Fiebre en pacientes inmunodeprimidos
Palabras clave:
fiebre, huésped inmunocomprometido, sistema inmunológico.Resumen
Introducción: La fiebre es un marcador de enfermedades infecciosas e inflamatorias que se da por una respuesta inmune innata y por diferentes mediaciones entre marcadores moleculares. En el paciente inmunodeprimido, uno o varios mecanismos inmunológicos pueden estar alterados, debido a que la respuesta inmune puede estar deprimida y la fiebre puede denotar un estado patológico grave subyacente. Se realizó una búsqueda exploratoria en las bases de datos PubMed/Medline, Scopus y Scielo entre septiembre y octubre de 2022. Se incluyeron los términos fiebre, pacientes inmunodeprimidos, tratamiento y sistema inmune. Se seleccionaron 41 artículos científicos con diferentes diseños epidemiológicos.
Objetivo: Describir aspectos relacionados con la fisiopatología de la fiebre, el tratamiento de la presencia de fiebre en pacientes con virus de inmunodeficiencia humana y síndrome de inmunodeficiencia adquirida, así como también en pacientes receptores de trasplantes de órgano sólido y de trasplantes hematopoyéticos, pacientes neutropénicos y pacientes tratados con corticosteroides y terapia biológica.
Desarrollo: El tratamiento del paciente inmunodeprimido con fiebre incluye aspectos fundamentales como una adecuada anamnesis y examen físico, además de pruebas diagnósticas orientadas para establecer la causa de la fiebre. En estos pacientes, las infecciones juegan un papel protagónico y su intervención temprana es fundamental para impactar en la morbimortalidad.
Conclusiones: El paciente inmunodeprimido con presencia de fiebre presenta un panorama desafiante para su manejo médico integral. Entre otros aspectos es relevante considerar el tipo y tiempo de inmunosupresión, así como los factores de riesgo, con el fin de orientar los diagnósticos y tratamientos.
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1. O'Grady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC, et al. American College of Critical Care Medicine; Infectious Diseases Society of America. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008;36(4):1330-49. DOI: 10.1097/CCM.0b013e318169eda9
2. Keck JM, Wingler MJB, Cretella DA, Vijayvargiya P, Wagner JL, Barber KE, et al. Approach to fever in patients with neutropenia: a review of diagnosis and management. Ther Adv Infect Dis. 2022;26(9):20499361221138346. DOI: 10.1177/20499361221138346
3. Hampton T. Fever Induces a Molecular Homing Response in Immune Cells During Infection. JAMA. 2019;321(17):1657-1658. DOI: 10.1001/jama.2019.4475
4. Siggins MK, MacLennan CA. An adsorption method to prepare specific antibody-depleted normal human serum as a source of complement for human serum bactericidal assays for Salmonella. Vaccine. 2021;39(51):7503-7509. DOI: 10.1016/j.vaccine.2021.10.023
5. Dolan JR. Re-Claiming Adrien Certes (1835-1903), Pioneer Deep-Sea Microbiologist, as a Protistologist. Protist. 2020;171(6):125772. DOI: 10.1016/j.protis.2020.125772
6. Drewry A, Mohr NM. Temperature Management in the ICU. Crit Care Med. 2022;50(7):1138-1147. DOI:10.1097/CCM.0000000000005556
7. Wright WF, Mulders-Manders CM, Auwaerter PG, Bleeker-Rovers CP. Fever of Unknown Origin (FUO) - A Call for New Research Standards and Updated Clinical Management. Am J Med. 2022;135(2):173-8. DOI: 10.1016/j.amjmed.2021.07.038
8. Walter EJ, Hanna-Jumma S, Carraretto M, Forni L. The pathophysiological basis and consequences of fever. Crit Care. 2016;20(1):200. DOI: 10.1186/s13054-016-1375-5
9. Pedaci M, Londoni C, Bertè R, Buscarini E. A stubborn fever. Dig Liver Dis. 2022;54(10):1444-5. DOI: 10.1016/j.dld.2021.09.013
10. Pincus D. Regulation of Hsf1 and the Heat Shock Response. Adv Exp Med Biol. 2020; 1243:41-50. DOI: 10.1007/978-3-030-40204-4_3
11. Wright WF, Auwaerter PG. Fever and Fever of Unknown Origin: Review, Recent Advances, and Lingering Dogma. Open Forum Infect Dis. 2020;7(5):ofaa132. DOI: 10.1093/ofid/ofaa132
12. Xu J, Ma C, Hua M, Li J, Xiang Z, Wu J. CNS and CNS diseases in relation to their immune system. Front Immunol. 2022;13:1063928. DOI: 10.3389/fimmu.2022.1063928
13. Osterhout JA, Kapoor V, Eichhorn SW, Vaughn E, Moore JD, Liu D, et al. A preoptic neuronal population controls fever and appetite during sickness. Nature. 2022; 606(7916):937-44. DOI: 10.1038/s41586-022-04793-z
14. Carnevale L, Perrotta M, Lembo G. A Focused Review of Neural Recording and Stimulation Techniques With Immune-Modulatory Targets. Front Immunol. 2021; 12:689344. DOI:10.3389/fimmu.2021.689344
15. Bonadio W. Commentary on New Guidelines for the Evaluation and Management of the Febrile Young Infant. Pediatrics. 2022;149(1):e2021055005A. DOI: 10.1542/peds.2021-055005A
16. Hasbun R. Progress and Challenges in Bacterial Meningitis: A Review. JAMA. 2022;328(21):2147-2154. DOI:10.1001/jama.2022.20521
17. Tuano KS, Seth N, Chinen J. Secondary immunodeficiencies: An overview. Ann Allergy Asthma Immunol. 2021;127(6):617-626. DOI: 10.1016/j.anai.2021.08.413
18. Vishnevetsky A, Anand P. Approach to Neurologic Complications in the Immunocompromised Patient. Semin Neurol. 2021;41(5):554-71. DOI: 10.1055/s-0041-1733795
19. Hajiabdolbaghi M, Ataeinia B, Ghadimi F, SeyedAlinaghi S, Badie BM, Dadras O, et al. Bone Marrow Aspiration/Biopsy in the Evaluation of Fever of Unknown Origin in Patients with AIDS. Infect Disord Drug Targets. 2021;21(3):394-8. DOI: 10.2174/1871526520666200705212903
20. Roberts MB, Fishman JA. Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression". Clin Infect Dis. 2021;73(7):e1302-e1317. DOI:10.1093/cid/ciaa1189
21. Lozano F, Torre-Cisneros J, Santos J, León E, Domínguez A, Montesdeoca M, et al. Impact of highly active antiretroviral therapy on fever of unknown origin in HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2002;21(2):137-9. DOI: 10.1007/s10096-001-0676-y
22. Haidar G, Singh N. Fever of Unknown Origin. N Engl J Med. 2022;386(5):463-477. DOI: 10.1056/NEJMra2111003
23. Sepkowitz KA, Telzak EE, Carrow M, Armstrong D. Fever among outpatients with advanced human immunodeficiency virus infection. Arch Intern Med. 1993 [acceso: 01/07/2023];153(16):1909-12. Disponible en: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/617709
24. Ramos-Rincon JM, Menchi-Elanzi M, Pinargote-Celorio H, Mayoral A, González-Alcaide G, de Mendoza C, et al. Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades. AIDS. 2022;36(2):249-56. DOI: 10.1097/QAD.0000000000003105
25. Hajiabdolbaghi M, Ataeinia B, Ghadimi F, SeyedAlinaghi S, Badie BM, Dadras O, et al. Bone Marrow Aspiration/Biopsy in the Evaluation of Fever of Unknown Origin in Patients with AIDS. Infect Disord Drug Targets. 2021;21(3):394-398. DOI: 10.2174/1871526520666200705212903
26. Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22(12):1748-55. DOI: 10.1016/S1473-3099(22)00499-6
27. Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, et al. Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies. Clin Infect Dis. 2021;72(7):1268-1278. DOI: 10.1093/cid/ciaa1243
28. Rajasingham R, Wake RM, Beyene T, Katende A, Letang E, Boulware DR. Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing. J Clin Microbiol. 2019;57(1):e01238-18. DOI: 10.1128/JCM.01238-18
29. Harjani RG, Hinduja RH, Iyer AK. Intracranial lymphoma in human immunodeficiency virus-infected patients: A diagnostic dilemma?. Indian J Sex Transm Dis AIDS. 2022;43(1):82-84. doi:10.4103/ijstd.ijstd_10_21
30. Arora N, Kotwani S, Chhabra M, H M. Hemorrhagic Lesions in the Central Nervous System: Toxoplasmosis in a Person Living With Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. Cureus. 2022;14(5):e24827. DOI: 10.7759/cureus.24827
31. Ison MG. Transplant infectious disease: Renewing a home for TID research. Transpl Infect Dis. 2022;24(1):e13760. DOI: 10.1111/tid.13760
32. Dettori M, Riccardi N, Canetti D, Antonello RM, Piana AF, Palmieri A, et al. Infections in lung transplanted patients: A review. Pulmonology. 2022:S2531-0437(22)00118-0. DOI: 10.1016/j.pulmoe.2022.04.010
33. Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, et al. Emerging and neglected zoonoses in transplant population. World J Transplant. 2020;10(3):47-63. DOI: 10.5500/wjt.v10.i3.47
34. Olnes MJ. Immune Therapies for Hematologic Malignancies. Cancers (Basel). 2021;13(2):295. Published 2021 Jan 15. DOI:10.3390/cancers13020295
35. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al. ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v118. DOI: 10.1093/annonc/mdw325
36. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017;96(11):1775-92. DOI.org/10.1007/s00277-017-3098-3
37. Malpica L, Moll S. Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases. Hematology Am Soc Hematol Educ Program. 2020;2020(1):319-27. DOI: 10.1182/hematology.2020000116
38. Shobha V, Chandrashekara S, Rao V, Desai A, Jois R, Dharmanand BG, et al. Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India. Int J Rheum Dis. 2019;22(2):280-287. DOI: 10.1111/1756-185X.13376
39. Malpica L, Moll S. Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases. Hematology Am Soc Hematol Educ Program. 2020;2020(1):319-327. DOI:10.1182/hematology.2020000116
40. Takabayashi K, Ando F, Ikeda K, Nakajima H, Hanaoka H, Suzuki T. Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study. Mod Rheumatol. 2022:roac133. DOI: 10.1093/mr/roac133
41. Voelker R. Biologic Treatment Approved for Rare Blood Disorders. JAMA. 2020;324(17):1715. DOI:10.1001/jama.2020.21140
2. Keck JM, Wingler MJB, Cretella DA, Vijayvargiya P, Wagner JL, Barber KE, et al. Approach to fever in patients with neutropenia: a review of diagnosis and management. Ther Adv Infect Dis. 2022;26(9):20499361221138346. DOI: 10.1177/20499361221138346
3. Hampton T. Fever Induces a Molecular Homing Response in Immune Cells During Infection. JAMA. 2019;321(17):1657-1658. DOI: 10.1001/jama.2019.4475
4. Siggins MK, MacLennan CA. An adsorption method to prepare specific antibody-depleted normal human serum as a source of complement for human serum bactericidal assays for Salmonella. Vaccine. 2021;39(51):7503-7509. DOI: 10.1016/j.vaccine.2021.10.023
5. Dolan JR. Re-Claiming Adrien Certes (1835-1903), Pioneer Deep-Sea Microbiologist, as a Protistologist. Protist. 2020;171(6):125772. DOI: 10.1016/j.protis.2020.125772
6. Drewry A, Mohr NM. Temperature Management in the ICU. Crit Care Med. 2022;50(7):1138-1147. DOI:10.1097/CCM.0000000000005556
7. Wright WF, Mulders-Manders CM, Auwaerter PG, Bleeker-Rovers CP. Fever of Unknown Origin (FUO) - A Call for New Research Standards and Updated Clinical Management. Am J Med. 2022;135(2):173-8. DOI: 10.1016/j.amjmed.2021.07.038
8. Walter EJ, Hanna-Jumma S, Carraretto M, Forni L. The pathophysiological basis and consequences of fever. Crit Care. 2016;20(1):200. DOI: 10.1186/s13054-016-1375-5
9. Pedaci M, Londoni C, Bertè R, Buscarini E. A stubborn fever. Dig Liver Dis. 2022;54(10):1444-5. DOI: 10.1016/j.dld.2021.09.013
10. Pincus D. Regulation of Hsf1 and the Heat Shock Response. Adv Exp Med Biol. 2020; 1243:41-50. DOI: 10.1007/978-3-030-40204-4_3
11. Wright WF, Auwaerter PG. Fever and Fever of Unknown Origin: Review, Recent Advances, and Lingering Dogma. Open Forum Infect Dis. 2020;7(5):ofaa132. DOI: 10.1093/ofid/ofaa132
12. Xu J, Ma C, Hua M, Li J, Xiang Z, Wu J. CNS and CNS diseases in relation to their immune system. Front Immunol. 2022;13:1063928. DOI: 10.3389/fimmu.2022.1063928
13. Osterhout JA, Kapoor V, Eichhorn SW, Vaughn E, Moore JD, Liu D, et al. A preoptic neuronal population controls fever and appetite during sickness. Nature. 2022; 606(7916):937-44. DOI: 10.1038/s41586-022-04793-z
14. Carnevale L, Perrotta M, Lembo G. A Focused Review of Neural Recording and Stimulation Techniques With Immune-Modulatory Targets. Front Immunol. 2021; 12:689344. DOI:10.3389/fimmu.2021.689344
15. Bonadio W. Commentary on New Guidelines for the Evaluation and Management of the Febrile Young Infant. Pediatrics. 2022;149(1):e2021055005A. DOI: 10.1542/peds.2021-055005A
16. Hasbun R. Progress and Challenges in Bacterial Meningitis: A Review. JAMA. 2022;328(21):2147-2154. DOI:10.1001/jama.2022.20521
17. Tuano KS, Seth N, Chinen J. Secondary immunodeficiencies: An overview. Ann Allergy Asthma Immunol. 2021;127(6):617-626. DOI: 10.1016/j.anai.2021.08.413
18. Vishnevetsky A, Anand P. Approach to Neurologic Complications in the Immunocompromised Patient. Semin Neurol. 2021;41(5):554-71. DOI: 10.1055/s-0041-1733795
19. Hajiabdolbaghi M, Ataeinia B, Ghadimi F, SeyedAlinaghi S, Badie BM, Dadras O, et al. Bone Marrow Aspiration/Biopsy in the Evaluation of Fever of Unknown Origin in Patients with AIDS. Infect Disord Drug Targets. 2021;21(3):394-8. DOI: 10.2174/1871526520666200705212903
20. Roberts MB, Fishman JA. Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression". Clin Infect Dis. 2021;73(7):e1302-e1317. DOI:10.1093/cid/ciaa1189
21. Lozano F, Torre-Cisneros J, Santos J, León E, Domínguez A, Montesdeoca M, et al. Impact of highly active antiretroviral therapy on fever of unknown origin in HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2002;21(2):137-9. DOI: 10.1007/s10096-001-0676-y
22. Haidar G, Singh N. Fever of Unknown Origin. N Engl J Med. 2022;386(5):463-477. DOI: 10.1056/NEJMra2111003
23. Sepkowitz KA, Telzak EE, Carrow M, Armstrong D. Fever among outpatients with advanced human immunodeficiency virus infection. Arch Intern Med. 1993 [acceso: 01/07/2023];153(16):1909-12. Disponible en: https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/617709
24. Ramos-Rincon JM, Menchi-Elanzi M, Pinargote-Celorio H, Mayoral A, González-Alcaide G, de Mendoza C, et al. Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades. AIDS. 2022;36(2):249-56. DOI: 10.1097/QAD.0000000000003105
