KA
Devine1, SC Kong1, JB Neilly2, EH Forrest1
1Departments of Gastroenterology and 2Nuclear Medicine, Glasgow Royal Infirmary.
SMJ 2007 52(4): 54
Abstract
We
report the case of a 38 year-old woman who presented with sensory symptoms of
her right foot with no history of trauma. Subsequent nuclear imaging was
suggestive of stage 1 complex regional pain syndrome type I (CRPS I).
Keywords:
Reflex sympathetic dystrophy, complex regional pain syndrome type I
Case
report
A 38-year old woman was admitted to hospital with sharp pain and altered sensation affecting her right foot. Two months earlier she had awoken with numbness in her right foot. This had occurred spontaneously and without a history of injury. The numbness settled over a few days but neuropathic features in her foot, mainly dysaethesia, tingling and allodynia became more apparent and caused difficulty with sleeping, mobility and dressing. There was a past medical history of childhood abuse, chronic anxiety and agoraphobia, pancreatitis, alcohol abuse (she had abstained for one year prior to admission), cholecystectomy and an ectopic pregnancy.
On examination, her right foot was exquisitely painful to touch, with even light touch provoking a disproportionate reaction. The sensory symptoms did not correspond to a dermatomal or peripheral nerve distribution. Tone and power were normal but both ankle reflexes were absent. The right foot was noted to be warm and moist compared to the left foot.
Initial blood tests revealed deranged liver function tests in a pattern that is normally typical of alcohol excess with a high AST to ALT ratio. These abnormal results resolved during admission. A full serological autoantibody screen and a haematinic profile revealed no positive findings. The CT brain was unremarkable apart from mild cerebral atrophy. An MRI of brain and lumbar spine showed no significant abnormality and specifically revealed no evidence of demyelination. Nerve conduction studies were also performed which showed a degree of small fibre nerve dysfunction, which could reflect an early distal axonal peripheral neuropathy. Subsequently, a 3-phase bone scan was requested as there was a high clinical suspicion that this was complex regional pain syndrome. The bone scan revealed markedly increased blood flow to the right lower extremity compared to the left (Image 1). Blood pool images (Image 2 Left) and delayed images (Image 2 Right) revealed increased uptake of tracer throughout the right foot. The differential diagnosis for these bone scan findings includes inflammatory arthritis, Charcot arthropathy, osteitis and fracture. In this case, there was no history of trauma or diabetes and no clinical or radiological evidence of arthritis or fracture of the bones of the feet, thus supporting the clinical diagnosis of CRPS I.
Image 1: Blood flow (Phase
1) bone scan images
Image 2: Bone Scan blood (Phase 2) pool images (left) and delayed (Phase 3) images (right)
This patient was commenced on gabapentin and referred to the pain clinic
for further guidance on management. Subsequently she has been treated using a
holistic approach to her pain. This included lamotrigine, capscasin cream and
input from the community mental health team to improve her coping strategies
with regard to her anxiety, which is often precipitated by her pain.
Unfortunately, whilst on lamotrigine, she encountered flu like symptoms,
which may have reflected hypersensitivity syndrome. This drug was therefore
discontinued and a trial of pregabalin has since been initiated.
Discussion
Complex regional pain syndrome type I (CRPS I), formerly known as reflex sympathetic dystrophy (RSD), is a clinical syndrome of variable course and unknown cause characterised by pain, oedema, and vasomotor dysfunction of an extremity. This condition is often the result of trauma or surgery without nerve injury but may occur spontaneously. This is distinct from causalgia or complex regional pain syndrome type II (CRPS II), in which the aetiology is a partial nerve injury.
The differential diagnosis of CRPSI is extensive. Firstly, peripheral tissue causes such as fasciitis, ligamental strain and arthritis should be considered. Causes of peripheral neuropathy and dorsal root pathology such as autoimmune and metabolic diseases can of course give rise to similar symptomatology as that experienced in CRPSI. Finally, it is important to exclude central causes of neurological deficit such as demyelinating diseases, cerebral tumours and spinal pathology.
