Background & Aims

Hereditary transthyretin ATTRv amyloidosis is a rare, progressive, life-threatening disease caused by misfolded transthyretin (TTR) protein that accumulates as amyloid fibrils in multiple organs, particularly the nerves and the heart (1). Clinical presentation includes a length-dependent polyneuropathy resulting in sensorimotor symptoms like burning neuropathic pain, loss of sensation in hands and feet as well as cardiac symptoms. Patients with ATTRv amyloidosis are often diagnosed with a significant delay of 3 to 4 years (1) and CIDP is often suspected as a differential diagnosis. It is also likely that some patients diagnosed with “polyneuropathy of unknown origin” actually have underlying ATTRv amyloidosis. Yet an early diagnosis of ATTRv amyloidosis is essential for the affected patients since early treatment can significantly improve the progress of the disease.

Methods

10 Patients with ATTRv amyloidosis and 15 Patients with CIDP were compared in regards to their pain quality, their sensory symptoms and their autonomic symptoms. Validated questionnaires were used to classify the pain of the patients, the autonomic dysfunction and the quality of life (2,3,4). In addition a laboratory quantitative sensory testing (lQST) and a bedside sensory testing (bQST) were performed according to the standardized protocol of the German Research Network on Neuropathic Pain (DFNS) (6,7). Different calibrated stimuli were used to detect positive and negative sensory signs. Both tests were performed in affected areas of the upper and lower limbs. Collected data were analyzed for significant differences between ATTRv amyloidosis and CIDP. Differences in dichotomized variables were calculated using the chi-square test (or Fisher’s exact test for n<5). Differences in metric variables were calculated using the Mann Whitney U test. P-values <0.05 were defined as significant.

Results

ATTRv amyloidosis patients and CIDP patients were similar in sex, age and BMI. A history of a carpal tunnel syndrome and symptoms of a restless legs syndrome were present in more patients with ATTRv amyloidosis than in patients with CIDP. Autonomic dysfunctions, in particular diarrhea and erectile dysfunction were also more frequently described by ATTRv amyloidosis patients. No significant differences were found between ATTRv amyloidosis and patients with CIDP in terms of pain quality. In sensory testing patients with ATTRv amyloidosis showed a significant lower pressure pain threshold at the upper limb and at the border zone on the lower limb and a higher cold detection threshold at the hand. Autonomic testing using tilt table test, heart rate variability and Sudoscan revealed no significant differences between patients with ATTRv amyloidosis and patients with CIDP.

Conclusions

For patients suffering from ATTRv amyloidosis an early diagnosis and a consecutive early treatment is of utmost importance. In spite of this fact patients are still often falsely labeled as polyneuropathy of unknown origin or as CIDP and are diagnosed with a delay of several years. Our results were able to show certain characteristics in patients with ATTRv amyloidosis which can help to differentiate between these two entities especially in regards to the results of the sensory profiling.

References

1Adams D, Koike H, Slama M, Coelho T. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol 2019;15:387–404.
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7Reimer M, Forstenpointner J, Hartmann A, Otto JC, Vollert J, Gierthmühlen J, Klein T, Hüllemann P, Baron R. Sensory bedside testing: a simple stratification approach for sensory phenotyping. Pain Reports 2020;5:e820.

Presenting Author

Stefanie Rehm

Poster Authors

Stefanie Rehm

medical doctor

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

Lead Author

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Juliane Sachau

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

Lead Author

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Lena Rhode

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

Lead Author

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Julia Forstenpointner

Division of Neurological Pain Research and Therapy, University Hospital Kiel

Lead Author

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Manon Sendel

Division of Neurological Pain Research and Therapy, University Hospital Schleswig-Holstein

Lead Author

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Ralf Baron

Lead Author

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Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral