Dolor neuropático, pensemos en Enfermedad de Fabry
Palabras clave:
enfermedad de Fabry, parestesias, neuralgia, analgésicos, diagnostico, terapia de reemplazo enzimático, sistema nervioso periférico, neuropatía de fibras finas, neuropatías dolorosas, herencia ligada al cromosoma x.
Resumen
El dolor es la razón más común de consulta y de búsqueda de atención médica, y el que presenta una mayor dificultad al recibir un paciente es el dolor neuropático. Una de las neuropatías de fibras finas por excelencia es la enfermedad de Fabry, un desorden poco conocido. El objetivo de esta revisión fue cotejar la bibliografía disponible para determinar los puntos clave en el manejo de esta enfermedad, usando herramientas de búsqueda como Up To Date, Pubmed y Google Scholar. Luego de la revisión de más de 30 artículos científicos se pudo concluir que el característico dolor y la hiposensibilidad térmica se deben al acúmulo de glicolípidos que producen una neuropatía de fibras finas. Esto se asocia a un cuadro de dolores quemantes en manos y pies que puede presentar gran dificultad al momento del diagnóstico y tratamiento. De este modo, sospechar el diagnóstico conlleva una serie de pasos desde la historia clínica y examen físico, que son de gran importancia, hasta la determinación bioquímica porcentual de la ausencia de actividad de la alfa-galactosidasa A hasta los exámenes neurológicos e histológicos. Se llegó a la conclusión de que las características clínicas de esta enfermedad pueden ser típicas en la mayoría de los pacientes, sin embargo se debería conocer la fisiopatología subyacente al problema y diferenciar el manejo de un dolor crónico con el de las crisis de dolor. Esto es imperioso debido a la importancia de instaurar la terapia especifica lo antes posible.
Citas
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2. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain. 2014; 155(4):654-62. doi:10.1016/j.pain.2013.11.013.
3. Murnion BP. Neuropathic paint: Current definition and review of drug treatment. Aust Prescr. 2018; 41(3):60-3. doi:10.18773/ austprescr.2018.022.
4. Levine TD. Small fiber neuropathy: Disease classification beyond pain and burning. J Cent Nerv Syst Dis. 2018; 10:1-6. doi:10.1177/1179573518771703.
5. Houge G, Skarbøvik AJ. [Fabry disease--a diagnostic and therapeutic challenge]. Tidsskr Nor Laegeforen. 2005; 125(8):1004.
6. Sanchez-Niño MD, Sanz AB, Carrasco S, Saleem MA, Mathieson PW, Valdivielso JM, et al. Globotriaosylsphingosine actions on human glomerular podocytes: Implications for Fabry nephropathy. Nephrol Dial Transplant. 2011; 26(6):1797-802.
7. Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep. 8(9):539-48. doi:10.109701.gim.0000237866.70357.c6.
8. Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, et al. Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest. 2004; 34(3):236–42. doi:10.1111/j.1365-2362.2004.01309.x.
9. Toyooka K. Fabry disease. Handb Clin Neurol. 2013; 115:629-42. doi: 10.1016/B978-0-444-52902-2.00037-0.
10. El-Abassi R, Singhal D, England JD. Fabry’s disease. J Neurol Sci. 2014 344(1-2): 5–19. doi:10.1016/j.jns.2014.06.029.
11. Biegstraaten M, Hollak CE, Bakkers M, Faber CG, Aerts JM, van Schaik IN. Small fiber neuropathy in Fabry disease. Mol Genet Metab. 2012; 106(2):135-41. doi:10.1016/j.ymgme.2012.03.010.
12. Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr. 2004; 144(5):S20-S6. doi:10.1016/j.jpeds.2004.01.051.
13. Gold KF, Pastores GM, Botteman MF, Yeh JM, Sweeney S, Aliski W, Pashos CL. Quality of life of patients with Fabry disease. Qual Life Res. 2002; 11(4):317–27.