The clinical progression of CRPS I is divided into 3 stages.1 The acute stage involves continuing pain, allodynia, or hyperalgesia with which the pain is disproportionate to any stimulus. Increased skin temperature, swelling, discolouration and acceleration in nail and hair growth in the affected area are also common. The second dystrophic stage is characterised by cold, pale skin and signs of hair loss and brittle nails. The final atrophic stage is manifested by muscle atrophy, joint contractures and reduced range of movement. However, many patients do not appear to progress consecutively through each stage, making the clinical course of CRPS1 quite variable.2
The current diagnostic criteria for CRSP1, set by the International Association for the Study of Pain (IASP) Table 1, are based on clinical signs and symptoms.2 These diagnostic guidelines do not account for the different stages of CRPS1 and as there is no gold standard test, the diagnosis of this disease is notoriously difficult.
Table 1: IASP Diagnostic
Criteria for CRPS1 (* Not required for diagnosis)
1.
The presence of an initiating noxious event or cause of immobilisation *
2.
Continuing pain, allodynia, or hyperalgesia, with which the pain is
disproportionate to any inciting event
3.
Evidence at some time of oedema, changes in blood flow, or abnormal
sudomotor activity in the region of the pain
4. The absence of conditions that would otherwise account for the degree of pain and dysfunction
The pathophysiological mechanism of CRPSI is poorly understood. It was initially believed that sympathetic dysfunction was the cause given that the increase in temperature, reddening of the skin and sweating could be explained by sympathetic over-activity. However, this hypothesis fell out of favour when it became apparent that not all patients benefited from chemical or surgical sympathectomies. Another theory suggests that following trauma, the efferent arm of the sympathetic nerve discharges and causes sensitisation of afferent C-nociceptors, thereby causing increased pain when they are exposed to catecholamines. Nevertheless, most research is being devoted to the involvement of neuropeptides in CRPSI. Substance P, calcitonin gene-related peptide (CGRP) and neuropeptide Y are released from unmyelinated C fibres that enter the dorsal horn of the spinal cord and synapse to central pain projecting neurons when action potentials reach a critical threshold. Indeed, most patients with CRPSI suffer oedema that persists and spreads. The evidence suggests that this is secondary to the release from C fibres of CGRP, which causes vasodilitation and substance P, which causes increased vascular permeability. Pain appears to be mediated by the release of a cascade of cytokines and neuropeptides when a peripheral nerve or its nociceptive endings are damaged. This in turn causes activation of intracellular kinases such as mitogen activated protein kinase, which leads to changes in gene expression in the dorsal root ganglion, and dorsal horn central pain-projecting neurons that establish and sustain central sensitisation.3
Three phase radionuclide bone imaging is the current investigation of choice to support the clinical diagnosis of CRPSI. The first (vascular) phase is obtained during the intravenous administration of Tc-99m-MDP. The second (blood pool) phase is acquired at 5 minutes following injection, and the third or delayed phase is obtained 4 hours after injection. Sensitivity and specificity of this scan are debated in the literature with values for sensitivity ranging from 80 to 96% and specificity between 96%-100%.4 One study showed that sensitivity of the bone scan increased with progression of the disease from only 25% sensitivity at stage 1 to 100% at stage 3.5
Initial treatment of CRPSI includes nonsteroidal anti-inflammatory drugs, steroids, tricyclic antidepressants, anti-convulsants, local anaesthesia and capsaicin cream often coupled with physiotherapy and hydrotherapy. Pharmacological therapies often fail to fully relieve symptoms alone and the efficacy of most of these agents in the treatment of CRSPI is yet to be clarified.6 Chemical and surgical sympathectomies are often offered if medical management fails but the evidence for this is poor. However, as the central role of neuropeptides in the pathophysiology of CRSPI has become more established, therapeutic targets now include inhibiting neuropeptide release or action on the post synaptic receptor. Indeed, intravenous bisphosphonates such as alendronate and clodronate have been shown to inhibit the release of neuropeptides thereby reducing pain.7
Our case illustrates the importance of obtaining a detailed history and careful examination in planning relevant investigations to arrive at the correct diagnosis. It would have been a disservice to the patient if her symptoms had been dismissed as ‘functional’ in view of her complex psychological history and high alcohol intake. CRPS1 should be considered in patients who present with atraumatic persistent neuropathic pain.
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