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Intravenous Immunoglobulin to Fight Complex Regional Pain Syndromes: Hopes and Doubts

Frank Birklein, MD, PhD; and Claudia Sommer, MD, PhD
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From University of Mainz, Mainz 55131, Germany; and University of Würzburg, Würzburg 97080, Germany.

Grant Support: By the German Research Foundation (Bi 579/1) and the University of Mainz.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-2704.

Requests for Single Reprints: Frank Birklein, MD, PhD, University of Mainz, Department of Neurology, Langenbeckstrasse 1, Mainz 55131, Germany; e-mail, birklein@neurologie.klinik.uni-mainz.de.

Current Author Addresses: Dr. Birklein: University of Mainz, Department of Neurology, Langenbeckstrasse 1, Mainz 55131, Germany.

Dr. Sommer: Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, Würzburg 97080, Germany.

Ann Intern Med. 2010;152(3):188-189. doi:10.7326/0003-4819-152-3-201002020-00013
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Chronic pain is multifaceted. It involves changes in somatosensory processing from the primary afferent neurons to the brain; it induces negative emotions, such as fear and depression; and it often entails serious consequences for working ability and personal life. Long-standing complex regional pain syndrome (CRPS) has all of these features and may be associated with substantial reduction of limb function, leading to physical impairment (1).

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Reply to Goebel et al, L10-0185
Posted on March 17, 2010
Frank Birklein
Dep. of Neurology, University Medical Centre Mainz
Conflict of Interest: None Declared

We appreciate the lively discussion with Dr. Goebel on his pilot RCT on IVIG in CRPS and would like to respond to his correspondence regarding our editorial. Of course we did not state that development of CRPS is of psychogenic origin, and of course CRPS patients are not psychiatrically ill in a classical sense. However, more vigorous and prospective testing might provide different results (1) and the experience of many researchers, which we systematically collected in the national German guideline of CRPS diagnosis and treatment (2) provide some indication that stressful life events (3), latent anxiety, post traumatic distress disorder and self confidence problems are prevalent in chronic CRSP, or even mimic chronic CRPS. Since CRPS develops after trauma, which often means compensation claims (4), goal conflicts might also contribute to chronic CRPS, in particular since treatment requires active participation of the subjects. Such factors cannot be assessed by routine checklists, and usually cannot be treated by unimodal pharmaceutical treatment of chronic CRPS. Therefore we remain reluctant - not only for IVIGs but also for other agents like ketamine, magnesium or tadalafil. The complete discussion about placebo effects and effect sizes could only be overcome if bigger and multicentre RCTs follow. There are plenty of examples of promising phase II studies with drugs for chronic pain treatment, which finally failed to overcome this obstacle (see also IVIG for MS (5)). In spite of our scepticism, we wish to the authors that this will not be the case in the planned future IVIG CRPS studies. We all need effective treatment for chronic pain and in particular for chronic CRPS.


(1) Zachariae L. Incidence And Course Of Posttraumatic Dystrophy Following Operation For Dupuytren's Contracture. Acta Chir Scand. 1964;15 SUPPL:1-51.

(2) Birklein F. Diagnostik und Therapie komplexer regionaler Schmerzsyndrome (CRPS). In: Diener HC, Putzki N, eds. Leitlinien fuer Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag; 2008: 640-652.

(3) Geertzen JH, de-Bruijn-Kofman AT, de-Bruijn HP, van-de-Wiel HB, Dijkstra PU. Stressful life events and psychological dysfunction in Complex Regional Pain Syndrome type I. Clin J Pain. 1998;14:143-47.

(4) Verdugo RJ, Ochoa JL. Reversal of hypoaesthesia by nerve block, or placebo: a psychologically mediated sign in chronic pseudoneuropathic pain patients. J Neurol Neurosurg Psychiatry. 1998;65:196-203.

(5) Fazekas F, Strasser-Fuchs S, Hommes OR. Intravenous immunoglobulin in MS: promise or failure? J Neurol Sci. 2007;259:61-66.

Conflict of Interest:

None declared

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