CRPS – physical condition or somatoform disorder?
|In this article, Dr Ivan Ramos-Galvez LMS, FRCA FFPMRCA explores Complex Regional Pain Syndrome (CRPS) in detail, looking at pathophysiology theories and different treatment approaches.
Dr Ivan Ramos-Galvez LMS, FRCA FFPMRCA has a NHS practice is at the Royal Berkshire Hospital and a private practice at Spire Dunedin and Circle Hospitals in Reading.He is fast becoming the “go-to” medico legal expert for cases involving CRPS.
Complex Regional Pain Syndrome (also referred to by the acronym CRPS) encompasses a group of symptoms that incorporate a neuropathic disorder with poor blood flow. It may follow trauma to a limb, surgery, a simple medical procedure or prolonged immobilisation. There have been reports of cases with spontaneous onset as well as onset related to life-related psychological trauma.
The incidence in Europe is 26/100,000 population. This is based on pan-European epidemiological studies that have shown that CRPS is more prevalent than previously reported. Under reporting, is common, as there is a significant lack of awareness of CRPS among health professionals. This means that a significant proportion of cases go undiagnosed and untreated.
Psychogenic issues, rather than CRPS are often blamed for the symptoms. The world of medicine is one where the gold standard for diagnosis is imaging and blood tests. In the absence of the expected healing process after a given course of treatment and satisfactory investigations, a proportion of patients get pigeon-holed as having developed a “pain syndrome”. This carries psychosomatic connotations in the mind of those involved including healthcare professionals and patients.
One of the difficulties with diagnosing CRPS arises from the evolution of the disease, as there is a natural tendency towards amelioration of the autonomic signs and symptoms with time. Therefore, after several years, and with only pain as a main complaint, a diagnosis of CRPS is not always possible, as the Budapest Criteria, which is the diagnostic criteria used to diagnose CRPS, will not be fully met.
The consequences of CRPS are devastating. Whilst 85% of patients achieve a significant reduction in pain over the first 2 years, only a minority consider themselves symptom free 6 years later and 40% of sufferers will never return to their previous employment. These patients therefore, represent a high cost to society.
The typical duration of symptoms before a patient is considered for a spinal cord stimulator is assumed by NICE to be 15 years. Even patients who have a successful implant of a spinal cord stimulator may never return to work. Overall, the quality of life of CRPS sufferers is very low, with Euroquol scores averaging 0.2 to 1 (Euroquol for MS average 0.4 to 1)
Typically, CRPS presents itself as a swollen/puffy, stiff, hot/cold purple/red/white/waxy/mottled limb with dry/flaky skin, poor nails that are brittle and flake off and hair that falls off in response to touch. There are some less common symptoms. These include skin manifestations with blisters, ulcerations and infected lesions; lymphedema; dystonia, muscle contractures, tremors; severe atrophy of the muscles in the affected area; widespread autonomic signs affecting the whole limb and with pain only in a specific area of the affected limb.
It can spread to the contralateral limb (other arm/leg), to the ipsilateral limb (to the other limb on the same side) or diagonal (to the other limb on the other side). Spontaneous spread has a mean interval between onset and a second limb of 10 to 21 months. The more limbs affected, the more likely it will be to spread and affect further limbs. In approximately 50% of cases of spread, the trigger has been new trauma. Over 90% of cases of diagonal spread are triggered by new trauma, whilst this is the case in only 30% of cases of contralateral spread. This is relevant for future surgery, where this can be a trigger for spread across to other parts of the body. Whilst surgery in the affected limb can be a trigger; the same applies to a lesser degree to any type of surgery. The risk of CRPS deteriorating, reactivating or spreading with new surgery is however, unknown.
The pathophysiology of CRPS remains unknown. Several theories have been postulated:
Sympathetically mediated disorder: This is based on the presence of changes in sweating and temperature in the affected limb. This appears to be the case in the acute early stages where there is increased response to the affected limb to circulating catecholamines. The affected limb also displays adrenergic receptors on nociceptive fibres. Therefore, the affected limb displays signs in keeping with increased sympathetic tone, as well as sympathetically mediated pain. The long-standing cold limb in chronic CRPS is secondary to endothelial dysfunction.
Central Sensitisation: Process by which, after a period of time when a part of the body has been painful, any stimulus becomes painful even after the original stimulus is no longer active. Initially this acts as a protective mechanism. However, after a period of time it simply increases pain felt with non-noxious stimulus. CRPS sufferers have increased windup to stimulation of the affected limb compared to the non-affected one.
