Wednesday, June 4, 2014

CRPS Ideology: A Timely Thread

An interesting, and timely, series of exchanges engendered by a "Personal View" statement entitled "Complex regional pain syndrome medicalises limb pain" submitted by Christoper Bass, a British psychiatrist. [BMJ 2014;348:g2631].

If you're a Faithful Reader, perhaps you'll recall two recent rants from this very blog as you read.
Good on ya!  For the Uninitiated, these two posts offer the reality that can result when entrenched ideology collides with actual patients:
Dr. Huddleston: A Presumption, I Presume?
Jose Ochoa, Famed Medical Turd, Has Doppelgänger in Metro Atlanta

Rembrandt's The Anatomy Lesson of Dr. Nicolaes Tulp

I am a psychiatrist who has worked in general hospitals and pain clinics since the 1970s and have assessed many patients given a diagnosis of type 1 complex regional pain syndrome (CRPS). The syndrome is often diagnosed by inexperienced junior doctors when confronted by patients with unexplained symptoms, especially pain in the hands and feet. CRPS was once called algodystrophy, then reflex sympathetic dystrophy, but by 1994 the sympathetic component was abandoned and the current term was introduced.1 CRPS is part of a larger problem in chronic pain and reflects our lack of knowledge of causal mechanisms.
It has been my impression that increasing numbers of patients are being diagnosed with this disorder, and that incidence rates are increasing (estimates in 2007 of 50 000 new cases annually in USA).2 In my opinion excessive reliance on this so called biomedical diagnosis for these patients is misguided. How has this occurred?
Several new diagnostic criteria have been proposed,3 but they are not sufficiently objective or reliable.4 For example, criteria such as “continuing pain that is disproportionate to … [continued HERE]
Here are a few of the responses to Dr. Bass. To keep an eye on the growing thread, check back through THIS LINK:

Richard Haigh, Consultant Rheumatologist & Hon Senior Lecturer
Prof Candy McCabe, Royal National Hospital for Rheumatic Diseases;
Dr Nick Shenker, Addenbrookes Hospital, Cambridge.
Royal Devon & Exeter Hospital, Exeter EX2 5DW
With colleagues, we have set up CRPS Network UK to improve clinical care and promote research into this condition. Our members have been involved in developing recent evidence based national guidelines. We are disappointed that Bass writes a provocative but poorly argued case that CRPS is over diagnosed and has psychological stress as the main trigger and thus is a ‘medicalised’ phenomena[i]. We would argue that the evidence points in the other direction, and it is sad that Bass has ignored much of the peer reviewed literature that supports the construct as a distinct clinical phenomena and fails to recognise significant scientific and clinical advances.
Firstly he claims, without evidence, that junior doctors are diagnosing this condition without support of senior doctors. A brief survey of Pain Clinic services in the South West region reveals they are wholly consultant led and readily accept urgent referrals of suspected CRPS. In our clinical experience and supported by data from the CRPS UK Register, it is far more likely that CRPS is under diagnosed, under treated and clinicians advise inappropriate coping strategies (i.e. immobilisation) due lack of knowledge of the condition throughout all levels of the health service[ii][iii].
Whilst the exact sequence of events determining the aetiology is unclear there is a huge amount known about the aberrant systems in CRPS Type 1 - cytokines, oxidative stress, vascular flow, neurogenic inflammation, markers of bone metabolism and significant peripheral and central nervous system abnormalities, none of which have been shown to be related to psychological distress - despite many researchers confident they would find a link.  Much of this work has demonstrated differences between CRPS and injury / fracture, refuting the notion that the construct is just a little more than reaction to injury[iv] [v]. Animal models demonstrate similar pathological patterns to human CRPS - again differentiating CRPS from a ‘normal’ response to injury[vi] [vii] and CRPS serum-IgG, when transferred to mice elicits abnormal behaviour consistent with that seen in animal models of CRPS[viii]. Some - but importantly not all - of the signs and symptoms of CRPS such as swelling and sensory phenomena can be seen following immobilisation. This is not evidence that the condition is merely due to immobilisation, but provides insight into some of the neurological mechanisms. It also confirms clinicians' observations that an active rehabilitation approach discourages the development of the syndrome, but even with this some people continue to have rapidly progressing CRPS.
The diagnostic criteria have been developed and modified until we have an internationally agreed set, combining both symptoms and signs. The ‘Budapest Criteria’ have excellent sensitivity (0.99), and greatly improved specificity (0.68).  The use of these criteria will reduce the possibility of false diagnosis[ix].
Bass cites evidence of psychosocial factors influencing outcome in chronic painful conditions such as CRPS. We do not doubt this and would expand this hypothesis that the outcome in more tangible conditions such as rheumatoid arthritis, stroke and malignancy are modified by such factors. He also claims “key psychological factors are ignored”. However, studies in both primary and secondary care have not found evidence that CRPS is associated with psychological distress[x] [xi]. A well controlled primary care study that examined 4 control cases for every CRPS case could not demonstrate an association with other pain syndromes or a pre-morbid psychological state before the development of CRPS[xii].
Bass then argues that the issue is that the diagnostic label is causing considerable disability. We can find no evidence for this. Our experience is that the diagnosis allows patients to make sense of distressing and often bizarre symptoms[xiii] and helps clinicians to develop active treatment programmes promoting functional restoration. Conversely, exactly the type of scepticism purported by Bass around the validity of their condition, greatly increases patients’ distress and leads to delayed diagnosis and access to appropriate rehabilitation. The invaluable multi-collegiate national guidelines published by the Royal College of Physicians in 2012 advocate active rehabilitation and do not recommend adoption of the sick role and disempowerment as claimed by Bass - they call for quite the opposite[xiv].
We agree that there is indeed a lack of psychological and psychiatric services for patients with severe chronic pain in the UK, but such deficiencies need addressing without dreaming up an alternative model for the aetiology, diagnosis and treatment of CRPS - without the evidence to support it! The huge amount of evidence and fascinating science supporting the existence of this syndrome has encouraged its recognition and early appropriate management - we don't need a step back towards attributing symptoms and signs of this condition to psychosocial factors as advocated by Bass.

