is this an exhaustive list and practice varies according to location, treatments available and medical discipline.
Analgesia is required to facilitate mobility. Simple analgesia is generally insufficient. Antineuropathic agents are trialled for modification of allodynia and hyperalgesia.
Anticonvulsants, such as gabapentin, and antidepressants, such as serotonin reuptake inhibitors (duloxetine) or tricyclic antidepressants (amitriptyline), are recommended for treatment of neuropathic pain, separately or in combination.
Five per cent lignocaine patches, applied to the affected area, may be tolerated with fewer side effects than oral antineuropathic agents.
Opioid escalation is discouraged. Tolerance occurs rapidly, and significant concerns around dependency and lack of functional improvement are commonplace. Non pure m-agonists such as tramadol and tapendatol in contained dosing may be more appropriate for moderate to severe pain.
In early CRPS (less than 12 months), a trial of oral corticosteroids over 6 weeks may be considered appropriate to dampen the inflammatory cascade. Anti-oxidant treatment is commenced or continued. This may be topical dimethyl sulfoxide
(50%), continuation of vitamin C or an alternative nutraceutical such as curcumin.
A short series of sympathetic ganglion blocks (stellate ganglion or lumbar sympathetic), one week apart, may provide analgesia to facilitate participation in physical treatment programs. Analgesia may extend beyond the duration of action of the local anaesthetic. Evidence to date is negative for sympathetic blocks assisting resolution of CRPS.
Intravenous bisphosphonate infusions are increasingly incorporated into CRPS treatment guidelines. Impaired bone metabolism is a feature of CRPS and a trial of a bisphosphonate such as pamidronate or zoledronic acid may assist with analgesia and improvement in function for reasons that are unclear.
Subcutaneous ketamine infusions at subanaesthetic doses may assist functional therapy. Significant side effects, including hepatic disfunction need to be monitored with repeat infusions (here and here).
A trial of neuromodulation following unsuccessful conservative treatment may be warranted. Implantation of a spinal cord stimulator follows a successful trial with continued emphasis on functional rehabilitation and normalisation of daily activities.
What is the prognosis of CRPS?
Chronic CRPS (greater than one year) is associated with lower resolution rates. Long term management highlights functional therapies, normalisation of daily activities and harm minimisation. Disability is profound, mood disorder is common, and the patient with CRPS requires an empathetic and holistic approach to care.
Early therapeutic intervention is desirable such that the transition to chronic CRPS is prevented. In the words of Frank Berklein and colleagues: “better to treat one too many than one too few”. Clinical suspicion of CRPS is prioritised for urgent review, and pain management clinics welcome several possible early presentations rather than one late presentation.
Dr Jane Standen is a consultant anaesthetist at Royal North Shore Hospital in Sydney and interventional pain specialist at Sydney Pain Specialists. She has expertise in the management of both early onset and persistent pain. Her areas of interest included complex regional pain syndrome, neuropathic pain and pain management in the elderly.
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