title: Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.
abstract: Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury.
authors.affiliation: aDepartment of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA bDepartment of Neurology, General Fürth Hospital, Fürth, Germany cDepartment of Pain Management, Cleveland Clinic, Cleveland, OH, USA dDepartment of Anesthesiology, VU University Medical Center and EMGO+ Institute for Health and Care Research, Amsterdam, the Netherlands eDepartment of Rehabilitation Medicine, Reuth Rehabilitation Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel fDepartment of Physical Medicine and Rheumatology, Balgrist University Hospital, Zurich, Switzerland gDepartment of Neurology, University Medical Center Mainz, Mainz, Germany hDepartment of Anesthesiology, Perioperative, and Pain Medicine, Stanford University Medical Center, Stanford, CA, USA iDepartment of Physical Medicine and Rehabilitation, University of Toronto, Toronto, Canada jDepartment of Physical Medicine and Rehabilitation, Northwestern University School of Medicine, Chicago, IL, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bruehl
authors.forename: Christian
authors.initials: C
authors.lastname: Maihöfner
authors.forename: Michael
authors.initials: M
authors.lastname: Stanton-Hicks
authors.forename: Roberto S G M
authors.initials: RS
authors.lastname: Perez
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Vatine
authors.forename: Florian
authors.initials: F
authors.lastname: Brunner
authors.forename: Frank
authors.initials: F
authors.lastname: Birklein
authors.forename: Tanja
authors.initials: T
authors.lastname: Schlereth
authors.forename: Sean
authors.initials: S
authors.lastname: Mackey
authors.forename: Angela
authors.initials: A
authors.lastname: Mailis-Gagnon
authors.forename: Anatoly
authors.initials: A
authors.lastname: Livshitz
authors.forename: R Norman
authors.initials: RN
authors.lastname: Harden
mesh_terms: D000328:Adult; D020918:Complex Regional Pain Syndromes / Q000175:diagnosis* / Q000503:physiopathology; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D010641:Phenotype; D011446:Prospective Studies