[i]BMJ 2014;348:g2631
[ii] Allen GGaler BSSchwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain. 1999;80(3):539-44.
[iii] Shenker NG, Goebel A, Rockett M, Batchelor J, Jones G, Parker RA, Williams ACdeC, McCabe CThe prognosis for patients with chronic Complex Regional Pain Syndrome: the value of the CRPS-UK Registry. British Journal of Pain In Press
[iv] Parkitny L, McAuley JH, Di Pietro F, Stanton TR, O’Connell NE, Marinus J, van Hilten JJ Moseley GL. Neurology. Jan 1, 2013; 80(1): 106–117. Inflammation in complex regional pain syndrome. A systematic review and meta-analysis.
[v]Marinus J1, Moseley GLBirklein FBaron RMaihöfner CKingery WSvan Hilten JJ. Clinical features and pathophysiology of complex regional pain syndrome.Lancet Neurol. 2011 Jul;10(7):637-48.
[vi] Bennett GJ. A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): pain due to deep-tissue microvascular pathology.Pain Med. 2010 Aug;11(8):1224-38.
[vii] TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS. Substance P signaling contributes to the vascular and nociceptive abnormalities observed in a tibial fracturerat model of complex regional pain syndrome type I. Pain. 2004;108(1-2):95-107.
[viii]Goebel A1, Leite MIYang LDeacon RCendan CMFox-Lewis AVincent A. The passive transfer of immunoglobulin G serum antibodies from patients with longstanding Complex Regional Pain Syndrome. Eur J Pain. 2011 May;15(5):504.
[ix]Harden RN1, Bruehl SPerez RSBirklein FMarinus JMaihofner CLubenow T,Buvanendran AMackey SGraciosa JMogilevski MRamsden CChont MVatine JJ. Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome. 2010;150(2):268-74.
[x]Beerthuizen A, Stronks DL, Huygen FJ, Passchier J, Klein J, Spijker AV. The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1)—a prospective multicentre study. Eur J Pain2011;15:971-5.
[xi]Beerthuizen Avan 't Spijker AHuygen FJKlein Jde Wit R. Is there an association between psychological factors and the Complex Regional Pain Syndrome type 1 (CRPS1) in adults? A systematic review. Pain. 2009 Sep;145(1-2):52-9.
[xii]de Mos M1, Huygen FJDieleman JPKoopman JSStricker BHSturkenboom MC. Medical history and the onset of complex regional pain syndrome (CRPS). Pain.2008 Oct 15;139(2):458-66.
[xiii]Lewis JSKersten PMcCabe CSMcPherson KMBlake DR. Body perception disturbance: a contribution to pain in complex regional pain syndrome (CRPS). Pain.2007;133(1-3):111-9.
[xiv] Goebel A, Barker CH, Turner-Stokes L et al . Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP, 2012.