14. Cole AL, Lee PJ, Hughes DA, Deegan PB, Waldek S, Lachmann RH. Depression in adults with Fabry disease: A common and underdiagnosed problem. J Inherit Metab Dis. 2007; 30(6):943–51. doi:10.1007/s10545-007-0708-6.
15. Politei JM, Aiziczon D, Aguilar M, Alberton V, Alonso S, Amoreo O, et al. Recomendaciones para el diagnóstico, tratamiento y seguimiento de la enfermedad de fabry en Argentina. Revista Nefrología Argentina. 2018; 16(2):1-29.
16. Politei JM, Bouhassira D, Germain DP, Goizet C, Guerrero-Sola A, Hilz MJ, et al. Pain in Fabry disease: Practical recommendations for diagnosis and treatment. CNS Neurosci Ther. 2016; 22(7):568-76. doi:10.1111/cns.12542.
17. Biegstraaten M, Binder A, Maag R, Hollak CE, Baron R, van Schaik IN. The relation between small nerve fibre function, age, disease severity and pain in Fabry disease. Eur J Pain. 2011; 15(8):822–9. doi:10.1016/j.ejpain.2011.01.014.
18. Tanislav C, Kaps M, Rolfs A, Böttcher T, Lackner K, Paschke E, et al. Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: A pilot study. Eur J Neurol. 2011; 18(4):631–6. doi:10.1111/j.1468-1331.2010.03227.x.
19. Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 2008; 105(8):2812–7. doi:10.1073/pnas.0712309105.
20. Lauria G, Merkies IS, Faber CG. Small fibre neuropathy. Curr Opin Neurol. 2012; 25(5):542–9. doi:10.1097/WCO.0b013e32835804c5.
21. Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small-fibre neuropathies–advances in diagnosis, pathophysiology and management. Nat Rev Neurol. 2012; 8(7):369–79. doi:10.1038/nrneurol.2012.97.
22. Schiffmann R, Moore DF. Neurological manifestations of Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry disease: Perspectives from 5 Years of FOS /Internet/. Oxford: Oxford Pharma Genesis; 2006. Chapter 22. /cited 2018 Jun 10/. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11602/
23. Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M. Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology. 2004; 62(7):1066-72.
24. Hande T, Cetin K A, Ayse O B. Neuropathic pain in Fabry disease. Open Access J Neurol Neurosurg. 2017; 2(4):555593. doi:10.19080/OAJNN.2017.02.555593.
25. Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, et. al. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018; 123(4):416-27. doi: 10.1016/j.ymgme.2018.02.014.
26. Lakomá J, Rimondini R, Donadio V, Liguori R, Caprini M. Pain related channels are differentially expressed in neuronal and non-neuronal cells of glabrous skin of fabry knockout male mice. PLoS One. 2014; 9(10):e108641. doi:10.1371/journal.pone.0108641.
27. Ries M, Mengel E, Kutschke G, Kim KS, Birklein F, Krummenauer F, et al. Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis. 2003; 26(4):413–4.
28. Burlina AP, Sims KB, Politei JM, Bennett GJ, Baron R, Sommer C, et al. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: The report of an expert panel. BMC Neurol. 2011; 11:61. doi:10.1186/1471-2377-11-61
29. García-Trabanino R, Badilla-Porras R, Carazo K, Courville K, de Luna E, Lemus P, et. al. Consenso del Grupo Centroamericano y del Caribe para el Estudio y Tratamiento de la Enfermedad de Fabry. Nefrol Latinoam. 2017; 14(1):27–38. doi:10.1016/j.nefrol.2016.11.003.
30. Liguori R, Di Stasi V, Bugiardini E, Mignani R, Burlina A, Borsini W, et al. Small fiber neuropathy in female patients with Fabry disease. Muscle Nerve. 2010; 41(3):409–412. doi:10.1002/mus.21606.
31. Choi L, Vernon J, Kopach O, Minett MS, Mills K, Clayton PT, et al. The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain. Neurosci Lett. 2015; 594:163–8. doi:10.1016/j.neulet.2015.01.084.
32. Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015; 52(5):353–8. doi:10.1136/jmedgenet-2014-102797.
