Background & Aims
Erythromelalgia (EM) is a rare and painful condition characterised by episodes of burning pain, redness, and heat primarily in the feet and sometimes hands, often triggered by physical activity or warm temperatures. EM pathophysiology remains incompletely understood, it is believed to involve blood vessel dysfunction and, in some cases, hyper-excitability of nociceptors. Inherited EM, accounting for about 5% of cases, is associated with a gain-of-function variants of the SCN9A gene, resulting in prolonged neuronal activation and heightened pain perception during episodes. Our study aimed to characterise the somatosensory profiles of patients with EM to better understand the underlying mechanisms.
Methods
We prospectively recruited 35 patients referred for clinical assessment of EM to a specialist neuropathy clinic in Oxford, UK. Following informed consent (As part of the Pain In Peripheral Lesion Study (PIPL), REC Reference Number: 18/SC/0263) all patients underwent neurological examination, nerve conduction studies, and skin biopsy for intra-epidermal nerve fibre assessment. The somatosensory phenotype of the hands and feet was determined using quantitative sensory testing (QST), assessing 13 parameters of sensory function following the German Research Network on Neuropathic Pain (DFNS) protocol. Patient data were compared to a large control population cohort to control for age and gender effects.
Results
The mean age of study participants was 44.5 years, with 75% being female. All patients met the criteria for EM, with skin biopsies revealing abnormalities in six patients. Thirteen per cent of patients had atypical EM, 19% had overlapping small fibre neuropathy (SFN) as defined by reduced intra-epidermal nerve fibre density, and 11% had inherited EM. QST profiles were consistent with mild impairment of small fibre function in both hands and feet, with hyposensitivity in cold and warm detection thresholds, and thermal sensory limen. Interestingly, there was a trend of increased sensitivity to heat pain (consistent with symptoms); however, the most striking finding was hypersensitivity to pressure pain. Brush-evoked allodynia was reported by 3% of patients, and paradoxical heat sensations were reported by 12% of participants.
Conclusions
Our study provides insights into the somatosensory profiles of patients with EM: there were changes in the thermal domains (impaired thermal detection and enhanced heat pain in a sub-set) as well as hypersensitivity to pressure pain. These findings suggest a complex sensory profile in EM which is not restricted to the thermal domains and furthermore highlight the distinct nature of this disorder to other peripheral neuropathic disorders.
References
Mann, N., King, T., & Murphy, R. (2019). Review of primary and secondary erythromelalgia. Clinical and experimental dermatology, 44(5), 477–482. https://doi.org/10.1111/ced.13891
Michelerio, A., Tomasini, C., Arbustini, E., & Vassallo, C. (2023). Clinical Challenges in Primary Erythromelalgia: A Real-Life Experience from a Single Centre and a Diagnostic-Therapeutic Flow-Chart Proposal. Dermatology practical & conceptual, 13(3), e2023191.
Rolke R, Baron R, Maier C, et al. Quantitative Sensory Testing in the German Research Network of Neuropathic Pain (DFNS): Standardised protocol and reference values. Pain. 2006; 123:231-43.
Tang, Z., Chen, Z., Tang, B., & Jiang, H. (2015). Primary erythromelalgia: a review. Journal of Rare Diseases, 10, 127.
Presenting Author
Jishi John
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral