Complex Pathophysiology and Differentiated Therapy

Letters to the Editor Modern Principles of Diagnosis and Treatment in Complex Regional Pain Syndrome by Alexandra Melf-Marzi, Dr. med. Bettina Böhringer, Dr. med. Matthias Wiehle, and Prof. Dr. med. Constanze Hausteiner-Wiehle in issue 51–52/2022

We thank the authors for reviewing the literature and explaining the diagnostic and therapeutic approach in complex regional pain syndrome (CRPS) (1).

Even though this was not the focus of the article, new insights into the pathophysiology of CRPS—while considering innate and adaptive autoimmune mechanisms in the development and sustained presence of pain in CRPS—deserve mentioning (2). Another possible topic of discussion relates to how reorganization processes in the entire nervous system (3) shape the often extremely varied clinical symptoms over the course of CRPS without having to take recourse to a somatoform disorder.

As regards the functionally relevant distinction between “warm” and “cold” CRPS we wish to specify that “cold” CRPS can exist as a primary syndrome and does not necessarily develop sequentially after “warm” stages late in the disease course (4).

Regarding medication therapy using bisphosphonates we wish to add—referring to the German Neurological Society’s guideline—that the preparations used in studies were either used in high dosages orally (alendronate, 40 mg/d over 8 weeks) or intravenously (clodronate 300 mg for 10 days, pamidronate once 60 mg, and neridronate four times 100 mg each on every third day). The authors have had good experiences of the benefits of administering glucocorticoids in phenotypically “warm” CRPS. In the differential indication, comorbid diabetes mellitus is a good argument for administration of bisphosphonates.

DOI: 10.3238/arztebl.m2023.0062

PD Dr. med. Christian Geber

DRK-Schmerz-Zentrum Mainz; Klinik und Poliklinik für Neurologie, Universitätsmedizin Mainz, [e-mail]

Prof. Dr. med. Hans-Raimund Casser

DRK-Schmerz-Zentrum Mainz

Prof. Dr. med. Frank Birklein

Klinik und Poliklinik für Neurologie, Universitätsmedizin Mainz

Conflict of interest statement

The authors declare that no conflict of interest exists

References

1. Melf-Marzi A, Böhringer B, Wiehle M, Hausteiner-Wiehle C: Modern principles of diagnosis and treatment in complex regional pain syndrome. Dtsch Arztebl Int 2022; 119: 879–86

2. Shi X, Guo TZ, Li WW, et al.: C5a complement and cytokine signaling mediate the pronociceptive effects of complex regional pain syndrome patient IgM in fracture mice. Pain 2021; 162:1400–15

3. Halicka M, Vittersø AD, Proulx MJ, Bultitude JH: Neuropsychological changes in complex regional pain syndrome (CRPS). Behav Neurol 2020; 2020: 4561831

4. Eberle T, Doganci B, Krämer HH, et al.: Warm and cold complex regional pain syndromes: differences beyond skin temperature? Neurology 2009; 72: 505–12