33. Tøndel C, Bostad L, Larsen KK, Hirth A, Vikse BE, Houge G, et al. Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol. 2013; 24(1):137–148. doi:10.1681/ASN.2012030316.
34. Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, et al. Analysis of left ventricular mass in untreated men and in men treated with agalsidase-B: Data from the Fabry registry. Genet Med. 2013; 15(12):958–65. doi:10.1038/gim.2013.53.
35. Arends M, Biegstraaten M, Wanner C, Sirrs S, Mehta A, Elliot PM, et al. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: An international cohort study. J Med Genet. 2018; 55(5):351-8. doi:10.1136/jmedgenet-2017-104863.
2. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: A systematic review of epidemiological studies. Pain. 2014; 155(4):654-62. doi:10.1016/j.pain.2013.11.013.
3. Murnion BP. Neuropathic paint: Current definition and review of drug treatment. Aust Prescr. 2018; 41(3):60-3. doi:10.18773/ austprescr.2018.022.
4. Levine TD. Small fiber neuropathy: Disease classification beyond pain and burning. J Cent Nerv Syst Dis. 2018; 10:1-6. doi:10.1177/1179573518771703.
5. Houge G, Skarbøvik AJ. [Fabry disease--a diagnostic and therapeutic challenge]. Tidsskr Nor Laegeforen. 2005; 125(8):1004.
6. Sanchez-Niño MD, Sanz AB, Carrasco S, Saleem MA, Mathieson PW, Valdivielso JM, et al. Globotriaosylsphingosine actions on human glomerular podocytes: Implications for Fabry nephropathy. Nephrol Dial Transplant. 2011; 26(6):1797-802.
7. Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep. 8(9):539-48. doi:10.109701.gim.0000237866.70357.c6.
8. Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, et al. Fabry disease defined: Baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Invest. 2004; 34(3):236–42. doi:10.1111/j.1365-2362.2004.01309.x.
9. Toyooka K. Fabry disease. Handb Clin Neurol. 2013; 115:629-42. doi: 10.1016/B978-0-444-52902-2.00037-0.
10. El-Abassi R, Singhal D, England JD. Fabry’s disease. J Neurol Sci. 2014 344(1-2): 5–19. doi:10.1016/j.jns.2014.06.029.
11. Biegstraaten M, Hollak CE, Bakkers M, Faber CG, Aerts JM, van Schaik IN. Small fiber neuropathy in Fabry disease. Mol Genet Metab. 2012; 106(2):135-41. doi:10.1016/j.ymgme.2012.03.010.
12. Desnick RJ, Brady RO. Fabry disease in childhood. J Pediatr. 2004; 144(5):S20-S6. doi:10.1016/j.jpeds.2004.01.051.
13. Gold KF, Pastores GM, Botteman MF, Yeh JM, Sweeney S, Aliski W, Pashos CL. Quality of life of patients with Fabry disease. Qual Life Res. 2002; 11(4):317–27.
14. Cole AL, Lee PJ, Hughes DA, Deegan PB, Waldek S, Lachmann RH. Depression in adults with Fabry disease: A common and underdiagnosed problem. J Inherit Metab Dis. 2007; 30(6):943–51. doi:10.1007/s10545-007-0708-6.
15. Politei JM, Aiziczon D, Aguilar M, Alberton V, Alonso S, Amoreo O, et al. Recomendaciones para el diagnóstico, tratamiento y seguimiento de la enfermedad de fabry en Argentina. Revista Nefrología Argentina. 2018; 16(2):1-29.
16. Politei JM, Bouhassira D, Germain DP, Goizet C, Guerrero-Sola A, Hilz MJ, et al. Pain in Fabry disease: Practical recommendations for diagnosis and treatment. CNS Neurosci Ther. 2016; 22(7):568-76. doi:10.1111/cns.12542.
17. Biegstraaten M, Binder A, Maag R, Hollak CE, Baron R, van Schaik IN. The relation between small nerve fibre function, age, disease severity and pain in Fabry disease. Eur J Pain. 2011; 15(8):822–9. doi:10.1016/j.ejpain.2011.01.014.
