1.11 Complex regional pain syndrome

Complex regional pain syndrome (CRPS), previously termed reflex sympathetic dystrophy (RSD), consists of abnormal pain, swelling, vasomotor instability, contracture, and osteoporosis (Box 1.11.1). It used to be considered a rare, devastating complication of injury, caused by abnormalities in the sympathetic nervous system and seen mainly in psychologically abnormal patients. Modern research is altering this view radically.

The International Association for the Study of Pain (IASP) has replaced the condition’s many synonyms with CRPS, which avoids suggesting aetiology or site. The IASP have produced diagnostic criteria which have not been universally adopted and we have proposed a different approach which is more relevant for the orthopaedic surgeon (Box 1.11.2).These two sets of criteria are identical for diagnostic purposes within an orthopaedic context.

CRPS is subdivided into type 2, where there is a causative major nerve injury (the original causalgia described by Mitchell in American Civil War casualties), and type 1, where there is not (previously reflex sympathetic dystrophy or algodystrophy). This distinction is clinically important since in type 2 CRPS, treatment can be directed directly at the damaged nerve.

CRPS is a biphasic condition with early swelling and vasomotor instability giving way to late contracture and joint stiffness The hand and foot are most frequently involved, although the knee is increasingly recognized The elbow is rarely affected, whereas shoulder disease is common and the hip is affected in transient osteoporosis of pregnancy.

CRPS usually begins up to a month after the precipitating trauma. As the effects of injury subside, a new diffuse, unpleasant, neuropathic pain arises. Neuropathic pain occurs without a noxious stimulus and spontaneous or burning pain (causalgia), hyperalgesia (increased sensitivity to a noxious stimulus), allodynia (pain provoked by innocuous stimuli, such as gentle touch), and hyperpathia (temporal and spatial summation of allodynia) are common. Pain is unremitting, worsening, and radiating with time (Box 1.11.3).

Vasomotor instability (VMI) and oedema dominate the early phase (Figure 1.11.1), although this is less marked with more proximal CRPS. Classically, initially the limb is dry, hot, and pink, later becoming blue, cold, and sweaty. In most cases there is merely an increase in temperature sensitivity. Oedema is marked and loss of joint mobility is due to swelling and pain.

Passing into the late phase, VMI recedes, oedema resolves, and atrophy of every tissue occurs (Figure 1.11.2). The skin is thinned and joint creases and subcutaneous fat disappear. Hairs become fragile, uneven, and curled while nails are pitted, ridged, brittle, and discoloured brown. Palmar and plantar fascias thicken and contract simulating Dupuytren’s disease. Tendon sheaths become constricted causing triggering and muscle contracture combined with tendon adherence leads to reduced tendon excursion. Joint capsules and collateral ligaments shorten and adhere, causing contracture.

Bone involvement is universal with increased uptake on bone scanning in early CRPS (Figure 1.11.3). This is not periarticular, suggesting arthralgia but generalized and may not occur in children. Later, the bone scan returns to normal and there are radiographic features of rapid bone loss: visible demineralization with patchy, subchondral or subperiosteal osteoporosis, metaphyseal banding, and profound bone loss (Figure 1.11.4).

Severe, chronic CRPS is uncommon and the prevalence is less than 2% in retrospective series. In contrast, prospective studies show that mild CRPS occurs after 20–40% of every fracture and surgery where it has been actively sought. Although these cases resolve substantially within a year, some features—particularly stiffness—remain, suggesting that CRPS may be responsible for significant long-term morbidity even when mild.

CRPS may occur after any particular trauma while an identical stimulus in a different limb does not cause it. The incidence is not changed by treatment method and open anatomic reduction and rigid internal fixation does not abolish it. It is unclear whether injury severity or quality of fracture reduction alters the incidence. There is, however, an association with excessively tight casts and there may be a genetic predilection. The following aetiologies have been proposed (Box 1.11.4):

CRPS is not primarily psychological and most patients are psychologically normal. There is an association with antecedent psychological stress which probably exacerbates pain in CRPS, as in other diseases. It seems likely that the severe chronic pain of CRPS causes depression and that a ‘Sudecky’ type of patient who develops CRPS is at risk of a poor outcome because they will not mobilize in the face of pain.

Pain is normally caused when a noxious stimulus activates high-threshold nociceptors. Neuropathic pain in CRPS occurs without appropriate stimulus and has no protective function. However, injured peripheral nerve fibres undergo cellular changes which cause usually innocuous tactile inputs to stimulate the dorsal horn cells via A-β fibres from low-threshold mechanoreceptors, causing allodynia in CRPS 2. Furthermore, axonal injury prevents nerve growth factor transport which is essential for normal nerve function. In CRPS 1, inflammatory mediators released by the initial trauma (and possibly retained due to a failure of free radical clearance), can sensitize nociceptors to respond to normally innocuous stimuli.