25. Hajiabdolbaghi M, Ataeinia B, Ghadimi F, SeyedAlinaghi S, Badie BM, Dadras O, et al. Bone Marrow Aspiration/Biopsy in the Evaluation of Fever of Unknown Origin in Patients with AIDS. Infect Disord Drug Targets. 2021;21(3):394-398. DOI: 10.2174/1871526520666200705212903
26. Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22(12):1748-55. DOI: 10.1016/S1473-3099(22)00499-6
27. Temfack E, Rim JJB, Spijker R, Loyse A, Chiller T, Pappas PG, et al. Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies. Clin Infect Dis. 2021;72(7):1268-1278. DOI: 10.1093/cid/ciaa1243
28. Rajasingham R, Wake RM, Beyene T, Katende A, Letang E, Boulware DR. Cryptococcal Meningitis Diagnostics and Screening in the Era of Point-of-Care Laboratory Testing. J Clin Microbiol. 2019;57(1):e01238-18. DOI: 10.1128/JCM.01238-18
29. Harjani RG, Hinduja RH, Iyer AK. Intracranial lymphoma in human immunodeficiency virus-infected patients: A diagnostic dilemma?. Indian J Sex Transm Dis AIDS. 2022;43(1):82-84. doi:10.4103/ijstd.ijstd_10_21
30. Arora N, Kotwani S, Chhabra M, H M. Hemorrhagic Lesions in the Central Nervous System: Toxoplasmosis in a Person Living With Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. Cureus. 2022;14(5):e24827. DOI: 10.7759/cureus.24827
31. Ison MG. Transplant infectious disease: Renewing a home for TID research. Transpl Infect Dis. 2022;24(1):e13760. DOI: 10.1111/tid.13760
32. Dettori M, Riccardi N, Canetti D, Antonello RM, Piana AF, Palmieri A, et al. Infections in lung transplanted patients: A review. Pulmonology. 2022:S2531-0437(22)00118-0. DOI: 10.1016/j.pulmoe.2022.04.010
33. Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, et al. Emerging and neglected zoonoses in transplant population. World J Transplant. 2020;10(3):47-63. DOI: 10.5500/wjt.v10.i3.47
34. Olnes MJ. Immune Therapies for Hematologic Malignancies. Cancers (Basel). 2021;13(2):295. Published 2021 Jan 15. DOI:10.3390/cancers13020295
35. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al. ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v118. DOI: 10.1093/annonc/mdw325
36. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017;96(11):1775-92. DOI.org/10.1007/s00277-017-3098-3
37. Malpica L, Moll S. Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases. Hematology Am Soc Hematol Educ Program. 2020;2020(1):319-27. DOI: 10.1182/hematology.2020000116
38. Shobha V, Chandrashekara S, Rao V, Desai A, Jois R, Dharmanand BG, et al. Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India. Int J Rheum Dis. 2019;22(2):280-287. DOI: 10.1111/1756-185X.13376
39. Malpica L, Moll S. Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases. Hematology Am Soc Hematol Educ Program. 2020;2020(1):319-327. DOI:10.1182/hematology.2020000116
40. Takabayashi K, Ando F, Ikeda K, Nakajima H, Hanaoka H, Suzuki T. Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study. Mod Rheumatol. 2022:roac133. DOI: 10.1093/mr/roac133
41. Voelker R. Biologic Treatment Approved for Rare Blood Disorders. JAMA. 2020;324(17):1715. DOI:10.1001/jama.2020.21140
Publicado
21.12.2023
Cómo citar
1.
Weir-Restrepo D, Zuluaga-Gómez M, Valverde-Legarda AE, Ardila CM. Fiebre en pacientes inmunodeprimidos. Rev Cubana Med Milit [Internet]. 21 de diciembre de 2023 [citado 20 de abril de 2025];53(1):e024017871. Disponible en: https://revmedmilitar.sld.cu/index.php/mil/article/view/17871
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