Autoimmune disorder: Anti-neuronal antibodies have been found in the surface of autonomic neurons in the limb affected by CRPS. Low dose IV immunoglobulin G has shown efficacy in even long-standing CRPS cases.
Secondary to limb ischaemia/reperfusion injury: This is based on anecdotal reports of improved pain perception with vasodilating drugs, but with no change on objective limb temperature readings.
Cortical Reorganisation: The advent of MRI has shown altered responses in the areas of the sensory cortex responsible for sensation in the affected area. Similar changes in other parts of the cortex may explain the alienation that patients feel and the affective changes they suffer with regards to their affected limb.
Nerve damage: There is a reduction in density in C and Aδ fibres in the afferent neurons from the affected limb when compared to the non-affected. These fibres are replaced by aberrant ones with unknown function that may be responsible for the neuropathic features. CRPS sufferers describe their pain with descriptors often associated with neuropathic pain. Also, they complain of sensory disturbance that, together with the type of pain they display, would amount to a diagnosis of neuropathy.
Inflammation: The signs of CRPS are the same as the signs of inflammation (pain, heat, redness, swelling and reduction in movements). Limbs affected by CRPS release inflammatory interleukins cytokines, tumour necrosis factor, neuropeptides bradykinin and substance p. These chemicals increase vasodilatation and capillary leakage and produce the features seen in early CRPS. However, whist steroids have some anecdotal early efficacy, they are not efficacious in long-established CRPS cases.
Genetics: There appears to be a genetic link in as much as family studies have found that siblings of CRPS sufferers who develop it under 50 years of age are 3 times more likely to develop CRPS themselves. Some genes within the HLA group appear to be linked to the development of CRPS.
Psychological: The lack of structural abnormality in CRPS has led to postulations that CRPS is a Somatoform disorder, akin to malingering. Stress in the pre-CRPS phase has been known to trigger CRPS in some patients. Despite the lack of scientific evidence for this rational, this theory is of paramount relevance in the medico legal setting, more so than in the clinical environment.
A Somatoform disorder is an array of physical symptoms that mimic physical disease or injury for which there is no identifiable organic cause, or if there is, the symptoms cannot be fully explained by the nature of the injury. Symptoms from a Somatoform disorder are due to the manifestations of mental distress or have a psychogenic aetiology. Therefore, the cardinal symptom of CRPS being pain out of proportion to the injury is in keeping with the paramount diagnostic criterion of Somatoform pain disorder. Research however has found no correlation between pre-existing depression/ anxiety and the subsequent onset of CRPS.
There is no indication that psychological factors cause the onset of pain in patients with CRPS. On the contrary, in controlled trauma, such as surgery, patients with CRPS have been found to have a higher level of depression than patients with lesser levels of pain. Therefore, there is a relationship between pain causing emotional distress, low mood, disuse of the affected limb and therefore maintenance of the disease.
This psychogenic model however, cannot explain the neurological and neuroanatomical deficits related to CRPS. 65% of patients with CRPS have a compromised ability to perform higher order mental tasks and to take decisions. They also lack the ability to improve their ability to react and take decisions based on learning from experience. Post-mortem studies on CRPS sufferers have revealed atrophy of the grey and white matter in regions of the brain involved in pain perception, emotional experience and autonomic regulation. These factors make CRPS patients different from a non-CRPS chronic pain sufferer who is on the same type of medications without suffering these effects.
The self-reported disturbance in body perception, hostility towards the affected limb and de-personalized description of their affected limb including the guarding of the affected limb are other features that are more prevalent in CRPS sufferers than in the non-CRPS chronic pain population. The psychogenic model of CRPS tries to explain these findings by relating CRPS to a Body Dysmorphic disorder. However, therapies that try to address limb immobility through mirror stimulation or graded motor imagery do reduce these manifestations in CRPS sufferers whist they are not efficacious in treating the Dysmorphic disorders.
Overall, it appears that indeed there is a link between psychology and CRPS. Chronic pain is linked with higher depression, anxiety and anger. However, there is little evidence to indicate that psychological factors cause the onset of pain, autonomic dysfunction and movement disorders seen in CRPS. There is no scientific evidence that any specific type of personality will be more prone to developing CRPS.
Whatever the aetiology, most patients feel stigmatised by healthcare professionals who do not believe that their pain is real.
