Sarcoidosis-related small fiber neuropathy: focus on fatigue, pain, restless legs syndrome, and cognitive function

##plugins.themes.themeTen.article.main##

Lisette Raasing https://orcid.org/0000-0003-0474-7550
Marcel Veltkamp
Mirjam Datema
Ingrid Korenromp
Jan C. Grutters
Oscar J.M. Vogels

Keywords

chronic pain, cognitive impairment, disease severity, fatigue, neuropathic symptoms, patient reported outcome, prevalence, quality of life, restless legs syndrome, sarcoidosis, severity, small fiber neuropathy, symptom burden, symptoms

Abstract

Background: Of all sarcoidosis patients 60-90% suffer from fatigue, 40-80% experience small fiber neuropathy, 35% suffer from cognitive impairment and 16-52% experience restless legs syndrome (RLS). The prevalence, severity and association between fatigue, pain, RLS and cognitive impairment in patients with sarcoidosis and small fiber neuropathy (SFN) is unknown and will be investigated in this study.


Methods: Healthy controls, patients with sarcoidosis with SFN and patients with sarcoidosis without SFN were compared. They completed multiple questionnaires (fatigue assessment scale (FAS), RLS rating scale, visual analogue scale (VAS) score for pain and cognitive failure questionnaire (CFQ)), to estimate the prevalence, severity, and correlation of fatigue, RLS, pain, SFN and cognitive impairment.


Results: Twenty healthy volunteers, 49 patients with sarcoidosis without SFN and 48 patients with sarcoidosis with SFN were included. Fatigue was the most prevalent symptom in patients with sarcoidosis with SFN (97%), followed by pain (85%), RLS (67%) and cognitive impairment (46%). Moreover, the severity of fatigue, pain, RLS and cognitive impairment was higher in patients with sarcoidosis with SFN compared with patients with sarcoidosis without SFN (resp. p=0.0006, p=0.003, p=0.02 and p=0.009). Finally, the FAS, RLS, VASmean, VASmax and CFQ showed a strong correlation with each other (R> 0.5, p<0.05).


Conclusions: Sarcoidosis patients with SFN showed an increased prevalence and higher severity of fatigue, pain, RLS and cognitive impairment compared to patients with sarcoidosis without SFN. Moreover, moderate to strong correlations were found between these symptoms.

