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Complex regional pain syndrome medicalises limb pain

BMJ 2014; 348 doi: (Published 28 April 2014) Cite this as: BMJ 2014;348:g2631

Re: Complex regional pain syndrome medicalises limb pain

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 G, Galer BS, Schwartz 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 C. The 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 GL, Birklein F, Baron R, Maihöfner C, Kingery WS, van 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 fracture rat model of complex regional pain syndrome type I. Pain. 2004;108(1-2):95-107.

[viii]Goebel A1, Leite MI, Yang L, Deacon R, Cendan CM, Fox-Lewis A, Vincent 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 S, Perez RS, Birklein F, Marinus J, Maihofner C, Lubenow T, Buvanendran A, Mackey S, Graciosa J, Mogilevski M, Ramsden C, Chont M, Vatine 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 Pain 2011;15:971-5.

[xi]Beerthuizen A, van 't Spijker A, Huygen FJ, Klein J, de 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 FJ, Dieleman JP, Koopman JS, Stricker BH, Sturkenboom MC. Medical history and the onset of complex regional pain syndrome (CRPS). Pain. 2008 Oct 15;139(2):458-66.

[xiii]Lewis JS, Kersten P, McCabe CS, McPherson KM, Blake 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.

Competing interests: No competing interests

04 June 2014
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