Psychological factors in Complex Regional Pain Syndrome  4 June 2014

Dr Michael D Spencer
Honorary Consultant Psychiatrist, Department of Pain Medicine, West Suffolk Hospital, Bury St Edmunds IP33 2QZ, UK.

Mr Stuart McKechnie
Barrister, 9 Gough Square, London EC4A 3DG.

Dr Rajesh Munglani
Honorary Consultant in Pain Medicine, Department of Pain Medicine, West Suffolk Hospital, Bury St Edmunds IP33 2QZ, UK.


This letter is in response to the personal viewpoint article “Complex regional pain syndrome medicalises limb pain1.

Whilst it is to be welcomed that Bass highlights the need for greater psychological input to NHS pain clinics, and the frequent role of psychological factors in the maintenance of chronic pain conditions such as complex regional pain syndrome (CRPS), we are concerned that the article appears to suggest that i) the causation of CRPS is largely within the psychological domain; and moreover that ii) somehow the condition could be minimised or averted if only it could be re-framed in a manner that demedicalised the problem – Bass states “there is a case for abandoning the term CRPS altogether because of its potential for iatrogenic harm” – and indeed he suggests we consider alternative descriptive terms such as “armache or legache”.

There is now abundant evidence to implicate autoimmune and oxidative stress processes within the causation of a significant number of CRPS cases2-4 and although not fully understood, it now looks very likely that any consideration of the aetiology of CRPS must largely focus upon neurophysiological and neurochemical pain processing pathways within a complex multifactorial context that also includes genetic and environmental factors. Furthermore, magnetic resonance imaging demonstrates structural abnormalities of connectivity between brain structures in CRPS – measures that are separable5 from those in other chronic pain conditions such as chronic back pain and fibromyalgia.  Clearly the position that CRPS arises because of pre-accident psychological factors or post-accident factors such as the pursuit of litigation are not in concordance with a growing body of evidence relating to the neuropathological aetiology of the condition.  As the UK guidelines on CRPS puts it lucidly, “It is also now clear that CRPS is not associated with a history of pain-preceding psychological problems, or with somatisation or malingering”6. Prospective studies also dismiss any such psychological factors in the genesis of CRPS7.

Nonetheless, psychological factors are of considerable importance in the management of CRPS, as with other chronic pain conditions, and the development of distress, helplessness and depression, in addition to dysfunctional pain beliefs and behaviours (for example the belief that the pain is harmful and that avoiding activity will help the recovery, and behaviours of guarding and avoidance of movement) are “Yellow Flags” associated with chronicity in acute back pain8 and which are equally applicable to outcome in CRPS6.  Authors of this letter include a psychiatrist and pain medicine clinician practicing within an NHS pain clinic, in cases where we encounter patients with CRPS in whom significant levels of disability have developed, psychiatric enquiry often reveals the onset of enhanced levels of disability to be chronologically associated with the onset or worsening ofdepression or some other form of psychological distress such as symptoms of post-traumatic stress disorder (PTSD).  In such cases, appropriate treatment of these psychological exacerbating and maintaining factors is hugely important as part of a multi-disciplinary approach to treating the CRPS9.

However, recognition of the underlying CRPS is vital and informs the provision of specialist treatments by Pain Medicine colleagues (in the form of specialist rehabilitation programmes and pharmacological and neuromodulatory interventions where appropriate).  To replace the CRPS diagnosis with a descriptive term such as “disproportionate pain” or “armache” would be a retrograde step, obfuscating that which has been clearly demarcated and elucidated through clinical and basic research.

Equally, one cannot ignore the serious impact that Bass’ proposed changes could have upon the assessment of chronic pain conditions in the courts.  Over the years, great strides have been made by the legal profession in recognising the validity of diagnoses in Pain Medicine. This has been reflected by the introduction of a separate section relating to Chronic Pain Disorders, including CRPS, within the 11th and 12th edition Judicial College Guidelines for the Assessment of General Damages in Personal Injury Cases. Judicial findings of CRPS are now commonplace, based on tested expert medical opinion, leading to financial awards that are commensurate with what is often a significant level of disability. Declassifying CRPS would have the potential to undermine the now generally accepted proposition that pain disorders should not be viewed through a prism of psychiatric injury or damage alone and therefore deny those suffering from CRPS a fair level of compensation. This would be a matter of some concern amongst those representing injured parties.

