Intravenous Immunoglobulin in Complex Regional Pain Syndrome
Andreas Goebel on the results of his latest clinical trial
.Just imagine the causes of some chronic pains are completely different from what you had thought. Complex Regional Pain Syndrome is a severe pain which persists after limb trauma. You are unlucky if you develop this nasty condition, but problems mount if you don’t belong to those 85% who get at least some relief within the first 1-2 years after trauma. If your pain is not better then, chances are that it is not going to recede any time soon. For this article I use the term ‘nCRPS’ to denote un-resolving CRPS after more than one year. The UK Institute for Clinical Excellence (NICE) estimates, that nCRPS will, on average last 15 years, although some people will get better earlier. Up to now it has remained a mystery what causes CRPS. The affected limb’s representation in the brain changes. And some treatments which gently focus the brain’s attention to the affected side can reduce nCRPS pain, may even help to resolve the condition. Amongst these treatments, Lorimer’s Graded Motor Imagery stands out because this treatment was efficacious in a randomized controlled trial for the rather large nCRPS subgroup after dorsal radius fracture (another treatment, mirror therapy was also successful, but only in the tiny subgroup of patients after stroke). Because of the described changes in the brain and the success of ‘brain training’, people have started to think that whatever biological cause initially elicits CRPS is perhaps not so important later – that nCRPS is essentially sustained by the brain.
However this may not be so. In February we published the results from a randomized controlled trial (1) which clearly show that the pain in nCRPS is reduced when patients receive a drug called ‘intravenous immunoglobulin’, IVIG. I would love to say that we thought really long and hard to come to the conclusion that we should try this treatment. Truth is we stumbled across it. IVIG is produced from the pooled blood antibodies from 3000-20000 blood donors. It can help people who, because of a genetic defect cannot make these antibodies and therefore get serious infections. And yes, we first came across the power of IVIG to relieve pain by chance, when we had a patient with antibody deficiency and concomitant chronic pain. We observed that whenever she got IVIG for her antibody deficiency, her pain was also profoundly relieved. In similarly serendipitous observations made all over the world since the early 1980’s, medics have reported that IVIG can help to treat some hitherto literally untreatable inflammatory or autoimmune conditions. We first published our results of the open treatment of 140 patients with various chronic pains in 2002. Patients with CRPS, trigeminal neuralgia and postherpetic neuralgia responded best, while patients with back pain had only rarely meaningful benefit.
So is nCRPS an inflammatory or autoimmune condition? It appears so, at least in some cases. In separate laboratory studies, we and others have since discovered that many patients with nCRPS have antibodies directed against their own nerves (=’autoantibodies’) suggesting that CRPS could be ‘autoimmune’ (i.e. it could be due to a reaction of the immune system against the own body). We don’t know exactly how these antibodies work, and whether they are indeed responsible for CRPS, however these laboratory findings, together with the clear cut positive results from our trial have raised the odds in favour of their importance. So is the brain then not important? Well – at least it is not the brain alone. There is something odd about our patients’ responses to IVIG: most patients respond to unusually low doses (0.5g/kg), and they respond much quicker than people suffering from other IVIG-responsive conditions. Equally unusual is that our patients very likely do not respond to treatment with steroids, the panacea of things going wrong with the immune system. I would not be surprised if the way by which the immune system causes CRPS is different from that by which is causes other conditions. It is possible that if we can figure this out, we may find an entirely new way by which the immune system can cause disease. Can brain-training override these immunological processes in some patients? – I don’t know, but I am keen to find out. It seems that confirmation of the efficacy of IVIG has opened a new puzzling chapter in the epic, oddysseic journey to find the CRPS cause and cure.
Andreas Goebel is a very fast walker. In fact, he is a fast talker too – insofar as he talks quickly, not insincerely. He is, I guess, a ‘Fast Sinceretalker’. A clever fellow and an astute observer of the patient’s lot, he works as a Pain Specialist with a background in Anaesthesia and Immunology. He has some heavy hitting publications in this area, which is why he is Senior Lecturer at the University of Liverpool, and Consultant in Pain Medicine at the Liverpool Walton Centre Hospital, one of the largest pain teams in the UK. Check out his website at the Centre for Immune Studies in Pain. Clearly, he didn’t write this bio.
 Goebel A, Baranowski A, Maurer K, Ghiai A, McCabe C, & Ambler G (2010). Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Annals of internal medicine, 152 (3), 152-8 PMID: 20124231
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