A number of features of CRPS suggest sympathetic nervous system (SNS) dysfunction (e.g. vasomotor and sudomotor disturbance); however, SNS activity is not usually painful. In CRPS, some pain (termed sympathetically maintained pain, SMP) is SNS dependent and is relieved by stellate ganglion blockade and worsened by noradrenalin injection. Furthermore, there is an abnormal difference in cutaneous sensory threshold between the limbs, which is reversed by local anaesthetic sympathetic chain blockade, while increasing sympathetic activity worsens pain. SMP is explained by the body’s reaction to injury. After partial nerve division, injured and uninjured somatic axons express α-adrenergic receptors and sympathetic axons come to surround sensory neurons cell bodies in dorsal root ganglia. These changes make the somatic sensory nervous system sensitive sympathetic mediators.

CRPS is associated with inflammatory changes including macromolecule extravasation and reduced oxygen consumption. In animals, infusion of free radical donors causes a CRPS-like state and amputated human specimens with CRPS show basement membrane thickening consistent with overexposure to free radicals. These considerations suggest that CRPS is an exaggerated local inflammatory response to injury. In other words, CRPS represents a local form of the systemic free radical disease that causes adult respiratory distress syndrome and multiple organ failure after severe trauma. This concept is supported by evidence that the free radical scavenger, vitamin C, is effective prophylaxis against post-traumatic CRPS. An alternative explanation is a primary capillary imbalance causing stasis, extravasation, and consequent local tissue anoxia.

Undue immobilization has been proposed as the cause of CRPS and all features of CRPS, except pain, are seen after cast immobilization. CRPS is associated with an often overlooked abnormality of motor function, varying from weakness to incoordination and tremor. The best description is that in CRPS-1, patients find it difficult to initiate or accurately direct movement. Learned pain avoidance behaviour in response to allodynia may exacerbate changes of disuse since normal tactile and proprioceptive input are necessary for correct central nerve signal processing. In some patients, there is a central sensory confusion: in response to an apparently painful non-noxious stimulus, the patient cannot determine whether it is truly painful. The consequent impairment of integration between sensory input and motor output may be the major cause of CRPS.

CRPS is a clinical diagnosis and there is no single diagnostic test which is definitive. The classic case is obvious and direct effects of trauma, fracture, cellulitis, arthritis, and malignancy are common alternative diagnoses. The patient is systemically well with normal general clinical examination, biochemical markers, and infection indices.

X-ray appearances and bone scans have already been discussed. Sudeck’s technique of assessing bone density by radiographing two extremities on one plate remains useful. A normal bone scan without radiographic osteoporosis virtually excludes adult CRPS. Temperature difference between the limbs is greater in CRPS than other pain syndromes but this is not usually applied in an orthopaedic context. Magnetic resonance imaging shows early bone and soft tissue oedema with late atrophy and fibrosis but is not diagnostic.

Proper scientifically constructed prospectively randomized blinded studies are few and uncontrolled investigations are particularly unreliable in CRPS. Most patients are sensible people, concerned at the development of inexplicable pain, but the occasional ‘Sudecky’ patient fares poorly and should be treated vigorously. Early treatment before contractures occur gives optimal results, so a high index of clinical suspicion must be maintained.

Modern CRPS treatment emphasizes functional rehabilitation of the limb to break the vicious cycle of disuse, rather than SNS manipulation. Initial treatment from the orthopaedic surgeon is by reassurance, excellent analgesia and intensive, careful physiotherapy avoiding exacerbation of pain. Non-steroidal anti-inflammatory drugs may be preferred to opiates. Immobilization and splintage are generally avoided, but if used, joints must be placed in a safe position and splintage is a temporary adjunct to mobilization. If the patient does not respond rapidly, a pain specialist should be involved and treatment continued on a shared basis. Second-line treatment is often unsuccessful and many patients are left with pain and disability. Further treatments include centrally-acting analgesic medications such as amitriptyline, gabapentin, or carbamazepine; regional anaesthesia; the use of membrane-stabilizing drugs such as mexiletine; calcitonin; sympathetic blockade and manipulation; desensitization of peripheral nerve receptors with capsaicin; transcutaneous nerve stimulation or an implanted dorsal column stimulator. A different approach including behavioural therapy may be necessary in children. Where the knee is affected, epidural anaesthesia and continuous passive motion may be appropriate (Box 1.11.5).

The role of surgery is limited. Where CRPS is caused by a surgically correctable painful lesion, such as median nerve compression at the wrist, surgery should be undertaken cautiously in the presence of active disease. Surgery is rarely indicated to treat fixed contractures which usually involve all of the soft tissues. Surgical release must therefore be radical and expectations limited. Surgery for contracture should be delayed until the active phase of CRPS has completely passed and ideally there should be a gap of at least 1 year since the patient last experienced pain and swelling.

Amputation in CRPS should be approached with extreme caution because pain may continue.