Finally, whilst psychological treatments are an essential part of the toolkit in treating CRPS and psychological processes are often key to understanding the perpetuation of chronic presentations, neuropathology and pain mechanisms not psychology are at the heart of causation of CRPS and psychological treatments cannot replace the specialist Pain Medicine rehabilitative, pharmacological and interventional treatments that CRPS patients often require.  To put it another way – just because one of the tools we need is a hammer, doesn't mean that the problem must be a nail.


1. Bass C. Complex regional pain syndrome medicalises limb pain. BMJ 2014;348:g2631.
2. Goebel A, Blaes F. Complex regional pain syndrome, prototype of a novel kind of autoimmune disease. Autoimmunity reviews 2013;12(6):682-6.
3. Tekus V, Hajna Z, Borbely E, et al. A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome. Pain 2014;155(2):299-308.
4. Taha R, Blaise GA. Update on the pathogenesis of complex regional pain syndrome: role of oxidative stress. Canadian journal of anaesthesia = Journal canadien d'anesthesie 2012;59(9):875-81.
5. Geha PY, Baliki MN, Harden RN, et al. The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional and autonomic regions. Neuron 2008;60(4):570-81.
6. Royal College of Physicians. Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. Royal College of Physicians: London, 2012.
7. Beerthuizen A, Stronks DL, Huygen FJ, et al. The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1)--a prospective multicenter study. Eur J Pain 2011;15(9):971-5.
8. Main CJ, Williams ACC. Musculoskeletal pain. In: Mayou R, Sharpe M, Carson A, eds. ABC of Psychological Medicine. London: BMJ Publishing Group, 2003:37-40.
9. Harden RN. Complex regional pain syndrome. British Journal of Anaesthesia 2001;87(1):99-106.

Andreas Goebel, Consultant and Senior Lecturer in Pain Medicine
William Campbell, Beverly Collett, Martin Johnson, Kate Grady

The Walton Centre NHS Foundation Trust and University of Liverpool, Liverpool L9 7LJ