18. Tanislav C, Kaps M, Rolfs A, Böttcher T, Lackner K, Paschke E, et al. Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: A pilot study. Eur J Neurol. 2011; 18(4):631–6. doi:10.1111/j.1468-1331.2010.03227.x.
19. Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci U S A. 2008; 105(8):2812–7. doi:10.1073/pnas.0712309105.
20. Lauria G, Merkies IS, Faber CG. Small fibre neuropathy. Curr Opin Neurol. 2012; 25(5):542–9. doi:10.1097/WCO.0b013e32835804c5.
21. Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small-fibre neuropathies–advances in diagnosis, pathophysiology and management. Nat Rev Neurol. 2012; 8(7):369–79. doi:10.1038/nrneurol.2012.97.
22. Schiffmann R, Moore DF. Neurological manifestations of Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry disease: Perspectives from 5 Years of FOS /Internet/. Oxford: Oxford Pharma Genesis; 2006. Chapter 22. /cited 2018 Jun 10/. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11602/
23. Hilz MJ, Brys M, Marthol H, Stemper B, Dütsch M. Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology. 2004; 62(7):1066-72.
24. Hande T, Cetin K A, Ayse O B. Neuropathic pain in Fabry disease. Open Access J Neurol Neurosurg. 2017; 2(4):555593. doi:10.19080/OAJNN.2017.02.555593.
25. Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, et. al. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018; 123(4):416-27. doi: 10.1016/j.ymgme.2018.02.014.
26. Lakomá J, Rimondini R, Donadio V, Liguori R, Caprini M. Pain related channels are differentially expressed in neuronal and non-neuronal cells of glabrous skin of fabry knockout male mice. PLoS One. 2014; 9(10):e108641. doi:10.1371/journal.pone.0108641.
27. Ries M, Mengel E, Kutschke G, Kim KS, Birklein F, Krummenauer F, et al. Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis. 2003; 26(4):413–4.
28. Burlina AP, Sims KB, Politei JM, Bennett GJ, Baron R, Sommer C, et al. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: The report of an expert panel. BMC Neurol. 2011; 11:61. doi:10.1186/1471-2377-11-61
29. García-Trabanino R, Badilla-Porras R, Carazo K, Courville K, de Luna E, Lemus P, et. al. Consenso del Grupo Centroamericano y del Caribe para el Estudio y Tratamiento de la Enfermedad de Fabry. Nefrol Latinoam. 2017; 14(1):27–38. doi:10.1016/j.nefrol.2016.11.003.
30. Liguori R, Di Stasi V, Bugiardini E, Mignani R, Burlina A, Borsini W, et al. Small fiber neuropathy in female patients with Fabry disease. Muscle Nerve. 2010; 41(3):409–412. doi:10.1002/mus.21606.
31. Choi L, Vernon J, Kopach O, Minett MS, Mills K, Clayton PT, et al. The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain. Neurosci Lett. 2015; 594:163–8. doi:10.1016/j.neulet.2015.01.084.
32. Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, et al. Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet. 2015; 52(5):353–8. doi:10.1136/jmedgenet-2014-102797.
33. Tøndel C, Bostad L, Larsen KK, Hirth A, Vikse BE, Houge G, et al. Agalsidase benefits renal histology in young patients with Fabry disease. J Am Soc Nephrol. 2013; 24(1):137–148. doi:10.1681/ASN.2012030316.
34. Germain DP, Weidemann F, Abiose A, Patel MR, Cizmarik M, Cole JA, et al. Analysis of left ventricular mass in untreated men and in men treated with agalsidase-B: Data from the Fabry registry. Genet Med. 2013; 15(12):958–65. doi:10.1038/gim.2013.53.
35. Arends M, Biegstraaten M, Wanner C, Sirrs S, Mehta A, Elliot PM, et al. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: An international cohort study. J Med Genet. 2018; 55(5):351-8. doi:10.1136/jmedgenet-2017-104863.