Abstract 0 | PDF Downloads 0

References

1. Crouser ED, Maier LA, Baughman RP, et al. Diagnosis and detection of sarcoidosis an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020 Apr 15;201(8):E26–51.
2. Drent M, Strookappe B, Hoitsma E, et al. Consequences of sarcoidosis. Clin Chest Med. 2015;36(4):727–37.
3. Drent M, Lower EE, De Vries J. Sarcoidosis-associated fatigue. Eur Respir J. 2012 Jul;40(1):255–63.
4. Tavee J, Culver D. Sarcoidosis and Small-fiber Neuropathy. Curr Pain Headache Reports. 2011;15(February):201–6.
5. Hovaguimian A, Gibbons CH. Diagnosis and treatment of pain in small-fiber neuropathy. Curr Pain Headache Rep [Internet]. 2011;15(3):193–200. Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L51257173
6. Tavee J. Peripheral neuropathy in sarcoidosis. J Neuroimmunol [Internet]. 2022;368(January):577864. Available from: https://doi.org/10.1016/j.jneuroim.2022.577864
7. Voortman M, Hendriks CMR, Elfferich MDP, et al. The burden of sarcoidosis symptoms from a patient perspective. Lung [Internet]. 2019;197(2):155–61. Available from: http://link.springer.com/10.1007/s00408-019-00206-7
8. Voortman M, De Vries J, Hendriks CMR, et al. Everyday cognitive failure in patients suffering from neurosarcoidosis. Sarcoidosis Vasc Diffus Lung Dis. 2019;36(1):2–10.
9. Elfferich MD, Nelemans PJ, Ponds RW, et al. Everyday cognitive failure in sarcoidosis: The prevalence and the effect of anti-TNF-α treatment. Respiration. 2010;80(3):212–9.
10. Indart S, Hugon J, Guillausseau PJ, et al. Impact of pain on cognitive functions in primary Sjögren syndrome with small fiber neuropathy: 10 cases and a literature review. Med (United States). 2017;96(16):1–6.
11. Patoulias D, Keryttopoulos P. Diagnostic dilemma between sarcoidosis and primary Sjögren syndrome: mimicry, concomitance or coincidence? An up-to-date clinician’s perspective. Folia Med Cracov. 2018;58(1):5–23.
12. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003 Mar;4(2):101–19.
13. Abetz L, Allen R, Follet A, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther. 2004;26(6):925–35.
14. De Kleijn WPE, Drent M, Vermunt JK, et al. Types of fatigue in sarcoidosis patients. J Psychosom Res. 2011;71(6):416–22.
15. Verbraecken J, Hoitsma E, Van Der Grinten CPM, et al. Sleep disturbances associated with periodic leg movements in chronic sarcoidosis. Sarcoidosis Vasc Diffus Lung Dis. 2004;21(2):137–46.
16. Polydefkis M, Allen RP, Hauer P, et al. Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology. 2000 Oct;55(8):1115–21.
17. Lim YM, Chang SE, Chung S, et al. Small fiber function in drug naïve patients with idiopathic restless legs syndrome. J Clin Neurosci Off J Neurosurg Soc Australas. 2012 May;19(5):702–5.
18. Gemignani F, Brindani F, Vitetta F, et al. Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy. J Peripher Nerv Syst. 2007 Mar;12(1):50–3.
19. Andréasson M, Lagali N, Badian RA, et al. Parkinson’s disease with restless legs syndrome-an in vivo corneal confocal microscopy study. NPJ Park Dis. 2021 Jan;7(1):4.
20. Devigili G, Rinaldo S, Lombardi R, et al. Diagnostic criteria for small fibre neuropathy in clinical practice and research. Brain. 2019;142(12):3728–36.
21. Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of a brief self-rated fatigue measure: The Fatigue Assessment Scale. J Psychosom Res. 2003;54(4):345–52.
22. Hendriks C, Drent M, Elfferich M, et al. The Fatigue Assessment Scale: Quality and availability in sarcoidosis and other diseases. Curr Opin Pulm Med. 2018;24(5):495–503.
23. Campbell WI, Lewis S. Visual analogue measurement of pain. Ulster Med J. 1990;59(2):149–54.
24. Rago R, Forfori F, Materazzi G, et al. Evaluation of a preoperative pain score in response to pressure as a marker of postoperative pain and drugs consumption in surgical thyroidectomy. Clin J Pain. 2012;28(5):382–6.
25. Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4(2):121–32.
26. Broadbent DE, Cooper PF, FitzGerald P, et al. The cognitive failures questionnaire (CFQ) and its correlates. Br J Clin Psychol. 1982;21(1):1–16.
27. Ponds R, Boxtel M Van, Jolles J. De “Cognitive Failure Questionnaire” Als Maat Voor Subjectief Cognitief Functioneren. Tijdschr voor Neuropsychol. 2006;2(1):37–45.
28. Singha A, Kirkland M, Drake W, et al. The influence of age and sex in sarcoidosis. Curr Opin Pulm Med. 2022 Jul;28(4):307–13.
29. Johnson SA, Shouman K, Shelly S, et al. Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability. Neurology. 2021;97(22):E2236–47.
30. De Vries J, Michielsen H, Van Heck GL, et al. Measuring fatigue in sarcoidosis: the Fatigue Assessment Scale (FAS). Br J Health Psychol. 2004 Sep;9(Pt 3):279–91.
31. Silber MH, Buchfuhrer MJ, Earley CJ, et al. The Management of Restless Legs Syndrome: An Updated Algorithm. Mayo Clin Proc. 2021;96(7):1921–37.
32. Drent M MRLADVJ. Association between physical functions and quality of life in sarcoidosis. Sarcoidosis Vasc Diffus Lung Dis. 2014 Jul;31(2):117–28.
33. Carrigan N, Barkus E. A systematic review of cognitive failures in daily life: Healthy populations. Neurosci Biobehav Rev. 2016 Apr;63:29–42.
34. Mackie S, Winkelman JW. Restless Legs Syndrome and Psychiatric Disorders. Sleep Med Clin. 2015;10(3):351–7.
35. Guay A, Houle M, O’Shaughnessy J, et al. Current Evidence on Diagnostic Criteria, Relevant Outcome Measures, and Efficacy of Nonpharmacologic Therapy in the Management of Restless Legs Syndrome (RLS): A Scoping Review. J Manipulative Physiol Ther. 2020;43(9):930–41.
36. Lower EE, Harman S, Baughman RP. Double-blind, randomized trial of dexmethylphenidate hydrochloride for the treatment of sarcoidosis-associated fatigue. Chest. 2008;133(5):1189–95.
37. Lower EE, Malhotra A, Surdulescu V, et al. Armodafinil for sarcoidosis-associated fatigue: A double-blind, placebo-controlled, crossover trial. J Pain Symptom Manage [Internet]. 2013;45(2):159–69. Available from: http://dx.doi.org/10.1016/j.jpainsymman.2012.02.016
38. Vis R, van de Garde EMW, Meek B, et al. Randomised, placebo-controlled trial of dexamethasone for quality of life in pulmonary sarcoidosis. Respir Med. 2020 Apr 1;165.
39. Kahlmann V, Moor CC, van Helmondt SJ, et al. Online mindfulness-based cognitive therapy for fatigue in patients with sarcoidosis (TIRED): a randomised controlled trial. Lancet Respir Med. 2023;11(3):265–72.
40. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: Updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria - history, rationale, description, and significance. Sleep Med. 2014;15(8):860–73.
41. Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285–93.
42. Devigili G, Tugnoli V, Penza P, et al. The diagnostic criteria for small fibre neuropathy: From symptoms to neuropathology. Brain. 2008;131(7):1912–25.