We have read with interest the recent Personal View by Dr. Chris Bass on Complex Regional Pain Syndrome1.
For clarification, Complex Regional Pain Syndrome (CRPS) is an uncommon disorder affecting limbs, which in over 90% of cases arises after trauma. Comprehensive reviews on CRPS have been published 2 3, and the UK Royal College of Physicians has supported the development of the UK Guidance, which was recently published with the support of over 20 UK professional organisations and Royal Colleges, including the British Psychological Society4 5. A guidance chapter for the diagnosis and management of CRPS in psychiatric practice is currently being written by a multidisciplinary group, which includes representation from the Royal College of Psychiatrists; this will be available with the first revision of the UK CRPS Guidance in 2015. Dutch and US guidance is also available.
Dr. Bass makes four propositions (a-d), which need to be refuted, and additional suggestions (e-f), which should be addressed:
a) Dr. Bass asserts that CRPS can be diagnosed on the basis of sensory and motor signs. This is incorrect – the Budapest diagnostic criteria require the presence of additional symptoms. A synopsis of the CRPS diagnostic criteria can be found in appendix 4 of the referenced ‘long’ UK Guidance.
b) Dr. Bass indicates that CRPS, when diagnosed in GP practice should best be managed first by identifying possible yellow flags, then arranging referral for an (unspecified) ‘appropriate intervention’. This proposed management strategy conflicts with the Royal College of Physicians guidance for the management of CRPS in GP practice, which has been supported by the RCGP. The latter guidance proposes that GPs refer patients to Pain Medicine Specialists or (for complex multiple disabilities) to Rehabilitation Specialists (except in mild cases). Specific treatments and expertise are then available through these services.
c) ‘..abundant evidence shows that it is psychosocial, not biological factors, that are associated with a higher likelihood of developing chronic painful disorders…’ Here Dr. Bass abandons the discussion on CRPS altogether for a more general discussion on chronic pain. In CRPS research, the pre-existence of major psychological factors has now been soundly refuted6. Dr. Bass would do well do acknowledge such population-based research. In these same studies CRPS was associated with ACE inhibitor intake (but not with intake of other anti-hypertensives) 7, and asthma (but not COPD) 6, highlighting a likely contribution from neurogenic inflammation, which had earlier already been suggested in microdialysis studies 8. The prospective (but not population-based) study of patients after limb fracture by Berthuitzen et al., which Dr. Bass cites, again found no correlation between psychological factors and the development of CRPS; in contrast biological factors such as intra-articular fractures and fracture dislocations were correlated 9. Further research is indeed called for to assess the impact of psychological factors on variability after trauma, but until the results of such research are available, they should not be pre-empted.
d) Dr. Bass calls for appropriate education and training for clinicians working in pain clinics. We could not agree more. Dr. Bass should feel reassured by the rigorous training and examination programme which Pain Medicine Consultants now undertake to achieve the professional qualification of Fellowship of the Faculty of Pain Medicine of the Royal College of Anaesthetists (FFPMRCA). It is disappointing that this has not been acknowledged.
e) Dr. Bass calls for adequate psychological services in pain clinics. Such a call is in keeping with a modern understanding of Pain Medicine, and should be applauded (see for details on UK initiatives to secure multidisciplinary provision of pain services). The primary goal is to treat patients in their biopsychosocial contexts. It is not to elucidate psychological causative factors (with selected exceptions where the input of psychiatrists is indeed important). The idea, that we should generally look for non-biological causative factors for CRPS in order to then help the patient by treating their psychology has been largely discredited 9-11, and has the potential to cause harm by suggesting their condition is psychological/psychiatric, when this is not the case.
f) We believe that Dr. Bass is right to point out the potential for causing iatrogenic damage by making an inappropriate diagnosis, which he says he has many times witnessed. We too have seen inappropriate diagnoses of CRPS, although these are normally relatively easily recognised and refuted by appropriately trained professionals. Of note, in medico-legal practice, the diagnosis of CRPS poses particular challenges, but a discussion around the judicial system is beyond the scope of this letter.
In summary, whilst we are mindful that this is a ‘personal view’, the viewpoint of Dr Bass leaves us somewhat underwhelmed as it lacks medical and diagnostic accuracy and makes only partial reference to the available literature. We are concerned that BMJ readers may have been misinformed or misguided. Full information and guidance on the management of CRPS are detailed in the UK CRPS Guidelines [6].
Dr. Andreas Goebel, Chair UK CRPS Guideline Group
Dr. William Campbell, President British Pain Society
Dr. Beverly Collett, Chair Chronic Pain Policy Commission
Dr. Martin Johnson, RCGP Lead for Chronic Pain
Dr. Kate Grady, Dean Faculty of Pain Medicine Royal College of Anaesthetists
1. Bass C. Complex regional pain syndrome medicalises limb pain. BMJ 2014;348:g2631.
2. Marinus J, Moseley GL, Birklein F, Baron R, Maihofner C, Kingery WS, et al. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011/7;10(7):637-48.
3. Goebel A. Complex regional pain syndrome in adults. Rheumatology (Oxford) 2011/10;50(10):1739-50.
4. Turner-Stokes L, Goebel A. Complex regional pain syndrome in adults: concise guidance. Clin Med 2011;11(6):596-600.
5. Goebel AB, Ch; Turner-Stokes, L; et al. Complex Regional Pain Syndrome in Adults. UK guidelines for diagnosis, referral and management in primary and secondary care. London: Royal College of Physicians, 2012.
6. de Mos M, Huygen FJ, Dieleman JP, Koopman JS, Stricker BH, Sturkenboom MC. Medical history and the onset of complex regional pain syndrome (CRPS). Pain 2008;139(2):458-66.
7. de MM, Huygen FJ, Stricker BH, Dieleman JP, Sturkenboom MC. The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS. Pain 2009/4;142(3):218-24.
8. Birklein F, Schmelz M, Schifter S, Weber M. The important role of neuropeptides in complex regional pain syndrome. Neurology 2001/12/26;57(12):2179-84.
9. Beerthuizen A, van 't SA, Huygen FJ, Klein J, de WR. Is there an association between psychological factors and the Complex Regional Pain Syndrome type 1 (CRPS1) in adults? A systematic review. Pain 2009/9;145(1-2):52-59.
10. Lohnberg JA, Altmaier EM. A review of psychosocial factors in complex regional pain syndrome. Journal of clinical psychology in medical settings 2013;20(2):247-54.
11. Feliu MH, Edwards CL. Psychologic factors in the development of complex regional pain syndrome: history, myth, and evidence. Clin J Pain 2010;26(3):258-63.

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