CRPS is difficult to manage. Many different avenues to treatment have been tried and often the results are mediocre at best:
Physical and Occupational therapy: Key in the rehabilitative process and should therefore be the first line of treatment as its aim is to regain use of the affected limb. There are many variants that can be used and these are largely tailored to the individual patient.
Psychological interventions: Given the effect that CRPS has in the entirety of the life of the sufferer, there is a large emotional and psychological burden placed on the sufferer and those close to them. Some techniques (CBT, Mindfulness, Biofeedback) try to return the control of their lives back to the patients.
Other techniques that increase parasympathetic nervous system activation (autogenic training, hypnotherapy, guided imagery, progressive muscle relaxation) may help reduce anxiety and depression as well as the CRPS symptoms. It is unclear if these therapies reduce pain by reducing anxiety and depression or if they do so by reducing psychological symptoms that maintain pain-related behaviours.
Graded motor imagery and mirror therapy can help to reset aberrant cortical reorganisation and reduce, not just the sensitivity, but also the abnormal affect. The success however, reduces as the longevity of the symptoms increases.
Medical Management: Given the inflammatory basis of CRPS, oral and intramuscular Corticosteroids have been tried with variable results for some patients. NSAIDs have never shown any efficacy. As active inflammation generates free radicals, oral and topical anti-oxidants have been used to try and reduce the spread and severity of the symptoms of CRPS. Of all, only Vitamin C has shown to have a clinical effect in preventing CRPS when used prophylactically before surgery.
Anti-convulsant antihyperalgesics (Gabapentin or Pregabalin) have a role in the management of the neuropathic symptoms (both pain and sensory deficit) of patients with CRPS. Perhaps they are more efficacious in the early stages, but overall, they are effective.
Because of the central sensatisation that involves NMDA receptors in the spinal cord, Ketamine or Magnesium may be efficacious. Ketamine has also shown an effect when administered topically. They can be extremely efficacious, but their administration is often plagued with very unpleasant side effects.
The sympathetic-mediated symptoms can be treated with oral antiadrenergic drugs (Phenoxybenzamine) or with α-2 agonists (clonidine), particularly in the early stages.
As the symptoms progress and the limb becomes permanently cold, the vasoconstriction can be managed with calcium channel blockers (Nifedipine) that try to vasodilate the limb. The tremor and dystonia of the late stages can be managed with Baclofen that can improve not just the muscle movements but the pain and functionality. Baclofen can be very effective when combined with a neuromodulation technique. Once the lack of use of the limb has initiated the process of bone reabsorption, the combination of Calcitonin (that increases bone deposit) and Bisphosphonates (that reduce bone destruction) can be beneficial. There is some controversy as to the time beyond which Bisphosphonates no longer affect the course of CRPS, which some sources quote at 6 months.
Opioids are efficacious in the short term. In the longer timeframe, the same reservations that apply to other non-malignant conditions prevail.
Invasive approaches: Some cases derive significant improvement with local anaesthetic blocks of the sympathetic ganglia (percutaneous chemical sympathectomy), but the effect is often not prolonged by repetition of the block. These blocks however can be very efficacious in restoring function and quality of life. Those patients who derive a good, but short-lived, result can be successfully treated with more permanent neurolytic sympathectomy techniques involving alcohol, phenol or radiofrequency. The complications however are high, including anhydrosis (inability to sweat) and neuralgia, and the result is unpredictable.
Neuromodulation, Spinal Cord Stimulation, is the gold-standard treatment for CRPS sufferers. It improves pain as well as mood, function and quality of life. Studies however suggest that it loses efficacy over time and despite the improvements in symptom control, a variable proportion of implanted patients do not return to work. It also has a very high incidence of complications and implication for the rest of the patient’s life.
Emerging therapies: Immunomodulation, Hyperbaric oxygen, Botulinum Toxin-A, Plasma exchange, Naltrexone, Canabinoids. They have been used in small case series and require further studies before any recommendation can be made.
When dealing with CRPS in a medico legal setting, knowledge and understanding of the likely challenge that will be made at some point during the case, that the claimant is suffering from a Somatoform disorder, akin to malingering should be factored in so that it can be reviewed and if necessary ruled out by a competent expert in pain medicine with experience of diagnosing and treating CRPS in a clinical setting. This is especially the case as stress can exacerbate the CRPS.
Our experts have a unique combination of clinical skills as well as medico legal experience acting for both the claimant and defendant, to assist you in reaching the right outcome for the claimant and the court. If you need advice please call us on 020 7118 0650.